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Biomedical subjects

P J Perry

Publications and source records attributed to P J Perry.

116 records · Page 7Linked to original sources

Is DST status associated with depression characteristics?

Depressed inpatients have a DST non-suppression rate that is several times greater than that of depressed outpatients. To explore what clinical features of depression might explain this difference, 25 depressed inpatients who were DST non-suppressors were compared with 16 DST suppressors, using 70 clinical variables. Those variables that were different between these two groups of inpatients were then used to compare depressed inpatients and outpatients. Three variables that were significantly associated with DST status in depressed inpatients were also found to differentiate between depressed inpatients and depressed outpatients. DST suppression was associated with a family history of alcoholism, with the symptom hypersomnia, and with a younger age at index interview.

Adult↗

Illicit anabolic steroid use in athletes. A case series analysis.

Because of recent anabolic steroid abuse scandals at all levels of athletic competition ranging from high school sports to the 1988 Olympics in Seoul, Korea, the investigators closely examined the anabolic steroid use histories of 20 competitive and noncompetitive weight lifters. Steroid efficacy studies only examine the anabolic effects of individual drugs. However, these 20 steroid users consistently practiced polypharmacy. During steroid use cycles lasting between 7 and 14 weeks, athletes commonly used two or three oral agents and two long-acting injectable products. Dosages of oral preparations tended to be similar to those used in efficacy studies, whereas dosages of the long-acting injectable agents were approximately three to eight times greater than those used in controlled studies. Subjects reported significant increases in body weight and strength. In addition, mental status changes were reported that included symptoms of depression, hostility, aggression, and paranoia. Based on the pattern of anabolic steroid use currently being practiced in the United States, it is apparent that past efficacy and toxicology studies are of limited value in delineating the benefits and hazards of these drugs.

Adolescent↗

Prednisolone psychosis: clinical observations.

Corticosteroid-induced acute psychoses in three Chinese patients receiving prednisolone 15-75 mg/d are described. The cases are compared with other cases of corticosteroid mental disturbances in the literature. It is concluded that the mental disturbance usually occurs within the first ten days of treatment, and presents most often in women, as either an acute manic or depressive episode accompanied by delusion and/or hallucinations. An exponential increase in the risk of the mental disturbance occurs as the corticosteroid dose increases.

Adult↗

Sedative/hypnotic dependence: patient stabilization, tolerance testing, and withdrawal.

Physical dependence to sedative/hypnotic drugs is not an uncommon clinical problem. The withdrawal syndrome is analogous to alcohol withdrawal, except the duration of the syndrome occurs over a longer period of time with the symptoms being less intense than generally encountered with alcohol. The potential for withdrawal reactions is probably greater for the shorter-acting agents than the longer-acting drugs. Potentially dependent sedative/hypnotic users require stabilization of their symptoms initially, followed by tolerance testing. If tolerant, the patients should be withdrawn using either a long-acting sedative/hypnotic (e.g., diazepam) or phenobarbital. Compared to other benzodiazepines and barbiturates, diazepam appears to be the drug of choice for treating dependent patients. Diazepam is rapidly absorbed and distributed to the brain and therefore useful for stabilization and tolerance testing. It is metabolized on chronic administration to a long-acting metabolite, desmethyldiazepam, which makes the drug ideal for a tapered withdrawal schedule.

Anti-Anxiety Agents↗

Two prospective dosing methods for nortriptyline.

This study compared two prospective pharmacokinetic dosing methods to predict steady-state concentrations of nortriptyline. One method required multiple determinations of the nortriptyline plasma concentration to estimate the drug's steady-state concentration. The second method required a single nortriptyline concentration drawn at a fixed time, preferably 36 hours, following a nortriptyline test dose. The 36-hour nortriptyline plasma concentrations (NTP 36h) were substituted into the straight-line equation of Cssav = 17.2 + 3.74 (NTP 36h), where Cssav is the average steady-state concentration for a 100 mg/day dose of nortriptyline. No differences were noted between the observed steady-state nortriptyline concentration of 121 +/- 19 ng/ml, the 36-hour single-point prediction mean concentration of 121 +/- 21 ng/ml, or the multiple-point prediction mean concentration of 122 +/- 19 ng/ml. Because of the similar findings between the two methods, the clinical advantages and disadvantages of each kinetic approach are discussed to put these prospective dosing protocols into their proper perspective.

Adult↗

Phenytoin dosage requirements and pharmacokinetic variables.

The relationships between phenytoin dose, pharmacokinetic variables, patient data, and serum phenytoin concentrations were studied. One hundred sixty-eight adult epileptic patients who were receiving phenytoin were randomly selected and studied retrospectively. The method of Ludden et al. or a Bayesian forecasting technique was employed to estimate the patients' pharmacokinetic values for maximum rate of drug metabolism (Vmax) and the Michaelis-Menten constant (Km). Resulting steady-state serum concentrations were estimated. The daily doses of phenytoin necessary to produce steady-state serum phenytoin concentrations of 10 and 20 micrograms/ml were also determined in patients whose values were definable. Analysis of variance was used to test possible correlations between patient demographic data, pharmacokinetic values, and doses. The majority of patients (85.6%) failed to achieve concentrations between 10 and 20 micrograms/ml when receiving phenytoin sodium 300 mg daily. Patients receiving more than one phenytoin dosage regimen had significant but weak correlations between Vmax and Km. The data suggest that low Km and Vmax values occur concurrently. Initial phenytoin dose based on patients' weights or body surface areas may be useful in determining initial dosage requirements, but estimated pharmacokinetic values for Vmax and Km provide the best guide for dosage adjustment.

Adult↗

N-desmethylclozapine, an insensitive marker of clozapine-induced agranulocytosis and granulocytopenia.

We reviewed the charts of 58 patients with treatment-refractory schizophrenia who were receiving clozapine, to determine if the drug's active metabolite, N-desmethylclozapine, is a biologic marker for impending clozapine-induced granulocytopenia and agranulocytosis. No significant correlation between granulocyte counts and patient demographic variables of clozapine and N-desmethylclozapine steady-state plasma concentrations, clozapine:N-desmethylclozapine ratio, age, gender, clozapine dosage, smoking status, and race were found. We believe N-desmethylclozapine is not a clinically useful marker for monitoring the effect of clozapine on granulocyte integrity. On the contrary, its plasma concentrations correlated positively with granulocyte counts.

Adolescent↗

Cyclosporine trough concentrations in predicting allograft rejection and renal toxicity up to 12 months after renal transplantation.

STUDY OBJECTIVE: To evaluate the utility of cyclosporine (CsA) trough concentrations as a monitoring tool for acute graft rejections and CsA nephrotoxicity. DESIGN: Retrospective chart review. SETTING: University-affiliated teaching hospital. PATIENTS: One hundred thirty-seven adults who had undergone kidney transplantation. MEASUREMENTS AND MAIN RESULTS: Clinical data extracted from the charts were CsA dosage, CsA trough levels (whole blood, HPLC method), biopsy findings to confirm acute rejections, and serum creatine to determine clearance by the Jelliffe method. Data were collected at up to 1 month, between 1 month and 3 months, and between 3 and 12 months after transplantation. For each time period, receiver's operating characteristics curves were generated to identify the optimum CsA concentration for avoiding acute rejection and CsA nephrotoxicity. At up to 1 month, the CsA therapeutic response threshold was 182 ng/ml (sensitivity 69%, specificity 84%, p<0.0001) and toxicity threshold for CsA nephrotoxicity was 204 ng/ml (sensitivity 89%, specificity 56%, p<0.0001). Between 1 month and 3 months, the respective figures were 175 ng/ml (sensitivity 58%, specificity 89%, p<0.0002) and 189 ng/ml (sensitivity 87%, specificity 65%, p<0.0001). Between 3 and 12 months, the CsA therapeutic response threshold decreased to 135 ng/ml (sensitivity 56%, specificity 40%, p>0.1) and the toxicity threshold for CsA nephrotoxicity remained relatively static at 204 ng/ml (sensitivity 100%, specificity 14%, p<0.0001). CONCLUSION: Early in CsA therapy it is essential to prevent graft rejection. Drug concentrations exceeding approximately 182 ng/ml threshold accomplish this goal. Later, successful therapy demands that CsA nephrotoxicity be avoided. This goal is accomplished by not exceeding a CsA concentration of 204 ng/ml.

Adolescent↗