Torsemide: a new loop diuretic

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of torsemide are reviewed. Torsemide belongs to the pyridine-sulfonylurea class of loop diuretics. Its primary site of activity is the thick ascending limb of the loop of Henle, where it blocks active reabsorption of sodium and chloride, resulting in diuresis, natriuresis, and other effects. Torsemide has high bioavailability, a relatively long half-life, and a prolonged duration of activity. It is highly protein bound. Clinical trials indicate that torsemide is effective in the treatment of hypertension and of edema and other symptoms in patients with chronic renal failure (CRF), hepatic dysfunction, or congestive heart failure (CHF). Torsemide has infrequent, mild, and transient adverse effects; among the most common are orthostatic hypotension, fatigue, dizziness, and nervousness. The recommended initial oral dosages of torsemide are 10-20 mg/day for CHF, 20 mg/day for CRF, 5 mg/day for hypertension, and 5-10 mg/day (in combination with a potassium-sparing diuretic or aldosterone antagonist) for hepatic cirrhosis. In most patients, the pharmacokinetic advantages of torsemide over other loop diuretics are unlikely to translate into a substantial edge in clinical outcomes, and in practice there may be no cost advantages. Although torsemide does not offer major advantages over other loop diuretics, it may be of benefit in patients who do not respond to or cannot tolerate other agents.     

Occurrence of aflatoxins, fumonisin B1, and zearalenone in foods and feeds in Botswana

Sorghum and maize form the main dietary staple foods in Botswana. Other products such as peanuts, peanut butter, phane (an edible larval stage of an emperor moth Imbrasia belina Westwood), and pulses (cowpeas and beans) are also widely used as food and for the manufacture of feeds. These important food and feed commodities were analyzed for the presence of aflatoxins, fumonisin B1, and zearalenone. Aflatoxins were detected in 40% of the samples analyzed. The concentration of total aflatoxins ranged from 0.1 to 64 microg/kg. The mean concentration ranged from 0.3 microg/kg in sorghum to 23 microg/kg in peanut butter. Peanut butter samples were the most contaminated (71%). No aflatoxins were detected in maize. Fumonisin B1 was detected in 36% of the samples. Maize samples were the most contaminated (85% of the samples) with the concentration ranging from 20 to 1,270 microg/kg. No fumonisin B1 was detected in peanuts, phane, and beans. Zearalenone was only found in 2.6% of the samples analyzed at 40 microg/kg. Aflatoxins were the most common toxins detected in foods and feeds in Botswana. However, fumonisin B1 was more prevalent in maize than aflatoxins or zearalenone.     

Trypanosoma cruzi genotypes associated with domestic Triatoma sordida in Bolivia

Triatoma sordida is the second species of Triatominae considered of epidemiological significance in Bolivia. Associated with Triatoma infestans in various regions, it is as yet the only triatomine species established in human dwellings in localities of Velasco province, Department of Santa Cruz. This domestication is considered as primary. Flagellate parasites were detected in 16.2% of domiciliary T. sordida and the kDNA-PCR confirmed the presence of Trypanosoma cruzi. Frequencies of T. cruzi clonets 20 and 39, common clonets in Bolivian domestic cycle (T. infestans), were established by their direct detection in feces using PCR and hybridization. These clonets present low frequencies in T. sordida and synanthropic mammals. Forty-six stocks were isolated and analysed by multilocus enzyme electrophoresis (MLEE). The MLEE showed a higher clonal diversity than in T. infestans domestic cycle and the genotypes were clustered in the two principal lineages of T. cruzi. Within each lineage, a broad variability was observed. Mixture of genotypes was mostly observed in mammals. The large diversity of T. cruzi in this cycle should be related to its sylvatic origin. Moreover, the current limited sample of stocks suggests a lineage association with specific hosts.     

Micelle formation in mixtures of nonionic and cationic detergents

The effect of a homologous series of polyoxyethylene n-dodecanols on the critical micelle concentration (cmc) of mixtures with n-dodecyl trimethyl ammonium bromide (DTAB) and of polyoxyethylene n-hexadecanols on the cmc of mixtures with n-hexadecyl trimethyl ammonium bromide (CTAB) has been studied in terms of the composition of the mixtures. The cmc of the nonionic component of the mixed micelles is approximately one hundredth of that of the cationic component. Only a gradual increase in the cmc values of the mixed micelles above the values of the nonionic components was observed in the composition range of 0–75 mole % or 0–90 mole %, respectively, of cationic detergent. This is followed by an abrupt transition to the high cmc values of the cationic component. This abrupt transition is considerably reduced by addition of NaBr. It is postulated that in the absence of added electrolyte the degree of ionic repulsion of the cationic component in mixed micelles is markedly decreased as the proportion of nonionic component reaches a threshold range of 25 or 10 mole %, respectively. Swamping of charges reduces ionic repulsion in NaBr solutions and, consequently, the abrupt transition in the cmc vs. composition curves is reduced.     

Patellofemoral complications in symmetrical total knee arthroplasty

A review of 356 Kinemax (Howmedica, Inc, Rutherford, NJ) cemented posterior cruciate ligament-retaining condylar total knee arthroplasties employing a symmetrical femoral component articulating with a medially offset symmetrical dome patella component was carried out to examine the results and determine the incidence and nature of the patellofemoral complications. Follow-up was from 3 to 8 years, with a mean of 5.1 years. A review of patellofemoral complications in previously reported homogeneous series of symmetrical and asymmetrical implants is presented. Mean postoperative Knee Society scores improved to 91, function scores to 86, and Hospital of Special Surgery scores to 90 yielding 95% good and excellent results. Mean postoperative range of motion was -1.5 degrees extension to 113 degrees flexion. There were five patellofemoral complications (1.4%), including two symptomatic subluxations, two distal pole avulsion fractures, and one lateral facet fracture. There were two reoperations necessary for patellofemoral problems (0.56%), one to correct subluxation and one for excision of the fractured lateral facet. These rates are lower than those previously reported for asymmetrical implants as well as current and phased-out symmetrical designs of total knee arthroplasty in the intermediate term. This review suggests that cemented total knee arthroplasty with symmetrical patellofemoral resurfacing with an offset patella dome and posterior cruciate ligament retention yields low patellofemoral complications and reoperations. The symmetrical femoral component appears to be a satisfactory compromise of "normal" femoral anatomy, which decreases inventory and cost without adversely affecting patellofemoral function and complications.     

Biosynthesis of progesterone derived neurosteroids by developing avian CNS: in vitro effects on the GABAA receptor complex

Although enthusiasm for measuring health-related quality of life (HRQL) in clinical trials exists, information is limited on the meaning of scores. We examined the relation between scores from the 34-item Medical Outcomes Study HIV Health Survey (MOS-HIV) and the more detailed HIV Overview of Problems-Evaluation System (HOPES) using the responses of 318 HIV-infected outpatients being treated in Los Angeles and Baltimore. With the HOPES problem statements as independent variables, statistically significant predictors of the variation in MOS-HIV scores for the Physical Function, Mental Health, and Energy/Fatigue scales were identified using stepwise regression. Approximately 60% to 70% of the variation in each of the scores was explained by five to seven different HOPES problem statements, with a single item explaining 47% to 59% of the variation. We created illustrative profiles for each of the three MOS-HIV scales using the HOPES items identified in the regressions. Independent of the scale, persons scoring in the top MOS-HIV quartile tended to report few if any problems, whereas a decline in score to the next quartile was characterized by functional difficulties (e.g., "HIV interferes with work"). The onset of specific problems might trigger further evaluation and potential intervention from health care providers to help maintain patient functioning.     

Signal losses in diffusion preparation: Comparison between spin-echo, stimulated echo and SEASON

Diffusion-weighted magnetic resonance imaging and spectroscopy commonly apply a spin-echo or stimulated echo preparation including sensitizing field gradients. The article reports on a systematic numerical approach to an optimum diffusion preparation considering undesired signal losses caused by relaxation. A large range of possible applications on whole-body units and animal scanners is covered. Instructions for an optimized type and timing of the diffusion preparation are provided for the readership, based on the desired diffusion weighting (b-value), the available maximum field gradient amplitudes, the RF pulse durations and gradient ramp times, and the relaxation characteristics of the specimen (or tissue) of interest. In addition, a new type of diffusion preparation named SEASON (simultaneous Spin-Echo And Stimulated echO preparatioN) is introduced and compared with spin-echo and stimulated echo diffusion preparation. It is demonstrated that spin-echo preparation is superior to stimulated echo preparation in all cases with T₂ ≈ T₁ and in all cases with relatively low diffusion weighting resulting in short duration of diffusion sensitizing gradients δ « T₂. For tissues with T₂ « T₁ (as musculature or red bone marrow) stimulated echo preparation becomes superior to spin-echo preparation for high ratios b/A² (b-value indicates diffusion weighting,A is the maximum gradient amplitude). The new SEASON technique allows a higher yield in signal intensity compared to spin-echo or stimulated echo preparations in clinically relevant cases. © 1998 Elsevier Science B.V. All rights reserved.     

Cluster analysis and disease mapping--why, when, and how? A step by step guide

Growing public awareness of environmental hazards has led to an increased demand for public health authorities to investigate geographical clustering of diseases. Although such cluster analysis is nearly always ineffective in identifying causes of disease, it often has to be used to address public concern about environmental hazards. Interpreting the resulting data is not straightforward, however, and this paper presents a guide for the non-specialist. The pitfalls include the fact that cluster analyses are usually done post hoc, and not as a result of a prior hypothesis. This is particularly true for investigations prompted by reported clusters, which have the inherent danger of overestimating the disease rate through "boundary shrinkage" of the population from which the cases are assumed to have arisen. In disease surveillance the problem of making multiple comparisons can be overcome by testing for clustering and autocorrelation. When rates of disease are illustrated in disease maps undue focus on areas where random fluctuation is greatest can be minimised by smoothing techniques. Despite the fact that cluster analyses rarely prove fruitful in identifying causation, they may-like single case reports-have the potential to generate new knowledge.