Association Between Insulin Resistance, Glucose Intolerance, and Hypertension in Pregnancy

There is an association between insulin resistance, glucose intolerance, and essential hypertension, but the relation between insulin resistance, glucose intolerance, and hypertension diagnosed during pregnancy is not well understood. Transient hypertension of pregnancy, the new-onset nonproteinuric hypertension of late pregnancy, is associated with a high risk of later essential hypertension and glucose intolerance; thus, these conditions may have a similar pathophysiology. To assess the association between insulin resistance, glucose intolerance, essential hypertension, and subsequent development of proteinuric and nonproteinuric hypertension in pregnancy in women without underlying essential hypertension, we performed a prospective study comparing glucose (fasting, I and 2 hours postglucose load), insulin, glycosylated hemoglobin (HbA1c), high-density lipoprotein cholesterol (HDL-C), and triglycerides levels on routine screening for gestational diabetes mellitus. Women who developed hypertension in pregnancy (n = 37) had higher glycemic levels (fasting, 1 and 2 hours postglucose load) on a 100-gram oral glucose loading test, although only the fasting values showed a statistical significance (p < 0.05), and a significantly higher frequency of abnormal glucose loading tests, two hours after glucose load (>= 140 mg/dL) (p < 0.05) than women who remained normotensive (n = 180). Glucose intolerance was common in women who developed both subtypes of hypertension, particularly preeclampsia. Women who developed hypertension had greater prepregnancy body mass index (p < 0.0001), higher frequency and intensity of acanthosis nigricans (p < 0.0001), and higher baseline systolic and diastolic blood pressures (p <= 0.0001 for both), although all subjects were normotensive at baseline by study design; they also presented lower levels of HDL-C (p < 0.05). However, after adjustment for these and other potential confounders, an abnormal glucose loading test remained a significant predictor of development of hypertension (p < 0.05) and, specifically, preeclampsia (p < 0.01). There was a trend toward higher insulin and homeostasis model assessment-insulin resistance (HOMA-IR) levels in women developing any type of hypertension. When comparing women that remained normotensive to term with those with transient hypertension and preeclampsia, the preeclamptic women were born with lower weight (p < 0.05) and shorter length (p < 0.005); at screening they were older (p < 0.005), showed higher frequency and intensity of acanthosis nigricans (p < 0.0001), had higher prepregnancy BMI (p < 0.0005), as well as higher baseline systolic and diastolic blood pressures (p <= 0.0001 for both). They also showed higher HOMA-IR levels that did not show a statistical significance. When glucose tolerance status was taken in account, an association was found between increasing indexes of hypertension (p < 0.05) and of HOMA-IR (p < 0.05) with the worsening of glucose tolerance. These results suggest that insulin resistance and relative glucose intolerance are associated with an increased risk of new-onset hypertension in pregnancy, particularly preeclampsia, and support the hypothesis that insulin resistance may play a role in the pathogenesis of this disorder.

Alcohol use disorders in patients with obsessive-compulsive disorder: The importance of appropriate dual-diagnosis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Medical conditions and body pain in patients presenting orofacial pain

OBJETIVO: Verificar a frequência de problemas médicos autorrelatados e a frequência de áreas de dor no corpo em pacientes com dor orofacial, comparando-os a pacientes submetidos a tratamento odontológico de rotina. MÉTODOS: Os dados foram coletados dos arquivos da Clínica de Dor Orofacial (Grupo A, n=319) e de clínicas de tratamento odontológico rotineiro (Grupo B, n=84) da Faculdade de Odontologia de Araraquara, São Paulo, Brasil. Os indivíduos responderam a questionários e preencheram um mapa corporal indicando os locais de dor. RESULTADOS: O teste de Mann-Whitney demonstrou que o Grupo A apresentou uma média de relatos de problemas médicos superior ao Grupo B (p=0,004). Para ambos os grupos, o teste de correlação de Pearson demonstrou correlação positiva entre os problemas médicos e a frequência de áreas dolorosas (respectivamente, 0,478, p=0,001 e 0,246, p=0,000). CONCLUSÕES: O Grupo A relatou maior número de problemas médicos e houve correlação positiva entre a frequência desses problemas e a de áreas de dor para ambos os grupos.

Laryngeal and voice disorders in patients with gastroesophageal symptoms. Correlation with pH-monitoring

OBJETIVO: Investigar as alterações laríngeas e vocais em pacientes com sintomas de refluxo gastroesofágico e correlacioná-las com o exame de phmetria. MÉTODOS: Estudo prospectivo que incluiu os pacientes atendidos nos ambulatórios de Distúrbios da Voz da Faculdade de Medicina de Botucatu no período de cinco anos com sintomas vocais e gastroesofágicos. Os pacientes foram submetidos à videolaringoscopia, às análises vocais perceptivo-auditivas, a analise vocal acústica computadorizada e ao exame de pHmetria de dois canais com monitorização durante 24 horas. RESULTADOS: Foram incluídos 57 pacientes (entre 21 a 65 anos; 45 mulheres e 12 homens). Desses, 18 apresentavam pHmetria normal (31,6%) e 39 alterada (68,4%). As videolaringoscopias registraram diversas lesões laríngeas tanto nos pacientes com pHmetria normal como alterada, sendo mais relevantes neste último grupo, destacando-se a paquidermia posterior. As avaliações vocais perceptivo-auditivas identificaram alterações vocais de diversas intensidades em ambos os grupos, mais importantes nos pacientes com pHmetria alterada. Todos os parâmetros acústicos, exceto Fo, mostraram-se alterados em ambos os grupos, quando comparados aos controles. CONCLUSÕES: Alterações vocais perceptivas e acústicas, e lesões laríngeas foram registradas tanto nos pacientes com phmetria normal como alterada, sinalizando para a importância da historia clínica e dos achados videolaringoscópicos no diagnóstico das laringites ácidas.

Microscopic evaluation of proliferative disorders in the gerbil female prostate: Evidence of aging and the influence of multiple pregnancies

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders: recruitment, assessment instruments, methods for the development of multicenter collaborative studies and preliminary results

OBJETIVO: Descrever o recrutamento de pacientes, instrumentos de avaliação, métodos para o desenvolvimento de estudos colaborativos multicêntricos e os resultados preliminares do Consórcio Brasileiro de Pesquisa em Transtornos do Espectro Obsessivo-Compulsivo, que inclui sete centros universitários. MÉTODO: Este estudo transversal incluiu entrevistas semi-estruturadas (dados sociodemográficos, histórico médico e psiquiátrico, curso da doença e diagnósticos psiquiátricos comórbidos) e instrumentos que avaliam os sintomas do transtorno obsessivo-compulsivo (Escala para Sintomas Obsessivo-Compulsivos de Yale-Brown e Escala Dimensional para Sintomas Obsessivo-Compulsivos de Yale-Brown), sintomas depressivos (Inventário de Depressão de Beck), sintomas ansiosos (Inventário de Ansiedade de Beck), fenômenos sensoriais (Escala de Fenômenos Sensoriais da Universidade de São Paulo), juízo crítico (Escala de Avaliação de Crenças de Brown), tiques (Escala de Gravidade Global de Tiques de Yale) e qualidade de vida (questionário genérico de avaliação de qualidade de vida, Medical Outcome Quality of Life Scale Short-form-36 e Escala de Avaliação Social). O treinamento dos avaliadores consistiu em assistir cinco entrevistas filmadas e entrevistar cinco pacientes junto com um pesquisador mais experiente, antes de entrevistar pacientes sozinhos. A confiabilidade entre todos os líderes de grupo para os instrumentos mais importantes (Structured Clinical Interview for DSM-IV, Dimensional Yale-Brown Obsessive-Compulsive Scale, Universidade de São Paulo Sensory Phenomena Scale ) foi medida após seis entrevistas completas. RESULTADOS: A confiabilidade entre avaliadores foi de 96%. Até março de 2008, 630 pacientes com transtorno obsessivo-compulsivo tinham sido sistematicamente avaliados. A média de idade (±SE) foi de 34,7 (±0,51), 56,3% eram do sexo feminino e 84,6% caucasianos. Os sintomas obsessivo-compulsivos mais prevalentes foram os de simetria e os de contaminação. As comorbidades psiquiátricas mais comuns foram depressão maior, ansiedade generalizada e transtorno de ansiedade social. O transtorno de controle de impulsos mais comum foi escoriação neurótica. CONCLUSÃO: Este consórcio de pesquisa, pioneiro no Brasil, permitiu delinear o perfil sociodemográfico, clínico e terapêutico do paciente com transtorno obsessivo-compulsivo em uma grande amostra clínica de pacientes. O Consórcio Brasileiro de Pesquisa em Transtornos do Espectro Obsessivo-Compulsivo estabeleceu uma importante rede de colaboração de investigação clínica padronizada sobre o transtorno obsessivo-compulsivo e pode abrir o caminho para projetos semelhantes destinados a integrar outros grupos de pesquisa no Brasil e em todo o mundo.

A comparative-analysis of glycosaminoglycans from human umbilical arteries in normal subjects and in pathological conditions affecting pregnancy

BACKGROUND: Vascular cells express different phenotypes in adult and fetal vessels, and the extracellular matrix they synthesize should reflect these differences. Alterations of vascular proteoglycan/glycosaminoglycan is verified in disorders such as hypertension and diabetes, and when occurring during pregnancy, they bring about structural changes to fetal vessels that often lead to impaired fetus growth. Yet there is little data about the extracellular matrix of an important human fetal vessel, the umbilical artery.EXPERIMENTAL DESIGN: This study involved the biochemical characterization of the extracellular matrix of normal umbilical arteries, umbilical arteries from complicated pregnancies (maternal hypertension and diabetes and intrauterine growth retardation syndrome), and, for purpose of comparison, normal adult arteries (aorta and iliac and pulmonary arteries). Although the collagen types I:III ratio was determined in some cases, emphasis was placed on analysis of glycosaminoglycans.RESULTS: Normal umbilical arteries differ from normal adult arteries in that they contain greater concentrations of hyaluronic acid and lesser concentrations of heparan sulfate and chondroitin 4-and 6-sulfate. The umbilical artery also differs from adult arteries in the disaccharide composition of its chondroitin and heparan sulfates and in the molecular weight of this latter glycosaminoglycan. The glycosaminoglycan distribution in umbilical arteries derived from complicated pregnancies is roughly similar to that of controls. However, total glycosaminoglycan and collagen were significantly reduced, and the collagen I:III ratio was increased in the umbilical arteries from hypertension-complicated pregnancies.CONCLUSIONS: the glycosaminoglycan composition of the normal umbilical artery, a fully differentiated tissue, differs in many aspects from that of normal adult arteries. of the cases of complicated pregnancies studied, the extracellular matrix of umbilical arteries was altered only in maternal hypertension. The changes, notably a mild fibrosis, were not very pronounced and should not impair hemodynamic properties of the vessel.

EFFECT OF EXERCISE DURING PREGNANCY AND DAM AGE ON MATERNAL BLOOD-CHEMISTRY AND FETAL GROWTH

In order to determine the effect of maternal exercise on maternal nutritional status and fetal growth, young (Y = 45-50 days old) Wistar rats were divided into 4 groups of 5 to 8 animals: control pregnant (CP), control non-pregnant (CNP), exercise-trained (swimming 1 h/day, 5 days/week, for 19 days) pregnant (TP) and exercise-trained non-pregnant (TNP). Four equivalent groups of adult rats (A - 90-100 days old) were also formed. Serum glucose, total protein, albumin, hematocrit and liver glycogen were determined in female rats and pups. There were no statistical differences in serum glucose, total protein and albumin levels, litter size ot birth weight among exercise-trained animals, controls and their respective pups. Hematocrit was significantly lower in pups of exercise-trained young rats than in all other groups (YCP = 38.6 +/- 3.0; YTP = 32.6 +/- 2.1; ACP = 39.0 +/- 2.5; ATP = 39.2 +/- 2.9%). Liver glycogen levels were lower in pregnant than in non-pregnant rats but similar in exercise-trained and control rats of the same age and physiological status (YCNP = 4.1 +/- 0.2; YCP = 2.7 +/- 0.9; YTNP = 4.9 +/- 0.8; YTP = 2.7 +/-0.4; ACNP = 6.1 +/- 0.6; ACP = 3.1 +/- 0.8; ATNP = 6.6 +/- 0.8; ATP = 2.2 +/- 0.9 mg/100 mg). We conclude that pups of adult female rats are spared from the effects of this kind of exercise training during pregnancy. on the other hand, it appears that maternal adaptations to exercise training in young rats are able to preserve only some aspects of pup metabolism.

Studies of natural-killer-cells in pregnancy-induced hypertension

The number and activity of natural killer (NK) cells were studied in 20 patients with pregnancy-induced hypertension (PIH), 15 uncomplicated pregnant women and 16 healthy non-pregnant women, All the pregnant women were primigravidae and were evaluated during the third trimester of gestation. Peripheral blood NK cells were detected with monoclonal antibodies by indirect immunofluorescence and cytotoxic activity was measured using a single-cell assay against K562 target cells. Hypertensive pregnant women had an increased number of circulating NK cells associated with a significant decrease of NK activity, the cytotoxic activity was significantly lower in normal pregnant and PIH women when compared with non-pregnant controls. The onset of immature NK cells in peripheral blood and the impairment of their cytotoxic activity in PIH patients may be associated with hormones and immunosuppressive substances produced by tissues occurring at the maternal-fetal interface.

DIABETES AND EXPERIMENTAL PREGNANCY IN RATS - COURSE OF MATERNAL BLOOD-GLUCOSE LEVELS AND ITS REPERCUSSIONS ON THE BLOOD-GLUCOSE LEVELS AND PANCREAS OF NEWBORN PUPS

The objective of the present investigation was to determine the course of maternal blood glucose levels in pregnant rats and its repercussions on the glucose levels and pancreas of their newborn pups. Diabetes was induced by alloxan (42 mg/kg body weight) and streptozotocin (40 mg/kg). Sixty-two pregnant Wistar rats weighing 180 to 250 g were divided into a control group and two groups with moderate (120 to 200 mg/dl glucose) and severe diabetes (greater than 200 mg/dl glucose), respectively. Blood glucose levels were measured in the dams on the 1st, 14th, and 21st days of pregnancy and in the pups at birth. The results were pooled for each litter. The fetal pancreases were removed after cesarian section performed on the 21st day of pregnancy, pooled for each litter and processed for histopathologic examination by light microscopy. Maternal blood glucose levels were significantly increased compared with the first day of pregnancy in both normal and diabetic rats starting on the 14th day of pregnancy. Fetal blood glucose levels correlated with maternal levels. The histopathologic changes characterized by vacuolization and basophilia of the cytoplasm of endocrine pancreas of newborn pups from darns with moderate or severe diabetes suggested pancreatic hyperactivity.

Comorbidity of obsessive-compulsive disorder and personality disorders. A Brazilian controlled study

The aim of this study was to evaluate the presence of personality disorders (PDs) in 40 patients with obsessive-compulsive disorder (DSM-III-R criteria) from the Medical School of Botucatu (UNESP), Sao Paulo, Brazil. It is a case-control study. Patients were 24 women and 16 men, 16-68 years old, referred to our outpatient psychiatric service for treatment. Controls were 40 nonpsychiatric outpatients matched to the cases by sex, age and marital status. The instrument used was the Portuguese version of the Structured Interview for DSM-III-R Personality Disorders (SIDP-R). All interviews (n = 80) were made simultaneously by 2 raters, with independent scoring, so that the interrater reliability of the instrument could also be assessed (kappa statistics). The consensual axis II diagnoses in the OCD group were: avoidant (52.5%, κ = 0.80), dependent (40%, κ = 0.84), histrionic (20%, κ = 0.83), paranoid (20%, κ = 0.74), obsessive-compulsive (17.5%, κ = 0.86), narcissistic (7.5%, κ = 1.00), schizotypal (5%, κ = 0.65), passive-aggressive (5%, κ = 0.79) and self-defeating (5%, κ 0.55). At least one PD diagnosis was made in 70% of the patients, while only 6 controls had a PD diagnosis (p < 0.01). A great deal of diagnostic overlap was found in the OCD group (57.5% had two or more PDs), especially between avoidant and dependent PDs. The features of these two PDs may be secondary to the OCD. The study also suggests that there is not a close relationship between OCD and obsessive-compulsive personality disorder (OCPD). Patients with OCPD or even 3 or 4 O-C traits had significantly less insight into their obsessions and compulsions (p < 0.01).

Hypertensive disorders in pregnant women with diabetes mellitus

The present study was performed to assess the rate of hypertensive complications in diabetic pregnant patients and the influence of White's classification and the quality of the diabetic control. This study included 169 diabetic pregnant women who had delivered at the University Hospital of Botucatu Brazil from 1980 to 1981. The hypertensive disorders occurred in 29.8% of the cases. The incidence of the hypertensive process was the same in all classes of diabetic patients, and it was independent of the glycemic control. In patients with gestational diabetes (classes A and AB), chronic hypertension was the commnest type found; in patients with short-term diabetes (classes B and C) pregnancy-induced hypertension (PIH) and chronic hypertension with superimposed PIH was the most frequent type, and diabetic patients with vasculopathies (classes D-R) had preeclampsia and chronic hypertension with superimposed preeclampsia as the commonest type found.