Bedside Rounds: How Do You Diagnose and Treat Diabetic Neuropathy

October 3, 2007

Feet 2Commentary by Judith Brenner MD, Associate Program Director, NYU Internal Medicine Residency Program

Diabetic neuropathy is one of the most commonly encountered complications of diabetes mellitus. It is seen in up to 20% of diabetics. Patients typically present with neuropathic pain in a “glove and stocking” distribution with the earliest signs in the feet. Night time complaints of “my feet are on fire” are common. Relying on a patient’s complaint of “pain” or “numbness” is inadequate in the diagnosis of peripheral neuropathy since almost half of patients with ulceration lack these complaints.

To briefly review, physical examination centers on assessment of vibration since it is often one of the earliest neurological signs. A 128-Hz tuning fork is applied to the bony prominence on the dorsal aspect of the first toe just proximal to the nail bed, over the interphalangeal joint. The patient is asked what he or she feels. If impairment exists at this distal bony prominence, the examiner can proceed to test more proximal prominences (such as the malleollus, patella, etc) to assess the extent. Testing the Achilles reflex is also useful. In Sapira’s text, “Art and Science of Bedside Diagnosis”, 15% of patients lack an Achilles reflex. Of those 15%, almost 80% have diabetes. The best technique for eliciting the reflex requires that the patient sit comfortably with legs dangling over the table. The examiner dorsiflexes the ankle and then taps the tendon. Dorsiflexion adds tone to the system, thus accentuating the reflex.

Today, the monofilament test is used most often because of its operating characteristics. It has been found that the inability to sense the monofilament is predictive of ulceration (LR of 2.9). Conversely, the presence of sensation argues against subsequent amputation.

As for treatment, it was first shown in DCCT in 1993(1) that intensive insulin therapy in type I DM reduced the risk of developing clinical neuropathy by 61%. The treatment goal is to slow the progression of neuropathy rather than to overcome pain. Beyond glucose control, treatment has traditionally included antidepressants and anticonvulsants. In a recent systematic review, Wong et al (2) investigated the analgesic efficacy of several different classes of analgesics in managing neuropathy. Studies included in this review included adult patients over 18 years of age who were treated with oral or topical analgesics for short periods of time (2 weeks- 6 months). The drugs investigated included antidepressants (TCAs and SSRIs), opioids, tramadol, capsaicin, anticonvulsants, and NMDA antagonists. In each study, the investigated drug was compared to a placebo. The primary outcome that the investigators were interested in was a 50% reduction of pain, which translated into a “moderate” improvement in global pain. The secondary outcome was the number of patients who withdrew secondary to adverse events.

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Rifaximin: A useful drug for travelers’ diarrhea

September 28, 2007

xifaxan_box.jpgCommentary by Sumathi Sivapalasingam MD, NYU Division of Infectious Diseases

Rifaximin is an oral semi-synthetic analog of rifampin which is essentially not absorbed (bioavailability <0.4%) making it useful for the treatment of intra-luminal intestinal infections, while having little systemic side effects. There are several advantages to using rifaximin: it does not appear to lead to bacterial resistance, a problem frequently encountered with rifampin; colonic fecal flora is minimally altered; and it has a safety profile similar to placebo. Like other rifamycins, it exerts its activity by inhibiting RNA synthesis.

FDA-Approved indications
Traveler’s Diarrhea: Rifaximin received FDA-approval for treatment of travelers’ diarrhea caused by non-invasive strains of E. coli in patients 12 years and older. The drug is not as effective in treating bloody diarrhea or diarrhea due to invasive pathogens (Shigella or Campylobacter). Three randomized double-blinded trials in travelers with diarrhea demonstrated a decrease in the duration of diarrhea compared to placebo or an equivalent response compared to ciprofloxacin. The symptoms that prompted treatment in these trials included having 3 or more unformed stools during the 24 hour period before enrollment with abdominal pain, excess gas, nausea or vomiting, fecal urgency, tenesmus, or fever.

A recent randomized double-blind placebo controlled study demonstrated that rifaximin is also effective for the prevention of travelers’ diarrhea, although the wide-spread use (there are 50 million travelers a year!) of an antibiotic to prevent mild to moderate diarrhea is controversial.

Non-FDA indications
Infectious diarrhea: Studies examining the usefulness of rifaximin in the treatment of diarrhea in the non-traveler are of poorer quality than those done in travelers, but one double-blind study did show a better reduction in the number of unformed stools in the rifaximin group compared to placebo.

Rifaximin is also being examined for the treatment of C. difficile-associated diarrhea and has been shown to be of similar efficacy in reducing diarrhea compared to oral vancomycin. One case-report by Johnson et al. describes their experience of using rifaximin after a course of oral vancomycin to prevent recurrences of C. difficile colitis in patients with multiple recurrences. One disturbing event, however, was the finding of a rifaximin-resistant strain of C. difficile in one their patients who failed therapy with vancomycin and rifaximin. Larger studies are necessary before rifaximin could be recommended for use in this clinical setting.

Hepatic encephalopathy: Compared with lactulose, several double-blind studies have shown improved cognitive function and reduction of ammonia levels with rifaximin treatment in patients with hepatic encephalopathy. Rifaximin has been given “orphan” status by the FDA for use for this indication which means that its cost can be reimbursed by insurance plans.

Small bowel bacterial overgrowth: Although rifaximin has little effect on large colon flora, it can reduce small bowel flora with subsequent reduction in gas and abdominal distention.

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Inpatient Diabetes Management: Case 3

September 27, 2007

lantus.jpgCommentary by Mary Vouyiouklis MD, Fellow, and Ann Danoff MD, Director, Division of Endocrinology, Diabetes and Metabolism, NYU Medical Center 

Welcome to Case 3 of our special diabetes series intended to highlight the essentials of diabetes care in the inpatient setting. For the next several weeks, we plan to present individual cases followed by some management questions and answers.

Case 3: The case of Mr. Mejia

3A. Mr. Mejia is a 30 year old man with Type 1 diabetes who is admitted for shortness of breath. He is made NPO for an imaging study the following morning. His usual insulin regimen is 10 units of rapid acting insulin qAC and 18 units of glargine qHS. You are covering for your co-intern and the nurse calls you asking you if you need to make any adjustments given that he is now NPO. What do you do?

  1. Do nothing.

  2. Discontinue the qAC but continue the qHS.

  3. Discontinue the qAC and half the qHS dose.

  4. Discontinue all and start a sliding scale.

3B. Mr. Mejia becomes hypoxic and unfortunately has to be intubated. He now is given continuous tube feeds. What are the adjustments (if any) that need to be made now?

3A. Answer: 2

Patients with type 1 diabetes have an absolute requirement for insulin, therefore basal insulin replacement is an absolute requirement to prevent ketoacidosis, even when they are NPO. In this instance, the patient’s qHS dose is providing < 50% of his/her TDD therefore it is reasonable to continue with this and to hold the pre-meal bolus dosing while the patient remains NPO. 

Although patients with T2DM may not be at risk for DKA, if insulin is not administered when they are NPO, these patients should receive ½ to 2/3rds of their basal insulin dose, depending upon degree of previous glycemic control, as assessed by report of fingerstick monitoring and/or recent HgA1C results. 

3B. Answer:

An insulin drip would be ideal for an intubated patient on tube feeds in a properly monitored setting. When he is extubated and stabilized, but still requires tube feeds, a number of options for insulin administration are reasonable.  He could be switched to a basal insulin regimen comprised of either NPH q8H or Lantus.  Alternatively, this is one of the few situations where “RISS” would also be acceptable. If the tube feeds are administered over a 8 – 12 hour period (rather than continuously), an insulin such as NPH (which has an onset of action in ~ 2 hours and a peak action in ~ 6 – 8 hours) would provide a better match for this carbohydrate load than “peakless” insulinization with glargine; therefore would be preferable in that circumstance.


Breaking News: FDA Issues New Warnings for Haldol

September 21, 2007

haldol.jpgCommentary by Helen Kourlas, PharmD

On September 17th 2007, the FDA issued an advisory warning healthcare professionals to avoid the use of higher than recommended doses of haloperidol, marketed as Haldol, Haldol Decanoate and Haldol Lactate. In addition to this warning, the FDA also emphasized that the injectable form of haloperidol is only approved to be administered as an intramuscular injection. Common off – label intravenous administration of haloperidol has led to numerous case reports of QT prolongation, Torsades de Piontes (TdP) and sudden death. Seventy three reports of TdP resulted because of haloperidol use, and 8 of the 11 fatal cases were linked to the intravenous administration of haloperidol at various doses. These cases occurred in the absence of predisposing factors, such as electrolyte imbalances, underlying cardiac abnormalities, or the use of medications that are known to prolong the QT interval. Additional cases have also demonstrated a dose-response relationship between the intravenous haloperidol dose and the development of TdP. These events have led the FDA to update the product labeling of haloperidol to include a warning statement alerting healthcare professionals to observe and monitor patients receiving higher than recommended doses of haloperidol as well as patients receiving haloperidol through intravenous administration. Currently, although intravenous administration of haloperidol is a relatively common off label use, this advisory serves as a reminder that injectable haldol is not FDA approved for intravenous administration.

Information for Healthcare Professionals. Haloperidol.

Recent Legionella Outbreak in the Bronx

September 20, 2007


Commentary by Elizabeth Hackett MD, PGY-3

On July 25th, 2007, the NYC Department of Health released an advisory requesting that all New York City physicians maintain a high index of suspicion for Legionnaires’ disease in patients presenting with community acquired pneumonia. This advisory was prompted by 27 cases of Legionella pneumonia reported in the Parkchester neighborhood of the Bronx during the fall of 2006 (zip code 10462 ). This cluster of cases represented an increase in incidence of the disease to 16.6 cases/100,000 in the Bronx, up from 2.3 cases/100,000 citywide.1

This increase in incidence set of an epidemiological quest for a common source for the outbreak, which has yet to be discovered. In order to assist the DOH in discovering and eradicating a source of this outbreak, they are requesting that we remain vigilant in testing for Legionnaires’ disease in our patients. Sputum or brochoalveolar lavage cultures are the preferred method of diagnosing Legionella pneumonia, with BAL being superior. The urine antigen test can be used as an adjunct, but should be accompanied by an attempt to validate the diagnosis by culture.

Legionnaires’ disease, of course, got its name from the 1976 outbreak during the Pennsylvania State American Legion Convention.  221 people were infected in the outbreak, thought to be caused by contaminated water in the hotel’s air-conditioning system, and 34 of them died.  McDade and Shepard, 2 biologists working for the US Centers for Disease Control and Prevention, discovered that the causative agent was small fastidious gram negative rod, which they named after the unfortunate victims.3

This was not the first outbreak of Legionella.  Once the pathogen was identified, antibody testing showed that several outbreaks of pneumonia in the 1950s and 60s were also likely caused by Legionella species.  In fact, it was subsequently discovered that a six-year long epidemic of Legionnaires’ disease was ongoing among British tourists staying at one particular hotel in Spain, which leads me to wonder about the common sense of British tourists.3

Legionella bacteria are naturally occurring aquatic bacteria that grow in warm water, particularly in cooling towers, water heaters and potable-water plumbing.  They are obligate aerobes, and are best grown on BCYEa agar, growing in about 2-5 days in the lab.  There are 49 different Legionella species, 20 of which have been reported to infect humans.  In addition, there are at least 16 different serogroups.  L. pneumophilia serogroup 1 caused the 1976 outbreak and is the cause of seventy to ninety percent of all cases where the bacteria have been isolated.2

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Inpatient Diabetes Management: Case 2

September 14, 2007

insulin.pngCommentary by Mary Vouyiouklis MD, Fellow, and Ann Danoff MD, Director, Division of Endocrinology, Diabetes and Metabolism, NYU Medical Center 

Welcome to Case 2 of our special diabetes series intended to highlight the essentials of diabetes care in the inpatient setting. For the next several weeks, we plan to present individual cases followed by some management questions and answers.

Case 2: The case of Mr. Jones
Mr. Jones is a man with (insulin requiring) type 2 diabetes who is admitted for pneumonia. He has had a decreased appetite for the last week since he has been ill. He is on 50 units 70/30 Insulin qAM and qHS. You are now admitting him to your service. His weight is 265lbs (120kg). What do you do now?
A. Calculate his total daily dose (TDD) of insulin and divide it into basal/bolus dosing.
B. Continue 50 units 70/30 insulin qAM and qHS.
C. Start a regular insulin sliding scale to determine insulin requirements.
D. Calculate his TDD and give 70/30 insulin qAM and qHS.

Answer: A
Most patients on outpatient insulin therapy should have their total daily dose of insulin (TDD) calculated when they are admitted to the hospital. This could be anywhere from 0.3-1unit/Kg/day. If information about outpatient glycemic control is available, and compliance with insulin regimen seems reliable, that information should be used to inform choice of insulin dosing. In the absence of such information, it is generally prudent to estimate the TDD insulin requirements at the low end (i.e. start with 0.3 units/Kg/day) and increase as necessary based on qAC and qHS finger stick monitoring results. Fifty percent of the calculated TDD should be given as a basal insulin (glargine or twice daily NPH in equally divided doses before breakfast and at 10 PM) and 50% of the TDD should be given as pre-meal boluses of insulin. For example, this 120Kg patient requires (120Kg X 0.3units) 36 units daily. This should be divided into 18 units basal and 18 units bolus (or 6 units qAC with meals). This seems like much less than what he is requiring at home; therefore, you can incorporate a correction dose of insulin to the pre-meal rapid acting insulin as a sliding scale (note that on average, 1 -2 Units of insulin will lower the blood glucose ~ 50 mg/dl in patients with T2DM). It is important to remember that because of the stress implicit in the hospitalization, coupled with changes in p.o. intake (which commonly is less in the hospital compared to the home setting) insulin requirements may be different when even previously well-controlled patients are hospitalized, and may change during the course of the hospitalization. If the decision is made to resume “70/30” insulin upon discharge, Mr. Jones must be educated about proper administration of this medication. He should be made aware that the “30” percent of his “70/30” is short acting (regular insulin) or rapid acting (lispro insulin). It is also a critically important safety issue that he understands that because of the short or rapid acting component that comprises the 30% of “70/30”, this medication must ONLY be given before meals (and NOT qHS) to avoid potentially fatal nocturnal hypoglycemia.

Image of insulin molecule, Courtesy of Wikimedia Commons

Tumor Lysis Syndrome and the Role of Urinary Alkalinization

September 13, 2007

fluid1.jpgCommentary by Bani Chander MD, PGY-2, and Sergio Obligado MD, Attending Physician, Nephrology

Tumor lysis syndrome (TLS) is characterized by a group of metabolic abnormalities including hyperkalemia, hyperuricemia, and hyperphosphatemia with secondary hypocalcemia, following the initiation of cytotoxic therapy. Although there is no well established definition for this syndrome, the Cairo-Bishop definition [1] is a commonly used classification system that stratifies the degree of severity by utilizing specific laboratory data and clinical features. The constellation of abnormalities that occurs in TLS is due to a rapid release of potassium, purine nucleic acids, and phosphorus when tumor cells abruptly lyse their contents into the extracellular space. These abnormalities can subsequently lead to acute renal failure and may result in multiple organ failure and/or death. It is therefore important to identify those patients who are at risk for this syndrome in order to initiate early preventative treatments [2], most often including a combination of allopurinol, IV hydration, and/or urinary alkalinization.

TLS is most often seen in acute lymphoblastic leukemia and high grade non hodgkins lymphoma, most commonly in Burkitt’s lymphoma [3]. Other common malignancies associated with TLS include CLL, AML, multiple myeloma, small cell lung cancer, breast and ovarian cancer, medulloblastomas, and sarcomas. The kidney is the primary organ involved in the clearance of potassium, phosphorous, and uric acid. Uric acid can precipitate in an acidic environment or if there is decreased tubular flow rate within the renal tubules. When uric acid crystals form, they can precipitate within the collecting ducts and ureters and can cause obstructive uric acid nephropathy. Calcium phosphate deposition in the renal collecting ducts, vessels, and ureters may also contribute to acute renal function in this setting.

Standard of care in patients who are to receive chemotherapy or radiation in a cancer with high cell turnover is at least 2 days of allopurinol prior to initiation of therapy. IV fluid hydration should also be used in order to maintain urine output at a minimum of 2.5 liters/day. More recently, rasburicase has been introduced and used to prevent uric acid nephropathy in patients who are at increased risk for tumor lysis syndrome. High risk features are characterized by increased uric acid levels, LDH levels greater than two times normal or WBC >50,000microL (both indicative of high tumor burden), certain tumors including Burkitt’s lymphoma, lymphoblastic lymphoma, ALL, AML, decreased intravascular volume status, and the presence of tumor infiltration in the kidney.

Early recognition of a fall in glomerular filtration or diuresis in patients with tumor lysis is critical, as prompt initiation of dialysis in this group can prevent both further renal deterioration as well as dangerous metabolic derangements. In contrast to most causes of acute kidney injury in which dialysis is initiated to treat the sequelae of decreased GFR (i.e. hyperkalemia, uremia, volume overload), dialysis can actually reverse the kidney injury, as both uric acid and phosphate are efficiently cleared by the dialysis membrane.

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X Ray Visions Mystery Quiz- The Answer

August 30, 2007

Before you read the answer, you may want to review the initial Mystery Quiz posted last week.

Commentary by Andrew Hardie MD, Fellow, NYU Department of Radiology

Although this patient’s symptoms were not the most typical of this entity, the CT findings in this case are diagnostic of a perforated anterior duodenal ulcer. The most essential observation, and the one that alters management, is the presence of intraabdominal free air (arrows). The small collections of air in this case are not unusual for bowel perforations, especially proximally. One can see how occasionally these small volumes of free air may not be able to be seen on plain films, especially inadequately positioned films.

The specific location of the free air in this case directs one to suspect a duodenal perforation. Air is seen in the periportal region, around the duodenum (green arrows), and in this case, at the site of the perforation in the duodenal wall (red arrow).


A point of interest is that only the anterior duodenal bulb wall is intraperitoneal. Therefore, this must be an anterior wall ulcer. A posterior wall ulcer will lead to gastrointestinal bleeding, because, if you remember your anatomy, the gastroduodenal artery lies directly posterior to the duodenal bulb. Although very rare, a perforated posterior wall ulcer would cause retroperitoneal air, not intraperitoneal air.

The patient in this case reported severe epigastric pain, which could be indicative of peptic ulcer disease. However, physical exam was not suggestive of peritonitis. It is important to remember that atypical presentations of perforated ulcers can occur, although this is more commonly seen in elderly patients. Also, in this case, the perforation could have occurred in the interval between admission and abdominal imaging. The patient was taken to the OR for immediate repair of the perforation and postoperative clinical course was uneventful. Upon further questioning, he did admit to heavy weekend alcohol use as well as recent increased NSAID use for some low back pain.

Inpatient Diabetes Management: Case 1

August 28, 2007

90px-glukometr_ot.jpgCommentary by Mary Vouyiouklis MD, Fellow, and Ann Danoff MD, Director, Division of Endocrinology, Diabetes and Metabolism, NYU Medical Center

Welcome to our special diabetes series intended to highlight the essentials of diabetes care in the inpatient setting. For the next several weeks, we plan to present individual cases followed by some management questions and answers.

Case 1: The case of Mr. Smith
Mr. Smith is a 65 year old obese male admitted to the hospital with acute renal failure. He reports a recent history of diarrhea (up to 6 episodes of loose non-bloody stools per day for one week). He cannot keep anything down. His laboratory data reveals a BUN of 45 and a creatinine of 3 (baseline creatinine is 1). His admission non-fasting glucose is 168. He was diagnosed with Type 2 Diabetes 5 years ago, and his outpatient medications include  glyburide 5 mg and metformin 1g bid. How would you manage his diabetes in the hospital?

A. Continue with both glyburide and metformin.
B. Discontinue glyburide. Continue with metformin.
C. Discontinue both oral meds. Do nothing else.
D. Start rapid acting insulin sliding scale qAC and check FS qAC, qHS.
E. QID Regular Insulin Sliding Scale (RISS)

Answer: D
As the patient is in renal failure, it is prudent to discontinue his glyburide and mandatory to discontinue the metformin. Glyburide has a long half life and is cleared by the kidney; therefore, he has an increased risk of becoming hypoglycemic under these conditions. In addition, because the risk of lactic acidosis increases in patients on metformin in the face of deteriorating renal function, metformin should not be used in men or women whose creatinine level is > 1.5 and 1.4 respectively. Several approaches would be acceptable in the patient described here. One approach would be to calculate the TDD (total daily dose) of insulin he requires, starting at a low 0.3 units/kg/day (especially in view of his compromised renal function). Half of the TDD should be given as a basal dose, provided either as a single injection of glargine or as NPH administered before breakfast and at 10 PM in equally divided doses. The remaining half the TDD of insulin should be given as a bolus of rapid acting insulin divided equally and administered ~15 minutes before each meal. Alternatively, the patient could be started on a rapid acting insulin sliding scale qAC. If the second approach is selected, after 48 hours, when total daily dose of insulin has been determined, his regimen should be adjusted to a qHS basal and pre-meal “bolus” regimen.

A regular insulin sliding scale insulin regimens (“RISS”) given “QID” (i.e., not given in relationship to meals), is strongly discouraged in patients who are eating. RISS treats rather then prevents hyperglycemia. Further, RISS is associated with the risk of insulin “stacking”. This may result in “roller coaster” glycemic control, i.e., hypoglycemia followed by rebound hyperglycemia. Whichever regimen is selected, fingerstick monitoring should be performed before each meal and qHS, and the regimen adjusted to achieve a fasting blood glucose of 80 – 120 mg/dl, and a 2 h post-prandial glucose of < 180 mg/dl. For patients admitted to the hospital who have excellent glycemic control on oral agents, these may be used as long as there are no contraindications (remember to stop metformin for 48 hours following a study using contrast; remember to stop a TZD for patients admitted in CHF, etc.). If changing needs are anticipated (as is often the case in hospitalized patients), these can usually be addressed more successfully with insulin.

X-Ray Visions: Mystery Quiz

August 22, 2007

A 46 year old male with a past medical history of hypertension presents to the emergency room complaining of constant throbbing epigastric pain for one day. He rates the pain as 7/10, with some radiation to his chest. He reports some mild nausea, but denies diarrhea or constipation.  He does endorse a bloated sensation for the past few days. He has not had any fevers and denies melana or hematochezia.  He is an avid biker and reports unlimited exercise tolerance. He denies any previous history of chest pain.

The patient works as a landscaper. He does not smoke and drinks socially on the weekends. His only medication is hydrochlorothiazide 25 mg daily. He has never had any surgeries. His father died of lung cancer at age 72, his mother is alive and well.

Pt appears mildly anxious but is otherwise in no distress. He is afebrile, BP 150/90, pulse 98, respiration rate 16.  Physical exam is remarkable only for some mild epigastric tenderness without rebound tenderness or guarding.

ECG is sinus rhythm, no st or t changes.

WBC is 16 (82% neutrophils), h/h 14/42, plt 247

Basic metabolic panel is within normal limits. Liver function tests, amylase, lipase are also all within normal limits.

Initial cardiac enzymes are negative.

The patient is admitted to the medicine service by the emergency room as a “r/o MI.”

A CT A/P with po and IV contrast is ordered by the medical team:




What is your leading diagnosis?

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An Update on Multiple Sclerosis

August 21, 2007

120px-monthly_multiple_sclerosis_mri.gifCommentary by Jacqueline Friedman, MD, Clinical Associate Professor of Neurology,  Director, New York Region Veterans Administration Multiple Sclerosis Center of Excellence

Multiple sclerosis (MS), a chronic disease of the central nervous system, is thought to be initiated by an inflammatory phase followed by degeneration of both white and grey matter. While there is no cure, great strides have been made in the past ten years—we now believe that the earlier a diagnosis is suspected and treatment is initiated, the better the long-term course of the disease, even if treatment is initiated before a definitive diagnosis is made.

Treatments are divided into two categories: symptomatic and disease-modifying. Though they have been used for decades, there has been recent progress in symptomatic treatments. For example, if spasticity is not relieved with oral muscle relaxants, options now include the use of botulinum toxin injected into muscles or the use of an implantable baclofen pump to deliver the muscle relaxant directly into the spinal fluid. The pump permits significantly lower doses to be administered and eliminates systemic side effects. Fatigue, a symptom that affects 2/3 of MS patients, has been treated mainly with amantadine, a dopamine agonist. Recent clinical studies and practice have involved the use of modafinil, a drug initially developed to treat narcolepsy, to help relieve daily fatigue in MS patients, thereby potentially improving their quality of life.

MS care has been revolutionized in the last decade by the use of disease-modifying agents, which are immunomodulators targeted to alter the natural history of the disease. The two primary agents in this category are beta interferon (Betaseron, Avonex) and glatiramer acetate (Copaxone). They have been shown to decrease MS exacerbations or attacks by a third when compared to placebo, though their mechanism of action is not well defined. Disease-modifying agents may work by stabilizing the blood-brain barrier, as well as by altering the profile of the immune system from helper to suppressor function. Their more significant effect is evident on magnetic resonance imaging–a decrease in the number and size of MS lesions in the brain and a decrease in the number of lesions enhancing with dye injections, which can be a sign of active, recent inflammation. It has been shown that these modifiers decrease the amount of tissue loss and atrophy that develop in the brain, which are perhaps the most significant signs of worsening of disease and markers for cognitive decline as well. Unfortunately, these medications are expensive ($12,000/year), must be given by weekly injection and can cause flu-like symptoms and depression. If the patient is carefully followed and treated, the overall benefits may be worth the first few months of discomfort.

The most recent advance in immunomodulators is the recently FDA-approved natalizumab (Tysabri) which stabilizes the blood-brain barrier by blocking adhesion molecules. This drug has caused much excitement, especially because it can be used as a monthly treatment. Moreover, it has twice the efficacy than the interferons as evident on MRI scans. Unfortunately, three cases of potentially fatal progressive multifocal leukoencephalopathy (JC virus) have emerged in patients treated with this medication. Therefore, while still available for use, it is reserved for patients who are part of a national registry and who have failed all of the other treatments.

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Reemergence of the Great Imitator: Overview of the Diagnosis and Treatment of Syphilis

August 17, 2007

382px-syphilis_is_a_dangerous_disease.pngCommentary by Rosemary Adamson, PGY2,  Deena Altman PGY-1 and Harold Horowitz, Professor of Medicine, Section of Infectious Diseases 

Syphilis is back! You know the drill: an 80-something year old man presents with dementia and you send the TSH, B12 and RPR and get a head CT, all the while expecting some microvascular disease & age-related cortical volume loss. Imagine my surprise when my VA patient had a positive RPR and then the lumbar puncture returned a positive VDRL. To be fair, he wasn’t married and was living with his third common-law wife, but I still find it hard to think of elderly people as having sexually-transmitted diseases! But we must think of all our patients as at least potentially having STDs and do our best to ask all the embarrassing questions of the sexual history and then screen appropriately – because syphilis is on the rise!

The Department of Health and Mental Hygiene recently released a report on the striking increase in reported cases of primary and secondary syphilis in New York City. Syphilis is a disease that has been documented for hundreds of years. Following a famous outbreak reported in 1494 in Europe, the poet Fracastoro wrote about the afflicted shepherd, Syphilus, in 1530. Also one must never forget the Tuskegee experiments documenting the natural history of syphilis in uninformed African-Americans that ran for a shocking thirty years between 1932 and 1962. Though Fleming discovered penicillin in 1943, and Mahoney and Moore showed it was effective against syphilis in 1946, the study subjects at Tuskegee didn’t receive this curative therapy until 1962. The last syphilis epidemic in the United States occurred between 1986 and 1990, after which rates began to steadily drop to an all-time low in 2002.

Syphilis has now made a comeback in NYC, with the DOH reporting twice as many primary and secondary syphilis cases in the first quarter of 2007 (260 cases) as compared to the same period last year (128 cases). 96% of cases were among men with a median age of 34 years, with the neighborhood of Chelsea holding the highest number of cases. The increase in syphilis cases is noted particularly among men who have sex with men (MSM), a trend that has been seen in other large U.S. cities. Of deeper concern is the fact that an increase in syphilis cases can precede an increased rate of HIV infection, since these infections are transmitted in a similar fashion but syphilis has a shorter incubation period. Also, the number of women with syphilis in New York has risen from three in the first quarter of 2006 to ten for the same period in 2007, raising concern that congenital syphilis will reemerge.

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