Urine screening for abused drugs in new admissions to a VA hospital.

The urine samples from two groups of Veteran's Administration patients newly admitted to general psychiatry units were screened in 1985 and in 1987-88 for abused drugs. The results were compared with urine samples from controls with similar age distributions admitted to an alcohol and drug abuse unit or to medical-surgical units. About 40% of all newly admitted patients were positive for one or more controlled drugs, but there were no significant differences among patient groups in the percentage of urine samples positive for these drugs. Marijuana and benzodiazepines were detected frequently in all patient groups and often in combination, although opiates also were frequently detected in the urine samples from the medical-surgical patients. There was a clear decrease in drug-positive samples with age in all patient groups, much of which could be accounted for by decreased marijuana detection.

Effects of repeated drug holidays on serum haloperidol concentrations, psychiatric symptoms, and movement disorders in schizophrenic patients.

In a crossover experiment the authors investigated the effects of repeated weekly, 2-day, haloperidol drug holidays on serum haloperidol concentrations, mental status, and neuroleptic-induced movement disorders in seven chronic schizophrenic patients. Haloperidol concentrations decreased about 64% during the initial 36 hours of drug holiday and subsequently increased slightly during the next 24 hours of drug holiday. Two-day weekly drug holidays for 6 weeks resulted in an average reduction of 25% in serum haloperidol concentrations at all drug holiday points. Mental status and movement disorders scores, rated by observers blind to the drug-holiday condition, were not significantly affected by drug holidays.

Dithiocarbamate-induced biliary platinum excretion and the control of cis-platinum nephrotoxicity.

Treatment with any one of six different dithiocarbamates subsequent to the administration of cis-platinum (CDDP) is shown to promote the biliary excretion of platinum. The administration of the most effective of these compounds, sodium diethyldithiocarbamate (DDTC) at 1.57 mmol/kg, led to a 30-fold increase in the biliary excretion of platinum. For the other dithiocarbamates investigated, a similar dosage led to increases ranging from approximately 5-fold for sodium iminodiacetic acid dithiocarbamate, to 26-fold for sodium sarcosine dithiocarbamate. The presence of alkyl groups on the nitrogen of the dithiocarbamate increased the effectiveness of the compounds. There is no increase in the platinum levels of the brain when DDTC is used in this manner. A histopathological evaluation of the kidneys of rats given 15 mg CDDP/kg in 6.3% saline with and without the use of dithiocarbamates for renal protection shows significant additional protection due to the use of the dithiocarbamates. Dithiocarbamates given at an appropriate dosing schedule can lead to a significant reduction in the renal damage which is revealed by microphotographs. It is suggested that part of the renal protection obtained by the use of dithiocarbamates may be due to this shift of platinum excretion to the bile which obviates additional renal exposure to platinum. It was also found that the simultaneous injection of a dithiocarbamate with the cis-platinum has no obvious effect on the anti-cancer action of cis-platinum against the Walker 256 carcinosarcoma in rats.

Reperfusion injury in ischemic myocardium: protective effects of ruthenium red and of nitroprusside.

Coronary reperfusion following myocardial ischemia may result in further damage to injured myocytes, as judged by their ultrastructural appearance. Ruthenium red is an inorganic dye with calcium flux-inhibiting properties which protects ischemic myocardium against reperfusion damage, as judged by biochemical indices of mitochondrial function. In this study, we produced myocardial ischemia in pigs by means of reversible coronary artery occlusion. The pigs were infused with either ruthenium red or nitroprusside (an after-load reducing agent with no known calcium flux-inhibiting properties) prior to and during coronary reperfusion. During reperfusion, both ruthenium red and nitroprusside produced similar lowering of mean arterial pressure, while mean arterial pressure rose in pigs not receiving these drugs. Myocardial samples from the ischemic reperfused region were examined by electron microscopy. Ischemic damage to nuclei, mitochondria, and myofibrils and glycogen depletion were graded independently on a three-point scale by two investigators. For each of the organelles studied, ischemic damage was significantly less for treated animals than for controls. This protective effect was similar for both ruthenium red-treated animals and nitroprusside-treated animals. These results suggest that the protective effects of ruthenium red treatment are attributable to its afterload reducing properties rather than to inhibition of transmembrane calcium flux in cardiac fibers.

Serum haloperidol and neuroleptic receptor levels in chronic psychosis.

Serum haloperidol and serum dopamine blocking activity were measured, and steady state levels were compared in 22 chronic male schizophrenic patients. Haloperidol levels were measured by high pressure liquid chromatography (HPLC), and dopamine blocking activity was measured by a radioreceptor assay (NRRA). Clinical status was determined by the Brief Psychiatric Rating Scale (BPRS) and the Abnormal Involuntary Movement Scale (AIMS). Patients were stabilized on individual doses of haloperidol for at least three weeks and dosages ranged from five to 200 mg per day. All measures were determined on two occasions, one week apart. All measures (AIMS, BPRS, HPLC, and NRRA) showed a high degree of repeated test reliability. The behavioral measures showed a high degree of interobserver reliability on both occasions. There were significant correlations at both time points among haloperidol dosage, serum haloperidol levels, and dopamine blocking activity. Although the correlations between serum levels measured by HPLC and NRRA were positive and significant on both occasions, they never accounted for more than 58 percent (coefficient of variation) of the total variance.

Incidence of serum acid phosphatase elevation after transurethral prostatectomy.

Serum acid phosphatase levels were measured in 402 patients after transurethral resection of the prostate for benign adenoma. All patients had normal preoperative serum acid phosphatase levels (less than 0.8 IU/L) and the tissue specimen was histologically benign in all patients. Ninety-three patients (23%) showed normal postoperative serum acid phosphatase levels, while 309 (77%) showed postoperative elevation of serum acid phosphatase. One hundred forty-eight patients (37%) had postoperative levels higher than 5 IU/L. Significant elevation of serum acid phosphatase may follow transurethral prostate resection in patients having no evidence of malignancy.

Sphenoid mucocele causing hyperprolactinemia: radiologic/pathologic correlation.

A suprasellar lesion masquerading as a pituitary tumor causing hyperprolactinemia in a 62-year-old man was found to be a large sphenoid mucocele. After it was successfully resected via a transsphenoidal approach, the patient's condition improved and the prolactin level fell to almost normal.

Effects of transurethral prostatectomy on nonelectrolyte components of serum.

The total serum protein, serum albumin, serum globulin, and serum cholesterol were measured in 220 patients having transurethral prostate resection. The measurements were made before surgery, at the termination of the operative procedure, and on the first postoperative day. The changes observed showed a decrease in each parameter and were compared with serum sodium measurements made at the same time intervals. The per cent change that occurred intraoperatively in total serum protein was -14.5 per cent, serum albumin -14.5 per cent, cholesterol -14.4 per cent, globulin -12.9 per cent, while serum sodium was -2.6 per cent. On postoperative day 1, only serum sodium and serum globulin showed a significant change from the immediate postoperative value. Since plasma sodium readily equilibrates with the interstitial fluid while plasma proteins do not, plasma dilution may be reflected more accurately in measurement of changes in plasma proteins and cholesterol than measurement of serum sodium.

Drug holidays and serum haloperidol levels in schizophrenic patients.

Chronic hospitalized schizophrenic patients receiving haloperidol were placed on drug holidays for 2 days. Serum haloperidol levels in these patients decreased to about 60% of the levels seen just prior to the usual morning dosing during the drug holiday. Control subjects not given a drug holiday showed stable day-to-day serum haloperidol levels. The small drop in serum haloperidol blood levels may relate to the lack of relapse observed in such patients.

Comparative antidotal effects of diethyldithiocarbamate, dimercaptosuccinate, and diethylenetriaminepentaacetate against cadmium-induced testicular toxicity in mice.

The compounds diethyldithiocarbamate (DDTC, Dithiocarb), 2,3-dimercaptosuccinic acid (DMSA), and diethylenetriaminepentaacetic acid (DTPA) were evaluated for effectiveness in protecting mouse testes following administration of an LD100 dose of CdCl2 X 2.5 H2O (Cd). Toxicologic responses were assessed by light microscopic techniques. DTPA gave the most effective testicular protection of the three compounds when given within 30 minutes prior to Cd, but only DDTC was effective when given 30 minutes or longer after Cd. Degenerative changes were minimal when DDTC was given as late as three hours after Cd, and were mild following a four-hour interval. However, the changes were marked, but less severe than in mice receiving Cd only, when DDTC was administered five hours after Cd.

Effects of acetaminophen on cadmium metabolism in mice.

Acetaminophen (ACM) administration to mice of the (C57BL/6 X DBA/2)F1 strain produced a typical hepatic centrilobular necrosis similar to that observed in rodents and humans. To determine the effects of this drug-induced necrosis on cadmium (Cd) metabolism, mice were given a sublethal dose of CdCl2 . 2.5 H2O containing 109CdCl2 and maintained for a period of time sufficient for Cd-metallothionein (Cd-MT) to be synthesized and distributed. Subsequent administration of ACM ip or po evoked a marked redistribution of Cd from livers to kidneys of mice, and increased the amount of Cd excreted in urine and feces. There were only minimal or no effects on Cd concentrations in other organs assessed. The effect of ACM on Cd redistribution was antagonized by administration of cysteine, a glutathione precursor, and was enhanced by pretreatment with phenobarbital, a potent inducer of the cytochrome P-450 mixed-function oxidase system. Pretreatment of mice with ACM 6 or 24 hr prior to Cd administration caused aberrations of the normal Cd distribution pattern, but no effect was noted when Cd administration was delayed for 48 hr after ACM injection, indicating recovery of the mechanisms of Cd-MT synthesis and sequestration. Sephadex G-75 gel filtration chromatography of serum from ACM-treated mice showed that most of the Cd was associated with high-molecular-weight proteins, and only a minor portion was present as Cd-MT. Cd excreted in urine was predominantly in a low-molecular-weight form, but there was evidence of two minor components of higher molecular weight, neither of which eluted as Cd-MT. Cd excreted in feces was insoluble following homogenization in 0.25 M sucrose solution. Cd in livers and kidneys of ACM-treated mice eluted as Cd-MT. It was concluded that persons who have a moderately high Cd burden may be at risk of Cd nephrotoxicity if they incur hepatic necrosis subsequent to ACM abuse.

Effects of 1.5% glycine infusion on the nonelectrolyte components of serum in dogs.

Plasma dilution resulting from absorption of a 1.5% glycine solution is difficult to evaluate on the basis of changes in serum sodium alone. In a canine animal model the effects of infusion of a 1.5% glycine solution and a 0.9% saline solution on the nonelectrolyte components of serum were compared with a noninfused control group. The outcome measurements included total serum protein, serum albumin, serum cholesterol, serum globulin, plasma fibrinogen, and serum osmolality. The infusion of each solution resulted in a significantly lower concentration in plasma proteins and cholesterol compared with the control group. The lowest concentration of plasma proteins and cholesterol occurred in the saline infusion group. The dilution produced by saline infusion was consistent with a distribution of the infused fluid in the extracellular compartment. The dilutional effect was less in the glycine solution infused group, which suggested partial distribution of residual free water from the glycine solution in the intracellular space as well as the extracellular compartment. Since plasma proteins are confined primarily to the intravascular compartment, the changes in the concentration of plasma proteins and cholesterol indicate the amount of dilution of the extracellular fluid.

The therapeutic value in the autopsy request.

Recently the number of autopsies performed in the United States has declined. Although the benefits of the autopsy for physicians are many, we maintain, based on our own experiences, that it helps them accept the reality of loss of a loved one and enables them to begin the process of "letting go". Realization of the therapeutic value of the autopsy request should enable those who work with the recently bereaved, such as physicians and clergy, to fulfill more effective roles.

Effects of drugs on the male and female reproductive systems.

Infertility, permanent or temporary, resulting from drug-induced injury is an important clinical problem. Many common used drugs are potentially toxic to gonads. It is well-known that estrogens are toxic to the male genital system, but androgens may also produce infertility. Anovulation may also be a consequence of exposure to sex steroids. Cimetidine regularly produces hypospermia in men; phenytoin does so occasionally. Marijuana has been shown to be a gonadal toxin, while the effects of lysergic acid diethylamide (LSD) remain controversial. The most significant group of drugs that may injure the gonads is the cancer chemotherapeutic agents, of which the alkylating agents are the worst offenders. Prediction of infertility induced by these agents may be possible based on the duration of therapy and the patient's age and sex.

Association of adenovirus type 16 with Reye's-syndrome-like illness and pneumonia.

Thirty-eight antigenically distinct viruses have been described as adenoviruses, though only about one third have been commonly associated with human illnesses. In mid-January 1981, adenovirus 16, one of the more rarely encountered ones, was isolated from three patients in separate hospitals in the Little Rock, Arkansas, area, even though it had not previously been isolated there. We report the details of these cases, which included a Reye's-syndrome-like illness and fatal viral pneumonia. The reports indicate a new and more important clinical role for adenovirus 16 infection.

Preanalytic variables. A management problem.

The problem of preanalytic variables in patient testing is a serious one. Although these considerations are often neglected, they can and do cause the best performed laboratory tests to yield completely spurious information. The laboratory director, by training and responsibility, is the appropriate individual to establish controls for eliminating errors. In this article the proper handling of specimens for common tests is outlined for every area of the laboratory except the blood bank.