Developmental,estrogen induced infravesical obstruction is reversible in adult male rodents

PURPOSE: We treat neonatally estrogenized rats and aromatase over expressing AROM+ male mice with infravesical obstruction using the specific aromatase inhibitors finrozole and letrozole, and analyzed whether developmentally induced alterations in urodynamics and rhabdosphincter are reversible in adulthood. MATERIALS AND METHODS: Adult estrogenized rats and AROM+ mice were treated with aromatase inhibitors for 6 weeks. Maximal and mean bladder pressure, the urinary flow rates and electromyography activity were recorded from the proximal rhabdosphincter. In addition, proximal rhabdosphincter thickness in the AROM+ mouse was measured and correlated with seminal vesicle size and serum testosterone concentrations. RESULTS: Finrozole and/or letrozole treatment significantly increased the mean maximal flow rate plus or minus SD in AROM+ mice (4.7 +/- 2.0 versus 13.3 +/- 4.4 ml. per minute, p = 0.0004) and in estrogenized rats (18.4 +/- 6.18 versus 31.1 +/- 10.85 ml. per minute for finrozole p = 0.005) and 32.4 +/- 14.3 for letrozole, p = 0.005), while bladder pressure slightly decreased. The reappearance of transient repolarization, indicating urethral lumen opening, coincided with an increased flow rate on electromyography in the proximal rhabdosphincter in rats. Relative thickness of the proximal rhabdosphincter (p = 0.007), seminal vesicle size (p = 0.0002) and mean serum testosterone concentration (472.5 +/- 230.35 versus 3,065.6 +/- 1,994.67 pg./ml., p = 0.0002) were restored after finrozole treatment in AROM+ mice. CONCLUSIONS: Current findings indicate that alterations in urodynamics, seminal vesicle size, and rhabdosphincter size and function in developmentally estrogenized male rodents are reversible when treated with aromatase inhibitor.     

Characterization of estrogen-dependent growth of cultured MCF-7 human breast-cancer cells expressing 17β-hydroxysteroid dehydrogenase type 1

17β-hydroxysteroid dehydrogenase (17HSD) type 1 converts the weakly active estrogen, estrone, into highly active estradiol. In addition to being essential for gonadal estradiol biosynthesis, the enzyme is also expressed in a significant proportion of breast tumors. In order to study the role of the enzyme in estrogen-dependent growth of breast cancer, MCF-7 breast-cancer cells stably expressing human 17HSD type 1 were generated. In control MCF-7 cells a very low 17HSD activity was observed and, in line with its low estrogenic activity, estrone was devoid of the growth-enhancing effect of estradiol. The presence of the enzyme in the stably transfected HSD-7 cells resulted in a rapid conversion of estrone into estradiol but did not alter the estrogen-receptor concentration in the cells. However, in transfected cells, estrone had a growth-promoting effect practically identical to that of estradiol. The presence or absence of 17HSD type 1 in breast-cancer cells may therefore be decisive with regard to estrogen exposure and the estrogen-responsive growth of breast-cancer tissues. © 1996 Wiley-Liss, Inc.     

Multiple structural and functional abnormalities in the p450 aromatase expressing transgenic male mice are ameliorated by a p450 aromatase inhibitor

The present study was undertaken to analyze the effect of a P450 aromatase inhibitor (finrozole) on 4-month-old transgenic mice expressing human P450 aromatase (P450arom) under the human ubiquitin C promoter (AROM+). AROM+ mice present several dysfunctions, such as adrenal and pituitary hyperplasia, cryptorchidism, Leydig cell hypertrophy and hyperplasia, and gynecomastia. The present study demonstrates that these abnormalities were efficiently treated by administration of a P450arom inhibitor, finrozole. The treatment normalized the reduced intratesticular and serum testosterone levels, while those of estradiol were decreased. The body weight and several affected organ weights were normalized with the treatment. Histological analysis revealed that both the pituitary and adrenal hyperplasia were diminished. Furthermore, the cryptorchid testes present in the untreated AROM+ males descended to scrotum, 4 to 15 days after inhibitor treatment. In addition, the disrupted spermatogenesis was recovered and qualitatively complete spermatogenesis appeared with the inhibitor treatment. This was associated with normalized structure of the interstitial tissue, as analyzed by immunohistochemical staining for Leydig cells and macrophages. One of the features was that the Leydig cell hypertrophy was markedly diminished in the treated mice. AROM+ mice also present with severe gynecomastia, while the development and differentiation of the mammary gland in AROM+ males was markedly diminished with the inhibitor treatment. Interestingly, the mammary gland involution was associated with the induction of androgen receptor in the epithelial cells, while estrogen receptors were still detectable in the epithelium. The data show that AROM+ mouse model is a novel tool to further analyze the use of P450arom inhibitors in the treatment of the dysfunctions in males associated with misbalanced estrogen to androgen ratio, such as pituitary adenoma, testicular dysfunction, and gynecomastia.     

Experience with Carbamazepine in the Treatment of Withdrawal Symptoms in Alcohol Abusers

The use of carbamazepine in the treatment of chronic alcohol abusers has been described by Brune and Busch (1971), Löfgren (1972), Roaldsnes (1972) and Gammer (1976), among others. Ritola (1975) compared the effects of clomethiazole and carbamazepine in the treatment of alcoholics using double-blind techniques at Törnävä Hospital in 1974. Björkqvist and co-workers (1976) carried out a comparative multi-centre trial with carbamazepine and placebo. The positive results obtained in these clinical trials encouraged us to study carbamazepine in the treatment of alcohol abusers in a withdrawal unit for alcoholics.     

Nosocomial acquisition of methicillin-resistant Staphylococcus aureus during an outbreak of severe acute respiratory syndrome.

OBJECTIVE: The four hospitals assessed in this study use active surveillance cultures for methicillin-resistant Staphylococcus aureus (MRSA) and contact precautions for MRSA-positive patients as part of routine infection control practices. The objective of this study was to determine whether nosocomial acquisition of MRSA decreased in these hospitals during an outbreak of severe acute respiratory syndrome (SARS) when barrier precautions were routinely used for all patients. DESIGN: Retrospective cohort study. SETTING: Three tertiary-care hospitals (a 1100-bed hospital; a 500-bed hospital; and an 823-bed hospital) and a 430-bed community hospital, each located in Toronto, Ontario, Canada. PATIENTS: All admitted patients were included. RESULTS: The nosocomial rate of MRSA in all four hospitals combined during the SARS outbreak (3.7 per 10,000 patient-days) was not significantly different from that before (4.7 per 10,000 patient-days) or after (3.4 per 10,000 patient-days) the outbreak (P = .30 and P = .76, respectively). The nosocomial rate of MRSA after the outbreak was significantly lower than that before the outbreak (P = .003). Inappropriate reuse of gloves and gowns and failure to wash hands between patients on non-SARS wards were observed during the outbreak. Increased attention was paid to infection control education following the outbreak. CONCLUSIONS: Inappropriate reuse of gloves and gowns and failure to wash hands between patients may have contributed to transmission of MRSA during the SARS outbreak. Attention should be paid to training healthcare workers regarding the appropriate use of precautions as a means to protect themselves and patients.     

Hemodynamic improvement is faster after percutaneous ASD closure than after surgery.

OBJECTIVES: Hemodynamic effects of surgical and percutaneous closure of atrial septal defect (ASD) were evaluated. BACKGROUND: ASD causes volume overload of right ventricle (RV) and is associated with distortion and dysfunction of left ventricle (LV). The amount and timing of hemodynamic changes after ASD closure are not well known. METHODS: The study group consisted of 7 children treated surgically and 17 treated in the catheterization laboratory. In the control group, there were 51 healthy children. RV size and LV end-diastolic and systolic dimensions, volumes, and function were examined by two- and three- dimensional echocardiography and serum concentrations of natriuretic peptides measured prior to ASD closure, and 1, 6, and 12 months thereafter. RESULTS: In all children with ASD, during the 1-year follow-up, the z score of RV end-diastolic diameter decreased from a median 5.00 SD to 2.25 SD (P < 0.001). Dilatation of RV did not resolve entirely during 1-year follow-up in either treatment group. End-diastolic LV diameter increased from -1.50 to -0.50 SD (P < 0.001). LV size increased slower in the surgical subgroup but reached control levels in both groups. Concentrations of natriuretic peptides increased during the first month after ASD closure and normalized thereafter in patients treated percutaneously but remained higher than in controls in patients treated surgically. CONCLUSIONS: During 1-year follow-up after ASD closure, RV size decreases but does not normalize in all patients. The size of the LV normalizes after ASD closure but the increase in LV size is slower in patients treated surgically. Serum levels of ANPN and proBNP are elevated prior to ASD closure but decrease thereafter to control levels in patients treated with the percutaneous technique but not in those treated surgically.     

High levels of the extracellular matrix proteoglycan decorin are associated with inhibition of testicular function

Decorin (DCN), a component of the extracellular matrix of the peritubular wall and the interstitial areas of the human testis, can interact with growth factor (GF) signalling, thereby blocking downstream actions of GFs. In the present study the expression and regulation of DCN using both human testes and two experimental animal models, namely the rhesus monkey and mouse, were examined. DCN protein was present in peritubular and interstitial areas of adult human and monkey testes, while it was almost undetectable in adult wild type mice. Interestingly, the levels and sites of testicular DCN expression in the monkeys were inversely correlated with testicular maturation markers. A strong DCN expression associated with the abundant connective tissue of the interstitial areas in the postnatal through pre-pubertal phases was observed. In adult and old monkeys the DCN pattern was similar to the one in normal human testes, presenting strong expression at the peritubular region. In the testes of both infertile men and in a mouse model of inflammation associated infertility (aromatase-overexpressing transgenic mice), the fibrotic changes and increased numbers of tumour necrosis factor (TNF)-α-producing immune cells were shown to be associated with increased production of DCN. Furthermore, studies with human testicular peritubular cells isolated from fibrotic testis indicated that TNF-α significantly increased DCN production. The data, thus, show that an increased DCN level is associated with impaired testicular function, supporting our hypothesis that DCN interferes with paracrine signalling of the testis in health and disease.     

Gender differences in child-related and parent-related determinants of oral health-related lifestyle among 11- to 12-year-old Finnish schoolchildren

Objective. The aim of this study was to ascertain whether child-related and parent-related characteristics were associated differently with oral health-related lifestyle among boys and girls. Material and methods. The study population consisted of 5th and 6th graders and their parents in Pori, Finland. There were 1691 children ranging in age between 11 and 12 years. The data were gathered by questionnaires. For the analyses, we grouped children and parents within three lifestyle groups: favorable, moderate and poor. Differences in child-related and/or parent-related characteristics between boys and girls were analyzed with logistic regression analyses; those with a favorable lifestyle comprised the healthy lifestyle group, and those with a moderate or poor lifestyle the unhealthy lifestyle group. Results. Oral health-related lifestyle was healthy more often among girls than among boys. In both genders, those who considered toothbrushing important for pleasing authorities more often had a healthy lifestyle. Girls who considered toothbrushing important for health and appearance were more likely to have a healthy lifestyle than those who did not. The effect of parents’ oral health-related lifestyle was slightly stronger among boys than among girls. Among girls, however, high occupational level of father was indicative of healthy lifestyle. Conclusions. Among girls and boys, there are similarities and differences in factors related to oral health-related lifestyle. The parents’ model is important for both, but the effect is stronger among boys than among girls. Among girls, attitudes on health and appearance are positively associated with a health-related lifestyle.