Correlation of growth factor receptor expression with clinical growth in vestibular schwannomas.

OBJECTIVE: To examine the relationship between growth rate of vestibular schwannomas and the expression of various growth factor receptors. STUDY DESIGN: Retrospective case review of clinical growth rate in conjunction with a histopathologic and immunohistochemical reexamination of archival specimens. SETTING: A tertiary referral neurotologic center. PATIENTS: Three groups: a historical group to act as controls, consisting of 30 patients with sporadic vestibular schwannomas removed before the unit adopted an initial interval scan policy; a group of 14 patients with sporadic vestibular schwannomas who had undergone an initial interval scan policy, showed radiologic evidence of growth, and therefore had their schwannoma removed; and a group of 16 schwannomas removed from 11 neurofibromatosis Type 2 patients. MAIN OUTCOME MEASURES: A comparison between the three clinical groups using immunohistochemical studies to determine the level of expression of the proliferation factor Ki-67, c-erbB-2, and c-erbB-3 receptors and fibroblastic growth factor receptors 1 and 4. RESULTS: The level of expression of the proliferation factor Ki-67 was very low and similar in all three groups. C-erbB-2 and c-erbB-3 receptors were not expressed in any of the groups. fibroblastic growth factor receptor 4 expression was not significantly different, but there was a variation in the expression of fibroblastic growth factor receptor 1 between the three groups that correlated well with the differing incidence of growth in the groups. The increase in expression of fibroblastic growth factor receptor 1 in the neurofibromatosis Type 2 group was not statistically significant, but the increase in expression of fibroblastic growth factor receptor 1 in the growing sporadic group was statistically significant when compared with the historical controls. The level of fibroblastic growth factor receptor 1 expression correlates significantly with the rate of growth as measured on interval magnetic resonance imaging. CONCLUSIONS: Overexpression of fibroblastic growth factor receptor 1 has a positive correlation with the incidence and the rate of growth of sporadic vestibular schwannomas.     

Calcium homeostasis in pregnant women receiving long-term magnesium sulfate therapy for preterm labor.

OBJECTIVES: The hypothesis of this study is that calcium homeostasis and bone mineralization are altered in pregnant women receiving long-term therapy with magnesium sulfate as compared with similar women not receiving magnesium sulfate to control preterm labor. STUDY DESIGN: Thirty-nine women between 24 and 32 weeks' gestation, matched for age, race, and duration of bed rest, were enrolled. Indices of calcium homeostasis in serum and urine were measured serially, and bone mineralization of the distal radius was measured at 1 and 11 weeks post partum. RESULTS: Magnesium therapy was administered for a mean duration of 26 +/- 14 days and a cumulative dose of 1405 +/- 963 gm. Serum concentrations of magnesium, phosphorus, and parathyroid hormone increased and those of calcium decreased from baseline values in the magnesium sulfate group and remained uniform throughout the 3-week investigation. The serum magnesium, phosphorus, parathyroid hormone, and calcium concentrations in the control group were unchanged during the study and differed significantly from those in the magnesium sulfate group (p < 0.001). Urinary output of magnesium, calcium, and copper was significantly greater in the magnesium sulfate group than in the control group throughout the study. Urinary losses of calcium in the magnesium sulfate group, approximately 800 to 900 mg/day, were substantial. Although radius bone density 1 week post partum did not differ between groups, the change in bone density from 1 to 11 weeks post partum was significantly lower in the magnesium sulfate group than in controls. CONCLUSIONS: These data suggest that calcium homeostasis is altered during and after long-term magnesium sulfate therapy. The marked, prolonged urinary calcium losses may affect maternal bone mineralization.     

Transvaginal sonography of cervical width and length during pregnancy.

Transvaginal ultrasonography has been proposed as a reliable method of assessing dimensions of the cervix. The purpose of the current investigation was to establish normative data for cervical width and length during pregnancy. This information may be helpful in predicting patients at risk for preterm birth. A transvaginal 5 or 7.5 MHz transducer was used on 132 consecutive low-risk pregnant women undergoing evaluation for gestational dating purposes. Even in cases of patient obesity or an empty bladder, high resolution was possible and permitted cervical measurement in all but one case. The external cervical width at the vaginal fornices was found to increase with advancing gestation (R = 0.512, P < 0.005). The cervical length from internal os to external os was found not to change with advancing gestation (R = 0.11, P = 0.30). Using these normative data, investigation is recommended to determine whether measuring cervical width and length is useful in predicting preterm labor and delivery.     

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.