Search

Uterine fibroids are benign tumours, which are associated with subfertility and early pregnancy loss. This study was carried out to examine the effect of submucous fibroids on concentrations of glycodelin, insulin-like growth factor binding protein-1 (IGFBP-1), interleukin-6 (IL-6), interleukin-10 (IL-10), tumour necrosis factor α (TNFα) and osteopontin in uterine flushings. Pre-menopausal women with a certain diagnosis of submucous fibroid confirmed on three-dimensional saline infusion sonohysterography were recruited into the study. The control group included women without ultrasonic evidence of any uterine or endometrial pathology. All women had uterine flushings performed 7 days post LH surge. Enzyme linked immunoassays were performed to analyse glycodelin, IL-6, IL-10, TNFα and osteopontin, whilst immunoradiometric assay was used to analyse IGFBP-1. In 23 women with submucous fibroids, the concentrations of glycodelin and IL-10 in uterine flushings were significantly lower compared with 17 women in the control group (P = 0.002; P = 0.007, respectively). There were no significant differences between the two groups in concentrations of IGFBP-1, IL-6, TNFα and osteopontin. Women with submucous fibroids had significantly tower concentrations of glycodelin and IL-10 in mid-luteal phase uterine flushings. This finding may explain the association with submucous fibroids and adverse reproductive outcomes. [ABSTRACT FROM AUTHOR] more...

Endometrial polyps have been associated with infertility and early pregnancy loss. The aim of this study was to investigate the effect of hysteroscopic polypectomy on the concentrations of endometrial implantation factors in uterine flushings. Pre-menopausal women with a certain diagnosis of endometrial polyp on contrast-enhanced transvaginal ultrasound scan were recruited into this prospective study. In all women, paired samples of uterine flushings were obtained on the same day of the menstrual cycle prior to and post hysteroscopic polypectomy. Enzyme-linked immunoassays were performed to analyse glycodelin, interleukin-6 (IL-6), interleukin-10 (IL-10), tumour necrosis factor α (TNFα) and osteopontin, whilst immunoradiometric assay was used to analyse insulin-like growth factor binding protein-1 (IGFBP-1). Concentrations of IGFBP-1, TNFα and osteopontin in uterine flushings were significantly lower in the mid-secretory phase prior to polypectomy in comparison to the measurements obtained after complete surgical removal of the polyp (P < 0.05). There were no differences in the concentrations of glycodelin, IL-6 and IL-10 in paired samples prior to and post-polypectomy. The presence of endometrial polyps is associated with decreased mid-secretory concentrations of IGFBP-1, TNFα and osteopontin, which are reversed following surgical polypectomy. [ABSTRACT FROM AUTHOR] more...

In the treatment of acromegaly, a‘test dose’ of octreotide is recommended prior to the use of depot somatostatin analogue (SSA) therapy. However, there remains no consensus regarding the criteria that predict a response to treatment. The ability to select patients who may benefit most from medical therapy is potentially of great value in clinical practice. The aim of the study was to determine the predictive value of both the nadir GH and the mean GH following an octreotide test dose in identifying patients who subsequently achieved disease remission with depot SSA therapy. Remission was defined as a mean GH < 5 mU/l (< 2 µg/l).Retrospective case–control study.A group of 41 patients with acromegaly underwent an octreotide test dose where GH was measured hourly for a total of 6 h following an injection of octreotide 50 µg subcutaneously. Nadir GH and mean GH following the octreotide test dose were determined. Thirty-three patients were subsequently treated with depot SSA therapy and mean GH and IGF-I levels were determined at follow-up.The nadir GH demonstrated superior predictive power to that of mean GH across a range of GH cut-off values. A nadir GH < 5 mU/l demonstrated 80% sensitivity and 83% specificity in predicting remission with depot SSA therapy. A nadir GH < 10 mU/l demonstrated 100% sensitivity and 56% specificity.The nadir GH following an octreotide test dose is a useful predictive marker of achieving disease remission with depot SSA therapy used as either a primary or an adjuvant agent. [ABSTRACT FROM AUTHOR] more...

Background: Serum sialic acid (TSA) has been shown to be a cardiovascular risk factor and an acute phase reactant, with elevated concentrations associated with increased cardiovascular mortality and to precede the onset of type 2 diabetes. Aim: The purpose of this present study was to test the hypothesis that serum TSA may be related to serum leptin concentrations in healthy individuals. Methods: Thirty Fijian individuals were studied (8 males and 22 females). They were urban Melanesians living in Raiwaga, a suburb of Suva in Fiji. Results: Serum TSA significantly correlated with subject body mass index (BMI, ρ 0.39, P<0.05) and serum leptin concentration (ρ 0.44, P<0.05). In stepwise multiple regression analysis serum TSA independently correlated with subject waist/hip ratio (r2=0.167, P<0.02) and diastolic blood pressure (r2=0.300, P<0.01) but not with age, BMI, serum insulin-like growth factor binding protein (IGFBP-1), fasting plasma glucose or systolic or diastolic blood pressure. Conclusions: Serum TSA is related to markers of obesity and adipose tissue metabolism which may help to explain why it is a reputed cardiovascular risk factor and why elevated serum TSA concentrations precede the development of type 2 diabetes mellitus. [Copyright &y& Elsevier] more...

OBJECTIVE Previous studies have suggested that chronic fatigue syndrome (CFS) is associated with changes in appetite and weight, and also with mild hypocortisolism. Because both of these features may be related to leptin metabolism, we undertook a study of leptin in CFS. DESIGN (i) A comparison of morning leptin concentration in patients with CFS and controls and (ii) a randomized, placebo-controlled crossover study of the effects of hydrocortisone on leptin levels in CFS. PATIENTS Thirty-two medication free patients with CFS but not comorbid depression or anxiety. Thirty-two age, gender, weight, body mass index and menstrual cycle matched volunteer subjects acted as controls. MEASUREMENTS We measured basal 0900 h plasma leptin levels in patients and controls. All 32 patients were taking part in a randomized, placebo-controlled crossover trial of low dose (5 or 10 mg) hydrocortisone as a potential therapy for CFS. We measured plasma leptin after 28 days treatment with hydrocortisone and after 28 days treatment with placebo. RESULTS At baseline, there was no significant difference in plasma leptin between patients [mean 13·8, median 7·4, interquartile range (IQR) 18·0 ng/ml] and controls (mean 10·2, median 5·5, IQR 11·3 ng/ml). Hydrocortisone treatment, for both doses combined, caused a significant increase in leptin levels compared to placebo. When the two doses were analysed separately, only 10 mg was associated with a significant effect on leptin levels. We also compared the hydrocortisone induced increase in leptin between those who were deemed treatment-responders and those deemed nonresponders. Responders showed a significantly greater hydrocortisone-induced rise in leptin than nonresponders. This association between a clinical response to hydrocortisone and a greater rise in leptin levels may indicate a greater biological effect of hydrocortisone in these subjects, perhaps due to increased glucocorticoid receptor sensitivity, which may be present in some patients with CFS. CONCLUSIONS We conclude that, while we found no evidence of alterations in leptin levels in CFS, low dose hydrocortisone therapy caused increases in plasma leptin levels, with this biological response being more marked in those CFS subjects who showed a positive therapeutic response to hydrocortisone therapy. Increases in plasma leptin levels following low dose hydrocortisone therapy may be a marker of pretreatment physiological hypocortisolism and of response to therapy. [ABSTRACT FROM AUTHOR] more...

Background: Severe hypertriglyceridaemia is a recognized complication of Type 2 diabetes mellitus (T2DM); however, there is no consensus on acute management despite the significant risk of developing associated complications such as acute pancreatitis and hyperviscosity syndrome.Aim: To identify the association between hyperglycaemia and severe hypertriglyceridaemia in patients with T2DM and assess the effect of continuous insulin infusion therapy on serum triglyceride (TG) concentrations and report any adverse events associated with this therapeutic approach.Design: Retrospective review of case records.Methods: Patients with uncontrolled hyperglycaemia and severe hypertriglyceridaemia (serum TG > 15 mmol/l) treated with continuous intravenous insulin infusion between October 2008 and September 2009 were retrospectively evaluated (n = 15). Details recorded included demographics, admission details, lipid profiles, glycaemic control, serum amylase and adverse events. Patients receiving treatment-dose unfractionated heparin infusion were excluded.Results: Severe hypertriglyceridaemia is associated with hyperglycaemia in our heterogeneous group of patients with T2DM presenting with new-onset diabetes or established disease on pre-existing insulin or oral hypoglycaemic agents. Administration of continuous exogenous insulin not only achieved normoglycaemia but also dramatically corrected severe hypertriglyceridaemia in all patients (P = 0.001).Conclusions: The administration of continuous insulin in patients with T2DM with severe hypertriglyceridaemia is a simple and safe method of significantly reducing the immediate risk associated with this metabolic complication and should be considered in any T2DM patient presenting with severe hypertriglyceridaemia and hyperglycaemia. [ABSTRACT FROM PUBLISHER] more...

Although chronic diarrhea affects heart function and morphology, the pathogenic mechanisms are unknown. It was our hypothesis that diarrhea imposes metabolic stress to inhibit the synthesis of new contractile proteins. To test this hypothesis, we investigated the effects of lactose-induced diarrhea in rats. The groups were: 1) freely fed controls, 2) rats with lactose-induced diarrhea or 3) pair-fed rats. After 1 wk, hearts from the rats were subjected to subcellular fractionation techniques to isolate the major protein fractions, including myofibrillar proteins. The rates of protein synthesis were measured with concomitant assay of cardiac composition and plasma analytes. In comparison with the control group, diarrhea induced the following changes (P < 0.05): a decrease in heart weight, reduced RNA and mixed protein contents and a reduction in the fractional rate of mixed protein synthesis. There was a reduction in the content of all protein fractions. The fractional synthesis rate was reduced only for the myofibrillar fraction. Plasma insulin-like growth factor-I, but not corticosterone, was reduced. Plasma cholesterol and triglyceride concentrations were also reduced. In comparison with the pair-fed group, diarrhea induced the following changes (P < 0.05): a reduction in heart weight and fractional rate of mixed protein synthesis, reduced myofibrillar absolute synthesis rate and increased sarcoplasmic/myofibrillar fractional synthesis rate ratio. Plasma bicarbonate, triglyceride and urea concentrations were reduced, with an increase in albumin. Diarrhea impaired cardiac biochemistry, including a reduction in protein content and synthesis. A substantial proportion of these changes is due to anorexia, but the selective reduction in the synthesis of contractile proteins is a feature exclusive to the diarrhea group and may be due to reductions in plasma insulin-like growth factor-I. [ABSTRACT FROM AUTHOR] more...

The insulin/IGF binding protein-1 (IGFBP-1) axis is important in coordinating insulin- and IGF-mediated regulation of glucose metabolism and glycemia. Dysregulation of the axis may play a role in the pathophysiology of disorders of insulin deficiency and resistance. We have investigated this hypothesis by generating transgenic mice that overexpress hIGFBP-1. To study the axis in its true physiological context, we used a human (h) IGFBP-1 cosmid clone so that transgene expression is responsive to normal hormonal stimuli. hIGFBP-1 mRNA is expressed in a tissue-specific fashion, and measurement of serum protein levels by specific immunoassay indicates normal physiological regulation in response to fasting/feeding and appropriate post-translational modification as indicated by the detection of phosphorylated and nonphosphorylated isoforms of the protein. The hypoglycemic response to exogenous IGF-I is attenuated in transgenic mice. Transgenic mice exhibit an enhanced insulin secretory response to a glucose challenge, although basal and stimulated blood glucose levels are similar to controls. There is a sexual dimorphism in phenotypic expression: male transgenic mice had higher stimulated glucose and insulin levels than did females. Transgenic mice exhibit fasting hyperglycemia and hyperinsulinemia and glucose intolerance in later life, indicating an age-related decline in glucocompetence. These findings demonstrate the importance of the normal inverse relationship between serum insulin and IGFBP-1 levels in glucoregulation and that sustained dysregulation of the insulin/IGF-I/IGFBP-1 axis is associated with impaired glucose tolerance and abnormalities of insulin action. [ABSTRACT FROM AUTHOR] more...

Acute ethanol toxicity has many deleterious effects on the gastrointestinal tract and, in particular, inhibits small intestinal protein synthesis. The mechanism(s) of the ethanol-induced inhibition of protein synthesis are unknown. This study was designed to investigate the role of adrenal and thyroid hormones on the ethanol-induced inhibition of whole jejunal protein synthesis in adrenalectomised and thyroidectomised male Wistar rats. Acute ethanol dosage significantly reduced protein synthesis in all subcellular protein fractions of the whole jejunum, in sham-thyroidectomized, thyroidectomized, sham-ardrenalectomized and adrenalectomized rats. Synthesis rates relative to RNA and DNA were also highly significantly reduced in all treatment groups in ethanol-dosed rats. However in most protein fractions the inhibition of protein synthesis was greater in thyroidectomized compared to sham-thyroidectomized rats, whereas the reverse was true in adrenalectomized rats. Neither adrenalectomy or thyroidectomy completely abolished ethanol-induced inhibition in protein synthesis, suggesting that ethanol or its metabolites, e.g. acetaldehyde, acts directly on the tissue. However, the ethanol-induced inhibition of protein synthesis was greater in thyroidectomized rats demonstrating that contractile and non-contractile proteins synthesis in the jejunum is under control of complex regulatory processes. [ABSTRACT FROM AUTHOR] more...

The article reports on the results of a study of adult growth hormone replacement using a fixed graded initiation phase followed by an individualized titration phase. A description of the experimental setup and measurement method is presented. The study showed that 76 percent of patients achieved a target IGF-I at 6 months, with an adverse event (AE) rate of 15 percent that fell by 1 year. more...

We describe a case of infective endocarditis due to Neisseria elongata , and review the literature. N. elongata is a constituent of the normal oral flora and a rare cause of infective endocarditis. Unfamiliarity with the organism and its rod-shaped morphology may lead to a delay in microbiological diagnosis. Although the organism is relatively sensitive to antibiotics, our experience in the management of the described case and a review of previous reports suggest that antibiotic therapy alone may not be sufficient. It is likely that patients with N. elongata endocarditis will require surgery. [ABSTRACT FROM AUTHOR] more...