Vav3 modulates B cell receptor responses by regulating phosphoinositide 3-kinase activation.

To elucidate the mechanism(s) by which Vav3, a new member of the Vav family proteins, participates in B cell antigen receptor (BCR) signaling, we have generated a B cell line deficient in Vav3. Here we report that Vav3 influences phosphoinositide 3-kinase (PI3K) function through Rac1 in that phosphatidylinositol-3,4,5-trisphosphate (PIP3) generation was attenuated by loss of Vav3 or by expression of a dominant negative form of Rac1. The functional interaction between PI3K and Rac1 was also demonstrated by increased PI3K activity in the presence of GTP-bound Rac1. In addition, we show that defects of calcium mobilization and c-Jun NH2-terminal kinase (JNK) activation in Vav3-deficient cells are relieved by deletion of a PIP3 hydrolyzing enzyme, SH2 domain-containing inositol polyphosphate 5'-phosphatase (SHIP). Hence, our results suggest a role for Vav3 in regulating the B cell responses by promoting the sustained production of PIP3 and thereby calcium flux.     

Prospective randomized controlled trial of urethral versus suprapubic catheterization

Sixty-six patients requiring catheterization in the course of general surgical operations were randomly allocated into two groups. Of the 34 patients catheterized urethrally 16 developed urinary tract infections whereas of the 32 suprapubically catheterized patients only 2 developed an infection (P less than 0.001). Five patients required recatheterization after removal of their urethral catheters. There were no major complications associated with the use of suprapubic catheters. We propose that, when catheterization is required during a general surgical procedure, the suprapubic route is to be preferred.     

Periodic lateralized epileptiform discharges: etiology, clinical aspects, seizures, and evolution in 130 patients.

The purpose of this study was to analyze the clinical aspects in 130 patients presenting periodic lateralized epileptiform discharges (PLEDs) in their EEG and to compare these results with those found in the literature. Etiology, neurologic deficit, seizure occurrence, and evolution were studied in each patient by historical review. The recordings were obtained on 8- or 16-channel EEGs with electrode placement according to the International 10-20 System. Recordings containing PLEDs were selected. PLEDs were defined as repetitive periodic, focal, or hemispheric epileptiform discharges (spikes, spike and waves, polyspikes, sharp waves) usually recurring every 1 to 2 seconds. The statistical study was carried out via the chi(2) test using the computer program SPSS. The main etiology found in this group of patients was stroke (61 of 130 patients). Other processes found were brain infections, tumors, hematomas, and several other entities grouped together as miscellaneous (anoxic encephalopathy, subarachnoid hemorrhage, craniocerebral trauma, Creutzfeldt-Jacob disease, migraine, multiple sclerosis, and aminophylline intoxication). Half of these patients (65 of 130) developed seizures, mostly partial motor seizures. No significant relation between etiology and seizures was found (chi(2) = 2.81, P = 0.4222). Seizures recurred in 14 of 130 patients during a follow-up of 14.5 months. PLEDs were not recorded in any EEG at the time of seizure recurrence. PLEDs constitute a distinctive but uncommon EEG phenomenon of repetitive, periodic, and stereotyped lateralized complexes. In agreement with the literature, PLEDs were associated with an acute process and occurred early during the course of the illness in all patients studied and were usually associated with structural lesions, with stroke being the main etiology. Traditionally, seizures occur with PLEDs but it is also accepted that they can exist in patients who never develop epileptic activity, either clinically or electrically, as demonstrated in 50% of the patients studied. No significant association between seizures and any etiology could be found. It was not demonstrated that the occurrence of seizures may influence the outcome in any way.     

Benefits of quadruple immunosuppressive therapy in recipients of living related donor kidneys. A review of 855 operations.

Eight hundred fifty-five living related donor transplant recipients were analyzed according to 15 potential risk factors with regard to patient and graft survival according to immunosuppression. Group I, 1968 to 1983, (n = 440 patients) received azathioprine and prednisone; group II, 1984 to 1987, (n = 229 patients) received triple therapy--azathioprine, prednisone, and cyclosporine; and group III, 1988-1991, (n = 186 patients), quadruple therapy--azathioprine, prednisone, cyclosporine, and Minnesota antilymphocyte globulin. Three important risk factors included immunosuppression, tissue typing, and race. Groups II and III had improved allograft survival over group I (p = 0.03). Patients with two haplotype matches had similar survival in all three groups. Kidney survival in one-haplotype-matched recipients improved in group II and was equal to that of the two-haplotype-matched patients in group III. Cyclosporine improved allograft survival in both races when combined with azathioprine and prednisone. Quadruple therapy improved early survival in one-haplotype black patients, even though long-term results remained better in whites. Cyclosporine did not improve graft survival in two-haplotype recipients. The addition of cyclosporine and quadruple therapy did not increase morbidity and mortality rates.     

Intensive versus standard blood glucose awareness training (BGAT) with insulin-dependent diabetes: mechanisms and ancillary effects

Insulin-dependent diabetes mellitus (IDDM) patients make critical daily self-care decisions on the basis of what they estimate their blood glucose (BG) levels to be. This study: a) replicated efficacy of Standard Blood Glucose Awareness Training (BGAT), b) evaluated the relative efficacy of an Intensive Blood Glucose Awareness Training (BGAT) to enhance patient accuracy of BG estimation, and c) evaluated the mechanisms and ancillary effects of BGAT. Thirty-nine subjects were randomly assigned to one of three groups. Compared with Control, both Standard and Intensive BGAT improved accuracy (p less than 0.001). Intensive BGAT post-treatment accuracy relative to Standard BGAT did not reach statistical significance (p = 0.177). Greater improvement in accuracy was associated with poorer pretreatment accuracy. Only Intensive BGAT improved metabolic control (glycosylated hemoglobin), and this improvement was associated with poorer pretreatment control. The effects of BGAT were highly specific, affecting only accuracy and metabolic control, and not affecting fear of hypoglycemia, diabetes knowledge, of frequency of blood glucose monitoring.