Glucose utilization in Type 1 (insulin-dependent) diabetes: Evidence for a defect not reversible by acute elevations of insulin

It has long been assumed that replacement of insulin in insulin-deficient diabetic patients will normalise glucose utilization. In this study, glucose utilization was measured in nine long-standing, poorly controlled diabetic patients and five control subjects, matched for age (33 +/- 3 versus 33 +/- 2 years) and ponderal index (22.9 +/- 1.3 versus 21.7 +/- 1.0). Glucose uptake was measured during steady state insulinaemia in the diabetic patients and control subjects, at euglycaemia (5.5 +/- 0.5 versus 5.4 +/- 0.3 mmol/l, respectively) and moderate hyperglycaemia (11.8 +/- 0.9 versus 10.2 +/- 0.7 mmol/l, respectively). At euglycaemia with similar free insulin levels (50 +/- 19 versus 43 +/- 9 mU/l; p greater than 0.6), the diabetic patients utilized less glucose than the control subjects (27.8 +/- 4.2 versus 56.4 +/- 5.7 mumol.kg-1.min-1;.p less than 0.005). During hyperglycaemia, the diabetic patients utilized almost as much glucose as the control subjects did at euglycaemia (49.9 +/- 6.4 versus 56.4 +/- 5.7 mumol.kg-1.min-1, respectively). In the control subjects, a 1-mmol/l rise in glucose concentration (with insulin remaining constant) resulted in a 12.3 +/- 1.3 mumol.kg-1.min-1 rise in glucose utilization. In contrast, in the diabetic patients, a 1-mmol/l rise in blood glucose resulted in a rise in glucose utilization of only 3.8 +/- 0.8 mumol.kg-1.min-1 (p less than 0.001), in the presence of similar concentrations of plasma insulin. This defect of glucose utilization in Type1 diabetic patients could not be reversed by acutely raising insulin to 247 +/- 23 mU/l.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low-molecular weight heparin induces in vitro trophoblast invasiveness: role of matrix metalloproteinases and tissue inhibitors

Heparin is used widely for the prevention of pregnancy loss in pregnant women with thrombophilia. However, it is still unknown if heparin may be able to affect trophoblast functions. Therefore, we investigated the hypothesis that low-molecular weight heparin (LMWH) might regulate in vitro trophoblast invasiveness and placental production of matrix metalloproteinases (MMPs) and tissue inhibitors (TIMPs). In the first-trimester placental tissue, the MMP-9 expression was observed in both villous and extravillous cytotrophoblast cells, and MMP-2 mainly in villous cytotrophoblast. In human choriocarcinoma cells (JAR), MMP-2 was the dominant form. Heparin significantly enhanced both pro-MMPs and the active forms, and increased Matrigel invasiveness of extravillous trophoblast and choriocarcinoma cells. In choriocarcinoma cells the heparin effect was also indirect, inducing a significant decrease in TIMP-1 and TIMP-2 protein expressions and mRNAs. The present data suggest that the increase in trophoblast invasion by heparin is due to a specific protein playing a role in placental invasion. These observations may help in understanding the effects of heparin treatment during pregnancy.     

Diagnostic yield of CT-guided lung biopsies: how can we limit negative sampling?

Objectives:To investigate whether lesion imaging features may condition the outcome of CT-guided lung biopsy (CTLB) and to develop a scoring system of biopsy outcome prediction.Methods:This is a single center retrospective study on 319 CTLBs that were performed in 319 patients (167 males/152 females, mean age 68 ± 12.2). Uni- and multivariate analysis were performed aiming to assess the imaging features that are likely to be correlated to a negative biopsy outcome and patients were stratified in groups accordingly.Results:Technical success was 100%. 78% of the biopsies (250/319) led to a concrete histology report (218 malignant/32 benign). The remaining lesions led to concrete histology at a second attempt that occurred on a later time. Multivariate analysis revealed increased risk of inconclusive result for nodules with low fludeoxyglucose uptake [odds ration (OR) = 2.64, 95% confidence interval (CI) 1.4–4.97; p = 0.003], for nodules with diameter smaller than 18 mm (OR = 2.03, 95% CI 1.14–3.62; p = 0.017) and for nodules that are located in one of the lung bases (OR = 1.96, 95% CI 1.06–3.62; p = 0.033). Three different groups of patients were identified accordingly with low (<30%), medium (30–50%) and high (>50%) probability of obtaining an inconclusive biopsy sample.Conclusion:This study confirms that percutaneous CT-guided biopsy in nodules that are either small in diameter or present low positron emission tomography-fludeoxyglucose uptake or are in one of the lung bases may lead to inconclusive histology. This information should be factored when planning percutaneous biopsies of such nodules in terms of patient informed consent and biopsy strategy.Advances in knowledge:Inconclusive histology after lung biopsy may be subject to factors irrelevant to technical success. Lung biopsy histology outcomes may be predicted and avoided after adequate planning.     

CA19-9 serum levels in obstructive jaundice: clinical value in benign and malignant conditions

Background

Obstructive jaundice is frequently associated with false CA19-9 elevation in benign conditions. The diagnostic accuracy of this tumor marker was evaluated in the present longitudinal study.

Methods

In 128 patients admitted for obstructive jaundice (87 with pancreato-biliary malignancy and 41 benign disease) serum CA19-9 was measured. Statistical analysis of marker levels obtained before and after endoscopic biliary drainage was performed in 60 patients.

Results

Elevated CA19-9 levels (>37 U/mL) were found in 61% of benign cases and 86% of malignancies. After biliary drainage, decrease of serum CA19-9 was observed in 19 of 38 malignant cases and in almost all benign cases (Wilcoxon matched pairs test: P = .207 and P <.001, respectively). Receiver operating characteristic (ROC) analysis identified a cut-off value of 90 U/mL to be associated with improved diagnostic accuracy after biliary drainage (sensitivity 61%, specificity 95%).

Conclusions

In the presence of successfully drained obstructive jaundice, CA19-9 serum levels that remain unchanged or measure more than 90 U/mL are strongly indicative of a malignant cause of obstruction. However, the real clinical utility of this marker remains controversial.     

Isolation and characterization of a mRNA encoding a novel insulin receptor (IR) subtype, IR2, from rainbow trout (Oncorhynchus mykiss) and patterns of expression of the four IR subtypes, IR1-IR4, in tissues and during embryonic development

Insulin (INS) plays a critical role in the growth, development, and metabolism of vertebrates. In this study, a cDNA encoding a novel insulin receptor (IR) subtype was isolated, cloned, and sequenced from the liver of rainbow trout. A 1525-bp cDNA encoding a partial amino acid sequence of the β-subunit including the transmembrane domain, the tyrosine kinase domain, and the 3′ untranslated region (UTR) was obtained and designated IR2 based on comparison with known IR subtypes, including the three previously reported IR subtypes of trout. Trout IR2 shares 90.0%, 82.8%, and 84.3% nucleotide identity with previously characterized trout IR1, IR3 and IR4, respectively. Quantitative real-time PCR revealed that the four IR mRNAs were differentially expressed, both in terms of distribution among tissues as well as in terms of abundance within selected tissues of juvenile trout. IR1 mRNA was most abundant in spleen, liver, kidney, and muscle (white, red and cardiac), but least abundant in adipose. IR3 mRNA was most abundant in liver, spleen, kidney, and pancreas; in other tissues, levels of IR3 mRNA were uniformly abundant. By contrast, levels of IR2 and IR4 mRNA were uniformly abundant in most tissues, except in spleen where levels of IR4 were significantly lower. All IR subtypes were detected over the course of embryonic development. In head and tail regions, levels of IR2 and IR3 mRNA declined from pre-hatch (29 days post-fertilization, dpf) to post-hatch (68-90 dpf), whereas levels of IR1 and IR4 remained relatively unchanged. These findings contribute to our understanding of the evolution, distribution, and function of insulin receptors.     

Food allergy is associated with an increased risk of asthma

Background The atopic march is well documented, but the interrelationship of food allergy (FA) and asthma is not well understood.
Objective The aim of this study was to examine the strength of the association and temporal relationships between FA and asthma.
Methods This analysis included 271 children 6 years (older group) and 296 children <6 years (younger group) from a family-based FA cohort in Chicago, IL. Asthma was determined by parental report of physician diagnosis. FA status was determined based on the type and timing of clinical symptoms after ingestion of a specific food, and results of prick skin test (Multi-Test II) and allergen-specific IgE (Phadia ImmunoCAP). Analyses were carried out using logistic regression accounting for important covariates and auto-correlations among siblings. Kaplan–Meier curves were used to compare the time to onset of asthma with the FA status.
Results Symptomatic FA was associated with asthma in both older [odds ratio (OR)=4.9, 95% confidence interval (CI): 2.5–9.5] and younger children (OR=5.3, 95% CI: 1.7–16.2). The association was stronger among children with multiple or severe food allergies, especially in older children. Children with FA developed asthma earlier and at higher prevalence than children without FA (Cox proportional hazard ratio=3.7, 95% CI: 2.2–6.3 for children 6 years, and hazard ratio=3.3, 95% CI: 1.1–10 for children <6 years of age). No associations were seen between asymptomatic food sensitization and asthma.
Conclusions Independent of markers of atopy such as aeroallergen sensitization and family history of asthma, there was a significant association between FA and asthma. This association was even stronger in subjects with multiple food allergies or severe FA.     

Low-dose aspirin and vascular response in pregnant patients sensitive to angiotensin II.

The angiotensin sensitivity test was performed in 25 high risk pregnant women before and after administration of low-dose aspirin (100 mg/day for 7 days). After aspirin administration there was a significant decrease in AII sensitivity in sensitive patients with no change in nonsensitive patients. Low-dose aspirin favorably affects sensitivity to AII in sensitive patients, thus indicating a reduced vascular reactivity as a consequence of this regimen.     

Circulating immunocomplexes and laryngeal carcinoma

Serum levels of circulating immunocomplexes (CIC) were studied in a group of 37 patients with laryngeal carcinoma using two polyethylene glycol-precipitation methods. The preoperative values of this group showed higher levels of CIC when compared with 140 normal controls. No correlation was noted between tumoral stage, oncotype, and serum levels of CIC. Previous studies have shown that the status of several different types of human tumors can be monitored by serial determinations of levels of CIC. We believe that this technique can be used to evaluate the efficacy of therapy and to detect the recurrence of laryngeal carcinoma.