Mullerian-inhibiting substance secretion is delayed in XX sex-reversed dog embryos

A mathematical multiple dosing model was designed so that human plasma concentration-versus-time curves of beta-lactams are reproduced in mouse plasma. The pharmacokinetic parameters of FK037, a new injective cephalosporin, in volunteers and in the mice model were 6,966 and 6,894 ml, respectively, for Vc, 2.592 and 2.698/h for alpha, 0.2875 and 0.3027/h for beta, and 0.9079 and 1.0506 for K21. Therefore, real pharmacokinetics of humans were reproduced in mice by this method. The 8-hour therapeutic efficacy (the decrease of the viable counts in the lung) against pneumonia with Staphylococcus aureus and Pseudomonas aeruginosa in mice was well correlated with the time above MIC value, but not with AUC, Cmax or AUC above MIC. These results indicate that this model was valuable to evaluate the beta-lactam antibiotics for predicting their clinical efficacy and that the time above MIC is an important factor in selecting beta-lactam agents and determining dosage in pulmonary infection.     

Efficient coexpression and secretion of anti-atherogenic human apolipoprotein AI and lecithin-cholesterol acyltransferase by cultured muscle cells using adeno-associated virus plasmid vectors

Plasma apolipoprotein AI (apoAI) and lecithin-cholesterol acyltransferase (LCAT) play important roles in reverse cholesterol transport, promoting the removal of excess cholesterol from peripheral cells and reducing formation of atherosclerotic lesions. Gene augmentation of either apoAI or LCAT, or both, are thus attractive targets for prevention or treatment of atherosclerosis. With the eventual aim of safe and efficient gene delivery to skeletal muscle, our chosen secretory platform for systemic delivery of anti-atherogenic proteins, we have constructed conventional and AAV-based plasmid vectors containing human apoAI or LCAT cDNAs; their efficacy was tested by lipoplex transfection of mouse C2C12 muscle cells or human 293 cells. The secretion of apoAI or LCAT by transduced cultures was two- to five-fold higher using AAV-based plasmid vectors than conventional plasmid vectors. Additionally, cells transfected with a bicistronic AAV-based vector containing an internal ribosome entry site (IRES) efficiently expressed both apoAI and LCAT simultaneously. Furthermore, AAV-based vector sequences were retained by host cells, whereas those of conventional plasmid vectors were lost. These studies indicate that ectopic overexpression of apoAI and LCAT in muscle tissue using AAV-based plasmid vectors might provide a feasible anti-atherogenic strategy in vivo.     

Heat shock protein--peptide complexes as immunotherapy for human cancer

Not all medical practices are equipped to provide diabetes self-management training. Physicians can incorporate a team approach in their practice by establishing collaborative relationships with recognized diabetes education programs. The ADA's education recognition program has identified diabetes education programs that meet the National Standards for Diabetes Self-Management Education Programs. This list is available on the ADA's web site at http://www.diabetes.org/recognition and is printed twice a year in Diabetes Forecast. The National Certification Board for Diabetes Educators (NDEA) can provide a list of CDEs in your area. The South Carolina Model Diabetes Patient Education Program of DSC and SCDCP/DHEC is an excellent critical step towards obtaining ADA recognition.     

Gap encoding by inferior collicular neurons is altered by minimal changes in signal envelope

Neural correlates of temporal resolution in the central auditory system are currently under intense investigation. The gap detection paradigm offers a simple, yet important, test of temporal acuity because changes in behavioral gap thresholds have been correlated with deficits in complex stimulus processing, such as speech perception. In gap detection studies, silent gaps are typically shaped by rapid (< 1.0 ms) rise/fall (R/F) times, i.e., rapid decreases and increases in sound intensity. However, in nature, the envelopes surrounding silent periods can vary significantly in R/F time. Therefore, we investigated whether changes in the R/F time surrounding the silent gap affect neural processing by inferior collicular (IC) neurons. Gap R/F times were varied between 0.5 and 16 ms and the discharge pattern, response rate, and first spike latency of IC neurons were measured for gap widths up to 100 ms. Neurons were classified into phasic or tonic discharge patterns based on peri-stimulus time histograms elicited to 100 ms noise carriers. The results indicate that (1) minimal gap thresholds increased with R/F time regardless of response type, (2) first spike latency variance increased systematically with R/F time for units which had small first spike standard deviations at short R/F times, and (3) the response rate of some units (called 'gap-tuned') changed as a function of both R/F time and gap width. Gap-tuned units responded strongly to a particular gap width only when the envelope of the gap was shaped by a particular R/F time. For gap-tuned units, increases in R/F time shifted the tuning to larger gap widths and also broadened the response profile. These results show that temporal acuity of neurons in the IC, as measured by the gap detection paradigm, is sensitive to the envelope surrounding gaps embedded in noise carriers.     

A longitudinal study of blood pressure in relation to performance on the Wechsler Adult Intelligence Scale

A growth curve analysis was used to examine estimated longitudinal decline (over 19 years) on the Wechsler Adult Intelligence Scale (WAIS; D. Wechsler, 1955) in relation to arterial hypertension and blood pressure (BP) for 55 men and 85 women (40 to 70 years old) who were free from overt major coexisting diseases. BP was associated with longitudinal decline for Visualization-Performance (VP) ability and Speed. Hypertension was a weaker predictor of VP and was unrelated to Speed. Age effects on VP were overestimated when averaged BP level, particularly systolic BP, was not controlled statistically. It was concluded that initial BP level and hypertension predict age-related longitudinal decline in specific major abilities assessed by the WAIS but that BP averaged over examinations is a stronger predictor.     

Effect of vitamin D metabolites and analogs on renal and intestinal calbindin-D in the rat

The effects of endotoxin (20 mg kg-1 i.p.) on the mesenteric vascular responses to acetylcholine, bradykinin, sodium nitroprusside, and to transient occlusion of the superior mesenteric artery were examined in rats anesthetized with pentobarbitone. Mesenteric vasodilator responses to close arterial injections of acetylcholine and bradykinin were reduced at 1.5 h after endotoxin and almost abolished by 4 h; responses to sodium nitroprusside were unaffected. Occlusion of the superior mesenteric artery for 30, 60, or 120 s produced, on release of the occlusion, a time-dependent vasodilator response in the mesenteric circulation (post-occlusion hyperemia). This hyperemia was markedly reduced by nitro-L-arginine methyl ester (L-NAME); L-NAME did not modify acetylcholine-induced vasodilation. Endotoxin-pretreatment did not modify mesenteric post-occlusion hyperemia 1.5 h after administration but markedly reduced the response by 2.5 h. The administration of L-NAME to endotoxin-treated rats did not further attenuate the hyperemic responses. Mesenteric vasoconstrictor responses to phenylephrine were not modified by endotoxin, although systemic pressor responses to this agent were impaired. We concluded that endotoxin impairs endothelium and nitric oxide-dependent vasodilator responses in the mesenteric circulation.     

Pancreaticoduodenectomy for benign disease

BACKGROUND: Surgeons are often called upon to perform pancreaticoduodenectomy for either suspicion of malignancy or symptoms due to benign disease. Perioperative morbidity and mortality following pancreaticoduodenectomy have decreased markedly over the last 2 decades. In response, many surgical centers advocate expanding the indications for pancreaticoduodenectomy to include lesions other than periampullary carcinoma. PATIENTS AND METHODS: A retrospective review of medical records for 108 patients undergoing pancreaticoduodenectomy for benign disease at The Johns Hopkins Medical Institutions over 100 months was completed. The subset of patients with a histopathologic diagnosis of chronic pancreatitis was identified and compared with patients undergoing pancreaticoduodenectomy for other benign conditions. RESULTS: The mortality rate for the present series was less than 1%. Perioperative complications, the majority of which were self-limited, occurred in 51% of patients. The most common complication was delayed gastric emptying. Pancreatic anastamotic leak occurred in 18% of patients and developed significantly more frequently in patients with benign diseases other than chronic pancreatitis (31% versus 8%, P < 0.05). CONCLUSION: Among appropriately selected patients, the rates of perioperative mortality and serious morbidity are low, and concerns about mortality and morbidity should not prevent an aggressive approach to surgical resection in patients with benign disease.