Predicting the risks and recognizing the signs: a two-year prospective population-based study on pregnant women with uterine rupture in The Netherlands.

OBJECTIVE: To estimate the incidence of uterine rupture in the Netherlands and evaluate risk indicators prelabour and during labor of women with adverse maternal and/or perinatal outcome. METHODS: This is a population-based nationwide study using the Netherlands Obstetrics Surveillance System (NethOSS). We performed a two-year registration of pregnant women with uterine rupture. The first year of registration included both women with complete uterine rupture and women with incomplete (peritoneum intact) uterine rupture. The second year of registration included women with uterine rupture with adverse maternal and/or perinatal outcome. We collected maternal and obstetric characteristics, clinical signs, and symptoms during labor and CTG abnormalities. The main outcome measures were incidence of complete uterine rupture and uterine rupture with adverse outcome and adverse outcome defined as major obstetric hemorrhage, hysterectomy, embolization, perinatal asphyxia and/or (neonatal) intensive care unit admission. RESULTS: We registered 41 women with a complete uterine rupture (incidence: 2.5 per 10,000 births) and 35 women with uterine rupture with adverse outcome (incidence: 0.9 per 10,000 births). No adverse outcomes were found among women with incomplete uterine rupture. Risk indicators for adverse outcome included previous cesarean section, higher maternal age, gestational age <37 weeks, augmentation of labor, migration background from Sub-Saharan Africa or Asia. Compared to women with uterine rupture without adverse outcomes, women with adverse outcome more often expressed warning symptoms during labor such as abdominal pain (OR 3.34, 95%CI 1.26-8.90) and CTG abnormalities (OR 9.94, 95%CI 2.17-45.65). These symptoms were present most often 20 to 60 min prior to birth. CONCLUSION: Uterine rupture is a rare condition for which several risk indicators were identified. Maternal symptoms and CTG abnormalities are associated with adverse outcomes and time dependent. Further analysis could provide guidance to expedite delivery.

Increasing trends in a low 5-min Apgar score among (near) term singletons: a Dutch nationwide cohort study.

OBJECTIVE: To investigate trends in low Apgar scores in (near) term singletons using the Dutch Perinatal Registry. METHODS: In a cohort of 1,583,188 singletons liveborn ≥35 weeks of gestation in the period 2010-2019, we studied trends in low 5-min Apgar scores (<7 and <4) using Cochrane Armitage trend tests. RESULTS: The proportion of infants with low Apgar scores <7 and <4 increased significantly between 2010-2019 (1.04-1.42% (p < 0.001), 0.17-0.19% (p = 0.009), respectively). Neonatal mortality remained unchanged. Induction of labour, epidural analgesia and planned caesarean section showed an increasing trend. Instrumental vaginal delivery and emergency caesarean section were performed less frequently over time, but these intervention subgroups showed the highest relative increase in infants with low Apgar scores. CONCLUSIONS: In the Netherlands, the risk of a low 5-min Apgar score increased over the last decade. The highest relative increase was observed in subgroups of instrumental vaginal delivery and emergency caesarean section.

Facilitators and barriers of preconception care in women with inflammatory bowel disease and rheumatic diseases: an explorative survey study in a secondary and tertiary hospital.

BACKGROUND: Preconception care (PCC) is care prior to conception to optimize parental health, and health of the future child, through biomedical and behavioral changes. Providing PCC to all women with a wish to conceive will improve perinatal health. PCC is especially important for women with a chronic disease, such as inflammatory bowel disease (IBD) and rheumatic diseases (RD). At present PCC is not part of routine care for these women. The aim of this study is to identify facilitators and barriers on a patient and professional level regarding the provision of PCC in women with IBD and RD. METHODS: An explorative survey study among women with IBD and RD, their treating physicians and obstetric professionals was performed. Patients with a wish to conceive, pregnant women or those with a recent pregnancy (< 1 year ago) visiting the outpatient clinic of a secondary and tertiary hospital and involved physicians and obstetric professionals were eligible. RESULTS: A total of 71% of the IBD patients (n = 22/31) and 35% of the RD patients (n = 20/58) received a PCC consultation. PCC consultation was considered easy to enter, short in time and patients felt comfortable. Patients (71% IBD; 62% RD) preferred a personal PCC consultation with their disease specific specialist together with an obstetrician. Patients specifically wanted to receive information about the safety of medication use and disease activity following delivery. Of the included healthcare professionals 67% (n = 31) agreed PCC was applicable to their patients. Main barrier to providing PCC was lack of time and unavailability of professionals. In total 41% (n = 16) of obstetric professionals felt they had the knowledge and skills to provide PCC compared to 33% (n = 1) and 75% (n = 3) of gastroenterologists and rheumatologists, respectively. CONCLUSION: Lack of awareness and urgency for the effectuation can be seen as important barriers for implementation of PCC. Due to the explorative nature generalisation of the results is not allowed. In the future, adaptation of the curricula of healthcare professionals by implementing interventions for pregnancy planning and preparation will generate awareness. Modelling of the impact of PCC might prove useful in resolving the lack of urgency for PCC realization.

SARS-CoV-2 infection in pregnancy during the first wave of COVID-19 in the Netherlands: a prospective nationwide population-based cohort study (NethOSS).

OBJECTIVE: To describe characteristics, risk factors and maternal, obstetric and neonatal outcomes of pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). DESIGN: Multi-centre prospective population-based cohort study. SETTING: Nationwide study in the Netherlands. POPULATION: Pregnant women with confirmed SARS-CoV-2 infection admitted to hospital or in home-isolation: 1 March 2020 to 31 August 2020. METHODS: Pregnant women with positive polymerase chain reaction or antibody tests were registered using the Netherlands Obstetrics Surveillance System (NethOSS). (Selective) testing occurred according to national guidelines. Data from the national birth registry (pregnant pre-coronavirus disease 2019 [COVID-19] cohort) and an age-matched cohort of COVID-19-positive women (National Institute for Public Health and the Environment; fertile age COVID-19 cohort) were used as reference. MAIN OUTCOME MEASURES: Incidence of SARS-CoV-2 infection in pregnant women. Maternal, obstetric and neonatal outcomes including hospital and intensive care admission. RESULTS: Of 376 registered pregnant women with confirmed SARS-CoV-2 infection, 20% (74/376) were admitted to hospital, of whom 84% (62/74) were due to SARS-CoV-2; 10% (6/62) were admitted to intensive care and 15% (9/62) to obstetric high-care units. Risk factors for admission were non-European country of origin (odds ratio [OR] 1.73, 95% CI 1.01-2.96) and being overweight/obese (OR 1.86, 95% CI 1.51-3.20). No maternal or perinatal deaths occurred. Caesarean section after labour-onset was increased (OR 1.58, 95% CI 1.09-2.28). Hospital and intensive care admission were higher compared with the fertile age COVID-19 cohort (OR 6.75, 95% CI 5.18-8.81 and OR 2.52, 95% CI 1.11-5.77, respectively). CONCLUSIONS: Non-European country of origin and being overweight/obese are risk factors for severe course of SARS-CoV-2 infection in pregnancy, risk of caesarean section and hospital and intensive care unit admission are increased. TWEETABLE ABSTRACT: Pregnant women with SARS-CoV-2 in the Netherlands show increased hospital/ICU admission and caesarean section.

Cell viability and electrical response of breast cancer cell treated in aqueous graphene oxide solution deposition on interdigitated electrode.

Breast cancer is one of the most reported cancers that can lead to death. Despite the advances in diagnosis and treatment procedures, the possibility of cancer recurrences is still high in many cases. With that in consideration, researchers from all over the world are showing interest in the unique features of Graphene oxide (GO), such as its excellent and versatile physicochemical properties, to explore further its potential and benefits towards breast cancer cell treatment. In this study, the cell viability and electrical response of GO, in terms of resistivity and impedance towards the breast cancer cells (MCF7) and normal breast cells (MCF10a), were investigated by varying the pH and concentration of GO. Firstly, the numbers of MCF7 and MCF10a were measured after being treated with GO for 24 and 48 h. Next, the electrical responses of these cells were evaluated by using interdigitated gold electrodes (IDEs) that are connected to an LCR meter. Based on the results obtained, as the pH of GO increased from pH 5 to pH 7, the number of viable MCF7 cells decreased while the number of viable MCF10a slightly increased after the incubation period of 48 h. Similarly, the MCF7 also experienced higher cytotoxicity effects when treated with GO concentrations of more than 25 µg/mL. The findings from the electrical characterization of the cells observed that the number of viable cells has corresponded to the impedance of the cells. The electrical impedance of MCF7 decreased as the number of highly insulating viable cell membranes decreased. But in contrast, the electrical impedance of MCF10a increased as the number of highly insulating viable cell membranes increased. Hence, it can be deduced that the GO with higher pH and concentration influence the MCF7 cancer cell line and MCF10a normal breast cell.

Management of prediabetes in Malaysian population: An experts' opinion.

INTRODUCTION: Prediabetes, typically defined as blood glucose levels above normal but below diabetes thresholds, denotes a risk state that confers a high chance of developing diabetes. Asians, particularly the Southeast Asian population, may have a higher genetic predisposition to diabetes and increased exposure to environmental and social risk factors. Malaysia alone was home to 3.4 million people with diabetes in 2017; the figure is estimated to reach 6.1 million by 2045. Developing strategies for early interventions to treat prediabetes and preventing the development of overt diabetes and subsequent cardiovascular and microvascular complications are therefore important. METHODS: An expert panel comprising regional experts was convened in Kuala Lumpur, for a one-day meeting, to develop a document on prediabetes management in Malaysia. The expert panel comprised renowned subject-matter experts and specialists in diabetes and endocrinology, primary-care physicians, as well as academicians with relevant expertise. RESULTS: Fifteen key clinical statements were proposed. The expert panel reached agreements on several important issues related to the management of prediabetes providing recommendations on the screening, diagnosis, lifestyle and pharmacological management of prediabetes. The expert panel also proposed changes in forthcoming clinical practice guidelines and suggested that the government should advocate early screening, detection, and intensive management of prediabetes. CONCLUSION: This document provides a comprehensive approach to the management of prediabetes in Malaysia in their daily activities and offer help in improving government policies and the decision-making process.

Mode of childbirth and neonatal outcome after external cephalic version: A prospective cohort study.

OBJECTIVE: to assess the mode of childbirth and adverse neonatal outcomes in women with a breech presentation with or without an external cephalic version attempt, and to compare the mode of childbirth among women with successful ECV to women with a spontaneous cephalic presentation. DESIGN: prospective matched cohort study. SETTING: 25 clusters (hospitals and its referring midwifery practices) in the Netherlands. Data of the Netherlands perinatal registry for the matched cohort. PARTICIPANTS: singleton pregnancies from January 2011 to August 2012 with a fetus in breech presentation and a childbirth from 36 weeks gestation onwards. Spontaneous cephalic presentations (selected from national registry 2009 and 2010) were matched in a 2:1 ratio to cephalic presentations after a successful version attempt. Matching criteria were maternal age, parity, gestational age at childbirth and fetal gender. Main outcomes were mode of childbirth and neonatal outcomes. MEASUREMENTS AND FINDINGS: of 1613 women eligible for external cephalic version, 1169 (72.5%) received an ECV attempt. The overall caesarean childbirth rate was significantly lower compared to women who did not receive a version attempt (57% versus 87%; RR 0.66 (0.62-0.70)). Women with a cephalic presentation after ECV compared to women with a spontaneous cephalic presentation had a decreased risk for instrumental vaginal childbirth (RR 0.52 (95% CI 0.29-0.94)) and an increased risk of overall caesarean childbirth (RR 1.7 (95%CI 1.2-2.5)). KEY CONCLUSIONS: women who had a successful ECV are at increased risk for a caesarean childbirth but overall, ECV is an important tool to reduce the caesarean rate. IMPLICATION FOR PRACTICE: ECV is an important tool to reduce the caesarean section rates.

Patients' and professionals' barriers and facilitators to external cephalic version for breech presentation at term, a qualitative analysis in the Netherlands.

OBJECTIVE: external cephalic version (ECV) is a relatively simple and safe manoeuvre and a proven effective approach in the reduction of breech presentation at term. There is professional consensus that ECV should be offered to all women with a fetus in breech presentation, but only up to 70% of women eligible for ECV undergo an ECV attempt. The aim of the study was to identify barriers and facilitators for ECV among professionals and women with a breech presentation at term. DESIGN: qualitative study with semi-structured interviews. SETTING: Dutch hospitals. PARTICIPANTS: pregnant women with a breech presentation who had decided on ECV, and midwives and gynaecologists treating women with a breech presentation. MEASUREMENTS: on the basis of national guidelines and expert opinions, we developed topic lists to guide the interviews and discuss barriers and facilitators in order to decide on ECV (pregnant women) or advice on ECV (midwives and gynaecologists). FINDINGS: among pregnant women the main barriers were fear, the preference to have a planned caesarean section (CS), incomplete information and having witnessed birth complications within the family or among friends. The main facilitators were the wish for a home birth, the wish for a vaginal delivery and confidence of the safety of ECV. Among professionals the main barriers were a lack of knowledge to fully inform and counsel patients on ECV, and the inability to counsel women who preferred a primary CS. The main facilitator was an unambiguous policy on (counselling for) ECV within the region. CONCLUSION: we identified several barriers and facilitators possibly explaining the suboptimal implementation of ECV for breech presentation in the Netherlands. This knowledge should be taken into account in designing implementation strategies for ECV to improve the uptake of ECV by professionals and patients.

Decision aids to improve informed decision-making in pregnancy care: a systematic review.

BACKGROUND: Rapid development in health care has resulted in an increasing number of screening and treatment options. Consequently, there is an urgency to provide people with relevant information about benefits and risks of healthcare options in an unbiased way. Decision aids help people to make decisions by providing unbiased non-directive research evidence about all treatment options. OBJECTIVE: To determine the effectiveness of decision aids to improve informed decision making in pregnancy care. SEARCH STRATEGY: We searched MEDLINE (1953-2011), EMBASE (1980-2011), CENTRAL (CENTRAL, the Cochrane Library; 2011, Issue 4), Psycinfo (1806-2011) and Research Registers of ongoing trials (www.clinicaltrials.gov, www.controlled-trials.com). SELECTION CRITERIA: We included randomised controlled trials comparing decision aids in addition to standard care. The study population needed to be pregnant women making actual decisions concerning their pregnancy. DATA COLLECTION AND ANALYSIS: Two independent researchers extracted data on quality of the randomised controlled trial (GRADE criteria), quality of the decision aid (IPDAS criteria), and outcome measures. Data analysis was undertaken by assessing group differences at first follow up after the interventions. MAIN RESULTS: Ten randomised controlled trials could be included. Pooled analyses showed that decision aids significantly increased knowledge, (weighted mean difference 11.06, 95% confidence interval 4.85-17.27), decreased decisional conflict scores (weighted mean difference -3.66, 95% confidence interval -6.65 to -0.68) and decreased anxiety (weighted mean difference -1.56, 95% confidence interval -2.75 to -0.43). CONCLUSIONS: Our systematic review showed the positive effect of decision aids on informed decision making in pregnancy care. Future studies should focus on increasing the uptake of decision aids in clinical practice by identifying barriers and facilitators to implementation.

Use of newly available febuxostat in a case of chronic tophaceous gout contraindicated to allopurinol and probenecid.

Urate lowering therapy in this country has mainly been achieved by the use of allopurinol and probenecid. A new xanthine oxidase inhibitor called febuxostat has been approved in 2009 for treatment of hyperuricaemia in gout. In this report, we describe the management of a patient with chronic tophaceous gout using febuxostat. The reduction in serum uric acid to target levels was rapid, and the tophi size had also reduced significantly while on therapy. There was no unwanted side effect observed during the therapy. Therefore, febuxostat would be a useful alternative drug in the treatment of hyperuricaemia in gout patients who have contraindications to allopurinol and probenecid.

A prospective assessment of renal impairment after preparation for colonoscopy: oral sodium phosphate appears to be safe in well-hydrated subjects with normal renal status.

BACKGROUND: The outcome of colonoscopy is highly dependent upon the quality of bowel cleansing prior to the procedure. Oral sodium phosphate solutions (OSPS) or preparations containing polyethylene glycol (PEG) are generally employed. However, the safety of administering OSPS prior to colonoscopy has been questioned because of the potential for renal failure. AIM: To compare rates of renal failure after OSPS and PEG in a randomized, prospective trial and to assess the quality of colonoscopy after these two bowel preparations. METHODS: Subjects with eGFR >or= 60 ml/min/1.73 m(2) and expressed willingness to adhere to hydration recommendations were randomized to OSPS or PEG solutions. Renal function was assessed 1 week prior to, immediately prior to, and 1 week after colonoscopy. RESULTS: No subject had acute kidney failure after OSPS or PEG. OSPS was associated with significant increases in the serum phosphate and sodium levels and significant decreases in the calcium and potassium levels. These values returned to normal limits in all subjects by 1 week after colonoscopy. The quality of colonic cleansing was superior after OSPS than after PEG (Ottawa score 2.5 +/- 2.2 vs. 3.5 +/- 2.3, respectively, P < 0.05). The detection of one or more adenomatous polyps was higher after OSPS than after PEG. CONCLUSIONS: Renal failure was not detected after the use of OSPS for colonoscopy preparation in subjects with recently documented normal renal function who were able to consume the required amounts of water after each dose. However, based on the number of subjects studied, the theoretical risk of this complication is still between 0 and 6.3%. Thus, it is appreciated that only a very large prospective trial would have yielded a more accurate estimate of the likelihood of renal compromise after OSPS. Despite this caveat, OSPS has advantages over PEG in terms of the adequacy of colonic visualization and the number of polyps detected.

Clinical trial: the efficacy and safety of routine bowel cleansing agents for elective colonoscopy in persons with spinal cord injury - a randomized prospective single-blind study.

BACKGROUND: As difficulty with evacuation is a common occurrence in individuals with spinal cord injury, preparation prior to colonoscopy may be suboptimal and, perhaps, more hazardous. AIM: To assess the safety and efficacy of bowel cleansing regimens in persons with spinal cord injury. METHODS: Randomized, prospective, single blind study comparing polyethylene glycol (PEG), oral sodium phosphosoda (OSPS) and combination of both for colonic preparation prior to colonoscopy in subjects with spinal cord injury. RESULTS: Thirty six subjects with eGFR > or =60 mL/min/1.73 m(2) were randomized to PEG or OSPS or PEG+OSPS. Regardless of bowel preparation employed, >73% of subjects had unacceptable colonic cleansing. No subject in the OSPS preparation group demonstrated a decrease in eGFR or an increase in serum creatinine concentration from the baseline. OSPS and PEG+OSPS preparations caused a transient change in serum potassium, phosphate and calcium concentrations, but no change in electrolytes was noted in the PEG group. CONCLUSIONS: Neither OSPS alone, PEG alone nor their combination was sufficient to prepare adequately the bowel for colonoscopy in most patients with spinal cord injury. However, administration of OSPS and/or PEG appears to be safe in the spinal cord injury population, provided adequate hydration is provided.

The renal safety of bowel preparations for colonoscopy: a comparative study of oral sodium phosphate solution and polyethylene glycol.

BACKGROUND: Rare cases of nephrotoxicity have been reported with oral sodium phosphate solution (OSPS). AIM: To evaluate whether OSPS is associated with changes in renal function. METHODS: A chart review performed on 311 patients who had colonoscopy at the James J. Peters VA Medical Centre prepared with either OSPS (n = 157) or polyethylene glycol (PEG) (n = 154). Patients had a baseline serum creatinine or=50% increase above their baseline creatinine was similar (OSPS vs. PEG, 5% vs. 3%, P = 0.77). CONCLUSIONS: Oral sodium phosphate solution was associated with a slight increase in serum creatinine, which was not clinically significant. Renal toxicity from OSPS appears to be minimal when used in patients with serum creatinine value <1.5 mg/dL.

Application of summary receiver operating characteristics (sROC) analysis to diagnostic clinical testing.

Summary receiver operating characteristics (sROC) analysis is a recently developed statistical technique that can be applied to meta-analysis of diagnostic tests. This technique can overcome some of the limitations associated with pooling the sensitivities and specificities of published studies. The sROC curve is initially constructed by plotting the sensitivity (true positivity) and false positivity (1 - specificity) of each study. After mathematical manipulation of the true and false positivities, linear regression is performed to calculate the slope and y-intercept. These coefficients are then entered into the sROC equation to generate the sROC curve. There are three commonly used methods to assess the accuracy of the test: the exact area under the curve (AUC) for the sROC function, the homogeneous AUC, and the index Q*. Statistical formulas can compare these values from different diagnostic tests. With the introduction of sROC software and better understanding of this method, the application of sROC analysis should continue to increase.

Decline in haemoglobin A1c values in diabetic patients receiving interferon-alpha and ribavirin for chronic hepatitis C.

Haemoglobin A1c (A1c) levels are lower during haemolysis because of the shorter exposure of haemoglobin (Hb) to plasma glucose. Ribavirin (RBV) used in combination with interferon-alpha (IFN) for chronic hepatitis C causes reversible haemolytic anaemia. This study examined the extent to which RBV treatment influences A1c levels in diabetic patients. A retrospective analysis identified 32 diabetic patients who underwent hepatitis C treatment with IFN and RBV. Each subject had at least three measures of A1c, Hb and glucose: before, during and after therapy. A1c values decreased from a mean pretreatment level of 7.2% to an on-treatment A1c level of 5.2% [mean paired difference -2.01%; 95% confidence interval (CI) -1.59% to -2.43%; P < 0.001]. During therapy, mean Hb levels decreased from 15.1 g/dL at baseline to a nadir of 11.7 g/dL (P < 0.001) with a rise in lactose dehydrogenase levels and reticulocyte counts, and unchanged mean corpuscular volume values confirming haemolysis. At the same time, glucose levels declined by a mean of 38.4 mg/dL (95% CI 13.4-63.5 mg/dL; P = 0.002) as did body weights by a mean of 3.15 kg (P < 0.001). According to published glucose-A1c correlation tables, this decline of glucose concentration by 38.4 mg/dL correlates to a decline in A1c level of 1.08%. In conclusion, reductions of A1c levels by a mean of 2.01% during hepatitis C therapy with IFN + RBV are due to a combination of decreased glucose levels (1.08%) and RBV-induced haemolysis (0.93%). A1c levels should not be measured during hepatitis C treatment with IFN + RBV because they do not adequately reflect glycaemic control.

Recent concepts in the management of bowel problems after spinal cord injury.

Bowel problems after SCI can be debilitating. Colonic inertia as a result of decreased parasympathetic (S2-4) stimulation of the left colon and rectosigmoid seems to be the principal abnormality accounting for DWE. The conventional measures used for decades have poor results in many people. Neostigmine, an anticholinesterase inhibitor, appears to be a more physiological agent for these individuals. The combination of neostigmine + glycopyrrolate infusion has shown encouraging results after intravenous administration and studies are under way to assess the efficacy of neostigmine by other routes.

Metaanalysis of trials comparing laparoscopic and open surgery for Crohn's disease.

BACKGROUND: Several studies in the literature have suggested that laparoscopic surgery for Crohn's disease is associated with faster postoperative recovery and a morbidity and recurrence rate similar to that for open surgery. Most of these studies have been limited by a small sample size and a short follow-up period. METHODS: To clarify whether open or laparoscopic resection results in a better outcome, a metaanalysis of studies was performed comparing the two procedures for Crohn's disease. Pooled effects were estimated using a random-effects model. RESULTS: Laparoscopic surgery required more operative time than open surgery (26.8 min; 95% confidence interval [CI], 6.4-47.2 min), but resulted in a shorter duration of ileus and a decreased hospital stay (-2.62 days; 95% CI, -3.62 to -1.62). Laparoscopic surgery also was associated with a decreased rate for postoperative bowel obstruction and surgical recurrences. CONCLUSIONS: Laparoscopic surgery for Crohn's disease is feasible, safe, and associated with shorter duration of ileus and a shorter hospital stay.

Disulfiram treatment increases plasma and red blood cell acetaldehyde in abstinent alcoholics.

BACKGROUND: Much of alcohol's toxicity is due to its product, acetaldehyde. The role of acetaldehyde derived from endogenous sources was assessed in alcoholic patients administered disulfiram, an inhibitor of aldehyde dehydrogenase. METHODS: The first part of the study included 23 subjects without biochemical or clinical evidence of chronic liver disease who were abstinent for 2 weeks; 11 patients were started on disulfiram (250 mg/day), whereas the other 12 were not given disulfiram and served as controls. The second part of the study included 13 alcoholic patients with clinical or pathological evidence of cirrhosis who also were administered disulfiram for 2 weeks. Plasma and red blood cell (RBC) acetaldehyde as well as serum transaminases were measured at baseline and after 1 and 2 weeks of treatment. RESULTS: In the disulfiram-treated group of alcoholics without known cirrhosis, RBC acetaldehyde levels increased from the pretreatment value of 2.98+/-0.18 microM to 4.14+/-0.33 microM after 1 week and to 4.14+/-0.26 microM after 2 weeks of treatment (p < 0.001). Compared with the pretreatment values (2.07+/-0.24 microM), plasma acetaldehyde levels also increased after 1 week (3.18+/-0.32 microM) and 2 weeks (3.15+/-0.26 microM) of disulfiram treatment (p < 0.001). There were no significant differences in sequential levels measured in either plasma or RBC acetaldehyde levels in patients who were not administered disulfiram. In the group of cirrhotic patients, the mean baseline RBC acetaldehyde value (3.60+/-0.22 microM) was significantly higher than in noncirrhotics. Disulfiram therapy increased the RBC acetaldehyde after 1 week (4.63+/-0.27 microM, p < 0.001) and 2 weeks of treatment (4.06+/-0.28 microM, p < 0.05). Compared with baseline values, plasma acetaldehyde levels were significantly higher after 1 week but not after 2 weeks of disulfiram. There were no significant differences among serum transaminases in alcoholics administered disulfiram, although three cirrhotic patients did have clinically significant elevations. CONCLUSIONS: In abstaining subjects given disulfiram, acetaldehyde concentrations increase, possibly due to diminished catabolism of endogenously generated acetaldehyde. Disulfiram should be given cautiously, especially in patients with cirrhosis.

Human atheromatous plaque extracts induce tissue factor activity (TFa) in monocytes and also express constitutive TFa.

Tissue factor activity (TFa) is a major activator of the coagulation cascade and may play a role in atheroma-induced thrombosis. Monocyte-macrophages (MO-MF) generate considerable quantities of TFa when stimulated by a variety of inducers. To test the hypothesis that MO could be induced by atheromatous plaque to generate TFa, plaque extracts obtained from patients with obstructive atheromatous disease were used. These extracts were also assayed for constitutive TFa. The constitutive activity was variable from extract to extract but could be very high, up to 250 U TFa. The TFa induced in MO could be also very high, up to 200 U (i.e. 1/5 of the TFa of full strength rabbit brain thromboplastin). These findings point to a major role for MO-MF TFa in the induction or thrombosis by atheromatous plaque.