Transient left homonymous hemianopsia and encephalopathy following treatment of testicular carcinoma with cisplatinum, vinblastine, and bleomycin

A 36-year-old man being treated with cisplatinum, vinblastine, and bleomycin for testicular carcinoma developed a dense left homonymous hemianopsia, encephalopathy, and a partial nondominant parietal lobe syndrome. He subsequently had a resolution of all signs and symptoms, suggesting that these alarming events were a toxic but reversible side effect of the chemotherapy.     

Prevalence of Helicobacter pylori in United States Navy submarine crews

Helicobacter pylori prevalence is elevated in German submarine crews and in United States Navy (USN) surface fleet personnel, but H. pylori prevalence in USN submariners was unknown. The goal of the study was to determine the prevalence of H. pylori in the crews of USN nuclear submarines compared to other military personnel and to the general US population. The presence of H. pylori IgG antibodies was determined in serum samples using a commercial ELISA. Only 47 out of 451 submariners (9.4%) were H. pylori positive, which is similar to that of the US general population with a similar level of education. In contrast, H. pylori prevalence is significantly higher in US Army recruits (26%), USN surface fleet personnel (25%), and German diesel submariners (38%). These data demonstrate that submarine service (and by inference activity requiring isolation and close contact, per se) is not a risk factor for H. pylori infection.     

Assay of bone resorption in vivo with3H-tetracycline

³H-Tetracycline (³H-TC) was used to quantify resorption in whole bones of growing rats and dogs. After repeated isotopic labeling of actively growing embryos or neonates,³H-TC was observed to be distributed homogeneously and in equilibrium with⁴⁵Ca. A rapid and large loss of³H-TC and a small loss of⁴⁵Ca occurred during the early weeks of rapid bone growth, suggesting thatabsolute amounts of⁴⁵Ca resorbed from bone, as reflected by losses of³H-TC, are five to ten times greater than thenet amounts of⁴⁵Ca lost from bone. Minimal loss of³H-TC occurred due to nonspecific physicochemical exchange in vivo or in vitro (5%) except with nonradioactive tetracycline, and³H-TC was not greatly exchanged or reused (10%) in vivo. The data are considered in terms of local and systemic conservation of calcium.     

Response to low-dose ketoconazole and subsequent dose escalation to high-dose ketoconazole in patients with androgen-independent prostate cancer

The review summarizes the outcomes of several landmark trials involving aromatase inhibitors that helped formulate current therapeutic approaches recommended by the American Society of Clinical Oncology for breast carcinoma treatment.     

In vitro adherence of Moraxella bovis to intact corneal epithelium

An in vitro assay is described using radiolabeled Moraxella bovis for studying adherence to intact bovine corneal epithelial surfaces. The assay was optimized for time (45 min) and for the ratio of epithelial cells to bacteria (1:1000) that demonstrated a significant difference in adherence between M. bovis strain 118F, a piliated organism and a nonpiliated variant, strain 118F/4-2. Adherence of these organisms correlated with previous pathogenicity studies involving experimental infection of calves. Scanning electron microscopy of tissues treated in the assay revealed a predilection of M. bovis for dark epithelial cells and for association with depressions in the tissue surface. This assay technique is discussed in comparison with other in vitro adherence assay methods.     

Quinazoline antifolates inhibiting thymidylate synthase: variation of the N10 substituent

The synthesis of 12 new 5,8-dideazafolates with isopropyl, cyclopropylmethyl, 2-fluoroethyl, carbamoylmethyl, phenacyl, 3-fluorobenzyl, 5-uracilylmethyl, carboxymethyl, 2-carboxyethyl, 3-cyanopropyl, 3-hydroxypropyl, and cyanomethyl substituents at N10 is described. In general, the synthetic route involved monoalkylation of diethyl N-(4-amino-benzoyl)-L-glutamate, coupling of the resulting secondary amine with 2-amino-6-(bromomethyl)-4-hydroxyquinazoline hydrobromide in N,N-dimethylacetamide with calcium carbonate as the base, and deprotection using mild alkali. The cyanomethyl derivatives was found to be unexpectedly base labile and was therefore prepared by mild acid deprotection of a di-tert-butyl ester. The compounds were tested as inhibitors of purified L1210 thymidylate synthase (TS). Four members of the series were more potent that the N10-hydrogen compound, but none was superior to the previously described N10-propargyl-5,8-dideazafolic acid. Selected compounds were examined as inhibitors of purified L1210 dihydrofolate reductase (DHFR). As desired, N10 substitution in general reduced DHFR inhibitory activity; these results are discussed. As a measure of cytotoxicity, the compounds were examined for their inhibition of the growth of L1210 cells in culture. None of the new substituents conferred enhanced potency relative to N10-propargyl-5,8-dideazafolic acid (ID50 = 5 microM), which, as the best TS inhibitor and a relatively poor DHFR inhibitor, continues to lead this series.