Of fruits and fats: high-sugar diets restore fatty acid profiles in the white adipose tissue of captive dwarf lemurs.

Fat-storing hibernators rely on fatty acids from white adipose tissue (WAT) as an energy source to sustain hibernation. Whereas arctic and temperate hibernators preferentially recruit dietary polyunsaturated fatty acids (PUFAs), tropical hibernators can rely on monounsaturated fatty acids that produce fewer lipid peroxides during oxidation. Nevertheless, compositional data on WAT from tropical hibernators are scant and questions remain regarding fat recruitment and metabolism under different environmental conditions. We analyse fatty acid profiles from the WAT of captive dwarf lemurs (Cheirogaleus medius) subjected to high-sugar or high-fat diets during fattening and cold or warm conditions during hibernation. Dwarf lemurs fed high-sugar (compared to high-fat) diets displayed WAT profiles more comparable to wild lemurs that fatten on fruits and better depleted their fat reserves during hibernation. One PUFA, linoleic acid, remained elevated before hibernation, potentially lingering from the diets provisioned prior to fattening. That dwarf lemurs preferentially recruit the PUFA linoleic acid from diets that are naturally low in availability could explain the discrepancy between captive and wild lemurs' WAT. While demonstrating that minor dietary changes can produce major changes in seasonal fat deposition and depletion, our results highlight the complex role for PUFA metabolism in the ecology of tropical hibernators.

Mild-to-moderate uncomplicated hypertension: further analysis of a cost-effectiveness study of five drugs.

A cost-effectiveness model was designed to explore the effect of adding a new angiotensin-II inhibitor, telmisartan, to the therapeutic options for treating mild-to-moderate uncomplicated hypertension. Incorporating the cost of drugs, physician visits, and adverse-event treatments, the model concluded that availability of telmisartan on formulary may shorten the mean time and costs to control. The stability of the initial findings over a range of sensitivity analyses lends credence to the model conclusions that availability of telmisartan on formulary improves the therapeutic options of care for hypertension.

Delphi panel study of current hypertension treatment patterns.

OBJECTIVE: The purpose of this study was to assess whether, and to what extent, usual practice in the management of patients with mild to moderate hypertension differs from that recommended in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI). The results were used as input for a clinical decision analytic model to assess the cost-effectiveness of a new treatment for hypertension. METHODS: A Delphi panel survey of general practitioners and cardiologists in the United States was conducted to determine current strategies for the treatment of mild to moderate uncomplicated hypertension. The purpose of the panel survey was to reach consensus on 3 key facets of the JNC-VI guidelines and how they relate to the respondents' clinical practices: (1) the definition of mild to moderate hypertension, (2) the treatment that adult patients with uncomplicated mild to moderate hypertension should receive, and (3) the management of patient follow-up. RESULTS: Of the 20 physicians contacted for the survey, 10 responded to both rounds of the questionnaire. There was considerable variation in the responses for defining the ranges of healthy, acceptable, unacceptable, and serious blood pressure. In general, the Delphi panel respondents cited higher limits than stated in the JNC-VI guidelines. Physicians followed the guidelines approximately 60% of the time. Primary determinants of initial drug choice among the panelists were comorbid conditions and the severity of hypertension; patients' age, race, and sex were secondary determinants. Follow-up typically occurred 1 month after therapy initiation. Panelists reported titrating the dose of new therapies upward once or twice before discontinuing the drug for lack of efficacy. Once adequate blood pressure control was achieved, patient follow-up was reported to occur every 3 to 4 months. CONCLUSIONS: This Delphi panel study highlights the differences between clinical practice and the JNC-VI guidelines in the treatment of hypertension. The results were used as a basis for defining a structure for a cost-effectiveness model and provided the management practice and prescribing practice patterns required by the model.

[Viral infection, the mask of decompression sickness and decompression sickness diagnosed as viral infection]. / Zakazenie grypopodobne maska choroby cisnieniowej i choroba cisnieniowa rozpoznana jako zakazenie grypopodobne.

Two cases of diving persons: a soldier from the military centre of divers training and a student amateur diver, have been presented in the study. On the basis of similar symptoms--among others: muscular pain, discomfort, subfebrile body temperature, extremely different, incorrect diagnoses were given and improper treatment was introduced. In the case of the soldier suffering from a viral infection decompression sickness was diagnosed only because he served in a divers unit. Whereas, in the second case a physician did not take into consideration all available history data and diagnosed influenza despite evident symptoms of decompression sickness. In the discussion the factors which should have guided the physician in both cases to proper diagnosis and proper therapeutic management have been indicated.

Pharmacokinetics and pharmacodynamics of recombinant human interleukin-12 in male rhesus monkeys.

The pharmacokinetics and pharmacodynamics of recombinant human interleukin-12 (rHuIL-12) were investigated in male rhesus monkeys. The monkeys received a 40-min i.v. infusion of 42.5 micrograms/kg of recombinant human interleukin-12 on day 1 followed by a s.c. injection of the same dose on day 5. Serum samples were collected at appropriate time points and assayed for interleukin (IL-12) by an IL-12 capture bioassay, interferon (IFN-gamma) by an IFN-gamma enzyme-linked immunosorbent assay, and neopterin by a neopterin radioimmunoassay. After i.v. infusion, the systemic clearance rate of this protein was very slow (average, 3 ml/hr/kg). The volume of distribution at steady state ranged from 59 to 90 ml/kg. After the s.c. dose, the mean Cmax was 61 ng/ml and the mean Tmax was 18 hr. The absolute bioavailability was moderate (20-30%) after s.c. injection. By compartmental analysis, by using a two-compartment model the T 1/2 lambda 1 ranged from 0.2 to 5 hr and the T 1/2 lambda 2 ranged from 13 to 19 hr. When determining the percentage of the area of the serum concentration-time curve, per phase, > 85% of the protein was found in the lambda 2 phase. We selected IFN-gamma as one of the pharmacodynamic markers to study because it is produced by T-lymphocytes and natural killer cells in response to IL-12. In addition, once IFN-gamma is produced, it primes macrophages for tumor killing that in turn secrete neopterin. We show that within 24 to 48 hr after the i.v. dose, IFN-gamma concentrations are elevated in these monkeys (average, 300 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of anti-IL-1 alpha autoantibodies in the sera from healthy humans.

Previously, we reported that pooled normal human serum contained anti-IL-1 alpha autoantibodies. Further characterization studies have been undertaken with sera from individual healthy humans. Molecular exclusion chromatography demonstrated that 9 of 38 test sera contained anti-IL-1 alpha autoantibodies that specifically bound 125I-IL-1 alpha. The autoantibodies formed immune complexes composed of either one IgG or two IgG molecules bound to one 125I-IL-1 alpha molecule. The data suggest that the autoantibodies recognize at least two separate antigenic sites on IL-1 alpha. The autoantibodies neutralized IL-1 alpha induced IL-2 secretion by mouse thymocytes (EL-4 NOB-1). Further, in an in vitro competitive receptor binding assay, the autoantibodies completely blocked 125I-IL-1 alpha binding to recombinant human IL-1 receptor expressed on CHO cells. Our previous studies have established a correlation between inhibition of 125I-IL-1 alpha binding to receptor bearing cells and neutralization of IL-1 bioactivity in vitro and in vivo. These data suggest that development of anti-IL-1 alpha autoantibodies may play a significant role in modulating the effects of high local or systemic concentrations of IL-1 alpha.

Quantification of recombinant human interleukin-1 alpha by a specific two cell immunobioassay.

The detection of picogram quantities of recombinant human IL-1 alpha in human and rat serum was accomplished by a sensitive and specific two cell immunobioassay. The specificity is provided by an IL-1 alpha specific mouse IgM monoclonal antibody which is non-neutralizing thus allowing for the addition of the EL-4 NOB-1 cell line directly to the IL-1 alpha monoclonal antibody complex. The above cell line is then converted to an IL-2 producer line in response to the captured IL-1 alpha. Supernatant from the EL-4 NOB-1 cells is then added to the IL-2 dependent CTLL-2 line and cell proliferation measured by thymidine incorporation. This assay has the advantage of specificity provided by the antibody capture step, sensitivity provided by the EL-4 NOB-1 line (1-50 pg/ml) and finally ease of maintenance of the responder cell line which requires no feeder cells or mitogens. Data are reported on the sensitivity, precision, reproducibility and specificity of the assay, the stability of rhIL-1 alpha in serum and the recovery of rhIL-1 alpha from serum. We also report on the use of this procedure to assay samples from rats given ascending doses of rhIL-1 alpha.

Validity and reliability issues in alternative patient classification systems.

The validity and reliability issues involved in using alternative patient classification systems were reviewed. Disease Staging and Patient Management Categories (PMCs) were applied separately and in conjunction with DRGs to three populations of patients drawn from a nine-hospital community data base. Data were examined with analyses that were as consistent as possible with hospital-based reviews of resource utilization. Questions focused on content and context validity (partially assessable by homogeneity), general and statistical reliability (measured by variance reduction), gaming, and cost. Ordinal stratifications were inconsistently produced, and improvement to DRGs' homogeneity was generally negligible. When used alone, staging produced only half the variance reduction of DRGs. PMCs, when used alone, appeared to produce sizeable variance reductions that may have been due to the large number of one- and two-case categories produced. Staging had category overlap, was expensive, and was unidimensional and subject to manipulation. PMCs had potentially serious logic problems, and both were inadequately documented. Neither system was considered appropriate for all needs, but each might work adequately under well-defined and limited conditions.

New input to hospital decision making.

To respond to the rapidly changing environment of the hospital industry and to the impact of a prospective reimbursement experiment, the Genesee Hospital has established a new structure and process to combine clinical and administrative expertise in management and planning activities. Various analyses and recommendations are developed from a data base of merged clinical and financial information. The result has been both better-informed decision-makers and more comprehensive analyses on which to base decisions.