Assessment of basal insulin requirement using fasting tests in insulin-treated patients with type 2 diabetes mellitus.

AIMS: Characterizing the time course of the rise of blood glucose concentrations in the fasting state during the day and night in patients with type 2 diabetes. METHODS: 40 consecutive insulin-treated patients with type 2 diabetes underwent fasting tests on two different days with either no breakfast and lunch (fasting time of 20 hours) or no dinner (fasting time of 21 hours). Glucose-lowering medication was stopped prior to the test according to the half-life of the medication prescribed. At the start of the fasting tests, blood glucose concentrations were lowered to below 7 mmol/L using an insulin infusion. RESULTS: 26 men and 14 women were included in the study. Mean (+/-SD) age was 61+/-10 years, BMI 31+/-7 kg/m (2), and HbA1c 7.5+/-1%. Diabetes duration was 14+/-8 years and duration of insulin therapy had been prescribed for a mean of 6+/-6 years. During the daytime fast, plasma glucose concentrations rose by a mean of 0.8+/-1.6 mmol/L. During the nighttime fast, plasma glucose concentrations increased particularly after midnight, by 4.3+/-2.1 mmol/L, i.e. significantly more than during the daytime fast. CONCLUSIONS: Fasting blood glucose concentrations in the majority of insulin-treated patients with type 2 diabetes increase markedly after midnight. No similar increase is observed during the day. Thus, for most patients with type 2 diabetes, an intermediate- or long-acting insulin injected at bedtime with a peak action six to eight hours after injection should be appropriate.     

Chlamydial etiology of acute lower respiratory tract infections in children in the Sudan

The role of Chlamydia pneumoniae in 110 Sudanese children with signs of acute lower respiratory tract infections (ALRI) was investigated. Four (3.6%) had evidence of C. pneumoniae infection, of whom 3 were culture-positive, while 1 had an antibody response suggesting a recent infection. IgG antibodies at a titer of ≥1:32 to C. pneumoniae, Chlamydia psittaci and Chlamydia trachomatis were detected in 27 (24.5%), 27 (24.5%) and 7 (6.4%) of the 110 ALRI cases, respectively. C. pneumoniae, C. trachomatis or C. psittaci were not detected in nasopharyngeal secretions from any of 110 patients when fluorescence-labeled specific monoclonal antibodies were used. In a seroepidemiological survey, 318 healthy Sudanese persons aged between 1 month and 67 years were studied for C. pneumoniae antibodies.     

TNF-alpha -308G>A polymorphism modulates cytokine serum concentrations and macrovascular complications in diabetic patients on aspirin.

BACKGROUND: Tumor necrosis factor (TNF)-alpha has pleiotropic effects in cytokine-mediated inflammation underlying atherogenesis. Activation of this inflammatory process is assumed to be different in diabetic and non-diabetic individuals. Previous studies in non-diabetic subjects showed no association between TNF-alpha -308G>A polymorphism and coronary artery disease. METHODS: Vascular complications and cytokine serum concentrations were assessed as a function of the TNF-alpha -308G>A polymorphism in 76 diabetic patients on low-dose aspirin. RESULTS: Of 76 adult diabetic patients, 18 (24%) carried the TNF-alpha -308A allele (17 AG, 1 AA) and 58 (76%) carried wild-type alleles (GG). Prevalence of macrovascular complications was 33% in TNF-alpha -308A allele carriers (AG+AA) and 78% in wild-type allele carriers (GG) (p<0.001). In contrast, prevalence of microvascular complications was 78% and 84%, respectively, and did not significantly differ between the study groups. TNF-alpha -308A allele carriers (AG+AA) compared to wild-type allele carriers (GG) had significantly lower median serum concentrations of hs-C-reactive protein (1.5 vs 2.9 mg/L, p=0.030), interleukin 1-beta (0.9 vs 1.2 ng/L, p=0.046), and interleukin-6 (3.6 vs 4.9 ng/L, p=0.023). In multiple regression analysis, the prevalence of macrovascular diabetic complications was significantly associated with TNF-alpha -308G>A polymorphism (p<0.001) and serum concentrations of HDL-cholesterol (p=0.007) while confounding effects of further variables were excluded. CONCLUSION: TNF-alpha -308G>A polymorphism modulates cytokine serum concentrations and macrovascular complications in diabetic patients on aspirin. Diabetic carriers of the TNF-alpha -308A allele might benefit more from a prophylaxis with low dose aspirin than non-carriers.     

Parental alcoholism and early child development

In a cohort of 532 pregnant women from the general population, it was found by compilation of the results from interviews, police records, hospital records and social welfare records that 23 mothers and 51 fathers in 64 families (12%) were suffering from alcoholism/heavy drinking. In these 64 families, the mother was an addict in only 13 families, both parents were addicts in 10 families, and in the remaining 41 families only the father was an addict. Pregnancy, delivery, the newborn child and the child's development until their fourth year of life have been described using a multidisciplinary approach and a longitudinal prospective design. An hypothesis on mental and physical development, and the occurrence of psychopathological symptoms in the children was tested. None of the children of the 13 alcoholic mothers was born with foetal alcohol syndrome, but foetal hazard was indicated by lower birth weight and a higher rate of perinatal deaths. Children of alcoholic parents had retarded mental development and showed more behavioural problems until 4 years of age than controls, but the differences related to physical development during the first year of life had then disappeared. Boys were found to be more vulnerable than girls. The consequences of behaviour seemed to be more pronounced when both parents were alcoholics. No obvious deviation was found when only the father was addicted. Regarding mental development, it appears that factors related to parental alcoholism, including genetic and social factors, and the sex of the child, are of greater importance than the neonatal score on reduced optimality.     

CDX-2 immunostaining in primary and secondary ovarian carcinomas

AIMS: To assess the value of homeobox protein CDX-2 expression in the distinction between primary ovarian carcinomas and carcinomas metastatic to the ovary. METHODS: CDX-2 expression was assessed by immunohistochemistry in 120 serous, 68 endometrioid, 24 clear cell, and 16 mucinous carcinomas of the ovary. In addition, CDX-2 immunoreactivity was investigated in 20 metastases from adenocarcinomas to the ovary (15 of colorectal, two of gastric, one of appendiceal, one of pancreatic, and one of cervical origin) and their corresponding primary tumours. RESULTS: Almost all of the primary ovarian carcinomas lacked immunoreactivity for CDX-2. In contrast, 14 of the 16 metastases to the ovary from intestinal primaries showed CDX-2 immunoexpression. CONCLUSION: CDX-2 is a useful marker for differentiating primary ovarian carcinoma from carcinomas metastatic to the ovary.     

Structural divergence of paralogous S components from ECF-type ABC transporters

Energy coupling factor (ECF) proteins are ATP-binding cassette transporters involved in the import of micronutrients in prokaryotes. They consist of two nucleotide-binding subunits and the integral membrane subunit EcfT, which together form the ECF module and a second integral membrane subunit that captures the substrate (the S component). Different S components, unrelated in sequence and specific for different ligands, can interact with the same ECF module. Here, we present a high-resolution crystal structure at 2.1 Å of the biotin-specific S component BioY from Lactococcus lactis. BioY shares only 16% sequence identity with the thiamin-specific S component ThiT from the same organism, of which we recently solved a crystal structure. Consistent with the lack of sequence similarity, BioY and ThiT display large structural differences (rmsd = 5.1 Å), but the divergence is not equally distributed over the molecules: The S components contain a structurally conserved N-terminal domain that is involved in the interaction with the ECF module and a highly divergent C-terminal domain that binds the substrate. The domain structure explains how the S components with large overall structural differences can interact with the same ECF module while at the same time specifically bind very different substrates with subnanomolar affinity. Solitary BioY (in the absence of the ECF module) is monomeric in detergent solution and binds D-biotin with a high affinity but does not transport the substrate across the membrane.     

The Hydrogen-Bond: computational approaches and applications to drug design

This mini-review begins with a presentation of the hydrogen-bond in the context of other intermolecular recognition forces of significance in molecular biology and molecular pharmacology. This is followed by a survey of the various computational methods available to calculate the hydrogen-bonding capacity of compounds. Such methods use quantum mechanics, molecular mechanics, or algorithms based on experimental fragmental values. A recent and promising advance in the computation of H-bonding capacity is the development of specific molecular interaction fields (MIFs) known as molecular hydrogen-bonding potentials (MHBPs). Their interest in relating molecular properties to pharmacokinetic behaviour is highlighted with two examples, namely oral drug absorption and blood-brain barrier permeation.     

Functional prognosis of paraplegia due to cord ischemia: a retrospective study of 23 patients

The functional prognosis of spinal cord infarct is not well known, complicating care of patients suffering from ischemic paraplegia. The aim of this study was to evaluate the clinical and functional outcome of patients with spinal cord infarct treated in rehabilitation centers in order to identify factors influencing functional outcome. We studied cases of non-trauma-related paraplegia treated between 1992 and 1999. Spinal compression and infectious and inflammatory myelopathy were excluded. Age, gender, cardiovascular risk factors, initial and final clinical findings according to the American Spinal Injury Association (ASIA/IMSOP) criteria, MRI findings, and initial urodynamic findings were analyzed. Two groups were identified regarding extension of the spinal cord infarct to the cone or not. Assessment of functional outcome was based on the Frankel classification, ambulatory ability, wheelchair use, and bladder control. Cases of spinal cord infarct were then classified according to extension to the cone or not, determined on the basis of initial clinical, MRI, and urodynamic findings. Twenty-three patients (19 males and 4 females) were selected for analysis. Mean age was 54 years, with no mortality during the follow-up period. At discharge, the group of nine patients whose infarct had not extended to the medullary cone had a significantly better motor recovery using the ASIA motor score (p<0.01). Patients whose infarct did not extend to the cone used wheelchairs less often, were more often in Frankel class D (p<0.05), and had normal bladder control more often (p<0.05) than patients whose infarct extended to the cone. Lack of extension to the medullary cone appeared to be a factor predictive of better functional outcome.     

Screening for minimal brain dysfunction (MBD/DAMP) at six years of age: results of motor test in relation to perinatal conditions, development and family situation

The aim of this study was to investigate if children aged 6 years of age, classified as having minimal brain dysfunction (MBD) or deficit in attention, motor control and perception (DAMP), exhibit special medical problems, specific developmental features or if special psychosocial conditions exist in the family. The screening program, using the psychoneurological part of the method developed by Gillberg et al., included 234 children who were followed-up prospectively from pregnancy and birth. The results were related to the physical and mental development of the children, to the psychosocial and socioeconomic conditions of the families, to pre- and postnatal conditions and to “reduced optimality score”, as defined by Prechtl. Mental development was assessed by the use of Griffiths' test at 10-14 months and at 4-5 years of age. At the second Griffiths' test, the mother was also interviewed about the presence of aggressiveness and other symptoms of childhood psychopathology in her child, as defined by the DSM-III criteria, and a psychological observation was also made. In addition to screening for MBD/DAMP, at 6 years of age the parents were asked to complete a questionnaire aimed at identifying attention deficit disorder (ADD). No medical or psychological intervention was made before this stage. Fourteen children (9M, 5F) (6%) were identified as having a positive MBD/DAMP screening result. The results of the screening procedure showed a weak correlation with those obtained using the questionnaire based on the DSM-III criteria for ADD. Compared with the rest of the children, those with a positive MBD/DAMP screening result had an increased number of complications during pregnancy but not a reduced optimality score. At 4 years of age the performance on the Griffiths' test was lower and the rate of child psychiatric symptoms such as aggressiveness and signs of the mother having difficulties in setting limits for the child were more common than among the rest of the cohort. No relation was found with the psychosocial or socioeconomic conditions of the family. We conclude that children suspected of having MBD/DAMP at the start of school may have exhibited signs of delayed psychoneurological development and symptoms of psychopathology at 4 years of age.