Kinetics and enzyme involvement in the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in microsomes of rat lung and nasal mucosa.

The rat lung and nasal cavity are two target organs for carcinogenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In order to characterize further the enzymes involved in the bioactivation of NNK, detailed kinetic and inhibitory studies were conducted with rat lung and nasal mucosa microsomes, and the results were compared with previous studies. The enzymes in rat lung microsomes catalyzed the alpha-hydroxylation, pyridine N-oxidation and carbonyl reduction of NNK. The apparent Km for the formation of the NNK-derived keto aldehyde, NNK-N-oxide, the NNK-derived keto alcohol and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were 28.8, 10.4, 7.0 and 178.1 microM respectively. In rat nasal microsomes, alpha-hydroxylation was the predominant pathway and the rate was approximately 200 times higher than that in lung microsomes. The apparent Kms for keto aldehyde and keto alcohol formation in rat nasal microsomes were 9.6 and 10.1 microM respectively. The cytochrome P450 inhibitors metyrapone and carbon monoxide markedly inhibited the metabolism of NNK in both rat lung and nasal microsomes. In rat lung microsomes, alpha-naphthoflavone and monospecific antibodies against P450s 1A2, 2A1 and 2B1 inhibited the formation of keto aldehyde by 39, 46, 64 and 23% respectively. In rat nasal microsomes, alpha-naphthoflavone and antibodies against P450s 1A2, 2A1 and 3A inhibited the metabolism of NNK by 80, 35, 20 and 14% respectively. The results indicate that cytochromes P450 play a major role in the metabolic activation of NNK in rat lung and nasal microsomes, and that there are tissue-related differences in NNK metabolism.     

Nutritional dwarfing: is it a consequence of disturbed psychosocial functioning?

Nutritional dwarfing refers to a condition in which maladaptive eating patterns play a primary role in poor linear growth and delayed pubertal development. The present controlled study assesses whether nutritionally dwarfed children and adolescents differ in their psychosocial adjustment from healthy children and adolescents of comparable height in ways that might account for their undernutrition. Children with nutritional dwarfing (n = 16) were compared by standardized questionnaires with a short-stature (ie, heights below the fifth percentile) control group composed of children and adolescents with constitutional growth delay and/or familial short stature (n = 31). Scores on a self-report screening questionnaire for eating disorders did not differentiate the groups. Moreover, the vast majority of nutritionally dwarfed patients expressed a desire to have a heavier physical appearance. Whereas the groups were generally similar in self-perceptions of domain-specific competencies and positive psychosocial adjustment, the parents of nutritionally dwarfed children reported that their children showed significantly fewer externalized behavior problems. These findings suggest the existence of an eating disturbance that compromises growth in childhood and/or adolescence which, unlike anorexia nervosa, is not associated with evidence of psychopathology.     

The hidden mortality in surgically treated necrotizing enterocolitis: fungal sepsis

From 1979 to 1986, 82 infants underwent surgical treatment for necrotizing enterocolitis (NEC), with 36 deaths. The records of 30 of the 36 infants who died were available for review. Fungal colonization and sepsis, the sites of infection, and timing of diagnosis and therapy were determined. Sixteen of 30 (53%) neonates had no evidence of fungus. Six (20%) were colonized with Candida species. Eight (27%) had fungal sepsis, with two of these eight found only at necropsy. Positive fungal blood cultures were a late finding. In only four of the six patients with positive blood cultures were the results known in time to initiate treatment with amphotericin B. Two of these four babies received less than 2 days of amphotericin B treatment prior to death. Fungal sepsis is a significant lethal factor in the surgical mortality of NEC. Vigorous efforts at earlier diagnosis are mandatory.     

Development of an alloantiserum (R2) that detects susceptibility of chickens to subgroup E endogenous avian leukosis virus

An alloantiserum, termed R2, specifically agglutinates red blood cells (RBC) from line 100B chickens that are susceptible to avian leukosis viruses (ALV) belonging to subgroups B and E, but does not agglutinate RBC from congenic inbred line 7(2 )chickens that are resistant to ALV B and E. The R2 antigen was also detected on lymphocytes and thrombocytes. Using chickens from a special cross, it was found that R2 reactivity requires that the chickens must: (1) be susceptible to infection by ALV-E; and (2) express a viral envelope gene with subgroup E specificity. With R2 antiserum, a nearly perfect association was observed between agglutination and susceptibility to ALV-B in F(2) chickens containing endogenous viral genes ev2 and/or ev3. These results support earlier evidence that ALV-B and ALV-E share receptors. Moreover, the R2 antiserum was shown to neutralize ALV-E. The R2 antigen showed Mendelian segregation in chickens of a commercial White Leghorn strain-cross containing ev3, ev6 and ev9. However, commercial chickens with or without the R2 antigen did not differ in susceptibility to lymphoid leukosis induction or immune response on infection with ALV of subgroup A for complex reasons we discuss.     

Reduced tracheal growth after reconstruction with pericardium

Four groups of piglets were used to test the use of pericardium and periosteum as free grafts in the repair of full thickness cervical tracheal defects. Pericardium provided an airtight, rapidly healing graft, but did not give sufficient structural rigidity to prevent narrowing and growth failure at the graft site. Composite grafts of pericardium and periosteum were also unsatisfactory, in that the periosteum failed to produce enough bone to prevent collapse of the graft. Since previous studies have shown that periosteal grafts result in good bone formation when applied alone or as an extramucosal support, it is concluded that the osteogenic potential is dependent on the available blood supply and speed of revascularization. It appears that the presence of pericardium in the composite grafts may have inhibited this property.     

CT of the pancreas with a fat-density oral contrast regimen

Visualization of the head of the pancreas by CT was prospectively evaluated in two groups of 100 patients who did not have pancreatic disease. Patients were given either a fat-density oral contrast material (12.5% corn-oil emulsion and metoclopramide) or a conventional high-density oral contrast material (barium suspension or iodinated solution). There was no statistically significant difference in the subjects' tolerance to the two regimens. There was, however, a significant improvement in ability to distinguish the head of the pancreas from the duodenal C-loop when the fat-density contrast material was given. When pancreaticoduodenal discrimination was graded, patients given corn-oil emulsion and metoclopramide received an average score of 0.94, whereas those given the high-density agent received an average score of 0.74, with 1.00 being the highest possible score (p less than .005). These data suggest that for routine CT evaluation of the head of the pancreas, a combination of corn-oil emulsion and metoclopramide may be superior to the conventional high-density oral contrast agents given without metoclopramide.     

Absence of persisting parenchymal damage after extracorporeal shock wave lithotripsy as judged by excretion of renal tubular enzymes

Four renal tubular enzymes, N-acetyl-beta-glucosaminidase, beta-galactosidase, angiotensin-converting enzyme and gamma-glutamyltransferase, were measured in the urine before, and 24 hours and 1 week after extracorporeal shock wave lithotripsy in 20 consecutive patients. Extracorporeal shock wave lithotripsy was performed on the Sonolith 2000 device with the patient under intravenous narcotic sedation with fentanyl. Enzymatic activity per gram of urinary creatinine was consistently but not significantly higher before extracorporeal shock wave lithotripsy than in control subjects. All 4 enzymes were elevated 24 hours after extracorporeal shock wave lithotripsy, with the increases in beta-galactosidase and angiotensin-converting enzyme being statistically significant. However, by 7 days after the procedure the enzymes had decreased to pre-procedure concentrations or below. These data suggest that any renal tubular damage induced by extracorporeal shock wave lithotripsy is of limited magnitude and brief duration.     

Males as a high-risk group for trauma: the Finnish experience

The high incidence of trauma among young men has been observed in many countries. To better understand this risk, we analyzed male injuries and their causes in Finland. The incidence peak of medically attended trauma in men aged 15-24 years was caused by occupational and sports injuries, whereas that of hospitalizations was due to motor vehicle injuries. Age patterns of nonfatal trauma resembled those recorded in the U.S.A. However, patterns and causes of fatal trauma were very different in the two countries: early adulthood in the U.S.A. and late middle-age in Finland were the ages of highest injury mortality. The majority of deaths in young men were caused by motor vehicle injuries in the U.S.A., whereas suicides and the extremely high rate of fatal non-motor vehicle accidents, largely due to alcohol poisoning and drownings, formed the main bulk of injury mortality in Finland. Similarities in early adulthood suggest general biological factors, whereas the deviance of the middle-aged male Finns from the general pattern may indicate more specific psychosocial factors.