Classification of antipsychotic drugs by gene expression in the frontal cortex of mice.

Antipsychotic drugs are classified as typical and atypical based on extrapyramidal effects. However, since the frontal cortex is one of the most important regions for antipsychotic actions, this study attempted to classify antipsychotic drugs based on gene expression in the frontal cortex. Chlorpromazine and thioridazine were selected as typical antipsychotics, and olanzapine and quetiapine as atypical antipsychotics. Since these drugs have similar chemical structures, the effect of the basic structure on gene expression can be eliminated. Cluster analysis of microarray experiments separated 4-drug-administered mice into chlorpromazine-quetiapine and thioridazine-olanzapine groups. This classification scheme is different from that which is based on criteria currently used to group the typical and atypical drugs and suggests that antipsychotic drugs can be further separated into multiple groups.     

Chemotherapy in the treatment of advanced or recurrent olfactory neuroblastoma

Background: Olfactory neuroblastoma is a rare sino‐nasal tumor arising from the olfactory epithelium and is often characterized by local invasion or metastasis. The role of chemotherapy in the treatment of this tumor is unclear. The purpose of this study was to review our institution’s experience of chemotherapy for advanced or recurrent olfactory neuroblastoma. Methods: Twenty‐one patients with histologically proven olfactory neuroblastoma were treated at our institution between 1992 and 2002. Twelve of these patients received chemotherapy in the setting of unresectable or recurrent disease and were retrospectively reviewed for clinical characteristics, treatment outcome or survival. Results: Eight patients of the 12 patients received cisplatin‐based chemotherapy and the remaining four patients received chemotherapy consisting of docetaxel plus irinotecan (three patients) or cyclophosphamide, doxorubicin, and vincristine (1 patient). A partial response was achieved in five patients, with an overall response rate of 42%, although the chemotherapeutic regimens were heterogeneous. Two partial responses were obtained among the three patients who received docetaxel plus irinotecan. The response rate to chemotherapy was 83% in the younger age group (<40 years), as opposed to 0% in the older age group (≥40 years), and the difference between the two groups was statistically significant (P = 0.02). Conclusion: Our study indicated that olfactory neuroblastoma would be sensitive to chemotherapy, especially with young patients. Docetaxel plus irinotecan has the possibility of showing favorable response, and warrants further investigation.     

Concurrent presence of metabolic syndrome in obstructive sleep apnea syndrome exacerbates the cardiovascular risk: a sleep clinic cohort study.

This cross-sectional study was conducted to examine whether the obstructive sleep apnea syndrome (OSAS) is associated with elevation of the pulse wave velocity (PWV) and increase in the plasma levels of C-reactive protein (CRP), both of which are known markers of cardiovascular risk, and also to determine if the concurrent presence of the metabolic syndrome might exacerbate this elevation in the levels of these cardiovascular risk markers in subjects with OSAS. With these objectives, the PWV and serum CRP were measured in 184 subjects attending a sleep clinic. It was found that the PWV and CRP were higher in the subjects with OSAS (n=94) than in those without OSAS (n=90). Furthermore, among the subjects with OSAS, the PWV and CRP were higher in those with the concurrent presence of the metabolic syndrome (n= 41; PWV=1,562+/-19 cm/s; CRP=1.8+/-0.2 mg/l) than in those without metabolic syndrome (n=53; PWV=1,432+/-21 cm/s; CRP=1.2+/-0.1 mg/l) (p<0.05). A general linear model analysis demonstrated that OSAS and metabolic syndrome were independently associated with elevated PWV and increase of the plasma levels of CRP. OSAS appears to be associated with increased cardiovascular risk, as reflected by both elevated PWV and increase of the plasma CRP. The concurrent presence of metabolic syndrome may exacerbate this increase in cardiovascular risk in subjects with OSAS. Therefore, the concurrent presence of metabolic syndrome may constitute an additive cardiovascular risk factor in subjects with OSAS.     

Steroid pulse therapy impaired endothelial function while increasing plasma high molecule adiponectin concentration in patients with IgA nephropathy.

BACKGROUND: Decreased plasma adiponectin is associated with impaired endothelial function and, thereby, increased risk for cardiovascular events. Glucocorticoid (GC) affects vascular endothelial cells either favourably or harmfully depending upon the dosages and duration. We examined the effect of GC pulse therapy on vascular endothelial function. METHODS: Fourteen young patients with IgA nephropathy were evaluated for flow-mediated vasodilation (FMD), plasma levels of adiponectin both in high molecular weight (HMW adiponectin) form and in single molecular form (total adiponectin), hepatocyte growth factor (HGF), asymmetric dimethylarginine (ADMA), and high-sensitive C-reactive protein, before and after a course of GC pulse therapy. RESULTS: GC pulse therapy significantly decreased FMD (from 7.2 +/- 2.6 to 5.7 +/- 2.5%, P < 0.01). Meanwhile, plasma adiponectin levels were significantly augmented (total adiponectin: from 10.2 +/- 4.0 to 12.1 +/- 6.3 microg/ml, P < 0.05; HMW: from 6.5 +/- 3.2 to 7.7 +/- 3.3 microg/ml, P < 0.05). In parallel, elevated concentrations of serum HGF (from 0.28 +/- 0.12 to 0.63 +/- 0.38 ng/ml, P < 0.01) and plasma ADMA (from 0.45 +/- 0.07 to 0.53 +/- 0.04 nmol/ml, P < 0.05) were observed. CONCLUSIONS: GC pulse therapy impaired endothelial function while increasing plasma adiponectin levels, which may in turn restore the endothelial function in patients with IgA nephropathy.     

Beta2-glycoprotein I-dependent anticardiolipin antibody in early recurrent spontaneous abortion

The objective of this study was to assess the clinical significance of autoimmune anticardiolipin antibody that can react with cardiolipin only in the presence of beta2-glycoprotein I (beta2-glycoprotein I- dependent anticardiolipin antibody) in the pathogenesis of early recurrent abortion. A total of 72 early recurrent spontaneous aborters and 175 normal healthy women were analysed for the occurrence of beta2- glycoprotein I-dependent anticardiolipin antibody in serum samples by an enzyme-linked immunosorbent assay specific for the detection of beta2-glycoprotein I-dependent anticardiolipin antibody. The incidence of beta2-glycoprotein I-dependent anticardiolipin antibody in the early recurrent spontaneous aborters was essentially the same as that of normal women. Thus, the beta2-glycoprotein I-dependent anticardiolipin antibody seemed to have little, if any, implication in the pathogenesis of early recurrent spontaneous abortion.      

Approach to early diagnosis of acute mesenteric ischemia: evaluation in canine model

The high mortality rate of patients with acute mesenteric ischemia may be mainly due to the difficulty of making an early diagnosis. Many clinical and experimental studies have been attempted to make an early diagnosis in the view of history, physical examination, laboratory data, X-rays and angiographies. This study was undertaken to estimate the diagnostic value of twenty one laboratory parameters and three clinical parameters measured after superior mesenteric artery occlusion (SMAO) in the mongrel dogs. Consequently, the valuable diagnostic indicators of SMAO that statistically had significant difference were serum CPK isoenzyme-BB, serum CPK isoenzyme-MB, serum inorganic phosphate, serum calcium and base excess of arterial blood gas analysis. In these indicators, serum CPK isoenzyme-BB, serum inorganic phosphate and serum calcium were especially valuable indicators of its early diagnosis, because they showed significant change in the early phase after SMAO. However, other indicators showed significant change within eighteen hours after SMAO. Therefore, if these indicators are able to be examined in a case of abdominal emergency, they are considered to play a valuable role in the diagnosis of acute mesenteric ischemia.     

Ultrasonographic study on kidneys in patients with acute renal failure]

Ultrasonotomograms of 22 kidneys were obtained in 11 patients with renal-acute renal failure (renal-ARF). The underlying diseases of renal-ARF were acute tubular necrosis in 8 patients and acute on-set chronic glomerulonephritis in 3 patients. They were treated by hemodialysis in 10 patients and intermittent peritoneal dialysis in 1 patient. Ultrasonic measurement of the size of kidneys revealed that the thickness (anterior-posterior diameter) and the ratio of thickness to length (T/L) were greater in patients with ARF than in those with chronic renal failure and normal renal function. The patients with a low value of T/L (under 0.60) had a significantly greater urine volume than those with high a value of T/L (0.60 or more). The sonographic features of renal-ARF kidneys were marked increase in parenchymal echogenicity and appearance of hypoechoic swollen renal pyramids with sharpness of the corticomedullary border. In the course of ARF, these sonographic changes gradually disappeared when the patients had recovered from ARF. However, the prognosis was poor in patients with severer sonographic findings. We believe that repeated ultrasonic examination of the kidneys in patients with renal-ARF is useful for not only differential diagnosis of post-renal urinary obstruction but evaluating the course of ARF.