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Biomedical subjects

R Miller

Publications and source records attributed to R Miller.

At least 379 records · Page 21Linked to original sources
PubMed1995

Determination of phenobarbitone population clearance values for South African children.

Non-liner Mixed Effects Modelling (NON-MEM) was used to estimate phenobarbitone population clearance values for South African children, using 52 serum levels gathered from 32 patients during their routine care. NONMEM was also used to evaluate the influence of fixed effects such as weight, age and concomitant medication. The final model describing phenobarbitone clearance was CL = [Exp(0.0288 Wt - 2.53)]M, where CL clearance (l x h(-1)), Exp = the base of the natural logarithm, Wt = patient weight (kg) and M = a scaling factor for concomitant medication with a value of 1 for patients on phenobarbitone monotherapy, 0.62 for those receiving concomitant valproate and 0.87 for those patients receiving concomitant carbamazepine or phenytoin. Mean (95% confidence interval) phenobarbitone clearance values were 7.6 ml x h(-1) x kg(-1) (6.2, 9.0 ml x h(-1) x kg(-1) for the monotherapy group, 5.0 ml x h(-1) x hg(-1) (4.0, 6.0 ml x h(-1) x kg(-1)) in the presence of concomitant valproate and 6.8 ml x h(-1) x kg(-1) (5.6, 8.0 ml x h(-1) x kg(-1)) in the presence of concomitant carbamazepine or phenytoin. These values are similar to those previously reported from both traditional and NONMEM pharmacokinetic studies.

Anticonvulsants↗
PubMed1995

Effect of dexamethasone treatment on the regional distribution of neutral endopeptidase activity in the rat trachea.

Treating rats with the glucocorticoid dexamethasone has been shown to reduce the amount of plasma extravasation produced in the trachea by tachykinins released from sensory nerves. We sought to determine whether dexamethasone works by increasing the activity of neutral endopeptidase (NEP), the principal enzyme thought to be responsible for degrading tachykinins in the airways. Rats were treated for 2 days with either saline or 4 mg/kg/day of dexamethasone, a dose we found to be maximally effective in reducing tachykinin-induced plasma extravasation. The tracheas were then removed and processed to reveal NEP-specific histofluorescence. Tissue sections were photographed through a fluorescence microscope, and the relative intensity of fluorescent staining was quantified in five regions of the tracheal wall using computerized image analysis. In the saline-treated rats, the rank order of fluorescent staining was perichondrium > chondrocytes = submucosal >> epithelium > lamina propria. Neither the amount nor distribution of NEP fluorescence was altered in the dexamethasone-treated rats. Biochemical measurements of NEP activity in tracheal homogenates (nmol product/h/mg protein) likewise revealed no significant difference between the two groups (34.1 +/- 3.5 vs 29.0 +/- 3.2; mean +/- SEM, n = 8). These findings suggest that dexamethasone may be working through a mechanism unrelated to NEP activation.

Animals↗
PubMed1995

Frequency of augmentation mammoplasty in patients with systemic sclerosis: data from the Johns Hopkins-University of Maryland Scleroderma Center.

The objective was to determine the frequency of augmentation mammoplasty in female patients with systemic sclerosis (SSc). Female patients with a clinical diagnosis of SSc were identified from the registry of the Johns Hopkins-University of Maryland Scleroderma Center, Washington D.C. Chapter of the Scleroderma Foundation, and files of practicing rheumatologists in the Baltimore-Washington metropolitan area. A pretested questionnaire was mailed to all eligible cases. Of 339 cases, 210 (62%) returned completed questionnaires. Three cases reported augmentation mammoplasty with silicone gel-filled prosthesis: 2 (1%) prior to and 1 (0.5%) after physician-diagnosis of SSc. The frequency of augmentation mammoplasty prior to physician-diagnosis of SSc of 9.5 per 1000 does not appear to differ from the expected frequency of 3.3-8.2 per 1000 derived from national population samples. A well-designed case-control study with population-based controls and adequate statistical power is being conducted to examine this possible association.

Adolescent↗
PubMed1995

Public reporting of performance measures in home care.

BACKGROUND: In 1992 DependiCare Home Health, Inc (Broadview, Ill), a 62-employee home medical equipment/respiratory therapy (HME) business in the Chicago metropolitan area, discovered that managed care organizations need quantifiable data from vendors in the form of measurements or outcomes. In response to this need, DependiCare developed its "Under the Microscope" program. This program provides quarterly reports (starting in April 1994) on service efficiency, patient satisfaction, and outcome statistics to referral sources, including physicians, discharge planners, and hospital executives. MEASUREMENTS: Performance measures, which represent information from DependiCare's internal operations, can be viewed as the company's quarterly report card. Areas reported on include target-time performance, same-day and under-two-hour delivery, patient (and referral source) satisfaction, equipment breakdown, and fillrate statistics. Outcome statistics include discontinuation of service by diagnosis and number of months on oxygen by diagnosis. USE OF RESULTS: Measurements help to identify weaknesses that need to be addressed by organizational or operational changes, as well as to uncover strengths that can be capitalized on for sales and marketing. Hospital-based discharge planning departments, a substantial referral source, most often use the Under the Microscope program to justify referring patients to DependiCare. Little is known about managed care customers' use of the data. CONCLUSIONS: In the long term, an integrated, automated way to track individual patients across the continuum of care from the physician, to the hospital, and to home care is needed. A centralized database of patient experience, including outcomes, could assist in health care decision making.

Capitation Fee↗
PubMed1995

Guidelines for counselling adolescents with haemophilia and HIV infection and their families.

Adolescents, poised between childhood and adulthood, and their families have many challenges. It is timely to review what these are for those with haemophilia, HIV and HCV (hepatitis C) infection in the 1990s. All three conditions are life long, life threatening and incurable. The main dilemmas facing these families are how, when and who should tell the adolescent about HIV and HCV; getting the right balance between the realities of the infections, the best interests of the adolescent and the risks of transmission of infection to others. HIV interrupts the adolescent's normal life stage expectations and development. How health carers relate to the adolescent is influenced by the split responsibilities to the adolescent and his parents as well as to others who might be at risk of infection. Clarity about the issues related to medical treatment and care, disease progression, and enhancing skills in dealing with families and young people are ways of helping to maintain hope in the face of life threatening illnesses for all concerned.

Adolescent↗
PubMed1995

Fas (CD95) participates in peripheral T cell deletion and associated apoptosis in vivo.

Following exposure to some types of antigen (superantigens), responsive T cells expand and then decline in numbers, a phenomenon that has been called 'peripheral deletion'. This process may play a role in limiting autoimmune reactions and in the maintenance of immune homeostasis. Here we describe experiments on peripheral deletion in mice carrying the lpr/lpr defect, which has been shown to be due to defective production of the CD95/Fas molecule. Young lpr/lpr mice with no apparent immunologic abnormalities display a defect in bacterial superantigen-induced peripheral deletion. Apoptotic death of the expanded T cell population associated with such peripheral deletion. Apoptotic death of the expanded T cell population associated with such peripheral deletion in normal animals is dramatically reduced in the mutant mice. Further, the levels of Fas on responding cells in normal mice increases and decreases together with increases and decreases in cell numbers, suggesting that cells with the highest levels of Fas are preferentially deleted. These observations are consistent with the known ability of CD95 to transduce a signal leading to apoptosis, and they implicate this signal transduction pathway in peripheral deletion. In contrast, bacterial superantigen-induced deletion of thymocytes appears to be fully functional in these mice, and thus Fas/APO-1 does not appear to be required for this process. Further, antibody ligation of the TCR on activated T cells from normal or young lpr/lpr mice can induce apoptosis and therefore under some circumstances this phenomenon is not dependent upon CD95/Fas. Thus, to avoid autoreactivity and ensure immune homeostasis, several different apoptotic mechanisms exist in peripheral T lymphocytes, only some of which involve Fas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The pharmacokinetics and neuromuscular effects of rocuronium bromide in patients with liver disease.

To determine the effect of liver disease on the pharmacokinetics of rocuronium, the authors administered 0.6 mg/kg (twice the ED95) to 10 patients with liver disease and compared these results to values in 10 healthy surgical patients. Anesthesia was induced with thiopental and maintained with isoflurane (0.9%-1.1% end-tidal concentration) and nitrous oxide (60%). Venous blood samples were obtained for 6 h after rocuronium injection and plasma concentrations were measured using gas chromatography. Pharmacokinetic differences between groups were determined using a population-based pharmacokinetic analysis (NONMEM). Hepatic impairment did not alter the plasma clearance of rocuronium (217 +/- 21.8 mL/min, mean +/- SE, for both groups), but did increase the volume of the central compartment (5.96 +/- 1.01 L for controls, 7.87 +/- 1.33 L for patients with liver disease) and volume of distribution at steady state (16.4 L for controls, 23.4 L for patients with liver disease). In turn, elimination half-life was longer in patients with liver disease (111 min) compared to controls (75.4 min). The authors conclude that liver disease alters the pharmacokinetics of rocuronium by increasing its volume of distribution. The longer elimination half-life might result in a longer duration of action of rocuronium in patients with liver disease, particularly after prolonged administration.

Adult↗
PubMed1995

Mental health services in Sydney nursing homes.

Senior nursing staff of the 58 nursing homes in one health area of Sydney were interviewed concerning mental health services and staff education. One or more psychiatrically trained staff were employed in 45 per cent of the nursing homes. Most nursing homes received services from a psychiatrist or another mental health professional, but the average time per month provided by them to see residents was less than one hour in 18 (31 per cent), one to two hours in 16 (28 per cent), and three hours or more in only 11 (19 per cent). Forty-four (76 per cent) wanted more mental health services to be provided, especially for advice on management of disturbed behaviour. A substantial number of the nursing homes (at least 28 per cent) provided no ongoing education to their staff about dementia or other psychiatric problems. There is good reason to encourage greater use of mental health professionals in Sydney nursing homes; enhanced funding of area psychiatric services for elderly people is desirable to allow these services to be more readily available.

Aged↗
PubMed1995

Lack of enhanced T-helper cell function in uremic patients with circulating alloreactive antibodies.

Some uremic patients with a history of blood transfusion, pregnancy, and previous transplantation maintain high levels of alloreactive cytotoxic antibodies in the absence of continuous exogenous allogenic stimuli and are thus considered sensitized to the major histocompatibility proteins. To differentiate into antibody-producing cells, B lymphocytes must interact with T-helper (CD4+) cells. Whether ongoing help from these cells is necessary for the B cells to continue producing cytotoxic alloreactive antibodies in these sensitized uremic patients is unknown. To gain insight into the cellular mechanisms that are associated with sustained alloantibody production, T cell activation markers were measured and specific and nonspecific T-helper cell function was studied in three uremic groups with different levels of panel reactive antibodies: 10 patients whose sera reacted to more than 80% of a panel of normal lymphocytes for at least 6 months before the study were highly sensitized, 20 patients whose sera reacted to less than 80% of the panel were moderately sensitized, and 10 nonsensitized patients whose sera did not react to any cell on the panel. The number of total and activated T-helper cells was similar in the highly sensitized and nonsensitized patients. Peripheral blood lymphocyte proliferation in response to plant lectins, soluble OKT3, or alloantigens was similar in the three uremic groups. The spontaneous proliferation of pure T-helper cells and proliferative responses to immobilized OKT3 or alloantigens were also similar in highly sensitized and nonsensitized patients. Alloreactive interleukin-2-producing cell frequencies with pure CD4+ cells as responding cells were 771 +/- 77.9/10(6) cells in highly sensitized, 945 +/- 252/10(6) cells in nonsensitized, and 973 +/- 114/10(6) cells in controls (P = not significant). Panel reactive antibody levels did not correlate with any of the measures of T helper responses. There was a significant decrease of peripheral blood lymphocyte responses to alloantigens and anti-CD3 antibody in all uremic patients as compared with normals, suggesting a dysfunction in accessory cells that was quantitatively similar in sensitized and nonsensitized patients. In spite of the continuous production of alloantibodies by B cells, there is no evidence of either specific or nonspecific enhancement of T-helper cell function in sensitized patients. The absence of T cell immunity to alloantigens suggests that sustained activation of T-helper cells with subsequent interleukin-2 production is not necessary to maintain alloreactive B cell function.

Adult↗
PubMed1995

Epilepsy and children's social and psychological adjustment.

This research investigates the effects of epilepsy on the social and psychological adjustment of the children studied in the National Health Interview Survey of 1988. Analyses examine the effect of epilepsy on four measures of adjustment--home behavior problems, school behavior problems, depressed mood, and impulsiveness. For each outcome, we address five questions: (1) Do children with currently active epilepsy have poorer adjustment than children with inactive epilepsy? (2) Do children with epilepsy fare worse than other children? (3) Do demographic background and family structure moderate the apparent effects of epilepsy? (4) Do family processes mediate the apparent effects of epilepsy? and (5) Do cooccurring conditions produce the apparent effects of epilepsy? Generally, we find that: (1) Children with active and inactive epilepsy fare about equally; (2) Children with any history of epilepsy fare worse than children without epilepsy; (3) Demographic and family background moderate only a small part of epilepsy's effect; and (4) A combination of family processes and cooccurring conditions appears to produce epilepsy's apparent effects.

Adaptation, Psychological↗
PubMed1995

Laparoscopy and thoracoscopy in evaluation of abdominal trauma.

The role of laparoscopy and thoracoscopy as diagnostic modalities in blunt and penetrating abdominal trauma was studied in 35 hemodynamically stable patients who otherwise would have undergone exploratory laparotomy because of equivocal diagnostic findings. Minimally invasive laparoscopic techniques (single 5 millimeter port) and minimal abdominal insufflation (8-10 millimeters mercury) were used with general anesthesia. Both laparoscopy and thoracoscopy appear to be safe (no complications), highly sensitive (100%), specific (88%), and accurate (91%) tools for determining the presence of surgically significant abdominal pathology and the need for therapeutic laparotomy. The appropriate application of these techniques, possibly under local anesthesia, offers potential cost savings.

Abdominal Injuries↗
PubMed1995

Homologous desensitization of 5-hydroxytryptamine4 receptors in rat esophagus: functional and second messenger studies.

We have studied agonist-induced desensitization of 5-hydroxytryptamine (5-HT4) receptor-mediated relaxation and 5-HT4 receptor-mediated increases in cAMP in rat esophageal tunica muscularis mucosae. In both cases, the desensitization time course was biphasic. The first phase was very rapid because more than 50% of desensitization was obtained after a 5-min incubation period with 10 microM of 5-HT. The second phase was slower and led to a complete suppression of the response after 2 h. Desensitization progressively reduced the maximal relaxation of esophagus induced by 5-HT without significantly affecting the EC50. Desensitization was a receptor-mediated event because cross-desensitization was observed between two chemically unrelated 5-HT4 receptor agonists, 5-HT itself and (S)-zacopride. Inasmuch as the kinetics of desensitization were the same when second messenger production or final responses were measured, this suggests that the limiting step in the desensitization process is at the level of the receptor itself or in its coupling to adenylyl cyclase. The desensitization was of the homologous type because exogenously applied cAMP, 8-Bromo-cAMP, or compounds increasing cAMP in the esophageal tunica muscularis mucosae such as isoproterenol and forskolin, were unable to induce any desensitization of the 5-HT4 receptor-induced relaxation response. Homologous desensitization was not followed by a rapid down-regulation of 5-HT4 receptors because no decrease in the Bmax of [3H]-GR113808 binding was observed after 30-min incubation with 10 microM 5-HT.

4-Aminobenzoic Acid↗