Changes in neurohormonal gut peptides following bariatric surgery

The rising prevalence of obesity has reached pandemic proportions, with an associated cost estimated at up to 7% of health expenditures worldwide. Bariatric surgery is currently the only effective long-term treatment for obesity and obesity-related co-morbidities in clinically severely obese patients. However, the precise physiological mechanisms underlying the postsurgical reductions in caloric intake and body weight are poorly comprehended. It has been suggested that changes in hormones involved in hunger, food intake and satiety via the neurohormonal network may contribute to the efficacy of bariatric procedures. In this review, we consider how gastrointestinal hormone concentrations, involved in appetite and body weight regulation via the gut–brain axis, are altered by different bariatric procedures. Special emphasis is placed on neurohormonal changes following Roux-en-Y gastric bypass surgery, which is the most common and effective procedure used today.

source: International journal of Obesity


Robots May Help Patients Recover From Stroke

Study Shows Robotic Therapy May Have Advantages Over Treatment by Human Physical Therapists
scientist demonstrating therapy robot

Robot-assisted therapy can help improve arm and shoulder mobility in people left paralyzed after a stroke.

In a study of 56 stroke survivors with paralysis on one side of the body, those who underwent robotic therapy improved more on a test of arm and shoulder motor function than those who received more standard rehab.

“We hypothesize that robots, [unlike human physical therapists], can help people to carry out repetitive exercises with the same movements every time, thereby re-educating the brain,” says Kayoko Takahashi, ScD, clinician and research associate in the department of occupational therapy in Kitasato University East Hospital in Kanagawa, Japan.

The study was presented at the American Stroke Association’s International Stroke Conference 2011.

Robots vs. Therapists

The study involved people who had suffered a stroke in the previous four to eight weeks. All received 40 minutes of standard rehabilitation therapy daily from an occupational therapist.

Thirty-two patients also received robotic therapy using the Reo Therapy System in 40-minute sessions every day for six weeks. The patient’s forearm is placed on a platform sticking out from the robot and a stick is used to repeatedly guide the forearm in various pre-programmed directions.

The other participants spent the same amount of time working through a standard self-training exercise program designed to teach stroke survivors how to change their clothes and perform other daily activities.

Improvements in Motor Function

Here are the results from the training sessions, as measured on the 36-point Fugl-Meyer shoulder/elbow/forearm scale. Higher numbers reflect better motor function:

  • Patients in the robot group improved 5 points, from an average of 19 points to 24 points.
  • Patients in the standard therapy group improved 2 points, from 22 to 24 points.
  • No patients complained of any side effects from the robotic therapy.

The Israeli-based company that makes the system could not be reached for comment on its cost. But Robert J. Adams, MD, director of the Medical University of South Carolina Stroke Center in Charleston, tells WebMD that if robot-assisted therapy can replace standard rehab, he “envisions that it could end up being cost-effective. One-on-one rehab with an occupational therapist is inefficient and not well paid for.”

However, this study shows only that it is useful in conjunction with standard rehab, not in place of it.

Many questions remain, Adams says. “For example, why do it four to eight weeks after the stroke? Why in 40-minute sessions? And how long does the effect last? These are all things we don’t know.”

The study was in funded in part by Teijin Pharma Limited, which makes the robotic system in Japan.

These findings were presented at a medical conference. They should be considered preliminary as they have not yet undergone the “peer review” process, in which outside experts scrutinize the data prior to publication in a medical journal.

Interim CDC Guidance on Pre-Exposure Prophylaxis for HIV Prevention in MSM

In the wake of the iPrEx study, the CDC offers some general guiding principles for the implementation of pre-exposure prophylaxis.

The iPrEx study recently demonstrated proof-of-principle for the efficacy of oral chemoprophylaxis in preventing HIV infection among men who have sex with men (MSM). Daily tenofovir/FTC (Truvada) was associated with a 44% reduction in the risk for HIV acquisition, relative to placebo; efficacy was strongly associated with medication adherence (JW AIDS Clin Care Nov 23 2010). These results are tremendously exciting, but many questions remain about the appropriate use of pre-exposure prophylaxis (PrEP) in real-world clinical settings. On January 28, 2011, the CDC offered some interim guidance.

The key points are as follows:

  • PrEP should be considered for use only in MSM who are at ongoing high risk for HIV acquisition.
  • PrEP candidates should undergo conventional HIV antibody testing to ensure that they are HIV-negative. Those with signs or symptoms of acute HIV infection should undergo viral-load testing or nucleic acid amplification testing (NAAT). All candidates should be screened for other sexually transmitted infections (STIs) and for hepatitis B.
  • Tenofovir/FTC, dosed at 1 tablet daily, is the only currently recommended PrEP regimen. It should not be used in people with creatinine clearance <60 mL/minute.
  • PrEP should be prescribed for only 3 months at a time, to ensure appropriate follow-up.
  • Every 2 to 3 months, PrEP recipients should receive HIV antibody testing, counseling regarding risk reduction and medication adherence, and assessment for possible signs and symptoms of STIs. STI testing should be conducted every 6 months. Serum creatinine levels should be assessed 3 months after PrEP initiation and then yearly.
  • HIV antibody testing should be performed at discontinuation of PrEP.

Comment: These guidelines provide basic recommendations for clinicians who are interested in implementing PrEP based on the data that are currently available. The recommendation for follow-up every 2 to 3 months is clearly a concession to the reality that monthly follow-up (as was done in iPrEx) is unlikely to be feasible or practical outside the research setting. Many prevention experts will also take issue with the instruction to provide baseline viral-load testing and NAAT only to candidates who are clinically symptomatic; in the iPrEx study, investigators inadvertently enrolled 10 individuals with acute HIV infection, presumably because they were asymptomatic. Given the resistance consequences of missing such infection, one could argue that if an individual is at sufficient risk to warrant PrEP intervention, he should be screened at baseline with both HIV antibody testing and viral-load testing or NAAT. Alternatively, the fourth-generation HIV test that involves both antigen and antibody detection could be employed as a compromise between sensitivity and cost for detection of acute infection. More formal PrEP guidelines from the U.S. Department of Health and Human Services and the FDA are eagerly anticipated and are likely to include guidance on the type of provider that should be prescribing PrEP, application to other populations, and longer-term safety follow-up.

— Raphael J. Landovitz, MD, MSc

Dr. Landovitz is Assistant Professor, Division of Infectious Diseases, Center for Clinical AIDS Research and Education, University of California, Los Angeles. He reports no conflicts of interest.

Published in Journal Watch HIV/AIDS Clinical Care February 14, 2011

Efficacy and safety of scorpion antivenom plus prazosin compared with prazosin alone for venomous scorpion sting:

Envenomation by Mesobuthus tamulus scorpion sting can result in serious cardiovascular effects. Scorpion antivenom is a specific treatment for scorpion sting. Evidence for the benefit of scorpion antivenom and its efficacy compared with that of commonly used vasodilators, such as prazosin, is scarce. We assessed the efficacy of prazosin combined with scorpion antivenom, compared with prazosin alone, in individuals with autonomic storm caused by scorpion sting.
DESIGN: Prospective, open label randomised controlled trial.
SETTING: General hospital inpatients (Bawaskar Hospital and Research Centre Mahad Dist-Raigad Maharashtra, India).
PARTICIPANTS: Seventy patients with grade 2 scorpion envenomation, older than six months, with no cardiorespiratory or central nervous system abnormalities.
INTERVENTIONS: Scorpion antivenom plus prazosin (n=35) or prazosin alone (n=35) assigned by block randomisation. Treatment was not masked. Analysis was by intention to treat.
MAIN OUTCOME MEASURES: The primary end point was the proportion of patients achieving resolution of the clinical syndrome (sweating, salivation, cool extremities, priapism, hypertension or hypotension, tachycardia) 10 hours after administration of study drugs. Secondary end points were time required for complete resolution of clinical syndrome, prevention of deterioration to higher grade, doses of prazosin required overall and within 10 hours, and adverse events. The study protocol was approved by the independent ethics committee of Mumbai.
RESULTS: Mean (SD) recovery times in hours for the prazosin plus scorpion antivenom group compared with the prazosin alone groups were: sweating 3 (1.1) v 6.6 (2.6); salivation 1.9 (0.9) v 3 (1.9); priapism 4.7 (1.5) v 9.4 (1.5). Mean (SD) doses of prazosin in the groups were 2 (2.3) and 4 (3.5), respectively. 32 patients (91.4%, 95% confidence interval 76.9% to 97.8%) in the prazosin plus antivenom group showed complete resolution of the clinical syndrome within 10 hours of administration of treatment compared with eight patients in the prazosin group (22.9%, 11.8% to 39.3%). Patients from the antivenom plus prazosin group recovered earlier (mean 8 hours, 95% CI 6.5 to 9.5) than those in the control group (17.7 hours, 15.4 to 19.9; mean difference -9.7 hours, -6.9 to -12.4). The number of patients whose condition deteriorated to a higher grade was similar in both groups (antivenom plus prazosin four of 35, prazosin alone five of 35). Hypotension was reported in fewer patients in the antivenom plus prazosin group (12 of 35, 34.3%) than in the prazosin group (19 of 35, 54.3%), but the difference was not statistically significant. No difference was noted in change in blood pressure and pulse rate over time between two groups.
CONCLUSION: Recovery from scorpion sting is hastened by simultaneous administration of scorpion antivenom plus prazosin compared with prazosin alone.

Source: this trial is registered in India

Effect of Occult Metastases on Survival in Node-Negative Breast Cancer.

Background Retrospective and observational analyses suggest that occult lymph-node metastases are an important prognostic factor for disease recurrence or survival among patients with breast cancer. Prospective data on clinical outcomes from randomized trials according to sentinel-node involvement have been lacking. Methods We randomly assigned women with breast cancer to sentinel-lymph-node biopsy plus axillary dissection or sentinel-lymph-node biopsy alone. Paraffin-embedded tissue blocks of sentinel lymph nodes obtained from patients with pathologically negative sentinel lymph nodes were centrally evaluated for occult metastases deeper in the blocks. Both routine staining and immunohistochemical staining for cytokeratin were used at two widely spaced additional tissue levels. Treating physicians were unaware of the findings, which were not used for clinical treatment decisions. The initial evaluation at participating sites was designed to detect all macrometastases larger than 2 mm in the greatest dimension. Results Occult metastases were detected in 15.9% (95% confidence interval [CI], 14.7 to 17.1) of 3887 patients. Log-rank tests indicated a significant difference between patients in whom occult metastases were detected and those in whom no occult metastases were detected with respect to overall survival (P=0.03), disease-free survival (P=0.02), and distant-disease-free interval (P=0.04). The corresponding adjusted hazard ratios for death, any outcome event, and distant disease were 1.40 (95% CI, 1.05 to 1.86), 1.31 (95% CI, 1.07 to 1.60), and 1.30 (95% CI, 1.02 to 1.66), respectively. Five-year Kaplan-Meier estimates of overall survival among patients in whom occult metastases were detected and those without detectable metastases were 94.6% and 95.8%, respectively. Conclusions Occult metastases were an independent prognostic variable in patients with sentinel nodes that were negative on initial examination; however, the magnitude of the difference in outcome at 5 years was small (1.2 percentage points). These data do not indicate a clinical benefit of additional evaluation, including immunohistochemical analysis, of initially negative sentinel nodes in patients with breast cancer.

source: NEJM

Efficacy and safety of pregabalin for treating neuropathic pain associated with diabetic peripheral neuropathy

To evaluate the efficacy, safety and pharmacokinetics of pregabalin in treating neuropathic pain associated with diabetic peripheral neuropathy in Japanese patients.
METHODS: A randomized, double-blind, placebo-controlled, multicentre 14 week clinical trial was conducted. Japanese patients with diabetic peripheral neuropathy (n = 317) were randomized to receive placebo or pregabalin at 300 or 600 mg/day. The primary efficacy measure was a change of mean pain score from baseline to end-point from patients` daily pain diaries.
RESULTS: Significant reductions in pain were observed in patients treated with pregabalin at 300 and 600 mg/day vs. placebo (P < 0.05). Improvements in weekly pain scores were observed as early as week 1 and were sustained throughout the study period (300 and 600 mg/day difference from placebo at study end-point, -0.63 and -0.74, respectively). Pregabalin produced significant improvements in weekly sleep interference scores, the short-form McGill Pain Questionnaire, the Medical Outcomes Study-Sleep Scale, the 36-item Short-Form Health Survey scale, and the Patient and Clinical Global Impression of Change. Patient impressions of numbness, pain and paraesthesia were also significantly improved. Regarding treatment responders, 29.1 and 35.6% of patients treated with 300 and 600 mg/day, respectively, reported >/= 50% improvement in mean pain scores (vs. 21.5% for placebo). Pregabalin was well tolerated; somnolence (26%), dizziness (24%), peripheral oedema (13%) and weight gain (11%) were the most common adverse events and generally were reported as mild to moderate.
CONCLUSIONS: Pregabalin was effective in reducing pain and improving sleep disturbances due to pain, and was well tolerated in Japanese patients with painful DPN.

source: BMJ evidence update

Potential of immunosuppressive agents in cerebral ischaemia

Ischaemic stroke is a disorder involving multiple mechanisms of injury progression including activation of glutamate receptors, release of proinflammatory cytokines, nitric oxide (NO), free oxygen radicals and proteases. Presently, recombinant tissue plasminogen activator (rtPA) is the only drug approved for the management of acute ischaemic stroke. This drug, however, is associated with limitations like narrow therapeutic window and increased risk of intracranial haemorrhage. A large number of therapeutic agents have been tested including N-methly-D-aspartate (NMDA) receptor antagonist, calcium channel blockers and antioxidants for management of stroke, but none has provided significant neuroprotection in clinical trials. Therefore, searching for other potentially effective drugs for ischaemic stroke management becomes important. Immunosuppressive agents with their wide array of mechanisms have potential as neuroprotectants. Corticosteroids, immunophilin ligands, mycophenolate mofetil and minocycline have shown protective effect on neurons by their direct actions or attenuating toxic effects of mediators of inflammation. This review focuses on the current status of corticosteroids, cyclosporine A, FK506, rapamycin, mycophenolate mofetil and minocycline in the experimental models of cerebral ischaemia.
source: Indian journal of medical research