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Biomedical subjects

K Reed

Publications and source records attributed to K Reed.

At least 37 records · Page 2Linked to original sources
PubMed1997

Paroxetine potentiates the central nervous system side effects of perphenazine: contribution of cytochrome P4502D6 inhibition in vivo.

BACKGROUND: Paroxetine is a frequently used antidepressant and a potent inhibitor of the CYP2D6 isozyme in vitro (inhibition constant [Ki] = 0.15 micromol/L). Most classic antipsychotic agents such as perphenazine are metabolized by the CYP2D6 isozyme and are often coadministered with antidepressant agents. This study assessed the extent of changes in CYP2D6 isozyme activity in vivo after pretreatment with paroxetine and its consequences on perphenazine kinetics and central nervous system effects. METHODS: Eight extensive metabolizers for CYP2D6 were administered a single dose of perphenazine (0.11 mg/kg orally) or placebo following a randomized double-blind design. Perphenazine plasma concentrations and effects were assessed for a period of 8 hours. Subsequently, subjects were treated with a standard therapeutic dose of paroxetine (20 mg/day orally) for 10 days and test sessions with perphenazine and placebo were repeated. RESULTS: Paroxetine treatment resulted in a twofold to 21-fold decrease in CYP2D6 activity (p < 0.001). After pretreatment with paroxetine, perphenazine peak plasma concentrations increased twofold to 13-fold (p < 0.01). This was associated with a significant increase in central nervous system side effects of perphenazine, including oversedation, extrapyramidal symptoms, and impairment of psychomotor performance and memory (p < 0.05). CONCLUSION: Coadministration of perphenazine after pretreatment with a standard therapeutic dose of paroxetine increased the plasma concentration and central nervous system side effects of perphenazine, primarily as a result of inhibition of the CYP2D6 isozyme. In patients who are at steady state with paroxetine, a reduction of perphenazine dose may be required to prevent central nervous system side effects.

Adult↗
PubMed1997

Employee reactions to ergonomic job design: the moderating effects of health locus of control and self-efficacy.

A field survey of 180 municipal government office employees (82% women, 21-75 years old) investigated the potential moderating effects of internal health locus of control (HLOC) and self-efficacy on employees' reactions to ergonomic job design. Internal HLOC moderated the associations between ergonomic job design and somatic complaints and turnover intentions, and, to a lesser extent, job satisfaction. Self-efficacy moderated the associations between job design and job satisfaction, somatic complaints, and, to a lesser extent, persistent pain. Employees with low self-efficacy or low internal HLOC were influenced more by their physical job conditions than those with high self-efficacy or high internal HLOC. Implications for the ergonomic design of offices are discussed.

Adult↗
PubMed1996

Maternal serum dehydroepiandrosterone sulfate levels and the efficiency of labor in young nulliparas.

OBJECTIVE: To evaluate the maternal serum dehydroepiandrosterone (DHEA) sulfate level as a factor influencing labor "efficiency" at term. METHODS: On admission to the labor and delivery unit, blood was collected from 55 term nulliparous women up to 25 years of age in active labor. Following delivery, umbilical venous cord blood was also collected. Pregnancies complicated by diabetes mellitus, hypertension, fetal growth restriction, tobacco use, corticosteroid use, or chorioamnionitis were excluded. Serum DHEA sulfate levels were measured by radioimmunoassay. Dehydroepiandrosterone sulfate levels and other obstetric variables were correlated retrospectively with the clinically determined requirement for oxytocin augmentation of labor. The unpaired Student t test, Mann-Whitney test, and linear correlation were used for statistical analysis. P < .05 was considered statistically significant. RESULTS: Oxytocin augmentation followed standard indications in 29 of the 55 patients. The mean (+/- standard error) maternal serum DHEA sulfate level was significantly lower in these patients than in the remaining 26 who progressed spontaneously through labor (99.31 +/- 8.92 versus 135.05 +/- 12.30 micrograms/dL, respectively; P = .02). With the exception of cervical dilation on admission, no significant demographic differences were identified between the two groups. The maternal serum DHEA sulfate level did not correlate significantly with cervical dilation on admission (r = 0.03, P = .81). CONCLUSION: Among term nulliparous women, maternal serum levels of DHEA sulfate are significantly lower in those clinically requiring pharmacologic augmentation than in those progressing spontaneously through labor. Dehydroepiandrosterone sulfate may be an important factor in efficient labor.

Adolescent↗
PubMed1995

Rapid identification of Acremonium lolii and Acremonium coenophialum endophytes through arbitrarily primed PCR.

Using a random decamer 5'-CCGAGGTGAC-3' in an arbitrarily primed PCR, similar band patterns were observed between Acremonium lolii and A. coenophialum DNA, which were somewhat different from those formed by other fungal DNA. Despite sharing bands of around 0.7, 0.9 and 2.1 kb, A. lolii can be distinguished from A. coenophialum by the presence of an additional band at around 0.5 kb in the arbitrarily primed PCR.

Acremonium↗
PubMed1995

Methylprednisolone pharmacokinetics, cortisol response, and adverse effects in black and white renal transplant recipients.

It is generally assumed that chronic glucocorticoid therapy is similar pharmacologically when administered to either black or white renal transplant recipients, resulting in adrenal suppression, low circulating plasma cortisol concentrations, and a similar degree of drug exposure and toxicity. To examine this theory and to investigate the relationship of glucocorticoid metabolism to steroid-induced adverse effects among specific ethnic groups of renal transplant recipients, 9 black and 9 white male patients chronically receiving methylprednisolone were enrolled. All patients had stable renal function and were matched for age, weight, and time since transplant. Standard pharmacokinetic parameters for methylprednisolone were determined and cortisol responses were characterized by total cortisol area under the concentration curve (AUC), return cortisol AUC, and cortisol suppression half-life. All patients received their daily oral dose of methylprednisolone (mean daily dose = 11 mg for blacks and 11 mg for whites) as an intravenous infusion with serial plasma samples obtained over 24 h. The patients were assessed for the presence of specific cushingoid manifestations (buffalo hump, moon facies) and steroid-associated diabetes. Methylprednisolone and cortisol were analyzed via HPLC. In the black patients, the mean clearance of methylprednisolone (206 +/- 70 ml/hr/kg) was significantly slower with a smaller volume of distribution (0.95 +/- 0.32 L/kg) when compared with the white group (327 +/- 129 ml/hr/kg, P = 0.03; volume of distribution = 1.33 +/- 0.27 L/kg, P = 0.015). Despite chronic methylprednisolone therapy, a definite 24-hr cortisol response pattern was noted in 15 of the 18 patients with a mean total cortisol AUC of 732 +/- 443 ng.hr/ml in blacks and 539 +/- 361 ng.hr/ml in whites (P = 0.17, black vs. white). The mean cortisol suppression half-life was 4.31 +/- 1.54 hr in black recipients and 4.11 +/- 1.49 hr in whites (P = 0.48). The mean return cortisol AUC for the black patients was 327 +/- 279 ng.hr/ml and 370 +/- 207 ng.hr/ml for white patients (P = 0.28). The serum cortisol nadir for black patients was 12.3 +/- 7.2 ng/ml, which was significantly higher than the cortisol nadir in white patients (6.4 +/- 4.4 ng/ml; P = 0.03). A majority (94%) of patients (9 black, 8 white) had moon facies and 27% of patients (3 black, 1 white) had a buffalo hump. While 5 of 9 black patients had steroid-associated diabetes, no white patients manifested this adverse effect. The black patients with diabetes had higher cortisol AUCs with lower methylprednisolone clearances than the white group.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Pharmacokinetics of methylprednisolone during acute renal allograft rejection.

High dose methylprednisolone is administered empirically by fixed daily boluses to renal transplant recipients who are experiencing acute rejection episodes. Little information is available characterizing the pharmacokinetics of high-dose methylprednisolone in these individuals, who are often acutely ill. Therefore, 5 renal transplant recipients (2 men; 3 women) were studied during an acute rejection episode (mean serum creatinine = 2.6 +/- 0.7 mg/dl) which occurred within the first 8 months post-transplantation. The rejection episode was characterized clinically by at least two of the following: fever, leukocytosis, graft tenderness and an increase in serum creatinine. All patients received bolus doses of methylprednisolone for 3 consecutive days during the rejection episode. All patients were studied on the 3rd day of bolus dosing and received 250 mg methylprednisolone by an i.v. infusion. In phase II, 4 patients were studied during a period of stable renal function when the methylprednisolone was given at lower chronic immunosuppressive doses. Serum samples were taken prior to infusion and serially over the following 24 hours. The serum samples were analyzed for methylprednisolone with high-performance liquid chromatography (HPLC) and pharmacokinetic parametes were generated. During rejection episodes, the methylprednisolone clearance values were 523 +/- 154 ml/h/kg with a corresponding mean volume of distribution of 1.89 +/- 0.72 l/kg. The mean methylprednisolone half-life was 2.61 +/- 0.62 h. During Phase II, the methylprednisolone clearance was 358 +/- 95 ml/h/kg with a half-life of 3.05 h. This observation indicates that methylprednisolone metabolism is increased during acute rejection compared to that seen during chronic immunosuppressive dosing with this agent.

Acute Disease↗
PubMed1995

Perinatal regionalization versus hospital competition: the Hartford example.

OBJECTIVES: The increasingly competitive health care environment may undermine effective traditional regional organizations. It is urgent to document the benefits of perinatal regionalization for the emerging health care system. We present a case study that illustrates many of the challenges to and benefits of perinatal regionalization in the 1990s. BACKGROUND: The controversy in Hartford was sparked by a proposed merger of two major pediatric services into a full-service children's hospital. Community hospitals reacted with plans to upgrade their obstetrics/neonatal facilities toward level II (intermediate) or II+ (intensive) neonatal intensive care units (NICUs). The fear that unrestricted competition would drive up overall health care costs prompted the hospital association and Chamber of Commerce to retain consultants to evaluate the number and location of regional NICU beds. METHODS: The consultant team interviewed stake-holders in area hospitals, health maintenance organizations, insurance companies, businesses, state agencies, and community groups, and analyzed quantitative data on newborn discharges. RESULTS: The existing system worked remarkably well for clinical care, training, referrals, and provider and patient satisfaction. There was a high level of inter-hospital collaboration and regional leadership in obstetrics and pediatrics, but strong and growing competition between their hospitals. Hospital administrators enumerated the competitive threats that obligated them to compete and the financial disincentives to support the regional structures. Business leaders and insurance executives emphasized the need to control costs. Analysis of discharge data showed marginal adequacy of NICU beds but maldistribution between NICUs, particularly between level III and level II units. The consultants recommended no new beds based on population projections, declining lengths of stay nationally, and substantial gains available from aggressive back-transport of convalescing infants. The consultants emphasized the need for all stakeholders to support the regional infrastructure (referral, transport, education, evaluation, quality assurance) and to modify competition when it impaired effective regionalization. CONCLUSIONS: Regionalization permits better care at lower cost, yet competition may disrupt this effective system. Active cooperation by stakeholders is vital. Substantial new research is required to define optimal regional organization.

Bed Occupancy↗
PubMed1995

24-hour immunologic assessment of CD4+ and CD8+ lymphocytes in renal transplant recipients receiving chronic methylprednisolone.

Glucocorticoids are commonly prescribed in the post transplant period as a component of combination immunosuppressive regimens. However, the daily 24-hour pattern of helper lymphocytes (CD4+) and suppressor cells (CD8+) during chronic methylprednisolone therapy has not been examined in renal transplant recipients in relation to glucocorticoid exposure and time post-transplant. The response of total lymphocytes, CD4+ and CD8+ lymphocytes was examined in 23 stable renal transplant recipients who received methylprednisolone for at least 8 months post-transplant. The patient's prescribed oral methylprednisolone dose (mean daily dose = 9.7 +/- 2.6 mg) was given intravenously and whole blood was sampled periodically over 24 h for lymphocyte counts and methylprednisolone concentrations. A complete blood count with differential was determined via an automated hemocytometer with CD4+ and CD8+ lymphocytes determined using flow cytometry. Methylprednisolone area under the concentration versus time curve (AUC) was determined and normalized for each patient's respective dose. A general lymphopenia resulted in all patients with a mean decrease of 61 +/- 15% and an average nadir time occurring at 6 h. The decline from baseline was 76 +/- 17% for absolute number of CD4+ and 59 +/- 18% for CD8+ lymphocytes with an average nadir time at 6 h. Twelve patients exhibited a baseline CD4+ count to be less than 688 cells/mm3 (the low end of the reference range) and the lymphocyte count of all the patients fell below this value at the nadir. Six patients had a CD8+ lymphocyte count below 380 cells/mm3 (low end of the reference range) at baseline with 21 of the 23 patients exhibiting less than 380 cells/mm3 at the nadir time. At the time of nadir, the mean CD4+ and CD8+ counts were 156 +/- 105 cells/mm3 and 256 +/- 270 cells/mm3, respectively. In 17 of the 23 patients, the CD4+ count was below 200 cells/mm3 at the time of nadir. The dose-normalized AUC of methylprednisolone ranged from 22.6 to 113.5 ng.h/ml with 48% of patients exhibiting morning cortisol concentrations greater than 60 ng/ml. No correlation was noted between daily methylprednisolone exposure and the extent of lymphocyte decline. Lymphocyte response patterns are not clinically recognized in renal transplant recipients, as a means of monitoring immunosuppression. The absolute CD4+ and CD8+ lymphocyte count and the timing of these sample collections post-steroid administration, may have clinical relevance when serially assessed as is done in other immunologic diseases. Prospective evaluation of lymphocyte subset patterns and correlation with susceptibility to overimmunosuppressive (i.e. opportunistic infections) is necessary to help determine if these complications can be minimized by more individualized steroid dose modification.

Adult↗
PubMed1993

CD4+/CD8+ lymphocyte patterns in renal transplant recipients receiving chronic methylprednisolone.

Circulating lymphocytes play a major role in mediating allograft rejection. The peripheral lymphocyte count is influenced by methylprednisolone administration, however, the relationship of methylprednisolone pharmacokinetics to lymphocyte trafficking patterns and its effect on selected lymphocyte subsets (CD4+, CD8+) in renal transplant recipients receiving chronic, fixed-doses of this glucocorticoid has not been studied. To examine this relationship, seven stable renal transplant recipients were given their usual oral methylprednisolone dose (mean daily dose = 15 mg) intravenously, and whole blood was obtained over 24 hr. CD4+ and CD8+ cells were quantitated with flow cytometry and serum concentrations of methylprednisolone were analyzed by high performance liquid chromatography (HPLC). Following methylprednisolone administration, a lymphocytopenia was noted in all patients with the CD4+ and CD8+ cells declining to less than 75% of baseline with a resultant nadir at 8 hr. The CD4+ and CD8+ count returned to baseline values by 12 to 24 hr in all patients. Interpatient variability in pharmacokinetic parameters of methylprednisolone was noted with a total body clearance of 240 +/- 112 mL/hr/Kg and half-life ranging from 2.2 to 3.9 hr. The variability seen in the clearance and distribution volume of methylprednisolone among these patients suggests that fixed doses result in a variable degree of systemic exposure. The poor correlation between methylprednisolone pharmacokinetic parameters and the decline of CD4+ and CD8+ cells indicates that other factors may play a role in the lymphocyte trafficking response. Nevertheless, nadir CD4+ and CD8+ cell counts may provide a measure of methylprednisolone immunosuppression in transplant recipients. Studies to examine their relationship to clinical outcomes (i.e., graft function, steroid toxicity, opportunistic infections) are currently in progress.

Adult↗
PubMed1993

Acutely psychotic patients receiving high-dose haloperidol therapy.

Despite the trend towards lower neuroleptic dosing in the treatment of psychosis, there continue to be patients who are administered doses that are higher than recommended. Thirty-six acutely psychotic patients receiving parenteral haloperidol were evaluated by the Brief Psychiatric Rating Scale, the Schedule for Affective Disorders and Schizophrenia-Change Version, and the Nurses' Observation Scale for Inpatient Evaluation, as well as by drug levels in plasma. Patients were compared on the basis of total haloperidol dose in the first 24 hours: regular dose (RD: 10-30 mg) and high dose (HD: 40-80 mg). At baseline, patients in the HD group scored significantly higher on the Brief Psychiatric Rating Scale factor Hostile-Suspiciousness and the Nurses' Observation Scale for Inpatient Evaluation factor Irritability. Assignment to regular-dose and HD groups could not be accounted for on the basis of age, gender, weight, or duration of illness. Moreover, drug levels in plasma indicated that the HD patients did not require higher doses on the basis of differences in haloperidol levels.

Acute Disease↗
PubMed1991

Cloning and expression of a rat cardiac delayed rectifier potassium channel.

We have cloned a cDNA (designated RAK) coding for a delayed-rectifier K current (IRAK) from adult rat heart atrium and expressed it in Xenopus oocytes. RAK differs from the cloned rat brain K current, BK2 [McKinnon, D. (1989) J. Biol. Chem. 264, 8230-8236], by one amino acid at residue 411. RAK expressed in oocytes compares closely to the intrinsic adult rat atrial delayed-rectifier current measured by using whole-cell recording of single isolated cells. Northern blot analysis confirmed the presence of the channel in adult rat atrium, and to a lesser extent, in rat ventricle. IRAK activates with time constants ranging from 58 ms at -20 mV to 6 ms at +60 mV and does not show significant inactivation over 800 ms. It is blocked by 4-aminopyridine greater than barium much greater than tetraethylammonium chloride, which is similar to the relative potencies of these blockers on the native delayed rectifier current. We conclude that the main delayed rectifier K current in adult rat atria is virtually identical to a neuronal delayed rectifier, BK2.

4-Aminopyridine↗
PubMed1991

Oral tocolysis with magnesium chloride: a randomized controlled prospective clinical trial.

A prospective randomized clinical trial was conducted to assess the efficacy and safety of enteric-coated magnesium chloride (SLOW MAG) as an oral tocolytic agent. Seventy-five patients between 24 and 34 weeks' gestation who were treated with intravenous magnesium sulfate for a first episode of preterm labor were enrolled. After a 12-hour contraction-free period on intravenous therapy, patients were randomized by sealed envelope to one of three groups: group 1, SLOW MAG (535 mg every 4 hours); group 2, oral ritodrine (20 mg every 4 hours); or group 3, no therapy (control). Patients receiving oral therapy were treated until delivery or completion of 36 weeks' gestation. No difference was found between groups with respect to time gained with the use of oral therapy or number completing 36 weeks' gestation. Therapy with enteric-coated magnesium chloride was associated with significantly fewer side effects (20%) as compared with ritodrine (48%) (p less than 0.01). Our results suggest that compared with ritodrine, enteric-coated magnesium chloride is as effective in prolonging pregnancy and preventing recurrent preterm labor. However, neither enteric-coated magnesium chloride nor ritodrine appeared to be any more effective in the prevention of preterm delivery than observation alone.

Administration, Oral↗
PubMed1991

The effect of glutathione monoethyl ester on the potentiation of the acute toxicity of methyl parathion, methyl paraoxon or fenitrothion by diethyl maleate in the mouse.

Depletion of hepatic glutathione in the mouse by pretreatment with diethyl maleate (DEM) is known to potentiate the acute toxicities of many dimethyl-substituted organothiophosphate insecticides. However, certain studies have raised doubts regarding the participation of glutathione in the detoxification of methyl parathion in the mouse, and hence the putative mechanism of action of DEM-induced potentiation of this insecticide. The present study evaluates the hypothesis that DEM potentiates the acute toxicities of methyl parathion, methyl paraoxon, and fenitrothion by a mechanism other than glutathione depletion. One hour following pretreatment of mice with DEM (0.75 ml/kg i.p.), glutathione was markedly depleted and the acute toxicities of methyl parathion, methyl paraoxon and fenitrothion were potentiated. Administration of glutathione monoethyl ester (20 mmol/kg p.o.) to DEM-pretreated mice attenuated DEM-depletion of hepatic glutathione, or maintained glutathione at or above control levels. However, glutathione monoethyl ester did not alter the DEM-induced potentiation of the lethality of these insecticides. Furthermore, administration of glutathione monoethyl ester to naive mice increased hepatic glutathione levels, but did not affect the percentage of animals succumbing to a challenge dose of methyl parathion, methyl paraoxon, or fenitrothion. These data indicate that DEM potentiates the toxicity of methyl parathion, methyl paraoxon or fenitrothion by a mechanism unrelated to hepatic glutathione content.

Animals↗
PubMed1991

A comparison of adinazolam and desipramine in the treatment of major depression.

Thirty-one patients with a DSM-III (R) diagnosis of Major Depression received adinazolam (n = 16) or desipramine (n = 15) during a 6 week double-blind randomized controlled trial. Both groups showed a significant decline in Hamilton Rating Scale for Depression scores (21.8 +/- 4.5 to 10.7 +/- 8.5 for adinazolam and 23.5 +/- 5.5 to 12.9 +/- 8.6) for desipramine. Melancholic and anxiety symptoms were reduced equally by both drugs. Initial sedation was the most common side-effect with adinazolam. Plasma levels of desipramine and hydroxy-desipramine correlated highly with oral dose after 3 weeks of treatment.

Adult↗