4 for 2, 2 for 4

This morning we reviewed the drugs involved in treatment of active tuberculosis.

The initial phase of treatment usually consists of two months of therapy with four drugs--typically isoniazid, rifampin, pyrazinamide, and ethambutol. The continuation phase in most cases consists of isoniazid and rifampin for four months (remember “4 for 2, 2 for 4”).

Treatment requires careful monitoring for drug toxicity. Baseline transaminases, bilirubin and ALP, CBD, creatinine, and uric acid should be obtained. When starting ethambutol, patients should be referred to ophthalmology for visual acuity and red-green color discrimination testing. Patients should be monitored closely for signs of hepatic toxicity.

Here is a recent update on TB management.
Current concepts in the management of tuberculosis. Sia IG, Wieland ML. Mayo Clin Proc. 2011 Apr;86(4):348-61

* Ghon's complex, seen in left middle field in the above image, is a lung lesion caused by tuberculosis that consists of a calcified focus of infection and an associated lymph node.

The Right dose at the Right time

This morning we discussed a case of fever and headache. We reviewd the approach to diagnosis and treatment of bacterial meningitis. Two key points from our discussion were:

1. Antibiotic therapy should not be delayed for any reason and should be given immediately after blood cultures are obtained. Dexamethasone should be given shortly before or at the same time as the first dose of antibiotics, when S. pneumoniae is suspected.

2. The "meningitis doses" of the empiric antibiotics in patients with normal renal function is: Vancomycin 1.5-2g IV q12, Ceftriaxone 2 g IV every 12 hours, and if Listeria suspected Ampicillin 2gr IV q4hr.


Here is a previous post on Meningitis.

*Steptococcus Pneumoniae, a gram postive cocci in chains, is the most common cause of community acquired bacterial meningitis in adults.

A case of bloody diarrhea

Today we discussed a case of bloody diarrhea caused by Enterohemorrhagic E. coli (EHEC), strain O157: H7.

Patients with this infection generally present with bloody diarrhea, mild leukocytosis, abdominal pain, but no fever. This bacteria produces a toxin called the Shiga toxin which can result in the dreaded Hemolytic-uremic syndrome (HUS)- the major systemic complication of EHEC infection. HUS is characterized by the triad of acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia

The treatment of EHEC infection consists of supportive care and monitoring for the development of microangiopathic complications. Administering antibiotic therapy to patients with EHEC is not recommended (Grade 1B- though the evidence is only in children <10).

Here is a review article on the topic.

Escherichia coli O157:H7 and the hemolytic-uremic syndrome.Boyce TG, Swerdlow DL, Griffin PM. N Engl J Med. 1995;333(6):364.

* Romanian greenhouse employees destroy tons of cucumbers for fear of E. coli. In May 2011, a new Shiga toxin-producing EHEC strain, O104:H4, was identified as the cause of an outbreak in Germany and other countries in Europe.

"a case of abnormal bone softening"

We talked about a case of newly diagnosed Multiple Myeloma. Here is a previous blog post on the topic.

*Sarah Newbury, the first reported patient with multiple myeloma. (A) Bone destruction in the sternum. (B) The patient with fractured femurs and right humerus. (C) Bone destruction involving the femur. Reported by Solly 1844.

Combined ASA and Plavix in setting of Acute Stroke

This morning we talked about the evidence behind dual therapy with ASA and plavix in the setting of acute stroke.

A large study called the MATCH trial, with over 7500 patients, did not find any benefic with the combined use of aspirin and clopidogrel but found significant increase in the risk of bleeding complications.


The FASTER trial, a much smaller study with 392 patients with TIA or mild stroke, compared either aspirin plus clopidogrel (300 mg loading dose, then 75 mg daily) or aspirin alone. The trial ended prematurely due to slow recruitment. At 90 days, there was no statistically significant difference between the groups but a trend toward decreased primary outcome measure of combined ischemic and hemorrhagic stroke (7.1 versus 10.8 percent).

Silk Road Disease

This morning we discussed a case of oral ulcers and our differential diagnosis included Behcet’s disease.

This disorder is a systemic vasculitis that can effect veins of variable sizes. The disease is characterized by relapsing episodes of oral and genital ulcers, skin lesions, and ocular lesions, and can affect other systems including vascular, gastrointestinal, and neurological systems.

It occurs most frequently in an area that coincides with the Old Silk Route, so the disease is sometimes referred to as the Silk Road Disease.

Mainstay of treatment is immunosuppression with corticosteroids, azathioprine, cychlophosphamide, cyclosporine A, and more recently biologics including interferon-alpha, anti-tumour necrosis factor alpha agents.


Here is a recent feview article on the topic.

Behçet's disease--a contemporary review. Mendes D, Correia M, Barbedo M, Vaio T, Mota M, Gonçalves O, Valente J. J Autoimmun. 2009 May-Jun;32(3-4):178-88. Epub 2009 Mar 26.


* The image is a picture of Hulusi Behçet, a Turkish dermatologist and scientist who first described the illness in 1936.

Tachycardia-induced Cardiomyopathy

We discussed a case of tachycardia-induced cardiomyopathy this morning. This condition results from prolonged periods of rapid ventricular heart rates, and often improves with heart rate control with a good prognosis in most patients.

Patients may present with palpitations, fatigue, decreased exercise tolerance, or symptomatic congestive heart failure.

Treatment of tachycardia-mediated heart failure is the same as any other heart failure (eg, ACE or ARB inhibitors, beta blockers, diuretics), with aggressive control of heart rate.

Here is a recent review article on the topic

Tachycardia-induced cardiomyopathy: evaluation and therapeutic options. Lishmanov A, Chockalingam P, Senthilkumar A, Chockalingam A. Congest Heart Fail. 2010 May;16(3):122-6.


* Chest x ray showing cardiomegaly (panel A) in a patient with tachycardia (panel B). Panel C shows improved cardiomegaly after 3 months of aggressive heart-rate control (panel D). Images in Cardiology. Heart 2001;86:642.

Diabetic Autonomic Neuropathy

This morning our we talked about diabetic autonomic neuropathy (DAN) in long-standing diabetes.

DAN is a common and distressing complication that can affect any or all parts of the autonomic nervous system (ANS). Many organs are innervated dually by the parasympathetic and sympathetic fiber. DAN can cause hypo- or hyperactivity of each or all parts of the ANS.

Clinical manifestations can include the cardiovascular system (tachycardia, exercise intolerance, cardiac denervation leading to silent ischemia, orthostatic hypotension), GI system (esophageal dysfunction, gastroparesis, diarrhea or constipation, fecal incontinence), GU system (erectile dysfunction, neurogenic bladder), skin (impaired sweating), and metabolic dysfunction(hypoglycaemia unawareness).

Here a review article on the topic.
Diabetic autonomic neuropathy. Vinik AI, Freeman R, Erbas T. Semin Neurol.(4):365-7.

* A plain abdominal radiograph showing a very dilated stomach (arrows) secondary to diabetic autonomic neuropathy (Images in Clinical Medicine NEJM)

Water Intoxication

This morning, we discussed a case of hyponatremia.

Remember that disorders of sodium are really problems with water balance, so it is helpful to think of hyponatremia as excess free water. Prior to being able to test for serum sodium concentrations, the clinical syndrome that is now known as hyponatremia, characterized by confusion, muscle cramps, fatigue, delirium, seizures, and death, was called “water intoxication” syndrome.

Here are two previous post on hyponatremia.
Hyponatremia
Hyponatremia - no it's Hyperhydroemia


* MRI scan of person with central pontine myelinolysis (Saggital view, the dark area inside the circle is the region of damage). CPM is a devastating consequence of rapid fluctuations in sodium status.

Equilibrium

Today in morning report a few of the presented cases had disorders of equilibrium with the two cardinal symptoms of either vertigo – an illusion of bodily or environment spinning- or ataxia- incoordination of limbs or gait.

Disorders of disequilibrium can be produced by conditions that affect the vestibular pathways, the cerebellum, or sensory pathways in the spinal cord or peripheral nerves.

We considered the diagnosis of stroke in all of the above cases. A recent article in CMAJ called "Does my dizzy patient have a stroke" addresses that same question. Here is the article.

*Jean Louis Forain's 19th Century Tightrope Walker. How many organ systems is the performer using to maintaining her balance in the dark?

Is This Patient Malnourished?

In our physical exam rounds today, we examined a patient for signs of malnutrition, and reviewed the JAMA RCE article on the topic.

The gist of the articles is to know the “Subjective Global Assessment” which includes the following:
•History (Weight change,Dietary intake change,GI symptoms,Functional capacity)
•Physical exam (Loss of subcutaneous fat, Muscle wasting, Edema)

Based the above, you can categorize patients into “well-nourished”, “moderately malnourished”, or “severely malnourished”. These categories then correlate with patient likelihood of being admitted, and post-operative complications.

Here is the article.
http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pubmed?term=is%20this%20patient%20malnourished%20detsky%20JAMA

* Given our topic of conversation, I like to remind everyone of the famine in East Africa. A devastating drought and crumbling infrastructure have created one of the worst hunger emergencies in our generation. If you would like to make a donation, the Government of Canada has created the East Africa Drought Relief Fund, and will match your donations.

An aspirin a day? ASA in secondary prevention of CVD.

This morning we briefly mentioned the Antithrombotic Trialists' Collaboration overview article. This group reviewed the results of 195 randomized trials of aspirin, among more than 135,000 high-risk patients with prior history of cardiovascular or cerebrovascular events. The following are the major conclusions:

• Aspirin, significantly reduced the relative risk of subsequent vascular events (nonfatal MI, nonfatal stroke, and vascular death) by approximately 22 percent.
• There was no difference in efficacy between doses of 75 to 150 mg/day (called low-dose aspirin) and 160 to 325 mg/day (called medium-dose aspirin).

Here is the link to the paper if you like.
Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Antithrombotic Trialists' Collaboration. BMJ. 2002;324(7329):71.

http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pubmed?term=BMJ.%202002%3B324(7329)%3A71.

* A French advertisement for aspirin from 1923. Aspirin (name originally coined by they Bayer company in 1897) lost its status as a registered trademark became a generic name in many countries. Today, Aspirin, with a capital "A", remains a registered trademark of Bayer Canada.

...and the QT was 580!!

Amuse-Bouche at today’s morning report was prolonged QT interval on the ECG. This conditions is associated with an increased risk of torsades de pointes, which is a life threatening polymorphic ventricular tachycardia.

Long QT can be genetic or acquired. Drugs are a common cause of prolonged QT. Among them are:
• Antiarrhythmic drugs such as sotolol, amiodarone, quinidine, procainamide
• Macrolide and floquinolone antibiotics
• Certain psychotropic medications like TCAs, haloperidol, methadone

Drug-induced prolonged QT is an idiosyncratic event, but there are some identified risk factors.
• Rapid IV infusion of the drug
• Electrolyte abnormalities (hypokalemia, hypocalcemia or hypomagnesemia)
• Use of other drugs known to prolong the QT interval
• Congenital long QT syndrome
• Underlying cardiac abnormalities
• Hypothyroidism
• Females
• Patients with stroke

Here is a review article on the topic.
Long QT syndrome: diagnosis and management. Khan IA. Am Heart J. 2002 Jan;143(1):7-14
http://www.ncbi.nlm.nih.gov/pubmed/11773906

* The term “torsade de pointes” means “twisting around the points in ballet where the dancer rotates around an imaginary axis. On the ECG, the QRS complex appears to twist around the electrical baseline with a continuously changing point of origin, reminiscent of the ballet movement.

Ascites

We talked about examination manoeuvres for clinically diagnosing ascites today in our physical exam rounds. Here is a good review of the topic in a previous post.

http://morningreporttwh.blogspot.com/2009/07/ascites.html

* The image is a painting of Bacchus, the Greek god of wine by Henri Millot,1730. How many stigmata of alcoholic cirrhosis can you identify in him?

Is it hot enough yet?

Given the recent heat wave in Toronto, morning report was aptly about a case of heat stroke today. As we discussed today, the most important causes of severe hyperthermia (greater than 40ºC) are heat stroke, neuroleptic malignant syndrome, thyroid strom, and malignant hyperthermia.

Heat stroke is diagnosed based on history, physical examination and the context in which symptoms developed (eg, high temperature and no air conditioner). Diagnostic studies are nonspecific. Heat stroke can cause cardiovascular, renal, or hepatic dysfunction or coagulopathy.

The management of heat stroke consists of ABC, rapid cooling, and treatment of complications.

Here is a recent review of the topic.

Heat-related illness. Becker JA, Stewart LK. Am Fam Physician. 83(11):1325-30
http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pubmed/21661715

Toxic Epidermal Necrolysis

This morning we discussed an unsolved mystery that involved a skin biopsy showing TEN. Toxic Epidermal Necrolysis (TEN) a severe type of hypsersensitivity reaction, affecting the skin and mucus membranes, that occurs in response to medications and some infections.

Treatment includes stopping the offending agent and supportive care including treating the complications such as superimposed skin infections.

Here is a recent review on the topic if you like to read more!
Toxic epidermal necrolysis and Stevens-Johnson syndrome: a review.
Gerull R, Nelle M, Schaible T. Crit Care Med. 2011 Jun;39(6):1521-32.

*The above picture is Mycoplasma pneumoniae, which is rarely associated with TEN

Systemic Lupus Erythematosis

This morning, we discussed a case of first presentation of lupus. Here is post from last year on the topic
http://morningreporttwh.blogspot.com/2010/07/systemic-lupus-erythematosus.html

* Contrary to popular belief, British singer Seal wasn't bitten by a seal and didn't wrestle a wild boar. His facial scars are manifestations of discoid rash of lupus.<

Neurologic Manifestations of Vitamin B12 Deficiency

In our discussion this morning about the causes of “fall and dementia” we briefly touched on Vitamin B12 deficiently. Vitamin B12 is a water soluble present in animal products (meat and dairy). B12 is involved in myelin synthesis, and hence, it’s deficiency has neurologic consequences.

Neurologic manifestations of B12 deficiency is the classic subacute combined degeneration of the dorsal (posterior) and lateral spinal columns. SCD manifests as symmetrical primarily lower limb neuropathy with loss of vibration and position sense, which can result in ataxia.

Other neurologic findings in B12 deficiency include axonal degeneration of peripheral nerves and central nervous system symptoms including memory loss, irritability, and dementia.

Interestingly, not all patients with neurologic abnormalities secondary to Vit B12 deficiency have hematologic manifestations.

Here is good review of B12 deficiency.
Current concepts in the diagnosis of cobalamin deficiency. Green R, Kinsella LJ. Neurology. 1995;45(8):1435.

*the picture is an axial image of the spinal cord of a patient with B12 Deficiency. Blue is where myeline is stained and you can see the loss of myeline latterally and posteriorly.

Cutaneous Manifestations of Sarcoid

Sarcoidosis is a multisystem disease characterized by the presence of noncaseating granulomas in tissues such as the skin, lung, lymph nodes, eyes, joints, brain, kidneys, and heart. Cutaneous lesions may present with a variety of morphologies, including papules, nodules, plaques, and infiltrated scars.

One-third of patients with sarcoidosis have skin lesions. These lesions can be the presenting finding of the disease. Some of these lesions are nonspecific, but others are highly suggestive of sarcoidosis. There are many different types of lesions.

Here are a few common skin findings in Sarcoidosis:
Lupus pernio (first picture) : Lupus pernio is a violaceous or erythematous indurated papules, plaques, or nodules that are primarily distributed on the central face (though can also happen in the extremities and buttocks)
Erythema nodosum (second picture): raised tender inflammatory nodules over lower legs. Common and non-specific.

If you’re interested in reading more on sarcoidosis, here is a great review article.

Sarcoidosis. Michael C. Iannuzzi, M.D., Benjamin A. Rybicki, Ph.D., and Alvin S. Teirstein, M.D.N Engl J Med 2007; 357:2153-2165.
http://www.nejm.org/doi/full/10.1056/NEJMra071714

Disseminated Gonococcal Infection

Stephan Russ, M.D., and Keith Wrenn, M.D. N Engl J Med 2005; 352:e15April 21, 2005

In our morning report discussion today, this image from NEJM was mentioned. The image shows the classic macular (arrows) and pustular lesions (arrowheads)seen in disseminated gonococcal infection.

Seizures in HIV-infected Patients

Today, morning report was a discussion of seizures in patients with HIV. Seizures are common in HIV positive individuals. Always think of HIV-related causes and non-HIV-related causes.

HIV-Related causes of seizure included direct cerebral HIV infection, CNS lymphoma, and opportunistic infections such as CNS Toxoplasmosis (most common), Cryptococcal meningitis, CNS TB (tuberculoma rather than TB meningitis). PML is a possible but uncommon cause of seizures. Some medications (such as Foscarnet used to in treatment of CMV infection) can provoke seizures as well.

Don’t forget the other common causes of seizures in adults such as bacterial meningitis, electrolyte and metabolic disturbances, and drug/EtOH intoxication/withdrawal.

Here is a great review on the topic.
Seizures in HIV-seropositive individuals: NIMHANS experience and review. Satishchandra P, Sinha S. Epilepsia. 2008 Aug;49 Suppl 6:33-41.
http://www.ncbi.nlm.nih.gov/pubmed/18754959

* The image is a CT scan slice showing a ring-enhancing lesion with an eccentric nodule, which also enhances. The corticomedullary location and marked surrounding edema are characteristic of toxoplasmosis.

Aspirin Toxicity

This morning we discussed a case of ASA toxicity. This is a potentially fatal clinical scenario that can occur with acute or chronic ingestion of ASA.

At supertherapeutic doses, ASA absorption is delayed because of pylorspasm and “cement” formation. At high doses, the elimination is via slow renal excretion.

Patients often present with nausea, vomiting, tachypnea, and tinnitus. Altered LOC, ranging from mild to coma, and non-cardiogenic pulmonary edema are severe consequences of ASA toxicity. Investigations often show an anion-gap metabolic acidosis and a respiratory alkolosis (secondary to direct stimulation of the respiratory centre).

Main principles of management are supportive care (A-B-Cs), GI decontamination by activated charcoal, and alkalanization of plasma and urine. Don’t forget to call poison control for any overdose, and check for other co-ingestions.

Give a glucose-containing IVF even in the presence of normal serum glucose as ASA can decrease CNS glucose levels. Call nephrology early as hemodialysis is our ultimate treatment for patients who deteriorate despite supportive care.

Uptodate has a really good review on the topic if you’re interested.

Tumour Lysis Syndrome

This morning we had an engaging discussion about Tumour Lysis Syndrome (TLS). As was also reviewed yesterday at noon rounds, TLS is an oncologic emergency.

It is caused by massive tumor cell lysis with the release of large amounts of potassium, phosphate, and nucleic acids Breakdown of nucleic acids to uric acid leads to hyperuricemia, and the precipitation of uric acid in the renal tubules causes acute renal failure. Calcium phosphate deposition can also contribute to renal failure.

Initiation of cytotoxic therapy in patients with high-grade lymphomas (particularly Burkitts lymphoma) and acute lymphoblastic leukemia is often the trigger to TLS. However, TLS can occur spontaneously.

Management of TLS consists of aggressive intravenous hydration, and the administration of the hypouricemic agents rasburicase (recombinant uric oxidase) or allopurinol.

Here is a recent review on the topic:

The Tumor Lysis Syndrome. Scott C. Howard, M.D., Deborah P. Jones, M.D., and Ching-Hon Pui, M.D.N Engl J Med 2011; 364:1844-1854.
http://www.nejm.org/doi/full/10.1056/NEJMra0904569

Familial Mediterranean Fever

FMF is a rare autosomal recessive disorder characterized by paroxysms of fever and serosal inflammation, seen primarily in several ethnic groups originating in the Mediterranean region. Typical clinical presentations of the disease are recurrent attacks of severe pain (due to serositis at one or more sites) and fever, lasting one to three days, and then resolving spontaneously. In between attacks, patients are entirely well.

Common manifestation are peritonitis, pleuritis, synovitis and an erysipelas-like skin lesion. Other less common findings are pericarditis, orchitis and recurrent aseptic meningitis also can occur. As was mentioned this morning, an increased incidence of some vasculitides, such as polyarteritis nodosa and Henoch-Schönlein purpura, has been described. Kidney involvement with these processes may be particularly common.

As discussed this morning, the most important long term complication of FMF is secondary (AA) amyloidosis which occurs insidiously and progressively. Amyloid A deposition occurs in the kidney, spleen, liver, and gut. Renal involvement is the dominant feature of FMF-related amyloidosis.

Colchicine is the mainstay of treatment of FMF, both to prevent attacks as well as prevent the development and progression of amyloidosis. Research is underway evaluating the role of anti-TNF-alpha therapy and IL-1 receptor blockade in severe FMF.

Here two good articles are treatment and clinical manifestations of FMF if you're interested.
http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pubmed/19530512
Familial Mediterranean fever. Ben-Chetrit E, Levy M. Lancet. 1998;351(9103):659.

Hepatocellular Carcinoma Risk Factors

A number of important risk factors for the development of hepatocellular carcinoma (HCC) have been identified, including the following:

- Hepatitis B carrier status
- Chronic hepatitis C infection
- Cirrhosis of almost any cause
- Hereditary hemochromatosis
- Environmental toxins (alfatoxin that commonly contaminates corn, soybeans and peanuts; contaminated drinking water; betel nut chewing)
- Tobacco and alcohol abuse
- Non-alcoholic fatty liver disease and diabetes mellitus
- Alpha-1 antitrypsin deficiency
- Epidermal growth factor polymorphisms

Also, it should be noted that HCC has been known to occur in patients without any identifiable risk factor.

For the coffee-lovers among us: several observational studies have implicated coffee consumption as a protective factor for liver cancer, including HCC. A meta-analysis estimated that consumption of two or more cups per day was associated with a 43% reduction of liver cancer. The benefit was observed in individuals with and without liver disease. The presumed mechanism surrounds the fact that coffee contains large amounts of antioxidants suggesting biological plausibility for the protective effect. The authors also noted that coffee and caffeine have been linked to lower liver enzyme levels and a reduced risk of cirrhosis, potentially further contributing to biological plausibility (Larsson SC, Wolk A. Coffee consumption and risk of liver cancer: a meta-analysis. Gastroenterology. 2007;132(5):1740)