Histological changes over time around the site of sustained release naltrexone-poly(DL-lactide) implants in humans.

In order to assess the histological tissue changes over time around the site of implant, tissue biopsies were taken at 1 to 38 months post-implant from 54 (34 male) consenting human subjects who had received the Australian subcutaneous naltrexone-poly(DL-lactide) implant for heroin dependence. The implant consists of multiple tablets containing compressed naltrexone-poly[trans-3,6-dimethyl-1,4-dioxane-2,5-dione] (DL-lactide) loaded microspheres. Assessment of tissue samples by pathologists showed an early phase (up to 12 months post-implant) of inflammation, foreign body reaction, and fibrosis. This subsided gradually over the next 12 months until tissue returned to normal by 25+ months. Sufficient evidence was not available to conclude that the poly(DL-lactide) implant matrix was totally biodegradable within the study period. While implant material was not identified in most of the latter biopsies, its presence was noted in one biopsy at 26 months post-implant. Nevertheless the study results did demonstrate the implant's biocompatibility by the lack of inflammation, foreign body reaction, and fibrosis detected by 25+ months. It seems highly probable that surgical technique rather than the implant itself was associated with the additional finding of fat necrosis. Moderate fat necrosis was observed as a common feature of biopsies carried out during the first 6 months following implant. It subsided to mild levels over the next 18 months, and was notably absent by 25+ months. The results of the study indicated that the Australian naltrexone-poly(DL-lactide) implant is well tolerated and may have a role for use in the management of medical conditions such as heroin dependence.     

One-stage penile/preputial island flap urethroplasty for difficult posterior urethral strictures

Summary Short traumatic strictures of the membranous urethra can be repaired by excision and end-to-end urethroprostatic anastomosis. Long membranous or bulbomembranous strictures with or without associated periurethral fibrosis, abscess or urinary fistulae require substitution urethroplasty. Tubed full-thickness skin grafts have a poor chance of survival in such circumstances. Scrotal flaps are hairy, but the penile/preputial island flap, which is relatively hairless, is ideal for such reconstructions in one stage. Difficult perineal exposure led to the development of the transpubic and the abdominoperineal routes. Modification of the incision for perineal prostatectomy by dividing the posterior part of the urogenital diaphragm in the midline up to the urethra improves the exposure so that almost all such reconstructions can be done by the perineal route. A total of 21 cases are reviewed. Flap survival is 100%, but stenosis or restricture at the anastomotic sites can occur as a result of faulty technique. These can be treated by internal urethrotomy or excision and reanastomosis.     

Male breast carcinoma. I. A study of the total material reported to the Swedish Cancer Registry 1958-1967 with respect to clinical and histopathologic parameters

During the time period 1958-1967 190 cases of male breast cancer were reported to the Swedish Cancer Registry. The reported cases were thoroughly re-evaluated from the evidence of the clinical records and histopathologic specimens. The material contained 166 cases of histologically verified invasive breast carcinoma which were analyzed with respect to different clinical and histopathologic parameters. In contrast to the rate in females, the breast cancer incidence rate in males did not increase significantly during the period under review, and the age-specific incidence rate did not show a Clemmesen's hook but increased relatively more rapidly at high ages than for female breast carcinoma. The mean age at diagnosis was 4 to 5 years higher in male breast cancer patients than in females. Larger tumours were more frequent among older patients and there was a 5-year shift between the age-distribution curves for small (less than 2 cm) and larger (2-5 cm) tumours. A similar difference was found between pN0 and pN1 tumours. This difference might reflect the progression rate of male breast cancer. The histopathology pattern and distribution of histologic malignancy grades were similar to those in female breast carcinoma with the exception that lobular carcinoma and medullary carcinoma with lymphoid infiltration were lacking in the male material.     

3-(Methylnitrosamino)propionitrile: occurrence in saliva of betel quid chewers, carcinogenicity, and DNA methylation in F344 rats

3-(Methylnitrosamino)propionitrile (MNPN), a potent carcinogen in F344 rats, was detected for the first time in the saliva of betel quid chewers at levels ranging from 0.5 to 11.4 micrograms/liter. The tumorigenic properties of MNPN and its potential to methylate DNA in F344 rats were evaluated. Groups of 21 male and 21 female rats were given 60 s.c. injections over a 20-week period (total doses 0.055 and 0.23 mmol per rat). The experiment was terminated after 106 weeks. MNPN at the higher dose induced 18 (86%) malignant tumors of the nasal cavity in male and 15 (71%) in female rats. The lower dose induced nine (43%) liver tumors. Groups of four or five male F344 rats were treated with a single s.c. or i.v. injection of MNPN (0.4 mmol/kg). MNPN was also administered to rats by swabbing the oral cavity (2.21 mmol/kg). The levels of 7-methylguanine and O6-methylguanine, formed 0.5-36 h after treatment, were measured in the liver, nasal mucosa, esophagus, and oral issues. The highest levels of methylated guanines were detected in the nasal cavity independent of the route of administration. The results of this study demonstrate that MNPN is present in the saliva of betel quid chewers and is a potent carcinogen in F344 rats.     

The effects of caffeine on various body systems: a review

Caffeine is the most widely consumed drug in Western society. The intake of caffeine-containing beverages in many adults and children often reaches levels that can induce pharmacological effects. Ninety-nine percent of ingested caffeine is absorbed and distributed to all tissues and organs. The effects of caffeine intake differ greatly according to acute or chronic intake, level of intake, and the development of tolerance. Caffeine administered acutely to non-users or recent abstainers can induce hypertension, arrhythmias, altered myocardial function, increased plasma catecholamine levels, plasma renin activity, serum cholesterol levels, increased production of urine, gastric acid secretion, and alterations in mood and sleep patterns. Tolerance to chronic caffeine intake develops in most individuals, with the cessation of its effects on the renal system, the cardiovascular system, the gastrointestinal system and, to some extent, the central nervous system. Moderate caffeine consumers probably need to have little concern for the effect of caffeine intake on their health if their other life-style habits are also moderate.     

Lumbar disc syndrome in Finland.

The prevalence of lumbar disc syndrome (herniated disc or typical sciatica) and its consequences in terms of disability, handicap, and need for medical care were studied as part of the Mini-Finland Health Survey. A sample of 8000 persons representative of the Finnish population aged 30 or over was asked to come for examination, and 7217 (90%) participated. A diagnosis of lumbar disc syndrome based on medical history, symptoms, and standardised physical examination was made for 5.1% of the men and for 3.7% of the women. Half of these patients were assessed to be in need of medical care, over 80% of which was considered to be adequately met. One third of all patients with lumbar disc syndrome had been previously hospitalised for that syndrome, and one fifth of the patients had undergone lumbar surgery. At least slight disability was found in almost 60% of the patients, though severe functional limitations were rare. About 6% of the population's work disability was estimated to be attributable to lumbar disc syndrome.     

Effects of danazol on mineral homeostasis in normal postmenopausal women: preliminary communication.

The effects of danazol on calcium homeostasis in normal postmenopausal women was examined in a 14-day study utilizing a dosage of 800 mg per day. Danazol caused significant falls in plasma ionized calcium and in the fasting urinary calcium/creatinine ratio, indicating inhibition of bone resorption. Retention of phosphate was also observed as expected with this anabolic agent. The plasma total alkaline phosphatase was also depressed by the drug, which had no effect on hepatocellular function as measured by plasma AST. Certain effects induced by treatment with danazol were still apparent two weeks after cessation of treatment. The drug was well tolerated and androgenic side effects were not seen. It is suggested that the minimal dose regimen of danazol which exerts a calcium-sharing effect should be identified, and that this regimen should be considered for use in a prospective study of the effects of danazol on bone mineral content in the postmenopause.