Missense mutations in codon 225 of ornithine transcarbamylase (OTC) result in decreased amounts of OTC protein: A hypothesis on the molecular mechanism of the OTC deficiency

Mutations P225L and P225R were identified in codon 225 of the gene for ornithine transcarbamylase (OTC) in two patients with the neonatal form of OTC deficiency. The mutations occur at a CpG dinucleotide and eliminate a unique MspI restriction site in exon 7 of the OTC gene. They do not alter existing splice sites or create new sites, as judged from the nucleotide sequence. Both mutations are associated with undetectable levels of OTC antigen in liver homogenates, and with either complete lack of OTC activity (P225R mutation) or very small residual activity (0.15% of normal in the P225L mutation). The residual activity observed with P225L exhibits normal pH dependence, little or no increases in the Km values for ornithine and carbamoyl phosphate and normal stability at either 37°C or, in the presence of 0.66 mol/L urea, at 0°C. The latter conditions were used to examine whether the P225L mutation favours dissociation of the active OTC trimer. Given the normal stability and lack of tendency to dissociation of the mutant enzyme, it appears likely that the dramatic reduction in the level of OTC protein is due to inefficient conversion of the mutant OTC precursor polypeptide (pOTC) into the correctly localized, appropriately folded, mature enzyme trimer, suggesting degradation of pOTC in transit to the mitochondria.     

MRI of a family with focal abnormalities of gyration

Focal abnormalities of gyration (FAG) are developmental disorders that may occur in isolated patients or, as in the case being reported, as part of a familial disorder. Analysis of individuals in a family spanning three generations was carried out using MRI. Abnormalities, present in all members of generations II and III, included focal cortical dysplasia (three patients), focal cortical infolding (two patients) and schizencephaly (one patient); associated minor anomalies, such as white matter abnormalities, were seen in the remaining three members of generations II and III. MRI recognition of FAG in the family being reported proved useful in defining their phenotypical expression and providing proper counselling for individual family members. Received: 22 August 1996 Accepted: 7 October 1996     

Knowledge and attitudes of primary health care personnel concerning mental health problems in developing countries: a follow-up study

Within the context of a World Health Organization coordinated collaborative study health workers in six developing countries were assessed 18 months after their training for improvement in their knowledge and attitude towards mental health problems and their management. The approaches to training varied between study areas, but the degree of improvement following the training, was of equal magnitude in all countries. The training process has formalized the recognition by the health workers that treatment of mental health problems is an integral part of their work.     

mdm2 gene alterations and mdm2 protein expression in breast carcinomas

This study investigates the mdm2 gene status and expression in 66 surgically resected human breast carcinomas, with correlations with clinico-pathological and biological data (histological type, grading, steroid receptor status, p53 expression, proliferative activity). Four (7.7 per cent) out of 52 informative cases bear mdm2 gene amplification (four- to ten-fold) and 8 (15.4 per cent) of 52 cases showed borderline amplification (three-fold). Nine (13.6 per cent) out of 66 cases showed strong mdm2 nuclear immunoreactivity. Twenty-seven (40.9 per cent) cases showed isolated mdm2 reactive nuclei. All cases with clear amplification showed a high percentage of mdm2 immunoreactive nuclei. The relationship between gene amplification and mdm2 protein expression is highly significant (P<0.0001). No association was observed between mdm2 gene amplification and any of the considered clinico-pathological and biological parameters, while mdm2 immunoreactivity showed a significant association only with oestrogen receptor immunoreactivity (P=0.009). p53 expression was associated neither with mdm2 gene amplification nor with mdm2 immunoreactivity. It could be tempting to hypothesize that the evaluation of the combined mdm2/p53 immunohistochemical phenotype in human breast carcinoma could give us better prognostic information than the evaluation of the expression of the p53 protein alone.     

Arachnoid cysts of the middle cranial fossa: a consideration of their origins based on imaging

Arachnoid cysts situated in the middle cranial fossa constitute the largest group of this type of lesion. Their origin has been the subject of debate since they were first described. There is still controversy as to whether they originate directly from the meninges adjacent to the temporal pole or whether partial agenesis of the temporal lobe favours secondary formation of the cyst. We assessed the morphology of the temporal lobe and the bulging of the squamous temporal bone. Paradoxical changes in adjacent-bone, described as very rare findings in arachnoid cysts of the middle cranial fossa, were common in our study and suggest, in association with direct signs of temporal atrophy, that this atrophy precedes, or is at least coexistent with, the formation of the cyst. The importance of being able to determine the origin of the cyst lies in its being a factor to assess as regards treatment.     

Factores pronósticos del cáncer de mama. Modelo predictivo

Introduction. Breast cancer remains the most frecuent tumor among women in developed countries. The prognosis is linked to a great variety clinic and pathological factors. The objectives from this study are to identify markers related to survival of patients with primary diagnosis of breast cancer. Material and methods. We have reviewed the medical dossier from 2.227 consecutive women diagnosed for infiltrating breast cancer between January 1966 and december 2000 in a single institution. For statistic analysis we used 10.0 SPSS software. Results. In the univariate analysis, factors with the strongest predictive value for overall survival were: PEV, estrogene and progesterone receptors, TNM stage, lymphatic vessel involvement, histologic grade, Scarff differentiation and mitosis rate, elastosis, presence of histiocitosis, and the percentage of involved stage I and III lymph nodes (Berg clasification). In the multivariate analysis, 5 factors; progesterone receptors, Scarff mitotic rate, lymphatic vessel involvement, percentage of involved stage I lymph nodes, and presence of metastasis; were independent prognostic markers of survival. Conclusions. Many independent factors interact in the survival of patients with primary breast cancer. Determination of hormonal receptors, mainly progesterone’s, appear as the most powerful indicators. The analysis has generated a prognostic simplified classification, based in the 5 independent variables, that provides specific rates for survival at 2, 5 and 10 years.     

Preoperative uracil, tegafur, and concomitant radiotherapy in operable rectal cancer: a phase II multicenter study with 3 years' follow-Up.

PURPOSE: To assess tolerance and efficacy of preoperative treatment with uracil/tegafur and radiotherapy (RT) followed by surgery and postoperative flurouracil (FU)/leucovorin (LV) in patients with rectal cancer. PATIENTS AND METHODS: Patients (n = 94) with potentially resectable tumors, ultrasound at stages T2N+ (n = 4), T3 (n = 77), T4 (n = 13) were treated with UFT (400 mg/m2/d, 5 days a week for 5 weeks) and concomitant RT to the pelvis (45 Gy; 1.8 Gy/d over 5 weeks). Patients underwent surgery 5 to 6 weeks later followed by four cycles of FU/LV. Primary end points included downstaging, pathologic responses, and sphincter-preserving surgery. Secondary end points were recurrence-free survival and overall survival. RESULTS: All patients received the full RT dose. Fifteen patients (16%) needed UFT dose reduction. Preoperative G3+ toxicities included diarrhea (14%), leukopenia (1%), thrombocytopenia (1%), and nausea (4%). The downstaging rate was 54%, pathologic complete response (pCR) was 9% and, in an additional 23%, there were only residual microscopic foci. When cellular viability criteria were taken into account, the pCR was 15%. From 43 patients with abdominoperineal resection indication, 11 (25%) had sphincter-preserving surgery performed. Postoperative scheduled chemotherapy dose was not administered to 24% of patients because of G3+ toxicity (diarrhea, 8%; mucositis, 9%; and leukopenia, 7%). Patients with downstaging had significantly higher survival and recurrence-free survival rates than those without. At 3 years, actuarial patterns of failure were pelvic, 5% and distant, 11%. OS was 75%. CONCLUSION: UFT combined with RT is safe and effective. In resectable rectal cancer, if preoperative treatment is considered, this approach can be an option.     

The use of the biofragmentable ring (BAR-Valtrac) in colon surgery

BACKGROUND: Clinical results of colic anastomosis using biofragmentable anastomosis ring (BAR-Valtrac) are presented. Such a method showed to be a real alternative technique to the usual ones. METHODS: Eighty-six colic anastomosis using BAR are collected, 76 of which performed as elective surgery and 10 in emergency. The patients were 47 males and 39 females, with a mean age of 64 years. In 63 cases the patients were affected by colic neoplastic disease, in 16 by complicated diverticular disease (stenosis or perforation) and 7 patients had neoplastic disease of other organs involving the colon BAR device was used in 48 colic reconstructions after segmentary resection and in 38 colic reconstructions after left hemicolectomy. In each case 31-34 mm BAR were used. RESULTS: No perioperative death occurred in our series. Only one case (2%) of anastomotic leak was observed, while in 3 cases (4%) intestinal canalization disorders occurred. No problems for ring expulsion occurred in any patient. Three late complications were observed, as three cases of asymptomatic substenosis discovered during instrumental follow-up and spontaneously cleared up. CONCLUSIONS: On the basis of clinical results, and according to those reported in literature BAR anastomosis is considered a safe, feasible and easy technique to perform colic anastomosis, even in emergency, limited to the intraperitoneal tract of the colon.     

Sequential endo-laparoscopic treatment in patients with common bile calculi

BACKGROUND: Laparoscopic treatment of common bile duct (CBD) stones is gaining great acceptance worldwide, but actually it requires skills and technologies too expensive for a great part of general surgeons. So endoscopic removal of CBD stones before cholecystectomy is usually performed. Since 1991 in our department we started a policy of selective preoperative cholangiopancreatography (ERCP) in patients suspected for choledocholithiasis and waiting for laparoscopic cholecystectomy. METHODS: A retrospective study has been made on a population of 1100 patients who underwent elective laparoscopic cholecystectomy in the period between January 1991 and December 1997. They were 391 male and 719 female with a mean age of 52 years, 126 of whom (11.5%) were selected to have ERCP preoperatively because they had clinical, biochemical and ultrasound signs of the presence of common bile duct stones (CBDS). RESULTS: Successful cannulation of the CBD was achieved in 124 cases (98.4%), with failures due to ampullary diverticula. In 7 cases (5.5%) a precut was necessary to obtain cannulation. Sphincterotomy was performed in 113 patients (89.7%). In 93 patients (73.8%) stones were found (87 macrolithiasis and 6 microlithiasis); in 91 (97.8%) stones were removed in one (87) or two (4) endoscopic session. There were 2 major complications (one bleeding and one severe pancreatitis) due to ERCP or a sphincterotomy. Two patients developed symptoms from unsuspected common bile duct stones after LC and were removed endoscopically. No complications during LC were due to ERCP or ES. CONCLUSIONS: Selective preoperative ERCP is an effective way of clearing the CBD stones before laparoscopic cholecystectomy, with low rate of complications related to endoscopic and laparoscopic procedures, and short mean hospital stay (5.5 days), according to the concept of minimally invasive treatment.