Sexually transmitted diseases and anal papillomas.
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Biomedical subjects
Publications and source records attributed to J Russell.
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OBJECTIVE: To compare the effectiveness and acceptability of three regimens of postcoital contraception. DESIGN: Randomised group comparison of ethinyloestradiol 100 micrograms plus levonorgestrel 500 micrograms repeated after 12 hours (Yuzpe method); danazol 600 mg repeated after 12 hours; and mifepristone 600 mg single dose. SETTING: Community family planning clinic. SUBJECTS: 616 consecutive women with regular cycles aged 16 to 45 years. MAIN OUTCOME MEASURES: Number of pregnancies, incidence of side effects, and timing of next period. RESULTS: The raw pregnancy rates (with 95% confidence intervals) for the Yuzpe, danazol, and mifepristone groups were 2.62% (0.86% to 6.00%), 4.66% (2.15% to 8.67%), and 0% (0% to 1.87%) respectively. Overall, these rates differed significantly (chi 2 = 8.988, df = 2; p = 0.011). The differences between the mifepristone and Yuzpe groups and between the mifepristone and danazol groups were also significant. Side effects were more common and more severe in the Yuzpe group (133 women (70%)) than in either the danazol group (58 (30%)) or the mifepristone group (72 (37%)). The Yuzpe regimen tended to induce bleeding early but mifepristone prolonged the cycle. Three women bled more than seven days late in the Yuzpe group compared with 49 in the mifepristone group. CONCLUSIONS: Mifepristone was effective in reducing expected pregnancy rates and the Yuzpe method also had a clinical effect. Danazol had little or no effect. A further multicentre trial is needed.
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In order to investigate new antiulcer agents, spizofurone 1 (AG-629) was fragmented and reassembled to generate 5-phenyl-2,2-dimethyl-3(2H)-furanone (bullatenone, 2). Because of the antiulcer activity of 2,5-phenyl-substituted 2,2-dimethyl-3(2H)-furanones (3-6) were made and shown to have poor activity. Insertion of an ethenyl link between the furanone and phenyl rings gave 5-(2-phenylethenyl)-2,2-dimethyl-3(2H)- furanone (7). This compound had better activity than 2. Compounds 8-41 were synthesized to evaluate the SAR in 5-(2-ethenyl substituted)-3(2H)-furanones. Electron-withdrawing substituents on the aromatic ring (8, 10, 19, and 20) gave 2-3-fold higher activity. Further increases in the activity were found when the phenyl ring was replaced by heterocyclic nuclei. Compounds that contained a thiophene (29), pyridine (24-26), or quinoline ring (32) had the best activity. Replacement of the methyl group on the furanone ring with a phenyl (34) or p-fluorophenyl (40) substituent in the 2-pyridine series gave compounds with activity that ranked with the best obtained in this study. The best compounds from the above SAR studies were evaluated in the ethanol-necrosis model for duration of cytoprotection action. Compounds 19, 24, and 29, which had the best duration of action, were tested with AG-629 in the acidified aspirin and indomethacin-induced lesion models. Only compound 24 had equivalent activity with AG-629 in both models.
This study assessed levels of depressive symptomatology in a household probability sample of Alaskan Native (N = 188) and Euro-American (N = 371) residents of 13 communities in Alaska. Our objective was to examine ethnic differences in both the association between depressive symptomatology and exposure to the Exxon Valdez oil spill and subsequent cleanup efforts, and in the role of family support as a moderator of exposure to this technological disaster. Level of exposure was significantly associated with mean Center for Epidemiological Studies-Depression Scale scores in both Natives (p less than .05) and Euro-Americans (p less than .01). Both ethnic groups also reported significant declines in traditional relations with increasing levels of exposure (p less than .001). However, Natives had a significantly higher mean Exposure Index score than Euro-Americans and were more likely to report working on cleanup activities, damage to commercial fisheries, and effects of the spill on subsistence activities. Depressive symptomatology was associated with reported participation in cleanup activities and other forms of contact with the oil in Natives, and reported damage to commercial fisheries, use of affected areas, and residence in a community in geographic proximity to the spill in Euro-Americans. Perceived family support was not directly associated with depressive symptoms in either ethnic group, but did serve to buffer the effects of exposure on depressive symptoms in Euro-Americans. The results suggest that cultural differences play an important role in determining the psychosocial impacts of a technological disaster, particularly with respect to exposure, appraisal of an event as stressful, perceived family support as a moderator of stress, and expression of depressive symptomatology.
Previous studies have demonstrated that low shear rates promote leukocyte adherence to microvascular endothelium in postcapillary venules. The objective of this study was to determine whether an accumulation of inflammatory mediators such as platelet activating factor and leukotriene B4 is responsible for shear rate-dependent leukocyte-endothelial cell adhesion. Postcapillary venules (25-39 microns in diameter) in cat mesentery were studied by intravital microscopy. Venular wall shear rate was varied over a wide range by graded occlusion of the mesenteric artery. Red blood cell velocity, vessel diameter, leukocyte rolling velocity, and the numbers of rolling and adherent leukocytes were measured at each shear rate. In one series of experiments, shear rate-dependent leukocyte adherence was monitored at different superfusion rates (1.0 and 2.5 ml/min). At the lower superfusion rate, the number of adherent leukocytes was significantly higher at any given shear rate when compared with results obtained at the higher superfusion rate. This suggests that reduced washout of inflammatory mediators contributes to shear rate-dependent leukocyte adhesion. Pretreatment with different platelet activating factor receptor antagonists (WEB 2086 or WEB 2170) had no effect on the number of adherent leukocytes normally observed at lower shear rates, suggesting that platelet activating factor does not play a major role in this process. However, shear rate-dependent leukocyte adhesion was largely prevented by pretreatment with either a leukotriene B4 receptor antagonist (SC-41930) or a leukotriene synthesis inhibitor (L663,536). The results of this study indicate that a reduced washout of leukotriene B4 is responsible for the enhanced leukocyte adherence that occurs at low venular wall shear rates.
Wingless (wg), the Drosophila homologue of the mouse Wnt-1 proto-oncogene, is a segment polarity gene essential in each segment for normal Drosophila development. We here report the isolation of two novel Drosophila Wnt homologues, DWnt-2 and DWnt-3, and thus the existence of a Wnt/wingless gene family in Drosophila. DWnt-2 and DWnt-3 map to chromosome 2 position 45E and chromosome X position 17A/B, respectively. DWnt-2 and DWnt-3, like the other known Wnt genes, encode amino-terminal signal peptides suggesting that the gene products are secreted proteins. The putative translation product of DWnt-2 and the carboxy-terminal half of the deduced DWnt-3 product are both rich in conserved cysteine residues. In comparison with other Wnt gene products, mostly about 40 x 10(3) relative molecular mass, the DWnt-3 protein has an extended amino terminus and a long internal insert, and its predicted relative molecular mass is 113 x 10(3). The expression patterns of these two Wnt/wg homologues are dynamic during Drosophila embryogenesis. The distribution of DWnt-2 transcripts is predominantly segmented, with the additional presence of transcripts in the presumptive gonads. Transcripts of both DWnt-2 and DWnt-3 appear to be associated with limb primordia in the embryo and may therefore specify limb development. DWnt-3 is also expressed in mesodermal and neurogenic regions. The distribution of DWnt-3 transcripts in cells of the central nervous system (CNS) during Drosophila embryogenesis suggests that DWnt-3 could be involved in CNS development.
Kleine-Levin Syndrome is an unusual sleep disorder occurring predominantly, but not exclusively, in late adolescent males. A case is described which illustrates some of the difficulties in diagnosis and management.
A study is described in which patients in three diagnostic groups were compared in an effort to delineate features of tardive anorexia (late onset anorexia nervosa). There were 18 patients in each diagnostic group. Patients with "classical" anorexia nervosa of less than 5 years duration were compared with patients older than 25 who had been chronically ill for more than 5 years and with those in whom the symptoms had begun de novo after the age of 25. Statistically significant differences were found to distinguish the third group as a distinct diagnostic entity. The association of loss precipitants and depressive symptoms has practical implications in the management of true anorexia tardive.
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BACKGROUND: The purpose of this study was to clarify the relationships of extractable and secreted parathyroid hormone (PTH) and parathyroid secretory protein (PSP) in human parathyroid tumors to PTH messenger RNA (mRNA), PSP mRNA, and cell replication. METHODS AND RESULTS: In tissue cultures of seven adenomas and five secondary hyperplasias, we found a direct correlation for secreted PTH versus PSP for both adenomas and secondary hyperplasias. Secreted PTH:PSP was elevated for adenomas (11:1) compared to that of secondary hyperplasias (2:1), and adenomas secreted significantly more PTH and PSP than did secondary hyperplasias. In extracts of eight adenomas and six secondary hyperplasias, the ratio of PTH:PSP was unexpectedly low (2:1) and similar for both adenomas and secondary hyperplasias. The ratio of extractable PTH mRNA:PSP mRNA was extremely low for both adenomas (1:7) and for secondary hyperplasias (1:5). Flow cytometry indicated that percent replication was inversely correlated with PTH mRNA and PSP mRNA. CONCLUSIONS: Increased PTH secretion by adenomas cannot be attributed to increased biosynthetic capacity because it is less than expected. Hypersecretion of PTH by adenomas and coincident marked reductions in PTH mRNA suggest either a defect in cytoplasmic storage of PTH or impairment of normal posttranslational degradation of PTH. As parathyroid tumor cells increase replication, PTH mRNA is reduced. Possible explanations for this include decreased PTH gene transcription or decreased mRNA half-life.
We have investigated the effect of transfection with the oncogenes c-myc and H-ras on cellular radiosensitivity. We obtained a mink lung epithelial line, Mv1Lu (ATCC CCL-64), and two sublines which had been transformed by transfection with c-myc and mutated (T24) H-ras 1. The cell survival parameters do not differ significantly between the three lines. These parameters were, for the parent line: D0 = 1.95 Gy, n = 2.0; for the c-myc transfected line: D0 = 2.10 Gy, n = 2.33; and for the H-ras transfected line: D0 = 2.40 Gy, n = 1.77. Although the terminal slope of the survival curve of the cells of the parent line is slightly steeper than that for the cells of either of the transfected lines, the differences are not significant. Nor is there any difference between the cell lines at the clinically relevant dose of 2 Gy. We conclude that neither activated H-ras nor c-myc oncogenes alter the radiosensitivity of the Mv1Lu line.
This paper describes an attempt to provide a learning environment conducive to the development of conceptual skills in critical exploration and problem solving. This is achieved by using a method of reflecting on and about critical incidents encountered by student nurses during their nursing practice. It is argued that students need help in making links between theory and practice and the article relates how this may be achieved in workshops using mainly experiential techniques. The authors conclude that the use of such a strategy can make a valuable contribution to nurse education, enabling students to look at situations from multiple perspectives and heightening awareness of the complex skills involved in nursing.
The purpose of this study was to determine the effects of 150 mg ranitidine, 300 mg ranitidine or placebo, administered every 8 h, on gastro-oesophageal pH and heartburn parameters in reflux patients. Twelve symptomatic reflux patients received each of the three treatments in a randomized, double-blind, crossover fashion. Intragastric and oesophageal pH were monitored continuously for a 24 h period. Meals were standardized, consumed at set times and patients were allowed to recline and sleep from 23.00 hours until 06.00 hours only. The gastric record was analysed for the percentage of time that the pH was greater than or equal to 4. The oesophageal record was analysed for acid contact time (percentage time (%) pH less than or equal to 4.0) and reflux episode frequency. Finally, patients recorded each new episode of heartburn and graded daytime heartburn severity at the end of each hour. Ranitidine increased the median (%) time that the intragastric pH remained at or above 4, from 4.5 (placebo) to 33.9% (150 mg dose) and 33.3% (300 mg dose). Ranitidine dose-dependently reduced the median 24-hour oesophageal acid contact time from 13.3% (placebo) to 6.8% (150 mg dose) and 2.5% (300 mg dose). The 300 mg dose significantly reduced daytime heartburn episode frequency and severity while the 150 mg dose reduced heartburn severity only. We conclude that 150 and 300 mg doses of ranitidine administered every 8 h have major, sometimes dose-dependent effects on the objective parameters and symptoms of gastro-oesophageal reflux.
The Wechsler Intelligence Scale for Children--Revised was administered to two independently identified samples of monozygotic (MZ) and dizygotic (DZ) twin children. Co-twins in the first sample were tested by the same examiner, while co-twins in the second sample were tested by different examiners. IQ intraclass correlations were similar for the two MZ twin samples (.84 and .88), and identical for the two DZ twin samples (.54). The implications of this analysis are discussed with reference to twin study methodology, research on IQ similarity and replication of child development research.
We investigated the state of the herpes simplex virus type 2 (HSV-2) genome during latency in vitro. Latent DNA was present in the cell nucleus in a nonlinear configuration. The joint fragment was represented at approximately double the molar concentration of fragments from unique regions, indicating that genome termini had fused. The HSV-2 genome copy number was estimated to be between 1.5 and 8, with a mean value of 4.5 per latently infected cell. Nonlinear HSV DNA can therefore exist during latency both in vivo and in vitro.
Interleukin 6 (IL-6) probably plays a central role in the acute phase response and in haemopoiesis and may be involved in the control of bone turnover. We have studied the release of IL-6 from human trabecular bone cells treated with a variety of stimuli using a specific bioassay. In serum free medium, unstimulated human osteoblast-like cells produced IL-6 in the range of 1000-2050 pg/ml/24 h. Recombinant human interleukin 1 (IL-1 alpha) (10(-13)-10(-11) M), tumor necrosis factor alpha (TNF alpha) (10(-9)-10(-7) M) and lipopolysaccharide (5-500 ng/ml) all stimulated release of IL-6 from human bone cells. Maximal levels of 17,000 pg/ml were observed using the highest concentration of IL-1. 1,25(OH)2D3 and PTH did not stimulate IL-6 release. Using a specific sheep antihuman IL-6 antibody, all IL-6 activity could be neutralized. In parallel studies, ROS 17/2.8 rat osteosarcoma cells released around 50 pg/ml of IL-6 under basal conditions which were increased to a maximum of 900 pg/ml by treatment with PTH (10(-9) M). The cytokines were less effective and 1,25(OH)2D3 again had no effect. Modulation of expression of IL-6 mRNA in human osteoblast cells was examined using a human complementary deoxyribonucleic acid probe. The mRNA was constitutively expressed, and IL-1 (10(-11) M) and TNF (10(-7) M) induced further mRNA expression within 2 h, which was sustained over 24 h. 1,25(OH)2D3 (10(-7) M), IL-6 (2000 pg/ml), and PTH (10(-9) M) exerted no effects at any time point. Dexamethasone (10(-6) M) suppressed both basal and IL-1- and TNF-induced IL-6 mRNA expression. IL-6 receptor mRNA was constitutively expressed but was not regulated by any of the above agents. It is clear that rodent and human osteoblasts differ in their production of IL-6 and its modulation. These data support the hypothesis that IL-6 is produced locally in human bone by osteoblasts under the direction of other cytokines. This could have implications in bone remodeling, haemopoiesis, and systemic responses to local injury.
BACKGROUND: This research investigated the accuracy of the injury-at-work item on the death certificate for surveillance of occupational injury deaths in Oklahoma during 1985 and 1986. METHODS: Representativeness of occupational injury deaths identified by death certificates was assessed by comparing these deaths with all occupational injury deaths identified through death certificates, workers' compensation reports, medical examiner reports, and OSHA records for categories of occupation, industry, and external causes of death. RESULTS: Certain external causes of death (e.g., motor vehicle traffic deaths) and certain occupations (e.g., farming) and industries (agriculture and services) are more often underidentified through death certificates. CONCLUSIONS: The findings of this study support Baker's observation that no single data source contains all deaths or all the data elements necessary to describe occupational injury deaths. Data sources may be combined to improve representativeness through more complete case ascertainment.