Neuropathology of schizophrenia: A mini review

The neuropathology of schizophrenia remains obscure despite the fact that many neuropathologists have investigated this area for over 100 years. While remarkable progress has been made in the neuropathological study of neurodegenerative diseases including Alzheimer's disease, progress in studying the neuropathological entity of schizophrenia has not kept pace; the phrase “schizophrenia is the graveyard of neuropathologists” has been stated in the field. Since the 1980s, the morphological or functional abnormalities in the brains of schizophrenia patients have been reported by means of CT or MRI and with advanced functional brain image technology such as positron emission tomography or single photon emission computed tomography. Results from such imaging studies have led to neuropathological examination of the post mortem brains of schizophrenia patients being undertaken again. These neuroimaging studies have influenced the neuropathological investigation of the schizophrenic brain. Not only the classical microscopic observation of neuropathology, but also measurement and statistical analysis using computer imaging software or using immunohistological techniques has been performed. Based on the neuropathological studies of schizophrenia over the last 20 years, it is clear that schizophrenia is not a pure functional disease without organic factors. Reports of neuropathological abnormalities in the post mortem schizophrenic brain indicated they were found in almost all areas of the brain, but there are more reports describing the temporal lobe and frontal lobe compared to those describing other areas of the brain. These observed neuropathological abnormalities are explained rationally by the hypothesis of a neurodevelopmental disorder in this disease. In recent molecular biology studies, several putative candidate genes were reported, and some of these genes might have the function of neurodevelopment or making neuronal networks. It is important to consider together these findings with morphometric studies in neuropathological observation, neuroimaging studies and genome studies to pursue the etiology of schizophrenia from various perspectives.     

Association of BRCA2 polymorphism at codon 784 (Met/Val) with breast cancer risk and prognosis.

PURPOSE: The association of BRCA2 polymorphisms at codon 372 [Asn (N)/His (H)]and codon 784 [Met (M)/Val (V)] with breast cancer risk was evaluated in Japanese women. In addition, the prognostic significance of these polymorphisms was studied in breast cancer patients. EXPERIMENTAL DESIGN: A case-control study was conducted to examine the association of the BRCA2 N/H372 polymorphism and M/V 784 polymorphism with breast cancer risk (cases = 149, controls = 154). The prognostic significance of these polymorphisms was evaluated in 139 patients with primary breast cancer. RESULTS: No significant association was observed between the N/H372 polymorphism and breast cancer risk. In contrast, a significant increase in breast cancer risk (odds ratio, 2.03; 95% confidence interval, 1.07-3.87) was observed in carriers of the variant allele (V784) of the M/V784 polymorphism as compared with noncarriers after adjustment for the classical risk factors, age, family history, parity, body mass index, and so forth. Among breast cancer patients, various clinicopathological parameters including menopausal status, tumor size, lymph node status, histological grade, and estrogen-receptor status were not significantly different between the carriers and noncarriers of the variant allele with regard to both N/H372 and M/V784 polymorphisms. The N/H 372 polymorphism was not significantly associated with patient prognosis. On the other hand, breast cancer patients carrying the variant allele of M/V784 polymorphism showed a significantly (P = 0.014) lower 3-year disease-free survival rate (63%) than noncarriers (92%). Multivariate analysis has revealed that the M/V784 polymorphism is a significant prognostic factor, being independent of the other conventional prognostic factors such as lymph node status and estrogen receptor status. CONCLUSION: These results suggest that the M/V784 polymorphism, but not the N/H372 polymorphism, would be useful in the selection of women at high risk for developing breast cancer and would also serve as a clinically useful prognostic factor in breast cancer patients.     

The influence of liver dysfunction on cyclosporine pharmacokinetics —A comparison between 70 per cent hepatectomy and complete bile duct ligation in dogs—

The influence of experimentally induced hepatic dysfunction on the pharmacokinetics of Cyclosporine A (CsA) was determined in dogs. The pharmacokinetics of oral (PO) and intravenous (IV) CsA were studied before and after 70 per cent hepatectomy or complete bile duct ligation (CBDL). Changes in liver function were monitored by serial measurements of serum bilirubin, and by the maximum removal rate (Rmax) and plasma disappearance rate (ICG-K) of indocyanine green (ICG). Concentrations of CsA in whole blood were measured by HPLC. Seventy per cent hepatectomy caused significant liver dysfunction: the ICG-Rmax decreased by 47.7±7.1 per cent (mean±SD) and the ICG-K decreased by 61.3±9.7 per cent during the first week after hepatectomy. At the same time, the systemic clearance (CLs) of IV-CsA decreased by 43.9±8.2 per cent, the area under the concentration curve (AUC) of IV-CsA increased by 35.4±20.8 per cent and the bioavailability of CsA decreased by 26.4±14.8 per cent. CBDL also induced significant liver dysfunction: the ICG-Rmax decreased by 39.1±12.8 per cent and the ICG-K decreased by 65.6±3.6 per cent in the second week after the operation. During the same period, the AUC of PO-CsA decreased by 69.9±10.7 per cent and the bioavailability of CsA also decreased markedly by 73.9±15.6 per cent. These data indicate that hepatic impairment significantly influences the pharmacokinetics of CsA, not only by the changes in intestinal absorption, but also by those in hepatic, metabolism. Dose adjustment is therefore necessary in the presence of hepatic dysfunction in order to maintain an adequate blood concentration of CsA without causing side effects. This research was performed in the Department of Surgery, University of Pittsburgh Health Center, University of Pittsburgh, USA     

Poor oxygenation in the lungs of patients with hyperosmolar hyperglycemic non-ketotic diabetic coma after cardiac surgery

The ratio of PaO₂ to FiO₂ was often low (300 or less) in four patients with complications of hyperosmolar hyperglycemic non-ketotic diabetic coma (HHNKDC) following open heart surgery. Four of our patients had poor oxygenation and subsequent spontaneous recovery from in the immediate post-operative period, although HHNKDC occurred only in one during this period. In the 3 others, poor oxygenation without accompanying HHNKDC lasted for 1–6 days and HHNKDC developed about 2 weeks after open heart surgery at time when poor oxygenation reoccurred. If a working diagnosis of congestive heart failure was made only on the basis of the most common probability, and the fluid supply was restricted, HHNKDC would readily occur or be aggravated by the dehydration iatrogenically produced. It is thus concluded that HHNKDC should be included in diagnoses for pulmonary dysfunction.     

Heat and chemical stability of blood group-specific immunoglobulins in the state of immunecomplex

Immune agglutinin or precipitin loses its reactivity with the corresponding antigen by heating or some chemicals. A. Se group saliva or M group blood stain was sensitized with human IgM anti-A or rabbit IgG anti-M serum, respectively. After being washed with saline, the stains were heated or treated with formalin or 2-mercaptoethanol (2-ME) of various concentrations. The immunoreactivity of the antibodies in the state of immunecomplex was examined by the mixed agglutination or elution test, indicating IgM and IgG antibodies in the state of immunecomplex were proof against heating up to 150 degrees C for 10 min and against formalin and 2-ME of high concentrations. It is considered that IgM and IgG acquire a new property of heat and chemical stability by formation of immunecomplex although they are substantially heat and chemical labile.     

The effects of long term Tranilast administration on bronchial hypersensitivity in asthmatics

Tranilast is an oral antiallergic agent developed in Japan. This study investigated the effect of prolonged administration of Tranilast on the bronchial sensitivity of 18 asthmatic subjects. They were treated for either less than 3 months or more than 3 months continuously. Methacholine loading testing was used to assess bronchial reactivity, and the respiratory parameters were recorded on an Astograph. Patients treated for longer than 3 months showed a significant decrease in bronchial sensitivity (p less than 0.05). The anticholinergic and bronchodilatory properties of Tranilast were also investigated in 8 subjects. No significant anticholinergic or bronchodilatory effects were observed following a single oral dose of 100 mg of Tranilast.     

Haloperidol metabolism in psychiatric patients: importance of glucuronidation and carbonyl reduction.

In 39 patients who received haloperidol regularly we measured plasma concentrations of haloperidol glucuronide (HAL-GL), reduced haloperidol glucuronide (RHAL-GL), haloperidol (HAL), reduced haloperidol (RHAL), and HAL reductase activity in red blood cells. Plasma HAL-GL concentrations were significantly higher than HAL, RHAL, or RHAL-GL concentrations. Concentration ratios of total glucuronide to nonglucuronide and RHAL/HAL ratios were calculated as indices of glucuronidation and reduction capacity in each patient. The plasma glucuronidation ratios showed a significant negative correlation (r = -0.63, p less than 0.001) with the dose, while the reduction ratios showed a positive correlation (r = 0.75, p less than 0.001). No correlations were found between the HAL reductase activity in red blood cells and either the dose or RHAL/HAL. Based on these findings we suggest that glucuronidation of HAL is the major metabolic pathway of HAL in humans and its activity is important in determining steady-state plasma HAL concentrations. Glucuronidation may also be a major contributing factor in the interindividual variability of HAL metabolism.     

Cosmetic benefits of lower midline skin incision for pediatric open heart operation

OBJECTIVE: Since we developed the procedure in 1996, we have now performed 100 pediatric open heart operations using a lower midline skin incision and a minimal sternotomy approach. METHODS AND RESULTS: To elucidate the benefits of this approach, we analyzed these 100 cases retrospectively. There was no death, and no major complication, caused by this approach, and the resulting scarring in each patient is difficult to be seen under a common undershirt. CONCLUSION: This review shows that the technique of a lower midline skin incision and minimal sternotomy approach is a safe reliable and cosmetically advantageous method for a pediatric cardiac operation.     

A case report of invasive thymoma presenting as a solitary metastatic lesion of the lung]

A 66-year-old woman visited our hospital for further investigation of a coin-shaped lesion in the right lower lung field. After admission, CT-scan revealed an anterior mediastinal tumor. Thymoma and lung metastasis from thymoma were suspected. At thoracotomy, an invasive thymoma involving the left phrenic nerve, the left upper lobe, and the pericardium was found, and the diagnosis of lung metastasis was made. Postoperative pathological findings showed a predominantly lymphocytic thymoma with round and oval-shaped epithelial cells, and the metastatic lung lesion revealed the same findings. Postoperative radiotherapy (4000 rads) and chemotherapy with a combination of CDDP, VDS, and CPA were administered. The metastasis of thymoma is not rare, but most often it is found after operation. In this case the diagnosis of metastatic thymoma was made pre-operatively from a solitary lung lesion.