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Over the past 15 years, there have been significant advances in the treatment of acute and chronic medical consequences of stroke in childhood. Given high rates of survival in pediatric stroke, practitioners are tasked with treating the ongoing motor and neuropsychological sequelae in patients over the course of their development. This article provides a review of the current literature on neuropsychological outcomes in pediatric stroke, including intelligence, academics, language, visual-spatial skills, attention, executive functions, memory, and psychosocial function. Recent developments in functional neuroimaging are discussed, with a particular focus on language outcomes. We further review the current research on cognitive and behavioral rehabilitation and introduce intervention models in pediatric stroke. In the final section, we discuss future directions for clinical practice and research in pediatric stroke.

Children with perinatal stroke are at increased risk for developmental language disorders, learning difficulties, and other mental health conditions. However to date, autism (ASD) prevalence in this group has not been reported. Given that early identification of ASD is essential to promoting optimal outcomes, our goal was to establish prevalence of ASD in children with perinatal stroke.A prospectively enrolled, single-center stroke registry maintained at our institution since 2005 was queried for all potentially eligible patients with a history of perinatal stroke. Information regarding stroke features, ASD diagnosis/concern, intellectual disability/global developmental delay, cerebral palsy/hemiparesis, epilepsy, and language disorder were collected via retrospective chart review from electronic health records.311 children were identified, of which 201 complete records were analyzed. Twenty-three cases were formally diagnosed with ASD (11.4%). First concerns were noted in toddlerhood (Mage = 2.66 years), yet the average age of diagnosis was 6.26 years. Children with ASD were more likely to have earlier diagnoses of intellectual disability/global developmental delay or a mixed receptive-expressive language disorder (Children with perinatal stroke have an increased prevalence of ASD (11.4%) than in the general population. ASD concerns arise at a similar age as the general population, yet ASD is diagnosed almost two years later than the general population and 3.60 years after first concerns present. Co-occurring neurological conditions are common. Clinicians must be aware of increased prevalence and implement screening as part of routine care for all pediatric patients with perinatal stroke.

Background Safety of HPV vaccines is still in question due to reports of autoimmune diseases (ADs) following HPV immunization. Objectives To assess the risk of ADs associated with HPV vaccination of female adolescents/young adults in France. Methods Systematic prospective case-referent study conducted to assess the risks associated with real-life use of HPV vaccines. Cases were female 11–25 years old with incident ADs [central demyelination/multiple sclerosis (CD/MS), connective tissue disease (CTD), Guillain-Barre syndrome (GBS), type-1 diabetes (T1D), autoimmune thyroiditis (AT), and idiopathic thrombocytopenic purpura (ITP)]. Cases were consecutively and prospectively identified at specialized centers across France (2008–2014) and individually matched by age and place of residence to referents recruited in general practice. Risk was computed using multivariate conditional logistic regression models adjusted for family history of ADs, living in France (north/south), co-medications and co-vaccinations. Results With a total of 478 definite cases matched to 1869 referents, all ADs combined were negatively associated to HPV vaccination with an adjusted odds ratio of 0.58 (95% confidence interval: 0.41–0.83). Similar results were obtained for CD/MS, AT, CT, and T1D, the last two not reaching statistical significance. No association was found for ITP and GBS. Sensitivity analyses combining definite and possible cases with secondary time window showed similar results. Conclusion Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs.

Children with perinatal arterial ischemic stroke (PAIS) have increased rates of attention and executive functioning (EF) weaknesses. Research in other pediatric disorders has documented poor consistency between parent report of these skills and performance-based measures. We compared these data sources in children with PAIS. Forty full-term (≥37 weeks) children ages 3-16 (median = 7.2 years; 58% male) with PAIS completed neuropsychological testing and composite scores were created for seven attention and EF domains (Processing Speed; Attention; Working Memory; Verbal Retrieval; Inhibitory Control; Flexibility/Shifting; Planning). Parents completed "real-world" functioning questionnaires (ADHD Rating Scale-IV, BRIEF). Correlational analysis were used to compare parent and performance measures. Correlations between ADHD Rating Scale-IV scores and the performance-based Attention and Inhibition composite scores were nonsignificant. Significant negative correlations were found between the BRIEF GEC and performance-based Verbal Retrieval and Processing Speed composites, but remaining GEC/composite comparisons were nonsignificant. Analyses between parent report BRIEF index scores and the corresponding performance-based domain identified one significant negative correlation between the BRIEF Working Memory Index and the Working Memory composite score. While children with PAIS demonstrate difficulties in attention and EF on both parent report and performance measures, little significance was found in comparisons of these two types of measures. There may be several explanations for this dissociation: measures assessing different aspects of the same underlying construct; performance-based measures lacking ecological validity; and parents underestimating/underreporting their child's deficits. Thus, multiple sources of informant and performance data are necessary to make more accurate conclusions about functioning in these domains.

Peripartum cardiomyopathy also known as cardiomyopathy associated with pregnancy, is rarely a cause of heart failure, it affects pregnant or puerperal women in the first 5 months. Although the first case reported was in 1849, it was recognized until 1930. In 2010 the European Society of Cardiology Working Group on peripartum cardiomyopathy, defined this pathology as an idiopathic cardiomyopathy that affects pregnant women between the third trimester and five months after delivery. Characterized by a left ventricular failure with an ejection fraction of ≤45% and an end-diastolic dimension ≥2.7 cm/m2 , in absence of an identifiable cause of heart failure.We report a case of a 39-year-old patient, diagnosed with a peripartum cardiomyopathy in the early puerperium, characterized by hypertension, tachycardia, dyspnea and oxygen desaturation. The transesophageal echocardiogram reported heart failure, a hypokinetic left ventricle and a ventricular failure with an ejection fraction40%. We could not identify an other cause to justify heart failure. Multidisciplinary management was administered successfully.The importance of this article relies in the fact that eripartum cardiomyopathy has a high morbidity and mortality. The impact of this pathology is unknow in our country. Here we establish and discuss the multidisciplinary management held in our hospital with this specific patient in order to improve the prognosis on future occasions.

The objective of the study was to compare executive functioning (EF) profiles across several pediatric medical conditions and explore the influence of age of diagnosis and evaluation. A retrospective, cross-sectional study of 734 children aged 5 to 18 years was conducted across five medical groups (brain tumor, leukemia [ALL], epilepsy [EPI], neurofibromatosis type 1 [NF1], and ornithine transcarbamylase deficiency [OTC-D]), attention deficit hyperactivity disorder (ADHD) controls, and matched healthy controls. We compared groups across the scales of a parent-completed Behavior Rating Inventory of Executive Functioning (BRIEF) using a repeated measures analysis of variance (ANOVA). Separate ANOVAs were conducted to look at age factors. The results showed that the ADHD group differed from all other groups and had the highest level of reported EF problems. The NF1 and OTC-D groups differed significantly from the healthy comparison group for overall EF problems, while the EPI and cancer groups did not. Working memory was the most elevated scale across medical groups, followed by plan/organize. Children with medical disorders were two to four times more likely than healthy controls to have clinically significant problems in several EF domains. There was a main effect for age at diagnosis and age at evaluation. A subset of children with medical disorders were found to have parent-reported EF difficulties, with particular vulnerability noted in working memory and organizational/planning skills. This has relevance for the development of interventions that may be helpful across disorders. Children with particular diagnoses and earlier age of diagnosis and evaluation had greater reported EF problems.

Cobalamin C (CblC) disease is the most common inborn error of cobalamin metabolism and recent data has indicated a higher prevalence among children of Hispanic heritage in particular. The purpose of this study was to (a) describe the neuropsychological characteristics of a pilot sample of Hispanic children with CblC disease and (b) explore potential differences in outcome based on underlying genetic mutation(s) and biochemical levels. Six Hispanic children (ages 2-10) diagnosed with CblC disease through newborn screening (NBS) underwent neuropsychological evaluation with a bilingual examiner. Biochemical levels and underlying mutation(s) were obtained through medical records. The overall sample performed below normative expectations across neuropsychological domains, including general cognition, adaptive functioning, language ability, and visual-motor integration. Underlying mutations and associative clinical phenotypes were found to significantly predict general cognitive abilities, while plasma methionine and Hcy at the time of diagnosis were significantly correlated with language outcomes. Despite limited sample size, results indicate that Hispanic children with CblC disease detected through NBS and treated early experience neuropsychological deficits even when treated with current standard treatments. However, consistent with prior research in non-Hispanic children with CblC disease, underlying mutations and early biochemical levels may predict better outcomes in this population as well.

Background Children with perinatal arterial ischemic stroke (PAIS) are at risk for later neurocognitive and behavioral deficits, yet the clinical predictors of these outcomes are understudied. We examined the influence of clinical and infarct characteristics on attention and executive functioning in children following PAIS. Methods Forty children born at term (≥37 weeks' gestation) with PAIS (28 with neonatal arterial ischemic stroke and 12 with presumed PAIS) underwent a comprehensive neuropsychological battery at age three to 16 years (median age 7.2 years; 58% male) to assess attention and executive functioning. Parents also completed questionnaires regarding real-world functioning. Clinical variables including perinatal stroke subtype, infarct characteristics (location, laterality, and volume), and the presence of comorbid epilepsy were ascertained from the medical record. Results Presumed PAIS, larger infarct volume, and comorbid epilepsy negatively influenced the performance on attention and executive functioning measures. These clinical variables were also associated with greater functional problems on parent reports, including a higher frequency of attention-deficit/hyperactivity disorder symptoms and greater difficulties in some subdomains of executive functioning. Infarct location and laterality were not associated with performance measures or parental report of functioning. Conclusion Although all children with PAIS are at risk for later deficits in attention and executive functioning, those with presumed PAIS, larger infarct size, and comorbid epilepsy appear to be the most vulnerable. As they approach and reach school age, these children should undergo neuropsychological assessment to ensure timely implementation of therapeutic interventions and behavioral strategies.

Perinatal arterial ischemic stroke (PAIS) is a form of childhood stroke; the majority of those affected experience neurologic sequelae, including motor, language and neurocognitive impairments. This study examines the attention and executive functioning (EF) profiles of children following PAIS, as well as the impact of age and sex. In this single-center cross-sectional study, 40 children aged 3 to 16 years (median age 7.2 years; 58% male) who have suffered a PAIS underwent a comprehensive neuropsychological battery to assess attention and EF. Parents completed behavioral questionnaires regarding real-world functioning. Composite scores were calculated for seven attention and EF domains (Attention, Working Memory, Verbal Retrieval, Inhibitory Control, Flexibility/Shifting, Planning/Organization, and Processing Speed). The results for all measured domains of attention and EF are significantly lower in the participants compared to the normative samples (p .001), with the exception of Working Memory. However, increasing difficulty with Working Memory is associated with developing age. Older age at time of testing is also associated with a higher incidence of clinically-elevated attention deficit hyperactivity disorder (ADHD) symptoms. Sex is not associated with performance measures or parental report of functioning. The participants demonstrate mild-to-moderate attention and EF impairment compared to the normative population. Clinicians, families, and educators should be informed about the neurocognitive sequelae of PAIS and the need for close developmental surveillance in this population to identify vulnerable children and initiate appropriate therapeutic interventions in a timely fashion.

The current pilot study examined functional magnetic resonance imaging (fMRI) activation in children with mild traumatic brain injury (mTBI) during tasks of working memory and inhibitory control, both of which are vulnerable to impairment following mTBI. Thirteen children with symptomatic mTBI and a group of controls completed a version of the Tasks of Executive Control (TEC) during fMRI scanning. Both groups showed greater prefrontal activation in response to increased working memory load. Activation patterns did not differ between groups on the working memory aspects of the task, but children with mTBI showed greater activation in the posterior cerebellum with the addition of a demand for inhibitory control. Children with mTBI showed greater impairment on symptom report and “real world” measures of executive functioning, but not on traditional “paper and pencil” tasks. Likewise, cognitive testing did not correlate significantly with imaging results, whereas increased report of post-concussive symptoms were correlated with increased cerebellar activation. Overall, results provide some evidence for the utility of symptom report as an indicator of recovery and the hypothesis that children with mTBI may experience disrupted neural circuitry during recovery. Limitations of the study included a small sample size, wide age range, and lack of in-scanner accuracy data. (JINS, 2011, 17, 1143–1152)

Hypothalamic-pituitary (HP) sarcoidosis has 2 main endocrine manifestations: diabetes insipidus and hyperprolactinemia. We conducted the current study to investigate pituitary dysfunction and perform imaging of the HP area in patients both immediately following diagnosis and after treatment. The study included 6 men and 3 women, with a mean age of 30 years at the onset of sarcoidosis. All patients had both hormonal and magnetic resonance imaging (MRI) HP disorders. All patients had anterior pituitary dysfunction, 7 of them with associated diabetes insipidus. Nine patients had gonadotropin deficiency and 3 had hyperprolactinemia. MRI revealed infundibulum involvement in 5 patients, pituitary stalk thickness abnormality in 5, and involvement of the pituitary gland in 2, associated with other parenchymal brain or spinal cord lesions in 6 patients. All patients had multiple localizations of sarcoidosis, and 5 had histologically confirmed sinonasal localizations. Mean follow-up of the HP disorder was 7.5 years. All patients received prednisone. There was no correlation between the number of hormonal dysfunctions and the area of the HP axis involved as assessed by MRI. Although corticoid treatment was associated with a reduction of radiologic lesions, only 2 patients had partial recovery of hormonal deficiency. In conclusion, hormonal deficiencies associated with HP sarcoidosis frequently include hypogonadism (all patients) and to a lesser degree diabetes insipidus (7 of 9 patients). MRI abnormalities improved or disappeared in 7 cases under corticosteroid treatment, but most endocrine defects were irreversible despite regression of the granulomatous process. Most cases presented with multivisceral localizations and an abnormally high proportion of sinonasal localizations.

Moderate and severe traumatic brain injuries (TBI) have been known for some time to significantly impact daytime behavioral and adaptive functioning. In recent years, there also has been increasing appreciation of the nocturnal effects of TBI. Sleep problems in adults after a TBI can persist several years post-injury, and include nightmares and dyssomnias that can present as inadequate sleep or as excessive sleep propensity due to poor sleep quality (Bryant, Marosszeky, Crooks, & Gurka, 2000; Masel, Scheibel, Kimbark, & Kuna, 2001; Thaxton & Myers, 2002). As these authors have noted, the etiology of such sleep problems may include pain or discomfort, damage to neural circuits important in the sleep process, and emotional trauma. All of these potential contributors to sleep pathology can occur in childhood TBI, yet very little relevant research has been published. A few studies have identified vaguely defined sleep disturbances after childhood head trauma (Farmer, Singer, Melleits, Hall, & Charney, 1987; Hooper et al., 2004; Nakayama, Gardner, & Rogers, 1990; Pillar et al., 2003). However, sleep problems may follow a wide range of traumatic injuries, including orthopedic injuries (OI) (Kaufman et al., 2001). Moreover, no study has systematically examined sleep across more severe grades of pediatric TBI, despite neuropsychological and behavioral evidence of worse outcomes in the most severely injured children (Yeates et al., 2002, 2004). Finally, the time course of post-injury sleep problems is unknown, as group studies have rarely followed children for more than a few months post-injury. The lack of research on pediatric sleep following TBI is noteworthy in light of evidence of an interrelationship between sleep pathology and the daytime functioning of children and their families. Children who have undergone experimental sleep restriction or have naturally occurring dyssomnias have elevated rates of daytime behavioral disturbances (Blunden & Beebe, 2006). Sleep pathology in children also is a major source of parent and family stress (Mindell & Owens, 2003). Insofar as sleep pathology following pediatric TBI contributes to diminished motivation, caregiver distress, and cognitive and behavioral disturbances, it may pose a significant threat to rehabilitation efforts and functional recovery. In this brief report, we analyze parent-reported sleep data that were collected in the course of a larger prospective study of the neuropsychological and family impact of moderate or severe pediatric TBI. Based upon the adult literature, we hypothesized that children who sustained a TBI, especially a severe TBI, would be reported to display more post-injury sleep problems than children who sustained only OIs. This study also examined the time course of post-injury sleep concerns up to several years post-injury, although we did not have specific hypotheses with regard to change over time.

International audience; Glutamic acid decarboxylase antibodies (GAD-abs) are an immunological factor involved in type 1 diabetes and other diseases involving the central nervous system. This report is of a patient with type 1 diabetes and a rare case of non-paraneoplastic limbic encephalitis mediated by anti-GAD65 antibodies that improved with the use of immunosuppressive drugs.

This study examined the effect of traumatic brain injury (TBI) in young children on sleep problems and the relationship of sleep problems to neuropsychological and psychosocial functioning. Participants were drawn from an ongoing longitudinal study of injury in young children recruited from 3 to 6 years of age. They constituted three groups: orthopedic injury (OI; n=92), complicated mild/moderate TBI (mTBI; n=55); and severe TBI (sTBI; n=20). Caregivers completed the Children's Sleep Habits Questionnaire (CSHQ), as well as ratings of behavioral adjustment, adaptive functioning, and everyday executive function at 1, 6, 12, and 18 months postinjury. Retrospective ratings of preinjury sleep and psychosocial functioning were obtained at the initial assessment. Children completed neuropsychological testing at all occasions. Children with complicated mTBI demonstrated more total sleep problems than children with OI at 6 months postinjury, but not at 12 or 18 months. Children with sTBI displayed more bedtime resistance and shorter sleep duration than those with complicated mTBI or OI at several occasions. Across groups, total sleep problems predicted more emotional and behavioral problems and worse everyday executive function as rated by parents across follow-up occasions. In contrast, sleep problems were generally not related to neuropsychological test performance. The results suggest that young children with TBI demonstrate more sleep problems than children with injuries not involving the head. Sleep problems, in turn, significantly increase the risk of poor psychosocial outcomes across time, but are not associated with worse neuropsychological test performance.

Idiopathic CD4 T lymphocytopenia (ICL) is a rare and severe condition with limited available data. We conducted a French multicenter study to analyze the clinical and immunologic characteristics of a cohort of patients with ICL according to the Centers for Disease Control criteria. We recruited 40 patients (24 female) of mean age 44.2 ± 12.2 (19–70) years. Patients underwent T-lymphocyte phenotyping and lymphoproliferation assay at diagnosis, and experiments related to thymic function and interferon (IFN)-γ release by natural killer (NK) cell were performed. Mean follow-up was 6.9 ± 6.7 (0.14–24.3) years. Infectious, autoimmune, and neoplastic events were recorded, as were outcomes of interleukin 2 therapy. In all, 25 patients had opportunistic infections (12 with human papillomavirus infection), 14 had autoimmune symptoms, 5 had malignancies, and 8 had mild or no symptoms. At the time of diagnosis, the mean cell counts were as follows: mean CD4 cell count: 127/mm3 (range, 4–294); mean CD8: 236/mm3 (range, 1–1293); mean CD19: 113/mm3 (range, 3–547); and mean NK cell count: 122/mm3 (range, 5–416). Most patients had deficiency in CD8, CD19, and/or NK cells. Cytotoxic function of NK cells was normal, and patients with infections had a significantly lower NK cell count than those without (p = 0.01). Patients with autoimmune manifestations had increased CD8 T-cell count. Proliferation of thymic precursors, as assessed by T-cell rearrangement excision circles, was increased. Six patients died (15%). CD4 T-cell count

Placenta accreta is recognized as a catastrophic disease in obstetrics. Diagnosed incidentally, it has been a rare disease in previous decades prior indiscriminate use of cesarean delivery. The World Health Organization has recently highlighted this disease as a new pandemic, which is directly related to patients who have two or more caesarean sections. Our country keeps high rates of caesarean section and therefore this problem will be increasing in diagnosis. It is necessary that medical units made ad hoc clinical guidelines, for prompt intervention in these cases. Early diagnosis should be given priority in women with these risk characteristics. With the advent of high-resolution sonography, specific images have been identified supporting the diagnosis during pregnancy; likewise, multidisciplinary treatments are especially of interest. The interventional radiology offers treatments semiconservative that have proven to reduce morbidity and mortality.

Influenza A H1N1 is an acute respiratory illness caused by a new strain of H1N1. Human influenza is a subtype of influenza Avirus, from the family of Orthomyxoviridae. This strain is the cause of new influenza pandemic declared by the World Health Organization in June, 2009. This paper reports the first case occurred in Mexico: a 39-year-old woman with a history of diabetes mellitus type 2 and obesity grade II, which suffered atypical and aggressive pneumonia positive to coronavirus. Patient died 98 hours after her admission to the hospital unit. Due to the clinical presentation of the case, the doctors sent samples to the Instituto Nacional de Diagnóstico y Referencia Epidemiológica that sent an aliquot of the National Center for Immunization and Respiratory Diseases of theAgency of Public Health in Canada, that reported positivity to influenza virus, and catalogued it as a new global strain called influenza A virus H1N1. The notice of 229E/NL63 coronavirus and its relationship to the recent outbreaks of avian influenza in humans and the clinical presentation of the case were the epidemiological circumstances that prevented the nation epidemiology system to establish global containment strategies to prevent the spread of this emerging infection. The consequence was the declaration of WHO pandemic alert level 6. Its behavior in pregnancy, reported by Assistant General Direction of Epidemiology in Mexico, has placed this infection as a risk factor for women.

International audience; OBJECTIVES: The aims of the study were to assess in patients with advanced HIV disease receiving antiretroviral therapy (ART) intensification with enfuvirtide (i) resistance at virological failure (VF), (ii) impact of baseline tropism on immunovirological response, and (iii) HIV-1 DNA tropism evolution during ART. METHODS: The ANRS 130 APOLLO randomized trial evaluated in naive patients the immunovirological impact of standard ART without (control arm) or with enfuvirtide. Tropism was determined on RNA and DNA by V3-loop sequencing interpreted using the Geno2Pheno algorithm. RESULTS: At baseline the median CD4 cell count was 30 cells/mm(3). Among the 170 patients assessable in this virological substudy, HIV-1 RNA tropism was as follows: 60% of viruses were R5 and 40% were R5X4/X4. HIV-1 DNA tropism was as follows: 54% were R5 and 46% were R5X4/X4. At week 24, 39% and 49% of patients experienced VF in the enfuvirtide and control arms, respectively. In the enfuvirtide arm, only resistance-associated mutations to enfuvirtide were detected. In the control arm, two patients displayed drug-resistant viruses at the time of VF. No impact of baseline tropism was observed on immunovirological response, regardless of the study arm. Among the 25 patients experiencing DNA tropism switch between baseline and week 24, 16 (64%) switched from R5 to R5X4/X4. These latter were mostly successfully suppressed patients receiving enfuvirtide and exhibiting poorer immunological response. CONCLUSIONS: Baseline RNA tropism had no impact on the immunovirological response. Drug resistance mutations were only detected for the fusion inhibitor. Finally, the mechanism of replenishment of the viral cellular reservoir with X4 viruses observed needs to be further analysed.

Urea cycle disorders (UCD) are rare inborn errors of metabolism which result from mutations in the genes encoding for one of six enzymes or two transporters necessary for normal function of the urea cycle and are characterized by hyperammonemia and life-threatening hyperammonemic crises1,2. Hyperammonemia-related neurologic injury ranges from lethal cerebral edema to mild or subclinical cognitive impairment among individuals with milder genetic defects3. Abnormalities in executive function, manifested by difficulty in goal setting, planning, monitoring progress and purposeful problem solving significantly impair day-to-day function among children with UCDs, even those with milder disease who present beyond the neonatal period4. Management of UCD patients typically involves dietary protein restriction, dietary supplements and, when dietary management alone is insufficient, sodium phenylbutyrate (NaPBA), which is the only approved drug (Ucyclyd Pharma, US trade name: BUPHENYL®, EU: AMMONAPS®) for treatment of UCDs2,5. Glycerol phenylbutyrate is an investigational agent being developed for UCDs 6,7,8. Like NaPBA, it contains phenylbutyric acid (PBA), a pro-drug that is converted via β-oxidation to the active moiety, phenylacetic acid (PAA), which conjugates with glutamine to form phenylacetylglutamine (PAGN). PAGN is excreted in the urine and mediates waste nitrogen excretion. Unlike NaPBA, glycerol phenylbutyrate consists of three molecules of PBA joined to glycerol in ester linkage that is hydrolyzed in the small intestine by pancreatic lipases to release PBA, contains no sodium, has minimal taste and no odor, and 17.4 mL contains the same amount of PBA as 40 tablets of NaPBA, the maximal approved daily dose 6,7,8. The development of glycerol phenylbutyrate for UCD, rare disorders with fewer than 500 patients in the US currently estimated to be treated with NaPBA, has involved a cooperative effort among investigators of the NIH-funded UCD Consortium, the National Urea Cycle Disorders Foundation and Hyperion Therapeutics 2,9,10. This report describes the results of the pivotal phase 3 study of glycerol phenylbutyrate for UCD, as well as short and long-term ammonia control and neurocognitive outcomes among a total of 91 UCD patients participating in four clinical trials.

Human immunodeficiency virus (HIV) infection and protease inhibitor (PI)-based antiretroviral treatment might increase large artery (aortic) stiffness compared with healthy untreated controls. To clarify the role of PI therapy in the progression of subclinical arteriosclerosis in patients with HIV, we investigated the impact of PI treatment on arterial stiffness.In our single-centre, cross-sectional study, normotensive male HIV patients free from overt cardiovascular disease received PI treatment (n=60) or no PI treatment (n=42). The PI group had a significantly higher pulse wave velocity (PWV) than the PI-free group (9.0 ± 1.4 vs. 8.1 ± 1.3m/s; P=0.016). There was a significant positive correlation between age and PWV in the PI-free group (R(2) 0.310; P0.0001) and, to a lesser extent, in the PI group (R(2) 0.181; P0.0001). PI treatment was associated with a significant increase in the adjusted slope of the curve relating age to PWV as compared with no PI treatment.In normotensive HIV patients, PI treatment significantly increases both aortic stiffness and the positive correlation between PWV and age. Aortic stiffness predicts cardiovascular mortality, thus these results provide new insight on the relationship between PI treatment, mechanical arteriosclerotic and cardiovascular risk.

The polymerase chain reaction (PCR) was used to detect hepatitis D (HD) viremia in patients infected with the human immunodeficiency virus (HIV). Nineteen (9%) of 206 such patients, unselected for liver disease or HBV infection, were found prospectively to be infected by HDV. Thirty-one anti-HIV-positive patients were studied by means of PCR, and the results were analyzed according to HDV and hepatitis B virus (HBV) serological status. HDV-PCR was positive in 5 patients. Two had detectable serum HDV antigen. Four patients had anti-HD IgM and IgG antibodies. All these patients were HBs antigen-positive, and 3 were HBV-DNA-positive. All the other patients were HDV-PCR-negative. Statistical analysis suggested more extensive liver damage and immunological impairment in HDV-PCR-positive patients. In this unselected HIV-infected population, HDV-RNA detection by PCR was restricted to HDV infected patients in whom 5/19 were positive. This test permitted direct diagnosis of HDV viremia and will be useful for monitoring HDV infection.

The Research Challenges in CNS Manifestations of Inborn Errors of Metabolism workshop was designed to address challenges in translating potential therapies for these rare disorders, and to highlight novel therapeutic strategies and innovative approaches to CNS delivery, assessment of effects and directions for the future in the treatment of these diseases. Therapies for the brain in inborn errors represent some of the greatest challenges to translational research due to the special properties of the brain, and of inborn errors themselves. This review covers the proceedings of this workshop as submitted by participants. Scientific, ethical and regulatory issues are discussed, along with ways to measure outcomes and the conduct of clinical trials. Participants included regulatory and funding agencies, clinicians, scientists, industry and advocacy groups.

The Urea Cycle Disorders Consortium (UCDC) was created as part of a larger network established by the National Institutes of Health to study rare diseases. This paper reviews the UCDC’s accomplishments over the first six years, including how the Consortium was developed and organized, clinical research studies initiated, and the importance of creating partnerships with patient advocacy groups, philanthropic foundations and biotech and pharmaceutical companies.

Inborn errors of urea synthesis lead to an accumulation of ammonia in blood and brain, and result in high rates of mortality and neurodevelopmental disability. The current study seeks to characterize the cognitive, adaptive, and emotional/behavioral functioning of children with Urea Cycle Disorders (UCDs). These domains were measured through testing and parent questionnaires in 92 children with UCDs (33 neonatal onset, 59 late onset). Results indicate that children who present with neonatal onset have poorer outcome than those who present later in childhood. Approximately half of the children with neonatal onset performed in the range of intellectual disability (ID), including a substantial number (~30%) who were severely impaired. In comparison, only a quarter of the late onset group were in the range of ID. There is also evidence that the UCD group has difficulties in aspects of emotional/behavioral and executive skills domains. In conclusion, children with UCDs present with a wide spectrum of cognitive outcomes. Children with neonatal onset disease have a much higher likelihood of having an intellectual disability, which becomes even more evident with increasing age. However, even children with late onset UCDs demonstrate evidence of neurocognitive and behavioral impairment, particularly in aspects of attention and executive functioning.

Sunitinib inhibits numerous tyrosine kinase receptors involved in tumor growth, angiogenesis, and metastatic invasion. It is indicated in case of metastatic renal carcinomas and gastrointestinal stromal tumors (GIST) resistant to imatinib. Prospective and retrospective studies have shown association between use of sunitinib and hypothyroidism affecting more than 50% of patients in some series. More amazing, was the non-visualisation of thyroid tissue evaluated with thyroid ultrasonography in two cases. Mechanisms of this side effect are not elucidated. Some studies have suggested destructive thyroiditis but no evidence of autoimmunity has been demonstrated. Anti angiogenic effect could be another hypothesis. Recently antithyroperoxidase activity of sunitinib has been demonstrated. Because hypothyroidism is easily accessible to treatment, screening of thyroid abnormalities is mandatory every three months to improve quality of life of these patients. This unique thyroid side effect of sunitinib with the non-visualisation of thyroid suggests a possible and promising antitumor activity in thyroid cancer.

Inhibin B is a direct marker of ovarian reserve and one of the earliest markers of ovarian aging. It has been used in assisted reproduction programs as a serum marker that can identify an altered follicular reserve and predict a good or poor response to the stimulation with exogenous gonadotropins.To correlate inhibin B levels with follicular response and quality of oocytes obtained through ovarian stimulation controlled in an in vitro fertilization cycle (IVFET), as well as relate it with variables such as: fertilization percentage and pregnancy rates.In a prospective and transversal study we included 71 patients that entered the IVFET program (February-April 2005). We determined inhibin B levels at the third day of the cycle and evaluated the follicular response and the oocyte quality during the ovarian stimulation, as well as fertilization and pregnancy rates. Statistical analysis was made with Spearman's and ANOVA tests.We observed a positive correlation between inhibin levels and quantity of developed follicles (0.457), number of captured oocytes (0.390), and quantity of metaphase II oocytes (0.324). We observed better oocyte quality in women with inhibin levels251 pg/ mL, and we considered that the ones that had levels50 pg/mL had poor follicular response (19.71%). There was no correlation with fertilization and pregnancy rates.In the early follicular phase inhibin B has direct correlation with ovarian reserve. Its high levels are related to better follicular response and oocyte quality. This enzyme levels are not useful as a predictive factor of pregnancy in IVFET cycles.

Churg-Strauss syndrome (CSS) is a systemic disease characterized by asthma, blood and tissue eosinophilia, and necrotizing vasculitis with extravascular eosinophilic granulomas.We describe two cases of patients with CSS: a 56-year-old man, whose presentation was highly unusual because its initial predominant manifestation was odynophagia, and a 35-year-old man whose disease was diagnosed after a work-up because of nausea, vomiting and abdominal pain. In both cases, thoracic computerized tomography scans showed congestive esophagitis with a markedly thickened esophageal wall at diagnosis and at relapse. Both the vasculitis and the esophageal involvement improved with treatment.Gastrointestinal (GI) involvement is frequent in CSS patients and is one of the major causes of death associated with CSS. Nonetheless, eosinophilic vasculitis-related esophagitis is very rare.

Determining if a statistical correlation can be established between those variables observed during the transference test performed before ovarian stimulation and those obtained during the real embryo transference.Clinical retrospective.Ninety four female patients included in the IVF-ET were studied and a transference test previous to ovarian stimulation was performed. The following parameters were considered in this test: hysterometry, type of catheter, degree of difficulty, and person performing it. A total of 117 embryonic transferences were carried out, and the same parameters observed during the test were measured. The chi square test was used for the statistical analysis.The most commonly used kind of catheter was the Cook Soft Pass (n = 92), and a statistically significant correlation was observed with the one used during the real transference (n = 94). Concerning the degree of difficulty, the transference test resulted complicated in 4.2% of the cases, difficult in 31.6% of them, and easy in 64.2% of them, presenting a statistical correlation with the real transference, where the procedure resulted complicated in 1.7% of the patients, difficult in 32.4% of them, and easy in 65.8%. In addition, and with the intention of ruling out the medical factor, we tried to have the same person performing the transference test and the real procedure, and a statistically significant correlation was also observed. Pregnancy rate per transference was 27.4%. When an association between the difficulty of a real transference and pregnancy rates was tried, no statistical association between an easy or a difficult transference was observed.Embrionic transference is a fundamental phase for IVF-ET programs. However, a variety of factors can influence this procedure, some are medical and others are mechanical. Our results allow us to conclude that there is a statistical correlation between those variables observed during the real embryonic transference and the test, so the latter can be considered as a very useful element in the integral in vitro fertilization process, which prevents the real transference from becoming a blind procedure.

To determine the integrity of the plasmatic membrane through phosphatidylserine (PS) translocation in two spermatic fractions and their correlation with the spermatic mitochondrial membrane potential.The analysis of both spermatic fractions was carried out through a discontinuous gradient separation with Percoli, in order to obtain two samples with high and low mobility (90-40%). Twelve patients were recruited for the initial evaluation of seminal parameters. Mitochondrial membrane integrity was determined using a second antibody (Mitosensor), and was analyzed by fluorescence microscopy, evaluating an average of 200 cells. A 450-490 nm excitation filter was used for this analysis. Cytoplasmatic assessment was carried out by anexine V bonding to PS, in order to determine the initial events of cellular death. Non parameter tests were used in order to determine the differences between mitochondrial potentials and plasmatic membrane processes. Linear correlation tests were used for the anexine V and Mitosensor ratios.Due to the study's design, some differences were observed regarding the displacement parameters and the presence of apoptosis, both, in the plasmatic membrane and in mitochondrial membrane potentials. A positive correlation between both, mitochondrial and cytoplasmic membrane functions was also found.This is the first study performing a comparative analysis between mitochondrial membrane function and cytoplasmatic PS expression as early cellular death markers. The male infertility population is probably associated with an increase in this kind of apoptosis processes.

The frequent etiology of panhypopituitarism is a hypopituitary adenoma. An exceptional cause, with less than 40 cases in the literature, is intra-sellar carotid aneurism.A 55 year-old woman was treated for panhypopituitarism related to bilateral aneurism of the carotid arteries. Hormone exploration revealed anterior pituitary deficiency involving all the axes except the corticotrophin and prolactin functions. Pituitary MRI showed an atrophic pituitary, compressed by two calcified aneurismal formations located on the terminals of two internal, partially thrombotic, carotid arteries. Surgical treatment was not envisaged 12 years later. Replacement therapy for life was initiated.The mechanisms explaining the occurrence of panhypopituitarism secondary to intra-cranial aneurism are hypothetical: compressive phenomena, ischemia and apoplexy of a pituitary adenoma related to the aneurism.

Medullary thyroid carcinoma is a rare tumour derived from the thyroid parafollicular calcitonin-secreting cells. Calcitonin is a very specific marker of this cancer that allows preoperative diagnosis. Serum calcitonin assay is particularly useful to define the postoperative state of patients (cured, apparently cured, not cured) and, because of its great sensitivity, it has a major place in the postoperative follow-up.To identify, among patients thyroidectomized for medullary thyroid carcinoma (MTC), the characteristics of authentic recurrent MTC [re-elevation of stimulated serum calcitonin (CT) level measured by a sensitive immunoradiometric assay, after postoperative normalization].We first collected, through the national registry of the French Calcitonin Tumour Study Group (GETC), patients who had undergone a total thyroidectomy with or without lymph node surgery and who were not cured at the last follow-up visit. Among 453 such patients included in the database, 15 patients met the criteria for authentic recurrence as defined in previous studies: they had been first considered as cured during the 6 months following the initial surgical procedure (basal and pentagastrin-stimulated serum calcitonin levelor= 10 ng/l) but had a secondary rerise of their pentagastrin-stimulated calcitonin level, over 10 ng/l. Eight of them even had an undetectable (2 ng/l) immediate postoperative CT, confirming the initial postoperative cure. The characteristics (age, nature of disease, stage at surgery and type of node dissection) of these 15 patients were studied.According to the Tumour Node Metastasis classification, nine patients were T1 and, among them, five patients had had complete lymph node surgery without any evidence of nodal metastases (N0). The recurrence was 3.2 +/- 2.2 years (range: 0.7-7.5) after the initial surgery.3.3% of patients not cured at the last visit had a recurrent MTC. This recurrence occurred whatever the stage, and even if the primary surgery for MTC was a priori complete. These results emphasize the need for a regular biochemical follow-up because recurrence may appear many years after the initial surgery.

The objective was to evaluate if the preovulatory molecular ratio between progesterone and estradiol has age-dependent changes in patients undergone controlled ovarian hyperstimulation. Were studied 180 cycles of conventional in vitro fertilization. Patients were divided in three groups: Group 1 (age less than 30 years; n = 40), group 2 (age between 30 and 35 years; n = 82), and group 3 (age between 36 and 40 years; n = 58). Leuprolide acetate was used in all cases. Molecular progesterone/estradiol ratio was calculate with the following formula: [Serum progesterone (ng/mL) x 3180 (SI x 10(3) divided by serum estradiol (pg/mL) x 3.671 (SI)]. In patients with age more than 38.5 years there was positive correlation between preovulatory progesterone and estradiol (R = 0.55, R2 = 0.30). There were significant difference in molecular progesterone/estradiol ratio between group 1 compared to group 2 (P less than 0.001), group 1 compared to group 3 (P less than 0.0001), as soon as group 1 compared to group 2 plus group 3 (P less than 0.0001). It is concluded that molecular progesterone/estradiol ratio decreases before any endocrino evidence of ovarian aging. The value of this putative test of ovarian reserve is discussed.

The objective was to evaluate if the preovulatory molecular ratio between progesterone and estradiol has age-dependent changes in patients undergoing controlled ovarian hyperstimulation. There were 180 cycles of conventional in vitro fertilization which were studied. Patients were divided in three groups: Group 1 (age less than 30 years; n = 40), group 2 (age between 30 and 35 years; n = 82), and group 3 (age between 36 and 40 years; n = 58). Leuprolide acetate was used in all cases. Molecular progesterone/estradiol ratio was calculated with the following formula: [Serum progesterone (ng/mL) x 3180 (Sl x 10(3)) + serum estradiol (pg/mL) x 3.671 (Sl)]. In patients older than 38.5 years there was positive correlation between preovulatory progesterone and estradiol (R = 0.55, R2 = 0.30). There were significant difference in molecular progesterone/estradiol ratio between group 1 compared to group 2 (P less than 0.001), group 1 compared to group 3 (P less than 0.0001), as well as group 1 compared to group 2 plus group 3 (P less than 0.0001). It is concluded that molecular progesterone/estradiol ratio decreases before any endocrine evidence of ovarian aging. The value of this putative test of ovarian reserve is discussed.

The control of hypertension in diabetic hypertensive patients prevents micro and macroangiopathy complications. Our prospective study was designed to evaluate the level of treatment of hypertension in type II diabetic patients at the time of referral to our endocrinology unit and after a mean follow-up of 9.2 months. Five hundred and sixty four patients (sex ratio: 1.15, mean age of 56 +/- 13, mean BMI of 28 +/- 15, mean duration of diabetes of 11.3 +/- 9.9) were referred to our unit. Among these, 42% had an antihypertensive drug (58% under monotherapy, 42% under combinations) and 92% had a documented history of CHD. Glycemic and blood pressure controls were stable during follow-up. HbA1c remained unchanged (8.95% at admission, 8.8% at 9 months) BP decreased from 143/84 +/- 26/13 mmHg to 142/82 +/- 23/13 mmHg. Fifty six percent reached a BP goal of 140/90 mmHg whereas 42% achieved a BP goal of 130/85 mmHg at 9 months compared to respectively 56% and 39% at admission. A multivariate logistic regression analysis showed that initial value of SBP (p0.0001), age (p0.0001), BMI (p = 0.006), HbA1c (p = 0.018) were independent factors of non control of hypertension. In conclusion, follow-up of hypertension diabetic patients would be focussed on identified and modifiable factors.

Idiopathic CD4+ lymphocytopenia (ICL) is a rare syndrome affecting adults and defined by a stable loss of CD4+ T cells in the absence of any known cause of immune deficiency. Defective T-cell proliferations to mitogens and antigens have been described in some of such patients displaying clinical signs of immune deficiency such as opportunistic infections. We investigated here the hypothesis that T-cell depletion and dysfunction could be due to biochemical defects of the CD3-TCR pathway in CD4+ and/or CD8+ subsets from three patients with severe stable ICL (below 150 CD4+ T cells/microliter) and opportunistic infections. Patient 1 had a general T lymphocytopenia, whereas patients 2 and 3 displayed a selective loss of CD4+ T cells. We observed in all patients a major reduction of the proliferative response to CD3-TCR stimulation that affected only the depleted T-cell subpopulation. Moreover, in two cases, impaired early biochemical events of the CD3-TCR pathway were detected. In patient 1 and 3, we found a defect (of distinct intensity) of CD3-induced protein tyrosine phosphorylation in CD4+ cells compared to control cells, whereas this process was normally induced in CD4+ T cells from patient 2. Taken together, this study reveals that the heterogeneity of the ICL syndrome was situated at the cellular level, and involved in two cases abnormalities of transducing molecules of the CD3-TCR pathway.

The objective was to evaluate the relationship between follicular fluid levels of Interleukin-6 (IL-6) and the seric concentrations of estradiol and progesterone during controlled ovarian hyper-stimulation. The levels of IL-6 were measured in follicular fluid of 15 patients undergone to in vitro fertilization and embryo transfer and correlated with the values of seric estradiol and progesterone. There were a negative correlation between follicular levels of IL-6 and either estradiol and progesterone. Four patients achieved pregnancy following embryo transfer (pregnancy rate 26.6%), one of them aborted. As conclusion, the increased levels of IL-6 may be a reaction to controlled ovarian hyper-stimulation and probably a protective response. According to the reduction of estradiol, there may be a subtle reduction in aromatase action by effect of IL-6 and other cytokines.

During recent decades, undeniable progress has been made with regard to the management of arterial hypertension. Larger numbers of patients are aware they have hypertension, receive treatment and benefit from this therapy. Furthermore, significant reductions have been observed in morbidity and mortality resulting from cardiovascular diseases. The objectives of hypertension treatment have been formulated on the basis of results of extensive epidemiological studies. Only a few patients receiving monotherapy actually achieve and maintain acceptable blood pressure levels. The complex pathogenesis of essential hypertension, the implications of nervous and humoral counter-regulatory effects, the heterogeneous character of individual responses to any given class of antihypertensive treatment and the onset of adverse effects all account for these failures. The search for a simple, effective and well-tolerated treatment based on a low dose combination of 2 classes of antihypertensive agents is consequently legitimate. The fixed combination of atenolol 50 mg and sustained release nifedipine 20 mg enables patients to benefit from the antihypertensive synergy of a beta-blocker and a calcium antagonist (dihydropyridine). Several open-ended or double-blind, controlled studies have shown that this combination produces a more marked antihypertensive effect than the individual components used alone or other reference monotherapies. Furthermore, it has been shown that this effect persists throughout the entire 24-hour period; this has been confirmed by 24-hour blood pressure monitoring. Short and medium term tolerability is significantly improved: the side effects commonly associated with the 2 drugs when used alone are reduced with the combination formulation since the 2 active substances have different and complementary mechanisms of action. In addition, long term studies have shown that therapeutic efficacy and tolerability remain stable and have even been seen to improve over a 12-month period. The fixed combination of atenolol-nifedipine has a role in strategies for the treatment of mild to moderate hypertension, particularly under the following conditions: when first-line monotherapy has failed to attain specific clearly defined objectives, including stabilised blood pressure levels together with acceptable tolerability. when patient compliance is jeopardised as a result of undesirable side effects. when the vascular burden is aggravated through lack of attention to individual risk factors in hypertensive patients. In more serious forms of hypertension, the atenolol-nifedipine combination can replace sequential monotherapies or other combination treatments that have failed to comply with the various criteria of therapeutic efficacy. Controlling arterial hypertension commonly requires polytherapy with 3 or even 4 different drugs in conjunction with particularly strict rules governing hygiene and diet. The addition of the fixed combination of atenolol-nifedipine simplifies the treatment of patients with arterial hypertension by limiting the daily doses and reducing laboratory monitoring.

Family adjustments, which are generated by a maternal death, have been analysed previously in Mexico by using a reduced number of cases in rural areas. This study was design in order to establish changes in family dynamic generated b y a maternal death and to analyse child surviving after one year of birth. Family members of maternal deaths cases, which occurred during 1988-89 in the Federal District, were interviewed by first time in order to know information related to family dynamic and women's characteristics. A second interview was made after one year of birth for cases in which the newborn survived hospital discharge. Simple frequencies were calculated and using X2 test compared groups. Main consequences were family disintegration, child acquiring new roles and economic problems when woman was the main or the only one support of the family. Child surviving was higher than we expected considering other national or international reports. Children were mainly integrated to their grandparent's family.

To compare the clinical course and outcome of patients diagnosed with one of 4 neonatal-onset urea cycle disorders (UCDs): deficiency of carbamyl phosphate synthase 1 (CPSD), ornithine transcarbamylase (OTCD), argininosuccinate synthase (ASD), or argininosuccinate lyase (ALD).Clinical, biochemical, and neuropsychological data from 103 subjects with neonatal-onset UCDs were derived from the Longitudinal Study of Urea Cycle Disorders, an observational protocol of the Urea Cycle Disorders Consortium, one of the Rare Disease Clinical Research Networks.Some 88% of the subjects presented clinically by age 7 days. Peak ammonia level was 963 μM in patients with proximal UCDs (CPSD or OTCD), compared with 589 μM in ASD and 573 μM in ALD. Roughly 25% of subjects with CPSD or OTCD, 18% of those with ASD, and 67% of those with ALD had a "honeymoon period," defined as the time interval from discharge from initial admission to subsequent admission for hyperammonemia, greater than 1 year. The proportion of patients with a poor outcome (IQ/Developmental Quotient70) was greatest in ALD (68%), followed by ASD (54%) and CPSD/OTCD (47%). This trend was not significant, but was observed in both patients aged4 years and those aged ≥ 4 years. Poor cognitive outcome was not correlated with peak ammonia level or duration of initial admission.Neurocognitive outcomes do not differ between patients with proximal UCDs and those with distal UCDs. Factors other than hyperammonemia may contribute to poor neurocognitive outcome in the distal UCDs.

The medical literature has noted the relationship between perinatal morbidity and mortality and cultural factors for more than twenty years. During this time, however, rates of diseases such as hypertension, which complicate pregnancy and delivery, threatened preterm delivery and premature rupture of the membranes have decrease little. These conditions required other, complementary actions such as health education. The purpose of this research was to explore existing knowledge about warning signs during pregnancy in a population using third level medical facilities as the first step in designing an educational program.We applied a 17 item multiple choice questionnaire regarding alarm sings during pregnancy to a group of 100 pregnant women. The sample was classified into six groups according to the age of the patient and the presence of aggregate risk. The analysis focused on the proportion of correct responses, applying different statistical tests according to the nature of the variables.In stepwise multiple regression, years of education explained 8.1% of the variance of correct responses, the number of pregnancies 5.5%, and gestational age 6.6%. The ANOVA of the complete regression was significant (F = 9.41; df = 99; p0.001) with a standard error of 2.23 ans a final adjusted r = 0.45. The number of consultations was positively associated with gestational age but had no relationships with correct responses. Groups with the greatest information deficits were adolescents and patients of adequate reproductive age with low reproductive risk.Patients with the least obvious alarm signs failed the most items in the alarm sing questionaire. The educational relationship between the physician and the patient should be more carefully explored. We are in agreement with other authors that educational level of patients is a determining to the attitude and knowledge of the population towards its own health.

Objective : Intravenous pentamidine induces hypo- and hyperglycaemia (dose-dependent toxicity on islet β cells), pancreatitis and nephrotoxicity. Conversely, aerosolized pentamidine (AP) is usually devoid of systemic side-effects : few reports of hypo- or hyperglycaemia have been published. Our study aimed to assess the influence on glucose homeostasis and insulin secretion of long-term exposure to AP used for prophylaxis of Pneumocystis carinii pneumonia in HIV-positive patients, and to compare the impact on insulin secretion of AP, whether administered for the first time or after prolonged monthly exposure. Design : Retrospective cross-sectional controlled study (main objective) and non-randomized prospective controlled study. Patients : We compared glucose homeostasis and C peptide response to 1 mg intravenous glucagon in patients who had previously inhaled ≥10 prophylactic aerosols (group 1, n = 21) and in HIV-positive controls (groups 2 and 3, n = 28) who had received none. Both groups were comparable for age and body-mass index, but CD4 T-lymphocyte counts and Karnofsky scores were both significantly higher in the control group. Results : Fasting (T 0 ) blood glucose, fructosamine and response to the first glucagon test were similar in both groups, but postprandial glucose, glycated haemoglobin and fasting C peptide were significantly higher (P

Identification of a responder to an antihypertensive treatment is helpful and also very difficult in an open uncontrolled study. The existence of many arbitrary methods to define a responder, the placebo effect and the regression to the mean phenomenon coexist and give spurious interpretation. We analysed an open study recruiting 6,530 hypertensive patients (DBPor = 95 mmHg at entry), treated with the same antihypertensive drug during 3 months. Mean initial and at 3 months blood pressures were respectively 178/101 mmHg and 151/86 mmHg. We observed significant variation in the % of responders (20 to 80%) to a drug when applying different methods. Placebo effect and regression to the mean lead to an overestimation. Without a placebo controlled design, we suggest to increase the BP level for inclusion to determine the % of responders with the standard goal pressure (DBP90 mmHg) and to use Oldham's method for adjusting for the regression to the mean unless the coefficient of correlation found is around zero and if upper level of DBP is not selected for inclusion.

The treatment of hypertension must fall within a strategy of the early and strict control of blood pressure levels. Only actual normalisation of blood pressure can offer long term benefit regarding the incidence of cardiovascular morbidity and mortality. While major studies undertaken up to now have already proven the benefit of treatment using classical drugs as monotherapy, it is now necessary to offer all young hypertension patients, even mild, with strict control of levels, a non-pharmacological action on risk factors, and a choice of treatments ensuring no loss of part of the prognostic benefit as a result of persistence or worsening or sub-clinical metabolic disorders. It seems logical, when first-line monotherapy is selected from among the five major drug groups recommended, is neither perfectly effective nor perfectly tolerated, and risks worsening a metabolic disorder in the long term, to use a combination of hypotensive drugs. This should enable blood pressure control in 80 to 90% of cases, and improved acceptability, a major factor in treatment compliance. It is reasonable to hope, in the long term, that the use of a combination of lower doses than as monotherapy, will ensure less interference with major metabolic, endocrine and vascular functions, leading to a further improvement in the prognosis of treated hypertension.

We used the polymerase chain reaction (PCR) to detect hepatitis D (HD) viremia in patients infected with the human immunodeficiency virus (HIV). Nineteen (9%) of 206 such patients were prospectively found to be infected by HDV. Thirty-one anti-HIV-positive patients were studied by means of PCR and the results were analysed according to HDV and hepatitis B virus (HBV) serological status. HDV-PCR was positive in five patients. Two had detectable serum HDV antigen. Four patients had anti-HD IgM and IgG antibodies. All these patients were HBs antigen-positive, and three were HBV-DNA positive. All the other patients were HDV-PCR-negative. Statistical analysis suggested more extensive liver damage and immunological impairement in HDV-PCR positive patients. In this unselected HIV-infected population, HDV-RNA detection by PCR was only evidenced in HDV infected patients in whom 5/19 were positive. This test allowed direct diagnosis of HDV viremia and will be useful for the monitoring of HDV infection.

Two hundred and ninety cases of pregnant patients with antecedents of sterility, were analyzed; 55.8% corresponded to primary sterility and 44.2% to secondary sterility. About cases 38.2% corresponded to endocrine-ovarian factor; 17.9% to tuboperitoneal; 7.4% to cervico-spermatic and 36.5% of undetermined cause. The main complications of pregnancy were: abortion, ectopic pregnancy, twin pregnancy, toxemia, pre-term delivery, placenta previa, and premature detachment of normoinserted placenta. The frequency of such complications, as well as the indexes of perinatal mortality and congenital malformations, were no higher than for general population. However, analyzing separetely the different groups, it was found a notable increase the abortion and twin pregnancy indexes in factor endocrine-ovarian (25.2% and 4.5%). In tuboperitoneal the ectopic pregnancy index was higher (7.5%), and one case of heterotopic pregnancy was found. The global index for cesarean section was 47.2%, increased due to frequent use of elective section (11.2%). It is concluded that currently and because the use of diagnostic technology and surveillance since early phases, the evolution and outcome of pregnancies in women previously sterile are similar to the ones for general population.

30 patients were studied, that were included in the IVF program of the INPer. The estradiol response was studied and was correlated with the number of retrieved oocytes. The previously known E2 values considered as indicative for cancellation did no were observed in this series, and there are proposed new ones, also prognostic criterion for oocyte retrieval are proposed.