An android body fat distribution in females impairs the pregnancy rate of in-vitro fertilization-embryo transfer

To assess if the waist:hip ratio (WHR) is associated with the pregnancy rate (PR) in in-vitro fertilization (IVF) and embryo transfer, waist and hip girths, in addition to height, weight, body mass index (BMI), indications for IVF, PR and other related variables, were measured in 220 women undergoing IVF-embryo transfer. Three variables were significantly negatively associated with PR; high age, smoking and WHR >0.80. Women with WHR between 0.70-0.79 had a PR of 29.9% as compared to 15.9% in women with WHR >0.80 [odds ratio 0.42, 95% confidence interval (CI) 0.2-0.9, P = 0.03]. There were no correlations between BMI and PR, nor were there any significant differences for the indications for IVF-embryo transfer, number of oocytes or oocyte fertilization rate, cleavage rate and number of embryos transferred. The association between a low PR and WHR >0.80 remained unchanged after adjustment for age, BMI, smoking, indication for IVF, parity and number of embryos transferred. In IVF-embryo transfer, fertilization is a laboratory and clinically controlled process, until the embryo is transferred to the uterus. Possible reasons for our finding of a decreased PR in women with an android body fat distribution include a different endocrinological and biochemical milieu for the oocyte in the growing follicle, oocytes of poor quality, or endometrial changes due to hormonal dysfunction.      

Localization of neuroendocrine tumours and insulinomas using radiolabeled somatostatin analogues, 123 I-Try3-octreotide and 111in-pentatreitide

OBJECTIVE A number of neoplasms are known to express somatostatin receptors; the use of somatostatin receptor imaging in their localization has recently been described, but the resolution and discrimination of the isotopes used remains sub-optimal. We have looked at the use of a new” In-labelled analogue of somatostatin, pentatreotide, in the visualization and functional characterization of a number of neoplastic conditions. PATIENTS Thirteen patients with proven neoplasms were scanned using this agent. Planar and single-photon-emission computerized tomographic (SPECT) images of the relevant part of the body were obtained using a gamma-camera at 10 minutes and 4 and 21 hours after injection of the radiopharmaceutical. In six patients (three carcinoid, three insulinomas) scanning was also performed using ¹²³l-Tyr-3-octreotide. RESULTS Primary tumours or metastases were visualized in six of the seven patients with neuroendocrine tumours, and three of six patients with insulinoma. One patient with an insulinoma who had a positive scan showed absent uptake when rescanned after tumour removal. A rise In blood glucose (more than twice basal) in response to octreotide was seen only in those insulinoma patients with positive scans. In cases where both ¹¹¹ln-pentatreotide and ¹²³l-Tyr-3-octreotide scans were performed, both radiopharmaceuticals identified the same 4/ 6 tumours; however, tumour definition (reflecting high tumour to background ratio) was better with pentatreotide on the 21-hour images with minimum biliary and gut activity, allowing better resolution of the tumour image. CONCLUSION It appears that ¹¹¹ln-pentatreotide scintigraphy is a rapid and safe procedure for the visualization of neuroendocrine tumours possessing somatostatin binding sites. A positive scan may be predictive of neuroendocrine responsiveness to octreotide therapy. In addition, it also appears that¹” In-pentatreotide has superior kinetics compared to ¹²³I-Tyr-3-octreotide, typically achieving more satisfactory tumour to background ratios, and may thus be more useful in the localization of endocrine tumours.     

Prevalence of Helicobacter pylori in acromegalic patients during treatment with octreotide

BACKGROUND Octreotide, a synthetic long-acting analogue of somatostatin, now has an establlshed role in the treatment of acromegaly. In acromegalic patients treated with octreotide there is an increased incidence of gallstones and possibly gastritis. OBJECTIVES (1) To compare the seroprevalence of Helicobacter pylori (H. pylori) infection, in acromegalic patients treated with octreotide to that in patients given other treatment modalities. (2) To study retrospectively the temporal relatlon between H. pylori acquisition and octreotide treatment. PATIENTS Three groups of acromegalic patients were studied; 35 (20 M) had been treated wlth octreotide, 17 (10 M) with bromocriptine and 19 (12 M) had received no pharmacological intervention (untreated, surgically treated or treated with radiotherapy). DESlGNlMEASUREMENTS The presence of H. pylori infection was assessed serologically (Bio-Rad GAP test for IgG), using stored serum, on the most recent sample from each patient and on serial samples from patients treated with octreotlde. RESULTS The prevalence of H. pylori seropositivity was similar in each treatment group, 34, 35 and 37%, respectively. Mean age and duration of acromegaly were similar in the first two groups. Patients who had never received medical treatment were slightly younger. GH levels were similar in all three groups. Patients on octreotide who were seropositive for H. pylori did not differ from those with negative serology with respect to age, duration of acromegaly, duration of octreotide treatment or serum GH level. Serial samples in octreotide treated patients showed a change in status in only one patient; 18 patients continued with negative serology during a mean period of 30 (range 4–62) months. In each of the 6 patients with persistently positive serology during octreotide treatment, stored samples predating octreotide therapy were shown to have already been positive. CONCLUSIONS The seroprevalence of H. pylori infection in acromegalic patients does not appear to be increased in a manner dependent on the type or duration of medical treatment. In particular, octreotide therapy, while causing the development of histological gastritis in some patients, does not appear to induce the development of H. pylori infection.     

Intracardiac metastases from neuroendocrine tumours

We report three cases of intra-cardiac metastases from neuroendocrine tumours of the carcinoid type. One presented in a manner identical to a left atrial myxoma; in one patient a left atrial mass was noted during investigations for weight loss and a lung mass; and in the third, two right ventricular deposits were detected on echocardiography when a patient with a disseminated GHRH-secreting tumour was investigated for dyspnoea. Although to our knowledge this is only the third report of these lesions, we believe that this represents a form of carcinoid heart disease that is distinct from the valvular abnormalities seen in some patients with carcinoid syndrome. Neuroendocrine metastases should be considered in the differential diagnosis of intra-cardiac tumours.     

Genetic Analyses in a Sample of Individuals With High or Low BMD Shows Association With Multiple Wnt Pathway Genes

Using a moderate‐sized cohort selected with extreme BMD (n = 344; absolute value BMD, 1.5–4.0), significant association of several members of the Wnt signaling pathway with bone densitometry measures was shown. This confirms that extreme truncate selection is a powerful design for quantitative trait association studies of bone phenotypes. Introduction : Although the high heritability of BMD variation has long been established, few genes have been conclusively shown to affect the variation of BMD in the general population. Extreme truncate selection has been proposed as a more powerful alternative to unselected cohort designs in quantitative trait association studies. We sought to test these theoretical predictions in studies of the bone densitometry measures BMD, BMC, and femoral neck area, by investigating their association with members of the Wnt pathway, some of which have previously been shown to be associated with BMD in much larger cohorts, in a moderate‐sized extreme truncate selected cohort (absolute value BMD Z‐scores = 1.5–4.0; n = 344). Materials and Methods : Ninety‐six tag‐single nucleotide polymorphism (SNPs) lying in 13 Wnt signaling pathway genes were selected to tag common genetic variation (minor allele frequency [MAF] > 5% with an r² > 0.8) within 5 kb of all exons of 13 Wnt signaling pathway genes. The genes studied included LRP1, LRP5, LRP6, Wnt3a, Wnt7b, Wnt10b, SFRP1, SFRP2, DKK1, DKK2, FZD7, WISP3, and SOST. Three hundred forty‐four cases with either high or low BMD were genotyped by Illumina Goldengate microarray SNP genotyping methods. Association was tested either by Cochrane‐Armitage test for dichotomous variables or by linear regression for quantitative traits. Results : Strong association was shown with LRP5, polymorphisms of which have previously been shown to influence total hip BMD (minimum p = 0.0006). In addition, polymorphisms of the Wnt antagonist, SFRP1, were significantly associated with BMD and BMC (minimum p = 0.00042). Previously reported associations of LRP1, LRP6, and SOST with BMD were confirmed. Two other Wnt pathway genes, Wnt3a and DKK2, also showed nominal association with BMD. Conclusions : This study shows that polymorphisms of multiple members of the Wnt pathway are associated with BMD variation. Furthermore, this study shows in a practical trial that study designs involving extreme truncate selection and moderate sample sizes can robustly identify genes of relevant effect sizes involved in BMD variation in the general population. This has implications for the design of future genome‐wide studies of quantitative bone phenotypes relevant to osteoporosis.