Pleural effusions appearing in the rehabilitation ward after ventriculoperitoneal shunts: a report of two adult cases and a review of the literature

This study presents two adult patients who experienced pleural effusion during hospitalization for stroke rehabilitation therapy after ventriculoperitoneal shunt placement for normal pressure hydrocephalus associated with aneurysmal subarachnoid haemorrhage. The pleural effusion appeared without migration of the catheter into the thoracic cavity. Because of respiratory insufficiency, which prevented progress in their rehabilitation programme, thoracentesis was repeated for recurrent pleural effusions, the composition of which differed significantly from that of cerebrospinal fluid. Both cases had past histories of laparostomies; therefore, the distal end of the catheter was placed in the right anterior subphrenic recess. One was able to resolve the pleural effusion and rehabilitate the patients by replacing the ventriculoperitoneal shunt with a vetriculoatrial shunt. In the literature, there have been only 23 reports of pleural effusion associated with a ventriculoperitoneal shunt. Among those reports, four involved pleural effusion without migration of the distal catheter; however, all of those cases were in children. Thus, this study reports the first adult cases of pleural effusion without migration of the catheter into the pleural cavity and discusses a putative mechanism.     

Tissue plasminogen activator in primary afferents induces dorsal horn excitability and pain response after peripheral nerve injury

The extracellular protease cascade of plasminogen activators and plasminogen are known to regulate neuronal plasticity and extracellular matrix modification, and to be important factors involved in producing long-term potentiation in the CNS. The purpose of this study is to examine the expression of plasminogen activators in primary afferents and its role in nociceptive pathways after peripheral nerve injury. We found the induction of mRNAs for tissue type plasminogen activator (tPA) and urokinase plasminogen activator (uPA) in the rat dorsal root ganglia following sciatic nerve transection. Immunoreactivity for tPA was increased in laminae I and II of the dorsal horn and, importantly, the increase in proteolytic activity mediated by tPA was observed in the same area. As neither immunoreactivity for uPA nor uPA-mediated proteolysis was observed, we further examined the effects of tPA on dorsal horn excitability and neuropathic pain behaviour. Intrathecal injection of a specific inhibitor of tPA decreased electrical stimulation-induced Fos expression in dorsal horn neurons following axotomy, and also prevented the development of thermal hyperalgesia following partial sciatic nerve ligation. These findings suggest that the increased tPA in the dorsal horn due to mRNA expression in the dorsal root ganglia increases the dorsal horn excitability and has an important role in pain behaviour after peripheral nerve injury. The tPA-mediated hypersensitivity in dorsal horn neurons may be a novel molecular mechanism of neuropathic pain.     

Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension

Adipocyte-derived leucine aminopeptidase (ALAP) inactivates angiotensin II and/or generates bradykinin in the kidney, suggesting a possible role for ALAP in the regulation of blood pressure. We considered the hypothesis that genomic variants of the ALAP gene are associated with hypertension or individual variations in blood pressure. We screened for mutations in the ALAP gene in 48 unrelated Japanese individuals and identified 33 polymorphisms including 15 novel polymorphisms. We then performed a two-stage analysis. In the first stage, the eight missense polymorphisms were evaluated for associations with blood pressure in 96 apparently healthy individuals. In the second stage, only the most promising polymorphisms were evaluated for association with essential hypertension in 143 hypertensive and 348 normotensive subjects. Among the eight missense polymorphisms, the Ile276Met and Lys528Arg polymorphisms showed significant association with blood pressure. Subsequent analysis confirmed association between the Lys528Arg polymorphism and essential hypertension. The estimated odds ratio for essential hypertension was 2.3 for presence of the Arg allele at codon 528, in comparison with presence of the Lys/Lys genotype (P = 0.004). These findings support involvement of ALAP in the regulation of blood pressure.     

Expression of BLM (the causative gene for Bloom syndrome) and screening of Bloom syndrome

Bloom syndrome (BS) is a rare autosomal recessive genetic disorder characterized by growth deficiency, unusual facies, sun-sensitive telangiectatic erythema, immunodeficiency and predisposition to cancer. The causative gene for BS is the BLM gene which encodes the BLM RecQ helicase protein. The BLM gene has 4437 bp and encodes 1417 amino acids. The detection of BLM gene mutations for laboratory diagnosis of BS is laborious and impractical, unless there are common mutations in a population. Here we describe the immunoblot and immunohistochemical analyses for the detection of the BLM protein using a polyclonal BLM antibody. The BLM gene and protein were consistently and clearly detected in Epstein-Barr virus (EBV)-transformed or phytohemagglutinin (PHA)-stimulated lymphoblasts from control and various human hematopoietic cell lines. In a 7-week old human fetal brain, the BLM gene expression was strongly detected in contrast to an adult human brain. The BLM protein was not detected in EBV-transformed lymphoblasts from three BS patients. By immunohistochemistry, nuclear dots of the BLM protein were detected in both EBV-transformed lymphoblasts and PHA-stimulated lymphoblasts from the control. However, in lymphoblasts from BS patients no nuclear dots of the BLM protein were detected. These results indicate that the combinational analysis of immunoblotting and immunohistochemistry is a useful approach to screening of BS, although a mutation analysis is necessary for a definitive diagnosis of BS.     

Cytogenetic remission 10 years after the start of monotherapy with interferon alpha-2b in elderly chronic myelogenous leukemia

A 69-year-old man was found to have leukocytosis and a bleeding tendency, when he underwent surgery for hemorrhoids in November 1992, at the age of 69. The patient was referred to our department for further examination, and was admitted on December 4. On admission, he had hepatomegaly (5 cm) and splenomegaly (12 cm). Laboratory data on admission showed that the leukocyte count was 173,400/microliter, erythrocyte count, 314 x 10(4)/microliter, hemoglobin level, 10.5 g/dl, hematocrit value, 29.7%, and platelet count, 14.4 x 10(4)/microliter, respectively. Peripheral hemogram revealed neutrophilia with a shift to the left to promyelocytes, and the positivity of neutrophil alkaline phosphatase (NAP) was very low. The bone marrow was hyperplastic with a high M/E ratio (5.8). As the chromosome analysis revealed that he had 9:22 translocation in all 20 karyotypes, chronic myelogenous leukemia in the chronic phase, was diagnosed. After the daily intramuscular administration of 9 megaunits interferon alpha-2b was started on December 9, 1992, his leukocyte count stabilized between 5,000 and 8,000/microliter. Thereafter, intramuscular administration of IFN alpha has been continued regularly almost twice a week at the outpatient clinic until now. The leukocyte count ranges from 3,000 to 6,000/ml and he is asymptomatic. In April 1995, complete cytogenetic response was achieved 28 months after the start of interferon alpha therapy. The recent bone marrow chromosomes examination showed Philadelphia-negative metaphases until now, December, 2002, although major bcr-abl still remains positive. This case suggests that treatment with interferon alpha may still be useful in some elderly patients with chronic myelogenous leukemia.     

Peculiar form of cerebral microdysgenesis characterized by white matter neurons with perineuronal and perivascular glial satellitosis: A study using a variety of human autopsied brains

Microdysgenesis (MD) is a neuropathological term that implies a variety of minor developmental abnormalities of the brain. Recently, MD has been used for pathological diagnosis of cerebral tissues surgically resected from epileptic patients. However, criteria or consensus on pathological diagnosis of MD is still vague and controversial because of the lack of control studies. Therefore, this study paid special attention to the presence of white matter neurons with perineuronal glial satellitosis (WMN-GS) and perivascular glial satellitosis (PVGS) in the white matter, which are occasionally observed in epileptic foci, in order to clarify whether they could be handled as definite findings of MD. The materials included 80 autopsied whole brains ranging from normal subjects to patients with cerebrovascular disorder, neurodegenerative diseases and malformations. In each case, the presence of WMN-GS and/or PVGS was searched in 10 gyri in all five lobes (rostral frontal lobe, caudal frontal lobe, parietal lobe, temporal lobe and oc-cipital lobe) and evaluated. Statistically significant, WMN-GS and/or PVGS preferentially appeared in a diseased group consisting of neuronal migration disorder and related conditions, such as polymicrogyria, nodular heterotopia or tuberous sclerosis, leading to a suggestive conclusion that the presence of WMN-GS and/or PVGS could be a peculiar form of MD possibly derived from neuronal migrational arrest or related events, even if they appear alone without any other gross abnormalities.     

Household transmission of Streptococcus pneumoniae among siblings with acute otitis media

Nasopharyngeal transmission of Streptococcus pneumoniae was evaluated among 23 siblings with acute otitis media (AOM). Restriction fragment length polymorphism revealed that the nasopharyngeal strains were identical between siblings in 12 of 13 clusters of AOM experienced in 11 families. This study demonstrated person-to-person transmission of S. pneumoniae, especially drug-resistant strains, among siblings with AOM.     

Mutation analysis of the retinoid X receptor beta, nuclear-related receptor 1, and peroxisome proliferator-activated receptor alpha genes in schizophrenia and alcohol dependence: possible haplotype association of nuclear-related receptor 1 gene to alcohol dependence

Because retinoid cascades are involved in the regulation and development of the central nervous system, including dopaminergic neurons, retinoic acid signaling defects may contribute to schizophrenia and substances dependence. Retinoid X receptors (RXRs) form heterodimer complexes with nuclear-related receptor 1 (NURR1) or with peroxisome proliferator-activated receptors (PPARs). We examined 48 Japanese patients with schizophrenia and 32 patients with alcohol dependence to detect mutations in the retinoid X receptor beta gene (RXRB) on chromosome 6p21.3, the NURR1 gene (NR4A2) on chromosome 2q22-q23, and the PPAR alpha gene (PPARA) on chromosome 22q12.2-13.1. A Val95Ala polymorphism of the RXRB gene, a Val227Ala polymorphism in the PPARA gene, and two synonymous single-nucleotide and CA repeat polymorphisms in the 5' region and 3' untranslated region of the NR4A2 gene were identified. Extended case control samples did not suggest an association between the diseases and the RXRB or PPARA polymorphisms. However, they revealed a significant association between the NR4A2 gene haplotype and alcohol dependence, indicating that 2q22-q23 including the NR4A2 gene locus is a possible genomic region contributing to genetic susceptibility to alcohol dependence.     

Angioscopic evaluation of stabilizing effects of an antilipemic agent,bezafibrate, on coronary plaques in patients with coronary artery disease: a multicenter prospective study

To evaluate the stabilizing effects of an antilipemic agent, bezafibrate, on coronary plaques, we carried out a prospective angioscopic and angiographic open trial. From April 1997 to December 1998, 24 patients underwent coronary angioscopy of plaques in non-targeted vessels during coronary interventions and then again 6 months later. The patients were divided into control (10 patients, 14 plaques) and bezafibrate (14 patients, 21 plaques) groups. Oral administration of bezafibrate (400 mg/day) was started immediately after the intervention and was continued for 6 months. The vulnerability score was determined based on the angioscopic characteristics of plaques and compared before and 6 months later. Six months later, the vulnerability score was reduced (from 1.6 to 0.8; P<0.05) in the bezafibrate group and unchanged (from 1.4 to 1.3; NS) in the control group. In the bezafibrate group, the changes in the vulnerability score were not correlated with those in % stenosis or minimal lumen diameter. The plasma total cholesterol level (T-C) was unchanged, triglyceride level (TG) was decreased, and high density lipoprotein cholesterol level (HDL-C) was increased in the bezafibrate group, but were unchanged in the control group. In the bezafibrate group, T-C and TG were decreased and HDL-C was increased in patients with a reduced vulnerability score but were unchanged in those with an unchanged score. These results indicate that 6 month administration of bezafibrate stabilizes coronary plaques and that the stabilization is not correlated with angiographic changes.     

Autopsy case of multiple anomalies with hypoplastic cerebrum,eyes, and endocrine organs,mimicking Micro syndrome

We report an autopsy case of multiple anomalies with severe micrencephaly, bilateral microphthalmos, and hypoplastic endocrine organs. We examined expressions of calcium-binding proteins and hypothalamic and pituitary hormones. A female proband presented with microcephaly, microphthalmia, and psychomotor development delay. At the age of 23 years, she died of cardiorespiratory failure. The endocrine organs demonstrated severe underdevelopment, and the hypoplastic eyeballs had remnant lens, vitreous hemorrhage, and retinal detachment. The brain weighed 260 g; the cerebrum, cerebellum, and brain stem were extremely small; and the tertiary sulci were absent in the cerebral surface. The cross-sectional area of cerebral cortex was reduced to about one third of those in the control, although six-layered lamination, density of pyramidal neurons, and expressions of calcium-binding proteins were comparatively preserved in the cerebral cortex. The third ventricle was hypoplastic, and the bilateral thalami appeared to be fused and the hippocampus was unrolled, whereas the corpus callosum was preserved. In the hypothalamus, the paraventricular nucleus was only identified, and the adenohypophysial somatotrophs were reduced. This may be the first autopsy report of Micro syndrome, which is characterized by microcephaly, brain malformations, optic atrophy, and hypogenitalism, although the case lacked agenesis of the corpus callosum.