Promotion of estrogen-induced mammary gland carcinogenesis by androgen in the male Noble rat: probable mediation by steroid receptors

Both endogenous and exogenous estrogen exposure is associated with an increased breast cancer risk. In some studies, elevated serum testosterone levels have also been linked to an increased breast cancer risk. Estrogen alone or combined with progesterone induces high mammary tumor incidences in various strains of both male and female rats. Mammary gland ductal adenocarcinomas were induced after 17beta- estradiol (E2) and testosterone propionate (TP) treatment in male Noble rats. Tumor incidence was 100% after 8-9 months of treatment. Such neoplasms were not detected after either estrogen or androgen exposure alone within this time period. TP alone caused disruption of mammary gland ducts and proliferation of stromal tissue, while E2 treatment alone induced both ductal epithelial growth and nodular atypical hyperplasia. To study the interaction of these hormones in mammary tumorigenesis, sex hormone receptors were characterized in mammary glands of Noble rats. Estrogen receptor-alpha (ER) was detected in age- matched, untreated mammary gland epithelium; in most early atypical hyperplastic lesions appearing after E2 and E2 + TP treatment and in E2 + TP-induced mammary tumors. Two major ER putative isoforms, 116 and 120 kDa, were detected in E2- and E2 + TP-treated mammary glands, and in the induced tumors. A 54 kDa ER protein was found in untreated and TP-treated mammary glands, and in the induced tumors. Both progesterone receptor-B (PR-B) and PR-A2, as well as androgen receptor-B (AR-B) and AR-A isoforms were markedly elevated in all E2 + TP-induced mammary tumors. However, the levels of both PR and AR were very low in mammary glands of E2- and E2 + TP-treated male rats. Low and moderate levels of AR and PR, respectively, were detected in most atypical hyperplastic lesions induced by E2- and E2 + TP-treated mammary glands. These results suggest that androgens may interact with either AR or PR, and perhaps both receptors, in E2 + TP-induced mammary glands and the induced tumors to effect the reduction in latency period, enhance tumor size, and increase incidence to 100%.      

Effect of promoter and intron 2 polymorphisms on murine lung K-ras gene expression

Differences in tumor formation among inbred mouse strains with high (A/J) and low (C3H) susceptibility for lung cancer have been linked to a repetitive element within the second intron of the K-ras gene. The purpose of this investigation was to determine whether differences within the K-ras gene promoter region or the intron 2 polymorphism affect K-ras gene expression in lung tumors and target alveolar type II cells isolated from A/J and C3H mice. Ribonuclease protection assays were performed using RNA isolated from 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK)-induced lung tumors from each mouse strain and alveolar type II cells isolated from A/J and C3H mice. An 838 bp fragment of the murine K-ras gene promoter region was amplified by PCR, cloned and sequenced from both mouse strains. Promoter regions from both mouse strains were inserted into a luciferase reporter gene vector, with and without the second intron polymorphism, and transfected into sensitive, intermediate and resistant lung tumor cell lines. No significant differences in K-ras gene promoter activity was found between the two strains using these specific reporter gene constructs. Consistent with these results, levels of K-ras expression did not differ between alveolar type II cells, whole lung or tumors induced by NNK in A/J or C3H mice. Moreover, in lung tumor cell lines derived from mice with differing susceptibility for lung cancer, K-ras expression did not correlate with the growth rate of tumors induced in nude mice from these cell lines. These results indicate that factors involved in modulating the rapid clonal expansion of the mutated K-ras allele from A/J mice are not directly linked to expression of this gene. Other genetic changes or losses in conjunction with hypothesized modifier loci, such as the Par1 locus, must play a significant role in establishing the phenotypic strain differences for lung tumor formation.      

Weaning practice in the Glasgow Longitudinal Infant Growth Study

AIMS: To assess compliance with Department of Health guidelines on weaning practice in a representative sample of 127 infants from Glasgow, and to identify factors influencing timing of weaning. METHODS: Questionnaires on feeding and weaning were completed during home visits. Ninety eight mothers completed a further questionnaire on attitudes to weaning. RESULTS: Median age at introduction of solid food was 11 weeks (range 4-35 weeks); only 7% of infants had not been weaned before age 4 months. There was no difference in timing of weaning between boys and girls. Younger mothers (< 20 years old), those of lower socioeconomic status, and those who formula fed their infants tended to introduce solids earlier. Infants who were heaviest before weaning were weaned earlier. Seventy three of 98 mothers reported that they weaned their babies because they felt that they required more food. Sources of information influencing time of weaning were previous experience (53/98), books and leaflets (43/98), advice from the health visitor (31/98), and family and friends (15/98). Sixty five of 98 mothers reported receiving formal information on weaning, in most cases (54) this was from the health visitor. Mothers who received formal information tended to wean their infants later. Two per cent of infants had been given cow's milk as a main drink by age 6 months, 17% by 9 months, and 45% by the end of the first year. CONCLUSION: Compliance with recommendations on timing of weaning (not before 4 months), weaning foods, and cow's milk consumption in Glasgow is poor, although no poorer than in many other areas of the UK as found by Office of Population, Censuses and Surveys. Public health messages in relation to weaning may not be reaching their target audience.     

Mycoplasma pneumoniae infection and neurological disease

The cases are reported of 13 children seen over a 22 month period who presented with a variety of acute neurological illnesses associated with Mycoplasma pneumoniae infection. Although presentation with a decreased level of consciousness or seizures was common, psychosis, hemiparesis, cranial nerve palsies, and Guillain-Barré syndrome were also seen. In contrast with published reports, only one child had an associated chest infection. Although some children have been left with residual disability, most have made a complete recovery. In this recent experience, M pneumoniae is a not rare cause of neurological illness in childhood and may present in unusual ways.     

Hormonal treatment of cryptorchidism—hCG or GnRH—a multicentre study

In a modified, double-blind controlled study, 163 prepubertal boys (aged 1.8-13.0 years) with bilateral and 94 (aged 1.5-13.1 years) with unilateral cryptorchidism were allocated to treatment with either human chorionic gonadotrophin (im), gonadotrophin releasing hormone (intranasally) or placebo (intranasally). In individuals with the bilateral condition treatment with human chorionic gonadotrophin resulted in complete descent of both testes in 23% of patients. Treatment with human chorionic gonadotrophin in unilateral cryptorchidism resulted in complete descent in 19% of patients; all results were significantly better than those obtained with gonadotrophin releasing hormone or placebo. Linear and logistic regression analysis of the results obtained by treatment of bilateral disease showed that all treatments were more successful the younger the age of the boys. The data indicated that bilateral and unilateral cryptorchidism respond differently to hormonal treatment. We suggest that human chorionic gonadotrophin should be the first choice of treatment for prepubertal boys older than one year.     

Dexamethasone and bacterial meningitis in Pakistan

The objective of this study was to assess, in a developing country setting, the effect of dexamethasone therapy on bacterial meningitis outcomes. A prospective double blind placebo controlled trial was conducted in 89 children aged from 2 months to 12 years suffering from bacterial meningitis. Neurological, developmental, and hearing assessments were conducted at one, four, and 12 months after discharge. Forty eight patients received dexamethasone and 41 placebo. Initial antimicrobial drugs used were ampicillin and chloramphenicol. For all patients at the time of admission the mean duration of illness was 5.7 days; 47% had had seizures and 56% had impaired consciousness. Seventeen of 89 (19%) patients died. The mortality for the dexamethasone group was 25% as compared with 12% in the group receiving placebo. Presentation to the hospital after four days of symptoms and with impaired conscious state were independent predictors of death. Of the dexamethasone group survivors, 26.5% had neurological sequelae and 42.3% had hearing impairment, whereas in the placebo group it was 24% and 30% respectively. Altered state of consciousness was a predictor of neurological sequelae. The presence of neurological sequelae and high cerebrospinal fluid protein independently predicted hearing loss. No beneficial effect of dexamethasone was observed on morbidity or mortality of this group of patients with bacterial meningitis. Dexamethasone is therefore not useful in developing countries as adjunctive treatment in patients seriously ill with bacterial meningitis, who present late for treatment and have been partially treated.     

Coronary artery fistula; coronary computed topography – The diagnostic modality of choice

Coronary artery fistulae (CAF) are rare anomalies. They are vascular communications between the coronary arteries and other cardiac structures, either cardiac chambers or great vessels. There can be considerable variation in the course of a coronary artery fistula. We report a case of a coronary artery fistula between the left circumflex coronary artery and the right and left atria. CAF are often diagnosed by coronary angiogram, however with the advent of new technologies such as Coronary Computed Tomography Angiography (Coronary CTA) the course and communications of these fistulae can be delineated non-invasively and with greater accuracy.     

Breast-feeding and a subsequent diagnosis of measles

Background: Breast-feeding protects against many infectious diseases and may also influence immunization outcomes.
Aim: This study investigated if breast-feeding protects against clinical measles and if it modified the effect of immunization.
Methods: We used logistic regression with data for 10 207 individuals from the 1970 British Cohort study (BCS70). Breast-feeding data were collected at five years of age, and information on clinical measles infection, as well as socio-economic measures was collected at the age of ten years. Breast feeding was categorized as: breast-fed <1 month (n = 1611), breast-fed for 1–3 months (n = 1016), breast-fed for more than three months (n = 1108), breast-feeding of uncertain duration (n = 21) and never breast-fed (n = 6451).
Results: Breast-feeding for more than three months was negatively associated with a diagnosis of clinical measles infection after adjustment for crowding, social class, measles vaccination, parity and sex with an odds ratio (95% confidence interval) of 0.69 (0.60–0.81) compared with those who never breast-fed. Measles vaccination was highly associated with low risk for measles with: 0.14 (0.13–0.16). Age at acute measles infection was not associated with breastfeeding. Breast-feeding did not notably alter measles immunization efficacy.
Conclusion: Immunization against measles provides effective protection against the disease. A more modest reduction in the risk of a measles diagnosis is associated with breast-feeding. The associations with a diagnosis of measles for breast-feeding and measles immunization are independent of each other.