Alcohol: "ice-breaker" yes, "gut barrier-breaker," maybe.
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Biomedical subjects
Publications and source records attributed to J Fields.
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Treatment outcome in congenital adrenal hyperplasia is often sub-optimal due to hyperandrogenism, treatment-induced hypercortisolism, or both. We previously reported better control of linear growth, weight gain, and bone maturation in a short term cross-over study of a new four-drug treatment regimen containing an antiandrogen (flutamide), an inhibitor of androgen to estrogen conversion (testolactone), reduced hydrocortisone dose, and fludrocortisone, compared to the effects of a control regimen of hydrocortisone and fludrocortisone. Twenty-eight children have completed 2 yr of follow-up in a subsequent long term randomized parallel study comparing these two treatment regimens. During 2 yr of therapy, compared to children receiving hydrocortisone, and fludrocortisone treatment, children receiving flutamide, testolactone, reduced hydrocortisone dose (average of 8.7 +/- 0.6 mg/m2 x day), and fludrocortisone had significantly (P < or = 0.05) higher plasma 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone levels. Despite elevated androgen levels, children receiving the new treatment regimen had normal linear growth rate (at 2 yr, 0.1 +/- 0.5 SD units), and bone maturation (at 2 yr, 0.7 +/- 0.3 yr bone age/yr chronological age). No significant adverse effects were observed after 2 yr. We conclude that the regimen of flutamide, testolactone, reduced hydrocortisone dose, and fludrocortisone provides effective control of congenital adrenal hyperplasia with reduced risk of glucocorticoid excess. A long term study of this new regimen is ongoing.
Mice infected with Listeria monocytogenes (LM) generate CD8 effectors specific for f-MIGWII, the amino terminus of the bacterial product lemA presented by the class Ib MHC molecule H2 M3wt. lemA has several distinctive properties: 1) it is readily presented as an exogenous Ag in the absence of bacterial infection; 2) it is processed by a TAP-independent pathway, which is sensitive to chloroquine, pepstatin, and brefeldin; and 3) the immunogenic portion of the molecule is extremely resistant to proteolytic degradation even by proteinase K. To assess the structural basis for these findings, we expressed a truncated variant (t-lemA) containing the amino-terminal hexapeptide and the subsequent 27 amino acids linked to a histidine tail in Escherichia coli, and purified the product by affinity chromatography. Purified t-lemA could be presented to f-MIGWII-specific effectors by macrophages and fibroblasts at 1-10 nM. Unlike f-MIGWII, which binds directly to H2 M3wt, t-lemA required processing by a chloroquine-, pepstatin-, and brefeldin-sensitive pathway. Brefeldin sensitivity often implies endogenous processing in the cytoplasm, but several lines of evidence suggest translocation to the cytoplasm and proteosomal degradation are not critical for t-lemA presentation. Unlike f-MIGWII, t-lemA was profoundly resistant to proteinase K, and, using 35S-labeled t-lemA, we could identify the region from position 1 to approximately 30 as the protease-resistant element. Thus, the hydrophobic peptide sequence following f-MIGWII can account for the unusual properties of lemA noted above. Analogous modification could be used to alter the properties of other peptide Ags presented by class I MHC products.
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This report summarizes five studies of culturally diverse women who were administered the Prenatal Psychosocial Profile (PPP). These data from 3,444 rural and urban women of all childbearing ages support the validity and reliability of the PPP as a measure of stress, support from partner, and support from others. The self-esteem scale is a valid and reliable measure for Caucasian and African American women. However, the cultural appropriateness of the self-esteem scale for Native American women is questionable, and it is neither valid nor culturally appropriate for traditional Hispanic women. The mean scores for stress, partner support, and other support were similar for all groups except for scales expected to differ by sample groups. Thus, suggested cutoff scores should be useful for screening purposes. The PPP provides a brief, yet comprehensive profile that is accepted by participants and useful to researchers and clinicians.
We report a case of pulmonary fibrosis in an infant receiving amiodarone for treatment of intractable atrioventricular reentrant tachycardia secondary to Wolff-Parkinson-White syndrome. At 9 months, a screening chest radiograph showed a diffuse interstitial infiltrate in an asymptomatic, thriving infant. Amiodarone was discontinued and the pulmonary fibrosis resolved gradually over 6 months. This case documents the first report of amiodarone induced pulmonary fibrosis in the pediatric age group. We speculate that as amiodarone is used more frequently to manage pediatric arrhythmias, pulmonary fibrosis, a known complication of this antiarrhythmia in adults may be seen with increasing frequency in children.
The diagnosis of maxillary sinusitis can be difficult, with clinical signs and symptoms leading to a correct diagnosis in only approximately half of cases. This study compared ultrasound and plain radiography of 50 maxillary antra (25 patients) with clinically suspected maxillary sinusitis. Ultrasound showed 100% concordance with plain radiographs reported as normal, and was abnormal in all cases where plain films were reported as showing complete opacification or an air fluid level, the only reliable plain film indicators of an inflamed antrum. We conclude that ultrasound can provide an alternative to plain radiography in the initial investigation of maxillary sinusitis.
Acute ethanol, in both man and cats, decreases contractility of both lower esophageal sphincter (LES) and smooth muscle portion of the lower esophageal (LE) body. Because these inhibitory effects were not abolished, in cats, by cervical vagotomy or intravenous tetrodotoxin, we surmised a direct inhibitory effect of ethanol on muscle cells. Accordingly, to test this possibility, we exposed isolated, esophageal smooth muscle cells (LES and LE) to ethanol (0-150 mM) for 0 to 40 min, and then a contractile agent, carbachol, or its vehicle was added. Thirty seconds later, cells were fixed and cell shortening was measured as an index of contractility. In the absence of ethanol, carbachol dose-dependently induced shortening of muscle cells from both LE and LES. Ethanol significantly attenuated carbachol-induced maximal shortening of cells from both LE and LES. Potency for carbachol in LES (but not LE) was also decreased by ethanol. Isolated muscle cells remained viable after incubation with ethanol. Thus inhibition by ethanol: can occur directly on esophageal muscle; occurs at pharmacologically relevant ethanol concentrations; and is not simply caused by cytotoxicity of ethanol.
PURPOSE: This study was a prospective phase I/II trial performed by the Radiation Therapy Oncology Group (RTOG) to test the tolerance and efficacy of preirradiation cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD) chemotherapy followed by large-volume, high-dose brain radiation therapy (RT) for patients with primary CNS lymphoma (PCNSL). PATIENTS AND METHODS: Fifty-four (52 assessable) human immunodeficiency virus (HIV)-negative patients with PCNSL were entered on study and received two (n = 20) or three (n = 32) cycles of CHOD (six patients with positive CSF cytology received intrathecal methotrexate in addition to CHOD). Whole-brain RT to 41.4 Gy and tumor boost to 18 Gy (total dose, 59.4 Gy) followed chemotherapy. RESULTS: As of July 1994, with a minimum potential follow-up time of 20 months, 12 of 52 assessable patients remain alive without evidence of progression. The median survival time for the entire group is 16.1 months, with a 2-year survival rate of 42%. By univariate analysis, patient age was found to be a significant prognostic factor with respect to survival (P = .005) in favor of age less than 60 years. Karnofsky performance status (KPS) was of borderline significance (P = .057). Survival for patients treated on RTOG 88-06 was compared with that of patients treated on RTOG 83-15, which tested RT alone. No difference in overall survival was found (P = .53). Grade 4 neutropenia developed in 29 of 51 patients during chemotherapy. There were two deaths during chemotherapy: one as a result of sepsis and one of a pulmonary embolus. The worst toxicity during RT was < or = grade 2 in 50 of 52 patients. CONCLUSION: Preirradiation CHOD chemotherapy does not significantly improve survival over RT alone for patients with PCNSL. Age remains a powerful prognostic factor independent of therapy and must be considered in testing alternative combined approaches.
Major reform in nursing education is underway, with increased emphasis being placed on the importance of the teacher-student relationship. An instrument for evaluation of teaching effectiveness, developed at the Oregon Health Sciences University School of Nursing, attempts to capture the student's perception of the quality of the teacher-student relationship as well as other salient aspects of teaching practices. The evaluation tool contains 26 items evaluating teaching effectiveness and 14 items that evaluate the course. The teaching effectiveness items yield five scales including: knowledge and expertise, facilitative teaching methods, communication style, use of own experiences, and feedback. Psychometric testing has been completed and there is evidence of construct validity in relation to teaching effectiveness and internal consistency reliability for the five scales.
In both humans and cats, EtOH administered in vivo and acutely decreases contractility of smooth muscle of lower esophageal sphincter (LES) and lower esophagus (LE), but not striated muscle of upper esophagus. To see if these effects are associated with perturbation of Ca++ homeostasis, esophageal muscle slices were incubated in vitro with EtOH and then 45Ca++. At steady-state Ca++ uptake, some slices were exposed to 1 microM carbachol (CCH). Although 100 mM EtOH had no effect on Ca++ uptake into resting or stimulated striated muscle of upper esophagus, it significantly inhibited Ca++ uptake into smooth muscle of LES and LE. For unstimulated LE and resting LES, 100 mM EtOH significantly inhibited both initial uptake and steady-state levels, whereas lower doses had no significant effect. EtOH at 100 mM also affected changes in Ca++ content induced by CCH stimulation. CCH increased total exchangeable tissue Ca++ content in LE, whereas it decreased Ca++ content in LES. EtOH at 100 mM blunted these CCH-induced effects in both LES and LE. In contrast to resting muscle, inhibition of CCH-stimulated LE muscle was not limited to 100 mM EtOH, because substantial and significant inhibition was also seen at EtOH doses of 25 and 50 mM, doses which are relevant even in social drinking. Thus, EtOH inhibition of Ca++ influx into esophageal muscle is selective for smooth muscle, can occur at pharmacologically relevant EtOH doses and could be the underlying mechanism for EtOH's inhibition of contractility of esophageal smooth muscle.
OBJECTIVES: The purpose of this study was to determine whether pulmonary artery responses to acetylcholine are abnormal in patients with chronic heart failure. BACKGROUND: Defective pulmonary artery endothelium-dependent responses have been observed in chronic heart failure models in animals. However, pulmonary artery endothelial responses in humans with chronic heart failure are unknown. METHODS: Twenty-two patients with chronic treated heart failure (12 with secondary pulmonary hypertension, Group I; 10 with normal pulmonary artery pressure, Group II) and 8 control patients constituted the study groups. Intravascular ultrasound measurements of pulmonary artery area just beyond the tip of an 8F infusion sheath were obtained in response to acetylcholine (10(-6), 10(-5) and 10(-4) mol/liter). The 10(-6) mol/liter infusion was repeated after methylene blue infusion. Indomethacin (5 micrograms/ml) was sequentially added to this combination in 17 patients. RESULTS: There were no significant differences among the three groups in vascular area responses to the lowest concentration (10(-6) and 10(-5) mol/liter) of acetylcholine, but the 10(-4) mol/liter infusion resulted in significant constriction in Group II patients (p < 0.05, analysis of variance [ANOVA]). Pretreatment with methylene blue in Group II also resulted in significant pulmonary artery vasoconstriction to even the 10(-6) mol/liter acetylcholine infusion (10.4 +/- 7.8% in Group II vs. 1.7 +/- 3.9% in the control group and 0.1 +/- 4.3% in Group I, p < 0.05, ANOVA). The addition of indomethacin resulted in reversal of the constriction in Group II patients. CONCLUSIONS: These responses indicate that the pulmonary artery endothelium may play a significant role in inhibiting vasoconstriction in patients with chronic heart failure who maintain normal pulmonary artery pressure.
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In a randomised single blind crossover study in children with cystic fibrosis and pancreatic insufficiency, two enteric coated microsphere preparations of pancreatin were compared on a capsule for capsule basis, by measuring the coefficient of fat absorption, nitrogen excretion, weight change, and symptom scores after four weeks' treatment with each preparation. Thirty nine subjects were randomly allocated to receive Pancrease followed by Creon or vice versa. Each individual subject received the same number of capsules per day in each study period. Data from 27 children (Pancrease/Creon, n = 13 and Creon/Pancrease, n = 14) wer suitable for analysis. Results showed no significant differences between the two preparations in any variable studied. We conclude that there is no significant difference between Pancrease and Creon when compared on a capsule for capsule basis.
The sexually dimorphic nucleus of the preoptic area (SDN-POA) in the rat represents a morphological substrate in which the influence of gonadal hormones on the process of sexual differentiation of the brain can be seen. Since the medial preoptic area (MPO) is a region rich in catecholamine (CA) terminals, it is possible that catecholamines may play a role either in the differentiation of the perinatal SDN-POA or in the function of this nucleus in the adult. It is not known whether catecholamine terminals exist within the SDN-POA or whether they can directly influence the activity of SDN-POA neurons. The present study was conducted to determine the extent to which catecholamines innervate this nucleus and further to elucidate the possibility of a potential sexual dimorphism in the innervation pattern. In order to determine which of the neurons in the MPO are within the SDN-POA we have utilized the fact that the SDN-POA has a prolonged period of neurogenesis in comparison to other neurons of the MPO. Thus, tritiated thymidine-labeled neurons can be used as a detection criterion for the SDN-POA. To conduct this experiment, timed pregnant Sprague-Dawley females were given a single injection of [3H]thymidine on Day 18 of gestation. Pups were killed as adults and prepared for fluorescence histochemistry of monoamines. Sections adjacent to those examined for catecholamine fluorescence were treated for autoradiographic localization of [3H]thymidine. Fluorescence innervation patterns were plotted within the boundaries of the nucleus following its identification from Nissl sections as well as from adjacent autoradiograms simultaneously viewed in a comparator bridge microscope with dark-field illumination.(ABSTRACT TRUNCATED AT 250 WORDS)
Molindone was compared with haloperidol in animal models of tardive dyskinesia. Treatment with molindone for 14 days at 3, 6, 20 and 40 mg/kg, enhanced the stereotyped behavioral response induced by apomorphine and increased the numbered of D-2 dopamine receptors in the striatum (Bmax) labelled by high affinity (Kd = 40 pmol) binding or [3H] spiroperidol in the guinea-pig. Molindone at 1 mg/kg, caused no behavioral supersensitivity or change in the binding of dopamine receptors. Chronic administration of haloperidol (0.1, 0.5 and 5.0 mg/kg) also increased both the behavioral response to apomorphine and the number of dopamine receptors. Haloperidol, at 0.02 and 0.004 mg/kg, had no effect. Molindone potentiated dopaminergic activity in animal models in a similar way to other neuroleptics, suggesting that its use may also result in tardive dyskinesia.