Vav1 haploinsufficiency in a common variable immunodeficiency patient with defective T-cell function.

Common variable immunodeficiency (CVID) is a primary immune disorder characterized by impaired antibody production, which is in many instances secondary to defective T cell function (T-CVID). We previously identified a subset of T-CVID patients characterized by defective expression of Vav1, a guanine nucleotide exchanger which couples the T-cell antigen receptor to reorganization of the actin cytoskeleton. Here we have addressed the possibility that an intrinsic defect in the Vav1 gene might underlie the reduction in Vav protein observed in T cells from these patients. We report the identification in one T-CVID patient of a heterozygous deletion in Vav1. The gene deletion, spanning exons 2-27, accounts for the reduction in Vav1 mRNA and protein in T cells from this patient. The disease-related pedigree of this patient suggests a de novo origin of the Vav1 deletion. The findings highlights Vav1 as an autosomal dominant disease gene associated with CVID with defective T-cell function.

Significant bacteriuria in outpatient diabetic and non-diabetic persons.

AIMS: The prevalence of significant bacteriuria (SB) in diabetes mellitus has not been clearly established. Having previously investigated SB frequency in inpatient diabetic women, we now screened for SB (both asymptomatic and symptomatic forms) in outpatients. METHODS: We examined 511 consecutive outpatients with Type 1 (T1D) or Type 2 diabetes (T2D), and 98 non-diabetic subjects. At least one uncontaminated midstream urine sample was available from 602 subjects: 64 T1D (37 female, age 49 +/- 13 years, diabetes duration 23 +/- 15 years), 441 T2D (212 female, 66 +/- 10 years, 12 +/- 10 years), and 97 healthy control subjects (39 female, 57 +/- 12 years). On the same day, we determined: blood cell count, fasting plasma glucose (FPG), glycated haemoglobin (HbA(1c)), plasma creatinine, urinary creatinine, and urinary albumin excretion (UAE; microg/mg urinary creatinine). RESULTS: The rate of SB was 14.1% in T1D, 9.3% in T2D and 6.2% in control subjects (P = NS). The 50 diabetic patients with SB differed from the 455 diabetic patients without SB in gender (43 male vs. 206 female, P < 0.001), FPG (10.2 +/- 3.6 vs. 9.2 +/- 2.9 mmol/l, P < 0.05), HbA(1c) (7.8 +/- 1.1 vs. 7.5 +/- 1.3%, P < 0.05), and UAE (median 15.6 vs. 7.6 microg/mg, P < 0.01). Eleven diabetic patients with SB had symptoms (vs. 48 without SB, P < 0.05); UAE levels were higher in the 39 asymptomatic diabetic patients with SB than in the 11 symptomatic patients. CONCLUSIONS: The prevalence of SB is similar in outpatient diabetic individuals and in non-diabetic subjects. The main risk factors for SB in diabetic patients were female gender and UAE. The likelihood of asymptomatic SB increased with UAE levels, i.e. with the presence of established microangiopathy. Poor glycaemic control is associated with bacteriuria, either as a cause or consequence of bacteriuria.

[Pneumothorax in severe chest injuries]. / Il pneumotorace nei gravi traumi toracici.

The authors reviewed CT scans and supine chest X-ray of 47 patients affected by severe thoracic trauma, examined in 1985-86. The sensibility of the two methodologies in the assessment of pneumothorax was compared. CT detected 25 pneumothorax, whereas supine chest X-ray allowed a diagnosis in 18 cases only. In 8 of the latter (44.4%) the diagnosis was made possible by the presence of indirect signs of pneumothorax only--the most frequent being the deep sulcus sign. The characterization of pneumothorax is important especially in the patients who need to be treated with mechanical ventilation therapy, or who are to undergo surgery in total anaesthesia.