Recommendations from a multi-study evaluation of proposed criteria for staging reproductive aging.

In 2001, the Stages of Reproductive Aging Workshop (STRAW) proposed bleeding and endocrine criteria for defining the early and late menopausal transition stages. Based on expert consensus, STRAW recommended a shorter interval of amenorrhea than the commonly used 90-day amenorrhea criteria for late transition and a >7-day change in cycle length for early transition. The ReSTAGE collaboration used prospective menstrual calendar data from four cohorts (TREMIN, Melbourne Women's Midlife Health Project, Seattle Midlife Women's Health Study, and Study of Women's Health Across the Nation) to quantitatively evaluate STRAW's recommendations. This empirical assessment supported the STRAW recommendations that (1) > or =60 days of amenorrhea be used to define the late menopausal transition and (2) that early transition is consistent with a persistent 7 or more day difference in length of consecutive cycles. Serum follicle stimulating hormone (FSH) values > or =40 IU/l was an independent marker of the transition and, when occurring together with a bleeding marker, increased prediction of final menstrual period. Such a FSH criterion could be incorporated into the STRAW paradigm to facilitate prediction of proximity of the final menstrual period.     

A phase II study of 5-fluorouracil and leucovorin in advanced carcinoma of the esophagus.

Thirty-five patients with advanced epidermoid carcinoma of the esophagus were treated with 5-fluorouracil (5-FU) 425 mg/m2 and leucovorin 20 mg/m2, day 1-5 every 28 days. Six patients had a partial response (95% confidence limit, 7-35%) with a median response duration of 32 weeks. The median survival time of the patients on study was 14 weeks. The toxicity was acceptable, with only two patients experiencing severe hematologic toxicity and one patient experiencing severe nausea and vomiting. The addition of leucovorin at this dose level in this population of patients with advanced disease does not appear to enhance the activity of 5-FU for patients with squamous cell cancer of the esophagus. Since only a small percentage of patients experienced significant toxicity, a higher response rate could be achieved in patients treated with the maximally tolerated dose.     

Improved cytosolic free calcium mobilization and superoxide production in bicarbonate-based peritoneal dialysis solution

Background. Intraperitoneal phagocytes play an important role in local host defence to prevent CAPD peritonitis. The intracellular calcium [Ca²⁺]i is thought to be involved in the regulation of various cell functions. This study therefore investigates the effect of lactate-based dialysis solution (LBDS) and bicarbonate-based dialysis solution (BBDS) on cytosolic free calcium mobilization and superoxide production (SP) as important steps in signal transduction and bacterial killing. Methods. We studied changes in [Ca²⁺]i and SP following stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP) in polymorphonuclear neutrophils (PMNs) incubated in either LBDS-pH 5.2, LBDS adjusted to pH 7.4, 1:10 diluted spent and fresh LBDS or BBDS-pH 7.4 with different glucose concentrations, comparing the data with cells treated with Hanks buffer (HBSS) pH 7.4 as control. To elucidate the effect of glucose and lactate PMNs were additionally incubated in HBSS-pH 7.4, containing glucose (HBSS-Glu-pH 7.4) or lactate (HBSS-Lact-pH 7.4) in the same concentrations as contained in CAPD solutions and tested as above. PMNs were isolated from healthy blood donors and incubated with dialysis solution 10 min prior to stimulation with fMLP. Results. [Ca²⁺]i mobilization and SP were completely inhibited in PMNs incubated in LBDS pH 5.2. pH adjustment of LBDS to 7.4 and 1:10 dilution of spent and fresh LBDS corrected some of the suppression of the calcium influx and superoxide production. BBDS pH 7.4, however, preserved physiological cell function significantly better at low (1.5 and 2.3%) glucose concentrations. Conclusion. In comparison to conventional lactate-based dialysis solution, pH adjusted and 1:10 diluted LBDS, bicarbonate-based dialysis solution is more biocompatible since it preserves significantly better neutrophil cell functions.     

Computed tomographic measurement of gluteal subcutaneous fat thickness in reference to failure of gluteal intramuscular injections.

OBJECTIVE: Casual observation of gluteal region fat thickness on computed tomography (CT) of the pelvis leads to the hypothesis that, in some individuals, intended intramuscular injections are not properly deposited in the gluteal muscle. We gathered and analyzed data to determine whether this hypothesis was true. METHODS: CT scans of the pelvis were analyzed over an 18-day period in the fall of 2005. The thickness of gluteal region subcutaneous fat was measured in a standardized manner. RESULTS: Measurement of gluteal region subcutaneous fat thickness was performed for 298 pelvic CT scans. There were 150 male subjects and 148 female subjects. The average gluteal fat thickness for female subjects was 33.2 mm, whereas the average for male subjects was 23.1 mm. Analysis revealed a significant difference in gluteal region fat thickness between male and female subjects. A 37-mm needle, allowing for 6-mm penetration of the gluteal muscle, would not have entered the gluteal muscle fibres in 81 of 148 female subjects (54.7%), in 21 of 150 male subjects (14%), and in 102 of the 298 total sample (34.2%). Analysis revealed a significant difference between male and female subjects with regard to gluteal muscle needle penetration. CONCLUSION AND RECOMMENDATION: An overall predicted failure rate of 34% was identified for intended gluteal intramuscular injections when the standard technique was used. This is important information for care providers who inject medications in the gluteal region. In a significant number of patients, the medications will be injected subcutaneously and not into the gluteal musculature, possibly altering the pharmacokinetics of the administered medication. An alternative injection site should probably be chosen to increase the success rate of intramuscular deposition of medications and vaccines in unselected adults.     

A New Method for Estimating Dermal Absorption from Chemical Exposure. 3. Compared with Steady-State Methods for Prediction and Data Analysis

Purpose. This paper compares unsteady-state and steady-state methods for estimating dermal absorption or analyzing dermal absorption data. The unsteady-state method accounts for the larger absorption rates during short exposure times as well as the hydrophilic barrier which the viable epidermis presents to lipophilic chemicals. Methods. Example calculations for dermal absorption from aqueous solutions are presented for five environmentally relevant chemicals with molecular weights between 50 and 410 and log₁₀K_ow between 0.91 and 6.8: chloromethane, chloroform, chlordane, 2,3,7,8-TCDD, and dibenz(a,h)anthracene. Also, the new method is used to evaluate experimental procedures and data analyses of in vivo and in vitro permeation measurements. Results. In the five example cases, we show that the steady-state approach significantly underestimated the dermal absorption. Also, calculating permeability values from cumulative absorption data measured for exposure periods less than 18 times the stratum corneum lag time will overestimate the actual permeability. Conclusions. In general, steady-state predictions of dermal absorption will underestimate dermal absorption predictions which consider unsteady-state conditions. Permeability values calculated from data sets which include unsteady-state data will be incorrect. Strategies for analyzing in vitro diffusion cell experiments and confirming steady state are described.     

Murine retroviral disease-enhancing effects of a pyrimidinone immunomodulator.

(B10.A x A/WySn)F1 mice, infected with the Friend virus (FV) complex, were used as a predictive therapeutic model for AIDS. These infected mice exhibit many of the viral and immunologic manifestations of AIDS. Bropirimine (2-amino-5-bromo-6-phenyl-4[3H]pyrimidinone, ABPP) is an immunomodulating compound which has been shown to inhibit other viral infections. Oral (per os treatment) dosages of ABPP ranging from 50 to 400 mg/kg/day for 3 days resulted in increased numbers of infectious centers in the infected mice and increased splenomegaly and percentage of Ig+ (B cells) in spleens of infected and uninfected mice. Decreased percentages of total Thy-1.2+ (total T) cells and L3T4+ (T-helper) cells were seen in both uninfected and infected mice and a slightly decreased percentage of Ly-2+ (T-suppressor/cytotoxic) cells was observed in spleens of the infected mice. No effect on Ly2+ cells in spleens of uninfected mice was found. Intraperitoneal injection, single or multiple, of 20-200 mg/kg ABPP prior to FV injection resulted in increased spleen weights but had no effect on numbers of infectious centers in the spleens or on FV antibody titers in the plasma. Intraperitoneal treatment of uninfected mice with ABPP resulted in slight or no changes in percentages of Thy-1.2+, L3T4+ and Ly-2+ cells. Mice receiving multiple exposures of ABPP had an increase in percentage of splenic B cells and a depressed response to the T cell mitogen PHA. Treatment with ABPP induced the production of interferon (IFN); however, a state of hyporesponsive IFN production was seen following multiple administrations of ABPP. These data suggest that the immunomodulator ABPP may have an enhancing effect on this retroviral disease.     

Comparison of lead levels in bone, feathers, and liver of herring gull chicks (Larus argentatus).

Bone, feathers, and liver were analyzed for lead in herring gull chicks (Larus argentatus) of two different ages. The highest levels were found in the bone, evidence of chronic exposure. No differences were found within the bones. Differences occurred between different bones, with the ribs having twice the amount of lead than any other bone. These studies indicate that type of bone affects lead levels; thus researchers should clearly state which parts of which bones are examined. It is also suggested that for humans consistent location should be used for analysis by in vivo X-ray fluorescence.