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.

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.

CD62L is required on effector cells for local interactions in the CNS to cause myelin damage in experimental allergic encephalomyelitis.

Adhesion molecules are believed to facilitate infiltration of leukocytes into the CNS of mice with experimental allergic encephalomyelitis (EAE). The role of the adhesion molecule CD62L (L-selectin) in the immunopathology of EAE is not known. To study this, we crossed CD62L-deficient mice with myelin basic protein-specific TCR (MBP-TCR) transgenic mice. CD62L-deficient MBP-TCR transgenic mice failed to develop antigen-induced EAE, and, despite the presence of leukocyte infiltration, damage to myelin in the CNS was not seen. EAE could, however, be induced in CD62L-deficient mice upon adoptive transfer of wild-type macrophages. Our results suggest that CD62L is not required for activation of autoimmune CD4 T cells but is important for the final destructive function of effector cells in the CNS and support a novel mechanism whereby CD62L expressed on effector cells is important in mediating myelin damage.

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.

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.

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.

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.

Three cases of familial hairy cell leukemia.

In a 10-year interval, a total of 12 cases of familial hairy cell leukemia have been published. They were noted in first degree relatives, mostly in men. In some instances, when the HLA type was performed, a specific HLA type was found in the studied family, but a different haplotype was seen in other families. It appeared that familial cases of hairy cell leukemia were not associated with a "specific HLA antigen" and other factor(s) such as environmental, or some kind of occupational exposure, were suggested to play a role in the familial occurrence of hairy cell leukemia. We add three more familial hairy cell leukemia cases which are different from other published cases, showing a female predominance. The HLA typing revealed interesting findings. The HLA type shared by case 1 and 3 was A2, A30/31(19), B27, Bw4, Bw6. From these, HLA A2, Bw4, and Bw6 were previously reported (Ward FT, Baker J, Krishnan J, Dow N, Kjobech CH: Cancer 65:319-321, 1990). Case 2, shared with the other two the antigen Bw6. Its specific HLA type was A3 and B7, the type previously reported in a family (Begley CG, Tait B, Crapper RM, Briggs RG, Brodie GN, Mackay IR: Leuk Res 11:1027-1028, 1987). Based on these observations, we may conclude that a "specific HLA type," A2, Bw4, Bw6 and A3, B7 might have a role in the genetic predisposition for hairy cell leukemia.

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)

Persistent infection of K562 cells by encephalomyocarditis virus.

Infection of human erythroleukemic K562 cells by encephalomyocarditis virus readily resulted in establishment of persistently infected cultures. In contrast to the usual typical lytic infection by encephalomyocarditis virus, in which trypan blue staining of cells reaches close to 100% by about 15 h postinfection, K562 cell cultures required 3 to 4 days postinfection to reach a maximum of about 80 to 90% cell staining. The proportion of K562 cells taking up stain gradually decreased to about 10% of those present by about 13 days postinfection; during this time, virus yield per day measured by either plaque or hemagglutination titration fell about 10-fold. The decrease in percent staining was followed by waves of increased staining accompanied by increased virus production. Virus-producing cultures were maintained for over 3 months. Evolution of both virus and cells accompanied establishment of persistence in that plaque size changed from about 7 mm in diameter for the original virus to less than 1.5 mm by day 20 postinfection and most of the cells cloned from persistently infected cultures were resistant to superinfection with the original virus. Resistance was due, at least in part, to reduced virus attachment in that binding of 3H-labeled virus to cloned resistant cells was about 2% of that to uninfected cells.

Isolated retinal telangiectatic masses.

The clinical findings of 20 patients with an isolated peripheral retinal mass secondary to retinal telangiectasis were reviewed. The important clinical features were subretinal exudation, vitreous haemorrhage and retinal detachment. No associated systemic abnormalities were identified. Early results suggest that cryotherapy is effective for the reduction of subretinal exudation but not for macular oedema. Patients with extensive retinal detachment complicated by vitreous haemorrhage and epiretinal membrane formation were treated with vitreoretinal surgery.