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Biomedical subjects

M A James

Publications and source records attributed to M A James.

At least 37 records · Page 2Linked to original sources

Orthostatic blood pressure changes and arterial baroreflex sensitivity in elderly subjects.

BACKGROUND: orthostatic hypotension in elderly people is often attributed to diminished afferent baroreflex sensitivity, but this has not been demonstrated. We examined the hypothesis that postural change in blood pressure is related to baroreflex sensitivity, independent of the confounding effect of baseline blood pressure. METHODS: we studied 25 active, untreated elderly subjects free of postural symptoms (mean age 70 +/- 1 years): 16 with hypertension (clinic blood pressure 194 +/- 6/98 + 3 mmHg) and nine normotensive controls (clinic blood pressure 134 + 3/77 + 3 mmHg). We assessed baroreflex sensitivity from the heart rate and blood pressure responses to the Valsalva manoeuvre and a pressor and depressor stimulus (bolus phenylephrine injection or sodium nitroprusside infusion respectively). Subjects were then passively tilted to 60 degrees and maximum changes in systolic blood pressure, heart rate, forearm blood flow and forearm vascular resistance recorded. RESULTS: maximum change in systolic blood pressure with head-up tilt was correlated with supine systolic blood pressure (r = 0.60, P = 0.001). Maximum change in systolic blood pressure with orthostasis was greater in the hypertensive subjects (45 +/- 4 mmHg versus 29 +/- 6, P = 0.04) and the heart rate increment was less (16 +/- 2 bpm versus 24 +/- 4, P = 0.02). The increase in forearm vascular resistance with tilt was similar in the two groups (47 +/- 11 versus 38 +/- 7 units, P = 0.52). All three methods of assessing baroreflex sensitivity showed a reduction in the hypertensive subjects (all P < or = 0.02). Lower values of baroreflex sensitivity were related to greater falls in systolic blood pressure with tilt, after adjustment for the baseline level of systolic blood pressure. CONCLUSIONS: we found a relationship between baroreflex sensitivity and the systolic blood pressure fall with orthostasis, even after adjustment for prevailing systolic blood pressure. Despite equivalent changes in forearm vascular resistance with tilt, greater falls in systolic blood pressure were seen in hypertensive subjects than in normotensive controls, due in part to an inadequate baroreflex-mediated heart rate response. The postural fall in blood pressure often observed in elderly hypertensive subjects may be related to the reduced baroreflex sensitivity seen in this condition.

Aged↗

Spinal cord stimulation significantly decreases the need for acute hospital admission for chest pain in patients with refractory angina pectoris.

OBJECTIVE: To assess the impact of spinal cord stimulation (SCS) on the need for acute admissions for chest pain in patients with refractory angina pectoris. DESIGN: Retrospective analysis of case records. PATIENTS: 19 consecutive patients implanted for SCS between 1987 and 1997. All had three vessel coronary disease, and all were in New York Heart Association functional group III/IV. METHODS: Admission rates were calculated for three separate periods: (1) from initial presentation up until last revascularisation; (2) from last revascularisation until SCS implantation; (3) from SCS implantation until the study date. Post-revascularisation rates were then compared with post-SCS rates, without including admissions before revascularisation, as this would bias against revascularisation procedures. RESULTS: Annual admission rate after revascularisation was 0.97/patient/year, compared with 0.27 after SCS (p = 0.02). Mean time in hospital/patient/year after revascularisation was 8.3 days v 2.5 days after SCS (p = 0.04). No unexplained new ECG changes were observed during follow up and patients presented with unstable angina and acute myocardial infarction in the usual way. CONCLUSIONS: SCS is effective in preventing hospital admissions in patients with refractory angina, without masking serious ischaemic symptoms or leading to silent infarction.

Angina Pectoris↗

Differential expression of systemic cytokine profiles in Chagas' disease is associated with endemicity of Trypanosoma cruzi infections.

Chagas' disease is a serious public health problem in Paraguay, however, the immunoepidemiology of the disease has not been well documented. A preliminary cross-sectional survey was carried out in two villages of the Paraguayan Chaco region and in five villages of the Oriental region to assess the endemicity of Trypanosoma cruzi infections. Thereafter, a subset of individuals (ages ranging from 23 to 65 years) participated in a follow-up study to evaluate clinical and parasitological parameters. Physical examinations and electrocardiograms (ECG) were conducted and blood samples collected for parasite detection and serology. The most frequent ECG abnormalities which were observed among chagasic individuals were left anterior hemifascicular block and right bundle branch block. Thirty-two of these subjects, seropositive and non-parasitemic from the high endemic Chaco (n = 16) and low endemic Oriental (n = 16) regions, were randomly selected for an analysis of T. cruzi-induced expression of cytokines IL-2, IFN-gamma, IL-4 and IL-10 by RT-PCR. The individuals were grouped (n = 8) according to the presence or absence of abnormal ECG. In subjects that exhibited abnormal ECG profiles, five of eight (63%) individuals from the high endemic area showed a dominant type 2 (IL-4) response, whereas a comparable number (63%) of subjects from the low endemic area expressed a strong type 1 (IFN-gamma) response; the remainder (37%) presented a Th0-type (IFN-gamma, IL-4) response. Subjects with normal ECG showed a defined cytokine profile according to endemicity. All subjects from the high endemic region showed a Th0 response, whereas 100% of the individuals from the low endemic area demonstrated a type 1 response. In most chagasic patients regardless of ECG profile and endemicity, IL-2 expression was depressed, while IL-10 mRNA transcripts were consistently elevated. Taken together, these data indicate that chronic human chagasic disease is associated with increased systemic production of type 2 cytokines in response to T. cruzi infection and may be involved in the reciprocal down-regulation of IL-2 production.

Adult↗

Evidence of defective cardiovascular regulation in insulin-dependent diabetic patients without clinical autonomic dysfunction.

(1) Autonomic dysfunction is a well recognised complication of diabetes mellitus and early detection may allow therapeutic manoeuvres to reduce the associated mortality and morbidity. We sought to identify early cardiovascular autonomic neuropathy using spectral analysis of heart rate and systolic blood pressure variability. (2) Thirty patients with Type 1 (insulin-dependent) diabetes mellitus (DM) and 30 matched control subjects were studied. In addition to standard tests of autonomic function, heart rate and systolic blood pressure variability were assessed using power spectral analysis. From the frequency domain analysis of systolic blood pressure and R-R interval, the overall gain of baroreflex mechanisms was assessed. (3) Standard tests of autonomic function were normal in both groups. Total spectral power of R-R interval was reduced in the Type 1 DM group for low-frequency (473 +/- 63 vs. 747 +/- 78 ms2, mean +/- S.E.M., P = 0.002) and high-frequency bands (125 +/- 13 vs. 459+/-90 ms2, P < 0.0001). Systolic blood pressure low-frequency power was increased in the diabetic group (9.3 +/- 1.2 vs. 6.6+/-0.7 mmHg2, P < 0.05). The low frequency/high frequency ratio for heart rate variability was significantly higher in the Type 1 DM patients (4.6+/-0.5 vs. 2.9+/-0.5, P = 0.002), implying a relative sympathetic predominance. When absolute powers were expressed in normalised units, these differences persisted. There were significant reductions in baroreceptor-cardiac reflex sensitivity in Type 1 DM patients compared to controls while supine (9.7+/-0.7 vs. 18.5 +/- 1.7 ms/mmHg, P < 0.0001) and standing (2.9+/-0.9 vs. 7.18+/-1.9 ms/mmHg, P < 0.001). (4) Spectral analysis of cardiovascular variability detects autonomic dysfunction more frequently in Type 1 DM patients than conventional tests, and is suggestive of an abnormality of parasympathetic function. The abnormality of baroreceptor-cardiac reflex sensitivity could be explained by this impairment of parasympathetic function and this may predispose to the development of hypertension and increase the risk of sudden cardiac death. Using spectral analysis methods may allow detection of early diabetic cardiac autonomic neuropathy and allow therapeutic intervention to slow the progression.

Adult↗

Forearm muscle activation during power grip and release.

The position of the hand during power grip is well-described, but the normal phasic activity of the extrinsic forearm muscles during power grip and release is unknown. People with neurologic impairment may have inadequate power grip or release because of abnormal muscle timing. This study describes the timing of the forearm muscles in 10 normal subjects during power grip and release, which was evaluated using electromyography. During power grip, subjects had consistent timing patterns for extrinsic finger motors and different but individually consistent patterns for wrist motors. This finding supports our hypothesis that different individuals habitually use a specific motor strategy and an intact central nervous system allows them to change their motor strategy to adapt to new environmental parameters.

Adult↗

Applicability of new techniques in the assessment of arterial baroreflex sensitivity in the elderly: a comparison with established pharmacological methods.

1. There has been considerable interest in techniques recently developed for the study of arterial baroreceptor-cardiac reflex sensitivity based on analysis of spontaneous baroreflex sequences and on spectral analysis. This study examined how these newer techniques agreed with the established pharmacological methods in elderly subjects. 2. In 20 elderly subjects [10 hypertensive (clinic blood pressure 180 +/- 4/88 +/- 2 mmHg) and 10 normotensive (clinic blood pressure 136 +/- 3/73 +/- 2 mmHg)], we assessed baroreflex sensitivity from spontaneous sequences of increasing and decreasing blood pressure and pulse interval and their mean, and from spectral analysis to derive alpha, the index of overall baroreflex gain. Pharmacological baroreflex sensitivity was derived from the blood pressure and pulse interval responses to depressor (sodium nitroprusside) and pressor (phenylephrine) stimuli, and their mean. 3. Baroreflex sensitivity was significantly lower in the hypertensive group by the pharmacological, sequence and spectral methods (all P < 0.05). 4. There was acceptable agreement between pharmacological baroreflex sensitivity and sequences of the same direction, but with some systematic bias. There was also reasonable agreement between pharmacological and spectral baroreflex sensitivity and close agreement without bias between sequence and spectral methods. 5. The newer and established techniques demonstrate acceptable agreement in the elderly, albeit with some systematic bias. Pharmacological methods have enjoyed historical precedence but newer techniques give equivalent results, and are preferable in some circumstances. The newer techniques may be more descriptive of the spontaneous behaviour of the arterial baroreflex at rest rather than under artificially stimulated conditions.

Aged↗

Expression of cytokine genes in Aotus monkeys immunized with synthetic and recombinant Plasmodium vivax and P. falciparum antigens.

Cytokine responses in human host-protective immunity to malaria have yet to be completely elucidated. No data appear to exist on the cytokine patterns in non-human primate models immunized with malarial antigens. Expression of mRNA transcripts of 10 cytokines, the adhesion molecule ICAM-1 and inducible nitric oxide synthase (iNOS) in peripheral-blood mononuclear cells (PBMC) from nine Aotus monkeys was analysed by reverse-transcriptase PCR. Five of the monkeys had been immunized with multiple-antigen peptides (MAP) of the Plasmodium vivax circumsporozoite protein and two with constructs of the P. falciparum merozoite surface protein-1 (MSP-1). The other two monkeys served as non-immunized controls. PBMC were cultured for 24 h after stimulation with phytohaemagglutinin mitogen, MAP and MSP-1 antigens. Elevated expression of interleukin-6 (IL-6), IL-10, IL-12, tumour necrosis factor-alpha (TNF-alpha), TNF-beta and iNOS was seen in response to the MAP. Monkeys immunized with either P. falciparum MSP r190L or synthetic 190L peptides expressed predominantly the type-1 cytokines (IL-1 beta, IL-12, interferon-gamma, TNF-alpha, TNF-beta) characteristic of splenic, cell-mediated activity with macrophage activation and nitric oxide production.

Animals↗

Cytokine responses in Trypanosoma cruzi-infected children in Paraguay.

Both parasite and host immune factors may contribute to the development and progression of chronic chagasic cardiomyopathy during Trypanosoma cruzi infections. The present study targeted infected children (5-14 years of age) from an endemic area of Paraguay in an analysis of T. cruzi-specific cytokine profiles. This age group is characteristically the most affected by the early phases of infection. Trypanosoma cruzi-induced cytokine gene expression (interleukin-2 [IL-2], and interferon-gamma [IFN-gamma], IL-4, and IL-10) was studied in 25 seropositive children categorized as being either acute, symptomatic, with Romana's sign (n = 2), or early, indeterminate (postacute, n = 23). Acutely infected children showed a distinct T helper cell-1 (Th1)-type (IFN-gamma) cytokine response to infection. The cytokine pattern that was observed in the seropositive, asymptomatic (early, indeterminate) group was of the Th0 type (expression of both IFN-gamma and IL-4). We hypothesize that selective induction of a Th0-type cytokine pattern is important for development of cell-mediated and humoral immune responses that suppress parasite burden, thereby prolonging the onset or limiting the severity of chronic Chagas' disease later in life.

Adolescent↗

Nonvascularized toe proximal phalanx transfers in the treatment of aphalangia.

The indications for nonvascularized toe phalanx transfers are limited. Radiolucency in the region of the transferred physis does not necessarily indicate a functional growth plate. Older age is not a contraindication to toe phalanx transfers. The results of this procedure can be improved and information from experimental physeal transplantation may help the surgeon to improve technique.

Fingers↗

The reproducibility of cardiac baroreceptor activity assessed non-invasively by spectral sequence techniques.

Baroreceptor sensitivity (BRS) is increasingly used as a prognostic indicator in cardiovascular disease. Traditionally it has been measured using invasive techniques with pharmacological manipulation of blood pressure (BP). With the advent of newer methods to measure pulse interval and beat-to-beat changes in BP it is now possible, using sophisticated mathematical modelling techniques, to calculate cardiac BRS non-invasively. However, there are virtually no data on the reproducibility of these newer techniques and what factors may affect the repeatability of these measurements. We studied 39 subjects, aged 22-82 years, with a supine systolic BP range 97-160 mmHg and a diastolic BP range 57-94 mmHg on two occasions between 1 week and 6 months apart. Cardiac BRS was measured by power spectral analysis using Fast Fourier Transformation (FFT), sequence analysis (using up, down and combined sequences) and from phase IV of the Valsalva manoeuvre. There was no significant difference between visits for any of the methods for measuring cardiac BRS. Mean BRS values were similar for FFT (16.7 +/- 11.2 ms/mmHg) and sequence analysis (15.8 +/- 11.4 ms/mmHg); however, results using phase IV of the Valsalva manoeuvre were significantly lower (8.1 +/- 2.9 ms/mmHg, p < 0.0001). The coefficient of variation for the five measures of cardiac BRS varied from 16.8% for Valsalva-derived values to 26.1% for 'down' sequence analysis. However, in ten subjects BRS could not be calculated from the Valsalva manoeuvre. None of the independent variables tested (including age, BP levels and time between testing) significantly influenced the degree of repeatability. In summary, there appears to be little difference between these non-invasive methods in their degree of reproducibility. These techniques would seem suitable for longitudinal studies of changes in cardiac BRS and overcome many of the problems associated with the invasive pharmacological methods.

Adult↗

Feasibility of mathematical models to predict success in video-assisted thoracic surgery lung nodule excision.

BACKGROUND: Pulmonary nodules are occasionally difficult to excise using video-assisted thoracic surgery (VATS). METHODS: To predict operative success, mathematical models using preoperative computerized tomography (CT) measurements were tested in 50 consecutive patients who underwent attempted or successful thoracoscopic lung biopsy. Unrelated technical problems resulted in the exclusion of 3 patients. RESULTS: No differences were noted with respect to lobar location, thoracic dimensions, gender, presence of chronic obstructive pulmonary disease, or nodule pathology. The expression S/(D + 1), where S = nodule size (cm) and D = distance (cm) to the nearest visceral pleura, yielded significantly higher values for visible nodules (P < 0.001). Resectable nodules had a higher score using the expression 1/(S + D + 1), (P < 0.001). Simple cases (n = 19) were defined as those in which nodules were both visible and resectable with very basic VATS techniques. All others (n = 28) were considered complex. The derived expression for Simplicity [1/(S(D + 1))] yielded significantly higher values for simple cases (0.8 +/- 0.3 vs. 0.3 +/- 0.2 cm(-2), P < 0.001) and all simple cases had a score > or = 0.4. Logistic regression analysis showed that the formulas for resectability and simplicity were significant independent predictors for resectability and simplicity. CONCLUSIONS: Equations based on objective CT measurements may be useful for planning VATS nodulectomy or studying the outcome of these minimally invasive operations.

Feasibility Studies↗

Endothelial function in subcutaneous resistance arteries from elderly hypertensive and normotensive subjects.

1. Previous studies have indicated that younger hypertensive subjects may have abnormal endothelium-dependent relaxation, which could contribute to the elevated peripheral resistance seen in established hypertension. This study was designed to examine the functional behaviour of the endothelium of small arteries from elderly hypertensive and normotensive subjects. 2. Resistance arteries were obtained from gluteal biopsies taken under local anaesthesia in 28 subjects of mean age 70 (range 60-76) years, and studied in an isometric myograph. Eighteen subjects had untreated essential hypertension, and 10 were normotensive. 3. After measurement of the contractile response to noradrenaline, relaxation responses to a variety of endothelium-dependent (acetylcholine and bradykinin) and endothelium-independent (iloprost and sodium nitroprusside) mechanisms were assessed in vessels precontracted with noradrenaline. Endothelium-dependent responses were also studied after incubation with NG-nitro-L-arginine to inhibit nitric oxide synthase. 4. There were no significant differences in the contraction or relaxation responses between elderly subjects with or without high blood pressure. Inhibition of nitric oxide synthase prevented any relaxation with acetylcholine and significantly attenuated the relaxation with bradykinin. Near-complete relaxation was however achieved with the endothelium-independent vasodilator sodium nitroprusside. 5. Hypertension in elderly subjects is not associated with a reduction in endothelial vasodilating function in the subcutaneous vessels of the gluteal region compared with age-matched normotensive controls. The results of this study do not support the hypothesis of a defect of resistance artery endothelium-dependent relaxation in the pathophysiology of hypertension in the elderly.

Acetylcholine↗

Impulse response analysis of baroreceptor sensitivity.

The impulse response function (IRF) can express the dynamic relationship between systolic arterial pressure (SAP) and pulse interval (PI) and, consequently, represents an alternative method to assess baroreceptor sensitivity (BRS) in humans. Five normotensive and 13 hypertensive subjects (age 68 +/- 5 yr, range 60-74 yr) were studied at rest in the supine position during baseline conditions and after injections of phenylephrine and sodium nitroprusside. SAP and PI signals were derived from multiple 5-min noninvasive recordings of arterial blood pressure (Finapres) and electrocardiogram. Standard estimates of BRS were obtained by the slopes of transient changes in SAP and PI after the injection of phenylephrine and sodium nitroprusside (BRS(PE) and BRS(SNP)) and by spectral analysis (alpha-index). Impulse responses were obtained by the inverse Fourier transform of the transfer function between PI and SAP. The temporal pattern of the IRF was characterized by a main peak at t = 0, preceded by a "trough" at t = -1 s. A mathematical model of the baroreflex suggests that the peak value of IRF is linearly related to the BRS. The peak value and its smoothed version were shown to be significantly correlated to alpha, BRS(PE), and BRS(SNP) and significantly reduced in the hypertensive group during the three stages of the protocol. We suggest that IRF might be the ideal method to assess BRS because it does not require any subjective preselection of data segments or spectral bands.

Aged↗