Natural history of pregnancy-related enhanced myometrial vascularity following miscarriage.

OBJECTIVES: Our primary aim was to report the incidence of enhanced myometrial vascularity (EMV) in consecutive women attending our early pregnancy assessment unit, following first-trimester miscarriage. We aimed further to evaluate the clinical presentation and complications associated with expectant and surgical management of EMV in these women. METHODS: This was a prospective cohort study conducted in a London teaching hospital between June 2015 and June 2018, including consecutive patients with an observation of EMV on transvaginal ultrasonography following first-trimester miscarriage. The diagnosis was made following the subjective identification of EMV using color Doppler ultrasonography and a peak systolic velocity (PSV) ≥ 20 cm/s within the collection of vessels. Women were followed up with repeat scans every 14 days. Management was expectant unless intervention was indicated because of excessive or prolonged bleeding, persistent presence of retained tissue in the endometrial cavity or patient choice. The final clinical outcome was recorded. Time to resolution of EMV was defined as the interval from detection of EMV until resolution. RESULTS: During the study period, there were 2627 first-trimester fetal losses in the department and, of these, 40 patients were diagnosed with EMV, hence the incidence of EMV following miscarriage was 1.52%. All cases were associated with ultrasound evidence of retained products of conception (RPOC) at presentation (mean dimensions, 22 × 20 × 20 mm). Thirty-one patients opted initially for expectant management, of which 18 had successful resolution without intervention, five were lost to follow-up and eight subsequently had surgical evacuation due to patient choice. No expectantly managed case required emergency intervention. Nine patients chose surgical evacuation as primary treatment. No significant correlation was seen between PSV within the EMV at presentation and blood loss at surgery. Median PSV was 47 (range, 20-148) cm/s. The estimated blood loss in all cases managed surgically ranged from 20-300 mL. Presence of RPOC was confirmed in all specimens that were sent for analysis following surgery. For cases successfully managed expectantly, the mean time to resolution was 48 (range, 21-84) days. In the nine cases managed surgically from the beginning, the mean time to resolution of EMV was 10.6 (range, 3-29) days. CONCLUSIONS: This study suggests that EMV is an uncommon finding following miscarriage and is associated with the presence of RPOC. Expectant management was a safe option in our cohort, with minimal bleeding, although it was associated with protracted time to resolution. In patients who opted for surgery, the maximum blood loss was 300 mL and no patient required blood transfusion or embolization. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Ovarian cancer prediction: development of a scoring system for primary care.

OBJECTIVE: Recent studies have identified specific symptoms of ovarian cancer at all stages, raising the hope of reducing diagnostic delays. We aimed to devise a scoring system for symptoms of ovarian cancer in primary care. DESIGN: Secondary analysis of data from a case-control study. SETTING: Thirty-nine general practices in Exeter, mid-Devon and east Devon. POPULATION: Two hundred and twelve women with ovarian cancer and 1060 age-, sex- and practice-matched controls. METHODS: Conditional logistic regression was used to produce an additive scoring system and its receiver operator characteristic (ROC) curve. Several different cut-offs were then tested using a simple costs model. MAIN OUTCOME MEASURES: The ROC curve value. RESULTS: Each woman was assigned a score based on her symptoms in the year before diagnosis: we added a score for women aged ≥ 50 years, reflecting their increased incidence of ovarian cancer. The area under the ROC curve was 0.883 (95% confidence interval 0.853-0.912). The chosen cut-off had a sensitivity of 72.6% and a specificity of 91.3%. CONCLUSION: This scoring system could potentially direct general practitioners to appropriate investigations for ovarian cancer on the basis of symptoms and save a substantial number of unnecessary ultrasound scans being requested.

Local expression of transgene encoded TNF alpha in islets prevents autoimmune diabetes in nonobese diabetic (NOD) mice by preventing the development of auto-reactive islet-specific T cells.

Lately, TNF alpha has been the focus of studies of autoimmunity; its role in the progression of autoimmune diabetes is, however, still unclear. To analyze the effects of TNF alpha in insulin-dependent diabetes mellitus (IDDM), we have generated nonobese diabetic (NOD) transgenic mice expressing TNF alpha under the control of the rat insulin II promoter (RIP). In transgenic mice, TNF alpha expression on the islets resulted in massive insulitis, composed of CD4+ T cells, CD8+ T cells, and B cells. Despite infiltration of considerable number of lymphoid cells in islets, expression of TNF alpha protected NOD mice from IDDM. To determine the mechanism of TNF alpha action, splenic cells from control NOD and RIP-TNF alpha mice were adoptively transferred to NOD-SCID recipients. In contrast to the induction of diabetes by splenic cells from control NOD mice, splenic cells from RIP-TNF alpha transgenic mice did not induce diabetes in NOD-SCID recipients. Diabetes was induced however, in the RIP-TNF alpha transgenic mice when CD8+ diabetogenic cloned T cells or splenic cells from diabetic NOD mice were adoptively transferred to these mice. Furthermore, expression of TNF alpha in islets also downregulated splenic cell responses to autoantigens. These data establish a mechanism of TNF alpha action and provide evidence that local expression of TNF alpha protects NOD mice from autoimmune diabetes by preventing the development of autoreactive islet-specific T cells.

Requirement for CD40 ligand in costimulation induction, T cell activation, and experimental allergic encephalomyelitis.

The mechanism of CD40 ligand (CD40L)-mediated in vivo activation of CD4(+) T cells was examined by investigation of the development of experimental allergic encephalomyelitis (EAE) in CD40L-deficient mice that carried a transgenic T cell receptor specific for myelin basic protein. These mice failed to develop EAE after priming with antigen, and CD4(+) T cells remained quiescent and produced no interferon-gamma (IFN-gamma). T cells were primed to make IFN-gamma and induce EAE by providing these mice with B7.1(+) antigen-presenting cells (APCs). Thus, CD40L is required to induce costimulatory activity on APCs for in vivo activation of CD4(+) T cells to produce IFN-gamma and to evoke autoimmunity.

Long-term clinical follow-up after directional coronary atherectomy.

Although several studies have been done to assess the safety, efficacy, and angiographic restenosis rates of directional coronary atherectomy (DCA), there have been no studies to document the need for repeat revascularization of the target vessel based purely on recurrence of symptoms. To answer this question, clinical and angiographic data were obtained for 187 consecutive patients undergoing this procedure on a native coronary artery utilizing a lesion specific approach in a referral hospital. Most of the patients had anginal symptoms that were not well controlled with medical therapy. The decision to perform DCA was based on the lesion characteristics (i.e., eccentric, ulcerated, or irregular discrete lesions in a large epicardial vessel). The procedure was successful in 96% of patients. In-hospital major complications were seen in 6 patients (3%) including acute myocardial infarction in 3 (1.5%) and emergency coronary artery bypass surgery in the other 3 (1.5%). There were no deaths. Among 141 consecutive successful patients on whom the procedure was performed between January 1992 and June 1994, 128 (91%) were contacted. At 6 months, revascularization was required in 20 patients for recurrent anginal symptoms, and there were no deaths or myocardial infarctions. The clinical restenosis rate, therefore, was 15.6%. At long-term follow-up (25 +/- 9 months), revascularization was performed in 3 more patients. One patient had a myocardial infarction and 3 patients died of noncardiac causes. Among those without clinical restenosis, 83% patients were asymptomatic and the rest had infrequent chest pains effectively managed with medications. The patients in the study group were using an average of 1.2 cardiac medications. Quality of life improved in 74% of the patients. Thus, in this study utilizing a lesion specific approach, the success rate for DCA was comparable to the published trials and in-hospital complications were few. The long-term clinical outcome was favorable with a low rate of clinical restenosis requiring repeat revascularization.

Effect of general anesthesia on the severity of mitral regurgitation by transesophageal echocardiography.

The effect of general anesthesia on the severity of mitral regurgitation (MR) was examined in 43 patients with moderate or severe MR who underwent preoperative and intraoperative transesophageal echocardiography. Systolic blood pressure, mean arterial pressure, and left ventricular end-diastolic and end-systolic dimensions were significantly lower during the intraoperative study, reflecting altered loading conditions. The mean color Doppler jet area and mean vena contracta decreased and the mean pulmonary venous flow pattern changed from reversed to blunted, reflecting a significant reduction in the severity of MR. Overall, 22 of the 43 patients (51%) improved at least 1 MR severity grade when assessed under general anesthesia. Thus, intraoperative transesophageal echocardiography may significantly underestimate the severity of MR. A thorough preoperative assessment is preferable when deciding whether to perform mitral valve surgery.

Plasmid RP4 host-lethal function kilA and its repressor korA sequences are part of the cryptic tellurite resistance transposon Tn521.

The normally silent 4.5 kb tellurite resistance transposon Tn521 of RP4 has been shown to carry sequences from both the flanking kilA and korA loci of this broad host range plasmid. The major portion of both of these sequences were used as probes to examine DNA homology in Southern transfer hybridization experiments with plasmid recipients of Tn521 chosen from varying incompatibility groups. In the case of every recipients molecule analyzed using either probe, DNA homology was observed.

Multiplane transesophageal echocardiographic identification of the involved scallop in patients with flail mitral valve leaflet: intraoperative correlation.

Although the role of multiplane transesophageal echocardiography in the diagnosis of flail mitral valve leaflet is well described, the accuracy of this modality in localizing the involved posterior leaflet scallop (medial, middle, or lateral) has never been validated. For 54 patients undergoing intraoperative transesophageal echocardiography for severe mitral regurgitation due to flail mitral valve leaflet, we assessed the accuracy of a systematic approach to localization of the flail mitral valve leaflet. Surgical confirmation was performed for all patients. At blinded review, a sensitivity of 78%, specificity of 92%, and overall diagnostic accuracy of 88% were achieved for correct localization of the flail posterior leaflet scallop. The middle scallop was most commonly affected in this series. The medial scallop was affected least often, and diagnosis of lesions in that area was least accurate. This diagnostic approach appears to be accurate and feasible and may assist in planning specific surgical therapy for this disorder.

Toxic impacts of cypermethrin on behavior and histology of certain tissues of albino rats.

In the present investigation, the behavioral, morphological, and histopathological effects of cypermethrin, a widely used synthetic pyrethroid insecticide, was ascertained in male and female albino rats (Rattus norvegicus). Cypermethrin administered at repeated oral doses of 5 and 20 mg/kg/day for 30 days produced varying degree of mild to moderate toxic symptoms and behavioral changes in both male and female rats. The lower dose produced very mild toxicosis characterized by intermittent diarrhea, decreased feed intake, and thick eye discharge, whereas higher dose displayed mild to moderate toxicosis with diarrhea, decreased feed intake, loss of body weight, dyspnoea, ataxia, eye discharge, and salivation. Two female and one male albino rats died between 23 to 28 days after displaying signs of incoordination and tremors. Repeated oral doses of cypermethrin for 30 days enhanced the relative weight of liver and heart, but significantly decreased that of brain, kidneys, and testes. Microscopically, cypermethrin produced neuronal degeneration and increase in glial cells in brain, and disorganization of hepatic laminae, increase in sinusoid, and necrosis of hepatocytes in liver. Section of kidney displayed hemorrhage and sloughing off renal epithelial cell in the convoluted tubules, shrinkage of glomeruli, and necrosis of renal tubules. Repeated administration of cypermethrin also produced hemorrhages within myocardium, disruption of branching structure, and loss of striation of cardiac tissue; thickening of alveolar septa in lungs, partial to extensive loss of various stages of spermatogenesis in testes, and loss of follicular cells and oocytes in ovaries. The study suggested that repeated oral exposure of cypermethrin has considerable harmful effects on body organs in R. norvegicus.

Peripheral bone mineral density and its predictors in healthy school girls from two different socioeconomic groups in Delhi.

UNLABELLED: Peripheral bone density measurements are scarce and the factors, which predict bone mineral density at these sites, especially in children, are not clearly known. In this study, age, height, weight and alkaline phosphatase had a significant association on peripheral bone mineral density in healthy Indian school girls. INTRODUCTION: Factors that lead to the attainment of peak bone mass at peripheral sites, during period of growth are not clearly known. METHODS: Six-hundred and sixty-four randomly selected 7- to 17-year-old girls from upper and lower socioeconomic status (USES/LSES) schools were assessed clinically and a recording of their height and weight was undertaken. Serum calcium, phosphorus, total alkaline phosphatase (ALP), 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) were measured in all of them. Bone mineral density (BMD) was measured at the distal forearm (BMDdf) and calcaneum (BMDca) by peripheral dual energy X-ray absorptiometry (pDXA). RESULTS: Girls belonging to the USES were significantly taller (149.7 +/- 12.3 cm vs 144.4 +/- 11.9 cm; P < 0.001) and weighed more (44.3 +/- 12.9 kg vs 35.9 +/- 10.0 kg; P < 0.001) than girls from the LSES. USES girls had a significantly higher mean serum calcium (9.3 +/- 0.7 mg/dl vs 9.2 +/- 0.8 mg/dl; P < 0.05) and significantly lower alkaline phosphatase (316 +/- 166 IU/l vs 423 +/- 228 IU/l; P < 0.01) and iPTH (29.9 +/- 18.4 pg/ml vs 45.7 +/- 64.6 pg/ml; P < 0.01). There was no significant difference in mean serum phosphorus and 25-OHD levels between the two groups. USES subjects had higher BMD at both sites than LSES subjects. BMDdf and BMDca increased with age and tended to plateau by 16 years and 12 years of age respectively in both the groups. Age, height and weight explained approximately 50% of the variability, while biochemical parameters explained approximately 30% of variability in BMD at both the sites. The only biochemical parameter which had a significant association with BMD was ALP at the distal forearm. CONCLUSION: In conclusion, age, nutrition, height and weight are significantly associated with BMD at peripheral sites.

Facilitation of laryngeal mask airway insertion: effects of remifentanil administered before induction with target-controlled propofol infusion.

Eighty-six adult day-case patients were recruited into a prospective, randomised study and allocated to one of two groups. Patients received either intravenous remifentanil 0.3 microg.kg(-1) or an equivalent volume of sodium chloride 0.9% followed by induction of anaesthesia with propofol target-controlled infusion until the effect (brain) site calculated concentration was 2 microg.ml(-1). Jaw opening and ease of laryngeal mask insertion were assessed immediately after mask insertion. A higher incidence of failure of induction of anaesthesia was observed in the control group compared with the remifentanil group [15 (35%) vs. 3 (7%); p < 0.01] and addition of remifentanil significantly increased the ease and success of laryngeal mask insertion, with grade 1 (no coughing/gagging) conditions observed in 29 (68%) of the remifentanil group and 21 (49%) of the control group (p < 0.01). The doses of remifentanil and propofol used were not associated with any significant cardiorespiratory instability. In conclusion, when combined with propofol target-controlled infusion, remifentanil 0.3 microg.kg(-1) facilitates laryngeal mask insertion with minimal adverse haemodynamic changes.

Intracellular calcium disruption as a secondary event in acetaminophen-induced hepatotoxicity.

To examine a role for disturbances in intracellular calcium homeostasis in acetaminophen-induced hepatotoxicity, freshly isolated mouse hepatocytes were incubated with 1.0 mM acetaminophen for 1.5 h to allow for covalent binding and initiation of cell damage. The hepatocytes were then washed and the cells incubated in fresh medium containing either 2.0 mM N-acetylcysteine or 1.5 mM dithiothreitol for the duration of a 4-h incubation period. These agents were used as tools in the elucidation of the biochemical events responsible for acetaminophen-induced cell necrosis. The reduced protein sulfhydryl content, cytosolic [Ca2+], and plasma membrane integrity were quantitated. Acetaminophen produced protein sulfhydryl depletion, an increased cytosolic [Ca2+], and cell injury; however, cytotoxicity preceded the increase in [Ca2+]. Both N-acetylcysteine and dithiothreitol restored the acetaminophen-induced protein sulfhydryl loss. Dithiothreitol prevented both further cell injury and an increase in the cytosolic [Ca2+]. However, cell death and a subsequent increase in cytosolic [Ca2+] proceeded unabated following N-acetylcysteine addition. Although both agents restored protein sulfhydryl content, in view of their contrasting ultimate effects on cell viability the role of reduced protein sulfhydryl depletion in acetaminophen-induced hepatic injury requires further investigation. The increase in cytosolic [Ca2+] with acetaminophen alone and with subsequent N-acetylcysteine addition was determined to be a secondary event in cell injury because cytotoxicity occurred by 1.5 h; however, the increase in cytosolic [Ca2+] was not observed until 2.5 h. Additional evidence for changes in cytosolic [Ca2+] as a secondary event was obtained by incubating the hepatocytes with acetaminophen in the presence of fura 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular analysis of the UV protection and mutation genes carried by the I incompatibility group plasmid TP110.

The imp genes, responsible for the UV protection and mutation effects of the I incompatibility group plasmid TP110, have been cloned into vector plasmids, and their products have been analyzed. The genetic information required for expression of these properties was carried in a continuous DNA sequence of approximately 1.7 kilobases, encoding the production of two proteins with molecular weights of 11,000 and 51,000. The genetic arrangement of this system therefore appears similar but not identical to the functionally related umuDC and mucAB operons. A third protein with a molecular weight of 40,000 was produced from sequences downstream from imp and could be overproduced by high-level transcription through the imp genes. This protein was not required for the protection and mutation properties.

Bromobenzene and furosemide hepatotoxicity: alterations in glutathione, protein thiols, and calcium.

The nature of the events whereby the reactive intermediates resulting from the bioactivation of bromobenzene and furosemide induce hepatotoxicity is unknown. To examine a role for disturbances in intracellular calcium homeostasis, secondary to a depletion in cellular reduced glutathione (GSH) and reduced protein thiols (PSHs), isolated mouse hepatocytes were exposed to cytotoxic concentrations of bromobenzene or furosemide. Cytosolic calcium concentration, as well as thiol status, was determined. The incubation of hepatocytes with 3.0 mM bromobenzene, and subsequent additions (1.2 mM) of the agent every hour, resulted in significant GSH depletion. The loss of plasma membrane integrity at 1.5 h preceded both a rise in the cytosolic Ca2+ concentration and depletion of total PSH content. Furosemide (1.0 mM) produced a 70% depletion in cellular GSH content in isolated hepatocytes. The initiation of cell damage occurred concurrently with both a rise in the cytosolic Ca2+ concentration and a depletion of total PSH content 4 h following furosemide addition. Since the increase in cytosolic Ca2+ did not precede cytotoxicity, these results do not support an initiating role for Ca2+ deregulation in bromobenzene and furosemide hepatotoxicities. In addition, depletion of PSH content did not correlate with bromobenzene- or furosemide-induced cytotoxicity.