Imaging of activated microglia with PET and [11C]PK 11195 in corticobasal degeneration.

Positron emission tomography (PET) using [(11)C]PK 11195, a ligand for peripheral benzodiazepine receptor binding sites, offers the opportunity to image activated microglia in vivo. This tool may therefore be used to display the occurrence of microglial activation in the course of neurodegeneration. A patient with the clinical diagnosis of corticobasal degeneration (CBD) and left-sided symptoms was studied using fluorodeoxyglucose (FDG) and [(11)C]PK 11195 PET. We found a marked right hemispheric hypometabolism and asymmetric microglial activation in corresponding areas of the basal ganglia and right temporal and parietal cortex. [(11)C]PK 11195 PET suggests involvement of microglial activation in the pathogenesis of CBD.     

Effect of olanzapine treatment on platelet glutamine synthetase-like protein and glutamate dehydrogenase immunoreactivity in schizophrenia.

According to contemporary views, the glutamatergic system is implicated in the pathogenesis of schizophrenia, and atypical neuroleptics exert their effects (at least partially) through the glutamatergic system. Immunoreactive glutamate-metabolising enzymes, such as glutamine synthetase-like protein (GSLP) and two glutamate dehydrogenase isoenzymes (GDH), have been discovered in human platelets. The amount of GSLP in the platelets of 40 chronic patients with schizophrenia was found to be significantly higher than in 33 controls (consistent with our previous finding of increased amounts of GSLP in the prefrontal cortex of chronic schizophrenia patients). Moreover, survival analysis of the group of patients treated with olanzapine for 28 weeks showed that the larger amount of GSLP measured in platelets before treatment, the shorter the treatment time needed to achieve a positive clinical response (defined a priori as > or = 20% reduction in PANSS total score from the initial level before the treatment). Hence, GSLP level may serve as a predictor of the treatment duration to achieve a positive outcome with olanzapine. Both GSLP and GDH were found significantly changed in the course of treatment; hence, treatment with olanzapine influences the amounts of glutamate-metabolising enzymes in the platelets of chronic schizophrenia patients.     

Radical prostatectomy for adenocarcinoma of the prostate: The influence of preoperative and pathologic findings on biochemical disease-free outcome

Objective. This retrospective study evaluated the outcome for a cohort of men undergoing radical retropubic prostatectomy alone as primary treatment for clinical T1–2 prostate adenocarcinoma.Methods. Sixty-two patients treated at Boston University Medical Center between 1987 and 1992 underwent radical prostatectomy alone without adjuvant or neoadjuvant endocrine therapy. Actuarial and multivariate analyses were made of disease-free outcome according to preoperative tumor T stage, prostate-specific antigen (PSA), and biopsy grade, and according to the pathologic findings at surgery. Recurrence was defined as the persistence or recurrence of detectable serum PSA four or more weeks following surgery.Results. Of all patients judged clinically to have localized disease (T1–2), 52 percent proved to have pathologic T3 tumors. Of these, 81 percent had positive surgical margins. The strongest preoperative predictors of pT3 disease were the biopsy Gleason grade and the initial serum PSA value. Actuarial analysis showed the overall likelihood of remaining free from detectable PSA at four years to be 43 percent (75% for those with organ-confined disease and 27% for those who were pT3). The poorest prognosis was seen in those with seminal vesicle involvement. Biopsy Gleason grade and initial PSA were independent preoperative predictors of biochemical failure in a Cox regression analysis but clinical T stage was not.Conclusions. The biopsy Gleason grade and initial PSA were identified as strong preoperative predictors of disease-free outcome. We confirmed the favorable prognosis of men with organ-confined disease, but emphasize the high likelihood of relapse in those with positive surgical margins or seminal vesicle invasion.     

Epididymal cystadenomas in von Hippel-Lindau disease

Objectives. Epididymal cystadenomas (ECs) are frequently found in association with von Hippel-Lindau disease (VHL), but little has been reported about their sonographic appearance. We review the sonographic appearance of ECs, the relationship of ECs to other manifestations of VHL, and the specific genetic mutations associated with ECs.Methods. Fifty-six male patients with VHL were examined with scrotal sonography and physical examination as part of a larger screening program for VHL. The head of the epididymis was measured in two planes on sonography and compared with age-matched normal controls. All VHL patients with palpable epididymal abnormalities or enlargement (more than two standard deviations) of the head of the epididymis on ultrasound were considered positive for EC.Results. Thirty of 56 (54%) male patients with VHL demonstrated a unilateral (n = 10; 33%) or bilateral (n = 20; 67%) solid abnormality in the head of the epididymis suggestive of EC. Sonographic appearances ranged from a solid mass with multiple tiny cysts to an almost completely solid mass. The most common appearance was a 15- to 20-mm solid mass with small cystic components. Dilated efferent ductules were seen within the testicle in 7 men, evidently a result of chronic obstruction. There was no association between the clinical subtype of VHL and the presence of ECs (P >0.10, chi square). Mutations resulting in a truncated gene product were associated with the development of ECs but the association did not reach statistical significance (P = 0.06).Conclusions. ECs are a common manifestation of VHL in men and exhibit a range of appearances on ultrasound. Sonography can be used to identify ECs and determine the extent of cystic dilation of the rete testes. The benign course of ECs and the usual absence of clinical symptoms favor a conservative approach to their management.     

How often do asymptomatic healthcare workers cause methicillin-resistant Staphylococcus aureus outbreaks? A systematic evaluation.

A systematic search was performed to identify outbreaks of methicillin-resistant Staphylococcus aureus infection and colonization caused by healthcare workers (HCWs). Of 191 outbreaks identified, 11 had strong epidemiological evidence that HCWs were the source. In 3 of these outbreaks, asymptomatic carriers were the cause. The frequent practice of screening asymptomatic HCWs should be reconsidered.     

The striatal-enriched protein tyrosine phosphatase gates long-term potentiation and fear memory in the lateral amygdala.

BACKGROUND: Formation of long-term memories is critically dependent on extracellular-regulated kinase (ERK) signaling. Activation of the ERK pathway by the sequential recruitment of mitogen-activated protein kinases is well understood. In contrast, the proteins that inactivate this pathway are not as well characterized. METHODS: Here we tested the hypothesis that the brain-specific striatal-enriched protein tyrosine phosphatase (STEP) plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation. RESULTS: STEP co-localizes with the ERKs within neurons of the lateral amygdala. A substrate-trapping STEP protein binds to the ERKs and prevents their nuclear translocation after glutamate stimulation in primary cell cultures. Administration of TAT-STEP into the lateral amygdala (LA) disrupts long-term potentiation (LTP) and selectively disrupts fear memory consolidation. Fear conditioning induces a biphasic activation of ERK1/2 in the LA with an initial activation within 5 minutes of training, a return to baseline levels by 15 minutes, and an increase again at 1 hour. In addition, fear conditioning results in the de novo translation of STEP. Inhibitors of ERK1/2 activation or of protein translation block the synthesis of STEP within the LA after fear conditioning. CONCLUSIONS: Together, these data imply a role for STEP in experience-dependent plasticity and suggest that STEP modulates the activation of ERK1/2 during amygdala-dependent memory formation. The regulation of emotional memory by modulating STEP activity may represent a target for the treatment of psychiatric disorders such as posttraumatic stress disorder (PTSD), panic, and anxiety disorders.     

Risk factors for wheezing in Ukrainian children: Ukraine European Longitudinal Study of Pregnancy and Childhood Group

The prevalence of wheezing in children varies widely around the world. The reasons for this geographic variability remain unclear but may be related in part to exposures in the home environment during pregnancy and early childhood. We investigated the prenatal and early childhood risk factors for wheezing symptoms among 2127 children aged 6–8 years who were participants in the Ukrainian component of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC). Cases included the 169 children whose parents answered yes to the International Study of Asthma and Allergy in Children (ISAAC) question: 'Has your child had wheezing or whistling in the chest in the past 12 months' during the ELSPAC assessment of the children at age 7. These were compared with the 1861 children in the cohort whose parents answered 'no' to this question.
Factors significantly associated with increased risk of wheezing illness at age 7 in adjusted analyses included mother's asthma [adjusted odds ratio (OR) 3.46, 95% confidence interval (CI) 1.22, 9.85]; mother's allergy problems (OR 1.43, [1.00, 2.05]); rarely playing with other children at age 3 (OR 1.84, [1.09, 3.11]); water intrusion (OR 1.62, [1.09, 2.39]) and inadequate heating of the home (OR 1.52, [1.06, 2.16]) during pregnancy. Factors protective of wheezing at age 7 included being first-born (adjusted OR 0.70, 95% CI 0.50, 0.98); living in the city of Dniprodzerzynsk as compared with Kyiv (OR 0.36, [0.24, 0.54]) and weekly contact with furry animals (OR 0.44, [0.20, 0.97]) before age 3. The constellation of risk factors for wheezing in Ukrainian children is similar to that of children in other parts of the world. Known risk factors do not account for the significant between-city variability of wheezing in Ukrainian children.