Heart rate dynamics and their relationship to psychotic symptom severity in clozapine-treated schizophrenic subjects

The analysis of heart rate variability (HRV) has proven to be useful in evaluating the neuroautonomic dysfunctions associated with various clinical conditions. The purpose of this study was to investigate the linear and non-linear dynamic measures of HRV, and to evaluate their relationship with the psychotic symptom severity, in clozapine-treated schizophrenic subjects. Fifty schizophrenic patients treated with clozapine as monotherapy and 50 normal control subjects were evaluated for HRV analysis. The HRV measurements were obtained from a 30-min resting electrocardiogram (ECG). The severity of psychotic symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). In the patient group, the complexity and symbolic dynamics measures as well as the time and frequency domain measures of HRV were significantly lower than in the control group (P<0.01). The intermediate-term fractal scaling component value was significantly higher in the patient group (P<0.01). The PANSS total score and the positive symptom subscale score had significant negative correlations with the sample entropy (SampEn) value (P<0.01). In conclusion, schizophrenic patients treated with clozapine had markedly different heart rate dynamics compared to normal control subjects. The severity of psychotic symptoms was associated with the SampEn value, suggesting that the non-linear complexity measure might be useful in assessing the neuroautonomic dysfunction in schizophrenia.     

NF-kappa B binding activity and cyclooxygenase-2 expression in persistent CCl(4)-treated rat liver injury

The involvement of NF-kappa B binding activity is known to be important in the mechanism of acute liver injury and in the induction of cyclooxygenase (COX-2). This study was performed to evaluate NF-kappa B binding activity and the expression of COX-2 in chronic liver injury induced by carbon tetrachloride (CCl(4)). Liver tissues from Sprague-Dawley rats were collected at 1, 3, 5, and 7th week after intraperitoneal injection of 0.1 mL of CCl(4)/100 g body weight twice a week. Reactive oxy-gen species (ROS) were measured in the postmitochondrial fraction by dichlorofluorescein formation with a fluorescent probe. An electrophoretic mobility shift assay was performed for NF-kappa B binding activity. Western blot was performed to measure the level of COX-1, COX-2, p65, p50, and I B proteins. ROS and NF-kappa B activity increased during the CCl4-induced chronic liver injury. The expression of nuclear p65 protein and p50 protein increased compared with that of the control, while the cytoplasmic I B protein decreased as the inflammation persisted. The expression of COX-2 in CCl(4)-treated rat liver increased compared with that of the control. It could be suggested that ROS produced by CCl(4) treatment increased NF-kappa B binding activity and thereby COX-2 expression, and these might be implicated in the progress of chronic liver damage.     

Electroconvulsive shock increases the phosphorylation of amphiphysin II in the rat cerebellum

Amphiphysin II (Amph2) is known to undergo rapid dephosphorylation and phosphorylation at nerve terminals. After in vivo electroconvulsive shock (ECS) in the rat cerebellum, we found an electrophoretic mobility retardation of Amph2, which suggested an increased degree of phosphorylation above the non-stimulated level. This shifted signal was observed from 1 min, reached the maximum level at 5 min and extended beyond 2 h after ECS. The shifted band was markedly decreased by the phosphatase treatment. Pretreatment with cyclosporin A augmented the mobility retardation of Amph2 after ECS. Our results indicate that ECS induces the phosphorylation of Amph2 in the rat cerebellum.     

Biphasic changes in the Ser-9 phosphorylation of glycogen synthase kinase-3beta after electroconvulsive shock in the rat brain

BACKGROUND: Glycogen synthase kinase-3beta (GSK-3beta) plays important roles in intracellular signaling pathways. Phosphorylation at Ser-9 reduces the activity of GSK-3beta, while phosphorylation at Tyr-216 enhances its activity. Mood stabilizing agents increase the phosphorylation of GSK-3beta at Ser-9, and hence inhibit its activity. This property has been considered to be related to the therapeutic action of these drugs. The effect of electroconvulsive shock (ECS), an effective mood stabilizing treatment, on the phosphorylation of GSK-3beta is not known yet. METHODS: In this study, the effect of ECS on the phosphorylation of GSK-3beta was examined in the rat frontal cortex, hippocampus, and cerebellum by Western blot analysis using antibodies specific for Ser-9 or Tyr-216 phosphorylated GSK-3beta. RESULTS: In all regions, the phosphorylation of GSK-3beta at Ser-9 was decreased immediately after ECS, but then increased above basal level within 10 min and maintained at an increased level for more than 30 min. Meanwhile, the phosphorylation at Tyr-216 of GSK-3beta did not show any significant changes after ECS. CONCLUSIONS: These results showed that ECS could induce biphasic changes in the Ser-9 phosphorylation of GSK-3beta in the rat brain, suggesting some similarities, as well as differences, in the actions of mood stabilizers and ECS in the signal transduction mechanisms of the brain.     

Treatment of the axilla in early breast cancer: past, present and future

Background: The optimal treatment of the axilla in early breast cancer is controversial. The present study reviews the pattern and predictors of regional recurrence (RR) and prognosis after RR in patients with early breast cancer treated by conservative surgery and radiotherapy (CS + RT). Implications of the results on current practice and future directions are explored. Methods: Between 1979 and 1994, 1158 patients with stage I or II breast cancer were treated with CS + RT at Westmead Hospital. Two groups of patients were compared: 782 patients who underwent axillary dissection (axillary surgery group) and 229 patients who received radiotherapy (axillary RT group) as the only axillary treatment. At least 10 lymph nodes were dissected in 82% of the axillary surgery group. Of the women in the RT group, 90% received RT to the axilla and supraclavicular fossa (SCF) only and 10% also received RT to the internal mammary chain (IMC). Results: With a median follow‐up period of 79 months for the axillary surgery group and 111 months for the axillary RT group, 27 patients developed a RR (2.8% and 2.2%, respectively). Seven patients (0.9%) in the axillary surgery group and three patients (1.3%) in the axillary RT group developed a RR in the axilla (P, not significant). Of the patients with SCF recurrences, 14 (1.8%) were in the axillary surgery group and one (0.4%) in the axillary RT group (P, not significant). One patient in the axillary surgery group developed concurrent axillary and SCF recurrences, while a patient in the axillary RT group developed an IMC recurrence. Twenty (74%) of the 27 patients with a RR developed a concurrent or subsequent distant relapse (30% and 44%, respectively). In the pathologically node‐positive patients, the axillary recurrence rate was higher in those who had less than five nodes removed (17%) than those who had 10 or more nodes removed (0%; P = 0.01). The SCF recurrence rate was higher in patients with four or more positive axillary nodes (9.5%) than in those with 0–3 positive nodes (1.5%; P = 0.003). Conclusion: Adequate treatment of the axilla by surgery or RT alone is associated with a low rate of RR. The incidence of distant relapse was substantial in patients who developed a RR, which gives emphasis to the importance of optimizing local–regional control.     

Tumor necrosis factor (TNFalpha) production by rat peritoneal macrophages is not polyacrylate surface-chemistry dependent.

Polyacrylate films in the absence of added endotoxin caused rat peritoneal macrophages to secrete a small amount of TNFalpha. There was little difference, if any, among the materials, which included various co- or ter-polymers of hydroxyethyl methacrylate, dimethylaminoethyl methacrylate, methacrylic acid, methyl methacrylate, and butyl methacrylate. The materials were surface characterized and endotoxin cleaned prior to testing. Equivalent endotoxin levels associated with the material were <0.03 EU/mL for all materials but two; for polyHEMA, the most contaminated material, it was 0.23 EU/mL. Films of the materials were incubated with freshly isolated rat peritoneal macrophages for 6 to 24 h before the TNFalpha levels in the supernatant were analyzed for biological activity, using L929 cells as a target. When endotoxin was added, far greater quantities of TNFalpha were generated at 24 h compared to 6 h, but still there was little effect with regard to material chemistry. Such an in vitro assay proved not to be useful for the screening of potential microencapsulation materials for peritoneal biocompatibility.     

The double puncture: an effective percutaneous technique for removing complex, multiple renal calculi

Percutaneous nephrostolithotomy, which can require a double puncture, is presently the method of choice in our institution for the removal of renal stones. Patients that underwent this procedure were evaluated to identify the possible reasons for the double puncture. Of 200 patients evaluated, 14 needed a second tract. The three variables that determined whether a second puncture was needed, in order of importance, were number and size of the stones, with second tracts needed in patients with multiple stones and staghorn calculi; anatomical variations of the renal collecting system itself, with bifid systems the most significant anatomic variation; and the dexterity of the radiologist in performing the puncture and the ability of the urologist to extract the stone. Second tracts were needed more frequently in patients who presented with stones in both the lower and middle poles of the collecting systems.