Enterovirus infections in neonates

Twenty-seven ill neonates with enterovirus infections were studied to learn if enterovirus infection can be distinguished from neonatal sepsis. Enterovirus infection was associated with the summer-fall season (93%), recent maternal illness (59%), absence of other perinatal problems (81%), and findings of fever (93%), viral meningitis (62%), diarrhea (81%), and rash (41%). Four children developed thrombocytopenia and three necrotizing enterocolitis. Three children died, all with Coxsackie B virus infections that likely were acquired in utero. Although no single feature is pathognomonic, this constellation of epidemiologic and clinical findings, coupled with negative bacterial cultures, should suggest the possibility of neonatal enterovirus infection.     

Systematic screening for diabetic eye disease in insulin dependent diabetes

It has been demonstrated that alveolar macrophages (AM) are permissive for human immunodeficiency virus (HIV-1) after in vitro infection. However, data concerning in vivo infection of AM by HIV-1 still conflict. Therefore, we investigated AM collected by bronchoalveolar lavage from 15 HIV-1-infected patients. HIV-1 p24 and Gp120 antigens and viral RNA were not detected by immunocytochemistry and in situ hybridization, respectively, using 35S-labeled 3 kb Pol-Env, 0.350 kb Gag, and 0.150 kb U5 LTR cRNA probes. In contrast, when using polymerase chain reaction on DNA extracted from purified AM, HIV-1 DNA was detected in the seven patients tested. After short-term culture of alveolar cells from three HIV-1-infected patients and in vitro stimulation with granulocyte/macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha), HIV-1 replication was observed in most of the AM. These results demonstrate that AM are latently infected by HIV-1 in vivo but are not a site for viral replication. In contrast, HIV-1 replication occurs when AM are withdrawn from their local environment, enhanced by GM-CSF and TNF-alpha stimulation. This suggests either a negative control or an inadequate stimulation of HIV-1 replication in the alveolar environment.     

Enterovirus infections in Ukraine

An analysis has been done of isolation of enteroviruses from infectious patients with various diagnoses, as well as from those persons examined on epidemiological indications, and healthy children over a period of twelve years (1980-1992). There have been determined serotypes of enteroviruses prevailing in one or another form of infection as well as in healthy (asymptomatic) carriers. Enteroviruses were shown to have a potential role in the etiology of a major portion of those medical conditions diagnosed as serous meningitis, neuroinfection, ARVI, and others.     

Enterovirus infections as a possible risk factor for myocardial infarction

BACKGROUND: An increasing body of evidence suggests that, in addition to the well-known classic risk factors, some microbial infections may be associated with the development of atherosclerosis and myocardial infarction (MI). The aim of our study was to evaluate the possible role of enteroviral infections in the pathogenesis of MI. METHODS AND RESULTS: Stored sera, collected in Eastern Finland in 1977, from a set of 12 155 randomly selected men and women aged 25 to 64 years were used in prospective, nested case-control study. The study sample comprised 183 men and 81 women with MI and matched controls. The sera were tested for IgG antibodies to a newly identified enterovirus-common (EVC) antigen, to heat-denatured coxsackievirus B5 (CBV-5), and to adenovirus hexon protein. Raw data from enzyme immunoassays were converted to relative units before analysis. In univariate analysis, EVC antibodies were significantly associated with the risk of MI in men (P=0.009) but not in women. Men with MI had a significantly higher mean level of EVC antibodies than matched controls (P=0.014). High antibody levels to EVC were associated with an increased risk of MI in men aged 25 to 49 years (relative risk [RR] 4.34, P<0.001) but not in older men (>50 years of age). Women with MI also showed a trend toward higher antibody levels than control women, but the difference was not statistically significant. Antibody levels to whole CBV-5 or adenovirus hexon protein appeared to be no different among case patients versus control subjects. CONCLUSIONS: If we assume that a high level of EVC antibodies reflects a history of relatively frequent enterovirus infections, the present observation might suggest that enterovirus infections increase the risk of MI at least in middle-aged men. Further studies are needed to understand possible clinical significance of this observation.     

Urinary excretion of extracellular matrix proteins in insulin dependent diabetes mellitus

The purpose of the study was to assess urinary excretion of extracellular matrix proteins and proteolytic enzymes in 12 subjects with IDDM with albuminuria, 12 subjects with IDDM without microalbuminuria and 10 normal healthy subjects. Urinary excretion of FN was significantly higher in subjects with IDDM and albuminuria as compared to patients with IDDM without microalbuminuria and healthy subjects (223.6 +/- 143.2 vs. 103.2 +/- 59.7 vs. 58.3 +/- 12.0 ng/mg creatinine, p < 0.01). Urinary level of type IV collagen was significantly elevated in subjects with IDDM and albuminuria as compared to IDDM without microalbuminuria and healthy subjects of cathepsin B was significantly higher in diabetic patients with albuminuria as compared to patients without microalbuminuria and healthy subjects (0.82 +/- 0.53 vs. 0.25 +/- 0.17 vs. 0.22 +/- 0.05 mlU/mg creatinine, p < 0.01). Urinary activity of plasmin was significantly elevated in diabetic patients with albuminuria as compared to subjects without microalbuminuria and healthy control (0.477 +/- 0.37 vs. 0.194 +/- 0.09 vs. 0.21 +/- 0.02 mlU/mg creatinine, p < 0.01). Our data indicate that increase in the urinary excretion of extracellular matrix proteins may be the useful tool for monitoring glomerular injury.     

Incidence of insulin dependent diabetes mellitus in children of Shanghai, China

Seven patients with seven acute slipped capital femoral epiphyses (SCFE) had computed tomography (CT) scan determination of femoral version. Version value differences were compared between the involved and uninvolved sides, and each was compared with a standard value for age. Comparison was also made with chronic slipped femoral version values. As compared to the standard of 20 degrees, the acute, involved side femoral version was 9.3 degrees (p = 0.057). Comparisons of involved and uninvolved sides showed no significant difference (p = 0.25). Analysis of differences of bilateral femoral version of patients with acute SCFE with that of patients with chronic SCFE version showed a significant difference (p = 0.009). Version in patients with acute SCFE more closely resembles the normal value than does that of patients with chronic SCFE, further emphasizing the uniqueness of the acute type of SCFE.     

Changes in attention with hypo- and hyperglycaemia in children with insulin dependent diabetes mellitus

We compared the results of a computerized attention test (TOVA) in 38 children with insulin dependent diabetes mellitus in relation to various spontaneously occurring blood glucose levels. Testing was performed at the following blood glucose levels: <3.3 mmol/1 (hypoglycaemia), 3.3-8.3 mmol/1 (normoglycaemia) and >8.3 mmol/1 (hyperglycaemia). The attention (sum of errors and response time) varied significantly with the blood glucose level (P = 0.002). The highest number of errors of omission and the longest response time was observed during the test run with hypoglycaemia. Age, sex, age at manifestation of the disease, metabolic control and the results of the intelligence test had no significant influence on these results. We found that attention in children with diabetes was significantly reduced compared to TOVA norms especially during mild hypoglycaemia (P < 0.001). Irrespective of the blood glucose levels, reaction time and the variability of the reaction time differed significantly between TOVA norms and diabetic children (P < 0.01). CONCLUSION: In children with diabetes mellitus a significant reduction in attention was found at mild hypoglycaemia but as well at low normal blood glucose levels. Attention deficits due to transient lowering of blood glucose may therefore occur in diabetic children even before they are aware of hypoglycaemic symptoms.     

Glycosylated hemoglobin and fetal growth in normal, gestational and insulin dependent diabetes mellitus pregnancies

Aims of the study were: evaluation of HbA1c levels in the peripheral blood of pregnant women with insulin dependent diabetes, gestational diabetes, glucose intolerance, and healthy pregnant controls; implications of HbA1c concentration on detection and the control of women with impaired carbohydrate metabolism in pregnancy; comparison of HbA1c levels with appearance of miscarriages, and premature deliveries; comparison of weight gain during pregnancy to HbA1c levels; comparison of difference from ideal body weight with HbA1c in diabetic pregnant women; comparison of neonatal birth weight and HbA1c levels. 290 pregnant women were enrolled to the study. The highest value of HbA1c was in the group IDDM pregnant women (7.7% +/- 1.8%), and the lowest value of HbA1c was in the control group (4.1% +/- 0.5%). Statistically significant coefficients were found between HbA1c and weight gain during pregnancy, between weight deviation from ideal body weight and HbA1c (r = 0.54 and r = 0.48 respectively); and between newborns weight and HbA1c (r = 0.51). Well regulated glycemia and intensive pregnancy follow-up of diabetic women reduces stillbirths, neonatal complications and neonatal macrosomia incidence.     

Reduced immune response to hepatitis B vaccine in children with insulin dependent diabetes

The aim of this study was to determine whether fasting gastric volumes could be reduced by preoperative administration of cisapride. One hundred and twenty-one patients undergoing elective general anaesthesia were randomly allocated to receive either cisapride 20 mg plus diazepam 10 mg or placebo tablets plus diazepam 10 mg, two hours prior to induction. Immediately following induction blind gastric aspiration was performed using a 16Fr multiorificed orogastric tube. Gastric volume, pH, and cisapride blood concentration were measured at this time. Gastric volumes were significantly smaller in the cisapride group, 20.5 (SD 22.2) ml compared to placebo 28.2 (SD 26.0) ml but there was no significant difference with respect to pH. Some patients in both groups had large gastric volumes despite fasting. No significant adverse effects were noted with cisapride.     

Enterovirus infections in acute pancreatitis - a possible etiological connection

All patients admitted with a preliminary diagnosis of acute pancreatitis during a one-year period were subjected to virus investigations. 142 patients were included in the study and of these 91 were found to have acute pancreatitis. Evidence of enteroviral infection was found in 18 of the 91 patients (19.8 per cent). From 17 of the 18 patients enterovirus was isolated from feces or urine, and in one a significant titer rise (CF-test) against Coxsackie virus B5 was found. A significant titer rise of antibodies against the virus type isolated could be demonstrated in 7 of the 17 patients. Thus in 8 cases there was obvious evidence of an acute enteroviral infection during the episode of acute pancreatitis. The etiological agents in these cases were Coxsackie viruses B2, B3, and B5, and ECHO-viruses 6, 11, 22, and 30.     

Homozygous parent affected sib pair method for detecting disease predisposing variants: application to insulin dependent diabetes mellitus

For complex genetic diseases involving incomplete penetrance, genetic heterogeneity, and multiple disease genes, it is often difficult to determine the molecular variant(s) responsible for the disease pathogenesis. Linkage and association studies may help identify genetic regions and molecular variants suspected of being directly responsible for disease predisposition or protection, but, especially for complex diseases, they are less useful for determining when a predisposing molecular variant has been identified. In this paper, we expand upon the simple concept that if a genetic factor predisposing to disease has been fully identified, then a parent homozygous for this factor should transmit either of his/her copies at random to any affected children. Closely linked markers are used to determine identity by descent values in affected sib pairs from a parent homozygous for a putative disease predisposing factor. The expected deviation of haplotype sharing from 50%, when not all haplotypes carrying this factor are in fact equally predisposing, has been algebraically determined for a single locus general disease model. Equations to determine expected sharing for multiple disease alleles or multiple disease locus models have been formulated. The recessive case is in practice limiting and therefore can be used to estimate the maximum proportion of putative susceptibility haplotypes which are in fact predisposing to disease when the mode of inheritance of a disease is unknown. This method has been applied to 27 DR3/DR3 parents and 50 DR4/DR4 parents who have at least 2 children affected with insulin dependent diabetes mellitus (IDDM). The transmission of both DR3 and DR4 haplotypes is statistically different from 50% (P < 0.05 and P < 0.001, respectively). An upper estimate for the proportion of DR3 haplotypes associated with a high IDDM susceptibility is 49%, and for DR4 haplotypes 38%. Our results show that the joint presence of non-Asp at DQ beta position 57 and Arg at DQ alpha position 52, which has been proposed as a strong IDDM predisposing factor, is insufficient to explain the HLA component of IDDM predisposition.     

Autoimmune diabetes: caught in the causality trap?

The lack of concordance between genotype and clinical diabetes has prompted a search for the infectious agent that precipitates this autoimmune disease. However, this approach may be misleading. It assumes that the disease-prone individuals that do not develop diabetes do not have autoimmunity. In the non-obese diabetic (NOD) mouse, the genotype is a primary determinant of autoimmunity. Not all animals of the disease-prone genotype develop clinical disease; however, all have autoimmunity. This is expressed as a destructive or non-destructive process. Multiple pathways are open to the immune system and whether or not the immune response is destructive and leads to the development of clinical disease, appears to be a random process. If this is the case, the most important questions relating to autoimmune disease are not those concerning the 'causative' agents. Instead we should be asking what are the differences between pathways open to the immune system and what factors affect the probability that one or another pathway is finally selected?     

Zinc, insulin and diabetes

Miso, a widely used Japanese fermented food was analysed for its lactic acid bacterial count on bromocresol purple agar. The binding of eight different foodborne carcinogenic heterocyclic amines to 25 bacterial isolates from miso were investigated. The heterocyclic amines used were 3-amino-1,4-dimethyl[5H]pyrido(4,3-b)indole (Trp-P-1), 3-amino-1-methyl[5H]pyrido(4,3-b)indole (Trp-P-2), 2-amino-6-methyldipyrido(1,2-a:3'2'-d)imidazole (Glu-P-1), 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), 2-amino-dimethylimidazo(4,5f)quinoline (IQ), 2-amino-3,4-dimethylimidazo(4,5-f) quinoline (MeIQ), 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx), and 2-amino-3-methyl-9H-pyrido(2,3)indole (MeA alpha C). The lyophilized cells of all of the isolates exhibited high binding activity towards Trp-P-1, Trp-P-2, MeA alpha C, and PhIP, while Glu-P-1 and IQ were not effectively bound. Of the isolates tested, the strongest and weakest binders were identified as Pediococcus acidilactici 1 and 2, respectively. Lyophilized cell wall fractions, heat-treated cells, and the cytoplasmic contents of P. acidilactici 1 and 2 were analysed for their ability to bind to different mutagens. Pure cell wall and peptidoglycan showed greater binding activity than the bacterial cells. Cytoplasmic content also showed some binding, but it was much less effective. The impact of enzymes (amylase, protease, cellulase, chitinase, muraminase, and peptidase) and acetylation of Trp-P-1 and IQ on the binding action of bacteria and cell wall material were also analysed to understand the possible processes involved in the binding of lactic acid bacteria to carcinogenic heterocyclic amines.     

Electrophoretic analysis of polypeptides and glycopeptides of erythrocyte membrane sampled from rats simulating mild insulin dependent diabetes mellitus

In order to understand the molecular mechanism of reduced life span of diabetic erythrocyte, polypeptides and glycopeptides were analyzed by disc gel preparative sodium dodecyl sulphate polyacrylamide gel electrophoresis. An additional glycopeptide (244.5 kDa) and two additional polypeptides (39.81 and 144.5 kDa) were observed on glycopeptide and polypeptide gel profiles of mild insulin dependent diabetes mellitus (mIDDM) sample as compared to control. On the basis of molecular weight, their position on gel profile and their widely accepted nomenclature they were termed as glycosylated-ankyrin, membrane accreted glyceraldehyde-3-phosphate dehydrogenease (G 3-PD) and stress induced band 2.3 peptide. Earlier we have reported an increase in heterogeneity associated with increase in the population of aged fragile cells having altered membrane bound cation dependent ATPases, cytosolic dehydrogenase and hexokinase activities of mIDDM simulating rat erythrocyte sample. Significance of above observation in view of our earlier observation is discussed to explain the molecular mechanism of reduced life span of diabetic erythrocytes.     

Anserine bursitis and non-insulin dependent diabetes mellitus

OBJECTIVE: To determine the relationship between non-insulin dependent diabetes mellitus (NIDDM), knee pain, and anserine bursitis, and its relation to sex, age, or body mass index (BMI). METHODS: Ninety-four consecutive patients with NIDDM, 66 women and 28 men, and 57 nondiabetic patients, 36 women and 22 men, were examined at an outpatient clinic of a tertiary care hospital. Date of onset in patients with NIDDM was noted, and serum was analyzed for either hemoglobin A1C (HbA1C) or glycosylated hemoglobin (GHb) in 69 of these patients. Anserine bursitis was diagnosed if knee pain and tenderness at the bursal site were found on examination. RESULTS: On examination 34 (36%) patients with NIDDM were found to have anserine bursitis. Of these, 31 (91%) were women and 3 (9%) were men (p < 0.05). Age, BMI, duration of diabetes, HbA1C or GHb, and age of onset of diabetes were found not to differ significantly between patients with and those without anserine bursitis. CONCLUSION: A relationship exists between NIDDM, knee pain, and anserine bursitis unrelated to age, BMI, duration and control of diabetes, and age at the diagnosis of diabetes.