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Oxantrazole is an anthrapyrazole analogue developed as an anthracycline-like agent with potentially reduced cardiotoxicity. A reversed-phase high-performance liquid chromatographic assay was developed using a C2 column and mobile solvent system of dimethylformamide-acetonitrile-0.2 M ammonium acetate, pH 4.5 (20:5:75, v/v/v) at a flow-rate of 1 ml/min. Drug and internal standard were detected by ultraviolet absorbance at 514 nm. Isolation of drug and internal standard was afforded by elution from C18 disposable isolation columns with a mixture of methanol-glacial acetic acid-0.02 M sodium acetate, pH 4.0 (12:1:3, v/v/v). The assay was linear (r2 greater than 0.99) over concentrations of 0.025-2.5 micrograms/ml and the limit of detection was 10 ng/ml plasma. Oxantrazole was unstable in neutral and particularly alkaline aqueous solutions. Utilizing this assay, plasma pharmacokinetics were determined following intravenous infusion of oxantrazole to beagle dogs. Plasma elimination was rapid with elimination phase half-life values less than 45 min.

Two schedules of teroxirone, a triazine triepoxide, were evaluated in a phase I study. Twenty-six patients were treated on 1 day every 5 weeks at doses of 36-2250 mg/m2. At doses greater than or equal to 1500 mg/m2, severe thrombophlebitis was seen without cytotoxic effect, and this schedule was closed. Twenty-seven patients were treated on 5 days every 5 weeks at daily doses of 16-450 mg/m2. Mild thrombophlebitis and moderate leukopenia were encountered. For phase II studies, a dose of 375 mg/m2 X 5 every 5 weeks is recommended. Pharmacologic studies showed rapid plasma elimination, which suggests the agent's possible usefulness for regional infusion.

Plasma and urine concentrations of amygdalin, whole-blood concentrations of cyanide, and thiocyanate concentrations in serum and urine were determined in cancer patients following intravenous (4.5 g/m2) and oral (500-mg tablet) administration of amygdalin. To measure low plasma concentrations of amygdalin following oral administration a GC/MS assay was developed. Following intravenous administration, concentrations of parent drug as high as 1,401 microgram/ml were observed, with no increase in plasma concentrations of cyanide or serum concentrations of thiocyanate. Plasma elimination of amygdalin was best described by a two-compartment open model with a mean distributive phase half-life of 6.2 min, mean elimination phase half-life of 120.3 min, and mean clearance of 99.3 ml/min. Following oral administration of amygdalin, plasma concentrations were much lower, with peak values of less than 525 ng/ml. Cyanide concentrations increased to values as high as 2.1 microgram/ml whole blood. Thiocyanate concentrations did not increase for several days, plateauing at values as high as 38 microgram/ml serum. Ingestion of almonds by two patients taking oral amygdalin increased cyanide concentrations compared with values obtained after oral amygdalin alone.

Paralytic hip dislocations in 37 children with myelomeningoceles have been treated by open reduction, iliopsoas tendon transfer and various other procedures about the hip. At follow-up, less than half the patients were community ambulators and had maintained their reductions. The level of the spinal lesion, alignment of the lower extremities in relation to the trunk and pelvis and the presence of scoliosis including pelvic obliquity were more important factors in determining the patient's degree of function than the status of the hip reduction.

Intrapericardial herniation is rare; 40 cases have been reported. To our knowledge, this is the first report of a case resulting from a recently developed surgical procedure: the pericardial and peritoneal window technique. Diagnostic modalities included plain films, barium studies, and a computed tomography scan.

The techniques used and results obtained in the surgical treatment of the kyphotic deformities of fourteen patients with paraplegia and myelomeningocele are presented. The best results were obtained by vertebral resection at the apex of the deformity, wiring together the facing vertebrae to promote interbody fusion, and correction and maintenance of the realignment with a Harrington distraction rod.

Clinical observations and empirical evidence suggest that, among Vietnam combat veterans, Blacks are more maladjusted than Whites (e.g., Parsons, 1985; Penk et al., 1985). The prediction that minority group status is associated with poorer post-war adjustment and higher rates of PTSD was examined among Vietnam combat veterans who were seeking treatment for addiction disorders. Adjustment scores among groups comparable in combat exposure were found to be similar for both Whites and Hispanics; Blacks, however, score significantly higher on both PTSD symptoms on MMPI scales. These findings indicate that ethnicity contributes importantly to PTSD in selected instances, but that minority group status alone does not account for observed differences. Additional research is indicated in which careful attention is given to the complicating and interacting role of addiction disorders in sampling.

Dianhydrogalactitol was administered as two 1-hr infusions separated by a 4-hr period once every 5 weeks to 21 patients with advanced solid tumors. Total doses ranged from 100 mg/m2 (50 mg/m2 twice on a single day) to 160 mg/m2 (80 mg/m2 twice on a single day). Peak concentrations of drug at the end of a 1-hr infusion ranged from 1.9 to 5.6 microgram/ml. Plasma elimination of dianhydrogalactitol was approximated best by a two-compartment open model. The alpha-half-life was 3.9 +/- 1.9 mins and the beta-half-life was 31.3 +/- 2.7 mins. Dose-limiting hematologic toxicity was encountered at a total dose of 160 mg/m2, with leukopenia occurring more frequently than thrombocytopenia. Other toxic effects included mild to moderate nausea in most patients and two instances of moderate alopecia. One patient with large cell cancer of the lung had a partial regression lasting 2 months and one patient with a carcinoid in the thymus had a partial regression lasting 7 1/2 months. A third patient with a mixed adenocarcinoma-squamous cell carcinoma of the lung had improvement (30% decrease) in his pulmonary tumor for greater than 2 months.

It has been claimed that high-dose vitamin C is beneficial in the treatment of patients with advanced cancer, especially patients who have had no prior chemotherapy. In a double-blind study 100 patients with advanced colorectal cancer were randomly assigned to treatment with either high-dose vitamin C (10 g daily) or placebo. Overall, these patients were in very good general condition, with minimal symptoms. None had received any previous treatment with cytotoxic drugs. Vitamin C therapy showed no advantage over placebo therapy with regard to either the interval between the beginning of treatment and disease progression or patient survival. Among patients with measurable disease, none had objective improvement. On the basis of this and our previous randomized study, it can be concluded that high-dose vitamin C therapy is not effective against advanced malignant disease regardless of whether the patient has had any prior chemotherapy.

One hundred and thirty male and 213 female college students responded to a self-report delinquency and crime measure and to a scale of sidedness preferences. Consistent with most of the literature on official delinquency and crime, left handedness was positively associated with involvement in several forms of delinquency (including some degree of criminality) among males. Other measures of sidedness among males largely failed to correlate with delinquency, however. Among females, sidedness was much less systematically related to delinquency than among males.

Indicine N-oxide, a pyrrolizidine alkaloid N-oxide that exhibits antitumor activity without some of the toxic effects associated with other pyrrolizidine alkaloids, is metabolized to indicine in rabbits and humans. Indicine can be detected in the plasma and is excreted in the urine in a dose-dependent manner following the i.v. administration of indicine N-oxide. The p.o. administration of indicine N-oxide leads to an increased plasma concentration and an increased urinary excretion of indicine. The hepatic microsomal fraction and the gut flora both catalyze the anaerobic reduction of indicine N-oxide to indicine in vitro. Whole-animal studies suggest that the gut flora play a major role in the metabolic reduction of indicine N-oxide by the rabbit. Indicine N-oxide is not actively excreted in the bile, and it is probable that indicine N-oxide finds its way into the gut by passive diffusion following i.v. administration. Neomycin and erythromycin, which reduce the number of anaerobic bacteria in the gut, lead to decreased plasma levels and a decreased urinary excretion of indicine.

Three term neonates presented with an unusual combination of skin changes (sclerema) and joint contractures at birth. In each case a prolonged period of fetal hyporeactivity was reported by the mother. Each child demonstrated a number of clinical findings consistent with chronic fetal hypoxia. Each child recovered with normal joint function. We postulate that sclerema neonatorum and joint contractures are another, though poorly recognized sequela of chronic in utero hypoxia and are preceded by a prolonged period of diminished fetal activity.

A simple enzymatic assay has been applied to the determination of amygdalin in urine and plasma of patients taking laetrile on their own initiative. Following parenteral administration of laetrile, amygdalin is excreted primarily as the unchanged molecule and urinary recoveries may approach 100 percent. Peak plasma levels after a 6 gm intramuscular dose were 180 microgram/ml. The ratio of amygdalin epimers was unchanged in the urine following parenteral injection.

Sexual orientation was measured as a continuous variable based upon reported percentage of sexual fantasies and percentage of sexual experiences involving members of the same sex. In the present sample (which probably somewhat overrepresented the homosexual end of the continuum) about one-third of both males and females reported at least occasionally fantasizing about sexually interacting with members of the same sex. The survey indicated about one-third of males also reported having had at least one intimate sexual experience with the same sex, whereas only 10% of females did so. Also, virtually all females who sexually fantasized about the same sex only did so occasionally, whereas most of the males who fantasized about the same sex did so much more exclusively. Although these results cannot be considered representative of the distribution of sexual orientation in any natural population, they suggest that there are advantages in measuring sexual orientation as a continuous variable instead of as one with only a few discrete categories. The results also support other studies that have concluded that when deviations from exclusive heterosexuality are present, they are likely to be much more extreme among males than among females.

We have developed a preparation of hexamethylmelamine (HMM), dissolved in a fat emulsion Intralipid 20%, that is potentially satisfactory for parenteral administration to man. Solid HMM can be dissolved in Intralipid 20% up to 5 mg/ml, with extensive agitation. Solubilization of HMM is facilitated first by dissolving the drug in ethanol or in dimethylacetamide and then by adding the solution to Intralipid 20%. The disposition of HMM in rabbits after iv administration of HMM dissolved in Intralipid 20% was similar to the disposition of the drug following iv administration of HMM dissolved in 0.1 N HCl.