Animal study on the role of serotonin in depression

1. In our series of experiments the role of serotonin in human depression was studied by using animal models of depression.

2. The results of these studies support the hypothesis that some types of human depression may be primarily due to an excessive transmission of serotonin at the synapse.     

Dynamic MRI of the gallbladder lesions: Differentiation of benign from malignant

Forty-nine pathologically proven gallbladder lesions were evaluated in 45 patients using dynamic MRI with a spoiled gradient pulse sequence (SPGR), to access the ability of this technique to differentiate benign from malignant gallbladder lesions. The studies were reviewed retrospectively. Signal intensity of the lesions were measured. Twenty-one malignant and 28 benign lesions were classified into three categories: polypoid, diffuse wall thickening, and exophytic. Early and delayed enhancement patterns were evaluated. For the polypoid masses, malignant lesions (n = 9) demonstrated early and prolonged enhancements, whereas benign lesions (n = 14) had early enhancement with subsequent washout (P < .05). For diffuse gallbladder wall thickening, malignant lesions (n = 6) demonstrated early and prolonged enhancement and benign lesions (n = 14) showed relatively slow, prolonged enhancement (P < .05). The exophytic masses (n = 6) all were malignant and demonstrated early and prolonged enhancement. Dynamic MRI can help differentiate benign from malignant gallbladder lesions.     

Genetic alteration in carcinoid tumors of the lung.

Surgically resected specimens of 13 carcinoid tumors of the lung including nine typical carcinoids and four atypical carcinoids, and eight salivary gland type carcinomas (six mucoepidermoid carcinomas and two adenoid cystic carcinomas) were analyzed regarding p53 expression, loss of heterozygosity (LOH) in chromosome 3p, 9p, and K-ras mutation. The overexpression of p53 was identified in four atypical carcinoid tumors, one mucoepidermoid carcinoma, and one adenoid cystic carcinoma, however, none of typical carcinoids showed p53 immunoreactivity. LOH in 3p14 was demonstrated in three of seven informative cases in all tumors. LOH in 9p was demonstrated in two of five informative cases in all tumors. Two of three cases with LOH at 3p14 had a poor prognosis, one of which also had LOH at 9p. No mutation of the K-ras gene was observed in any of these tumors. These data thus indicate that p53 overexpression might distinguish atypical carcinoid tumors from typical tumors and might therefore be useful as an adjunct modality in the differential diagnosis of pulmonary carcinoid tumors. The presence of LOH at 3p14 or 9p may thus help to identify lung cancer patients with a poor prognosis.     

Normothermic cardiopulmonary bypass: effect on the incidence of persistent postoperative neurological dysfunction following coronary artery bypass graft surgery

We retrospectively reviewed the records of 250 consecutive patients undergoing coronary artery bypass graft surgery (CABG) from January 1994 through January 1996 to determine the incidence of persistent postoperative neurological dysfunction after CABG and to compare normothermic and moderate hypothermic cardiopulmonary bypass (CPB). Normothermic CPB was used in 128 patients (36°–37°C) and hypothermic CPB (27°–28°C) in 122 patients. Postoperative neurological dysfunction included focal motor deficits, delayed recovery of consciousness (>24h) after surgery, and seizures within 1 week postoperatively. Persistent neurological dysfunction was diagnosed if complete resolution had not occurred within 10 days of surgery. The incidence of persistent postoperative neurological dysfunction was 4.1% in the hypothermic CPB group and 2.3% in the normothermic CPB group. There were no statistically significant differences between the two groups (P=NS). These results suggest that normothermic CPB did not increase the incidence of persistent postoperative neurological dysfunction compared to hypothermic CPB.     

Current role of liver transplantation for the treatment of urea cycle disorders: a review of the worldwide English literature and 13 cases at Kyoto University.

To address the current role of liver transplantation (LT) for urea cycle disorders (UCDs), we reviewed the worldwide English literature on the outcomes of LT for UCD as well as 13 of our own cases of living donor liver transplantation (LDLT) for UCD. The total number of cases was 51, including our 13 cases. The overall cumulative patient survival rate is presumed to be more than 90% at 5 years. Most of the surviving patients under consideration are currently doing well with satisfactory quality of life. One advantage of LDLT over deceased donor liver transplantation (DDLT) is the opportunity to schedule surgery, which beneficially affects neurological consequences. Auxiliary partial orthotopic liver transplantation (APOLT) is no longer considered significant for the establishment of gene therapies or hepatocyte transplantation but plays a significant role in improving living liver donor safety; this is achieved by reducing the extent of the hepatectomy, which avoids right liver donation. Employing heterozygous carriers of the UCDs as donors in LDLT was generally acceptable. However, male hemizygotes with ornithine transcarbamylase deficiency (OTCD) must be excluded from donor candidacy because of the potential risk of sudden-onset fatal hyperammonemia. Given this possibility as well as the necessity of identifying heterozygotes for other disorders, enzymatic and/or genetic assays of the liver tissues in cases of UCDs are essential to elucidate the impact of using heterozygous carrier donors on the risk or safety of LDLT donor-recipient pairs. In conclusion, LT should be considered to be the definitive treatment for UCDs at this stage, although some issues remain unresolved.     

Near-infrared spectroscopy for monitoring cerebral ischemia during selective cerebral perfusion.

OBJECTIVE: To minimize the neurological complications following cardiovascular surgery, it is essential to prevent an occurrence of cerebrovascular embolism and to detect and solve cerebral malperfusion without delay in the operating theater. Although we have introduced near-infrared spectroscopy (NIRS) monitoring for the purpose of detecting cerebral malperfusion, no criterion has been available. We searched for this criterion by examining the relationship of sustained drop in the regional oxygen saturation (rSO2) of the frontal lobes to the occurrence of neurological events. METHODS: The 59 consecutive patients undergoing aortic surgery with selective cerebral perfusion (SCP) were examined. The rSO2 was monitored throughout the surgery and the durations of drops in rSO2 to below 55% and those below 60% were determined for each patient. The durations of rSO2 drop and other surgery-related parameters were compared between the patients in whom neurological events occurred and those without such events. RESULTS: A total of 16 cases (27.1%) presented with neurological events. Newly developed cerebral infarction was documented in 6 of these 16 cases. Operation time and the durations for which rSO2 dropped were significantly longer for the 16 patients with neurological events than for the 43 patients without events (Op time: 546.8 versus 448.1 min, P=0.0064; rSO2 below 60%: 141.2 versus 49.8 min, P=0.0032; rSO2 below 55%: 66.6 versus 10.6 min, P=0.0011), while there was no significant difference in age, bypass time, aortic clamping time, SCP time, and circulatory arrest time between the two groups. In the 3 patients with infarcts suggestive to hypoperfusion, sustained decrease in rSO2 was observed, while it was not significant in the remaining 3 patients with infarcts suggestive to embolism. Among the 53 patients without infarction, transient neurological events occurred more frequently in patients with sustained drop in rSO2 below 55% for over 5 min (44.4% versus 5.7%, P=0.0014). CONCLUSIONS: A sustained drop in rSO2 during aortic surgery is closely related to the occurrence of neurological events following surgery. We recommend that recovery of drop in rSO2 below 55% should be addressed without delay. However, use of NIRS is limited for detecting embolic events or hypoperfusion in the basilar region.     

Cortical reflex myoclonus in adult onset Huntington's disease]

We report a case of cortical reflex myoclonus in adult onset Huntington's disease (HD). The patient is a 51-year-old woman. Chorea and myoclonus were observed on her face and extremities. Neurophysiological tests showed C reflex and abnormal waves preceding myoclonus by jerk-locked back averaging method but no giant somatosensory evoked potential. Gene analysis revealed the prolongation of CAG repeats (13/44) in IT15 gene. Oral administration of clonazepam was transiently effective for myoclonus. We should inscribe that the cortical reflex myoclonus may exceptionally manifest in HD.     

A suspected case of alcoholic pellagra encephalopathy with marked response to niacin showing myoclonus and ataxia as chief complaints]

We report a 47-year-old alcoholic man with alcoholic pellagra encephalopathy (APE) showing myoclonus and ataxia as chief complaints. He had been a heavy drinker for 30 years. He had noticed appetite loss and subsequently showed a subacutely progressive gait disturbance. He had no history of diarrhea, dementia, or dermatitis. On admission, he showed severe alcoholic liver cirrhosis with a large amount of ascites, limbs and truncal ataxia, myoclonus of the limbs and areflexia, although his consciousness was alert and there were no sign of dermatitis. Though the plasma level of ammonia was normal, we started administration of amino acids suspecting hepatic encephalopathy. Symptoms showed no improvement, and subsequent administration of thiamine was also ineffective. A decreased serum level of niacin was demonstrated. After administration of nicotinamide, the symptoms improved gradually. This patient received a diagnosis of APE. Endemic pellagra, characterized by the classical triad of dermatitis, diarrhea and dementia, is known to be caused by a dietary deficiency of the niacin, and has now become very rare in developed countries. At present, pellagra is encountered most often in patients with chronic alcoholism, which is called APE. APE patients often show only disturbance of consciousness. Although several reports has described ataxia and myoclonus in patients with APE, APE patients with myoclonus and ataxia as chief complaints have not previously been reported. On autopsy cases, central chromatolysis of neurons in the dentate nucleus of the cerebellum, gracile and cuneate nuclei, and the Clarke's column has been demonstrated. The APE patients would show myoclonus and ataxia as their first symptoms. In conclusion, we would like to emphasize that administration of niacin should be started for the treatment of chronic alcoholic patients showing myoclonus and ataxia even without the classical triads found in endemic pellagra patients.     

Preoperative chemotherapy increases cytokine production after lung cancer surgery.

OBJECTIVE: Many phase II trials have shown that preoperative chemotherapy for lung cancer is feasible but associated with postoperative morbidity and mortality. However, little is known about the effect of preoperative chemotherapy on surgical stress and postoperative complications associated with surgical intervention. We evaluated the effect of preoperative chemotherapy on perioperative inflammatory cytokine production as a surgical stress marker. METHODS: The study group comprised 38 patients undergoing anatomical lung resection and mediastinal nodal dissection for clinical stage IB/II non-small cell lung cancer during the period October 2001-December 2003. Nineteen patients received a single cycle of cisplatin (80 mg/m(2)) and docetaxel (60 mg/m(2)) chemotherapy prior to surgery (neoadjuvant group), and 19 patients underwent surgery without any previous chemotherapy (control group). White blood cell and neutrophil counts and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), and granulocyte colony-stimulating factor (GCSF) were determined before surgery and on postoperative days 1 and 3. Postoperative complications were reviewed. Differences were assessed by repeated analysis of variance. RESULTS: Serum concentrations of IL-6 and GCSF rose significantly on postoperative days 1 and 3 in the neoadjuvant group in comparison to concentrations in the control group, but white blood cell count, neutrophil count, and CRP did not differ between the groups. No major complication occurred in either group. CONCLUSIONS: A single cycle of cisplatin and docetaxel chemotherapy followed by surgery can exacerbate overproduction of inflammatory cytokines during the perioperative period in lung cancer patients.     

Malignant Rhabdoid Tumor of the Breast: A Case Report

A 66-year-old woman time of 10 days. One month after radicalmastectomy, there was local recurrence, followed by multiplepulmonary metastases, and the patient died of respiratory failure5 months after surgery. The gray-white-colored tumor measured13x12x;10 cm, and its border was well defined. The tumor wascomposed of diffusely growing round or polygonal cells withvesicular nuclei, prominent nucleoli, and ample cytoplasm containingeosinophilic inclusions. Lymph node involvement was widespread.Both vimentin and keratin were clearly demonstrated by immunohistochemicalstaining. Ultrastructural studies revealed that the MRT cellscontained cytoplasmic whorls of intermediate filaments.