Endocrine studies of azoospermia. I. Serum steroid levels in Sertoli cell only syndrome.

Estrone, estradiol, estriol, progesterone, 17 alpha-hydroxyprogesterone, testosterone, and dihydrotestosterone levels were determined in sera of 20 fertile men and 15 male patients with Sertoli cell only syndrome. In men with Sertoli cel only syndrome there was a significant decrease in serum estrone, estradiol, progesterone, 17 alpha-hydroxyprogesterone, and dihydrotestosterone and a significant increase in serum estriol and testosterone. Changes in endocrine profile discussed in relation to the possible role of inhibin.     

Antitumor activity of 2-fluoro-2'-deoxyadenosine against tumors that express Escherichia coli purine nucleoside phosphorylase

The selective expression of Escherichia coli purine nucleoside phosphorylase (PNP) in solid tumors has been successfully used to activate two purine nucleoside analogs [9-(2-deoxy-beta-D-ribofuranosyl)-6-methylpurine (MeP-dR) and 9-beta-D-arabinofuranosyl-2-fluoroadenine (F-araA)] resulting in lasting tumor regressions and cures. E. coli PNP also cleaves 2-fluoro-2'-deoxyadenosine (F-dAdo) to 2-F-adenine, which is the toxic purine analog liberated from F-araA that has high bystander activity and is active against nonproliferating tumor cells. As F-dAdo is 3000 times better than F-araA as a substrate for E. coli PNP, we have evaluated its antitumor activity against D54 gliomas that express E. coli PNP and have characterized its in vivo metabolism in order to better understand its mechanism of action with respect to the other two agents. Like MeP-dR and F-araA-5'-monophosphate (F-araAMP, a prodrug of F-araA), treatment of mice bearing D54 tumors that express E. coli PNP with F-dAdo resulted in excellent antitumor activity. Although F-dAdo was as active as MeP-dR and better than F-araAMP, it was not dramatically better than either compound because of its short plasma half-life and the limited activation of F-adenine to toxic metabolites. Regardless, these results indicated that F-dAdo was also an excellent prodrug for use with gene vectors that deliver E. coli PNP to tumor cells.     

Diagnosis of gestational diabetes by use of a glucose polymer

The oral glucose tolerance test is the recommended method for the assessment of carbohydrate metabolism in pregnancy. However, available glucose drinks are often associated with varying degrees of gastrointestinal symptoms that might preclude meaningful studies. Polycose (Ross Labs, Columbus, Ohio) is a glucose saccharide polymer mixture containing 3% glucose, 7% maltose, 5% maltotriose, and 85% polysaccharide of 4 to 15 glucose units, with an osmotic load one fifth that of glucose. We assessed the efficacy of this glucose polymer in the performance of a 3-hour carbohydrate tolerance test with glucose and glucose polymer used 3 to 5 days apart in each patient tested. After 2 days of 300 gm carbohydrate-enriched diets, 48 patients underwent 3-hour carbohydrate tolerance tests at a mean gestational age of 30 +/- 3 weeks. Statistical analysis revealed a moderate level of agreement (kappa = 0.45, p less than 0.001) between the results of both carbohydrate tolerance test preparations. Patients experienced fewer gastrointestinal symptoms with the glucose polymer than with glucose. These preliminary data suggest that glucose polymer may be effectively used in the performance of a 3-hour carbohydrate tolerance test.     

Hypolipidemic activity of cyclic imido alkyl ethers, thioethers, sulfoxides, and sulfones

N-Substituted alkyl ethers, thioethers, sulfoxides, and sulfones of cyclic imides (e.g., phthalimide, saccharin, 1,8-naphthalimide, succinimide, and 2,3-dihydrophthalazine-1,4-dione) were shown to have potent hypolipidemic activity at doses of 10 and 20 mg/kg/d in rodents. These N-substitutions afforded no improvement over other known N-substitutions (e.g., butyl, 3-butanone, or the propionic acid derivatives of phthalimide, saccharin, and 2,3-dihydrophthalazine-1,4-dione) compared with the respective parent compounds. However, 2-(methoxyethyl)-1H-benz[de]isoquinoline-1,3-(2H)dione (3a), 2-[2-methylsulfinyl]ethyl-1H-benz[de]isoquinoline-1,3-(2H)dione (3c), 1-(2-methylsulfinyl)-2,5-pyrrolidenedione (4c), and 1-(2-methoxyethyl-2,5-pyrrolidenedione (4a) significantly improved activity compared with parent compounds, as well as previously reported N-substituted analogues, reducing serum cholesterol levels and serum triglyceride levels by 40%. The thioether of succinimide afforded a 54% reduction of serum cholesterol and a 41% reduction of serum triglyceride levels in mice after 16 d. The alkyl thioethers of 1,8-naphthalimide and succinimide significantly lowered cholesterol levels in serum VLDL and LDL, while the alkyl thioethers of succinimide elevated HDL cholesterol content. Tissue lipids were reduced in the liver and aorta by these selected derivatives. The activities of regulatory enzymes in de novo synthesis of hepatic cholesterol and triglyceride were inhibited by the selected 1,8-naphthalimide derivatives. In situ cholesterol and cholic acid reabsorption from intestines were suppressed by the presence of the agents.     

Tumor size predicts vascular invasion and histologic grade: Implications for selection of surgical treatment for hepatocellular carcinoma.

Vascular invasion and high histologic grade predict poor outcome after surgical resection or liver transplantation for hepatocellular carcinoma (HCC). Despite the known association between tumor size and vascular invasion, a proportion of patients with large tumors can be treated surgically with excellent outcomes. Clarification of the association between tumor size, histologic grade, and vascular invasion has implications for patient selection for resection and transplantation. The objective of this study was to examine the relationship between HCC tumor size and microscopic (occult) vascular invasion and histologic grade in a multicenter international database of 1,073 patients who underwent resection of HCC. The incidence of microscopic vascular invasion increased with tumor size (< or =3 cm, 25%; 3.1-5 cm, 40%; 5.1-6.5 cm, 55%; >6.5 cm, 63%) (P < 0.005). Both size and number of tumors were important factors predicting vascular invasion. Among all patients with tumors 5.1 to 6.5 cm, microscopic vascular invasion was present in 55% compared with 31% for all patients with tumors 5 cm or smaller (P < 0.001). Among patients with solitary tumors only, microscopic vascular invasion was significantly more common in tumors measuring 5.1 to 6.5 cm (41%) compared with 27% of tumors 5 cm or smaller (P < 0.003). Tumor size also predicted histologic grade: 36% of tumors 5 cm or smaller were high grade, compared with 54% of lesions 5.1 to 6.5 cm (P = 0.01). High histologic grade, an alpha-fetoprotein level of at least 1000 ng/mL, and multiple tumor nodules each predicted occult vascular invasion in tumors larger than 5 cm. The high incidence of occult vascular invasion and advanced histologic grade in HCC tumors larger than 5 cm, as well as biologic predictors of poor prognosis, should be considered before criteria for transplantation are expanded to include these patients.     

The pharmacokinetics and pharmacodynamics of the new Soviet anti-arrhythmia preparation allapinin

Pharmacokinetics and pharmacodynamics of a new antiarrhythmic drug allapinin was studied in patients with frequent ventricular and supraventricular extrasystoles. The technique of determining allapinin by high performance liquid chromatography is described. Intravenous administration of the drug in a dose of 20 mg was shown to be effective in 50% of patients.     

Cell cycle distribution of erythroblasts in P. falciparum malaria

The cell cycle distribution of the erythroblasts of 6 Gambian children with P. falciparum malaria was determined using the technique of combined Feulgen microspectrophotometry and 3H-thymidine autoradiography. The data showed evidence of a perturbation of erythroblast kinetics in all 6 children. The abnormalities were more marked in the children with chronic malaria than in those with acute malaria and predominantly affected the early polychromatic erythroblasts. The disturbances observed in chronic malaria included an increased proportion of cells in the G2 phase and an arrest during the progress of some cells through the S phase. The latter defect was not seen in the children with acute malaria.