A randomized controlled trial of estrogen replacement therapy in long-term users of depot medroxyprogesterone acetate

Long-term use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA, Depo-Provera) is associated with a reduction in bone mineral density (BMD), particularly in the lumbar spine. The cause of DMPA-associated bone loss is not known, but the relative estrogen deficiency induced by DMPA use could be responsible. We have undertaken a randomized, double-blind controlled trial of oral estrogen replacement therapy in 38 premenopausal women (mean age 37) with a minimum 2 yr DMPA use who had a below average baseline lumbar spine BMD (T score < or = 0). Nineteen women were allocated to receive conjugated estrogens (0.625 mg/d orally) and 19 to receive a matching placebo. All continued with regular DMPA injections throughout the study. Areal bone density was measured by dual energy x-ray absorptiometry at the lumbar spine, femoral neck, and total body sites every 6 months for 2 yr; the main outcome measure being the change in areal BMD at the lumbar spine. At baseline, the two groups were well matched for demographic, anthropometric, and biochemical variables, and for BMD. Twenty-seven subjects completed at least 18 months in the study, and 26 the full 2 yr, with similar numbers dropping out from each group (mainly for personal reasons). In the estrogen-treated group, mean lumbar spine BMD increased 1%, whereas in the placebo group it fell 2.6%, over 2 yr. The between group differences were 2.0% at 12 months (P = 0.058), 3.2% at 18 months (P < 0.01), and 3.5% at 24 months (P < 0.002). Differences of lesser statistical magnitude were seen at the femoral neck (between group differences at 2 yr: 2.7%, P = 0.24), Ward's triangle (5.0%, P = 0.055), greater trochanter (3.6%, P = 0.056), total body (1.3%, P = 0.046), legs (1.3%, P = 0.065), and trunk (2.0%, P = 0.029). There were no major adverse events. These data support the view that the likely cause of DMPA-associated bone loss is estrogen deficiency and demonstrate that it can be arrested by estrogen replacement therapy.     

Learning needs of patients with congestive heart failure

BACKGROUND: It is suggested that more effective and efficient educational intervention can be created by matching the program to patient learning needs. Previous attempts to determine the learning needs of patients with congestive heart failure (CHF) find all types of information endorsed as very important to learn. OBJECTIVES: To increase differentiation between patients' ratings of information needs by modifying the CHF Patient Learning Needs Inventory (CHFPLNI) and examined predictors of learning needs. METHODS: Thirty-four inpatients with CHF from the Toronto General Hospital, Toronto, Ontario completed the modified CHFPLNI and rank ordered the perceived importance of eight categories of CHF knowledge measured by the CHFPLNI. Patients also completed measures of emotional distress, fatigue, health beliefs, locus of control and current CHF knowledge. RESULTS: Ratings across all information categories were similar (M=4.4-5.3/7) and highly correlated (r=0.52-0.87). Patients indicated information on medication, cardiovascular anatomy and physiology, and treatment were the most important to learn on both the CHFPLNI and by rank ordering. Higher fatigue was correlated with information needs on diet (r=0.37), activity (r=0.37), psychological (r=0.38) and risk (r=0.37) factors. No other variables consistently predicted learning needs. CONCLUSIONS: Changing the format of the CHFPLNI did not increase the differentiation of patients' ratings across information categories. The assessment of patients' learning needs using extensive questionnaires does not appear warranted because simple rank ordering obtained similar information. Individuals who are more fatigued wanted more information on those aspects of care that they managed on a day-to-day basis.     

In vivo modulation of intestinal CYP3A metabolism by P-glycoprotein: studies using the rat single-pass intestinal perfusion model

P-Glycoprotein (P-gp) has been hypothesized to modulate intestinal drug metabolism by increasing the exposure of drug to intracellular CYP3A through repeated cycles of drug absorption and efflux. The rat single-pass intestinal perfusion model was used to study this interplay in vivo. N-Methyl piperazine-Phe-homoPhe-vinylsulfone phenyl (K77), a peptidomimetic cysteine protease inhibitor (CYP3A/P-gp substrate), and midazolam (CYP3A substrate) were each perfused through a segment of rat ileum alone and with the P-gp inhibitor N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)-ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamine (GG918). Samples were obtained continuously from the outlet perfusate and the mesenteric vein at 5-min intervals for 40 to 60 min. The parent drug and two main metabolites of K77 (N-desmethyl and N-oxide) and midazolam (1-OH and 4-OH) were quantitated by liquid chromatography/mass spectrometry. K77 appearance in the mesenteric blood (P(blood) = 5 +/- 3 x 10(-6) cm/s) was increased 3-fold with GG918, whereas midazolam permeability (P(blood) = 1.1 +/- 0.3 x 10(-4) cm/s) was unchanged by GG918. K77 metabolites were preferentially excreted into the lumen, 4-OH midazolam was found equally in lumen and blood, and 1-OH was mainly excreted into blood. The extent of metabolism was estimated by calculating the fraction metabolized = 1 - P(blood)/P(lumen) and the extraction ratio (ER) determined from the direct measurement of known metabolites as ER = sum metabolites(all)/(sum metabolites(all) + drug in blood). When P-gp was inhibited, the fraction metabolized for K77 was decreased (95 to 85%) and the ER tended toward a decrease, whereas no differences in either parameter were observed for midazolam (not a P-gp substrate). These data support a role for P-gp in modulating the extent of intestinal metabolism in vivo by controlling drug access to the enzyme.     

Laboratory confirmation of meningococcal disease in Scotland, 1993-9

AIMS: To describe the laboratory confirmation of meningococcal disease, using culture and non-culture based techniques, between 1993 and 1999 as part of a national service in Scotland. METHODS: Samples from patients with suspected meningococcal disease in Scotland were analysed by culture and non-culture based techniques to gain a laboratory confirmation of disease. Data were analysed to establish the number of disease cases, the serogroups of the organisms involved, and the importance of the techniques used. RESULTS: Between 1993 and 1999, there was a total of 1749 notified cases of meningococcal disease in Scotland. Culture based methods provided a laboratory confirmation of 788 cases whereas non-culture techniques confirmed 461 cases. CONCLUSIONS: Non-culture techniques were a useful addition to culture based techniques in Scotland and improved the dataset required for public health management, disease surveillance, and vaccine policy.     

An intra-individual comparison of the previous conventional hearing aid with the bone-anchored hearing aid: The Nijmegen group questionnaire

By spring 2000, a total of 351 patients were implanted in the Birmingham bone-anchored hearing aid (BAHA) programme. This group consisted of 242 adults and 109 children. The aim of this retrospective questionnaire study was to directly assess patient satisfaction with their current bone-anchored hearing aid in comparison with their previous conventional air and/or bone-conduction hearing aids. The Nijmegen group questionnaire was sent by post to 312 patients who used their BAHA for six months or longer. The questionnaire used was first described by Mylanus et al. (Nijmegen group) in 1998. The total response rate was 72 per cent (227 of 312 patients). The bone-anchored hearing aid was found to be significantly superior to prior conventional hearing aids in all respects.     

Neonatal spinal cord injury

Neonatal spinal cord injury (SCI) is well described in the literature, though its diagnosis is often delayed or missed in the neonatal period. We present a neonate who was referred with upper gastrointestinal bleed and a diagnosis of spinal cord injury was subsequently made clinically and confirmed radiologically.     

Neuropsychological consequences of HIV in children: a review of current literature

Pediatric HIV has reached epidemic proportions. In 1997, 1.1 million children younger than 15 were living with HIV or AIDS. The virus affects children cognitively and developmentally due to the immaturity of their nervous systems and immune systems. Studies in the area of neuropsychological deficits are as yet limited in number and less well developed than studies on adult HIV. However, despite methodological weaknesses, the literature has proven conclusively that pediatric HIV affects children cognitively, developmentally, emotionally, psychologically, behaviorally, and educationally. Although treatments are allowing these children to live longer, the effects of the virus remain, requiring special care. This review examines the mechanisms behind HIV in children, the neuropsychological findings to date, and the limitations of this work. Possible useful future approaches in understanding the neuropsychological course of the disorder, as well as directions for treatment and prevention are addressed.     

Alpha(1)-adrenoceptor-mediated depolarization and beta-mediated hyperpolarization in cultured rat dorsal root ganglion neurones

The effect of excitotoxic injury on the production of monocyte chemoattractant protein-1 (MCP-1) was examined in rat cortico-striatal slice cultures. Treatment with 50 microM N-methyl-D-aspartate (NMDA) for 4 h, which caused severe damage in neurons, induced the production of MCP-1 in astrocytes. Production levels were markedly elevated immediately after the treatment, peaked at 4-8 h, and had decreased to nearly the basal level by 72 h. Since the treatment promoted the release of MCP-1 in the slice cultures, but not in the enriched astrocyte cultures, it is unlikely that NMDA directly acted on the astrocytes. These results suggest that information on neuronal injury induced by NMDA is transmitted to astrocytes to induce the production of MCP-1. Organotypic slice cultures are useful for investigating the inflammatory responses of astrocytes in the process of neuronal injury.     

Response decision processes and externalizing behavior problems in adolescents

Externalizing behavior problems of 124 adolescents were assessed across Grades 7-11. In Grade 9, participants were also assessed across social-cognitive domains after imagining themselves as the object of provocations portrayed in six videotaped vignettes. Participants responded to vignette-based questions representing multiple processes of the response decision step of social information processing. Phase 1 of our investigation supported a two-factor model of the response evaluation process of response decision (response valuation and outcome expectancy). Phase 2 showed significant relations between the set of these response decision processes, as well as response selection, measured in Grade 9 and (a) externalizing behavior in Grade 9 and (b) externalizing behavior in Grades 10-11, even after controlling externalizing behavior in Grades 7-8. These findings suggest that on-line behavioral judgments about aggression play a crucial role in the maintenance and growth of aggressive response tendencies in adolescence.