Erythromycin-induced hypotension.
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Anti-Bacterial Agents↗
Biomedical subjects
G R Brown
Publications and source records attributed to G R Brown.
The use of methylphenidate for cognitive decline associated with HIV disease.
OBJECTIVE: Complaints of cognitive changes are often expressed by patients at all stages of HIV infection. Such changes include decreased memory and attention span, diminished concentration, apathy, and "slowing." Methylphenidate (MPD) has been used in several clinical studies in men with late-stage HIV disease in an attempt to ameliorate these difficulties. The objectives of this review article are to review salient psychopharmacological characteristics of MPD and to describe the research and clinical literature supporting the use of MPD in patients at all stages of HIV infection. METHODS: Seven studies, case reports, or abstracts from International Conferences on AIDS were available in the English literature through August, 1993, directly addressing the use of MPD in patients with HIV disease. Twenty-nine papers were reviewed for pharmacokinetic data, eighteen for safety and side effects issues, and seventeen for relevant contributions from the neuropsychological testing literature. RESULTS: Studies in clinical settings have used doses ranges from 10-90 mg. per day in two or three divided doses with reportedly good results in improving both affective and cognitive symptoms associated with HIV disease. Side effects have been relatively mild and patient satisfaction with treatment has been high. However, no studies have been conducted in early stage HIV disease, where a significant minority of patients have similar complaints in the absence of clinically apparent immunosuppression. Likewise, placebo-controlled, dose-finding studies in AIDS patients are entirely lacking, and no studies in women with HIV disease and cognitive changes have been published. CONCLUSIONS: In spite of these important research short-comings, clinical experience with MPD treatment of cognitive changes in men with HIV/AIDS is consistent with the notion that this medication holds significant promise to improve the quality of life for persons living with HIV/AIDS. Controlled studies to test this hypothesis are warranted.
AIDS Dementia Complex↗
Characterisation of a novel Ca2+ pump inhibitor (bis-phenol) and its effects on intracellular Ca2+ mobilization.
Bis-phenol, a phenolic antioxidant, is an inhibitor of sarcoplasmic reticulum (SR), endoplasmic reticulum (ER) and plasma membrane Ca2+ ATPases. The concentration of bis-phenol giving half-maximal inhibition of the SR Ca(2+)-ATPase is 2 microM. On binding to the SR Ca(2+)-ATPase it shifts the E2 to E1 transition towards the E2 state and slows the transition between E2 to E1. Bis-phenol completely inhibits Ca(2+)-dependent ATP hydrolysis and Ca2+ uptake by rat cerebellar microsomes at a concentration of 30 microM. The plasma membrane Ca(2+)-ATPase is also completely inhibited at similar concentrations, however, the Na+/K(+)-ATPase is only marginally affected. Other inhibitors of the ER Ca(2+)-ATPases, thapsigargin and 2,5-di-(tert-butyl)-1,4-benzohydroquinone (BHQ), inhibit Ca2+ uptake by approximately 75%. Bis-phenol therefore inhibits all types of ER Ca(2+)-ATPases present in cerebellum. This inhibitor is also able to mobilize Ca2+ from intracellular Ca2+ stores, including those sensitive to InsP3, in intact HL-60 cells.
Adenosine Triphosphate↗
Women in relationships with cross-dressing men: a descriptive study from a nonclinical setting.
Over a 6-year period, 106 women involved with men who cross-dress (mostly heterosexual transvestites) completed a questionnaire regarding themselves, their male partners, and their relationships. Interview data supplemented these questionnaires for 75% of the respondents. All respondents were recruited from nonclinical settings. The "modal" female partner was a 40-year-old Protestant, Caucasian woman, who was a firstborn child, in her first marriage. She was more likely than other women her age to be childless, and to have earned at least a 2-year college degree. She was no more likely to have had lesbian experiences or substance use problems than comparably aged American women. She had been married to her cross-dressing mate for 13 years and had known of his activities for 9 years. A quarter of women reported at least occasional sexual arousal to their mate's cross-dressing. The two variables associated with low acceptance of cross-dressing were discovery of their partner's cross-dressing after marriage and lack of sexual arousal to cross-dressing stimuli. Low acceptance was unrelated to firstborn status, amount of exposure to cross-dressing activities, or having had children. This group may be more representative of women in relationships with cross-dressing men than previous reports limited to cross-dressers and spouses who are in treatment.
Adult↗
Inositol 1,4,5-trisphosphate-, GTP-, arachidonic acid- and thapsigargin-mediated intracellular calcium movement in PANC-1 microsomes.
Inositol 1,4,5-trisphosphate (IP3)-, GTP-, arachidonic acid- and thapsigargin-mediated Ca2+ release from endoplasmic reticulum (ER)-enriched microsomes was studied in a PANC-1 cell line. IP3 maximally caused an approximately 20% release of actively accumulated Ca2+. This effect was completely blocked by heparin. In the presence of 3% polyethylene glycol (PEG), GTP maximally discharged about 60% of Ca2+ from the microsomes. This effect involved a GTP hydrolytic process, not the IP3-activated Ca2+ channel. Arachidonic acid maximally released approximately 80% of Ca2+ from PANC-1 microsomes. Metabolites of arachidonic acid did not appear to be involved in arachidonic acid-mediated Ca2+ release. However, other fatty acids also induced similar releasing effects suggesting that arachidonic acid-induced Ca2+ release appeared to be non-specific. Thapsigargin was shown to inhibit Ca2+ accumulation into and induce Ca2+ release from PANC-1 microsomes. The thapsigargin-releasable Ca2+ pool included the IP3- or arachidonic acid-sensitive pool. Studies on liposomes suggested that both arachidonic acid and thapsigargin did not exert either a Ca2+ ionophore-like or a membrane detergent-like effect. The present results have provided evidence for the existence of multiple non-mitochondrial Ca2+ pools in PANC-1 cells. These Ca2+ pools could be released by various Ca2+ mediators via different mechanisms.
Arachidonic Acid↗
Analysis of the interactions of calcium and trifluoroperazine with skeletal muscle calsequestrin.
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Calcium↗
Divergent effects of epidermal growth factor and calcipotriol on human rectal cell proliferation.
Vitamin D may protect against colorectal cancer by reducing cell proliferation and inducing differentiation. By contrast, epidermal growth factor (EGF) stimulates cell proliferation and may encourage gastrointestinal mucosal healing. This study investigated the effect of a synthetic vitamin D analogue, calcipotriol, and EGF on human rectal epithelial cell proliferation in patients with familial adenomatous polyposis (FAP). In addition, a new technique to measure the cell cycle time is described. Sigmoidoscopic biopsy specimens were obtained from 14 patients with FAP. Tissue was established in organ culture, with or without the addition of EGF (n = 8), or calcipotriol (n = 6). Proliferation was determined using (a) metaphase arrest to measure the crypt cell production rate, (b) native mitotic index, and (c) the growth fraction using PC10 antibody. EGF receptor expression was shown using a polyclonal antibody AP12E. Calcipotriol reduced crypt cell production rate by 52% from mean (SEM) 5.29 (1.18) to 2.56 (0.80) cells/crypt/hour (p < 0.01) and EGF increased crypt cell production rate by 102% from 3.62 (0.59) to 7.33 (0.90) cells/crypt/hour (p < 0.05), and this tissue expressed the EGF receptor. The growth fraction was 48.40 (4.0)%, and the native mitotic index 1.08 (0.14)%. The cell cycle time was estimated as 94.5 hours and the time for mitosis as one hour. Thus, calcipotriol and EGF have divergent effects on human rectal mucosal proliferation.
Adenomatous Polyposis Coli↗
Drug- and nutrition-induced hypophosphatemia: mechanisms and relevance in the critically ill.
OBJECTIVE: To provide an outline of the drugs and nutritional therapy that could contribute to the development of hypophosphatemia in the critically ill patient. DATA SOURCES: Computerized abstracting services, references to primary literature articles, and review publications were screened for references to drug- or nutrition-related hypophosphatemia. STUDY SELECTION: Studies primarily describing responses in adults were selected. Animal research is described that illustrates findings in humans. DATA EXTRACTION: Information was abstracted from the findings of individual case reports and clinical trials. DATA SYNTHESIS: Data are organized by mechanism of possible effect on serum phosphate concentration. No reference is made to drugs that do not have an effect on phosphate metabolism. CONCLUSIONS: Hypophosphatemia can have significant effects that would hinder recovery of the critically ill patient. Antacids, catecholamines, beta-adrenergic agonists, sodium bicarbonate, and acetazolamide are commonly used therapeutic agents that could contribute significantly to the development of hypophosphatemia. Provision of nutrition to the chronically malnourished individual or chronic administration of phosphate-depleted parenteral nutrition could produce symptoms associated with hypophosphatemia. Other drugs could have a mild effect on lowering serum phosphate concentrations, but would be unlikely to produce symptoms unless combined with other etiologies of hypophosphatemia.
Critical Illness↗
Diagnosing child maltreatment.
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Battered Child Syndrome↗
Dipeptidyl peptidase I is enriched in granules of in vitro- and in vivo-activated cytotoxic T lymphocytes.
Recent studies have suggested that dipeptidyl peptidase I (DPPI) is the major post-translational processing enzyme responsible for generating activated myeloid and lymphoid granule serine proteases. The current studies assessed the relative levels of DPPI and granzyme A (BLT esterase) in B6 anti-H-2d-specific CTL generated in mixed lymphocyte cultures (in vitro-activated CTL), by infusion of B6 spleen cells into irradiated H-2d mice (graft-vs-host, GVH CTL) or by 1 degree and 2 degrees peritoneal immunization of B6 mice with P815 (H-2d) cells (PE CTL). In contrast to low levels of DPPI activity in unstimulated CD4+ spleen T cells, both unstimulated CD8+ spleen T cells and in vitro-activated CTL populations were several-fold enriched in DPPI activity, while PE CTL and GVH CTL expressed even higher levels of DPPI. Depletion of DPPI-enriched cells by treatment with Leu-Leu-OMe resulted in loss of cytolytic effector function from each CTL population. However, PE CTL and GVH CTL were more sensitive to the toxicity of Leu-Leu-OMe than were in vitro-activated CTL. While standard BLT esterase assays detected much higher levels of this serine protease activity in GVH CTL or in vitro-activated CTL than in PE CTL, levels of BLT esterase activity significantly above the basal levels present in unstimulated CD8+ or CD4+ T lymphocytes were found in association with immunoreactive granzyme A in lysates of PE CTL. In both PE CTL and in vitro-activated CTL, DPPI and BLT esterase activity co-localized in the granule fraction of cell lysates, and similar percentages of total cellular BLT esterase and DPPI were exocytosed upon cross-linking of surface CD3. Thus, both in vivo- and in vitro-activated CTL were found to possess functional granules containing readily detectable albeit somewhat different levels of DPPI and granzyme A activity.
Animals↗
The effects of thimerosal on calcium uptake and inositol 1,4,5-trisphosphate-induced calcium release in cerebellar microsomes.
Thimerosal inhibits calcium uptake in skeletal muscle sarcoplasmic reticulum and rat cerebellar microsomes by inhibiting the Ca(2+)-ATPase. In the presence of 5 mM dithiothreitol (DTT), Ca2+ uptake and ATPase activity were not inhibited by thimerosal, indicating that thimerosal modifies cysteine residues of the Ca(2+)-ATPase. Low thimerosal concentrations (2 microM) sensitize the inositol 1,4,5-trisphosphate (InsP3)-sensitive Ca2+ channel, making it open at lower InsP3 concentrations. Higher concentrations of thimerosal, however, cause inhibition of InsP3-induced Ca2+ release. Both sensitization and inhibition of the InsP3 receptor by thimerosal can be prevented by DTT. The binding and metabolism of InsP3 by cerebellar microsomes is not affected by thimerosal. The amount of InsP3-induced Ca2+ release is co-operatively linked to the InsP3 concentration with a Hill coefficient of 2.0 +/- 0.3. This is decreased to 1.0 +/- 0.2 at inhibitory concentrations of thimerosal. Under our experimental conditions, we observed no dependence of quantal Ca2+ release on intraluminal Ca2+ concentration.
Adenosine Triphosphate↗
Polylysine-coated polyacrylamide resins as sorbents for bile acids.
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Absorption↗
Psychiatric length of stay determinants in a military medical center.
In this 2-year prospective study, 1040 consecutive admissions to an adult inpatient psychiatric unit of the United States Air Force's largest tertiary care medical center were assessed for length of stay (LOS) determinants. Twenty-one demographic, clinical, and diagnostic variables were examined for their effect on LOS. The median LOS at our medical center was 9 days and was similar to the national median LOS of 10 days for psychiatric units in general hospitals. We found several clinical, nonclinical, and diagnostic variables to be independent predictors of LOS, accounting for 31% of the variance, but that much of the variance remained unaccounted for. Primary DSM-III-R discharge diagnoses were helpful in distinguishing a nonoverlapping, short-stay group from a long-stay group. HCFA Diagnostic Related Group (DRG) estimates for LOS were assessed for their ability to predict LOS in our institution. With the exception of substance abuse/dependence disorders, DRGs consistently underestimated LOS. Previous studies using the coefficient of variation (COV) have demonstrated the inability of DRGs to distinguish homogeneous diagnostic groups. However, in this study, COV was helpful in differentiating a majority of DRGs by LOS despite the general underestimation of LOS by DRG. These results continue to support the inadequacy of the DRGs in determining equitable reimbursement and the difficulties in predicting psychiatric LOS despite the inclusion of clinical and nonclinical variables.
Adolescent↗
A prospective study of psychiatric aspects of early HIV disease in women.
Few studies of psychiatric morbidity associated with HIV disease have included women. The authors prospectively studied a cohort of HIV-seropositive women, none of whom had AIDS, to assess changes in their psychiatric status over time. All seropositive women admitted to the U.S. Air Force's HIV evaluation unit for comprehensive evaluations since 1987 were eligible for enrollment in an open-ended prospective study. Forty-three women without AIDS enrolled between 1987 and 1991 (83% of those eligible), 29 of whom have been interviewed at least twice. The Structured Clinical Interview for DSM-III-R and a semistructured interview were administered to assess psychiatric diagnoses, suicidality, sexual functioning, affective status, and other psychosocial variables. Women were more likely to have a psychiatric diagnosis at follow-up, largely accounted for by a substantial increase in sexual dysfunction (41% of reevaluated group). None engaged in suicidal behavior or required psychiatric hospitalization during the 86.9 woman-years of observation. High-risk sexual behavior occurred after seroconversion in at least 35% of the group, with no interval decline. Most women with early stage disease were free of major psychiatric disorders at both assessments. Many developed sexual dysfunction that impaired intimate relationships and detracted from quality of life. The psychiatric natural history of HIV infection in women appears to differ from that observed in studies of men.
AIDS Serodiagnosis↗
Neuropsychiatric morbidity in early HIV disease: implications for military occupational function.
The Military Medical Consortium for Applied Retroviral Research Program's (MMCARR) Behavioral Medicine Human Immunodeficiency Virus (HIV) Research component is conducting a tri-service, comprehensive, and longitudinal research study in military HIV-infected personnel at all stages of infection. Identification of neuropsychiatric and psychosocial outcomes and their determinants will help the military minimize the impact of the HIV epidemic on military readiness and function. Neuropsychiatric and psychosocial findings are among the most common complications seen in early HIV disease and among the most likely to have an adverse impact on military readiness and function. The study has demonstrated that the average HIV-infected service person experiences at least transient military occupational difficulty following notification of HIV status. More than 15% at any given time have levels of clinical or subclinical anxiety or depression that are referrable for mental health intervention. Ten per cent of study subjects have a current major mood disorder and 5% have a psychoactive substance use disorder. Finally, 17% of study subjects have experienced serious suicidal ideation or behaviours at least once since notification of seropositivity. Fortunately, however, data also indicate at least partial effectiveness of current primary, secondary and tertiary preventive efforts. Only about 1% of Air Force HIV-infected persons are discharged for psychiatric reasons prior to eventual medical discharge. Further, a large majority of active-duty patients demonstrate solid military occupational and social performance. Though military HIV neurobehavioural research is still in progress, preliminary data identify social support and pre-HIV psychiatric predisposition as important factors associated with current neuropsychiatric status.
Aerospace Medicine↗
Inhibition of the sarcoplasmic and endoplasmic calcium pump by bis(2-hydroxy-3-tert-butyl-5-methyl)methane, (bis-phenol).
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Animals↗
Drug concentration monitoring. An approach to rational use.
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Drug Monitoring↗
Cephalosporin-probenecid drug interactions.
The effect of concurrent probenecid administration on the pharmacokinetics of cephalosporin antibiotics varies with the available cephalosporins. Most cephalosporins are affected to some degree by concurrent probenecid administration, although ceforanide, ceftazidime, ceftriaxone and latamoxef (moxalactam) have no significant changes in pharmacokinetics. For those cephalosporins affected by probenecid, the predominant findings are impairment in renal clearance resulting in increased peak serum concentrations, an increased area under the concentration-time curve (AUC), and both delayed and prolonged recovery of the cephalosporin in the urine. The distribution of the cephalosporins is affected to varying degrees, with reports of increased penetration into ocular, central nervous system and blister fluids noted with some agents. The clinical relevance of the changes in cephalosporin distribution associated with probenecid administration has not been investigated. The dose and timing of probenecid administration appear to be major determinants in any possible interaction. Studies with ceftizoxime and cefoxitin suggest that larger probenecid doses result in greater changes in the pharmacokinetics of cephalosporins. Prolonged probenecid therapy before administration of a cephalosporin did not seem to be as relevant as the probenecid dosage in determining the magnitude of the interaction. Probenecid administration with or immediately before cephalosporin administration appears able to produce these documented changes in cephalosporin pharmacokinetics. The route of administration (oral versus parenteral) of either prolosporin pharmacokinetics. The route of administration (oral versus parenteral) of either probenecid or the cephalosporin does not appear to influence the characteristics of the interactions. The therapeutic efficacy of a combination of a cephalosporin with probenecid has been most thoroughly studied for single-dose treatment of gonorrhoea. The addition of probenecid to cephalosporin therapy results in sustained systemic concentrations adequate for eradication of Neisseria gonorrhoeae. Regimens involving either second or third generation cephalosporins demonstrate good success rates with single-dose therapy. However, the success of ceftriaxone administered alone for treatment of both penicillase-producing and non-penicillase-producing strains of N. gonorrhoeae suggests that the addition of probenecid is unnecessary. The use of probenecid, in combination with cephalosporins, to enhance the treatment of other venereal and systemic infections has preliminary, inconclusive support.
Cephalosporins↗