Low prevalence of human papillomavirus in a geographic region with a high incidence of head and neck cancer

BACKGROUND: The main purpose of this study was to determine the prevalence of human papillomavirus (HPV) infection in patients with head and neck carcinomas from Brazil. MATERIALS AND METHODS: Forty-five patients with head and neck squamous cell carcinoma were included in the study, from 1995 to 1996. Forty-two were male and 3 female, with age ranging from 32 to 82 years (median 61). Five patients (11%) did not have previous history of use of tobacco and 38 (90.5%) were heavy smokers. Tumor sites were pyriform sinus, 10; tongue, 11 (oral, 6; base, 5); larynx, 7; floor of mouth, 3; tonsil, 6; retromolar area, 3; inferior gingiva 2; buccal mucosa, 2; and maxillary sinus in 1 patient. Twenty-five were stage IV, 17 stage III, and 3 stage II. RESULTS: The presence of HPV DNA was detected in 5 of 45 patients (11%), all of them with HPV 16. Two patients had HPV DNA in normal mucosa and tumor tissue, 1 patient had HPV DNA only in the normal mucosa and tumor tissue, 1 patient had HPV DNA only in the normal mucosa, and 2 patients were positive for HPV DNA in tumor tissue. Four patients were male and 1 was female; 2 patients were nonsmokers. Three patients had tonsil carcinoma, 1 patient had a tongue carcinoma, and 1 patient had a pyriform sinus cancer. CONCLUSIONS: The role of chemical carcinogens seems to be more important in the genesis of head and neck cancer than is HPV infection. The presence of HPV DNA in 5 of 45 patients stimulates further investigation to determine the role of HPV as a risk factor for head and neck carcinoma.     

Campylobacter enteritis in Johannesburg

In order to establish a reasonable protocol for a diagnostic laboratory we conducted a survey during which we confined the routine culture of stool samples for Campylobacter fetus to two groups--all infants under 2 years of age, and older children and adults with obviously diarrhoeic stools. Camp. fetus was isolated from 100 of 2323 stool specimens (4,3%). This is within the 3 - 8% isolation rates previously reported from surveys in which all specimens were cultured. Camp. fetus isolates represented 16,9% of all bacterial pathogens isolated, and Black infants showed a significantly greater isolation rate than White infants. We feel that culture for Camp. fetus is an essential part of any routine bacteriological investigation of diarrhoea. A partially selective culture policy for Camp. fetus will result in a recovery rate at least equal to that of Salmonella and enteropathogenic Escherichia coli.     

Enhancement by hyperthermia of the in vitro cytotoxicity of mitomycin C toward hypoxic tumor cells

Mitomycin C and hyperthermia are both toxic to chronically hypoxic EMT6 tumor cells. Combinations of this drug and heat were tested in vitro in normally aerated and chronically hypoxic EMT6 mouse mammary tumor cells to establish whether greater than additive cytotoxicity could be achieved by combined treatment. Cell survival was measured at four concentrations of mitomycin C (0.01, 0.1, 1.0, and 10 microM) at 37 degrees or at elevated temperatures (41, 42, and 43 degrees) for durations of 1, 2, 3, and 6 hr. At 42 degrees, exposure to mitomycin C for 3 and 6 hr produced a 2- to 3-fold increase in hypoxic tumor cell kill at all drug concentrations over that expected for strict additivity. A 15-fold enhancement in the kill of hypoxic tumor cells was obtained at 1.0 and 10 microM mitomycin C at 43 degrees for 6 hr of exposure. Under most conditions, additivity was observed for the antibiotic and heat in oxygenated cells, except at 43 degrees with 0.01 and 0.1 microM mitomycin C following 3 and 6 hr of treatment, conditions under which a 5- to 10-fold potentiation of tumor cell kill was obtained. The rate of formation of reactive metabolites from mitomycin C under anaerobic conditions in EMT6 cell-free preparations was measured. A 30 to 50% increase in alkylating activity was observed at elevated temperatures, suggesting that the enhanced cytotoxicity of mitomycin C with heat toward hypoxic cells may, in part, be due to an increase in activation of the drug.     

Specific changes in the in vitro production of prostanoids by the ovine cervix at parturition

A method of tissue superfusion has been used to measure in vitro prostanoid production by the ovine cervix during late pregnancy and at parturition. In late pregnancy (105-135 days of gestation) cervical tissue produced relatively large amounts of prostaglandin E (PGE); in comparison, the production rates of prostaglandin F (PGF), 13, 14-dihydro-15-oxo-prostaglandin F (PGFM) and 6-oxo-prostaglandin F1 alpha were generally low. Thromboxane B2 (TXB2) production was minimal and often unmeasurable. There were significant increases in the production rates of PGE and 6-oxo-PGF1 alpha by cervical tissue taken immediately after delivery, when compared to late pregnancy. Mean production rates of PGE increased from 19.8 +/- 4.1 to 43.8 +/- 7.4 ng/g. dry wt./min; 6-oxo-PGF1 alpha production rates increased more than three-fold from 10.0 +/- 2.7 to 34.6 +/- 9.8 ng/g. dry wt./min (means +/- S.E.M.). There were no significant differences in the rates of production of PGF, PGFM and TXB2 by the two groups.     

Effects of 2,2'-dipyridyl and related compounds on platelet prostaglandin synthesis and platelet function

2,2'-dipyridyl, a chelator of ferrous iron and inhibitor of platelet aggregation, was studied together with several similar compounds to determine the mechanism of their effects on platelets. All of these compounds were more potent inhibitors of arachidonic-acid-mediated aggregation (IC50, 0.17-1.8 mM) than of ADP-mediated aggregation (IC50, 7.6-19.7 mM). At low concentrations required to inhibit arachidonic-acid-mediated aggregation, 2,2'-dipyridyl, 4,4'-dipyridyl and 2-chloropyridine specifically inhibited the platelet cyclo-oxygenase. The mechanism of inhibition of ADP-induced aggregation was investigated, but was not explained. At concentrations needed to inhibit ADP-induced aggregation, 2,2'-dipyridyl did not alter cell ultrastructure, serotonin or nucleotide content or interfere with release of [14C]arachidonic acid or calcium movements. Therefore, our results indicate that 2,2'-dipyridyl and related compounds have two effects on platelets, both due to the unprotonated form. The inhibition of cyclo-oxygenase by low concentrations of these compounds is not due to bidentate iron chelation, since 4,4'-dipyridyl was almost as effective as 2,2'-dipyridyl, but is compatible with binding of these inhibitors to the iron in the heme of the cyclo-oxygenase.