Stress across three cultures: Great Britain, the United States, and China.
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Biomedical subjects
Publications and source records attributed to L Golden.
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OBJECTIVE: To describe trends in the prescription of menopausal estrogens and medroxyprogesterone in the United States. METHODS: Annual estimates of the number of prescriptions for menopausal estrogens and medroxyprogesterone and descriptive information on patients and providers were obtained from two pharmaceutical marketing research data bases, the National Prescription Audit and the National Disease and Therapeutic Index of IMS America. RESULTS: An estimated 13.6 million prescriptions were dispensed for oral menopausal estrogens in 1982, and 31.7 million in 1992, a 2.3-fold increase (P = .0001). In 1992, Premarin, the only oral conjugated estrogen currently approved for use, was the most frequently dispensed brand-name pharmaceutical in the United States. Dispensed prescriptions for Estraderm, a transdermal estradiol first marketed in 1986, increased from 1.5 million in 1987 to 4.7 million in 1992. Dispensed prescriptions for oral medroxyprogesterone also increased from 2.3 million prescriptions in 1982 to 11.3 million in 1992, a 4.9-fold increase (P = .0001). An estimated one in six to one in four postmenopausal women were taking menopausal hormones in 1992. These drugs were prescribed mainly by obstetrician-gynecologists. CONCLUSION: The use of menopausal estrogens and medroxyprogesterone has increased substantially over the past decade. These trends indicate that American women are widely exposed to menopausal hormone replacement.
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A 69-year-old man receiving monotherapy for lung cancer with dichloromethotrexate (DCM), and without exposure to other chemotherapeutic agents or known ototoxic drugs, developed profound cochleovestibular dysfunction. The initial presentation was vestibular. This resolved, but unilateral hearing loss ensued and continued to progress to a total of 80 db loss in the low frequency range and 40 db in the high range, despite discontinuation of the drug. Because DCM may be used in combination with the known ototoxin cisplatin, the potential of DCM as an ototoxin should also be considered in such patients.
The isolation and identification of a material present in the plasma of hypertensive dogs and hypertensive human patients has been under study since 1972. The earliest experiments in relation to this work, noted that plasma from hypertensive dogs cause a hyperresponse to norepinephrine when both were administered by way of the vein. Employing a rat assay system that consisted of an anesthetized rat with polyethylene catheters in the vein for giving norepinephrine and the test fractions and a catheter in the artery for blood pressure monitoring, fractions from hog kidney were tested for hyperresponsiveness activity. The active material is very comparable to cyclic AMP in molecular weight, ultraviolet spectrum, paper chromatography, Enzyme hydrolysis and activity in the anesthetized rat system. This evidence indicates that the hyperresponsiveness factor of renal origin is cyclic AMP.
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We have determined the DNA sequence of the H-2Kb gene of the C57B1/10 mouse. Comparison of this sequence with that of the allelic H-2Kd shows surprisingly that the exons have accumulated more mutations than their introns. Moreover, many of these changes in the exons are clustered in short regions or hot spots. Additional comparison of these sequences with the H-2Ld and H-2Db sequences shows that, in several cases, the altered sequence generated at the hot spot is identical to the corresponding region of a non-allelic H-2 gene. The clustered changes are responsible for 60% of the amino acid differences between the H-2Kb and H-2Kd genes and suggest that micro-gene conversion events occurring within the exons and involving only tens of nucleotides are an important mechanism for the generation of polymorphic differences between natural H-2 alleles.
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The influence of cimetidine (1.2 g/day for 7 days) on the disposition and pharmacodynamic effects of a single oral dose of quinidine was studied in 6 normal volunteers. Cimetidine reduced the mean apparent oral clearance of quinidine (+/- standard error of the mean) from 25.5 +/- 2.7 to 16.2 +/- 1.4 liters/h (p less than 0.05). This was reflected in a 55% (range 30 to 109) increase in the mean half-life from 5.8 +/- 0.2 to 9.0 +/- 0.6 hours (p less than 0.05). Peak quinidine plasma concentrations and times to peak were also increased (p less than 0.05). Plasma protein binding and urinary excretion of quinidine were unchanged by cimetidine treatment. Alterations in the pharmacokinetic variables of quinidine were mirrored in simultaneously measured electrocardiographic parameters. Changes in Q-T, rate-corrected Q-T, QRS, and R-R intervals after a single oral dose of quinidine sulfate (400 mg) were significant. Treatment with cimetidine potentiated these pharmacodynamic changes, but failed to achieve significant differences from quinidine alone. Thus, cimetidine impairs the elimination of oral quinidine in normal volunteers. This interaction may lead to quinidine toxicity in patients in whom cimetidine is concomitantly administered.
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Cosmids containing H-2 histocompatibility antigen genes of the H-2b haplotype have been isolated. One of these genes expresses a 45,000 molecular weight protein, indistinguishable from H-2Kb when introduced into mouse L cells. These H-2Kb transformed L cells can be killed by allospecific anti-H-2Kb cytotoxic T cells. Moreover, when infected with influenza virus, they can be killed by an H-2Kb-restricted, influenza virus-specific cytotoxic T cell line. These results show that expression of the H-2Kb gene product on the L-cell surface is sufficient to make it a target for specific T-cell killing.
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Existing animal models for inducing intrauterine growth retardation (IUGR) involve severe maternal compromise or acute fetal insult. We postulated that superovulation would produce IUGR gradually by enhancing fetal competition for nutrients. Mice were superovulated with pregnant mare serum and human chorionic gonadotrophin and killed on day 19 of gestation. Compared to controls, the mean number of fetuses was significantly increased; body, brain, liver, and placental weights were reduced; and brain/liver weight ratios were increased. Additional mice underwent partial unilateral oophorectomy before superovulation. Marked asymmetry in the number of fetuses in the two uterine horns of the same mother was produced, and the fetuses on the more crowded side manifested smaller brains and livers an increased brain/liver ratios. In the mouse, superovulation is a simple, preconceptual method for achieving IUGR and may be combined with partial unilateral oophorectomy to permit comparisons between fetuses with different growth characteristics within the same mother.
RNA metabolism during amphibian oogenesis has been investigated by the analysis of individual cDNA cloned sequences. Two cDNA clone libraries were constructed from the pA+ RNA of Xenopus ovary and of tadpole. The accumulation of RNAs complementary to individual clones was examined during oogenesis by isolating RNA from oocytes of different stages. There are only two patterns of accumulation during oogenesis. Mitochondrial mRNA sequences accumulate throughout all the stages of oogenesis, whereas all other sequences detected cease accumulation early in oogenesis and remain at a constant steady state level for the remainder of oocyte development. In the earliest stages examined, the individual RNAs are already present at approximately 1/4 their final level, and the subsequent increase of all sequences appears to be coordinant. These basic observations were confirmed by colony screening approximately 500 clones. The pattern of RNA accumulation observed is significant, because it had been determined that the total steady state pA+ RNA levels in the oocyte also ceased to increase at the same stage in oogenesis in which each individual sequenced reached a plateau level. In addition, lampbrush chromosomes, which have traditionally been thought to be the site of oocyte pA+ RNA synthesis, are maximally active after the stage in which all pA+ RNAs seem to have reached their final level of accumulation.
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