Hypocupremia occurred in an adult with sickle cell anemia who received zinc as an antisickling agent for two years. The hypocupremia was associated with microcytosis and relative neutropenia. Administration of copper resulted in an increase in RBC size and leukocyte counts. We have since observed hypoceruloplasminemia of varying degrees in several other sickle cell anemia patients who were receiving oral zinc therapy. This complication was easily corrected by copper supplementation.

Valproic acid, a new anticonvulsant, is most effective in absence seizures (simple and complex), but it has produced improvement in tonicclonic seizures, mixed absence with tonic-clonic seizures, and myoclonic epilepsy. It is useful alone or as an adjunct to other anticonvulsants and may allow the dosage of the latter to be reduced. Some patients who are refractory to other anticonvulsants may respond to valproic acid. Adverse reactions occur in about 20% of patients. Gastrointestinal disturbances and drowsiness (usually noted when valproic acid is given with other anticonvulsants) are the most common reactions; hair loss is observed less frequently. Untoward effects are usually transient and do not require discontinuation of use of the drug.

In a double-blind crossover study, the effectiveness of furosemide, 40 mg twice daily, was compared with hydrochlorothiazide, 50 mg twice daily, in hypertensive patients. Both hydrochlorothiazide and furosemide significantly reduced blood pressure (BP) during three months of therapy. However, the fall in BP was consistently greater with hydrochlorothiazide than with furosemide, although the difference was significant only with respect to systolic BP. The somewhat greater antihypertensive effectiveness of hydrochlorothiazide may be related to its longer action permitting a more continuous diuretic effect and, hence, maintenance of reduced extracellular fluid volume throughout the 24-hour period.

The effectiveness of cyclobenzaprine hydrochloride, a new tricyclic skeletal muscle relaxant, was shown in patients with long-term intractable pain of cervical and lumbar origin aggravated by skeletal muscle spasm and tenderness. The investigation was double-blind and randomized, comparing cyclobenzaprine hydrochloride (10 mg three times a day) with diazepam (5 mg three times a day) and with placebo. After two weeks of treatment, the 16 patients in the cyclobenzaprine group showed an overall improvement in pain variables as did the 16 patients in the diazepam group. No serious adverse reactions to cyclobenzaprine were observed in the study. However, dry mouth due to cyclobenzaprine's anticholinergic action and mild degrees of drowsiness were encountered more often than with diazepam or placebo.

To compare the effectiveness of manual and mechanical chest compression during cardiopulmonary resuscitation, 50 patients who suffered cardiac arrest were randomly allocated to receive manual or mechanical chest compression. Randomization was performed after failure of initial resuscitative measures but within ten minutes after the onset of cardiac arrest (mean, 6.4 +/- 1.2 min). Ten patients from each group survived longer than one hour following resuscitation. Three from the mechanical group and two from the manual group were eventually able to leave the hospital. Thus mechanical compression appears comparable with manual compression when manual compression is performed under ideal conditions. Mechanical chest compression may be employed when trained personnel are not readily available or where manual compression is technically difficult to perform.

A randomized double-blind crossover trial included 16 patients with severe congestive heart failure who received isosorbide dinitrate or placebo for eight weeks, and then the opposite treatment for eight more weeks. All patients received their usual maintenance therapy with digitalis and diuretics. Seven morbid events occurred during 85 patient-weeks of isosorbide dinitrate therapy compared with 17 during 76 patient-weeks of placebo. Severity of congestive heart failure improved in all eight patients who received isosorbide dinitrate compared with two patients who showed improvement and five whose symptoms became worse with placebo. No significant differences in physical findings, cardiac dimensions, or resting hemodynamics were observed. Maximal exercise duration increased significantly by 2.54 minutes with isosorbide dinitrate therapy, and rose insignificantly by 1.24 minutes with placebo. This preliminary trial suggests that long-term vasodilator therapy may be clinically beneficial in congestive heart failure.

The University Group Diabetes Program is a long-term prospective clinical trial designed to evaluate the effects of various hypoglycemic agents on vascular complications in patients with asymptomatic adult-onset diabetes. Mortality and blood glucose levels were determined as well as certain nonfatal events for patients assigned to diet alone or to either of two insulin treatment regimens. Lower levels of blood glucose with mean values close to normoglycemia were achieved in the treatment group in which the insulin dosage was adjusted to achieve normoglycemia compared with the levels achieved in patients treated with diet alone or with a fixed dose of insulin. In spite of differences in blood glucose levels among the treatment groups, there were only minor differences in the occurrence of fatal or nonfatal events.

Forty-nine patients with Graves' disease were randomly divided into two groups. One group received propylthiouracil, 150 mg every eight hours, and the other group received propylthiouracil, 450 mg as a single daily dose. All patients' conditions were evaluated clinically anc chemically at two-week intervals. The response to the divided dosage schedule was prompt and predictable, and by ten weeks all but one patient had achieved remission. The group that received the single daily dose regimen responded less favorably, and at ten weeks ten patients had failed to achieve remission (P less than .001). However, when these patients' regimens were switched to the every-eight-hour schedule, all but one patient became euthyroid in an additional four weeks.

We administered deanol acetamidobenzoate, 2.0 g/day for four weeks, a double-blind, placebo-controlled crossover trial, to 14 patients with tardive dyskineasia. The patient population included both inpatients and outpatients. The response was evaluated by subjective clinical impression and scoring of filmed sequences. Patients' conditions improved significantly from baseline scores while receiving both deanol and placebo, but there was no distinction between the two treatments.

The efficacy and side effects of a low-potency neuroleptic, thioridazine hydrochloride, and those of a high-potency neuroleptic, fluphenazine hydrochloride, were compared in 30 elderly chronic schizophrenic patients. Through a crossover design, each patient received both drugs with an intervening washout period. Although both drugs produced a similar degree of improvement, their side effects differed. Fluphenazine caused slightly more extrapyramidal effects than thioridazine, though few occurred with use of either drug. Thioridazine caused weight gain, blood pressure decreases, and ECG changes. High-potency neuroleptic agents appear to be the drugs of choice for elderly schizophrenic patients.

Zoster immune plasma (ZIP) was evaluated for treatment of cutaneous disseminated zoster in immunocompromised hosts. Twenty patients were studied: 13 were enrolled in a double-blind protocol, five received ZIP under an open protocol, and two were observed without receiving a transfusion. In the double-blind study, eight patients actually received ZIP; five were given plasma lacking varicella-zoster virus antibodies (control plasma). The clinical course of zoster in the group given ZIP was the same as that of patients given control plasma or no transfusions. Because ZIP did not alter the clinical course of zoster and because zoster patients produced high-antibody titers without ZIP, we concluded that ZIP is not useful for treatment of cutaneous disseminated zoster and should be reserved for prevention or modification of varicella in exposed, susceptible immunocompromised patients.

A prospective, randomized, double-blind study on the effect of cephaloridine prophylaxis in the surgical management of appendicitis was performed. Of the 139 patients studied, 70 received cephaloridine and 69 received placebo prophylaxis. Both groups of patients were well matched with regard to age, sex, operative findings, and bacteria isolated at operation. Postoperative wound infections were detected in 11.6% of placebo-treated patients and in 1.4% of cephaloridine-treated patients (P less than .02). Prophylactic treatment with cephaloridine of patients undergoing surgery for uncomplicated appendicitis resulted in a perceptible reduction in the rate of postoperative wound infection.