Psychiatric morbidity in children with KCNJ11 neonatal diabetes.

AIMS: Mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the pancreatic KATP channel, cause neonatal diabetes. KCNJ11 is also expressed in the brain, and ~ 20% of those affected have neurological features, which may include features suggestive of psychiatric disorder. No previous studies have systematically characterized the psychiatric morbidity in people with KCNJ11 neonatal diabetes. We aimed to characterize the types of psychiatric disorders present in children with KCNJ11 mutations, and explore their impact on families. METHODS: The parents and teachers of 10 children with neonatal diabetes due to KCNJ11 mutations completed the Strengths and Difficulties Questionnaire and the Development and Wellbeing Assessment. Strengths and Difficulties Questionnaire scores were compared with normative data. Diagnoses from the Development and Wellbeing Assessment were compared with known clinical diagnoses. RESULTS: Strengths and Difficulties Questionnaire scores indicated high levels of psychopathology and impact. Psychiatric disorder(s) were present in all six children with the V59M or R201C mutation, and the presence of more than one psychiatric disorder was common. Only two children had received a formal clinical diagnosis, with a further one awaiting assessment, and the coexistence of more than one psychiatric disorder had been missed. Neurodevelopmental (attention deficit hyperactivity disorder and autism) and anxiety disorders predominated. CONCLUSIONS: Systematic assessment using standardized validated questionnaires reveals a range of psychiatric morbidity in children with KCNJ11 neonatal diabetes. This is under-recognized clinically and has a significant impact on affected children and their families. An integrated collaborative approach to clinical care is needed to manage the complex needs of people with KCNJ11 neonatal diabetes.

Finite element modeling for soft tissue surgery based on linear and nonlinear elasticity behavior.

New surgical techniques require fine control from the surgeon's point of view. Until recently, the necessary experience was only obtainable through traditional training protocols (using cadavers, animals, etc.). However, numerous training simulators have now been developed for use in this area. We present a new approach based on a three-dimensional finite element software and on different kinds of linear and nonlinear elastic constitutive equations that is able to predict realistic results. To classify these equations in terms of accuracy, we performed ex-vivo experimental measurements on lamb kidneys. The software has been applied to soft tissue deformation, namely lamb kidney and human uterus, and the numerical results have been compared to experimental ones.

[Pregnancy in type 1 diabetes: insulin pump versus intensified conventional therapy]. / Grossesse et diabète de type 1: pompe à insuline versus traitement intensifié conventionnel.

OBJECTIVES: To evaluate and compare the outcome of pregnancies in women with type 1 diabetes treated with continuous subcutaneous insulin pump or multiple insulin injections. PATIENTS AND METHODS: Thirty-three patients treated with pump, 23 with multiple injections. Were mainly investigated: glycemic control (HbA1C), fetal outcome (congenital malformations, preterm delivery, perinatal mortality), rates of gestational hypertension and cesarean section. RESULTS: HbA1C (1st, 2nd and 3rd trimester) with pump was not significantly different from that obtained with multiple injections (respectively, 7.5 +/- 1.24 vs 7.6 +/- 1.4; 6.34 +/- 0.6 vs 6.6 +/- 0.8; 6.6 +/- 0.7 vs 6.4 +/- 0.7). Fetal prognosis was also similar. The occurrence of gestational hypertension was linked to diabetic complications [OR 5,7, IC95% 1.24-25, p = 0.0025]. The rate of cesarean section (70% in women treated with pump) was influenced by diabetes duration. In planned pregnancy, independently of therapeutic device, HbA1C during organogenesis was better (6.9% +/- 0.78 vs 8.51 +/- 1.3, p < 0.0001) with no perinatal death and no major congenital malformation. DISCUSSION AND CONCLUSION: Fetal prognosis is not overall significantly different with insulin pump compared with intensified conventional therapy. The initiation of insulin pump therapy should not be systematic. Instead, the benefits risks ratio must be assessed resulting in a tailored prescription according to individual needs. This therapeutic choice should be discussed before conception, as planned pregnancy is a main prognostic factor. Diabetes duration and complications remain key factors for the prognosis.

[Pregnancy and type 2 diabetes: which fetal prognosis?]. / Grossesse et diabète de type 2 : quel pronostic foetal ?

OBJECTIVES: The rise in the prevalence of type 2 diabetes in women of childbearing age leads to an increasing number of pregnant women with type 2 diabetes. But published data on fetal outcome are scarce. PATIENTS AND METHODS: In a prospective study from 1999 to 2002, we assessed fetal outcome (preterm delivery, perinatal mortality, congenital malformations) in 20 pregnancies associated with type 2 diabetes and compared the outcome to 40 pregnancies associated with type 1 diabetes. RESULTS: Women with type 2 diabetes are older (32 +/- 5 vs. 27 +/- 5, P = 0.003), more obese (body mass index: 28.3 +/- 4.8 vs. 22.8 +/- 5.5, P < 0.001) than women with type 1 diabetes. Their pregnancy usually is not planned (10% vs. 55%, P < 0.001). HbA1c during organogenesis is above 8% in 46.6% of type 2 vs. 26.4% of type 1 (P < 0.001). Compared with data obtained in the general population, a fivefold increase in preterm delivery (26.3% vs. 4.7%), a sevenfold increase in perinatal mortality (5% vs. 0.7%) and congenital malformations (15.8% vs. 2.2%) are observed. These results are similar to those obtained in type 1. In planned pregnancy, HbA1c during organogenesis is under 7% with no perinatal death and no major congenital malformation. DISCUSSION AND CONCLUSION: Pregnancy complicated by type 2 diabetes is a high-risk one, as much as in type 1 diabetes. Efficient pre-pregnancy care needs to be strongly encouraged in women with type 2 diabetes who also display many risk factors for adverse fetal outcome.

[Gynecologic laparoscopy and abdominal scars: what approach for the peritoneal cavity?]. / Coeliochirurgie gynécologique et ventre cicatriciel: quel abord de la cavité péritonéale?

To identify and discuss the advantages of the different methods of entry into the peritoneal cavity during gynecological laparascopy in patients who have previously undergone abdominal surgical procedures. Literature review comparing the strengths of each method of entering the peritoneal cavity during gynecological laparoscopic procedures. Adhesions increase the risks of access into peritoneal cavity during laparoscopy. Many techniques or safety rules have recently been described or re-evaluated as an alternative to using the traditional combination "Veress needle and blind introduction of the first trocar". The most relevant were the "open laparoscopy", the use of optical trocar, the double laparoscopy and the use of microlaparoscope. There remains no clear conclusion regarding the optimal form of laparoscopic entry in high risk patients. Relevant data emphasizes that critical to the surgeon's choice of technique is the immediate ability to recognize accidental injury and the capacity to avoid the scarred area. According to the literature review on the procedures used for entering the peritoneal cavity in high risk patients, we conclude that double laparoscopy may indeed be an underused procedure in such cases.

Delayed delivery of second twin: a multicentre study of 35 cases.

OBJECTIVE: The aim of this study was to conduct a statistical analysis to determine the outcome of conservative treatment after delivery of a first fetus in multiple pregnancy and thus define new prognostic factors. STUDY DESIGN: Multicentre retrospective study involving 12 centers over a 10-year period. RESULTS: Twenty-eight twin pregnancies and seven triplet pregnancies which were managed conservatively. In twin pregnancies, 79% of the delayed-delivery fetuses survived; only 7% of the first delivered fetuses survived. The mean interval between deliveries was 47 days. No statistical difference was found concerning cerclage, antibiotic therapy, tocolysis and hospitalization. Earlier delivery of the first twin and premature rupture of membranes for the second twin were significantly related to a longer interval between deliveries. CONCLUSION: Delayed delivery in multifetal pregnancies can be successful if there are no contraindications and these pregnancies are managed in a tertiary perinatal center. Publications limited to successful cases have undoubtedly introduced some bias in assessment.

Histological features and HLA class II alleles in hepatitis C virus chronically infected patients with persistently normal alanine aminotransferase levels.

OBJECTIVE: A significant proportion of individuals with chronic hepatitis C virus (HCV) infection have persistently normal alanine aminotransferase (ALT) levels. Although data are controversial, such patients usually have weaker histological damage and a lower progression rate of fibrosis. The aims of this study were: (1) to compare demographic, virological, and histological parameters of HCV patients with normal ALT values with those of HCV patients with elevated ALT levels; and (2) to determine whether HLA class II alleles contribute to the persistence of normal ALT levels in HCV patients. PATIENTS AND METHODS: Eighty three patients with chronic HCV infection and persistently normal ALT values (group 1) and 233 patients with chronic HCV infection and elevated ALT levels (group 2) were studied. Histological features were expressed using Knodell and Metavir scores. HLA DRB1* and DQB1* genotyping was performed using hybridisation with sequence specific oligonucleotides after genomic amplification. The kappa2 and Fisher's exact tests were used to compare discrete variables and phenotype frequencies between the two groups, and Wilcoxon's test was used for continuous variables. A multivariate logistic regression model was used to determine which variables predicted normal ALT values. RESULTS: ALT levels were correlated with the severity of liver damage. In group 1, 93% of patients had an F0 or F1 Metavir index of fibrosis compared with 47% of patients in group 2 (p<0.001). A longer duration of infection (p<0.001) and increased DRB1*11 phenotype frequency (pc=0.03) were observed among patients with normal ALT. The two groups did not differ with regard to the mode of contamination or viral genotype. After logistic regression, young age (p=0.0008), female sex (p=0.01), long duration of infection (p=0.0001), and HLA DRB1*11 (p=0.050) were more strongly associated with persistence of normal ALT. CONCLUSIONS: Our study confirms that patients with chronic hepatitis C and normal ALT levels have less severe liver disease than those with elevated ALT levels. This particular biochemical outcome may be explained, at least in part, by host immunogenetic factors such as the presence of HLA-DRB1*11.

[Update on maternal-fetal infections by hepatitis C, HIV and cytomegalovirus]. / Mise au point sur les infections materno-foetales par l'hépatite C, le V.I.H. et le cytomégalovirus.

Maternal infections with hepatitis C virus, human cutomegalovirus and HIV and their management problems continue to raise concern in obstetrics. What should we recommend to decrease the incidence of hepatitis C virus congenital infection? We know that congenital human cytomegalovirus infection can lead to major neurological disease with sensorineuronal loss. The current lack of trusted prognostic elements to predict impact on the infected fetus makes any prenatal diagnosis questionable. Should we thus track the initial maternal antibody status and the newborn infection? For the last 10 years, HIV mother-to-infant transmission has decreased from 25% to less than 3%. The new problem is how to answer the more and more frequent request for pregnancy from an infected woman. The treatment must be adapted to the pregnancy in order to reduce the risks for the mother and the infant. All these questions emphasize the problems of viral infection which will require answers in the years to come.

[Diagnosis of an ectopic pregnancy on a cesarean scar]. / Diagnostic d'une grossesse ectopique sur cicatrice de césarienne.

We report the diagnostic and therapeutic debate raised by an ectopic pregnancy on a cesarean scar. There were three phases. The first was to differentiate between an ongoing abortion and an ectopic pregnancy on a cesarean scar. The second was to determine whether the tissue was a mass of persistent trophoblasts or an invasive mole. Finally to determine the nature of a residual mass after chemotherapy and normalization of the beta CG level.

Developmental mucin gene expression in the human respiratory tract.

The epithelial surface of the respiratory tract is coated with a protective film of mucus secreted by epithelial goblet and submucosal gland cells. Histology of the airway mucosa and composition of secretions during the second trimester of fetal life are known to differ from the normal adult in that these secretions show similarities with those of hypersecretory disorders. To provide information regarding cell-specific expression of mucin genes and their relation to developmental patterns of epithelial cytodifferentiation, we studied the expression of eight different mucin genes (MUC1-MUC4, MUC5AC, MUC5B, MUC6, MUC7) in human embryonic and fetal respiratory tract using in situ hybridization. These investigations demonstrated that MUC4 is the earliest gene expressed in the foregut at 6.5 wk, followed by MUC1 and MUC2 from 9. 5 wk of gestation in trachea, bronchi, epithelial tubules, and terminal sacs before epithelial cytodifferentiation. In contrast, MUC5AC, MUC5B, and MUC7 are expressed at later gestational ages concomitant with epithelial cytodifferentiation. During this developmental stage, MUC1 and MUC4 mRNAs are located in goblet and ciliated cells, whereas MUC2 mRNAs are located in basal and goblet cells. MUC5AC expression is confined to goblet cells. In the submucosal glands, MUC2 mRNAs are located in both mucous and serous cells, whereas MUC5B and MUC7 mRNAs are expressed in mucous and in serous cells, respectively. These data suggest distinct developmental roles for MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC7 in the elongation, branching, and epithelial cytodifferentiation of the respiratory tract during ontogenesis. Distinct patterns of mucin gene expression are also likely to play an important role in regulating appropriate epithelial cell proliferation and cytodifferentiation in adult airway mucosa as it is indicated by aberrant expression in hypersecretory disorders.

[Ovarian mucinous tumor of gastric and intestinal type associated with Peutz-Jeghers syndrome: in situ hybridization study of apomucin gene transcripts]. / Tumeur mucineuse ovarienne de type gastrique et intestinal associée au syndrome de Peutz-Jeghers; étude en hybridation in situ des transcrits des gènes d'apomucines.

Occurrence of mucinous tumors is favored by Peutz-Jeghers syndrome (PJS). A case of bilateral ovarian mucinous tumor associated with ovarian mature teratoma occurring in a 22-year-old woman with PJS was reported. Tumor cells included 5 cell types: tall columnar mucinous pale cells with neutral mucins; goblet cells with acidic nonsulfated mucins; non mucinous columnar cells; mucinous cuboidal cells lining small glands; endocrine cells. Expression of the MUC2, MUC3, MUC5AC and MUC6 genes was demonstrated by in situ hybridization according to cell type. Some atypia and numerous mitotic figures were observed in basal glands. Diagnosis was ovarian borderline mucinous tumor with gastric and intestinal phenotype associated with PJS.

[Ultrasonic diagnosis of placenta percreta. Apropos of a case with hemorrhagic complication]. / Diagnostic ultrasonore du placenta percreta. A propos d'une complication hémorragique.

Placenta percreta is a rare but severe disease, which is more and more frequent. The reported case shows that diagnosis can be made with B mode and color Doppler ultrasonography. Extension of high-vascularized placenta to the myometrium, abnormal placental-subplacental complex and vascular flow through the myometrium were suggestive of the diagnosis. Early diagnosis should decrease mortality and morbidity.

[Uterine leiomyosarcomas: a surprising pathology. Review of the literature. Six case reports]. / Léiomyosarcomes utérins: une surprise anatomopathologique. Revue de la littérture. A propos de 6 observations.

OBJECTIVE: The aim of this study was to determine the clinical features and laboratory tests which define a population with a high risk of leiomyosarcoma. METHOD: A retrospective analysis of 660 hysterectomies performed between 1989 and 1994 was conducted. There were 414 cases of leiomyoma and 6 leiomyosarcomas (1.4%). RESULTS: The indication for hysterectomy was complication of fibromyomatous uterus in all cases. Diagnosis of leiomyosarcoma was never suspected before surgery and the pathology examination. Complimentary radiotherapy was given in 2 patients among the 6 with leiomyosarcoma. Mean survival was 35 months. There were no cases of recurrence or metastasis. None of the laboratory tests performed provided clues to diagnosis. CONCLUSION: Physicians should be aware of possible misdiagnosis of a leiomyosarcoma when proposing medical treatment of uterine fibroma.

[Myasthenia and pregnancy. Two case reports]. / Myasthénie et grossesse. A propos de 2 observations.

OBJECTIVE: Assess obstetrical care in rare cases of pregnant women with myasthenia. METHOD: Two personal cases led to a brief recall of the disease process and the literature and an assessment of proposed optimal care. RESULTS: Both pregnancies were carried to term without aggravation of the myasthenia. According to the data in the literature, pregnancy has a variable effect on myasthenia (1/3 stability, 1/3 improvement, 1/3 aggravation). The risk of decompensation during expulsion is great and the patient's efforts should be limited, although cesarian section is not required (excepting classical surgical indications). Peridural anaesthesia is not required (excepting classical surgical indications). Peridural anaesthesia is recommended because it reduces patient fatigue and facilitates instrumental extraction. Nursing is authorized except in case of severe episodes with a major rise in antibody levels. Pre-eclampsia was reported in only 5 cases: both maternal and fetal risk is high in such cases requiring intensive care. Fetal risks include rare neuro-muscular disease in which prognosis is poor and in 15 to 20% of the cases, neonatal myasthenia. CONCLUSION: Myasthenia is an autoimmune disease rarely occurring in young women of childbearing age. Care for pregnant women with myasthenia requires close collaboration between the different specialists.

Does elective sclerotherapy improve the efficacy of long-term propranolol for prevention of recurrent bleeding in patients with severe cirrhosis? A prospective multicenter, randomized trial.

We conducted a prospective, multicenter, randomized trial to compare the efficacy of sclerotherapy plus propranolol with that of propranolol alone in the prevention of recurrent gastroesophageal bleeding in severely cirrhotic patients. For 2 yr (1987 to 1988) 131 patients (96% of whom were alcoholic) with Child-Pugh class B or C cirrhosis (56% were class B and 44% were class C) were randomly assigned to one of our two treatment groups after cessation of variceal bleeding, without hemostatic sclerosis, and were observed for at least 2 yr. Treatment observance was good in 89% of cases; alcohol withdrawal was observed in 62% of cases. Sclerotherapy was performed weekly with 1% polidocanol, and variceal obliteration was obtained in 83% of cases, in a mean number of four sessions. The cumulative percentages (expressed as mean +/- S.D.) of recurrent bleeding at 2 yr were 42% +/- 6% for propranolol plus sclerotherapy and 59% +/- 6% for propranolol alone (a nonsignificant difference). Twenty-eight patients from the propranolol group but only 12 patients from the propranolol-plus-sclerotherapy group had recurrent bleeding from esophageal variceal rupture (p less than 0.01). The total number of blood units per patient with recurrent bleeding was slightly but not significantly more important in the propranolol group (8 +/- 7) than in the propranolol-plus-sclerotherapy group (5 +/- 5; p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Ileal compensation for age-dependent loss of jejunal function in rats.

Adaptive responses of brush border hydrolases and crypt cell proliferation were measured in the jejunum and ileum of 4-mo-old adult and 28-mo-old senescent male Wistar rats. Responses were measured after rats were deprived of food and then refed with a normoprotein diet (17% protein) or an isoenergetic high protein diet (70% protein). The young rats deprived of food then refed for 18 h with the high protein diet showed better body weight recovery than did old animals. Withholding food for 48 h induced a more pronounced drop of sucrase activity in the intestine of the old rats relative to young rats. Refeeding the high protein diet caused a better recovery of sucrase activity in the jejunum of young rats relative to senescent rats. In the aged animals, sucrase activity in the jejunum remained significantly lower after refeeding both diets. Compared with nourished controls, aged rats showed enzyme activity to be completely restored in the ileum. The high protein diet increased aminopeptidase activity in the jejunum and ileum of young rats, in contrast to the senescent rats in which the increase of enzyme activity was restricted to the ileum. In the jejunum of aged rats, the cell migration rate from crypt base to villus tip was reduced after refeeding, but no age-related changes were observed in the ileum. Our results indicate that the jejunum of senescent rats exhibits reduced adaptive capacities that may be partly compensated by enhanced ileal functions.

Regional cardiac adrenergic function using I-123 meta-iodobenzylguanidine tomographic imaging after acute myocardial infarction.

The effect of acute myocardial infarction (AMI) on regional cardiac adrenergic function was studied in 27 patients mean +/- standard deviation 10 +/- 4 days after AMI. Regional adrenergic function was evaluated noninvasively with I-123 meta-iodobenzylguanidine (MIBG) using a dedicated 3-detector tomograph. Four hours after its administration, there was reduced MIBG uptake in the region of infarction, 0.38 +/- 0.31 counts/pixel/mCi x 103 compared with 0.60 +/- 0.30 counts/pixel/mCi x 103 and 0.92 +/- 0.35 counts/pixel/mCi x 103 in the zones bordering and distant from the infarct area, respectively, p less than 0.001. In all patients, the area of reduced MIBG uptake after 4 hours was more extensive that the associated thallium-201 perfusion defect with defect scores of 52 +/- 22 and 23 +/- 18%, respectively, p less than 0.001. After anterior wall AMI, the 4-hour MIBG defect score was 70 +/- 13% and the degree of mismatch between myocardial perfusion and MIBG uptake was 30 +/- 9% compared with 39 +/- 17 and 21 +/- 17% after inferior AMI, p less than 0.001 and p = 0.016, respectively. The 4-hour MIBG defect score correlated inversely with the predischarge left ventricular ejection fraction, r = -0.73, p less than 0.001. Patients with ventricular arrhythmia of greater than or equal to 1 ventricular premature complexes per hour, paired ventricular premature complexes or ventricular tachycardia detected during the late hospital phase had higher 4-hour MIBG defect scores, 62.5 +/- 15.0%, than patients with no detectable complex ventricular ectopic activity and a ventricular premature complex frequency of less than 1 per hour, 44.6 +/- 23.4%, p = 0.036.(ABSTRACT TRUNCATED AT 250 WORDS)

[Consequences of hyperglycemia on glucose and nitrogen metabolism in liver cirrhosis. A study using a hyperglycemic clamp]. / Conséquences de l'hyperglycémie sur le métabolisme glucidique et azoté dans la cirrhose. Exploration par une épreuve de clamp hyperglycémique.

To study the consequences of hyperglycemia on glucose and nitrogen metabolism in cirrhosis, an hyperglycemic clamp was performed in 5 cirrhotic patients and 5 normal controls during two subsequent periods of 90 min, at 7.78 and then at 13.89 mmol/l. In the first period, glucose infusion and metabolic clearance rates were decreased in cirrhotics vs controls (p less than 0.05). In the second period, this difference between the two groups disappeared because of a more important enhancement in cirrhotics. Baseline plasma C peptide levels and those during hyperglycemia were the same during hyperglycemia in both groups, but plasma insulin level rose more in cirrhotics (p less than 0.05). Baseline insulin secretion following IV glucagon was reduced in cirrhotics vs controls (p less than 0.05), but became normal in the hyperglycemic state. Plasma glucagon levels were enhanced at all times in cirrhotics vs controls (p less than 0.01), but dropped more in cirrhotics vs controls (p less than 0.05). Insulin responsiveness, defined as the "glucose consumption: plasma insulin concentration" ratio was reduced in cirrhotics at 7.78 mmol/l (p less than 0.01), but was the same in both groups at 13.80 mmol/l because of a more important enhancement in cirrhotics, reflecting an improvement of insulin action probably at the post-receptor level and of non-insulin-mediated glucose transport. Hyperglycemia induced a drop in plasma concentration and muscular release of all aminoacids, excepted alanine, between the basal state and the end of the study. Aminoacid concentration rose only in cirrhotics, without any change in muscular output. In the same time, blood ammonia level rose only in cirrhotics, without reduction of muscular uptake.(ABSTRACT TRUNCATED AT 250 WORDS)