Biomedical subjects
Publications and source records attributed to H Newman.
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The hypothalamus-pituitary-adrenal axis of the sheep fetus plays a critical role in fetal development, responsiveness to stress, and initiation of parturition. We have recently reported that the fetal lung contains and secretes significant amounts of immunoreactive adrenocorticotropin (iACTH). The present study was designed to identify the molecular weight profile and the cellular location of iACTH in this tissue. iACTH extracted from fetal lung was immunoprecipitated, electrophoresed, and immunoblotted. Pulmonary iACTH was found in several molecular forms. The largest peptides appeared as doublets, and had molecular weights similar to POMC (32, 33 kD). Smaller peptides appeared in molecular weights (17, 24, and 27 kD) which were not consistent with the post-translational processing of POMC in fetal pituitary, but which were consistent with known processing of POMC by chromaffin granule aspartyl protease. None of the molecular forms of iACTH were glycosylated. Immunohistochemistry revealed that the iACTH was contained within bronchial epithelium and within groups of cells within the parenchyma of the lung. Both of these types of cells are consistent with pulmonary neuroendocrine cells. The distribution of neuroendocrine cells and apparent concordance with the iACTH-positive cells was confirmed by immunostaining for neuron specific enolase, a marker for neuroendocrine cells within the lung. We conclude that the lung contains unprocessed and partially processed POMC within cells known to contain neuropeptides. We speculate that secretion of the POMC-related peptides from these cells is physiologically important in the late-gestation fetus.
Interleukin 6 (IL-6) is a multi-functional cytokine which has a major role in tissue damage. It is secreted by many types of cell, including oral fibroblasts, and has been implicated in the pathogenesis of periodontal diseases, particularly those associated with sex hormones. In the present study we investigated whether the androgen dihydrotestosterone (DHT) affects the expression and regulation of IL-6 in gingival fibroblasts. Using a 'capture' ELISA assay, it was found that increasing DHT concentrations progressively reduced IL-6 production by gingival cells from normal individuals and from patients with gingival inflammation and gingival hyperplasia. In contrast, cells from periodontal ligament tissue produced only barely detectable levels of IL-6. The anti-androgen cyproterone acetate acted as an androgen analogue in the gingival fibroblasts, potently inhibiting IL-6 production, and did not reverse the DHT-mediated downregulation of the cytokine. Flutamide also failed to abrogate DHT inhibition of IL-6 production, and it had no effect on IL-6 production in the absence of DHT. Moreover, semi-quantitative RT-PCR showed that DHT acted at the level of transcription of the IL-6 gene, causing a marked reduction in the relative level of IL-6 mRNA in the gingival cells.
OBJECTIVE: The purpose of this study was to evaluate the technique of cortical optical imaging (COI) of intrinsic cortical optical signals related to neuronal activation. The specific goals of the study were to evaluate some of the technical aspects of COI and thus maximize the intensity of the image of this intrinsic signaling process and to determine the physiological reliability of COI in a well-defined animal system. METHODS: The intrinsic optical signal of activated whisker barrel cortex of rat was imaged using a computer-based technique for rapid acquisition of enhanced images. Single-unit microelectrode recordings of cortical neuronal responses to whisker movement were used to confirm the locations of the whisker barrels. RESULTS: Narrow band incident light at 600- to 610-nm wavelength was most effective for producing optical images. Images could be obtained during activation by a single long (40 s) stimulus or by averaging the signal generated by repeated shorter (1-8 s) stimuli. Focusing slightly below the cortical surface, minimizing movement, and abolishing extraneous light were all important in increasing the signal-to-noise ratio. The locations of whisker movement-evoked cortical activity determined using COI are consistent with the known functional anatomy of rat whisker barrel cortex. The images obtained with this experimental arrangement are shown to be accurate predictors of the location of neuronal activity determined by comparing the locations of active sites identified with COI with locations of areas of neuronal activity determined using single-cell recording techniques. CONCLUSIONS: COI is able to rapidly identify areas of cortex containing elicited neuronal activity. The technique allows cortical activation maps to be made rapidly with a very high degree of spatial resolution. COI is reliable and consistent over time. COI, if used carefully, holds promise as an intraoperative technique to study both human and experimental animal cortical function.
Comorbid diagnoses were examined in 55 principal generalized anxiety disorder (GAD) clients, and the effect of treatment for the principal disorder on those conditions was evaluated. High rates of comorbid diagnoses were present at pretherapy, with social and simple phobia being most common. The presence of additional diagnoses declined dramatically from pretherapy to follow-up and was significantly greater among clients for whom the GAD therapy had been successful than among clients for whom GAD outcome had been ambiguous. This was generally true regardless of whether clients reported at follow-up that they had received further therapy since the posttherapy assessment.
We report our results in eight consecutive patients with idiopathic subclavian-axillary vein thrombosis treated at a community hospital with systemic streptokinase therapy. Seven of the eight patients were treated within 1 week of symptoms. All seven patients had partial or total recanalization documented by venography. One patient developed rethrombosis that did not respond to therapy with tPA and had mild persisting symptoms of postphlebitic syndrome. None of the other patients had symptoms of postphlebitic syndrome on follow-up up to 5 years' duration.
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In a double-blind randomized trial involving five Sydney hospitals and the city ambulance paramedical service, 145 patients with a first evolving myocardial infarction and with onset of pain less than 2.5 (mean 1.9 +/- 0.5 [SD]) hr previously were allocated to intravenous infusion of 100 mg recombinant tissue-type plasminogen activator (rt-PA) or placebo over 3 hr. The groups at entry were similar. At assessment 21 days later, left ventricular ejection fraction measured both by contrast and radionuclide ventriculography was higher in the rt-PA compared with the placebo group (61 +/- 13%, n = 64, vs 54 +/- 14%, n = 62, contrast, 2p = .006; 52 +/- 13%, n = 66, vs 48 +/- 13%, n = 62 isotope, 2p = .08). This indicates limitation of myocardial infarction by rt-PA.
3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a serotonergic neurotoxin in laboratory animals that has been used for recreational purposes by humans. The subjective effects of this drug were determined in recreational users at a university campus. Of individuals who had admitted to using MDMA recreationally, 100 of 143 agreed to complete a detailed questionnaire concerning the subjective effects of this Schedule I compound. The most common effect of MDMA was a heightened sense of "closeness" with other people (90% of subjects). Tachycardia, dry mouth, bruxism and/or trismus were reported by the majority of users. These effects probably result from the amphetaminelike properties of the drug. Visual hallucinations were reported by 20% of users. Untoward side effects were most common on the day following the use of MDMA, with complaints of muscle aches, fatiguability, depression, and difficulty concentrating noted by 21% to 36% of subjects. Sixty-seven percent of frequent users of the drug (six or more separate doses) reported that the "positive" effects of the drug decreased with successive doses while the "negative" effects increased. Although these observations should be considered preliminary, they represent the first documentation of the subjective effects of MDMA in recreational users and confirm previous reports obtained from patients treated with this drug.
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Exercise electrocardiography and thallium scanning were performed a mean of 24 days after uncomplicated acute myocardial infarction in 103 patients, aged 36 to 60 years, who also underwent coronary angiography. The purpose of the study was to determine the ability of the noninvasive tests to predict multivessel coronary artery disease (CAD) and prognosis. Patients were followed up to document medical complications (incidence 12%: 3 deaths, 1 resuscitated cardiac arrest, 4 recurrent infarctions, 4 admissions with unstable angina) and combined events (medical events or bypass surgery, incidence 23%). The sensitivity, specificity and predictive accuracy for predicting multivessel CAD were 64%, 77% and 64% for a positive exercise electrocardiographic (ECG) response, 64%, 88% and 80% for a remote thallium defect, and 42%, 96% and 88% for a combination of the 2 tests. With 2 tests yielding negative findings the probability of multivessel CAD was 13%. No variable (positive exercise ECG response, remote thallium defect and presence of multivessel CAD) predicted medical events, although there were nonsignificant trends to more events in patients with any of those findings. The relative risk of combined events was 2.5 (p less than 0.05) for a positive exercise ECG response; 1.8 (NS) for a remote thallium defect; 2.6 (p less than 0.05) for multivessel CAD; and 3.1 (p less than 0.025) for both positive ECG response and remote defect. A combination of exercise electrocardiography and thallium scanning early after acute myocardial infarction helps to identify subsets of patients with high and low probabilities of multivessel CAD and combined medical or surgical events.
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Recently the association of recurrent spontaneous abortions and intrauterine fetal death was linked to the lupus anticoagulant (LA). LA is an immunoglobulin directed against phospholipid, causing characteristic changes in coagulation tests, and is associated with an increased risk of thrombosis. We treated a pregnant woman who presented with an embolic stroke and laboratory evidence of LA.
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Left ventricular cineangiograms performed at the time of diagnosis in 88 patients with hypertrophic cardiomyopathy were digitized to evaluate the relation of left ventricular function and prognosis in hypertrophic cardiomyopathy. Eleven patients died suddenly after a mean follow-up period of 7.5 +/- 7 years, 10 patients died of congestive heart failure or after cardiac surgery and 67 were alive after a mean follow-up period of 8.6 +/- 4 years. Measurements of left ventricular volume, ejection fraction, peak rate of ejection and filling and time to peak rate of ejection and filling were derived from curves of ventricular volume and its rate of change during the cardiac cycle. Patients who died suddenly had a lower peak rate of ventricular ejection (stroke volume-normalized peak ejection rate 5.41 +/- 0.69 versus 6.24 +/- 1.33 s-1; p = 0.006) and lower peak rate of ventricular filling (end-diastolic volume-normalized peak filling rate 4.02 +/- 0.94 versus 4.88 +/- 1.53 s-1; p = 0.02) and stroke volume-normalized peak filling rate (4.75 +/- 1.08 versus 5.82 +/- 1.70 s-1; p = 0.01) compared with survivors. Stepwise regression analysis revealed that sudden death was best predicted by the combination of increased end-diastolic volume, small end-systolic volume and low peak filling rate (predictive accuracy 32%, false negative 18% and false positive 28%). The addition of clinical features and hemodynamic measurements to the analysis improved predictive accuracy to 43% (false negative 18% and false positive 18%). Ambulatory electrocardiographic monitoring performed in 57 of the 88 patients 1 month to 17 years (median 8 years) after diagnosis revealed ventricular tachycardia in 14 (25%). Of these, 10 who survived had hyperkinetic systolic function at diagnosis, whereas the 4 who died suddenly had impaired systolic function (end-diastolic volume-normalized peak ejection rate 5.93 +/- 1.2 versus 4.01 +/- 1.2 s-1, respectively; p = 0.04). In hypertrophic cardiomyopathy, ventricular tachycardia is a sensitive but nonspecific marker of adults who are at risk of sudden death. Impaired systolic function may be an important determinant of which patients with ventricular tachycardia die suddenly. This study shows that indexes of ventricular function contribute to the identification of patients at particular risk of sudden death. However, the predictive power of the clinical features and hemodynamic and angiographic measurements that could be assessed was poor.(ABSTRACT TRUNCATED AT 400 WORDS)
Proximal vein thrombosis has been associated with residual disability from the postphlebetic syndrome in patients receiving symptomatic therapy or heparin and sodium warfarin. This paper describes a man with painless swelling of the right arm secondary to subclavian-axillary vein thrombosis that was successfully treated with streptokinase and conventional anticoagulant therapy.