Microsomal UDP-glucuronyltransferase-catalyzed bilirubin diglucuronide formation in human liver

Human liver microsomal bilirubin UDP-glucuronyltransferase catalyzes formation of bilirubin mono- and diglucuronide. KmUDPGA and Vmax of the enzyme are 0.6 mM and 1.69 nmol/mg protein X min. In vitro, bilirubin readily dissolves in the microsomal lipid phase. Taking this into account a Kmbilirubin of 60.6 microM was found, which is much higher than the in vivo microsomal UCB concentration of human liver (2.9-11.4 microM). The total capacity of human liver to form bilirubin mono- and diglucuronide in vitro exceeds the in vivo mono- and diglucuronide production rates by a factor 8 to 10. Radiation-inactivation studies reveal that human liver microsomal bilirubin UDP-glucuronyltransferase is a tetrameric enzyme with a molecular mass of 209 000 +/- 20 000 Da. The complete tetrameric enzyme catalyzes both glucuronidation steps, formation of bilirubin monoglucuronide and conversion of mono- to diglucuronide. In its monomeric form, the enzyme with molecular mass of 55 000 +/- 1 500 Da catalyzes only the first step of bilirubin glucuronidation, the formation of bilirubin monoglucuronide.     

Results of irradiation in the squamous cell carcinomas of the anterior faucial pillar-retromolar trigone

Between January 1966 and August 1981, 159 patients with previously untreated squamous cell carcinomas of the anterior faucial pillar or retromolar trigone received definitive radiation therapy at The University of Texas M. D. Anderson Hospital and Tumor Institute. All except 11 patients were treated by external radiation including combination of electron beams with high-energy photons or 60Co to doses ranging from 60 Gy to 75 Gy. In the N0 patients, as a rule, only the ipsilateral subdigastric nodes were treated electively to a dose of 50 Gy. The 5-year determinate survival rate for the overall group was 83%. The cumulative recurrence rate showed that 92% of the patients had recurrence by 2 years. Therefore, all patients except those who died with no evidence of local disease less than 2 years after treatment were evaluated for local control. The failure rate for the evaluable patients was 29% for T1 lesions, 30% for T2 lesions, 24% for T3 lesions, and 40% for T4 lesions. After salvage surgery, which consisted of intraoral resection in one-third of the patients and of a composite operation in the other two-thirds, the ultimate failure rate was 0% for T1 lesions, 6% for T2 lesions, 8% for T3 lesions, and 20% for T4 lesions. Whereas stage was a poor indicator for treatment outcome, there was a significantly higher failure rate for infiltrative and/or ulcerated lesions (35%) than for exophytic or superficial lesions (15%). Histologic grade was of no prognostic significance, nor was there any significant difference in the failure rate for lesions originating on the anterior faucial pillar versus that for lesions on the retromolar trigone. Following radiotherapy, 30% of the patients developed some degree of bone exposure but only 5.6% (9 patients) required a segmental mandibular resection. The probability of bone exposure was not dose related and more likely reflected tumor location on the mucoperiosteum. Of the whole group, 16 patients (10%) experienced a neck failure with 8 ultimate failures after salvage surgery. Among the 16 patients who had neck failures, 13 were originally staged N0; 6 of these patients had failures that occurred in the electively treated ipsilateral subdigastric area, but the field was too small to cover the nodes adequately. Aspects of the radiotherapy techniques with combined electron and photon beams that may influence the treatment outcome are discussed.     

Inspired Oxygen Fraction of 0.8 Does Not Attenuate Postoperative Nausea and Vomiting after Strabismus Surgery

Background: Postoperative nausea and vomiting (PONV) is a distressing problem after strabismus surgery. An inspired oxygen fraction has been reported to decrease PONV in patients after colon resection and to be more effective than ondansetron after gynecologic laparoscopy. Therefore, in a randomized, prospective, placebo-controlled study, the authors tested whether an inspired oxygen fraction of 0.8 decreases PONV in patients undergoing strabismus surgery and whether oxygen is more effective than ondansetron.

Methods: With approval of the authors' institutional review board, 210 patients were randomly assigned to receive one of three treatments: (1) 30% inspired oxygen in air plus intravenous administration of saline, (2) 80% inspired oxygen in air plus intravenous administration of saline, or (3) 30% inspired oxygen in air plus 75 [mu]g/kg ondansetron intravenously during induction. General anesthesia was standardized and included etomidate, alfentanil, and mivacurium for induction and sevoflurane for maintenance. PONV was evaluated 6 and 24 h postoperatively by an investigator unaware of treatment assignment.

Results: Overall postoperative incidence of nausea and vomiting was 41% for inspired oxygen fraction of 0.3 plus placebo, 38% for inspired oxygen fraction of 0.8 plus placebo, and 28% for inspired oxygen fraction of 0.3 plus ondansetron, respectively (P = 0.279). Therefore, there was no statistically significant difference of PONV incidence among groups.     

Alcohol consumption of patients attending two accident and emergency departments in north-west England.

The impact of alcohol use on the workload of two accident & emergency departments in north-west England was assessed by blood alcohol concentration (BAC) measurement, inspection of clinical records and interview of all patients aged 16 and over attending throughout a two-week period. The frequency of intoxication was similar to the previous reported rate in Scotland: 13.2% of all patients had a positive BAC. Inebriated injured patients arrived at all times of the day--varying in frequency from 2.5% of midday attenders to 78% of those presenting after midnight. The incidence of alcohol-related industrial accidents was low, but 60% of all assaulted patients were inebriated, many having sustained head injuries. Of patients attending within 2 hours of an accident at home, 19% also had a positive BAC, but 92% of those with ankle sprains were sober. Patients in lower social classes reported higher rates of alcohol consumption. The popularity of beer in comparison to wines and spirits was inversely related to age and unrelated to social class. Alcohol abuse is commonly associated with injuries sustained at home and with assaults occurring in public places. Prevention campaigns directed at the reduction of these types of incidents should be as concerned with the inebriation of the patient as with the architectural, environmental and legal framework within which the 'accident' occurs.     

Predictors of residual mass histologyafter chemotherapy for advanced testis cancer

The records of 15 patients with Stage B3 or B2/C germ cell testis tumors who underwent full surgical debulking of a residual mass after completion of chemotherapy were reviewed retrospectively to look for predictors of residual mass histology. The density, character, and change in volume of the retroperitoneal mass on computerized tomography before and after chemotherapy were compared with the histology in the primary tumor and in the residual mass. One of 6 patients without teratoma in the primary tumor had a 97 percent reduction in the mass which contained residual teratoma. Two patients with residual seminoma had a 50 percent decrease in tumor volume, and both patients died of tumor progression despite salvage chemotherapy. Two patients with pure seminomas had only residual fibrosis in masses that decreased in volume by 77 and 75 percent, respectively. One of these masses was discrete and the other was diffuse. Seven of 9 patients (78%) with teratoma in the primary tumor had either teratoma (4 of 9, 44%) or carcinoma (3 of 9, 33%) in the residual mass, and the change in mass volume ranged from a 93 percent decrease to a 540 percent increase in size. All 7 patients with residual teratoma and/or carcinoma remain free of disease after observation or further chemotherapy. For the entire series, the mass density and character did not correlate consistently with the primary tumor or residual mass histology. Residual fibrosis alone or teratoma and/or carcinoma were seen with least (0 to 50%) and greatest (more than 90%) decreases in mass volume.     

Maternal stress increases fetal brain and neonatal cerebral cortex 5-hydroxytryptamine synthesis in rats: a possible mechanism by which stress influences brain development.

Previous studies have shown that maternal stress modifies 5-hydroxytryptamine (5-HT) receptor binding in several brain regions of the adult offspring and alters the intensity of the behavioral responses to 5-HT receptor agonists. We now report that the same stress, crowding combined with daily saline injections during the final week of pregnancy, elevates maternal plasma free tryptophan level without significantly affecting total tryptophan. The increased maternal plasma tryptophan was associated with significantly increased fetal brain levels of tryptophan, 5-HT and 5-hydroxyindoleacetic acid. These increases were maintained after birth until at least postnatal day 10. Since 5-HT is recognised as having a role in the control of neuron development during the perinatal period, we suggest that the stress-induced increase in fetal brain 5-HT synthesis may play a part in the mechanisms by which prenatal stress alters adult behavior.