Productive retirement: stimulating greater volunteer efforts to meet national needs.
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Biomedical subjects
Publications and source records attributed to R Morris.
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Several experimental models have been proposed to explain the electrocardiographic and electrophysiological characteristics of atrial flutter. In animal models based on anatomical obstacles, intercaval crush or Y like shaped lesion located in the right atrium, it has been possible to induce sustained atrial arrhythmias in which the entrainment criteria could be demonstrated. Additionally these tachycardias presented an atrialwave morphology similar to the F waves of type 1 or typical atrial flutter. Flutter type 2 could better be explained by models based on functional reentry like the leading circle. Typical atrial flutter in human, saw teeth morphology in inferior ECG leads, is though to be a circus movement located in the right atrium, as deduced of the analysis of activation sequence, resetting and entrainment phenomena from right and left atrium. Moreover the successful results of RDF ablation procedures confirm this idea. Nevertheless the delimitation of the anatomical boundaries of the reentry pathway remains inconclusive.
In the present manuscript the information concerning electrical therapy of atrial fibrillation (AF) to prevent its development and to control its consequences (excluding ablation which will be covered in separate manuscripts of this series) is reviewed. Both presently conventional approaches and those undergoing investigation will be considered, under three general headings. Electrical stimulation to prevent the development of AF. Based on non controlled studies comparing VVI stimulation with other modalities that include stimulation of the atria, it was suggested that atrial stimulation could prevent AF recurrences in patients with sinus node dysfunction. This concept has been questioned in recent studies. In contrast, the hypothesis that specific ways of atrial stimulation (stimulation at sites other than the high right atrium, multisite simultaneous or with certain "delays" atrial stimulation) may be more efficacious is presently under enthusiastic assessment. Electrical stimulation to control ventricular response. Despite the evidence that ventricular stimulation may contribute to regularization and rate control during AF, its quantitative value seems to be scarce and, thus, is not of regular use in practice. Automatic implantable atrial defibrillator. Both animal experiments and clinical studies have demonstrated that the atria can be defibrillated using intracavitary electrodes with less than 3 joules in most cases, and without risk of inducing ventricular tachyarrhythmias as long as shocks are synchronized to the R wave and the preceding R-R interval is not short. Although an implantable atrial defibrillator is already undergoing clinical evaluation, the subject of tolerability of patients to shocks for non malignant arrhythmias is still controversial, since even low energy shocks seem to be painful.
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We conducted a combined biochemical modulation trial of N-(phosphonacetyl)-L-aspartate (PALA), dipyridamole (DP), and fluorouracil (5-FU) in patients with cancer. Eighty-eight patients with advanced cancer were entered into this Phase I trial. During the first part of the study, four doses of PALA (125, 250, 500, and 1000 mg/m2, administered on day 1) were evaluated to determine the PALA dose with maximal suppression of aspartate transcarbamylase (ATCase) activity that was clinically tolerable. Patients were randomized to receive DP (or no DP), 50 mg/m2, p.o. every 6 h on days 1-6, and all patients received 5-FU, 400 mg/m2, by bolus administration on days 2-5. Prior to and during therapy, WBCs were collected and assayed for ATCase activity. After the maximally tolerated PALA dose with 400 mg/m2 5-FU +/- 50 mg/m2 DP was defined, the 5-FU dose was escalated using the same administration schedule of 5-FU, PALA, and DP. The dose of 5-FU was escalated by 25% in each of the DP cohorts until dose-limiting toxicity was reached. ATCase activity was inhibited in a dose-dependent manner with PALA doses of 125, 250, 500, and 1000 mg/m2, resulting in 0, 13, 17, and 49% inhibition of ATCase activity. Only at the higher PALA doses (i.e., 500 and 1000 mg/m2) was ATCase activity suppressed during days 2-5, but the activity returned to pretreatment levels by day 15. Based on the clinical tolerance and significant suppression of ATCase activity, a PALA dose of 500 mg/m2 was selected for the 5-FU dose escalation phase. At a 5-FU dose of 625 mg/m2, dose-limiting toxicity (leukopenia, stomatitis, and diarrhea) occurred in both DP cohorts. We recommend that for this monthly treatment schedule, 500 mg/m2 PALA and 500 mg/m2 5-FU, with or without 50 mg/m2 DP, be used in subsequent Phase II trials.
Electrical stimulation of the brain, particularly in the periventricular grey areas, caused long-lasting increases in behavioural escape thresholds to heating and mechanical stimuli applied to the facial region of the rat. The brain stimulation selectively suppressed responses to noxious stimuli. Responses to non-noxious stimuli, evoked by low threshold brush, were unaffected. The same animals that were studied in the behavioural tests were then anaesthetized with urethane and the inhibitory effect of the same brain stimulation was studied in single neurones recorded in the caudal trigeminal nucleus. A clear correlation (rs = 0.63) emerged between degree of behavioural antinociception and the amount of inhibition seen in nociceptive neurones. In addition the mean duration of the inhibition (6 min) was similar to the mean duration of the antinociceptive effect (7.3 min). Other classes of non-nociceptive neurones were unaffected by the stimulation. The neurones were also studied using iontophoretically applied monoamine candidates for the inhibitory neurotransmitter noradrenaline (NA) and 5-hydroxytryptamine (5-HT). The profile of the effects of NA most closely fitted that of the inhibitory neurotransmitter. This profile was expressed in terms of depression and excitation of different classes of neurones, and by the duration of effects. The depressants effects could be antagonized by iontophoretic idazoxan. In addition clonidine induced long-lasting depression of firing. 5-HT was more likely than NA to excite nociceptive neurones and to depress non-nociceptive neurons. Only NA consistently elevated thermal response thresholds in a similar manner to that produced by brain stimulation. These results provide some support for the hypothesis that selective descending inhibition of nociceptive responses in neurones of the rat caudal trigeminal nucleus is mediated by NA, possibly by an action at alpha2-adrenoceptors.
In the December 1952 smog disaster in London, a substantial increase in mortality was closely associated with the increase in air pollution. Deaths from cardiovascular causes were elevated as well as respiratory deaths. The increase was greatest in the elderly. Hospital admissions were increased for both respiratory and cardiovascular diseases. Since then, many studies have reported associations between lower concentrations of air pollution and daily mortality. Little attention has been paid to the question of hospital admissions for cardiovascular illness, however. This study examined the association between air pollution and cardiovascular hospital admissions for persons aged 65 years and older in the Detroit, Michigan, metropolitan area during the years 1986-1989. After controlling for seasonal and other long-term temporal trends, temperature, and dew point temperature, the particulate matter with an aerodiameter of < or = 10 microns (PM10) was associated with daily admissions for ischemic heart disease (relative risk (RR) = 1.018, 95% confidence interval (CI) 1.005-1.032 for an interquartile range (32 micrograms/m3) increase in pollution). SO2, CO, and ozone made no independent contribution to ischemic heart disease admissions. Both PM10 (RR = 1.024, 95% CI 1.004-1.044) and CO (RR = 1.022, 95% CI 1.010-1.034 for an interquartile range (1.28 ppm) increase in pollution) showed independent associations with heart failure admissions. These results were robust to alternate methods of estimation and weather control.
OBJECTIVE: To establish and quantify the presence of contraction-stimulating activity in pathologic vitreous and correlate this activity with clinical presentation and outcome, especially with proliferative vitreoretinopathy. METHODS: Contraction-stimulating activity of vitreous collected during surgery was quantified with a tissue culture assay using fibroblasts as target cells. The activity of each sample was correlated with patient history, clinical presentation, risk factors, proliferative disease, and postoperative proliferation. RESULTS: Pathologic vitreous contained measurable quantities of contraction-stimulating activity and stimulated contraction in vitro, with elevated activities in samples from patients with proliferative vitreoretinopathy, epimacular proliferation, retinal detachment, retinal defects, pigmented cells in the vitreous, hemorrhage, or uveitis. Patients with postoperative proliferation had significantly elevated mean activities. CONCLUSIONS: Levels of contraction-stimulating activity in pathologic vitreous correlate with some risk factors for the development of proliferative vitreoretinopathy and may ultimately be useful in the assessment of disease severity and the prediction of postoperative proliferation.
The use of meta-analysis in environmental epidemiology can enhance the value of epidemiologic data in debates about environmental health risks. Meta-analysis may be particularly useful to formally examine sources of heterogeneity, to clarify the relationship between environmental exposures and health effects, and to generate information beyond that provided by individual studies or a narrative review. However, meta-analysis may not be useful when the relationship between exposure and disease is obvious, when there are only a few studies of the key health outcomes, or when there is substantial confounding or other biases which cannot be adjusted for in the analysis. Recent increases in the use of meta-analysis in environmental epidemiology have highlighted the need for guidelines for the application of the technique. Guidelines, in the form of desirable and undesirable attributes, are presented in this paper for various components of a meta-analysis including study identification and selection; data extraction and analysis; and interpretation, presentation, and communication of results. Also discussed are the appropriateness of the use of meta-analysis in environmental health studies and when meta-analysis should or should not be used.
Chloroethane and bromoethane have been shown to cause a marked uterine tumor response in B6C3F1 mice exposed for 2 years. These chemicals are nearly unique in this regard among the nearly 400 chemicals studied by the National Toxicology Program, and the reasons for this carcinogenic activity are unclear. The possible relationship of changes in blood concentrations of sex hormones to this response was evaluated by examining the estrous cycle of mice prior to and during a 21-day exposure to concentrations of the haloethanes which resulted in the tumorigenic response in the 2-year studies. Serum concentrations of estradiol and progesterone were determined at the termination of the exposures and compared to exposure group and stage of the estrous cycle. No consistent patterns of change were found in estrous cyclicity or in blood concentrations of sex hormones. Thus, the findings suggest that early changes in circulating sex hormones are not important contributing factors in the uterine neoplasia caused by these chemicals.
During normal postnatal development, there is an overproduction and subsequent partial elimination of the callosal projections of cortical areas 17 and 18 in the cat. In the present study, we investigated how neonatal splitting of the optic chiasm affects this process. Our results indicate that neonatal splitting of the optic chiasm exaggerates the normally occurring partial elimination of immature callosal projections: it causes a significant reduction in the total number of neurons in the supragranular layers that send an axon through the corpus callosum. It does not, however, cause a significant change in the number of callosally projecting neurons in the infragranular layers. These data suggest that in addition to other factors previously described, the level or spatial distribution of correlated binocular input to visual cortical neurons may influence the stabilization/elimination of immature callosal connections.
OBJECTIVE: Our purpose was to compare systolic and diastolic blood pressures obtained with the Spacelabs 90207 (Spacelabs Medical Products, Dee Why, Australia) or Accutracker II (Suntech Medical Instruments, Melbourne, Australia) ambulatory blood pressure monitoring devices with intraarterial blood pressures in pregnant women. STUDY DESIGN: Direct (intraarterial) and resting blood pressures with the ambulatory blood pressure monitoring device were compared in 39 pregnant women (14 Accutracker II and 25 Spacelabs 90207). RESULTS: The Accutracker II device underestimated direct systolic pressure by -9 (-13, -3) mm Hg (median, interquartile range) (p = 0.028) but gave similar diastolic pressure. The Spacelabs 90207 device gave similar systolic pressures but overestimated direct diastolic pressure by 7 (2, 12) mm Hg (p < 0.001). Variability for systolic and diastolic blood pressures within subjects was similar with the two devices. Both received poor gradings by standards of the British Hypertension Society and did not meet criteria of the Association for the Advancement of Medical Instrumentation, with intraarterial recordings used as the reference. CONCLUSIONS: The Accutracker II device significantly underestimated resting direct systolic pressure, whereas the Spacelabs 90207 device significantly overestimated resting direct diastolic pressure in pregnant women. Although poor gradings were achieved for both devices when intraarterial pressures were used as the reference, this is similar to comparisons of routine mercury sphygmomanometry with intraarterial recordings and does not mean these devices are unsuitable for use in pregnancy.
OBJECTIVE: To determine if the pregnancy rates (PRs) in infertile women could be improved with fallopian sperm perfusion in comparison with IUI. DESIGN: Randomized prospective analysis. SETTING: Academically affiliated infertility center. PATIENTS: Consecutive patients undergoing controlled ovarian hyperstimulation (COH). INTERVENTIONS: After hCG administration, patients were randomized to either IUI or fallopian sperm perfusion. MAIN OUTCOME MEASURES: Pregnancy rates with the two treatment modalities. RESULTS: Of 240 COH cycles, those randomized to IUI included 44 clomiphene citrate (CC) (group I) and 76 gonadotropin (group III) cycles. Patients receiving fallopian sperm perfusion included 44 cycles of CC (group II) and 76 cycles of gonadotropin (group IV) treatment. The overall PRs per cycle (10.8% versus 10.8%) were similar for IUI and fallopian sperm perfusion, respectively. The PRs were also similar when compared for ovulation induction with CC (6.8% versus 9.1%) and gonadotropins (13.2% versus 11.8%). CONCLUSION: We conclude that fallopian sperm perfusion offers no advantage over IUI. Because the process of fallopian sperm perfusion is more time consuming and more costly (because of increased media usage), fallopian sperm perfusion does not seem indicated as a routine infertility therapy and should not replace IUI.
BACKGROUND: The treatment of symptoms of seasonal allergic rhinitis often requires the use of a decongestant to improve nasal congestion, along with an antihistamine to adequately control other nasal, as well as nonnasal symptoms. METHODS: In this double-blind, placebo-controlled, multicenter study, 874 patients with moderate to severe symptoms of seasonal allergic rhinitis were treated with one of the following: SCH 434 QD (a combination of 10 mg of loratadine in the coating and 240 mg of pseudoephedrine sulfate in an extended-release core) once daily, 10 mg of loratadine once daily, 120 mg of pseudoephedrine sulfate every 12 hours, or placebo for 2 weeks. RESULTS: SCH 434 QD was consistently superior to placebo in controlling the symptoms of seasonal allergic rhinitis. Composite symptom scores (total, total nasal, and total nonnasal) were reduced significantly in patients treated with SCH 434 QD as compared with placebo (p < 0.01). When compared with its individual components, reductions in mean symptom scores were consistently greater, numerically, in patients treated with SCH 434 QD than in patients who were treated with either loratadine or pseudoephedrine alone. SCH 434 QD was superior to pseudoephedrine in reducing nonnasal symptoms at all time points (p < 0.01), and superior to loratadine in relieving nasal stuffiness at end point (p < 0.01). In the physicians' evaluation of therapeutic response, the SCH 434 QD group had the greatest number of patients with a good or excellent response at end point (58%). All treatments were generally well tolerated with no serious or unusual adverse events. Insomnia and nervousness, adverse events commonly associated with pseudoephedrine, were noted in a significantly greater number of patients treated with SCH 434 QD or pseudoephedrine (p < or = 0.04) as compared with those treated with loratadine or placebo. CONCLUSIONS: The results of the study demonstrate that SCH 434 QD is more effective than placebo or either of its components alone in the treatment of seasonal allergic rhinitis.
To establish whether p53 mutation precedes or follows clonal divergence in human colorectal carcinomas, 17 tumours were analysed at multiple sites (2-5 each) for single-strand conformation polymorphisms (SSCP) within exons 5-8 of the p53 gene. A previous study had demonstrated subclones of differing DNA ploidy in these tumours, but all showed immunocytochemical evidence for p53 stabilisation, using the monoclonal antibody PAb 1801. Mutations within exons 5-8 of p53 were identified by the presence of an abnormally migrating band in 10 of the 17 carcinomas: five in exon 5, four in exon 7 and one in exon 8. In each of these positive cases, samples from different parts of the carcinoma showed identical gel migration patterns in SSCP analysis. Similarly, the remaining seven tumours were concordant for absence of band shift across all samples of each tumour. Six SSCP-positive cases contained multiple populations differing in DNA ploidy, while four were homogeneously diploid or aneuploid throughout. Very similar proportions were observed in the SSCP-negative cases. In four positive tumours the mutation was confirmed by sequencing or through alteration of nucleotide-specific restriction enzyme cleavage. Identical mutations appeared in every sample from the same tumour. The results provide unequivocal evidence that the same mutant allele of p53 is present throughout each tumour bearing a mutation, regardless of the clonal variation identified by analysis of DNA ploidy. We conclude that in colorectal tumorigenesis mutation of p53 occurs as a single event which precedes and may facilitate the aneuploid clonal divergence of carcinomas.
Although traffic-related mortality and morbidity figures have improved in recent years in the United States, motor vehicle crash remains a leading source of death and injury, requiring additional efforts to reduce its toll. The rationale for equipping passenger vehicles with air bags was to introduce a mechanical cushion between occupants and the car's hard interior surfaces. Although air bags have proven to be effective in saving lives and preventing injuries, a growing number of reports indicate that the air bag is also a potential source of ocular trauma. This article analyzes 24 eye injuries alleged to be air bag-related. The posterior segment was injured in less than half of cases, and only one eye sustained severe visual impairment. Although such reports may help to improve air bag design, the air bag should remain "innocent until proven guilty." We report that in motor vehicle crashes, the rate of ocular trauma increases 2.5 times if the car is not air bag-equipped. In contrast to injuries seen in vehicles without air bags, eye trauma sustained in vehicles with air bags is typically closed globe.
Renal insufficiency following periods of infrarenal aortic cross clamping has been reported by some investigators but not by others, and conflicting views have been expressed concerning the ability of renal autoregulation to overcome the adverse circulatory effects of cross clamping. The object of this study was to examine the blood flow distribution to four layers within the renal cortex (subcapsular to juxtamedullary) and measure global renal function following application and release of an aortic cross clamp after 90 min. Nine juvenile female pigs weighing 25 to 50 kg were anaesthetized and subjected to intensive physiological monitoring. Throughout the study the blood pressure and cardiac output were maintained as close as possible to control levels by fluid administration and varying the depth of anaesthesia. Renal cortical blood flow was estimated by means of radionuclide labelled microspheres and global renal function was determined by the measurement of creatinine clearance. The aortic cross clamp was applied for 90 min immediately distal to the renal arteries and proximal to the inferior mesenteric artery. Cardiovascular and renal parameters were recorded on four occasions during each experiment, prior to, 10 and 60 min after cross clamping, and 30 min after clamp release. No significant changes in cardiac output, systemic blood pressure of global renal function were recorded during the study. There was, however, a significant fall in renal blood flow following release of the aortic cross clamp but this was not associated with any significant redistribution of blood flow within the renal cortex. In the pigs studied, the application of an infrarenal aortic cross clamp did not have any adverse effects on the cardiovascular system or on global renal function.(ABSTRACT TRUNCATED AT 250 WORDS)