Internal Medicine

Tumefactive Multiple sclerosis

Potjana Jitawatanarat, Bhatraphol Tingpej and Paul Deringer

Cite this article as: BJMP 2011;4(2):a419
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Keywords:  Multiple sclerosis, Tumefactive multiple sclerosis


Tumefactive multiple sclerosis (MS) is a rare variant of MS.  This form of MS can masquerade as neoplasm or infectious etiology.  Understanding of the disease is limited to case report but it is associated with high morbidity and mortality.

Case report

A 44 year old man presented with a 2-month history of progressive right upper extremity weakness, confusion and visual change.  Physical exam revealed weakness, hyperreflexia on the right side and right homonymous hemianopia.  MRI of the brain showed multiple ring-enhancing lesions located in both cerebral hemispheres.  CSF analysis disclosed elevated protein with positive oligoclonal bands and myelin basic protein.  Stains and cultures for bacteria and mycobacteria were negative.  Serologies including HIV, Toxoplasmosis, and Lyme were all negative.  Patient was treated with high-dose IV corticosteroid and clinically improved.  One month later, he presented with increasing confusion, aphasia and progressive weakness.  Repeat MRI of the brain revealed worsening multiple ring-enhancing lesions with surrounding vasogenic edema in most lesions.  High-dose corticosteroid was promptly started.  There was also concern about infection, especially brain abscess; hence, intravenous ceftriaxone, vancomycin, and metronidazole were empirically given.  Due to uncertainty of diagnosis, first brain biopsy at right frontal lobe lesion yielded non-specific gliosis.  Repeat MRI brain showed increasing number of ring-enhancing lesions in both cerebral hemispheres.  As a result, a second brain biopsy was performed, which showed an active demyelinating process consistent with multiple sclerosis.  Patient experienced severe disability and was discharged to long-term facility with slowly tapered schedule of corticosteroid. He was readmitted several times and eventually family decided hospice care.


Multiple sclerosis is diagnosed by demonstrating clinical and/or radiographic evidence of dissemination of disease in time and space1.  Tumefactive MS is a term used when the clinical presentation and/or MRI findings are indistinguishable from a brain tumor2.  Not all case of tumefactive MS are fulminant.  Marburg variant MS is an acute rare variant of MS which has a rapidly progressive course with frequent, severe relapses leading to death or severe disability within weeks to months3.  The tumefactive demyelinating lesions are defined as large (>2 cm.) white matter lesions with little mass-like effect or vasogenic edema, and post-gadolinium magnetic resonance imaging (MRI) typically showing an incomplete ring enhancement2,4.  The clinical and imaging characteristics of these demyelinating lesions may mimic primary and secondary brain tumors, brain abscess, tuberculoma, and other inflammatory disorders e.g. sarcoidosis, primary sjogren’s syndrome5. As a result, tumefactive MS is frequently misdiagnosed. There are some MRI characteristics that are more suggestive of tumefactive demyelinating lesions than of other etiologies.  These include incomplete ring enhancement, mixed T2-weighted iso-and hyperintensity of enhanced regions, absence of a mass effect and absence of cortical involvement2,6.   Differential diagnosis of rapidly progressive neurological deficit with ring-enhancing lesions include brain abscess, primary brain neoplasm or brain metastasis, acute disseminated encephalomyelitis (ADEM) and tumefactive multiple sclerosis.  Careful clinical history, CSF study, serial MRI evaluation and follow-up are usually sufficient to make a diagnosis. Some cases pose considerable diagnostic difficulty owing to clinical and radiographical resemblance to brain tumor, for which biopsy may be warranted.  Pathologically, the lesions are characterized by massive macrophage infiltration, acute axonal injury, and necrosis.  No specific histological features distinguished specimens derived from patients developing classic multiple sclerosis from those who had tumefactive form7.  A limited number of cases of Marburg’s variant MS have been reported in the literature whereby most patients died within a period of weeks to months.  Only two cases survived after one year7,8.  There is no current standard treatment for this condition.  Plasma exchange and Mitoxantrone are reportedly showed some promising options9,10.

Figure A: FLAIR imaging at first presentation showed lesion in both hemisphere. Figure B: FLAIR imaging at one month later showed progression of multiple lesion in both hemisphere. Figure C: T1 Post contrast imaging showed intense ring enhancement pattern in almost all lesions  with mild edema and minimal mass effect. Figure D: Showed lesion view as sagittal section.

Our patient presented somewhat like a stroke with visual field defect and right hemiparesis which is unusual in MS, but MRI and CSF exam yielded a diagnosis of probable MS.  Because of his abrupt clinical deterioration and impressive worsening of his MRI, concern was raised about possibility of infection or neoplasm.  Hence, he received two brain biopsies, the second of which showed active demyelination, confirming the diagnosis of severe tumefactive multiple sclerosis and can be consider as a Marburg variant multiple sclerosis.


Marburg variant multiple sclerosis carries a high morbidity and mortality.  This disease notoriously mimics other conditions leading to delay diagnosis and treatment.  Absence of definitive diagnosis test apart from brain biopsy makes diagnosis, prognosis and treatment decisions difficult. 

Competing Interests
None declared
Author Details
POTJANA JITAWATANARAT, MD Internal Medicine Resident, Bassett Medical Center, Cooperstown, NY BHATRAPHOL TINGPEJ, MD Internal Medicine Resident, Bassett Medical Center, Cooperstown, NY PAUL DERINGER, MD Neurology Attending, Bassett Medical Center, Cooperstown, NY
CORRESSPONDENCE: POTJANA JITAWATANARAT, MD Internal Medicine resident, Bassett Medical Center, Cooperstown, NY



1.  McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of multiple sclerosis. Ann Neurol.2001; 50: 121–7.2.  Dagher AP, Smirniotopoulos J. Tumefactive demyelinating lesions. Neuroradiology. 1996; 38: 560–5.3.  Canellas AR, Gols AR, Izquierdo JR, et al. Idiopathic inflammatory-demyelimating disease of central nervous system. Neuroradiology.2007; 49:393-409.4.  Lucchinetti CF, et al. Clinical and radiographic spectrum of pathologically confirmed tumefactive multiple sclerosis. Brain.2008; 131:1759-75.5.  Sanahuja J, Ordonez-Palau S, Beque R, Brieva L, Boquet D. Primary Sjogren syndrome with tumefactive central nervous system involvement. Am J Neuroradiol.2008 Nov; 29(10):1878-79.6.  Kim DS, et al. Distinguishing tumefactive demyelinating lesions from glioma or central nervous system lymphoma: Added value of unenhanced CT compared with conventional contrast-enhanced MR imaging. Radiology. 2009; 251:467-75.7.  Turatti M, Gajofatto A, Rossi F, et al. Long survival and clinical stability in Marburg variant multiple        sclerosis. Neurol Sci. 2010; 31(6):807-11.8.  Giubilei F, Sarrantonio A, Teisei P, et al. Four-year follow-up of a case of acute multiple sclerosis of the Marburg type. Ital J Neurol Sci.1997; 18:163-166.9.  Jeffery DR, Lefkowitz DS, Crittenden JP. Treatment of Marburg variant multiple sclerosis with mitoxanthrone. J Neuroimaging. 2004; 14:58-6210.  Rodriguez M, Karnes WE, Bartleson JD, Pineda AA Plasmapheresis in acute episodes of fulminant CNS inflammatory demyelination. Neurology.1993; 43 (6):1100-4.

Malignant Hypertension Masquerading as Thrombotic Thrombocytopenic Purpura

Muhammad Zohaib Bawany, Zeeshan Tariq, Thomas Sodeman and Anand Mutgi

Cite this article as: BJMP 2011;4(2):a418
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Hypertension is common, but with early detection and treatment, it is rare to see malignant hypertension.  Malignant hypertension is a medical emergency with an incidence of 1% in hypertensive patients.  We report on a patient who presented with signs suggestive of Thrombotic Thrombocytopenic Purpura and severe hypertension, which resolved with the treatment of hypertension.

Keywords:  Malignant Hypertension, Thrombotic Thrombocytopenic Purpura


Hypertension is common but, with early detection and treatment, it is rare to see malignant hypertension. We report a patient who presented with signs suggestive of thrombotic thrombocytopenic purpura and severe hypertension, which resolved with the treatment of hypertension.


A 34 year old African American male presented to the emergency department (ED) having experienced nausea, vomiting and diarrhoea for two days.  He denied haematochezia, meleana or sick contacts at home.  He complained of blurred vision without photophobia, headache and mild chest discomfort.  His past medical history was unremarkable.  The patient did not have any significant family history. Smoking history was significant for a pack of cigarettes daily for seven years.  He reported occasional alcohol intake, and denied use of recreational drugs.  On presentation, this patient’s blood pressure was 201/151 mmHg, with a mean of 168 mmHg.  Pulse 103 beats per minute, respirations 20 per minute and temperature 98.4F.  Physical examination was otherwise unremarkable, including absence of focal neurological deficits.

Blood tests showed: Haemoglobin 12.6 g/dl, White cell count 13.9 g/dl, Platelets 67000, Sodium 136, Potassium 3.4, BUN 24, Creatinine 2.56 and LDH 556. Chest x-ray showed cardiomegaly.  A non-contrast computed tomography scan of the brain did not show any sign of stroke (haemorrhage).  Urinalysis was positive for proteins 4+, a large amount of blood, 0-2 white blood cells/high power field (HPF) and 0-2 red blood cells/HPF.

Figure 1

The patient’s initial treatment whilst in the ER consisted of a Labetalol drip.  His mean arterial pressure decreased to approximately 115 mmHg during the first hour, and his chest pain and headache improved with the control of elevated mean arterial pressure.  Furthermore, over the next 24 - 48 hours, the patient’s blood pressure was brought down to 138/86 mmHg and his blurred vision improved significantly.  Subsequently, intravenous medications were switched to an oral regimen.  Blood peripheral smear from the day of admission was significant for the schistocytes (Figure 1) suggesting ongoing haemolysis.  Renal ultrasound was unremarkable.  His cardiac ultrasound revealed an enlarged left ventricle, however no valvular abnormality was seen.  Serum calcium and thyroid stimulating hormone levels were normal, as were urine catecholamines and vanillylmandelic acid level.  On two week follow up in the outpatient clinic, the patient’s platelet count and creatinine had returned back to baseline and peripheral smear did not reveal any schistocytes as the blood pressure came under better control. [Table 1]

Variable On day 1 Day 3 Day 5 Day 6 Follow-up in 2 weeks
Haemoglobin 12.6 9.3 9.3 10.3 11.4
Platelets 67, 000 65,000 90,000 125,000 204,000
Retic. count 3.9 -- -- 4.3 --
Creatinine 3.06 2.86 2.69 2.4 2.3
BUN 29 27 28 27 27
LDH 556 370 333 240 --
Troponin 0.10 0.08 0.06 0.05 --
Peripheral Smear Schistocytes -- -- -- No Schistocytes

Table 1


Malignant hypertension is a medical emergency with an incidence of 1% in hypertensive patients1and is more common in the African American population2.  Depending on the clinical presentation, it must be differentiated from thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), glomerulonephritis and vasculitis.

Suspicion for TTP was initially high in this patient because of haemolysis, thrombocytopaenia, central nervous system (CNS) manifestations and renal insufficiency.  However, TTP did not explain the presence of elevated blood pressure3,4nor the improvement in symptoms and signs with the management of this, which clearly supports our diagnosis.  Rapidly progressive glomerulonephritis did not explain the CNS symptoms, and a normal prothrombin time and activated partial thromboplastin time ruled against disseminated intravascular coagulation5.  The patient did not have a history of preceding diarrhoea6, which could possibly direct towards haemolytic uraemic syndrome (HUS)4.  There was no history of prosthetic valves, nor clinical evidence of vasculitis. The patient’s symptoms of severe hypertension, haemolysis, thrombocytopaenia and renal failure were consistent with malignant hypertension, and treating the hypertension7gradually resolved the thrombocytopaenia, haemolysis and renal failure8


This case report highlights that malignant hypertension is a medical emergency which can present with features resembling a wide variety of diseases, including TTP and HUS.  Using appropriate management to control the elevation in blood pressure can help reveal the underlying diagnosis.

Competing Interests
None declared
Author Details
Muhammad Zohaib Bawany MD, Zeeshan Tariq MD, Thomas Sodeman MD FACP, Anand Mutgi MD FACP, University of Toledo Medical Center, Toledo, OH
CORRESSPONDENCE: Muhammad Zohaib Bawany, University of Toledo Medical Center, 3000 Arlington Ave Mail stop 1150, Toledo OH, USA 43614



1.    Kitiyakara C, Guzman NJ. Malignant hypertension and hypertensive emergencies. J Am Soc Nephrol 1998;9:133-42.2.    Khanna A, McCullough PA. Malignant hypertension presenting as hemolysis, thrombocytopenia, and renal failure. Rev Cardiovasc Med 2003;4:255-9.3.    Patel A, Patel H. Thrombotic thrombocytopenic purpura: the masquerader. South Med J 2009;102:504-9.4.    Shibagaki Y, Fujita T. Thrombotic microangiopathy in malignant hypertension and hemolytic uremic syndrome (HUS)/ thrombotic thrombocytopenic purpura (TTP): can we differentiate one from the other? Hypertens Res 2005;28:89-95.5.    Kitchens CS. Thrombocytopenia and thrombosis in disseminated intravascular coagulation (DIC). Hematology Am Soc Hematol Educ Program 2009:240-6.6.    Hertig A, Ridel C, Rondeau E. [Hemolytic uremic syndrome in adults]. Nephrol Ther 2010;6:258-71.7.    Varon J, Marik PE. The diagnosis and management of hypertensive crises. Chest 2000;118:214-27.8.    Gassanov N, Pollok M, Er F. Acute renal failure associated with malignant hypertension. Dtsch Med Wochenschr 2009;134:2224-7.

MRSA infection of a Primary TKA following an infected IV cannula site complicated by Stevens-Johnson Syndrome- A Case Report

SKM Annamalai, SS Raju and VG Langkamer

Cite this article as: BJMP 2011;4(2):a415
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We present here a 63 year old lady who had a primary total knee arthroplasty( TKA) for  osteoarthritis of knee. She developed methicillin resistant staphylococcus aureus( MRSA )infection of the primary  prosthesis following an intravenous(IV) cannula site infection with MRSA bacteraemia. This was complicated by Stevens-Johnson syndrome following vancomycin therapy for the infection, which was confirmed by clinical features including typical skin rashes and skin biopsy. She was treated with alternative antibiotics and was referred to a specialist orthopaedic unit where she had a two- stage revision.

In retrospect, the infection could have been avoided if the IV cannula was not left in for so long. She also unfortunately had an adverse reaction to the vancomycin which complicated the situation, making management difficult. A team consisting of orthopaedic surgeons, microbiologists, dermatologists and physiotherapists was essential for successful management of this difficult and complicated  situation.

Abbreviations: MRSA (methicillin resistant staphylococcus aureus), IV( intravenous), TKA (total knee arthroplasty), DM( diabetes mellitus)


Infection of a prosthetic total knee joint is a serious complication1 and should be diagnosed promptly2 and treated aggressively. We present an interesting case of MRSA infection of a primary total knee replacement following  an IV cannula infection leading to bacteremia and subsequent infection of  the knee prosthesis, complicated by stevens- Johnson syndrome .

There were many challenging issue which are outlined including diagnosis and management.

Case Report

A 63-year- old lady had an elective total knee arthroplasty for severe osteoarthritis of the knee. She had a background history of well-controlled type 2 diabetes mellitus and was on warfarin for a previous pulmanory embolism. As per the hospital protocol her warfarin was stopped before surgery until her INR was <1.5 and she was heparinised with a view of

warfarinizing after the surgery. She had an uneventful knee arthoplasty, but unfortunately one of her IV cannula site became cellulitic. She was empirically started on oral flucloxacillin after taking blood cultures and sending the cannula tip for microscopic culture and sensitivity (which is routinely done has hospital protocol for infected cannula sites).

Surprisingly the tip grew MRSA and also had MRSA bacteraemia. She became systemically unwell and septic, and was treated aggressively with parentral vancomycin for MRSA bacteraemia. She had a transeosphageal echocardiogram to rule out cardiac vegetation. She gradually improved but developed typical papular rashes over her palm, dorsum of hand, extensor surface of arm and forearm and trunk and buccal mucosa (Fig 1 and 2) .

Fig 1: Rash over the dorsum hands

Fig 2: Rash over the extensor aspects of forearm

She had a severe allergic reaction to vancomycin and the skin biopsy of the lesion confirmed that she had developed Stevens-Johnson syndrome. An alternative antibiotic was started following discussion with the specialist bone infection unit. She gradually improved over the next few weeks without any problem in her prosthetic replaced knee. At about 6 weeks post- operatively she developed severe pain and hot swelling of her replaced knee with decrease range of motion. Her inflammatory markers were markedly raised and the knee aspirate confirmed MRSA infection of the total knee replacement. She was referred to a specialist bone infection unit due to the complexity of the case, where she successfully underwent two- stage revision.


Infection of  a Knee replacement is a serious complication that requires significant hospital-based recourse for successful management3. The rate of infection of a primary knee replacement varies from 0.5- 12%1. Rheumatoid arthritis , previous surgery , diabetes mellitus are all associated with an increased risk of infection 4. Although there is no absolute diagnostic test for peri-prosthetic infection2 , a high index of clinical suspicion is essential. There has been a case report on MRSA cervical epidural abscess following IV cannulation 5, but to the best of our knowledge there has been no previous report of MRSA- infected knee arthroplasty following complications of IV cannulation. Stevens-Johnson syndrome involves rare but severe cutaneous adverse reactions related to a variety of medications including antibiotics6. Parenteral vancomycin is the first line treatment for MRSA bacteraemia. It is recognised that vancomycin is indicated in inducing Stevens -Johnson syndrome, mortalitiy being 30-100%7. It is vital that Stevens- Johnson syndrome is recognised early so that offending agents are stopped and supportive treatment commenced. Early dermatological consultation, skin biopsy and direct immunofluorescence7 are essential to confirm diagnosis  so that effective treatment can be instituted.The diagnosis and management of this serious complication is complex and requires considerable recourse allocation by the patient, the hospital, the infectious disease specialist, and the orthopaedic surgeon1,5.

Competing Interests
None declared
Author Details
SKM Annamalai, MBBS MRCS, Orthopaedic Registrar, Peterborough City Hospital, UK SS Raju, F2 Trainee, Western General Hospital Western Super Mare, UK VG Langkamer, Consultant Orthopaedic Surgeon, Western General Hospital Weston Super Mare, UK
CORRESSPONDENCE: SKM Annamalai, MBBS MRCS, 2, Boulton Court, Oadby, Leicester, LE2 4XA


  1. Blom AW, Brown J, Taylor AH, Pattison G, Whitehouse S, Bannister GC. Infection after total knee arthroplasty. J Bone Joint surgery Br 2004 Jul;86(5):688-91.
  2. Elie Ghanem et al. Cell Count and Differential of the Aspirated fluid in the Diagnosis of the Infection at the Site of Total Knee Arthroplasty.  J Bone Joint Surg Am. 2008;09: 1637-43.
  3. Buechel F F, Femino FP, D’Alessio J. Primary Exchange Revision Arthroplasty for Infected Total Knee Arthroplasty: A Long-Term study The Americal journal Of Orthopaedics .2004;April.190-98.
  4. Bengtson S, Knutson K. The infected Knee arthoplasty. A 6 year follow-up of 357 cases. Acta Orthop Scand 1991 Aug;62(4):310-11.
  5. Burgess CM, Wolverson AS, Dale MT.Cervical epidural abscess: a rare complication of intravenous cannulation. Anaesthesia. 2005 Jun;60(6):605-8.
  6. Mockenhaupt-Maja et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The Euro SCAR- study: J-Invest- Dermatol, Jan2008, vol128, no. 1, p 35-44.
  7. Jones DH, Todd M, Craig TJ. Early diagnosis is key in vancomycin-induced linear IgA bullous dermatosis and stevens- Johnson syndrome. J Am Osteopath Assoc. 2004 Apr;10494):157-63

Interview with Prof. Robert Moots

Cite this article as: BJMP 2011;4(2):a414
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Robert Moots is Professor of Rheumatology at the University of Liverpool and Director for Research and Development at the University Hospital, Aintree. He is also a Consultant Rheumatologist at the hospital.

He graduated from St Mary’s Hospital, London University in 1985 and also worked at Harvard Medical School. He became a Consultant Rheumatologist at University Hospital Aintree in 1997 and the youngest full-time professor of Rheumatology and Head of Department in 2003.

Professor Moots has published extensively in rheumatology, winning the prestigious Michael Mason prize for rheumatology research. He advises the UK Department of Health and NICE. His research interests are inflammatory rheumatic diseases, in particular innate cellular immunity in rheumatoid arthritis, immunotherapy, new therapeutic targets and clinical trials.

How long have you been working in your speciality?

I’ve been working as a consultant in rheumatology since1997, when I returned to the UK from the USA. Of course I was a trainee in rheumatology for a few years before then.

Which aspect of your work do you find most satisfying?

Its hard to single out any one thing. The great fun of being Professor is that no two days are the same. My job varies so much from looking after patients, to teaching, running research and also communicating and sharing research findings with other clinicians and scientists throughout the world – giving me the opportunity to visit countries, where I would not normally have visited.

What achievements are you most proud of in your medical career?

Clinically, I often deal with rare rheumatic diseases, or situations where normal treatments have failed and other doctors have said there is “no more that can be done”. Each patient that I see in this situation, who then goes on to recover and have a normal happy life, gives me a great satisfaction. Academically, building up a successful research team of talented individuals in Liverpool, the first academic rheumatology unit in that city, has been a great privilege.

Which part of your job do you enjoy the least?

Trying to balance the demands of patient care with the many other calls on my time can be rather wearing. But nothing is worse than the ever expanding administration tasks and bureaucracy!

What are your views about the current status of medical training in your country and what do you think needs to change?

When I visit other countries to lecture, I always try to see how medicine runs there. I attend clinics and hospitals, see patients and learn how practice compares to the UK. I am pleased to note that the standard in the UK remains amongst the highest of all countries.

How would you encourage more medical students into entering your speciality?

Its hard to image why students and doctors could consider any specialty other than Rheumatology! Rheumatology provides the opportunity to see patients of all ages, develop a close rapport with patients as the diseases tend to be chronic and prevalent, perform cutting edge research to understand pathophysiological process underlying the diseases and access drugs that can make a revolution to lives with great outcomes.

What qualities do you think a good trainee should possess?

Be keen to learn, open, honest and bright. I also like trainees to challenge accepted wisdom – a considered critical approach is needed to move things forward and to keep us on our toes.

What is the most important advice you could offer to a new trainee?

Don’t accept non-evidence based dogma. Don’t learn bad habits. Be critical and try to improve things. Try to spend some time away from your unit and ideally out of your country – seeing how medicine works in other environments to get life and work in a better perspective.

What qualities do you think a good trainer should possess?

Good trainers should be excellent clinicians, inspirational leaders and listeners with patience. If you know someone like this, you should really treasure them!

Do you think doctors are over-regulated compared with other professions?

No – but I fear that we are getting there in the UK.

Is there any aspect of current health policies in your country that are de-professionalising doctors? If yes what shouldbe done to counter this trend?

With a recent change in government in the UK and major changes to the Health Service planned, it’s a little too early to tell. We have to be vigilant though.

Which scientific paper/publication has influenced you the most?

For much of my working life, I was focused on the T cell as the major driver for diseases such as rheumatoid arthritis. The paper that changed that was: Edwards SW, Hallett MB. Seeing the wood for the trees: the forgotten role of neutrophils in rheumatoid arthritis. Immunol Today.1997 Jul;18(7):320-4. This crucial paper from Steve Edwards, the world leader in neutrophil biology opened my eyes to a whole new field of work. I didn’t know at the time that I would eventually have the privilege of working with Steve.

What single area of medical research in your specialty should be given priority?

That’s an easy one – it should be whatever my group are working on at the time.(I just wish that were the case!)

What is the most challenging area in your specialty that needs further development?

Many rheumatic diseases such as rheumatoid arthritis can be treated extremely successfully (with patients enjoying a full remission) if they can access the right drugs at the right time. There is still much variability in time to diagnosis and in provision of appropriate medications – the challenge is to ensure that best practice can be rolled out more effectively.

Which changes would substantially improve the quality of healthcare in your country?

There needs to be a greater understanding of the importance of rheumatic diseases in the UK. These conditions are prevalent, may cause significant morbidity (and indeed mortality), cost the nation considerably in reduced productivity and in disability payments – yet many of these conditions can be treated most effectively.

Do you think doctors can make a valuable contribution to healthcare management?  If so how?

Its crucial that doctors are fully engaged in management. We are in the best position to be advocates for our patients but cannot do this effectively without understanding the health care system and take the lead in ensuring this works for the best.

How has the political environment affected your work?

The consequences of the recent change in Government in the UK are likely to be considerable for the National Health Service. This will involve major changes to the work of staff at all levels. It is too early to know the full extent of this – but we all wait with trepidation

What are your interests outside of work?

With so much to do, its hard to find the time for much else apart from relaxing with my family. I travel a lot and especially enjoy taking my children with me. My 10 year old has heard me lecture so much that I suspect she can give my talk for me (and do it better). She has also taken to asking questions at the end of my lecture, which always scares the chairperson of the meeting!

If you were not a doctor, what would you do?

I’m not sure that I would be fit for anything else!

An Unusual Cause of Chronic Dyspnoea

Fadi Seif and Lamia H. Ibrahim

Cite this article as: BJMP 2011;4(1):a408
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A 73 year old lady presented for assessment of her recurrent right sided pleural effusion. She had a history of gallstones and underwent open cholecystectomy.  One month after surgery the patient had recurrent pleural effusion requiring thoracocentesis on a monthly basis. On the chest x-ray, the pleural effusion was seen exclusively on the right side occupying the whole right hemithorax. 

The pleural fluid was transudative on multiple occasions and there was no evidence of malignant cells. Her echocardiography revealed preserved cardiac function. An abdominal ultrasound showed findings of cirrhosis and splenomegaly consistent with portal hypertension.

Image 1

Computerised tomography (CT) of the chest and abdomen revealed a large right-sided pleural effusion and minimal ascites (Image 1). An ultrasound guided paracentesis was performed with difficulty and only 17cc of fluid.was obtained.  The abdominal fluid showed similar consistency as the pleural fluid. The blood workup at the same time was unremarkable.

Image 2

Intra-peritoneal administration of 99mTc-sulphur colloid was attempted but failed in the absence of ascites. Computed tomography with three dimensional reconstruction at the diaphragmatic level revealed a defect in the posterior aspect of the right hemidiaphragm (Image 2 black arrow) and also revealed irregular contours of the liver, an indirect sign of diaphragmatic defect (Image 2 white arrow).

The patient declined any surgical intervention at that point including the option of pleurodesis. She was started on diuretics and a low salt diet with significant improvement. 


Pleural effusion due to hepatic cirrhosis and ascites is well known, but hepatic hydrothorax in the absence of ascites is a rare complication. We report a case of liver cirrhosis with a large and recurring right sided pleural effusion that had an apparent abdominal source in the absence of ascites. We review the characteristics and treatment for hepatic hydrothorax in the absence of ascites.

Hepatic hydrothorax is defined as the presence of significant pleural effusion in a cirrhotic patient without primary pulmonary or cardiac disease1. Postulated mechanisms for the development of pleural effusions in patients with hepatic cirrhosis include: hypoalbuminemia and decreased oncotic pressure leakage of the plasma from the hypertensive azygos vein, lymphatic leak from the thoracic duct, passage of ascitic fluid to the pleural space by way of lymphatic channels in the diaphragm, and transfer of peritoneal fluid directly via diaphragmatic defects2.

The usual unilaterality of hepatic hydrothorax could be attributed to a congenital factor, but not to physiologic mechanisms3. The most likely explanation appears to be that ascitic fluid passes through congenital or acquired fenestrations in the diaphragm directly into the pleural space2. The description of hepatic hydrothorax in the absence of ascites is very rare1. The flow of the ascitic fluid into the pleural space equaled the rate of ascites production in patients with this entity3.

The composition of pleural fluid from hepatic hydrothorax is similar to that of ascitic fluid. Pleural effusions associated with portal hypertension are always transudative1. Nuclear scans can be performed to establish the diagnosis of hepatic hydrothorax with fairly high accuracy. Intra-peritoneal administration of 99mTc-human serum albumin or 99mTc-sulphur colloid can be used to demonstrate the communication between the peritoneal and pleural space. Recent advances in radiological imaging have enabled investigators to examine in detail the diaphragmatic defects responsible for the development of hepatic hydrothorax1.

The management is challenging and frequently associated with poor outcomes in most cases. Dietary restriction of sodium intake and the addition of diuretics is the initial approach. Thoracocentesis can be performed in patients with dyspnoea due to hepatic hydrothorax for immediate relief of symptoms. When thoracocentesis is required too frequently in patients on maximal sodium restriction and optimal diuretics, alternative treatment options must be considered1, 3.

Over the last few years, new insights into the pathogenesis of this entity have lead to improved treatment modalities such as portosystemic shunts (TIPS) and video-assisted thoracoscopy (VATS) for closure of diaphragmatic defects. Both, though temporary  measures, are perhaps the best available bridging to liver transplantation in selected patients with refractory hepatic hydrothorax2, 3.

Competing Interests
None declared
Author Details
Fadi Seif, M.D. Fellow, Pulmonary Critical Care and Sleep Medicine, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine Lamia H. Ibrahim, M.D., FCCP, Director of Asthma Center, Director of Medical Student and Resident Pulmonary Education, Division of Pulmonary, Critical Care and Sleep, University Hospitals Case Medical Center. Assistant Professor of Medicine, Case Western Reserve University School of Medicine, Louis Stokes Cleveland VAMC
CORRESSPONDENCE: Fadi Seif, M.D. Fellow, Pulmonary Critical Care and Sleep Medicine, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine


  1. Kiafar C, Gilani N. Hepatic hydrothorax: Current concepts of pathophysiology and treatment options. Annals of Hepatology 2008; 7(4): 313-320
  2. Mentese BB, Kayhan B,  Görgül A, et al. Hepatic Hydrothorax in the Absence of Ascites. Report of Two Cases and Review of the Mechanism. Digestive Diseases and Sciences 1997; 42(4): 781-788
  3. Gur C,  Ilan Y, Shibolet O. Hepatic hydrothorax – pathophysiology, diagnosis and treatment – review of the literature. Liver International 2004; 24(4): 281-284

COPD Exacerbation with Concurrent Stress Cardiomyopathy: A Case of Double Dyspnoea

Jennifer L. Pham, Steven R Bruhl and Mujeeb Sheikh

Cite this article as: BJMP 2011;4(1):a407
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We present an interesting case of severe dyspnea due to chronic obstructive airway disease exacerbation and upon further evaluation a diagnosis of stress cardiomyopathy was entertained. We highlight a management of this particular case and provide a brief review of stress cardiomyopathy.

Case presentation

A 52 year-old Caucasian male with a history of chronic obstructive airway disease (COPD) presented to the emergency department complaining of progressive shortness of breath. Two days prior, the patient had presented to the ED with similar complaints that resolved with aerosol treatments and the patient was discharged on a metered dose inhaler (MDI).  The patient had been prescribed MDI’s (metered dose inhalers) previously for management of his COPD, but due to financial constraints he had been unable to fill his prescription for the past month. Emergency medical services (EMS) suspected COPD exacerbation and administered 40 mg prednisone IV and two albuterol-ipratropriumnebulisertreatments en route to the hospital, which improved the patient’s breathing symptoms.                                             

Upon arrival to the hospital, his blood pressure was 129/90, respirations 28, pulse 127, and he had an oxygen saturation of 100% on 7L/min. Physical examination revealed increased work of breathing, and wheezes in all lung fields with prolonged expiratory phase. The cardiovascular exam was normal except for tachycardia.  A Routine electrocardiogram (ECG) revealed sinus tachycardia and T wave inversions in anterior leads. Chest x-ray showed old scarring in the left lower lobe. Routine cardiac enzymes showed mild elevation with a serum troponin level of 0.68ng/ml (normal range 0.0ng/ml-0.05ng/ml). The second set of troponin peaked at 1.66 ng/ml (normal 0.0ng/ml-0.05ng/ml). In view of the elevated cardiac enzymes atransthoracicechocardiogram was performed which demonstrated multiple wall motion abnormalities and reduced left ventricular ejection fraction of 25%. Coronary angiography demonstrated normal coronary arteries. Left ventriculography revealed hypokinetc mid-anterior and apical segment with a hypercontractile base with reduced ejection fraction (EF) of around 25% (normal range EF 55-65%)  (Figure 1)


Figure 1. Left ventriculography demonstrating the classic appearance of Takotsubo cardiomyopathy

In light of the systolic dysfunction not in proportion with the degree of coronary artery stenosis and the multiple areas of wall motion abnormalities seen on echocardiogram, the diagnosis of Takotsubo cardiomyopathy (TCMP) was made. The diagnosis was further supported by the presence of ECG changes, troponin elevation, and the added social stresses of being unemployed. Over the course of his stay in hospital, the patient’s breathing improved with oral prednisone, inhaled tiotropium, and fluticasone/salmeterol. The patient was also treated with an angiotension converting enzyme inhibitor (ACE inhibitor), aspirin, statin, and beta-blockers. There were no adverse coronary events during the course of his hospital stay and the patient was discharged after four days. A Follow up echocardiogram after 4 weeks showed normal left ventricular systolic function.


Takotsubo cardiomyopathy (TCMP), also called stress-induced cardiomyopathy, apical ballooning syndrome, or broken heart syndrome, is a transient systolic dysfunction of the ventricles in the absence of significant coronary artery disease. Once thought to be a rare syndrome, TCMP is increasingly being identified in clinical practice, however, the prevalence and incidence are not known. It is estimated that 0.7-2.5% of patients who present with acute coronary syndrome are found to have TCMP1 .The majority of these patients are postmenopausal females, with a mean age of 62-75 years. They may present with chest pain and have a recent history of an emotional stress or severe medical illness. 1

The clinical manifestations of TCMP can mimic those of an acute myocardial infarction. Although, chest pain is a common presenting symptom, patients may also have complaints ofdyspnoeaand arrhythmias. In our casedyspnoeawas the predominant symptom and was easily confused with COPD exacerbation. Recently a few cases of concomitant stress cardiomyopathy with obstructive airway disease have been documented in literature. 2-4 While the pathophysiology of the coexistence of these two disorders is not fully understood, it is thought that both stress induced cardiac dysfunction due to exaggerated sympathetic activation and use of sympathomimetic bronchodilators instigates the myocardial stunning in such patients.  Furthermore, an emotional stressor, such as death of a family member, or a physiological stressor, such as an acute medical illness, is thought to be a trigger for cardiomyopathy. 5 It is believed that the syndrome is not a result of anischemia, but there is some evidence to suggest thatoestrogenlevels may have a role in modulating the sympatho-adrenal outflow in TCMP. In mice models, chronic oestrogen supplementation seemed to have protective effects from exaggerated sympathetic outflow from the heart and brain6 . Postmenopausal women with low levels ofoestrogenmay be more vulnerable to the exaggerated catecholamine release in responses to stressors. 7  

The characteristic finding in TCMP is a transient mid-ventricular or apical ballooning due to a hypokinetic portion seen on echocardiogram or on a left ventriculography. Systolic dysfunction is usually transient, inconsistent to the perfusion area of a single coronary artery, and usually resolves within 4-6 weeks. 8 Additional findings include ECG changes with ST segment deviations in precordial leads being the most common. Cardiac enzymes have been noted to have moderate elevations.9.

As data regarding the treatment of TCMP is limited, medical management mainly consists of symptomatic therapy with aspirin, ACE inhibitors, beta-blockers, and diuretics, also used in acute coronary syndrome.10   Patients who present acutely are treated as acute coronary syndrome and often receive emergency coronary angiography. However, less invasive imaging techniques, such as echocardiograms, should first be examined carefully.  Due to the transient nature of the syndrome, the duration of treatment is unknown with some studies suggesting that there is no benefit with chronic treatment. 11   The prognosis is fairly good, with in hospital mortality rates being reported to range from 0-8%, and recovery of left ventricular function in the majority of patients. 9, 12 

TCMP is difficult to distinguish from acute coronary syndrome on first presentation. Our patient had significant social stress. She presented with severedyspnoeaand was treated for COPD exacerbation. Elevation of cardiac enzymes and ECG changes lead to further evaluation and diagnosis of stress cardiomyopathy. This atypical presentation of TCMP showcases the importance ofutilisingthe routine noninvasive imaging and laboratory values to guide the diagnosis. Furthermore physicians need to maintain a high clinical suspicion for this syndrome.

Competing Interests
None Declared
Author Details
Mujeeb Sheikh, M.D Cardiovascular Fellow, University of Toledo Medical Center, Toledo, OH, 43614 Steven Bruhl, M.D Cardiovascular Fellow, University of Toledo Medical Center, Toledo, OH, 43614 Jennifer L. Pham, B.S ,Fourth year medical student, Medical College of Ohio, Toledo, 43614
CORRESSPONDENCE: Mujeeb Sheikh, M.D Cardiovascular Fellow, University of Toledo Medical Center, Toledo, OH, 43614


1.       Bybee, K.A., et al., Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med, 2004. 141(11): p. 858-65.

2.       Bilan, A., et al., Dyspnea as a dominant clinical manifestation in a patient with takotsubo cardiomyopathy treated for chronic obstructive pulmonary disease and hyperthyroidism. Pol Arch Med Wewn, 2009. 119(4): p. 265-8.

3.       Hernandez Lanchas, C., et al., [Tako-Tsubo syndrome in a patient with exacerbated bronchial asthma]. Rev Clin Esp, 2007. 207(6): p. 291-4.

4.       Saeki, S., et al., [Case of bronchial asthma complicated with Takotsubo cardiomyopathy after frequent epinephrine medication]. Nihon Kokyuki Gakkai Zasshi, 2006. 44(10): p. 701-5.

5.       Tsuchihashi, K., et al., Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina Pectoris-Myocardial Infarction Investigations in Japan. J Am Coll Cardiol, 2001. 38(1): p. 11-8.

6.       Ueyama, T., Emotional stress-induced Tako-tsubo cardiomyopathy: animal model and molecular mechanism. Ann N Y Acad Sci, 2004. 1018: p. 437-44.

7.       Ueyama, T., et al., Catecholamines and estrogen are involved in the pathogenesis of emotional stress-induced acute heart attack. Ann N Y Acad Sci, 2008. 1148: p. 479-85.

8.       Nef, H.M., et al., Mechanisms of stress (Takotsubo) cardiomyopathy. Nat Rev Cardiol. 7(4): p. 187-93.

9.       Banihashemi, M.R. and I.A. Khan, Acute stress-induced cardiomyopathy: a brief observation. Int J Cardiol, 2009. 134(2): p. 273-7.

10.     Cocco, G. and D. Chu, Stress-induced cardiomyopathy: A review. Eur J Intern Med, 2007. 18(5): p. 369-79.

11.     Fazio, G., et al., Chronic pharmacological treatment in takotsubo cardiomyopathy. Int J Cardiol, 2008. 127(1): p. 121-3.

12.     Regnante, R.A., et al., Clinical characteristics and four-year outcomes of patients in the Rhode Island Takotsubo Cardiomyopathy Registry. Am J Cardiol, 2009. 103(7): p. 1015-9.

Community-acquired urinary tract infection in the elderly

Mahesh E, Medha Y, Indumathi V A, Prithvi S Kumar, Mohammed Wasim Khan and Punith K

Cite this article as: BJMP 2011;4(1):a406
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Background: Urinary tract infection (UTI) in the elderly poses a very serious problem. The knowledge of microbiology and antibiotic susceptibility of micro-organisms causing the disease is vital for defining the empirical treatment.  There are no large-scale studies on the same from India.

Aim: To find out the common presenting symptomatology and risk factors associated with UTI and distribution of isolated uropathogens and their resistance pattern.

Settings and design: Prospective study done in a tertiary care centre in Bangalore.

Methods and material: The study included elderly patients aged 65 years and above who were admitted, or visited the outpatient departments in the hospital, and had confirmed UTI.

Results and conclusions: Fever (57/194 - 29.4%) and dysuria (52/194 - 26.8%) were the most common symptoms of UTI. Diabetes Mellitus (DM) was the most common risk factor associated with UTI. Extended Spectrum Beta-Lactamase (ESBL) producing Escherichia coli (E.coli) (93/194 - 47.94%) was the most commonly isolated pathogen. Of the total, 56.2% of the uropathogens showed ESBL positivity. Overall, the highest antibiotic resistance was recorded for Fluoroquinolones (79.9%).

Keywords:  Uropathogen, Elderly, Antibiotic Resistance, ESBL


Urinary tract infection (UTI) is the second most common infectious complaint in geriatric clinics overall, and the most common outpatient complaint caused by bacteria.1 The diagnosis and treatment of UTI in the elderly is not the same as treating UTI in adults. In frail elderly patients with age-associated multiple severe underlying disorders and cognitive impairment, early recognition of bacteraemic UTI and prompt, appropriate treatment are critical in reducing the mortality.2Also, the extensive and inappropriate use of antimicrobial agents has invariably resulted in the development of antibiotic resistance which, in recent years, has become a major problem worldwide.3 The diagnosis and empirical treatment of UTI in the elderly is challenging and a sound knowledge of the prevalent epidemiology of bacteria and their resistance pattern is necessary for the same. However, there is not much information on the aetiology and resistance pattern of UTI in the elderly in India. This study was done to find out the present uropathogen profile causing UTI in our centre and their antibiotic resistance patterns.


Subjects and methods

This prospective study was done at our tertiary care centre from January to December 2008. The study included all patients who were admitted or visited the outpatient departments in the hospital with symptoms of UTI during the study period and had UTI confirmed by positive urine culture reports. Only one sample from each subject was considered. Subjects with clinical symptoms of UTI but no growth on culture were excluded from final analysis. Subjects who were treated with another antimicrobial within the previous 48 hours, or within 24 hours if only a single dose and in the presence of an appropriate positive culture and ileal loops or vesicoureteral reflux were also excluded from the study. Complete data regarding demography, sex preponderance, associated symptoms, pathogenic organisms causing UTI and their antibiotic resistance were collected.

Overall, 194 subjects were included in the study (male: 116, female: 78). The mean age of the study population was 73.54±7.19 years, ranging between the ages of 65 and 96. The distribution of patients according to gender across various age groups is given in table 1. A general trend of more male subject enrolment was seen across all the age groups. 

Table 1. Age and gender distribution of complicated and uncomplicated urinary tract infection.

Age group












































Isolation and identification of uropathogens

A clean catch midstream specimen, or suprapubic aspirate in subjects who were unable to give the former, was collected in a sterile, wide-mouth, leak-proof container to hold approximately 50ml from these subjects. Using a calibrated loop method of loop diameter 4 mm, 10 µL of the uncentrifuged specimen was transferred onto the agar plate and streak, using the modified Mayo’s technique without flaming the loop for isolation, and incubated at 35- 370C for 24 hours. A specimen was considered positive for UTI if a single organism was cultured at a concentration of >105 Colony Forming Units/ml. The Gram-positive and Gram-negative organisms culture isolates were further identified by using various biochemical reactions up to genus/species level wherever applicable.


Antibiotic sensitivity testing

In the presence of any potential growth, antibiotic sensitivity testing was done by the Modified Kirby-Bauer disc diffusion method according to the Clinical and Laboratory Standards Institute (CLSI) guidelines.4 The antibiotics tested were Imepenem, Meropenem, Ciprofloxacin, Ofloxacin, Norfloxacin, Amikacin, Gentamicin, Nitrofurantoin and Cotrimoxazole (Pathoteq Labs, India).


Extended Spectrum Beta-Lactamase (ESBL) detection

The screening for ESBL was done using Cefpodoxime (<17mm), Ceftazidime (<22mm), Aztreonam (<27mm), Cefotaxime (<27mm) and Ceftriaxone (<25mm). If the organisms showed the zone of inhibition lower than the minimum for any antibiotic disc, ESBL positivity was suspected. The phenotypic confirmation was done by testing the strain against Ceftazidime (Ca) and Ceftazidime/Clavulanic Acid. A > 5mm diameter of the zone of inhibition for Ceftazidime/Clavulanic Acid in comparison to Ceftazidime was considered indicative of ESBL production. Escherichia coli (E. coli) ATCC 25922 was used as ESBL negative and Klebsiella pneumoniae (K. pneumoniae) 700603 was used as ESBL positive reference strain.4


Statistical analysis

Descriptive statistics (totals, means, percentages, and standard deviations) were conducted using the statistical software package - SPSS Version 16.0 (SPSS Inc., Chicago, USA). Age, gender, organisms causing UTI, their antibiotic sensitivity and resistance, symptomatology of these subjects, and risk factors for UTI were included in the analysis and the results presented in tables and figures.



Fever (57/194 - 29.4%) and dysuria (52/194 - 26.8%) were common symptoms of most UTI patients (Fig. 1). Diabetes mellitus (DM) and recent uro-genital instrumentation were the most common risk factors associated with UTI in the present study (Table 2). The organism profile and their antibiotic resistance profile were similar in patients with or without DM.

Figure 1. Various symptomatologies seen in patients with urinary tract infection during the initial presentation


Table 2. Frequency of various risk factors in subjects with urinary tract infection.

Risk Factor






Diabetes Mellitus






Recent history of uro-genital Instrumentation



Recurrent  urinary tract infection



Renal stones





E. coli (138/194 - 71.1%) was the most commonly isolated pathogen responsible for UTI in the present study (Figure 2). 56.2% of the total infection was caused by ESBL positive organisms. The antimicrobial potency and spectrum for nine selected antimicrobial agents (Imepenem, Meropenem, Ciprofloxacin, Norfloxacin, Ofloxacin, Gentamicin, Amikacin, Nitrofurantoin and Cotrimoxazole) against the uropathogens were studied. The highest and least antibiotic resistance was noted against fluoroquinolones (79.9%) and carbapenems (3.61%) respectively (Fig. 3).

Figure 2. Frequency and distribution pattern of urinary tract infection pathogens and percentage Extended Spectrum Beta-Lactamase (ESBL) production.


Figure 3. Resistance pattern to various antibiotics of the uropathogens



While increased frequency and dysuria are usual symptoms of UTI, uncertainty looms around the same as these symptoms can be masked by catheterisation, or be common and chronic in the elderly even in the absence of UTI.5-10Fever was the most common symptom of UTI in the present study as with similar studies worldwide.11-13 Studies have found that the elderly do not lack a febrile response; that an elevated temperature was the most common initial symptom, a marker for a serious infection, and the most important clinical indicator for antibiotic treatment.14-16 Whitelaw et al17 reported that a delay in interpreting fever as a symptom of UTI led to a high mortality rate in the elderly within 24 hours of admission.

Diabetes isconsidered as an important risk factor for UTI with manyauthors having defined UTI in patients with DM as complicated when the UTI is symptomatic.18-19 However, the authors did not find that DM influenced the organism profile and their antibiotic resistance in the present study. Bonadio et al20 studied the influence of DM on the spectrum of uropathogens and antimicrobial resistance in elderly adult patients with asymptomatic UTI (mostly hospital-acquired). They found that DM per se did not seem to influence the isolation rate of different uropathogens and their susceptibility patterns to antimicrobials. These findings indicate that, although DM is a known immunomodulator, the role played by the same in altering the antibiotic resistance is minimal compared to recent invasive procedures.

Although the uropathogen profile of the present study resembles similar studies worldwide, the antibiotic resistance of these organisms was unusually high.2, 21 Cotrimoxazole is the recommended drug for treating UTI. However, more than one third of the study subjects were resistant to the first-line drug. 79.9% of the uropathogens were resistant to fluoroquinolones, which are considered as the second-line drug.  As prior fluoroquinolone use is a known risk factor for fluoroquinolone-resistantE. coli infection, it is plausible that frequent fluoroquinolone prescriptions may be contributing to the observed resistance.22-23 Aypak et al 24 found that treatment durations were statistically longer than the recommended three-day course when patients were empirically treated with fluoroquinolones due to increased resistance rates, and suggested to discourage the empirical use of fluoroquinolones in UTI.

The most troublesome finding of the present study is that ESBL-positive organisms accounted for 56.2% of the total infection. Not much information on ESBL-producing organisms causing UTI is available from India and most of these reports are from the younger population. The prevalence of ESBL-positive UTI in these studies varied between 26.6% and 48.3%.25-26 To the best of our knowledge, this is the highest ever reported prevalence of ESBL-positive UTI in the elderly worldwide. ESBL-producing organisms are frequently resistant to many of the antimicrobial agents usually recommended for the treatment. As lesser new antibiotics are available for their management, we need to be concerned of this issue in years to come especially in tertiary care centres.  A unified antibiotic protocol is necessary to limit the morbidity and mortality associated with inappropriate and under-treatment of UTI.

The limitations of the present study were that altered mental status was not considered as one of the clinical manifestations of UTI in the elderly, which could have mitigated the total number of study subjects included in the study.  In addition, the phenotypic confirmation of ESBL-positive organisms was done using only Ceftazidime/Clavulanic Acid and not Cefotaxime/Clavulanic Acid as per the latest CLSI guidelines. As a result, there may be under-reporting of the incidence of ESBL organisms in the present study.

In conclusion, we report a significantly high resistance to common antibiotics among the uropathogens in the present study. Furthermore, the very high rate of ESBL-positive UTI is of concern, and monitoring for the same is necessary to prevent treatment failure and increased morbidity and mortality with UTI.

Competing Interests
None declared
Author Details
MAHESH E, Associate Professor, Department Of Nephrology, M S Ramaiah Medical College MEDHA Y, Professor And Head, Department Of Medicine, M S Ramaiah Medical College INDUMATHI V A, Consultant Microbiologist, Gokula Metropolis Clinical Labs, M S Ramaiah Medical College PRITHVI S KUMAR, MOHAMMED WASIM KHAN, PUNITH K, Residents, M S Ramaiah Medical College
CORRESSPONDENCE: Punith K, Address: No. 28/18, 19th Main Road, MC Layout, Vijaynagar, Bangalore-560040, India


  1. O'Donnell J, Gelone S, Abrutyn E. Selecting drug regimens for urinary tract infection: current recommendations. Infect Med 2002;19:14-22.
  2. Tal S, Guller V, Levi S, Bardenstein R, Berger D, Gurevich I et al. Profile and prognosis of febrile elderly patients with bacteremic urinary tract infection. J Infect 2005;50:296-305.
  3. Goldstein FW. Antibiotic susceptibility of bacterial strains isolated from patients with community-acquired urinary tract infections in France. Multicentre Study Group. Eur J Clin Microbiol Infect Dis 2000;19:112-7.
  4. Clinical and Laboratory Standards Institute.  Performance standards for antimicrobial susceptibility testing; 16th informational supplement. M100-S16. Clinical and Laboratory Standards Institute, Wayne, PA, 2006.
  5. Nicolle L. Urinary tract infection in the elderly.J Antimicrob Chemother 1994;33: 99-109.
  6.  Fune L, Shua-Haim J, Ross J, Frank E. Infectious diseases in the elderly. Clinical Geriatrics 1998;6:31-50.
  7. Beier MT. Management of Urinary tract infections in the nursing home elderly: a proposed algorithmic approach. Int J Antimicrob Agents 1999;11:275-84.
  8. 8.Nicolle LE; SHEA Long-Term-Care-Committee. Urinary tract infections in long-term-care facilities. Infect Control Hosp Epidemiol 2001;22:167-75.
  9. 9.Baldassarre JS, Kaye D. Special problems of urinary tract infection in the elderly. Med Clin North Am 1991;75:375-90.
  10. Rudman D, Hontanosas A, Cohen Z, Mattson DE.Clinical correlates of bacteremia in a Veterans Administration extended care facility. J Am Geriatr Soc 1988;36:726-32.
  11. Meyers BR, Sherman E, Mendelson MH, Velasquez G, Srulevitch-Chin E, Hubbard M, Hirschman SZ. Bloodstream infections in the elderly. Am J Med1989;86:379-84.
  12. Richardson JP, Hricz L. Risk factors for the development of bacteremia in nursing home patients. Arch Fam Med1995;4:785-9.
  13. Chassagne P, Perol MB, Doucet J, Trivalle C, Ménard JF, Manchon ND et al. Is presentation of bacteremia in the elderly the same as in younger patients? Am J Med 1996;100:65-70.
  14. Katz PR, Beam TR Jr, Brand F, Boyce K. Antibiotic use in the nursing home. Physician practice patterns. Arch Intern Med 1990;150:1465-8.
  15. Yoshikawa TT, Norman DC. Approach to fever and infection in the nursing home. J Am Geriatr Soc 1996;44:74-82.
  16. Alessi CA, Harker JO.  A prospective study of acute illness in the nursing home. Aging (Milano) 1998;10:479-89.
  17. Whitelaw DA, Rayner BL, Willcox PA. Community-acquired bacteremia in the elderly: a prospective study of 121 cases. J Am Geriatr Soc. 1992 Oct;40(10):996-1000
  18. Stapleton A. Urinary tract infections in patients with diabetes. Am J Med. 2002 Jul 8;113 Suppl 1A:80S-84S 
  19. Ronald A, Harding G. Complicated urinary tract infections. Infect Dis Clin North Am 1997;11:583-592.
  20.  Bonadio, M., Costarelli, S., Morelli, G., Tartaglia, T. The influence of diabetes mellitus on the spectrum of uropathogens and the antimicrobial resistance in elderly adult patients with urinary tract infection. BMC Infect Dis 2006;6:54.
  21. Ackermann RJ, Monroe PW. Bacteremic urinary tract infection in older people. J Am Geriatr Soc 1996;44:927-33.
  22. Cohen AE, Lautenbach E, Morales KH, Linkin DR. Fluoroquinolone-resistant Escherichia coli in the long-term care setting. Am J Med 2006;119:958-63
  23. Das, R., Perrelli, E., Towle, V., Van Ness PH., Juthani-Mehta, M. Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing Home Residents. Infect Control Hosp Epidemiol 2009;30: 1116-9.
  24. Aypak, C., Altunsoy, A., Düzgün, N. Empiric antibiotic therapy in acute uncomplicated urinary tract infections and fluoroquinolone resistance: a prospective observational study. Ann Clin Microbiol Antimicrob 2009;8:27.
  25. Khurana S, Taneja N, Sharma M. Extended spectrum beta-lactamase mediated resistance in urinary tract isolates of family Enterobacteriaceae. Indian J Med Res 2002;116:145-9.
  26. Tankhiwale SS, Jalgaonkar SV, Ahamad S, Hassani U. Evaluation of extended spectrum beta lactamase in urinary isolates. Indian J Med Res 2004;120:553-6.

Diffuse Alveolar Haemorrhage with ANCA associated vaculitis-review of Literature

Fadi Hammoudeh, Muhammad K. Perwaiz, Setu Patolia, Frances M. Schmidt, Narayan Neupane,Neerja Gulati, Danilo Enriquez, Joseph Quist, Mehjabeen Zahir and Eneh Kennedy

Cite this article as: BJMP 2011;4(1):a402
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Patients with Wegner’s Granulomatosis often present with diffuse alveolar haemorrhage alongside the classical triad of haemoptysis, anaemia and progressive dyspnoea. The diagnosis is confirmed by bronchoalveolar lavage with serial aspirated aliquots of fluid revealing persistently bloody returns. Lung biopsy is very helpful if it shows granulomatous inflammation and vasculitis however it lacks sensitivity and specificity. Studies suggest that the detection of antineutrophilcytoplasmic antibodies (ANCA) along with Proteinase-3 can substitute for biopsy for the diagnosis of Wegner’s Granulomatosis in patients who present with diffuse alveolar haemorrhage.

Keywords:  Diffuse Alveolar Haemorrhage (DAH), Wegener&rsquo;s Granulomatosis (WG), Anti-neutrophil cytoplasmic antibodies (ANCA), classical antineutrophil cytoplasmic antibodies (C-ANCA), anti proteinas-3 (PR3)


Diffuse Alveolar Haemorrhage (DAH) is a rare but serious and frequently life-threatening complication of a variety of conditions. DAH refers to a clinical syndrome resulting from injury to the alveolar capillaries, arterioles, and venules leading to red blood cell accumulation in the distal air spaces because of leakage of alveolar capillaries. Most cases of DAH are caused by capillaritis associated with systemic autoimmune diseases such as ANCA-associated vasculitis, anti-GBM disease, and systemic lupus erythematosus.1 Treatment is with immunosuppressants for patients with autoimmune causes and respiratory support if needed.
Diffuse alveolar haemorrhage syndrome is not a specific entity but is a syndrome that suggests a differential diagnosis and a specific sequence of testing.
Many disorders can cause alveolar haemorrhage; they include
  1. Autoimmune disorders (e.g., systemic vasculitides, Goodpasture's syndrome, antiphospholipid antibody syndrome)
  2. Pulmonary infections (e.g., invasive aspergillosis, hantavirus infection)
  3. Toxic exposures (e.g., trimellitic anhydride, isocyanates, crack cocaine, certain pesticides)
  4. Drug reactions (e.g., propylthiouracil, diphenylhydantoin, amiodarone, methotrexate, , nitrofurantoin, bleomycin, montelukast, infliximab
  5. Cardiac disorders (e.g., mitral stenosis)
  6. Coagulation disorders caused by diseases or anticoagulant drugs
  7. Isolated pauci-immune pulmonary capillaritis
  8. Idiopathic pulmonary haemosiderosis
  9. Bone marrow or solid organ transplantation.
Clinical Presentation
The clinical presentation of diffuse alveolar haemorrhage may reflect either alveolar bleeding alone or features of the underlying cause (e.g., haematuria in Wegener granulomatosis, arthritis in systemic lupus erythematosus). Hence, its recognition requires a high degree of suspicion. Some patients present with severe acute respiratory distress requiring mechanical ventilation. However, dyspnoea, cough, and fever are the common initial symptoms and are most often acute or subacute (i.e., present for less than a week). The fever is usually due to the underlying cause, such as lupus. Haemoptysis may be absent at the time of presentation in up to a third of patients because the total alveolar volume is large and can absorb large amounts of blood, without extending more proximally into the airways. Apparent haemoptysis, if present, must be differentiated from haematemesis or pseudohaemoptysis (alveolar flooding with fluid that resembles blood, as in Serratia marcescens pneumonia, in which the reddish hue of the infecting organism can create the impression of alveolar bleeding).
Chest X-ray and Chest CT scan typically shows bilateral infiltrates (figure 1 &2)
Figure 1
Figure 2
DAH & ANCA associated vasculitides
Wegener's Granulomatosis (WG) is an uncommon disease that affects about 1 in 20,000 to 1 in 30,000 people.  WG is defined by the triad of granulomatous inflammation of the respiratory tract, vasculitis of small to medium-size vessels and necrotizing glomerulonephritis. The onset of WG may be indolent with few symptoms, or it may have a rapid and severe onset. About 90% of patients have symptoms of a cold or runny nose or sinusitis that fail to respond to the usual therapeutic measures and last considerably longer than the usual upper respiratory tract infection. Other symptoms include nasal membrane ulcerations and crusting, saddle-nose deformity, inflammation of the ear with hearing problems, inflammation of the eye with sight problems, cough (with or without the presence of blood), pleuritis, (inflammation of the lining of the lung), rash and/or skin sores, fever, lethargy weakness, loss of appetite, weight loss, arthritic joint pain, night sweats, and haematuria which may or may not be indicated by a change in urine colour.Thediagnosis of WG depends on the combination of clinical presentation, serological markers, and histopathological findings. ANCA is a sensitive and specific marker for ANCA-associated systemic vasculitis. In a study done by U. Schönermarck et al,9 624 ANCA- positive patients were included, (C-ANCA: 333, P-ANCA: 291). C-ANCA were highly sensitive (81%) and specific (99.5%) for WG, resulting in high positive predictive value (PPV) (94%). Many studies showed that combining proteinase 3 (PR3) and C-ANCA results(C-ANCA/PR3) increases specificity and Positive Predictive Value close to 100%, but reduces sensitivity close to 70%.10,11,13,14 In summary, the presence of C-ANCA & PR3 antibody is highly suggestive of WG. This led to reevaluation of the role of biopsy for diagnosis of WG in multiple studies.4, 14, 15
The site of biopsy is dependent upon the clinical status. A nasal or sinus biopsy may be the least invasive way to diagnose WG. Renal biopsy is helpful if there is evidence of renal insufficiency or glomerulonephritis. A lung biopsy should only be considered if potentially diagnostic tissue cannot be obtained from any other site.1 Hoffman et al performed a total of 82 open lung biopsies in patients with small vessel vasculitis of which 89% showed evidence of combined vasculitis and necrosis, granulomas and necrosis were found in 90%.16 59 transbronchial biopsies were performed in 48 patients and only four specimens had evidence of vasculitis and granulomas were identified in an additional three. Thus, the role of transbronchial biopsies in these patients is limited and open lung biopsies are more informative but carry a higher morbidity and mortality.
The incidence of DAH has beenreported as between 7-45% in Wegner’s Granulomatosis (WG), and 10-30% in Microscopic Polyangitis (MPA).3, 5, 6 The lungs are the most commonly affected organ in WG with evidence of involvement in over 90% of patients during the course of their disease; in 9% it is the only organ affected. 5,7 In MPA lung involvement is less common than inWG, and occurs in up to 50% of cases during the course of the disease.8 Pulmonary involvement ranges from subclinical changes on high resolution computed tomography to devastating haemoptysis. Approximately 5% of patients will have a fulminant presentation requiring assisted ventilation.
Patients with DAH with or without glomerulonephritis, who are found to have ANCA positive can be generally assumed to have WG or MPA. The type of ANCA (PR3-ANCA or MPO-ANCA) found is irrelevant with respect to the initial management of this patients.1 The backbone of therapy is the early identification of disease followed by the rapid induction of disease control with immunosuppression. Early recognition is crucial, because the prompt institution of supportive measures and immunosuppressive therapy is required for survival. The intensity of the initial treatment depends on the severity of the disease. Based on the European Vasculitis Study Group (EUVAS), which categorized the patients in groups according to the severity of their disease, the presence of DAH put the patient in the severe disease group.17 The management of these patients is a combination of corticosteroid and cyclophospamide. S.L Hogan showed that cyclophosphamide reduces mortality and increase the likelihood of inducing remission in patients with ANCA-associated vasculitis. 18
DAH is animportant cause of morbidity and mortality in ANCA- associated vasculitis, the mortality rate may reach 66%, which is six times greater than vasculitis without alveolar hemorrhage.3,19,20,21 Based on the high mortality rate with DAH in ANCA-associated vasculitis, and reduction in mortality shown with cyclophosphamide, treatment with cyclophosphamide should be started as early as possible, based on the clinical presentation and the presence of ANCA, without waiting histological confirmation.
DAH leading to acute respiratory distress syndrome is a rare and life threatening condition in adults with ANCA positive vasculitis. Patients with DAH with or without glomerulonephritis, who are found to have ANCA positive can be generally assumed to have WG or MPA, and diagnostic lung biopsy may be deferred. Early institution of treatment with prednisone and cyclophosphamide can significantly reduce morbidity and mortality.
Key points
1.      Patients with Wegner’s Granulomatosis often present with diffuse alveolar haemorrhage. These patients must be treated promptly as delay in treatment results in high morbidity and mortality.
2.      Lung biopsy is very helpful if it shows granulomatous inflammation and vasculitis however it lacks sensitivity and specificity.
3.      Detection of C-ANCA with Proteinase-3 can substitute for biopsy in the diagnosis of WG in patients who present with diffuse alveolar haemorrhage.

Competing Interests
None declared
Author Details
<p> Fadi Hammoudeh MD,&nbsp;Muhammad K. Perwaiz MD, Setu Patolia MD,&nbsp;Frances M. Schmidt MD,&nbsp;Narayan Neupane, MD,&nbsp;Neerja Gulati MD,&nbsp;Danilo Enriquez MD,&nbsp;Joseph Quist,MD&nbsp;Mehjabeen Zahir MD, Eneh Kennedy MD, - Interfaith Medical Center at 1545 Atlantic Avenue Brooklyn, NY</p>
CORRESSPONDENCE: Muhammad K. Perwaiz MD, Fellow pulmonary department, Interfaith medical center at 1545 Atlantic Avenue Brooklyn, NY


1.  Specks U. Diffuse alveolar haemorrhage syndromes. Curr Opin Rheumatol 2001; 13:12-17.2.  Travis W. Colby T. Lombard C, et al: A clinicopathologic study of 34 cases of diffuse pulmonary haemorrhage with lung biopsy confirmation. Am J Surg Pathol 1990 ;14:11123.  D. R. Thickett, A. G. Richter, N. Nathani, G. D. Perkins and L. HarperPulmonary manifestations of anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis.  Rheumatology 2006;45:261–2684.  Travis WD, Hoffman GS, Leavitt RY et al. Surgical pathology of the lung in Wegener's granulomatosis. Review of 87 open lung biopsies from 67 patients. Am J Surg Pathol. 1991;15(4):315-335.  J F Cordier, D Valeyre, L Guillevin, R Loire and J M Brechot Pulmonary Wegener's granulomatosis. A clinical and imaging study of 77 cases. Chest 1990; 97: 906-9126.  S J HAWORTH, C 0 S SAVAGE, D CARR, J M B HUGHES, A J REES Pulmonary haemorrhage complicating Wegener's granulomatosis and microscopic polyarteritis British Medical Journal.  1985;290(15);1775-17787.  Aine Burns Pulmonary Vasculitis Thorax 1998; 53:220–2278.  Octavian C. Ioachimescu. Diffuse alveolar haemorrhage: Diagnosing it and finding the cause. Cleveland Clinic Journal of Medicine .2008;75(4): 258-2809.  U. Schönermarck, P. Lamprecht, E. Csernok, W. L. Gross. Prevalence and spectrum of rheumatic diseases associated with proteinase 3-antineutrophil cytoplasmic antibodies (ANCA) and myeloperoxidase-ANCA. Rheumatology 2001;40:178-18410.  Langford CA. Wegener granulomatosis. Am J Med Sci 2001;321:76-82.11.  Falk RJ, Jennette JC. ANCA small-vessel vasculitis. J Am Soc Nephrol 1997; 8:314-22.12.  Hagen EC, Daha MR, Hermans J et al. Diagnostic value of standardized assays for anti neutrophil cytoplasmic antibodies in idiopathic systemic vasculitis. EC/BCR Project for ANCA Assay Standardization Kidney Int. 1998;53(3):743–53.13.  Moosig F, Lamprecht P, Gross WL. Wegener's Granulomatosis: the current view. Clin Rev Allergy Immunol.  2008;35(1-2):19-2114.  Bosch X, Guilabert A, Espinosa G, et al. Treatment of antineutrophil cytoplasmic antibody associated vasculitis: a systematic review. JAMA. 2007; 298(6):655–6915.  Mar EJ, Matsubara O, Nelia S. Tan-Liu et al. The pulmonary biopsy in the early diagnosis of Wegener's (pathergic) granulomatosis: A study based on 35 open lung biopsies. Hum Pathol. 1988;19(9):1065-7116.  Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener’s granulomatosis: an analysis of 158 patients. Ann InternMed 1992;116:488–9817.  Stephen K. Frankel, Gregory P. Cosgrove, Aryeh Fischer, Richard T. Meehan and Kevin K. Brown Update in the Diagnosis and Management of Pulmonary Vasculitis Chest 2006;129;452-46518.  SL Hogan, PH Nachman, AS Wilkman, JC Jennette and RJ Falk Prognostic markers in patients with antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis Journal of the American Society of Nephrology.1996;7:23-3219.  Gisele Zandman-Goddard MD Diffuse Alveolar Haemorrhage in Autoimmune Diseases. IMAJ 2002;4:461-46220.  Lin Y, Zheng W, Tian X, Zhang X, Zhang F, Dong Y. Antineutrophil cytoplasmic antibody-associated vasculitis complicated with diffuse alveolar haemorrhage: a study of 12 cases. J Clin Rheumatol. 2009;15(7):341-4.21.  Chen GX, Dong Y, Ju ZB . A clinical analysis of 32 patients with diffuse alveolar haemorrhage in diffuse connective tissue diseases. Zhonghua Nei Ke Za Zhi. 2008;47(5):362-5

Painless aortic dissection presenting with congestive heart failure

Usman Ali, Wai Hang Cheung and Ashis Banerjee

Cite this article as: BJMP 2011;4(1):a401
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A 44 year old man, previously in good health, presented with congestive heart failure, the onset of which was probably four weeks previously. A diagnostic label of community acquired pneumonia led to delay in the diagnosis of type A aortic dissection.

This required surgical management which resulted in a good outcome. The absence of chest pain may have contributed to the delay in diagnosis. Aortic dissection should form part of the differential diagnosis of unexplained acute congestive heart failure. 

Case History

A 44 year old male presented to the emergency department complaining of shortness of breath. The symptoms had commenced suddenly four weeks ago. He had been breathless at rest, and subsequently developed a productive cough with white sputum. He denied chest pain. He was known to have the sickle cell trait but was otherwise in good health. He was a non-smoker.
Since the onset of symptoms, and prior to this admission, the patient presented to two different emergency departments. The working diagnosis was, and remained, community acquired pneumonia. On initial presentation empirical treatment for a community acquired pneumonia was commenced. Failure to improve resulted in additional cover for atypical organisms and the prescription of a short course of steroids on the subsequent admissions.
Initial observations revealed the patient was tachypnoeic and tachycardic, with a respiratory rate of 25 breaths per minute, heart rate of 114 beats per minute. He was apyrexial (temperature of 36.5°C ). Pulse oximetry showed an oxygen saturation of 94% on room air. His blood pressure was recorded as 183/99 millimetres of mercury.
On examination large volume peripheral pulses, raised jugular venous pressure (5 cm), bi-basal crepitations, and bilateral ankle oedema were elicited/identified. Auscultation of the heart revealed a loud diastolic murmur audible throughout the praecordium.
A 12 lead ECG showed normal sinus rhythm, normal axis and left ventricular hypertrophy. Arterial blood gas analysis on room air showed a pH of 7.46, pa02 9.6 kPa, pCO2 4.3 kPa, HCO3 23.8 mmol/L, BE + 0.8 and lactate of 0.7 mmol/L. Routine venous blood tests did not identify any elevated markers of infection or inflammation. A chest radiograph (Figure 1) showed cardiomegaly and pulmonary oedema.
Figure 1
The patient was administered oxygen and given a diuretic to improve his ventilation.
The working diagnosis was congestive cardiac failure in the presence of what was presumed to be a new murmur. Urgent echocardiography revealed an aortic root of 6.2cm diameter at sinus level, with an evident dissection flap. There was no obvious haematoma. Severe free flowing aortic regurgitation, a dilated hyperdynamic left ventricle and a 0.7 cm diameter pericardial effusion anteriorly were also noted. It was concluded that the patient had a sealed 7cm type A aortic dissection. This was confirmed by a CT scan (Figure 2).
Figure 2
Large bore venous access was obtained and an intravenous beta blocker (Labetalol) administered. Urgent transfer to a tertiary cardio-thoracic surgical centre was made. He underwent aortic root and valve replacement, along with coronary artery bypass grafting to the right coronary artery using a reversed long saphenous vein graft. Postoperatively, he was anticoagulated on Warfarin, and was also placed on beta blockade therapy (Bisoprolol), a diuretic (Frusemide), an ACE inhibitor (Ramipril), and a statin (Simvastatin).
Aortic dissection is a medical emergency. If left unrecognised or untreated mortality can be as high as 80% in two weeks, or 90% within three months1,2. 96 % of patients with aortic dissection present primarily with chest pain. The remaining 10% present with symptoms secondary to impairment of blood supply to other organ systems3. Dissections involving the ascending aorta present with retrosternal chest pain, while interscapular pain suggests involvement of the descending aorta. Pleuritic pain may indicate haemorrhage in the pericardial sac, with the potential for acute cardiac tamponade.
Only 6% of aortic dissections present with acute congestive cardiac failure. Patients presenting with aortic dissection and congestive cardiac failure are more likely to present without chest pain and have a valvular abnormality. When chest pain is present, the pain is more often mild and less likely to be abrupt in onset. Patients are less likely to be hypertensive on presentation and more likely to present in shock. These patients are more likely to have Stanford type A dissection . Congestive cardiac failure does lead to a delay in surgical intervention4.
Congestive cardiac failure is usually due to aortic regurgitation from aortic valve disease, incomplete aortic leaflet closure, or aortic valve disruption. In the setting of unexplained cardiac failure aortic dissection should be considered, especially when an aortic regurgitant murmur has been detected clinically. Heart failure has been associated with supravalvular aortic stenosis in the presence of a painless type A dissection, in a patient presenting with persistent cough5. Rupture of aortic dissection into the right atrium, right ventricle, or main pulmonary artery may lead to a left to right shunt and congestive heart failure6.
Painless aortic dissection has been recorded in other contexts, particularly with chronic dissection and in patients with Marfan’s syndrome.The absence of chest pain should not exclude aortic dissection.

Competing Interests
<p> None declared</p>
Author Details
<p> Usman Ali, MB,BS FY2 doctor, Wai Hang Cheung, MB,BS ST3 in Medicine, Ashis Banerjee, MS, FRCS, FCEM Consultant, Emergency Department Chase Farm Hospital, Enfield</p>
CORRESSPONDENCE: <p> Ashis Banerjee, Consultant/ lead clinician in emergency medicine Chase Farm Hospital, The Ridgeway, Enfield EN2 8JL, Middlesex</p>


1. Hirst AE, Johns VJ, Kime SW, Dissecting aneurysm of the aorta. A review of 505 cases. Medicine 1958; 37:217-279

2. Harris PD, Malm JR,  The management of acute dissection of the thoracic aorta. Am Heart J 1969; 78: 419-422

3. Link MS, Pletrzak MP, Aortic dissection presenting as superior vena cava syndrome. Am J Emerg Med 1994; 12:326-328

4. Januzzi, JL, Eagle KA, Cooper JV, Fang J, Sechtem U, Mymel T, Evangelista A, Oh JK, Llovet A, O’Gara PT, Nienaber CA, Isselbacher EM: Acute aortic dissection presenting with congestive heart failure: results from the International Registry of Acute Aortic Dissection. J AM Coll Cardiol. 2005,46:733-735

5. Sakamoto, H, Watanabe, Y, Sugimori, H, Heart failure due to severe supravalvular aortic stenosis in painless type A aortic dissection. Ann Thorac Surg, 2008, 85: 1441-1443

6. Spier, LN, Hall, MH, Nelson, RL, et al. Aortic dissection: rupture into right ventricle and right pulmonary artery. Ann Thorac Surg,1995, 59: 1017-1019

To ‘D’ or not to ‘D’ in the older person, that is the question.

John Agens

Cite this article as: BJMP 2010;3(4):a352
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In anticipation of new recommendations from the Institute of Medicine and others, it behooves physicians and healthcare providers to review their knowledge base concerning adequate vitamin D intake for fall and fracture prevention in the elderly. There is enough new data for the Institute of Medicine to consider a new Dietary Reference Intake, or DRI, for vitamin D.1 A recent review by Bischoff-Ferrari et al, of numerous randomized controlled trials of vitamin D supplementation in older persons, concluded that both falls and fractures could be prevented. In addition, a dose-response relationship suggested that the optimal supplementation dose is 700 IU to 1000 IU per day.2 Epidemiologic associations between low vitamin D status and various cancers has led some to recommend balancing risk and benefit of moderate ultraviolet light (UV) exposure against complete UV protection for prevention of skin cancer.3 Others have reviewed the epidemiologic evidence for vitamin D supplementation in treatment of hypertension and prevention of cardiovascular disease.4 These epidemiologic studies are tantalizing, yet the evidence is not sufficient to support a causal relationship in making decisions about vitamin D supplementation for the prevention of cancer and cardiovascular disease. I will limit my editorial comments to preventing falls and fractures.

I would suggest looking at potential short- and long-term risks as well as the benefits of any intervention. What evidence do we have for the risks of vitamin D use for prevention? One recent study using a single dose of 500,000 IU of vitamin D daily showed an increased relative risk of fractures,5 but the dose of vitamin D in that study was far higher than other randomized controlled trials. Bischoff-Ferrari et al reviewed documented cases of hypercalcaemia in the randomized controlled trials;2 those authors add that only one trial reported nephrolithiasis, the Women’s Health Initiative.6 It is noteworthy that only the self-reported vitamin D and calcium dose was determined in that study, not the vitamin D status of the subjects. My opinion is that hypercalcaemia is uncommon and its complications are rare.
Many interventions that are routinely recommended for the older person probably have higher risks than the 700 IU to 1000 IU of vitamin D per day suggested by the evidence. Medications for hyperlipidaemia are one case in point; antihypertensives are another. Both are considered relatively safe and effective in primary and secondary prevention of cardiovascular disease. The long-term risks of the supplementation of 700 IU to 1000 IU of vitamin D are not well known compared to those long-term risks associated with lipid-lowering drugs or antihypertensives. On the other hand, some older persons at increased fall risk have more immediate threats to their health from a fall or fracture than any long-term risks of vitamin D supplementation. Given the detrimental consequences of falls and fractures in the elderly, the risks of vitamin D supplementation may be worth it. 




Competing Interests
None declared
Author Details
JOHN AGENS MD, FACP. Associate Professor Geriatrics, Florida State University College of Medicine, 1115 West Call Street Suite 3140- H, Tallahassee, Florida 32306-4300
CORRESSPONDENCE: JOHN AGENS MD, FACP. Associate Professor Geriatrics, Florida State University College of Medicine, 1115 West Call Street Suite 3140- H, Tallahassee, Florida 32306-4300


1.  Yetley EA, Brulé D, Cheney MC et al. Dietary reference intakes for vitamin D: justification for a review of the 1997 values. The Am J Clin Nutr. 2009 Mar;89(3):719-727.

2.   Bischoff-Ferrari HA, Shao A, Dawson-Hughes B et al. Benefit-risk assessment of vitamin D supplementation. Osteoporosis Int. 2010 Jul;21(7):1121-1132.
3.   Zeeb H, Greinert R. The role of vitamin D in cancer prevention: does UV protection conflict with the need to raise low levels of vitamin D? Dtsch Arztebl Int. 2010;107(37):638-643.
4.   Holick MF. The D-bate: do calcium and vitamin D affect cardiovascular health? Menopause. 2010;17(4):667-668.
5.   Sanders KM, Stuart AL, Williamson EJ Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303(18):1815-1822.
6.   Jackson RD, LaCroix AZ, Gass M Women's Health Initiative trial of calcium plus vitamin D supplementation and the risk of fractures. NEJM. 2006;354:669-683.



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