Prospective study of exogenous hormones and risk of pulmonary embolism in women

BACKGROUND: Current use of oral contraceptives (OCs) is a well-recognised risk factor for venous thrombosis and consequent pulmonary embolism (PE). Little is known about residual effects of past OC use. Furthermore, few epidemiological studies have assessed the relation between postmenopausal use of hormones and thrombotic disease. METHODS: In this prospective study information was obtained through questionnaires sent every 2 years (1976-92) to 1125,93 women aged 30-55 in 1976. We excluded women with previously diagnosed cardiovascular disease or cancer in 1976 and at the beginning of each subsequent 2-year follow-up period. FINDINGS: From self-reports and medical records, we documented 123 cases of primary PE (no identified antecedent cancer, trauma, surgery, or immobilisation). Current users of postmenopausal hormones had an increased risk of primary PE (relative risk adjusted for multiple risk factors 2.1 [95% CI 1.2-3.8]). However, past use showed no relation to PE (1.3 [0.7-2.4]). In current users of OCs the risk of primary PE was about twice that in non-users (2.2 [0.8-5.9]), but this finding was based on only five cases who were current OC users. Users of OCs in the past had no increase in risk of PE (0.8 [0.5-1.2]). These relations were consistent irrespective of cigarette-smoking status. INTERPRETATION: Primary PE was uncommon in this cohort. The risk was increased by current though not past use of postmenopausal hormones or OCs.     

Pharmacokinetic parameters of sisomicin

Sisomicin in doses of 1 mg/kg was administered intramuscularly to 10 healthy volunteers, and 1 week later the same volunteers received sisomicin at the same dose intravenously. A peak serum concentration of sisomicin of 3.08 mug/ml was obtained 1 h after intramuscular injection, and a peak serum concentration of 7.12 mug/ml was achieved 30 min after a 30-min intravenous infusion. The sisomicin elimination data were analyzed according to a two-compartment model. Pharmacokinetic parameters derived from the intramuscular and intravenous studies were quite similar.     

Vicryl-mesh wrap for the implantation of hydroxyapatite orbital implants: an animal model

OBJECTIVE: To evaluate host fibrovascularization of hydroxyapatite orbital implants wrapped in sclera or in Vicryl (polyglactin 910) mesh in a rabbit model. NUMBERS: Eight adult New Zealand white rabbits that received hydroxyapatite orbital implants wrapped in homologous donor sclera (four animals) or Vicryl mesh (four animals). INTERVENTIONS: The rabbits had one eye enucleated and then received a 12-mm hydroxyapatite implant wrapped in sclera or Vicryl mesh. Magnetic resonance imaging (MRI) and bone scintigraphy were done to assess host fibrovascularization of the implant 4, 8, 12 and 20 weeks after implantation. Two animals (one in each group) were killed at each of these times, and the implant was removed for histopathological examination. MAIN OUTCOME MEASURES: Enhancement on MRI, uptake on bone scintigraphy, fibrovascularization seen on histopathological examination. RESULTS: The degree of fibrovascularization was substantial in all the specimens but appeared greater in the Vicryl-mesh-wrapped implants in the first 12 weeks after implantation on both histopathological and MRI studies. At 20 weeks these findings were similar in the two groups. A granulomatous foreign-body giant-cell reaction to both the Vicryl mesh and the implant itself was present up to 8 weeks after implantation. Bone scans showed only grade 1+ activity in all the implants. CONCLUSIONS: Host fibrovascularization in the rabbit appears to occur to a greater degree in Vicryl-mesh-wrapped hydroxyapatite implants than in those wrapped in donor sclera during the first 12 weeks after implantation. Vicryl mesh appears to be an acceptable alternative wrap for the hydroxyapatite implant, eliminating the need for donor sclera and its potential risks of transmissible diseases.     

Differences in body composition of black and white girls

Adults have racial differences in body composition that may modulate risks resulting from obesity. Although black and white children have been shown previously to have differences in bone mineral density and subcutaneous body fat, differences in visceral adipose tissue have not been evaluated. We studied 20 black and 20 white normal-weight girls aged 7-10 y, who were matched for weight, body mass index (BMI), bone age, chronological age, Tanner breast stage, and socioeconomic status. Each underwent anthropometric measurements, bioelectrical impedance analysis, dual-energy X-ray absorptiometry (DXA), and abdominal magnetic resonance imaging (MRI) for determination of total (TAT), visceral (VAT), and subcutaneous (SAT) adipose tissue. Serum lipids and fasting and 2-h oral-glucose-tolerance test (OGTT) glucose and insulin concentrations were also measured. There were no differences between groups in absolute waist circumference or waist-to-hip ratio, but waist-to-thigh ratio was smaller in black than in white girls. Black girls had greater bone mineral density and less TAT, VAT, and SAT than whites. VAT was not significantly correlated with any measure of insulin, or with serum lipids. However, both basal and 2-h OGTT serum insulin were significantly correlated with SAT as assessed by MRI in black girls (r2 = 0.46 for basal insulin, P = 0.001: r2 = 0.31 for 2-h insulin, P = 0.01) but not in white girls (r2 < 0.05, for basal and 2-h insulin, NS). We conclude that there are significant racial differences in body composition and differences in the strength of association between abdominal adipose tissue depots and insulin sensitivity in black and white girls.     

A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds

Congeners of nitrogen monoxide (NO) are neuroprotective and neurodestructive. To address this apparent paradox, we considered the effects on neurons of compounds characterized by alternative redox states of NO: nitric oxide (NO.) and nitrosonium ion (NO+). Nitric oxide, generated from NO. donors or synthesized endogenously after NMDA (N-methyl-D-aspartate) receptor activation, can lead to neurotoxicity. Here, we report that NO.- mediated neurotoxicity is engendered, at least in part, by reaction with superoxide anion (O2.-), apparently leading to formation of peroxynitrite (ONOO-), and not by NO. alone. In contrast, the neuroprotective effects of NO result from downregulation of NMDA-receptor activity by reaction with thiol group(s) of the receptor's redox modulatory site. This reaction is not mediated by NO. itself, but occurs under conditions supporting S-nitrosylation of NMDA receptor thiol (reaction or transfer of NO+). Moreover, the redox versatility of NO allows for its interconversion from neuroprotective to neurotoxic species by a change in the ambient redox milieu. The details of this complex redox chemistry of NO may provide a mechanism for harnessing neuroprotective effects and avoiding neurotoxicity in the central nervous system.