IVF outcomes in patients with a history of bariatric surgery: a multicenter retrospective cohort study.

STUDY QUESTION: How does a history of dramatic weight loss linked to bariatric surgery impact IVF outcomes? SUMMARY ANSWER: Women with a history of bariatric surgery who had undergone IVF had a comparable cumulative live birth rate (CLBR) to non-operated patients of the same BMI after the first IVF cycle. WHAT IS KNOWN ALREADY: In the current context of increasing prevalence of obesity in women of reproductive age, weight loss induced by bariatric surgery has been shown to improve spontaneous fertility in obese women. However, little is known on the clinical benefit of bariatric surgery in obese infertile women undergoing IVF. STUDY DESIGN, SIZE, DURATION: This exploratory retrospective multicenter cohort study was conducted in 10 287 IVF/ICSI cycles performed between 2012 and 2016. We compared the outcome of the first IVF cycle in women with a history of bariatric surgery to two age-matched groups composed of non-operated women matched on the post-operative BMI of cases, and non-operated severely obese women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The three exposure groups of age-matched women undergoing their first IVF cycle were compared: Group 1: 83 women with a history of bariatric surgery (exposure, mean BMI 28.9 kg/m2); Group 2: 166 non-operated women (non-exposed to bariatric surgery, mean BMI = 28.8 kg/m2) with a similar BMI to Group 1 at the time of IVF treatment; and Group 3: 83 non-operated severely obese women (non-exposed to bariatric surgery, mean BMI = 37.7 kg/m2). The main outcome measure was the CLBR. Secondary outcomes were the number of mature oocytes retrieved and embryos obtained, implantation and miscarriage rates, live birth rate per transfer as well as birthweight. MAIN RESULTS AND THE ROLE OF CHANCE: No significant difference in CLBR between the operated Group 1 patients and the two non-operated Groups 2 and 3 was observed (22.9%, 25.9%, and 12.0%, in Groups 1, 2 and 3, respectively). No significant difference in average number of mature oocytes and embryos obtained was observed among the three groups. The implantation rates were not different between Groups 1 and 2 (13.8% versus 13.7%), and although lower (6.9%) in obese women of Group 3, this difference was not statistically significant. Miscarriage rates in Groups 1, 2 and 3 were 38.7%, 35.8% and 56.5%, respectively (P = 0.256). Live birth rate per transfer in obese patients was significantly lower compared to the other two groups (20%, 18%, 9.3%, respectively, in Groups 1, 2 and 3, P = 0.0167). Multivariate analysis revealed that a 1-unit lower BMI increased the chances of live birth by 9%. In operated women, a significantly smaller weight for gestational age was observed in newborns of Group 1 compared to Group 3 (P = 0.04). LIMITATIONS, REASONS FOR CAUTION: This study was conducted in France and nearly all patients were Caucasian, questioning the generalizability of the results in other countries and ethnicities. Moreover, 950 women per group would be needed to achieve a properly powered study in order to detect a significant improvement in live birth rate after bariatric surgery as compared to infertile obese women. WIDER IMPLICATIONS OF THE FINDINGS: These data fuel the debate on the importance of pluridisciplinary care of infertile obese women, and advocate for further discussion on whether bariatric surgery should be proposed in severely obese infertile women before IVF. However, in light of the present results, infertile women with a history of bariatric surgery can be reassured that surgery-induced dramatic weight loss has no significant impact on IVF prognosis. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by unrestricted grants from FINOX-Gédéon Richter and FERRING Pharmaceuticals awarded to the ART center of the Clinique Mathilde to fund the data collection and the statistical analysis. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NCT02884258.

[The Confusion Assessment Method: Transcultural adaptation of a French version]. / Adaptation transculturelle francophone de la Confusion Assessment Method.

INTRODUCTION: The Confusion Assessment Method (CAM) is a validated key tool in clinical practice and research programs to diagnose delirium and assess its severity. There is no validated French version of the CAM training manual and coding guide (Inouye SK). The aim of this study was to establish a consensual French version of the CAM and its manual. METHODS: Cross-cultural adaptation to achieve equivalence between the original version and a French adapted version of the CAM manual. RESULTS: A rigorous process was conducted including control of cultural adequacy of the tool's components, double forward and back translations, reconciliation, expert committee review (including bilingual translators with different nationalities, a linguist, highly qualified clinicians, methodologists) and pretesting. A consensual French version of the CAM was achieved. CONCLUSION: Implementation of the CAM French version in daily clinical practice will enable optimal diagnosis of delirium diagnosis and enhance communication between health professionals in French speaking countries. Validity and psychometric properties are being tested in a French multicenter cohort, opening up new perspectives for improved quality of care and research programs in French speaking countries.

Screening for von Willebrand disease: contribution of an automated assay for von Willebrand factor activity.

Measuring von Willebrand factor (VWF) activity is essential to the diagnosis of von Willebrand disease (VWD). The VWF activity is usually assessed based on measurement of the ristocetin cofactor (VWF:RCo). However, that test is technically challenging and has high intra- and inter-assay variabilities. The HemosIL VWF activity (VWF:AC) is a fully automated assay, recently proposed as a good alternative to VWF:RCo for VWD diagnosis. This study was undertaken to assess this new method. First, the analytical performance of VWF:AC on an automated coagulo-meter (ACLTop) was determined, and then this new method was compared with VWF:RCo and the platelet function analyzer (PFA100) for 160 patients referred for VWD screening. The VWF:AC achieved acceptable precision with within-run and between-run coefficients of variation ranging from 2.3% to 14.1%, and linearity from 10% to 100%. Despite some marked differences between VWF:AC and VWF:RCo for 10 plasmas tested, their agreement for VWD diagnosis was good. The VWF:AC had sensitivity similar to that of PFA100 (close to 100%), but better specificity (97.7% vs. 66% or 60%, depending on the cartridge used). The good analytical performance, and the sensitivity and specificity of VWF:AC to detect VWF deficiency renders it a suitable method for VWD screening. Our findings support VWF:AC use for the diagnostic work-up of VWD, paying close attention to concomitant clinical signs and bleeding score, as recommended for VWD.

Spectral amplitude and phase measurement of a 40 GHz free-running quantum-dash modelocked laser diode.

We present a linear self-referenced measurement of the spectral amplitude and phase of a free-running quantum-dash modelocked laser diode. The technique is suitable for measuring optical signals with repetition rates up to 100 GHz. In contrast to many other linear techniques it requires no external electronic clock synchronized to the signal under test. Using this method we are able to compensate for the intracavity dispersion of the diode to demonstrate 500 fs pulses at a repetition rate of 39.8 GHz. We also use the technique to characterize the dependence of the diode's intracavity dispersion on the applied current.

Change in hip fracture incidence over the last 6 years in France.

UNLABELLED: Controversies exist about the change in hip fracture incidence among countries. In France, over the last 6 years, the incidence in people aged 40 years and over of hip fractures decreased in women over 39 years and increased in men; a decrease in the incidence was observed in both genders in the elderly. INTRODUCTION: Controversies exist about the change in hip fracture incidence among countries. The aim of this study was to assess the incidence of hip fractures in men and women aged 40 years and over between 2002 and 2008 in France. METHODS: Data were drawn from the French Hospital National Database. The absolute number of admissions was described and the incidence rates per 1,000,000 adjusted on age (40-59, 60-74; 74-84, and ≥ 85 years), and gender was calculated using the data of the French population. RESULTS: The number of hip fractures increased in men (+13%; from 14,736 in 2002 to 16,611 in 2008) and remained stable in women (+0.2%, 50,910 in 2008). Between 2002 and 2008, the French population increased by 9% in both genders. Incidence over 39 years decreased by 8% in women (3,356 and 3,093 per million in 2002 and 2008, respectively) and increased by 4% in men (1,131 and 1,172 per millions in 2002 and 2008, respectively). An age-specific incidence decrease was found, in particular, in the elderly in both genders (74-84 and ≥ 85 years), most importantly in women. CONCLUSION: Over the last 6 years, the incidence of hip fractures decreased in women aged over 39 years and increased in men aged over 39 years; a decrease in the incidence of these fractures was observed in both genders in the elderly. Such epidemiological data may help policy making, planning resource allocation, and setting up complementary health decisions for the management of osteoporosis.

Hemoglobin level variability in hemodialysis patients treated with epoetin-ß during 1 year.

AIM: This analysis was performed to assess the prevalence and the factors associated with hemoglobin (Hb) variability during treatment with erythropoiesis-stimulating agents (ESA) in France. METHODS: Hb variability was evaluated in a subgroup of hemodialysis (HD) patients of the French cohort DiaNE. Eligible patients had received epoetin-ß at least 6 months before entering DiaNE, 12 months during DiaNE and had no missing monthly Hb measurements. Up and down excursions (Hb variations > 1.5 g/dl with duration > 8 weeks) were assessed. RESULTS: Of the 499 patients evaluated in this analysis, 295 (59%) had Hb levels inside the target range of 11 - 13 g/dl at baseline. The number of patients with constantly stable Hb level inside the target range decreased from baseline to 27.5% at 6 months and 10.8% at 12 months. More than 70% of patients experienced Hb variability. The number of excursions was 1.7 ± 0.8 per patient/year. The amplitude of up excursions was 2.8 ± 1.0 g/ dl with a duration of 14.7 ± 4.7 weeks. The amplitude of down excursions was 2.6 ± 0.9 g/dl with a duration of 14.5 ± 4.6 weeks. The main factors associated with Hb variability were number of epoetin-ß dose changes, adverse events and iron therapy changes. CONCLUSION: Hb variability is frequent in French ESA-treated HD patients and closely related to practices. Further efforts are needed to improve anemia management.

[Methodological and statistical aspects of equivalence and non inferiority trials]. / Aspects méthodologiques et statistiques des essais d'équivalence et de non-infériorité.

BACKGROUND: - The existence of effective reference treatments means that the superior therapeutic efficacy of new treatments is less marked and thus more difficult to demonstrate statistically. Moreover, the potential value of a new treatment is also based on other criteria, such as costs, ease of use, non invasiveness, and immediate or long-term side effects. In this context, methodological issue becomes one of looking for equivalence or non inferiority of the new treatment in comparison with an existing, high-performance reference treatment. METHODS: - In the present work, we reexamine the statistical rational and methodological features of equivalence and non inferiority trials. RESULTS: - We address equivalence margin choice, hypotheses building, and the different approaches for establishing equivalence (hypothesis testing and confidence intervals). We then discuss key aspects of equivalence trial design and the important methodological quality criteria involved in performing such studies: choice of the reference treatment, subject eligibility criteria, primary endpoint, study population and the required sample size. Lastly, we consider the possibility of adopting a new analytical strategy (non inferiority/superiority). CONCLUSION: - A checklist of items to include when reporting the results of randomized controlled trials (Consolidated Standards of Reporting Trials, the CONSORT recommendations) has been adapted for use in non inferiority and equivalence randomized controlled trials.

Circulating leptin in normal children and during the dynamic phase of juvenile obesity: relation to body fatness, energy metabolism, caloric intake, and sexual dimorphism.

In 112 obese compared with 42 lean children, we found that serum leptin is elevated early in the evolution of childhood-onset obesity (28.4 +/- 1.4 vs. 4.5 +/- 0.4 ng/ml in lean children, P < 0.0001) and correlates with adiposity. Obese children also had higher serum leptin normalized to fat mass. Despite high serum leptin, obese children ingested 2-3 times more calories than did lean control subjects (P < 0.0001) and gained weight rapidly (10.2 +/- 0.3 vs. 2.9 +/- 0.1 kg/year in control subjects, P < 0.0001). Girls had higher leptin levels than did boys, in obese as well as in nonobese children, and showed a closer correlation between adiposity and serum leptin. Elevation of serum leptin was comparable before and after puberty in obese boys, but puberty further increased leptin levels in obese girls (36 +/- 3 ng/ml), resulting in a clear sexual dimorphism with pubertal obese boys (22 +/- 5 ng/ml, P < 0.005). In conclusion, increased serum leptin reflects but does not halt fat deposition in childhood obesity. After normalization to body adiposity, leptin was found to be increased independently by obesity status, female sex, and female sexual maturation.

Limited duration of remission of insulin dependency in children with recent overt type I diabetes treated with low-dose cyclosporin.

Preliminary data from our group indicated that cyclosporin A induced frequent remissions of insulin dependency in a group of 40 insulin-dependent (type I) diabetic children if given at the onset of clinical manifestations of diabetes. We report a 2-yr analysis of the response to cyclosporin A in the group of 81 patients included in the initial study. As observed before, a remission could be obtained in most of the patients (65%) in association with a shorter duration of symptoms, less severe hyperglycemia, lower incidence of ketoacidosis, and higher plasma C-peptide concentrations. All remissions ended during the follow-up period after a mean +/- SE duration of 316 +/- 21 days (range 31-850 days). Two parameters were linked to the duration of remissions: the mean circulating level of cyclosporin during the first 3 mo and the duration of prediagnostic polyuria. We were unable to relate the end of a remission to variations in the cyclosporin regimen, titer of autoantibodies, or progression of beta-cell failure. The euglycemic clamp technique revealed that insulin sensitivity decreases with time in patients not taking insulin. At 24 mo, the patients who had a remission of insulin dependency had better glycemic control, lower insulin dosages, and C-peptide levels two- to threefold higher than the nonremission patients and four- to sixfold higher than the historical control subjects. The cyclosporin regimen was well tolerated over the observed period: more specifically, serum creatinine remained unchanged, and kidney biopsies performed at 18-24 mo of treatment were within normal limits.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholangiocellular carcinoma in polycystic kidney and liver disease.

Cholangiocellular carcinoma developed in two uremic patients with polycystic kidney and liver disease, who had been treated with intermittent hemodialysis for one and nine years. In one case, in situ transformation of the liver cyst epithelium into cholangiocellular carcinoma could be demonstrated. The incidence of cholangiocellular carcinoma in patients undergoing long-term dialysis for polycystic kidney and liver disease, however, has yet to be determined.

Dupuytren's disease in France--1831 to 2001--from description to economic burden.

We recorded all elective admissions for Dupuytren's disease from the French National Hospital Database. We used the data from first hospitalizations to calculate the 2001 hospitalization rates for this condition and determine geographical differences between different regions of France. We also calculated the hospital costs of treating admissions with this disease. Fourteen thousand eight hundred and sixty hospitalizations for Dupuytren's disease were reported in France in 2001, of which 93% were for a first treatment. The disease was mostly present in men and was mostly managed by surgical fasciectomy. Most operations were carried out in private hospitals, with a mean stay of 2 days. Geographical differences were found in men only. The total hospital cost for all elective admissions was 14, 179, 998 Euros, indicating the considerable financial burden to the State of treating this condition.

[Knee arthroscopy for gonarthrosis in France in 2001]. / Arthroscopie pour gonarthrose en France en 2001.

PURPOSE OF THE STUDY: The purpose of this study was to describe the number of arthroscopic procedures conducted for gonarthrosis in France in 2001 and to establish the corresponding hospital costs. MATERIAL AND METHODS: The national database of the medicalization program information system (PMSI) which records all public and private hospitalizations was used to identify all arthroscopic procedures performed for gonarthrosis (principal diagnosis=indication for operation). We noted the number of procedures, the type of hospitalization (< 24h vs > or = 24h), hospital sector (private vs public), associated diagnoses involving the knee, interventions, and hospital cost (using the 2004 schedule). We compared these data with hospitalizations for arthroscopy where gonarthrosis was noted as an associated diagnosis (secondary diagnosis). RESULTS: In 2001, a total of 148,870 hospitalizations were recorded (4,059 for gonarthrosis and 5755 with a secondary diagnosis of gonarthrosis). The 9814 arthroscopies performed were mainly in persons aged over 50 years with meniscal lesions, hospitalized for > 24 h, in the private sector, with joint wash-out and meniscectomy and/or removal of a foreign body. Significantly more meniscal conditions and joint wash-out with meniscectomy and/or removal of a foreign body were observed when gonarthrosis was the secondary diagnosis. The mean hospital cost was 1724 +/- 501 euros and 501 +/- 623 euros for gonarthrosis as the primary and secondary diagnosis respectively. The overall hospital cost for all arthroscopic procedures was 15,644,225 euros. CONCLUSION: The national database (PMSI) can be used as a complementary tool to help in the evaluation of arthroscopic procedures associated with gonarthrosis.

Hypersensitivity to insulin during remissions in cyclosporin-treated IDDM patients.

OBJECTIVE: To test the sensitivity to insulin in recent-onset IDDM patients, its course according to treatment, and the advent of remissions. RESEARCH DESIGN AND METHODS: The euglycemic hyperinsulinemic clamp was used in 54 recent-onset IDDM patients and 14 healthy control subjects. Patients were tested after 1,2, and 4 wk of treatment with either insulin or insulin plus cyclosporin A, during cyclosporin A-associated long-lasting remissions, and during relapses. RESULTS: Insulin sensitivity was markedly decreased in all patients at onset. It was rapidly restored by insulin therapy, whether immunosuppression was associated with it or not. Insulin sensitivity was even higher than normal in the remission patients, who also were characterized by the reappearance of some endogenous insulin secretion and the sustained normalization of blood glucose profiles. During relapses, the deterioration of the blood glucose profiles was associated with some loss of insulin sensitivity. CONCLUSIONS: Cyclosporin A-associated remissions represent an original situation that associates euglycemia with the persistence of low endogenous insulin secretion. Cyclosporin A by itself had no influence on sensitivity to insulin, but allowed the reappearance of some insulin secretory capacity that contributed, with the improvement of insulin sensitivity, to the development of the diabetes honeymoon. The secretion of endogenous insulin, although lower than normal, was sufficient to secure a high sensitivity to insulin and the maintenance of normal blood glucose profiles, presumably because of the fact that insulin was released directly into the portal vein in these conditions. This metabolic state was precarious: the optimal sensitivity to insulin disappeared in patients who relapsed. These results have important clinical consequences: the preservation of islet residual secretory capacity by the use of newer nontoxic immunosuppressive protocols, combined with a minimal supportive insulin therapy in remission patients, may prolong remissions and maintain an optimal insulin sensitivity.

Improvement of diabetic control and acceptability of a three-injection insulin regimen in diabetic adolescents. A multicenter controlled study.

OBJECTIVE: To compare the effectiveness and acceptability of a three-injection insulin regimen with the conventional two-injection therapy in an unselected population of diabetic adolescents. RESEARCH DESIGN AND METHODS: Some 205 patients aged 10-18 yr with IDDM, who were previously treated with two daily insulin injections, were included without any selection into a randomized trial. They were either switched to three (regular prebreakfast, regular prelunch, and [regular+ultralente] predinner) or remained on two ([regular+intermediary] prebreakfast and predinner) subcutaneous injections. They were evaluated after 1 yr of treatment. The major criteria of outcome of efficacy were the concentration of GHb, the frequency of severe hypoglycemia and DKA, and body weight. RESULTS: Of the patients, 82% accepted the three-injection regimen, and 83% accepted the two-injection regimen. At entry into the trial, no significant differences appeared between the two treatment groups nor among patients refusing the allocated regimen. Significant explanatory variables predicting initial diabetes control were duration of disease and adherence to diet. GHb, decreased from 9.8 +/- 0.1 to 9.3 +/- 0.2% (P < 0.05) in the three-injection group, whereas it increased from 9.5 +/- 0.3 to 9.8 +/- 0.3% (P < 0.05) in the two-injection group, resulting in a modest (0.75%) but significant difference (P < 0.05) between GHb change in the two groups. The difference reached 1.4% (P < 0.0002) in patients with GHb > 11.2% at entry. The frequency of hypoglycemia and DKA was similar in the two groups. None of the parameters known to potentially influence glycemic control changed during the trial, and, therefore, the improvement of GHb could be attributed to the pattern of daily insulin distribution per se. CONCLUSIONS: In the general diabetic adolescent population, the efficacy of a three-injection regimen is somewhat superior to that of a conventional two-injection regimen, particularly in patients previously poorly controlled. The acceptability of this regimen being excellent, its increased use should be considered in this age-group.

Simultaneous vitality and DNA-fragmentation measurement in spermatozoa of smokers and non-smokers.

BACKGROUND: Because cigarette smoke is a powerful ROS producer, we hypothesized that the spermatozoa of smokers would be more at risk of having increased DNA fragmentation than spermatozoa of non-smoking men. METHODS: A cross-sectional study was performed on consenting smokers and non-smokers, consulting in an infertility clinic for routine sperm analysis. The application of a novel TUNEL assay coupled to a vitality marker, LIVE/DEAD®, allowed both DNA fragmentation and viability measurement within spermatozoa of participants to be analyzed by flow cytometry. RESULTS: The coupled vitality-DNA fragmentation analysis revealed that non-smokers and smokers, respectively presented medians of 3.6% [0.6-36.8] and 3.3% [0.9-9.6] DNA fragmented spermatozoa among the living spermatozoa population (P > 0.05). CONCLUSION: No deleterious effect of smoking on spermatozoa was found in our study. More studies concerning potential mutagenic capacities of cigarette smoke on spermatozoa are necessary. In addition, the coupled vitality-DNA fragmentation analysis may orient Assisted Reproductive Technology teams when confronted with patients having a high percentage of DNA-fragmented living spermatozoa.

Harmful long-term impact of hepatitis C virus infection in kidney transplant recipients.

BACKGROUND: The long-term impact of hepatitis C virus (HCV) infection in renal transplant recipients remains controversial. We report here our experience, in a homogeneous single center, of 499 patients with a fairly long follow-up. METHODS: We retrospectively studied 499 hepatitis B virus-negative patients who received an initial cadaver donor kidney transplantation at Necker Hospital between January 1, 1979 and December 31, 1994, with a graft or patient survival of at least 6 months. Anti-HCV antibodies were detected at time of transplantation in 112 patients (22%). Patient survival and causes of death were compared among anti-HCV-positive and -negative patients RESULTS: Our results clearly indicate that first cadaver kidney transplant recipients with anti-HCV antibodies had a significantly shorter patient and graft long-term survival than recipients without anti-HCV antibodies (P<0.01 and P<0.0001 respectively). Mean follow-up time after transplantation was 79+/-2 months in the former group and 81+/-5 months in the latter (NS). Increased mortality was primarily caused by liver disease (P<0.001) and sepsis (P<0.01). In a multivariate analysis, HCV infection significantly affected the mortality rate (odds ratio: 2.8). CONCLUSIONS: These results suggest that HCV infection has a harmful long-term impact on the survival of kidney transplant recipients.

Reduction of morbidity and cytokine release in anti-CD3 MoAb-treated mice by corticosteroids.

In keeping with the in vitro mitogenic properties of anti-CD3 MoAbs, the first injections of anti-CD3 are invariably responsible for an in vivo cellular activation. This activation induces a massive cytokine release in the circulation (TNF, IFN gamma, IL-2, IL-6, and IL-3). Paralleling this release, a severe clinical reaction occurs in OKT3-treated patients and in 145 2C11-treated mice. Corticosteroids both in vitro and in vivo inhibit the production of several cytokines involved in the anti-CD3 reaction. A single 1 mg hydrocortisone dose was administered to 145 2C11-treated mice according to different kinetics schedules. When given 1 hr prior to the anti-CD3 MoAb, hydrocortisone exerted a beneficial effect on the mouse physical reaction. Hypothermia was totally abrogated at the 4-hr time point. Diarrhea decreased by 50%. Hypomotility improved although not significantly. This improvement correlated with a major modification in the anti-CD3 pattern of cytokine release. At the 90-min blood withdrawal time point cytokine serum levels showed a 100% decrease for IFN gamma, an 88% decrease for IL-6, and 85% decrease for IL-2, and a 75% decrease for TNF. At 4 hr IL-2 serum levels were diminished by 65%; IL-6, IL-3, and IFN gamma serum levels were comparable to controls; and, interestingly, TNF was still detected, whereas it has already disappeared when 145 2C11 was administered alone. Importantly, when given more than 1 hr prior to anti-CD3 injection, corticosteroids were ineffective. To conclude, high doses of corticosteroids must be given with a precise kinetics--i.e. 1 hr prior to anti-CD3 MoAb--to achieve their maximal beneficial effect in the prevention of the anti-CD3 reaction.

Intravenous immunoglobulin therapy for prevention of infection in high-risk premature infants: report of a multicenter, double-blind study.

The effectiveness of intravenously administered immunoglobulin (Ig) therapy for prophylaxis of infection was evaluated in high-risk preterm infants. Two hundred thirty-five premature newborns were randomly assigned, in a double-blind controlled trial, to treatment and placebo groups. Thirty-five infants (29%) of the Ig group and 29 (25%) of the placebo group had one or more episodes of certain infection. Thirty infants (25%) of the Ig group and 18 (16%) of the placebo group had one or more episodes of probable infection. No significant differences were observed in the incidence of certain or probable infection in treated and control infants. Nevertheless, among the infants who had one or more certain or probable episodes of infection, more of them belonged to the Ig group than to the placebo group. The possible deleterious effect of the administration of large amounts of polyspecific Ig is discussed.

Allele doses of apolipoprotein E type epsilon 4 in sporadic late-onset Alzheimer's disease.

Apoliprotein E, type epsilon 4 allele (ApoE-epsilon 4) is associated with late-onset sporadic Alzheimer's disease (AD). We have found that the cumulative probability of remaining unaffected over time decreases for each dose of ApoE-epsilon 4 in sporadic, late-onset French AD. The effect of genotypes on age at onset of AD was analyzed using the product limit method, to compare unaffected groups during aging.

Intrauterine versus postnatal repair of created pulmonary artery stenosis in the lamb. Morphologic comparison.

Experimental lamb models were used for intrauterine creation of pulmonary artery stenosis and later intrauterine repair or postnatal repair. Intrauterine creation of pulmonary artery stenosis was performed in 23 fetal lambs at 90 +/- 1 days of gestation. Eight lambs underwent intrauterine repair of pulmonary artery stenosis at 135 +/- 1 days of gestation and were studied 110 +/- 13 days after repair. Seven lambs underwent postnatal repair at 57 +/- 9 days after birth and were studied 162 +/- 32 days after repair. Eight fetal lambs with unrepaired pulmonary artery stenosis were studied 89 +/- 18 days after birth. All study lambs were compared with normal control lambs. The systolic right ventricular pressure was significantly higher after unrepaired stenosis (78.6 +/- 6.8 mm Hg) than in other lambs, but there was no statistically significant difference after intrauterine repair (23.3 +/- 2.9 mm Hg), postnatal repair (25.9 +/- 3.4 mm Hg), and normal lambs (21.6 +/- 1.1 mm Hg). The systolic pulmonary artery pressure was also not statistically different in these three groups. The weight measurements were age-adjusted for comparison of postnatal and intrauterine repair with normal lambs. The adjusted heart weights were similar in the three groups. The comparison of the adjusted heart weight/adjusted body weight ratio (10(-3) showed a significantly higher ratio in postnatal repair (7.4 +/- 0.1) than in intrauterine repair (6.1 +/- 0.1). The adjusted right ventricular weight/adjusted left ventricular weight ratio was significantly higher in the postnatal repair group (0.71 +/- 0.01) than in both the intrauterine repair group (0.59 +/- 0.01) and normal lambs (0.59 +/- 0.01). The transverse myocyte diameter was not statistically different in all groups of animals and there were no ultrastructural changes even when the pulmonary stenosis was unrepaired. We conclude that intrauterine repair was more satisfactory than postnatal repair in terms of age-adjusted heart weight results, but we did not find any advantages of intrauterine repair in terms of histologic and ultrastructural changes.