NADPH-diaphorase in glandular cells and nerves and its relation to acetylcholinesterase-positive nerves in the male reproductive tract of man and guinea-pig.

The presence of NADPH-diaphorase activity and acetylcholinesterase in the testis, epididymis, vas deferens, seminal vesicle, pelvic plexus, prostate and urethra of man and guinea-pig was investigated with the nitro blue NADPH technique and the thiocholine method, respectively. In human material NADPH-diaphorase activity was found in the Leydig cells, Sertoli cells and the epithelial linings of the rete testis, the excretory ducts, seminal vesicle, prostate and urethra. The guinea-pig material showed staining of the Leydig cells and spermatozoa and similar epithelial staining of the tract as man. Nerves beneath the epithelium and in the muscle layers of cauda epididymis, vas deferens, seminal vesicle, prostate and urethra were also stained. NADPH-diaphorase-positive nerve cells were seen in the pelvic plexus. Some cells also displayed acetylcholinesterase activity but others showed activity for only one of the enzymes or no activity for either enzyme. In the cauda epididymis, vas deferens, seminal vesicle, prostate and urethra acetylcholinesterase-positive nerve fibres formed a plexus beneath the secretory cells. It is concluded that NADPH-diaphorase, generally accepted as a nitric oxide synthase, is present in glandular cells of the male genital tract. The enzyme is also present in nerves, where it is partly co-localized with acetylcholinesterase.

Culture of human urothelial cells on a cell-free dermis for autotransplantation.

OBJECTIVE: Techniques for in vitro culturing and autotransplantation have been developed for a variety of human cells and are used today in several fields of medicine. In reconstructive surgery within the genitourinary tract, autologous urothelial cells cultured in vitro could be of considerable value but have not yet been used clinically. The aim of this study was to facilitate transplantation of cultured urothelium by establishing a reliable method for culturing urothel on an immunologically inert and biodegradable structure. METHODS: Normal human urothelial cells were cultured in vitro using a feeder-cell system. To achieve an optimal carrier structure, cells were removed enzymatically from a split thickness skin graft. Human urothelial cells were then seeded on the cell-free dermis and incubated in vitro. The seeded dermis samples were investigated histologically and with immunohistochemical methods at days 7, 14 and 21. RESULTS: The human urothelial cells incubated in vitro reached confluence after 7-10 days and the cells could be cultured through 9 passages with preserved proliferative potential. When the cells were seeded on a cell-free dermis they attached, formed colonies and became confluent and stratified up to three cell layers after 21 days of incubation. The urothelial origin of the cells was confirmed by immunohistochemical staining against cytokeratin. CONCLUSION: The advantages of culturing the urothelial cells on a cell-free dermis include a short time lag until grafts are available, probably facilitated transplantation procedure, transplantation of undifferentiated cells and the formation of a vascularised base under the new urothelium. The method described in this study may be of great value in providing autologous urothelium for reconstructive surgery in the genitourinary tract.

Long-term follow up after sex reassignment surgery.

A long-term follow up of 136 patients operated on for sex reassignment was done to evaluate the surgical outcome. Social and psychological adjustments were also investigated by a questionnaire in 90 of these 136 patients. Optimal results of the operation are essential for a successful outcome. Personal and social instability before operation, unsuitable body build, and age over 30 years at operation correlated with unsatisfactory results. Adequate family and social support is important for postoperative functioning. Sex reassignment had no influence on the person's ability to work.

Resection margins of 2 versus 5 cm for cutaneous malignant melanoma with a tumor thickness of 0.8 to 2.0 mm: randomized study by the Swedish Melanoma Study Group.

BACKGROUND: The traditional surgical treatment for primary malignant melanoma has often been a wide excision with a margin of about 5 cm. Since the risk of local recurrences is dependent on tumor thickness, thin tumors (<1 mm) have routinely been excised with a narrow margin. For thick tumors, the optimal resection margin is controversial, and can be determined only by prospective, randomized trials. METHODS: The Swedish Melanoma Study Group performed a prospective, randomized multicenter study to evaluate an excision margin of 2 versus 5 cm for patients with cutaneous malignant melanoma with tumor thickness > 0.8 and < or = 2.0 mm. The trial includes 769 patients. Patients with melanomas of the skin of the head, neck, hands, feet, or vulva were not included in the trial. In the event of an excision biopsy for diagnosis, radical surgery was completed within 6 weeks. The median follow-up time was 5.8 years for estimation of survival and 4.0 years for diagnosis of recurrent disease. RESULTS: No significant differences have been observed between the treatment groups regarding local or regional recurrences or survival. CONCLUSIONS: We recommend an excision with a margin of 2 cm for cutaneous malignant melanoma with a tumor thickness > 0.8 and < or = 2.0 mm.

Elective lymph node dissection in stage I cutaneous malignant melanoma of the head and neck. A report from the Swedish Melanoma Study Group.

The effect of elective lymph node dissection in patients with cutaneous malignant melanoma of the head and neck was investigated in a retrospective study. Of 517 patients in clinical stage I, 84 underwent elective dissection of the ipsilateral neck lymph nodes. In six of these patients, lymph node metastases were demonstrated at histopathological examination. There was a slight reduction in the incidence of recurrent disease in the regional lymph nodes in the group of patients who had undergone elective lymph node dissection, but this difference was not statistically significant. No significant differences were seen between the two groups regarding overall survival of disease-related survival.

Androgen treatment of abdominally obese men.

Middle-aged men with abdominal obesity were treated in a double-blind study with moderate doses of transdermal preparations of testosterone (T), dihydrotestosterone (DHT), or placebo. This resulted in moderately elevated T concentrations and marked decreases in follicle stimulating and luteinizing hormones in the group treated with T, while the DHT group showed elevated DHT, markedly lower T values, and less diminution of gonadotropin concentrations. In the group treated with T visceral fat mass decreased (measured by computerized tomography) without significant changes in other depot fat regions. Lean body mass did not change. In the group treated with T, glucose disposal rate, measured with the euglycemic hyperinsulinemic clamp method, was markedly augmented. Plasma triglycerides, cholesterol, and fasting blood glucose concentrations as well as diastolic blood pressure decreased. There were no such changes in the DHT or placebo treatment groups. The men treated with T reported increased well-being and energy. In none of the groups did prostate volume, specific prostate antigen concentration, genito-urinary history, or urinary flow measurement change. It is suggested that supplementation of abdominal obese men with moderate doses of T might have several beneficial effects.

Construction of a neovagina with preservation of the glans penis as a clitoris in male transsexuals.

In 20 male-to-female transsexual patients, a neovagina has been constructed using a combination of penile and scrotal flaps. By dissecting the dorsal vessels and nerves of the penis from the base to the tip, the blood supply and sensation to the glans have been preserved. After resection of the corpora cavernosa, the glans has been left as an innervated island flap and repositioned as a clitoris. There were few complications. Circulatory problems in the flaps resulted in short vaginas in three patients. Stricture of the urethral meatus and excessive length of the urethra were easily corrected with another operation in three patients. Nineteen of the patients expressed an excellent sexual sensation of the clitoris, and all 20 were very satisfied with both the cosmetic and functional results.

Cutaneous malignant melanoma of the head and neck. Analysis of treatment results and prognostic factors in 581 patients: a report from the Swedish Melanoma Study Group.

BACKGROUND: Results of surgical treatment of cutaneous malignant melanoma (CMM) have been highly variable, probably because of patient selection. Therefore, a study of representative patients with this disease was performed. METHODS: In a defined area of Sweden, 581 patients were analyzed. Clinical records and histopathologic findings were reviewed. The minimum follow-up time was 7 years. Prognostic factors were evaluated by the Cox proportional hazards model. RESULTS: Evaluation of sex distribution, age, and anatomic site of the primary tumor showed that the patients were representative of all Swedish patients with CMM of the head and neck. The mean patient age at diagnosis was 64 years for both sexes. Fifty-three percent of the patients were women. Female patients had more tumors of the face than did male patients, whereas male patients were overrepresented among patients with tumors of the auricle-external ear canal and scalp-neck area. Localization to the face was observed in 68%, which is an overrepresentation of three to four times when skin surface is taken into consideration. Twenty-four percent of the patients had lentigo maligna melanoma. Only 33% of the patients had superficial spreading melanoma. In univariate analyses, sex, anatomic site of the primary tumor, histogenetic type, Clark level of invasion, and tumor thickness had prognostic power. In a multivariate analysis, tumor thickness, anatomic site of the primary tumor, and sex of the patient were independent prognostic factors. CONCLUSIONS: In representative patients with CMM of the head and neck, tumor thickness, anatomic site of the primary tumor, and sex of the patients were independent prognostic factors.

Management of deep sternal wound infection after cardiac surgery--Hanuman syndrome.

Deep sternal wound infection following open-heart surgery caused sternal osteitis in eight patients and mediastinitis in 27 during 1980-1989. The incidence of such infection was 0.5%. Infection was more common during the last 2 years than in 1980-1987 (0.8% vs. 0.4%), and when bilateral internal mammary artery grafts were dissected (3.2% vs. 0.6% when only one internal mammary artery was used). Cure of mediastinitis was achieved by primary closed irrigation in four of 13 patients and by primary open treatment in five of ten. Muscle flap was employed in totally ten patients and omentum in four before final elimination of infection. Of the 27 patients with mediastinitis, eight (30%) died in the post-operative period of cardiac failure (3 cases), disseminated infection (2), bleeding (2) or aspiration (1). The 5-year survival rate was 43%. Prosthetic value endocarditis caused one late death and necessitated one reoperation. If eradication of postoperative mediastinitis is not achieved by early diagnosis, debridement and closed irrigation, transposition of muscle or omentum should be considered.

Steroid hormone receptors in human adipose tissues.

Administration of glucocorticoid, estrogen, and progesterone is followed by changes in human adipose tissue distribution, morphology, and function. Therefore, specific receptors for these hormones were determined in different regions of human adipose tissue using ligand techniques, with separation of bound and free hormone by chromatography, absorption techniques, or isoelectric focusing, as well as protein quantitation with monoclonal antibodies against human estrogen and progesterone receptors. Furthermore, mRNAs were measured by solubilization hybridization technique with glucocorticoid, estrogen, and progesterone receptor cRNA probes for human receptors. Saturable specific cytosolic glucocorticoid binding was found. Quantitative analyses indicated more binding sites and mRNAs in intraabdominal than sc adipose tissue samples. In contrast, neither specific estrogen or progesterone binding, cytosolic or nuclear receptor protein, nor mRNAs for these receptors could be identified in abdominal, femoral, or omental adipose tissues. Parallel control experiments confirmed the presence of both estrogen and progesterone receptors in rat adipose tissues. It was concluded that while glucocorticoid receptors are clearly present in human adipose tissues, female sex hormone receptors are not present in quantities detectable with presently available methods. Effects of these hormones on human adipose tissue might, therefore, be mediated via a minute nondetectable quantity of receptors, the glucocorticoid receptor, or indirect mechanisms.

Prognosis for localized cutaneous melanoma treated with wide excision only, with special reference to development of regional node metastases.

A consecutive series of 564 patients with localized (Stage I) melanoma treated by wide excision only were followed for at least 5 years. The median tumor thickness was 1.50 mm, and 30% were ulcerated. The female/male ratio was 54/46. The overall survival rates were 80% at 5 years and 73% at 10 years. The survival rates were statistically significantly better for females, even when tumor thickness and ulceration were taken into consideration. Twenty percent developed regional node metastases after an average remission period of 13 months. The actuarial survival rates after node dissection were 32% at 5 years and 27% at 10 years. A subgroup with an exceptionally poor prognosis and a high rate of regional node dissemination was looked for. Only 26% of the intermediate thickness group (1.50-3.99 mm, Breslow) developed nodal metastasis, whereas patients with thick lesions (greater than 4 mm) had a metastasis rate of 43%. Patients with thick lesions may therefore benefit more from elective node dissection than patients with lesions of intermediate thickness. Patient characteristics, e.g., sex and tumor characteristics (ulceration), may prove to be of importance in a prospective trial on elective node dissection.

Metabolism of mammary, abdominal, and femoral adipocytes in women before and after menopause.

In 23 women before and 11 after menopause, adipocyte size, lipoprotein lipase activity, and lipolytic responsiveness to norepinephrine were compared in different regions of adipose tissue. In premenopausal women femoral adipocytes were characterized by a higher lipoprotein lipase activity than abdominal or mammary adipocytes. On the other hand, lipolytic responsiveness and sensitivity in the latter two was higher than in femoral tissue. In postmenopausal women no differences in lipoprotein lipase or lipolysis were found among the three regions. Consequently, menopause in women seemed to be associated with a diminution of not only the increased lipoprotein lipase activity of femoral adipocytes, but also of the high lipolytic response in abdominal and mammary adipose tissue. It is therefore suggested that female sex steroid hormones exert regionally specific effects, ie, increasing lipoprotein lipase in femoral adipocytes, which therefore become enlarged. It also seems possible that stimulation of lipolysis in abdominal and mammary adipocytes is an effect of sex steroid hormones. From the results obtained it is hypothesized that the secondary sex characteristics of adipose tissue distribution in women might be caused by regionally specific effects of sex steroid hormones on adipocyte metabolism.

Surgical treatment of carcinoma of the clitoris.

Thirty-eight consecutive patients were treated with either vulvectomy (14) or in combination with groin dissection (24) according to the same treatment protocol. The crude 5-year survival was 50% and the corrected 5-year survival was 66%. Three patients died postoperatively. Endophytic tumor, poor degree of differentiation, and involvement of lymph nodes resulted in higher mortalities. No patient with involvement of deep inguinal or pelvic nodes could be cured. The study concludes that invasive squamous cell carcinoma of the clitoris should be treated, in the same was as the same tumor in other areas of the vulva, with radical surgery.

Reconstruction of large anterior full-thickness defect in the chest wall after resection of chondrosarcoma.

Radical removal of a chondrosarcoma resulted in a very large full-thickness defect of the anterior chest wall, including the body of the sternum and adjacent parts of the ribs on both sides. The defect was closed with a double layer of Marlex mesh supported by metal bars bridging the gaps between the ends of resected ribs. This prosthesis was covered with bilateral latissimus dorsi muscle flaps and a split-thickness skin graft. The result, from both the functional and the cosmetic points of view, was excellent. The method permits closure of very large chest wall defects, enabling extensive radical removal of malignant tumours to prevent local recurrence.

Surgical treatment of carcinoma of the vulva.

In a prospective study, 169 patients with invasive squamous cell carcinoma of the vulva were treated by radical surgery. One hundred patients, without palpable inguinal lymph nodes, had a vulvectomy only, and the remaining 69 underwent vulvectomy in combination with groin dissection. Different prognostic factors were analyzed, and the results of radical surgery were evaluated. It was found that a small, exophytic, microscopically well differentiated tumor confined to one anatomic area will carry the best prognosis. Conversely, a patient with a large, endophytic, poorly differentiated tumor with inguinal lymph node metastasis will have the least favorable outcome. If there is metastatic spread to the deep inguinal node, Rosenmüller, the prognosis is quite bad. The crude five year survival rate was 56 per cent and the corrected survival ate was 65 per cent. Eleven patients died of early complications, seven of pulmonary embolism. It was concluded that radical surgery gives the best cure rate. It is suggested that operation for invasive squamous cell carcinoma of the vulva in all patients should consist of vulvectomy with primary skin grafting and bilateral superficial inguinal gland excision en bloc.

Bacteriological and serological studies after ileovesical diversion in dogs.

The risk of urinary tract infection after ileovesical diversion was studied by means of bacteriological and serological analyses in 8 mongrel dogs. Cultures of bladder contents showed heavy growth of the same bacterial strains as were found in the distal ileum. Cultures of the pelvic urine contained lower amounts of the same strains of bacteria. The levels of serum antibody titres to Escherichia coli and Proteus mirabilis were elevated only in 3 out of 100 sera examined. These slightly increased titres were not related to any obvious infection in the urinary tract. High C-reactive protein concentrations were noted in 3 dogs in connection with diagnosed inflammatory conditions. Colonization of the urinary tract after oral administration of selected test-strains could not be shown.