The use of laparoscopic ovarian electrocautery in preventing cancellation of in-vitro fertilization treatment cycles due to risk of ovarian hyperstimulation syndrome in women with polycystic ovaries

Fifty women with polycystic ovaries took part in a prospective randomized study. All women required treatment by in-vitro fertilization (IVF) for reasons other than anovulation. They had all previously undergone ovarian stimulation with gonadotrophin therapy which had failed to result in pregnancy or had been abandoned due to high risk of developing ovarian hyperstimulation syndrome (OHSS). Twenty-five women were treated by long-term pituitary desensitization followed by gonadotrophin therapy, oocyte retrieval and embryo transfer (group 1). Twenty-five women underwent laparoscopic ovarian electrocautery after pituitary desensitization followed by gonadotrophin therapy, oocyte retrieval and embryo transfer (group 2). A significantly higher number of women in group 1 had to have the treatment cycle abandoned due to impending or actual OHSS, determined by endocrine and clinical findings. In addition, the development of moderate or severe OHSS in completed cycles was higher in group 1. The pregnancy rate and miscarriage rates in the two treatment groups were similar. The authors propose that laparoscopic ovarian electrocautery is a potentially useful treatment for women who have previously had an IVF treatment cycle cancelled due to risk of OHSS or who have suffered OHSS in a previous treatment cycle.      

The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive,non-randomized study of cancer-free and oral squamous cell carcinoma subjects

Background  

The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls.     

Biallelic somatic inactivation of the mismatch repair gene MLH1 in a primary skin melanoma

Inactivation of mismatch repair (MMR) genes has been linked to the hereditary nonpolyposis colon cancer syndrome and to a subset of sporadic cancers. A phenotypic characteristic of tumors with defective MMR is microsatellite instability (MSI). Although MSI has been reported in a proportion of cutaneous melanomas, inactivation of MMR genes in this tumor type has not been detected thus far. We recently described a human melanoma cell line, PR-Mel, and a cutaneous metastasis from the same patient, which displayed a MMR defect, and showed high MSI. Here we report that in the PR-Mel cell line both MLH1 alleles are somatically inactivated. One allele is lost through a chromosomal deletion of the region 3p21-24, whereas the remaining allele harbors a G --> A transition at position -1 of the acceptor splice site of intron 15, leading to the in-frame skipping of exon 16. The primary melanoma of the PR patient shows loss of heterozygosity at the BAT21 microsatellite marker, located in the MLH1 gene, and does not express the MLH1 and PMS2 proteins. Moreover, it harbors the same mutation detected in the PR-Mel cells. These results demonstrate that biallelic inactivation of MLH1 had occurred in the primary melanoma of the PR patient and suggest that disruption of MMR might have had a role in the development of the melanoma. This is the first report in which genetic defects leading to disruption of MMR function in a human melanoma have been identified.     

Effects of grade retention on academic performance and behavioral development

This study examined the controversial practice of grade retention and children's academic and behavioral adjustment using data from the Quebec Longitudinal Study of Kindergarten Children. We employed an autoregressive modeling technique to detect the impact of being held back during primary school on subsequent academic performance and behavioral development until age 12 years. The results indicate both a short- and long-term negative influence on academic performance for boys and girls. Children's anxious, inattentive, and disruptive behaviors persisted and, in some cases, worsened after grade retention. These prospective associations were long lasting and more pronounced when grade retention occurred early in primary school. Boys were more vulnerable to the negative influence of grade retention on academic performance and classroom disruptiveness. Disruptive behavior in girls was comparatively less associated with long-term consequences than boys. Nevertheless, girls experienced both short- and long-term academic performance problems in the aftermath of grade retention. Children's prosocial behavior appeared unaffected by grade retention. These results are independent of what would have been expected by the natural course of academic and behavioral development.     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Cholinergic control of gastric acid secretion

Summary In the perfused stomach preparation of the anaesthetized rat the cholinergic agonists acetylcholine (ACh) and bethanechol stimulated gastric acid secretion. Both agonists produced similar maximal acid output (70 mol/15 min) when infused intravenously. However, bethanechol was more potent, eliciting half maximal stimulation at 1.98 mol/kg/h. Secretory responses to either agonist were antagonized in a dose related fashion by blockade of muscarinic receptors with atropine. In contrast, inhibition of nicotinic receptors with hexamethonium produced a striking potentiation of ACh stimulated secretion whilst the bethanechol elicited secretion remained unaffected. In the presence of full nicotinic receptor blockade the ACh response curve was shifted to the left sixfold, half maximal stimulation being produced at 1.79 mol/kg/h. Cimetidine partially inhibited the secretory responses elicited by either ACh or bethanechol while blockade of adrenoceptors ( and ) did not affect acid output induced by cholinergic agonists. Secretion elicited by ACh is interpreted as being the composite effect of prosecretory action and an inhibitory mechanism due to the activation of nicotinic receptors. Hexamethonium, through nicotinic receptor blockade, inhibits the restricting mechanism and thus reveals the full stimulatory action of ACh.     

Stability of DNA methylation of X-chromosome genes during aging

The stability of DNA methylation during aging was assessed in two groups of young (5–20 years old) and old (85–95 years old) women in DNA from blood leukocytes. Three X-linked genes were investigated. Two,G6PD andGdX, are located on Xq28, on the inactivated portion of the X chromosome: demethylation of specific regions of both genes was shown previously to be directly correlated with gene reactivation. The third,MIC2, is located on the pseudoautosomal region of the X chromosome and escapes X inactivation. The 5 region of theG6PD andGdX genes and the body of theG6PD, GDX, andMIC2 genes were analyzed with specific DNA probes. No age-related changes in methylation pattern were detected. We can conclude therefore that the methylation pattern of the three X-linked genes is stable during aging in female leukocytes and that a high rate of age-related reactivation of X-linked genes may not be a feature of all X-linked loci.     

Menstrual cycle and timing of breast surgery in premenopausal node-positive breast cancer: Results of the International Breast Cancer Study Group (IBCSG) Trial VI

Purpose: It has been postulated that breast cancer surgery performedduring the follicular phase of the menstrual cycle is associated with pooreroutcome.Patients and methods: We tested this hypothesis by evaluatingdisease-free survival (DFS) for 1033 premenopausal patients who receiveddefinitive surgery either during the follicular phase (n = 358) or theluteal phase (n = 675). All patients were enrolled in a randomized trialconducted between July 1986 and April 1993. All had node positive breastcancer and randomization was stratified by estrogen receptor (ER) status.All patients received at least three cycles of adjuvant cyclophosphamide,methotrexate, and 5-fluorouracil (CMF). The median follow-up was 60 months.Results: Patients who underwent definitive surgery for breast cancer inthe follicular phase had a slightly worse disease-free survival than thoseoperated on during the luteal phase (five-year DFS percentage: 53%versus 58%; hazard ratio, 1.13; 95% confidence interval (CI),0.94–1.38; P = 0.20). The effect was significantly greater for thesubpopulation of 300 patients with ER-negative primaries (P = 0.02interaction effect; five-year DFS percentages 42% vs. 59%;hazard ratio 1.60; 95% CI, 1.12–2.25; P = 0.008). The effect oftiming of surgery diminished for analyses based on lesser surgicalprocedures, e.g., excisional biopsies. In particular, no effect of timingwas observed for fine needle aspiration procedures.Conclusions: Surgical procedures which are more extensive than a fineneedle aspiration biopsy might be associated with worse prognosis if conductedduring the follicular phase of the menstrual cycle. This phenomenon was seenpredominantly for high risk breast cancer with low levels or no estrogenreceptors in the primary tumor.     

Postzygotic instability of the myotonic dystrophy p[AGC]n repeat supported by larger expansions in muscle and reduced amplifications in sperm

We have analysed the [AGC] expansion in leucocytes, muscle and sperm from 17 individuals affected by myotonic dystrophy (DM). Skeletal muscle showed a larger repeat number than leucocytes in the same patient. A similar degree of expansion was detected in differently affected muscles of a single patient. The germline mutation ( 350 repeats) was expanded in somatic cells of the progeny in all patients examined. Our results provide evidence of an early postzygotic instability of the [AGC] repeat in DM.