Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies

Summary Cytosine arabinsodie (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m² as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9–12 and 21–24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m²×2 doses of ara-C and 50 mg/m² of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.Supported in part by grants from the National Cancer Institute (CA-12197 and CA-09422) and the American Cancer Society CF-85-182     

Platelet antibodies in systemic lupus erythematosus

In systemic lupus erythematosus (SLE), the precise cause of the thrombocytopenia is unknown. Since platelet associated IgG is increased in many patients, it has been suggested that the destruction of platelets might be dependent on specific antibodies. In nine patients with SLE, platelet associated immunoglobulins were found together with free serum antibody which bound to platelets from all normal subjects. Using an immunoblotting technique with membrane proteins from normal platelets incubated with patient sera, target antigens were localized on a band of mol wt 108,000 in two cases (B. and N.) and on a band of mol wt 66,000 in a third (M.). When the same technique was applied to autologous platelets of patient N., autoantibody binding to the protein of mol wt 108,000 was demonstrated. The antigenic determinants were not removed from the platelets by enzyme treatment or by disulphide bond reduction, and were localized in the cytoplasmic fraction of the platelets.     

Office care of the premature infant

The family physician should follow the small premature infant in the neonatal intensive care center and review the baby's problems and risk factors. In the office, special attention is required in monitoring the infant. Proper hospital and office care greatly improve the prognosis.     

Peripheral neuropathies during treatment with cisplatin: clinical and electrophysiologic study of 11 cases

Eleven patients with bronchial epidermoid carcinoma and undergoing treatment with cis-D.D.P. (II) were kept under electrophysiological and clinical surveillance. No other neurotoxic medication was added. The total dose of cis-D.D.P. was 300 mg/m2 over a period of three months: namely, three courses of 100 mg/m2 distributed over 5 days. Following the pretreatment check-up, the patients were divided into two groups: those without any electrophysiological abnormality (group A), and those without clinical abnormality but with a delayed latency H of the Hoffmann Reflex (group B). Patients in group A showed a slowing down of the motor nerve conduction velocity of the Median and Peroneal Nerves after a course of 100 mg, without accompanying worsening of the conduction velocity after 300 mg/m2, and prolongation of the distal latency of the sensory Median Nerve after 300 mg/m2; in group B, no significant change of electrophysiological clinical features were noted. In the two groups a non-significant reduction in amplitude of evoked responses were noted. These findings are more consistent with an axonal injury than with functional myelin injury. The authors review the existing literature and discuss the physiopathologic mechanisms of cis-D.D.P. peripheral neuropathies.     

Angiotensin-converting enzyme in sarcoid and chalazion granulomas of the conjunctiva

Angiotensin-converting enzyme (ACE) was studied immunohistochemically in conjunctival biopsies from 6 patients with systemic sarcoidosis, 4 patients with posterior non-sarcoid uveitis and in specimens from 4 patients with chalazion of the eyelid. Specimens with sarcoid granulomas showed intense ACE-positive immunoreactivity in epitheloid cells of the granuloma, whereas chalazion granulomas did not contain ACE-immunoreactivity. There was no difference in staining patterns between specimens without granulomas. Thus immunohistochemical staining for ACE may be of help in differentiating conjunctival granulomatous tissue of a chalazion from sarcoid granuloma.     

Wheat Germ Agglutinin is Mitogenic, Non-Mitogenic and Anti-Mitogenic for Human Lymphocytes

Wheat germ agglutinin (WGA) was found to stimulate DNA synthesis in human peripheral blood mononuclear cells at relatively low concentrations and to inhibit DNA synthesis at higher concentrations. Both actions were inhibited by oligomers of N-acetyl-D-glucosamine. Significant mitogenic activity was dependent on the use of human (as opposed to fetal calf) serum to supplement the culture medium. Purified T cells responded to WGA very weakly and the incorporation of thymidine into non-T cells in response to WGA was less than the lectin-free control. The full ability of T cells to respond to WGA was restored by the addition of monocytes, but not by any other blood cells. Interleukin 2 partially restored the ability of T cells to respond to WGA; interleukin 1 was less effective. WGA displayed a strong synergistic action with the tumour promoter, 12-O-tetradecanoyl-13-acetate (TPA), in stimulating DNA synthesis in separated T (but not non-T) cell fractions, and in unfractioned mononuclear cells. These results reconcile most of the conflicting reports in the literature concerning the interaction of WGA with human lymphocytes.     

Growth of children from 0-5 years: with special reference to mother's smoking in pregnancy

A cohort of 1163 pregnant women in two small towns in South Wales, UK, was identified and followed until the children born to them were five years of age. Growth in these children is described and a number of determinants identified. Social-class differences were very small at birth but differences in height became clear by the age of two years and in head circumference before this. In height the differences were largely accounted for by greater growth in social class I, but there was a gradient in head circumference throughout all the social classes. The social class effects gradually increased as the children became older. Parity of the mothers had a small effect on size at birth but age of the mother had no effect once parity was allowed for. Data on illnesses in the children were collected but no effect on growth could be detected. By far the most important determinant of growth which could be controlled is maternal smoking. About 40% of the women smoked, about 17% heavily (15 or more cigarettes per day) and the prevalence of smoking altered little during pregnancy. There was a graded effect of smoking on growth up to a 9% deficit in birth-weight, a 2% deficit in length at birth and a 1.5% deficit in head circumference in the babies born to the mothers who smoked most heavily (25 or more cigarettes per day) compared with non-smokers. There effects decreased with age but there were still residual effects at age five years.