Fetal neural grafts for Huntington's disease: a prospective view.

Intrastriatal transplantation of striatal neuroblasts from human fetuses is a promising approach for treatment of Huntington's disease, on the basis of many experimental animal studies and, most recently, pilot clinical trials. Technically, several issues remain to be resolved (e.g., the precise site of dissection of the fetal tissue; the number and location of the fetal striatal implants; or the use of immunosuppressive therapy), and await larger-scale trials and purposely designed protocols. Further clinical data must also be obtained, and preliminary promising results must be replicated in a patient group large enough to provide conclusive results. It is important to establish (1) the amount of clinical benefit provided to the patient by the grafted cells; (2) the anticipated duration of clinical benefits; and (3) the secondary rate of decline after the benefit of the graft has been overbalanced. Evaluation of these parameters will require very long-term follow-up of the patients involved, over several years after grafting, before the technique can eventually be proposed widely to patients.     

How to assess fetal metabolic acidosis from cord samples.

The degree of metabolic acidosis at birth has been calculated in cord artery and vein samples from 21 term fetuses with cord artery pH less than 7.20. The aim of the study was to compare base deficit values calculated from either Siggaard-Andersen alignment nomogram (BD blood) or the Acid-Base chart (BD extra cellular fluid, BDecf). BDblood was found to be consistently higher in the cord artery as compared with BDecf, 13.2 +/- 3.5 and 9.9 +/- 2.9 mmol/l (Mean +/- SD), respectively. A significant correlation was found between cord artery PCO2 and BDblood whereas BDecf appeared unaffected by PCO2. In cases with cord entanglement BDecf a-v differences were increased to 3.4 +/- 2.3 mmol/l as compared with the small a-v difference noted in acidotic cases without cord entanglement, 1.1 +/- 1.25 mmol/l. It is speculated that with acutely emerging, intermittent asphyxia due to cord compression, a cord artery and vein difference in metabolic acidosis may exist and where the vein captures the basal level and the artery the acute changes. It is concluded that BDecf in both cord artery and vein add valuable information on the mechanisms behind metabolic acidosis.     

Effect of the amount of body fat on the age-associated increase in serum cholesterol

This study investigates the contribution of body fat stores on the age-associated increase in serum cholesterol and triglyceride levels. Percentage of body fat was measured by hydrostatic weighing, and serum cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels were determined in a sample of 472 healthy men and women ages 18-50 years. In both sexes, body fat mass was significantly correlated with serum cholesterol (r = 0.21 in men and r = 0.24 in women, P less than 0.01) and triglyceride (r = 0.33 in men and r = 0.24 in women, P less than 0.01) levels. After adjustment for the association between age and serum cholesterol, no correlation was observed between body fat mass and serum cholesterol (r = 0.01 in men and r = 0.09 in women). After correction for age, serum triglyceride levels remained significantly correlated with body fat mass (r = 0.26 and r = 0.17 in men and women, respectively, P less than 0.05). As body fat also increases with age, the possibility that a partial correlation coefficient procedure eliminated a portion of the age effect mediated by an age-related increase in fat, was addressed by performing further analyses. Within each sex subsample two sets of analyses were performed on (a) three groups of subjects individually paired for age but with different levels of body fat stores, and (b) three groups of subjects paired for the amount of body fat but differing in age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Is colonic electrical activity a similar phenomena to small-bowel electrical activity?

PURPOSE: This study was designed to investigate colonic spike bursts regarding 1) their migration behavior, 2) their pressure correlates, and 3) comparing colonic short spike bursts with spike bursts from migrating myoelectric complex from the small bowel. METHODS: Rectosigmoid electromyography and manometry were recorded simultaneously in seven normal volunteers and electromyography alone in five others during two hours of fasting and for two hours after one 2,100-kJ meal. One patient with an ileostomy was also studied by the same method to record the migrating myoelectric complex from the terminal ileum during fasting. RESULTS: Three kinds of spike bursts were observed in the pelvic colon: rhythmic short spike bursts, migrating long spike bursts, and nonmigrating long spike bursts. The meal significantly increased the number of migrating and nonmigrating long spike bursts (from 25 to 38.7 percent of the recording time; P <0.01). These bursts of potentials showed a peak 15 minutes after the meal, which may be caused by the gastrocolic reflex. Migrating long spike bursts started anywhere along the rectosigmoid and migrated from there aborad 82 percent of the time and orad or in both directions in 10 or 7 percent of the time, respectively. They originated pressure waves 99 percent of the time. Short spike bursts were more frequent before the meal (15.1 percent before and 9.6 percent after the meal), but the difference was not significant; they neither propagated nor initiated pressure waves detected by the miniballoon. CONCLUSIONS: Migrating long spike bursts were the only potentials that migrated, sometimes for short distances. Short spike bursts are a different phenomenon from the small-bowel migrating myoelectric complex because they do not migrate; they can occur during the postprandial period and never originated intraluminal pressure waves.Supported by a grant from the Instituto Nacional de Investigação Científica, Proc. DBI-22086.Presented at the meeting of the Portuguese Congress of Gastrenterology, Vila Moura, Portugal, June 2 to 5, 1993.     

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.     

Mortality prognostic factors in chest injury

1,026 multiple trauma patients (P) were compared to P with chest injuries (PCT) (407). Severity indices were related to type of thoracic injury and mortality. The Injury Severity Score (ISS), Glasgow Coma Scale (GCS), Trauma Score (TS), CHOP, and the Respiratory Index (RI) were used. The mortality rate of P was 27.1% but increased to 32.9% for PCT (p less than 0.05). We noted that mortality rate was highly dependent on major chest trauma: 68.6% for flail chest (FC), 56% for lung contusion (LC), 42.3% for hemothorax (HA), and 38.1% for pneumothorax (PN). ISS and RI scores for PCT survivors were greater than ISS + RI scores for P survivors (p less than 0.05 and p less than 0.01). ISS values for LC, HA, and PN PCT survivors were greater than the ISS of P survivors (p less than 0.01). Nonsurviving PCTs, especially those with lung contusion, showed a highly significant increase in ISS and RI scores.     

Uptake of Adriamycin in tumour and surrounding brain tissue in patients with malignant gliomas

Summary Eight patients with malignant gliomas verified on CT scan, received an intravenous injection of 50 mg of Adriamycin R, 24 hours prior to surgical removal of the tumour. Peroperatively, both tumour and surrounding tissue specimens were obtained for determination of the tissue concentrations of Adriamycin and its reduced metabolite Adriamycinol. It was found that Adriamycin could be detected in tumour tissue from all patients. The concentration varied between 0,9 and 4,6 nmol/g tissue. In contrast, Adriamycin could only be detected in surrounding brain tissue from one patient.In anin vitro study a human malignant glioma cell line (U-251 MG) was exposed to various concentrations of Adriamycin for 24 hours. It was found that an intracellular drug concentration above 30 nmol/g cells caused a concentration dependent inhibition of cell growth. Thus, it is likely that the poor effect of Adriamycin on patients with malignant gliomas is due to an ineffective drug accumulation in the tumour tissue.