Comparison between stimulated in-vitro fertilization and stimulated intrauterine insemination for the treatment of unexplained and mild male factor infertility

A prospective trial was undertaken to evaluate the efficacy of stimulated in-vitro fertilization (SIVF) and stimulated intrauterine insemination (SIUI) in couples with unexplained and mild male factor infertility. In all, 80 couples were allocated to treatment with SIVF or SIUI, both treatments following the same protocol [clomiphene citrate and follicle stimulating hormone (FSH) injection], except that higher doses of FSH were used in the SIVF treatment cycles. Initially, 41 couples were allocated to and started treatment with SIVF but eight cases were eventually converted to SIUI because of under-response. Similarly, although 39 couples were initially allocated to SIUI treatment, five of these converted to SIVF because of over-response. The treatment cycles that were converted either to SIUI or to SIVF were not considered as treatment failures but as treatment changes and so were included in the analyses. Of the final 38 SIVF cycles, four were cancelled (dysfunctional response), failed fertilization occurred in five cycles and 29 subjects reached embryo transfer. There were two biochemical pregnancies [positive human chorionic gonadotrophin (HCG) only], two clinical abortions and seven live births. Of the final 42 SIUI cycles, only two were cancelled, insemination being performed in the remaining 40 cases. The result was one clinical abortion, three ectopics and eight live births. The proportion of cycles with positive HCG was identical (28.9% per cycle treated for SIVF and 28.6% for SIUI) and the livebirth rates were also not different (18.4% per cycle treated for SIVF and 19.0% for SIUI). The cost per maternity of SIUI was approximately half that of SIVF (Pounds Sterling 1923 versus Pounds Sterling 4611) and so we conclude that, as SIUI had an efficacy that was not significantly different from SIVF (using similar protocols) but was more cost-effective, it must be considered the more appropriate form of management for the treatment of unexplained and mild male factor infertility. Indeed, it is hard to justify the routine use of IVF, as a first approach, in unexplained infertility.      

Autoradiographic analysis of 125I-insulin-like growth factor II internalization into pancreatic acini

The internalization and intracellular distribution of 125I-insulin-like growth factor II (125I-IGF II) in mouse isolated pancreatic acini was studied by electron microscope autoradiography. 125I-IGF II was rapidly internalized; after 30 min over 70% of silver grains derived from the bound hormone were localized over the interior of the cells. The grain distribution from 125I-IGF II differed significantly from both a random grain distribution and that derived from bound 125I-insulin. The majority of intracellular 125I-IGF II grains were over the endoplasmic reticulum and Golgi; the Golgi showed the highest density of intracellular grains. Pretreatment of acini with 10 nM cholecystokinin octapeptide (CCK 8) reduced both the amount of acinar-associated IGF II and the density of intracellular 125I-IGF II grains. Moreover, CCK 8 altered the relative distribution of grains from 125I-IGF II between organelles. These studies indicate, therefore, that 125I-IGF II is internalized by pancreatic acini, and that this internalization is regulated by CCK 8.     

The ability of Listeria monocytogenes PI-PLC to facilitate escape from the macrophage phagosome is dependent on host PKCbeta

Listeria monocytogenes are facultative intracellular pathogenic bacteria that can infect macrophages as well as non-professional phagocytes. After entry in the host cell, the bacteria escape from the phagosome into the cytoplasm. In murine macrophages and in cell lines derived from these cells, escape of L. monocytogenes from the phagosome is absolutely dependent on listeriolysin O (LLO) and facilitated by a secreted phosphatidylinositol-specific phospholipase C (PI-PLC). Work in this laboratory has previously demonstrated a LLO and PI-PLC-dependent translocation of host PKCbeta isoforms. Pharmacological inhibition of PKCbeta resulted in a significant reduction in permeabilization of the phagosome, and in the number of bacteria reaching the cytosol. These findings led to the prediction that the bacterial PI-PLC promotes escape through the production of diacylglycerol leading to the activation of host PKCbeta. To test this hypothesis, bone marrow-derived macrophages (BMMf) obtained from PKCbeta knockout (PKCbetaKO) or C57Bl/6 mice were infected with L. monocytogenes. We observed that wild-type L. monocytogenes escapes from the phagosome of PKCbetaKO BMMf as well as from C57Bl/6 BMMf. However, in PKCbetaKO BMMf, L. monocytogenes uses a PI-PLC-independent, but phosphatidylcholine-preferring PLC (PC-PLC)-dependent pathway to facilitate escape. These findings strongly support the hypothesis that PI-PLC promotes escape through mobilization of host PKCbeta.     

Cytokines and immuno-endocrine factors in recurrent miscarriage

Recurrent miscarriage remains an enigma. The main aetiologiesare endocrinological, immunological and unexplained. With thegrowth in molecular biology, it is now possible to look at theeffect of these aetiologies in more detail, allowing greaterunderstanding of the underlying pathogenesis. Keywords: cytokines/recurrent miscarriage     

Contaminant Loading in Drainage and Fresh Water Used for Wetland Management at Stillwater National Wildlife Refuge

Throughout the western United States, studies have identified various detrimental effects of contaminants to aquatic biota from the use of agricultural drainage water for management of arid wetlands. However, little is known about the relative contributions of contaminant loading from pollutants dissolved in water compared with those carried by drifting material (e.g., detritus) associated with drainage water. Consequently, we determined loading rates for contaminants dissolved in water and those incorporated by drifting material for drainage (Diagonal Drain) as well as fresh (S-Line Canal) water used for wetland management at Stillwater National Wildlife Refuge (SNWR), Nevada during the early, middle, and late periods of the irrigation season (June through mid-November) in 1993. We found loading rates for trace elements throughout the irrigation season were almost entirely (> 98%) associated with contaminants dissolved in the water rather than incorporated by drift. Although drift contributed little to the total loading for trace elements to SNWR wetlands, contaminant concentrations were much greater in drift compared with those dissolved in water. Loading rates for dissolved As, B, Hg, and total dissolved solids (TDS) differed among periods for the Diagonal Drain. Along the Diagonal Drain, loading rates for dissolved As, B, Hg, Mo, unionized ammonia (NH₃-N), TDS, and Zn differed among its three sampling sites. B was the only trace element with differences in loading rates for drift among periods from the Diagonal Drain. In contrast, loading rates for As, B, Cr, Cu, Hg, Se, and Zn in drift differed among periods for the S-Line Canal. Along Diagonal Drain, loading rates in drift for B (middle and late periods), Cr, Cu, and Zn differed among sites. Hg (xˉ ≥ 12.0 ng/L) and NH₃-N (xˉ ≥ 0.985 mg/L) dissolved in water as well as B (xˉ ≥ 97.4 μg/g DW) and Hg (xˉ ≥ 0.461 μg/g DW) in drift from the Diagonal Drain and S-Line Canal exceeded screening levels (SLs) for protection of aquatic biota throughout the irrigation season. Dissolved As (xˉ ≥ 0.0426 mg/L) in water from the Diagonal Drain during all periods exceeded the SL for protection of aquatic biota. Dissolved B (xˉ = 1.03 mg/L) in water from the Diagonal Drain during the early period exceeded the SL for protection of aquatic biota. Received: 18 September 1997/Accepted: 5 February 1998     

Effect of metformin on carbohydrate and lipoprotein metabolism in NIDDM patients

The effect of metformin treatment on various aspects of carbohydrate and lipoprotein metabolism has been defined in 12 patients with non-insulin-dependent diabetes mellitus (NIDDM). Patients were studied before and after approximately 4 mo of metformin therapy. Treatment was initiated with a single dose of 500 mg/day, increased at weekly intervals, and maintained at a final dose of 2.5 g/day (given at divided intervals) for the last 3 mo of the treatment program. Results demonstrated that both fasting and postprandial glucose concentrations were significantly lower after metformin administration, with the greatest change seen after meals. As a result, the total incremental plasma glucose response above basal measured from 0800 to 1600 after metformin was less than 25% of that seen initially. The improvement in ambient plasma glucose concentration in association with metformin occurred despite a modest but statistically significant decrease in circulating plasma insulin concentration. In addition, insulin-stimulated glucose uptake measured during hyperinsulinemic clamp studies was similar before and after metformin treatment. Furthermore, changes in insulin binding and insulin internalization by isolated monocytes did not correlate with the improvement in glycemic control. Thus, the ability of metformin to lower plasma glucose concentration in NIDDM does not appear to be secondary to an improvement in insulin action. Finally, metformin treatment was associated with a significant (P less than 0.01) decrease in plasma triglyceride concentration and an increase in plasma high-density lipoprotein cholesterol concentration. These results indicate that metformin treatment of patients with NIDDM led to an improvement in both glycemic control and lipoprotein metabolism.     

Physical Activity in Obese Type 2 Diabetes After Gastric Bypass or Medical Management

Background

The purpose of this study was to compare effects of Roux-en-Y gastric bypass versus a multidisciplinary, group-based medical diabetes and weight management program on physical fitness and behaviors.