The syndrome of self-induced water intoxication in psychiatric patients

This is a report on six psychiatric patients who indulged in excessive ingestion of water and subsequently developed tonic-clonic seizures in the course of the underlying mental disorders. On the basis of the DSM-III criteria, they were diagnosed as follows: schizophrenic disorder, 4; schizo-affective disorder, 1; borderline personality disorder, 1. The levels of serum electrolytes were estimated during five episodes of seizures in three patients. Hyponatremia was a consistent finding (serum sodium: mean = 120.6 mEq/liter). Plasma osmolality and plasma levels of arginine vasopressin (AVP) were determined during two episodes in two patients. The inappropriately high circulating levels of AVP relative to plasma hypoosmolality were documented. However, the response to the overnight fluid deprivation and acute water load during the period of no seizures in two patients revealed no evidence of the persistent SIADH, suggesting the temporal association of hyponatremic encephalopathy with inappropriate AVP secretion. It is not conclusive whether the transient SIADH is the cause or the consequence of hyponatremic encephalopathy, although a delusion or an auditory hallucination could play a critical role in drinking water excessively in three patients.     

The mechanical strength of the growth plate under the influence of sex hormones

As sex hormones are considered to play a role in the etiology of the slipped upper femoral epiphysis, the influence of sex hormones on the mechanical strength of the epiphyseal plate was investigated in 310 female and 70 male rats. Ovariectomy weakened the strength of the growth plate while orchiectomy strengthened it. Estrogen given after ovariectomy, markedly strengthened the plate. Histologic examination revealed that the width of the growth plate was narrower in the mechanically stronger group. Hydroxyproline content increased and hexosamine content decreased in the epiphyseal plates of the mechanically stronger group. These observations confirm the view that sex hormones, especially estrogen, regulate the mechanical, morphologic, and biochemical functions of the growth plate.     

Report of a case of an atypical huge patent ductus arteriosus

An atypical huge patent ductus arteriosus (PDA) associated with extreme pulmonary hypertension in a 6-month old female infant was reported. The left 3rd intercostal thoracotomy revealed huge PDA which has an appearance of pulmonary-ductus-descending aorta-trunk (PDDT) on the left side. The right side of the ductus continued to the aortic arch without demarcation between the ductus and the aorta. The median sternotomy clarified the ascending aorta, normal aortic arch, and main pulmonary artery. However, the top of the main pulmonary artery seemed to be fused with the aortic arch. The diagnosis of distal type of aortopulmonary window with wide communication was made and the total circulatory arrest with deep hypothermia and the intracavitary patching for separation of systemic and pulmonary blood flow seemed to be required for the complete repair. Total repair was decided to be postponed one week later and the chest was closed. The patient died of multi-organ failure originating from acute respiratory failure 23 days after exploratory thoracotomy without being repaired. Postmortem examination revealed a huge PDA freely communicating with the ascending aorta and the aortic arch. This is a report of an atypical huge PDA rarely seen and the conventional division or ligation is unfeasible. The circulatory arrest with deep hypothermia and intracavitary patching are obligatory for the surgical repair.     

Effects of ACE inhibitor and AT1 blocker on dystrophin-related proteins and calpain in failing heart

OBJECTIVES: Genetic depletion of dystrophin-related protein (DRP) complex causes cardiomyopathy in animals and humans. We found in a previous study that some types of DRP were degraded and that calpain content was increased in rats with non-genetically induced heart failure. The present study was aimed at examining the effects of an angiotensin-I-converting enzyme inhibitor (ACEI) trandolapril (Tra) or an angiotensin II type 1 receptor blocker (ARB) candesartan (Can), both of which are known to improve the pathophysiology of chronic heart failure (CHF) on degradation of DRP in failing hearts. METHODS: Coronary artery-ligated (CAL) and sham-operated rats (Sham rats) were treated orally with 3 mg/kg/day trandolapril (Tra) or 1 mg/kg/day candesartan (Can) from the 2nd to 8th week after surgery. RESULTS: Hemodynamic parameters of CAL rats at the 8th week after CAL (8w-CAL) indicated heart failure. alpha-Sarcoglycan (SG) and dystrophin in the surviving left ventricle (surviving LV) of 8w-CAL rats decreased, whereas beta-, gamma-, and delta-SGs remained unchanged. Calcium-activated neutral proteases mu-calpain and m-calpain increased in the surviving LV at the 8th week of postmyocardial infarction. Proteolytic activity in the presence of 5 mM Ca2+ markedly increased at the 2nd and 8th weeks, whereas 50 microM Ca2+ slightly but significantly increased proteolysis of casein. Tra or Can treatment improved the hemodynamic parameters, attenuated changes in alpha-SG and dystrophin, and reversed both calpain contents and activities of the failing heart back to sham levels. CONCLUSION: These results suggest that attenuation in calpain-induced degradation of DRP complex is a possible mechanism for the Tra- or Can-mediated improvement of the pathogenesis of CHF following myocardial infarction.     

CpG island methylator phenotype is a strong determinant of poor prognosis in neuroblastomas

Neuroblastoma, one of the most common pediatric solid tumors, is characterized by two extreme disease courses, spontaneous regression and life-threatening progression. Here, we conducted a genome-wide search for differences in DNA methylation that distinguish between neuroblastomas of the two types. Three CpG islands (CGI) and two groups of CGIs were found to be methylated specifically in neuroblastomas with a poor prognosis. By quantitative analysis of 140 independent cases, methylation of all the five CGI (groups) was shown to be closely associated with each other, conforming to the CpG island methylator phenotype (CIMP) concept. The presence of CIMP was sensitively detected by methylation of the PCDHB CGIs and associated with significantly poor survival (hazard ratio, 22.1; 95% confidence interval, 5.3-93.4; P < 0.0001). Almost all cases with N-myc amplification (37 of 38 cases) exhibited CIMP. Even in 102 cases without N-myc amplification, the presence of CIMP (30 cases) strongly predicted poor survival (hazard ratio, 12.4; 95% confidence interval, 2.6-58.9; P = 0.002). Methylation of PCDHB CGIs, located in their gene bodies, did not suppress gene expression or induce histone modifications. However, CIMP was significantly associated with methylation of promoter CGIs of the RASSF1A and BLU tumor suppressor genes. The results showed that neuroblastomas with CIMP have a poor prognosis and suggested induction of silencing of important genes as an underlying mechanism.