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Biomedical subjects

D H Martin

Publications and source records attributed to D H Martin.

13 recordsLinked to original sources

A controlled trial of a single dose of azithromycin for the treatment of chlamydial urethritis and cervicitis. The Azithromycin for Chlamydial Infections Study Group.

BACKGROUND: Currently, there is no single-dose therapy that is effective in the treatment of urethral or endocervical infections with Chlamydia trachomatis. Azithromycin is a new azalide antibiotic that has substantial activity against C. trachomatis, is concentrated intracellularly, and has a long half-life in serum and tissue. METHODS: We conducted a trial in which 299 female patients and 158 male patients with uncomplicated genital infection and a positive C. trachomatis antigen test were randomly assigned to receive either azithromycin (1 g once orally) or doxycycline (100 mg orally twice daily for seven days). Only patients subsequently determined to have a culture positive for C. trachomatis at base line were included in the evaluation of efficacy. RESULTS: Among the patients who could be evaluated, 5 of the 141 patients (4 percent) treated with azithromycin did not respond to treatment, as compared with 3 of the 125 patients (2 percent) treated with doxycycline (difference between groups, 2 percent; 95 percent confidence interval, 0 to 6 percent). Of the patients evaluated 21 to 35 days after treatment, none of 112 treated with azithromycin and 1 of 102 treated with doxycycline had a positive culture. The rates of bacteriologic cure were similar for the 98 female patients (97 percent) and the 43 male patients (95 percent) treated with azithromycin. Seventeen percent of the patients who received azithromycin and 20 percent of those treated with doxycycline had mild-to-moderate drug-related side effects, mainly gastrointestinal symptoms. CONCLUSIONS: A single 1-g dose of azithromycin is as effective for the treatment of uncomplicated genital chlamydial infections as a standard seven-day course of doxycycline.

Adolescent

Alterations of nucleic acid and protein syntheses in vivo in the chick embryo mediated by captan.

1. The objective of this investigation was to measure the effects of captan on DNA, RNA and protein biosyntheses in limbs of developing chick embryo, in vivo. 2. Captan (12p.p.m.) was injected into the egg on day 4 of incubation and macromolecular syntheses were measured on days 8--14. 3. Total DNA content was unaffected by captan, but incorporation of [3H]thymidine was inhibited over the entire time range; the period of peak specific activity (day 11) was inhibited in treated samples to 67% of control. 4. Total RNA content was reduced in the earlier days but returned to normal by day 14, whereas incorporation of [3H]uridine was lowered throughout the period. The timing of peak specific activity for RNA synthesis was delayed by 2 days in treated eggs and was inhibited by 32% when peak days were compared. 5. Total protein concentration was slightly lowered by captan treatment in the mid-range of the days measured and the incorporation of [3H]valine was retarded in the early days; peak periods of synthesis were similar in magnitude but were shifted from days 9--10 in control to day 11 in treated embryos.

Animals

Enzootic and epizootic Venezuelan equine encephalomyelitis virus in horses infected by peripheral and intrathecal routes.

Forty-five horses were infected peripherally or intrathecally with enzootic or epizootic strains of Venezuelan equine encephalomyelitis (VEE) virus. Low titers of virus appeared in cerebrospinal fluid (CSF) after peripheral inoculation of enzootic or epizootic VEE virus strains. Intrathecal infection with either epizootic or enzootic VEE virus produced higher titers of virus in CSF than did peripheral infection. In contrast to peripheral infections with enzootic strains, intrathecal infections with these strains caused death. The animals that died had widespread histopathologic changes and large amounts of virus in brain tissue. The attenuated VEE virus vaccine strain, TC-83, also multiplied in the brain of horses inoculated intrathecally but caused no clinical disease and little histopathologic damage.

Animals

A randomized controlled trial of selective planned delivery.

A prospective randomized controlled trial designed to investigate selective planned delivery is reported: 264 obstetrically normal women in the 38th week of pregnancy were admitted to this trial and 184 completed it. The infants of mothers in the planned delivery group had higher serum bilirubin levels on the fifth day post partum than control infants but no baby required treatment for hyperbilirubinaemia. Mothers in the planned delivery group required significantly greater amounts of pethidine while control mothers had a significantly higher incidence of meconium staining of the amniotic fluid. However, the infants in the two groups had similar Apgar scores at birth. There was one stillbirth in the control group; this was due to unrecognized fetal hypoxia during labour induced at 42 weeks for postmaturity.

Apgar Score

Pathologic changes induced in respiratory tract mucosa by polycyclic hydrocarbons of differing carcinogenic activity.

Seven aromatic polycyclic hydrocarbons (PCHs) were investigated for their toxic effects on respiratory mucosa: benzo(e)pyrene (BeP), pyrene, anthracene, benz(a)anthracene(BaA), dibenz(a,c)anthracene(DBacA), benzo (a)pyrene (BaP), and dimethylbenz(a)anthracene (DMBA). The compounds were chosen because they comprise a spectrum of PCHs ranging from noncarcinogens, to initiators, to weak and strong carcinogens. All of them except DMBA are environmentally relevant chemicals. The chemicals were tested over an 8-week period. Heterotopic tracheal transplants were continously exposed and the histopathologic effects induced by the various PCHs were periodically assessed semiquantitatively. All PCHs exhibited varying degrees of toxicity for respiratory epithelium and submucosa. BeP clearly showed the least toxicity followed by pyrene and anthracene. BaA and DBacA caused marked epithelial and submucosal changes. In addition to epithelial hyperplasia, undifferentiated epithelium and squamous metaplasia developed. Marked mononuclear infiltration occurred in the subepithelial connective tissue. With BaP the epithelial and submucosal changes were similar but were much stronger. DMBA was the most toxic substance, causing epithelial necrosis followed by generalized keratinizing squamous metaplasia; the subepithelial changes consisted of an early acellular exudate and, later (at 8 weeks), marked condensation and hyalinization of the lamina propria. The toxic response pattern of the tracheal mucosa to carcinogenic agents was characterized by the chronicity of epithelial and connective tissue damage, as opposed to the short-lived hyperplastic and inflammatory response elicited by the noncarcinogens and weak initiators.

9,10-Dimethyl-1,2-benzanthracene

Quantitative exposure of grafted rat tracheas to 7, 12-dimethylbenz(a)anthracene.

A method was developed for continuously exposing tracheal epithelium to measured amounts of carcinogen. Beeswax was the vehicle for sustained release of carcinogen, and tracheas transplanted to s.c. sites were target tissues. In the experiment reported here, transplanted rat tracheas were exposed to a potent carcinogen, 7,12-di-methyl benz(a)anthracene (DMBA). The rate of release of DMBA from the beeswax carrier within the tracheal lumen approached first order when the initial concentration of carcinogen was high (3200 to 325 microng in a 24.45-mg pellet). With lower concentrations, where the carcinogen was dissolved in the beeswax, initial release was rapid, and most of the carcinogen was delivered within 4 weeks. At high DMBA dose levels, the entire tracheal epithelium was uniformly replaced by keratinizing squamous metaplasia after 1 week of exposure, and after 2 months, when from 280 to 910 microng DMBA had been delivered, all transplants had developed invasive squamous carcinomas. Sarcomas also developed in 19% of the transplants. At lower dose levels the epithelial reactions were more varied, and tumor development was more protracted. The lowest DMBA dose presently known to diduce carcinomas in this experimental model is 40 microng, which is in the dose range used for tumor initiation in skin carcinogenesis studies in mice.

9,10-Dimethyl-1,2-benzanthracene

Induction of preneoplastic and neoplastic lesions in grafted rat tracheas continuously exposed to benzo(a)pyrene.

Heterotopically transplanted rat tracheas were continuously exposed to measured amounts of benzo(a)pyrene over a period of 1 to 6 months. The cumulative doses ranged from 10 to 2490 microng. The morphological response of the tracheal epithelium was characterized by hyperplasis during the first 2 weeks, followed by atrophy. Squamous metaplasias did not appear until after 4 months of exposure; at 4 and 6 months numerous dysplastic lesions and noninvasive carcinomas resembling those seen in the airways of humans were found in the higher carcinogen dose groups. The first invasive carcinomas developed at 4 months in the groups given 1250 microng or more benzo(a)pyrene. The lowest dose tested that produced a carcinoma within the observation period of 22 months was 300 microng benzo(a)pyrene. The majority of the neoplasms were squamous cell carcinomas, although several adenocarcinomas and sarcomas also developed. Since a variety of metaplastic and dyplastic lesions can be induced by carcinogenic polycyclic hydrocarbons in the transplanted rat tracheas, this experimental model appears to be well suited for the study of the sequential epithelial changes that lead to respiratory tract neoplasia.

Animals

Selective planned induction in conditions of civil strife.

Selective planned induction may be defined as the initiation of labour by artificial means for reasons not strictly medical. Where the indications are merely social or for conveniencewhether patient's, hospital's, or doctor'sīt is doubtful that the procedure is acceptable until we have more detailed knowledge of its effects on the mother and fetus. However, the civil strife that occurred in Belfast in 1972 provided conditions in which the present study of the technique seemed justified. The results suggest that, provided the selection criteria are sufficiently rigorous and meticulously applied, there are no serious maternal risks. The main fetal risk is of unexpected prematurity; this can be avoided, but the precautions applied in this preliminary study reduced significantly the number of patients for whom the method could be used. A second series, with controls and using less rigorous selection criteria, is at present being studied.

Apgar Score

Experimental tumor induction in a circumscribed region of the hamster trachea: correlation of histology and exfoliative cytology.

A method for the induction of carcinomas in a circumscribed region of the hamster trachea is reported. By means of a special catheter, a solution of N-nitroso-N-methylurea was applied twice a week to about a 6-mm length of the trachea 10- to 16-mm distal from teh vocal cords. Slight alteration of this catheter allowed sampling of cytologic specimens directly from the surface of the carcinogen0exposed epithelium. This procedure permitted the simple and accurate correlation of sequential histologic and cytologic changes observed during tumor development in the hamsters. Noninvasive dysplastic and metaplastic lesions were seen in animals killed after 5 and 10 weeks of carcinogen application. These epithelial changes could be readily correlated with abnormal exfoliated cells abundantly present in cytologic specimens from these animals. Exposure to carcinogen for 15 weeks induced a 100% tumor incidence exclusively at the application site. More than 75% of the malignancies appeared within 15-20 weeks after the start of carcinogen administration. Most tumors were epidermoid carcinomas but some anaplastic large-cell carcinomas were also observed. Cytologic specimens of tumor-bearing animals had many cells conclusive of malignancy. The new experimental system lends itself to study of the effect of topically applied anticarcinogenic or cocarcinogenic agents on different carcinogen-induced epithelial lesions whose regression or progression can be followed by exfoliative cytology.

Animals

Species differences in the effect of benzo(alpha)pyrene-ferric oxide on the respiratory tract of rats and hamsters.

When given intratracheal injections of a suspension of benzo(alpha)pyrene-ferric oxide, rats and hamsters showed striking species differences in the response of their respiratory tracts to the carcinogen. Hamsters produced squamous metaplasia of the trachea and large bronchi; in contrast, squamous cell nodules of bronchioloalveolar origin developed in rats within a few weeks after carcinogen application. The different sites of the early proliferative and metaplastic responses correlated in their location with the sites of later tumor development. There were no obvious differences between the two species in retention of benzo(alpha)pyrene in the lungs or tracheas. A species difference was observed, however, in the localization of the benzo(alpha)pyrene in the tracheal tissues using ultraviolet fluorescence microscopy. Carcinogen was found to be present in the epithelium of hamsters but not in the epithelium of rats, suggesting a species difference in penetration of carcinogen from the lumen into the tracheal tissues.

Animals