Flow diagram or prose: does the format of practice guidelines matter?

BACKGROUND: Hematopoietic and organ transplantations are increasing worldwide with more patients receiving immunosuppressive therapy. Neurological problems may complicate the posttransplant period. Possible causes include the conditioning regimen (e.g., seizures with busulfan), central nervous system infections (viral, bacterial, and fungal), or factors secondary to the immunosuppressive therapy and side effects of drug treatment (e.g., cyclosporine and tacrolimus). Sinus venous thrombosis, the occlusion of a cerebral venous vessel or a sinus, is an unusual cause of neurologic symptoms in patients after transplantation, and this has not been reported in the literature previously. METHODS: Three patients presenting with various neurological symptoms after allogeneic bone marrow transplantation underwent computed tomography scans and magnetic resonance imaging as a primary diagnostic procedure. RESULTS: In all patients, sinus venous thrombosis was found as the cause for seizures; it was the cause of disturbance of consciousness in two patients and headaches in two patients. All symptoms resolved without any neurologic deficiency after anticoagulation therapy with heparin followed by dicumarol. CONCLUSION: We conclude that sinus venous thrombosis should be considered as a cause of neurological symptoms in patients after transplantation under immunosuppressive therapy. Diagnosis is rapidly confirmed by noninvasive magnetic resonance imaging angiography. Therapeutic heparinization is the treatment of choice.     

Clinical presentation of experimentally induced rabies in horses

Twelve naive and nine test-vaccinated horses which developed clinical signs of rabies as a result of the required protocol of a vaccine trial were prospectively observed. Nineteen of the 21 cases were confirmed positive for rabies infection of the brain by fluorescent antibody test. The two horses with negative results had ganglioneuritis of the trigeminal ganglion or lymphocytic perivascular cuffing in the brain stem in addition to clinical signs. Average incubation period was 12.3 days and average morbidity was 5.5 days. Naive animals had significantly shorter incubation and morbidity periods (P < 0.05). Muzzle tremors were the most frequently observed (81%) and most common initial sign. Other common signs were pharyngeal spasm or pharyngeal paresis (71%), ataxia or paresis (71%), lethargy or somnolence (71%). The furious form was manifested in 43% of rabid horses and some of these furious animals initially manifested the dumb form. The paralytic form was not observed. Histopathology was characteristics for rabies. The results of this trial do not reflect on the efficacy of commercially licensed equine rabies vaccines.     

Phosphoinositide 3-kinase regulates phospholipase Cgamma-mediated calcium signaling

It has been demonstrated that the lipid products of the phosphoinositide 3-kinase (PI3K) can associate with the Src homology 2 (SH2) domains of specific signaling molecules and modify their actions. In the current experiments, phosphatidylinositol 3,4, 5-trisphosphate (PtdIns-3,4,5-P3) was found to bind to the C-terminal SH2 domain of phospholipase Cgamma (PLCgamma) with an apparent Kd of 2.4 microM and to displace the C-terminal SH2 domain from the activated platelet-derived growth factor receptor (PDGFR). To investigate the in vivo relevance of this observation, intracellular inositol trisphosphate (IP3) generation and calcium release were examined in HepG2 cells expressing a series of PDGFR mutants that activate PLCgamma with or without receptor association with PI3K. Coactivation of PLCgamma and PI3K resulted in an approximately 40% increase in both intracellular IP3 generation and intracellular calcium release as compared with selective activation of PLCgamma. Similarly, the addition of wortmannin or LY294002 to cells expressing the wild-type PDGFR inhibited the release of intracellular calcium. Thus, generation of PtdIns-3,4,5-P3 by receptor-associated PI3K causes an increase in IP3 production and intracellular calcium release, potentially via enhanced PtdIns-4, 5-P2 substrate availability due to PtdIns-3,4,5-P3-mediated recruitment of PLCgamma to the lipid bilayer.     

American College of Sports Medicine position stand. Exercise and fluid replacement

It is the position of the American College of Sports Medicine that adequate fluid replacement helps maintain hydration and, therefore, promotes the health, safety, and optimal physical performance of individuals participating in regular physical activity. This position statement is based on a comprehensive review and interpretation of scientific literature concerning the influence of fluid replacement on exercise performance and the risk of thermal injury associated with dehydration and hyperthermia. Based on available evidence, the American College of Sports Medicine makes the following general recommendations on the amount and composition of fluid that should be ingested in preparation for, during, and after exercise or athletic competition: 1) It is recommended that individuals consume a nutritionally balanced diet and drink adequate fluids during the 24-hr period before an event, especially during the period that includes the meal prior to exercise, to promote proper hydration before exercise or competition. 2) It is recommended that individuals drink about 500 ml (about 17 ounces) of fluid about 2 h before exercise to promote adequate hydration and allow time for excretion of excess ingested water. 3) During exercise, athletes should start drinking early and at regular intervals in an attempt to consume fluids at a rate sufficient to replace all the water lost through sweating (i.e., body weight loss), or consume the maximal amount that can be tolerated. 4) It is recommended that ingested fluids be cooler than ambient temperature [between 15 degrees and 22 degrees C (59 degrees and 72 degrees F])] and flavored to enhance palatability and promote fluid replacement. Fluids should be readily available and served in containers that allow adequate volumes to be ingested with ease and with minimal interruption of exercise. 5) Addition of proper amounts of carbohydrates and/or electrolytes to a fluid replacement solution is recommended for exercise events of duration greater than 1 h since it does not significantly impair water delivery to the body and may enhance performance. During exercise lasting less than 1 h, there is little evidence of physiological or physical performance differences between consuming a carbohydrate-electrolyte drink and plain water. 6) During intense exercise lasting longer than 1 h, it is recommended that carbohydrates be ingested at a rate of 30-60 g.h(-1) to maintain oxidation of carbohydrates and delay fatigue. This rate of carbohydrate intake can be achieved without compromising fluid delivery by drinking 600-1200 ml.h(-1) of solutions containing 4%-8% carbohydrates (g.100 ml(-1)). The carbohydrates can be sugars (glucose or sucrose) or starch (e.g., maltodextrin). 7) Inclusion of sodium (0.5-0.7 g.1(-1) of water) in the rehydration solution ingested during exercise lasting longer than 1 h is recommended since it may be advantageous in enhancing palatability, promoting fluid retention, and possibly preventing hyponatremia in certain individuals who drink excessive quantities of fluid. There is little physiological basis for the presence of sodium in n oral rehydration solution for enhancing intestinal water absorption as long as sodium is sufficiently available from the previous meal.     

Characterization of extracellular beta-lactamases from penicillin G-resistant cells of Streptococcus thermophilus

In this study, biochemical properties of two extracellular beta-lactamases produced by penicillin-resistant Streptococcus thermophilus cells were investigated. Both beta-lactamases showed specificity for penicillins but not for cephaloridins. The beta-lactamases exhibited different affinities for penicillin G. The one with the higher molecular weight (FI) had a Km value of 3.44 microM and a Vmax value of 8.33 mumol/min/mg of protein, whereas the beta-lactamase with the lower molecular weight (FII) had a Km value of 4.76 microM and a Vmax value of 3.13 mumol/min/mg of protein. Both beta-lactamases were inhibited by iodine, copper sulfate, and iron sulfate but not by EDTA. The optimal pH ranged between 6 and 7, and the optimal temperatures were between 40 and 45 degrees C for both enzymes.