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Biomedical subjects

A J Smit

Publications and source records attributed to A J Smit.

At least 55 records · Page 3Linked to original sources

Re-evaluation of the cold face test in humans.

The cold face test has been found to be a simple clinical test to elicit the diving reflex, which assesses function of the sympathetic and parasympathetic nerve systems at the same time. However, there is no consensus about how the test should be performed without confounding the results by eliciting other reflexes, such as the oculocardiac reflex. The object of this study was to compare and standardize methods for performing the cold face test. Reproducibility of results was assessed. Groups of 6 to 11 subjects participated in each protocol. To act as a cold stimulus a bag filled with iced-water and having a wet surface was used. The effects of allowing breathing to continue, of different masses of the bag, and of avoiding ocular pressure by wearing diving goggles were investigated. Blood pressure and heart rate were measured beat to beat using an automatic blood pressure measuring device. The cold stimulus used in this study was too small to elicit the oculocardiac reflex: wearing diving goggles and different masses of the bag had no influence on the response. The prevention of breathing, however, tended to enhance the fall in heart rate during the cold stress. Reproducibility was highest when the subjects were habituated to the intensity of the stimulus. We recommend practising the test method in advance and performing it in a setting where the subject is unable to breathe.

Adult↗

Dopamine in heart failure and critical care.

Dopamine is widely used in critical care to prevent renal function loss. Nevertheless sufficient evidence is still lacking of reduction in end points like mortality or renal replacement therapy. Dopaminergic treatment in chronic heart failure (CHF) has provided an example of unexpected adverse outcome. Pharmacoepidemiological data. Provide additional evidence, finding excess mortality in current ibopamine users (relative risk 2.03 in NYHA I-II CHF, 1.37 in NYHA III-IV), while no relation was found with antiarrhythmic use. In critical care, studies after infrarenal aortic surgery or during septic shock, respectively, failed to find, expected specific renal effects of dopamine. Effects on splanchnic flow mainly depend on baseline flow levels. The implications of recently documented unwanted effects of dopamine, like reduced ventilation and oxygenation during hypoxia, are discussed. In conclusion, controlled clinical trials remain mandatory to assess the overall clinical effects of dopamine in critical care.

Cardiotonic Agents↗

Diabetic neuropathy examination: a hierarchical scoring system to diagnose distal polyneuropathy in diabetes.

OBJECTIVE: Existing physical examination scoring systems for distal diabetic polyneuropathy (PNP) do not fulfill all of the following criteria: validity, manageability, predictive value, and hierarchy The aim of this study was to adapt the Neuropathy Disability Score (NDS) to diagnose PNP in diabetes so that it fulfills these criteria. RESEARCH DESIGN AND METHODS: A total of 73 patients with diabetes were examined with the NDS. Monofilaments and biothesiometry were used as clinical standards for PNP to modify the NDS. RESULTS: A total of 43 men and 30 women were studied; mean duration of diabetes was 15 years (1-43), and mean age was 57 years (19-90). A total of 24 patients had type 1 diabetes, and 49 patients had type 2 diabetes. Clinically relevant items were selected from the original 35 NDS items (specific item scored positive in >3 patients). The resulting 8-item Diabetic Neuropathy Examination (DNE) score could accurately predict the results of the clinical standards and is strongly hierarchical (H value 0.53). The sensitivity and specificity of the DNE at a cut-off level of 3 to 4 were 0.96 and 0.51 for abnormal monofilament scores, respectively. For abnormal vibration perception threshold scores, these values were 0.97 and 0.59, respectively. Reproducibility as assessed by inter- and intrarater agreement was good. CONCLUSIONS: The DNE is a sensitive and well-validated hierarchical scoring system that is fast and easy to perform in clinical practice.

Adult↗

Baroreflex sensitivity is depressed in microalbuminuric Type I diabetic patients at rest and during sympathetic manoeuvres.

AIMS/HYPOTHESIS: To evaluate baroreflex sensitivity (BRS) in microalbuminuric and normoalbuminuric Type I (insulin-dependent) diabetic patients without autonomic neuropathy and in healthy control subjects. METHODS: Microalbuminuric Type I diabetic patients (n = 15) were matched for age, sex, body mass index (BMI) and smoking habits with 15 normoalbuminuric patients and with 15 healthy control subjects. All subjects had a blood pressure less than 160/95 mmHg, a BMI less than 30 kg/m(2) and normal autonomic function on standard tests. Blood pressure and heart rate were measured non-invasively (Finapres) at rest and during sympathetic activation (handgrip, mental stress, standing). The baroreflex sensitivity was defined as the mean gain between blood pressure variability and heart rate variability in the 0.07-0.15 Hz frequency band. RESULTS: Resting baroreflex sensitivity was decreased in the microalbuminuric patients (3.5 +/- 0.4 ms/mmHg) compared with the normoalbuminuric patients and the healthy subjects (7.6 +/- 1.6 and 9.5 +/- 1.1 ms/mmHg, respectively, p < 0.001). The sympathetic tests reduced baroreflex sensitivity similarly in the groups without changing the between group differences. CONCLUSION/INTERPRETATION: Baroreflex sensitivity is reduced in Type I diabetic patients with microalbuminuria but without autonomic neuropathy. A prospective study should indicate whether this early abnormality in cardiovascular reflex function is a risk factor of cardiovascular mortality in these patients. [Diabetologia (1999) 42: 1345-1349]

Albuminuria↗

Carotid intima-media thickness: influence of drug treatment and clinical implications.

With B-mode ultrasound measurements of the intima-media thickness (IMT) of the carotid arterial wall (asymptomatic) atherosclerosis can be detected. In this article several studies are reviewed in which IMT was used as a surrogate endpoint to assess effects of lipid-lowering or antihypertensive drugs on peripheral atherosclerosis, and the clinical implications are discussed. After 1 year of treatment with lipid-lowering drugs an improvement of the blood lipid profile and retarded progression of the carotid IMT was seen. No incontrovertible evidence can be provided for a correlation between induced changes in the carotid and coronary arteries. Carotid IMT appears to be of prognostic value for cardiovascular events. The range of treatment-induced changes in IMT do not support the use of IMT in an individual patient to monitor treatment effects. However, with increased IMT as independent cardiovascular risk factor, IMT measurements are valuable in risk assessment in the individual patient in clinical practice. Looking forward to some ongoing studies, there is so far insufficient evidence that treating hypertension also inhibits progression of the IMT.

Anticholesteremic Agents↗

Capillary permeability is increased in normo- and microalbuminuric type 1 diabetic patients: amelioration by ACE-inhibition.

BACKGROUND: Capillary leakage of sodium-fluorescein (NaF) in the skin reflects capillary permeability and may be a marker of diabetes-associated microcirculatory abnormalities. DESIGN: We evaluated transcapillary skin NaF leakage by fluorescence videodensitometry in 10 normoalbuminuric, 10 microalbuminuric Type 1 diabetic men (diabetes duration > 10 years) and 10 healthy subjects. The microalbuminuric patients were restudied after 6 weeks treatment with the ACE-inhibitor enalapril, 10 mg once daily. All measurements were performed at a blood glucose level of 5 mmol L-1. RESULTS: Transcapillary NaF leakage was strongly increased in normoalbuminuric Type 1 diabetic patients compared to healthy subjects (P < 0.001) and was still further increased in microalbuminuric Type 1 diabetic patients (P < 0.01 compared to normoalbuminuric patients). Enalapril reduced NaF leakage (P < 0.05), mean arterial blood pressure (P < 0.05) and microalbuminuria (P < 0. 05). After treatment, NaF leakage was not different from that in normoalbuminuric patients. CONCLUSIONS: Capillary permeability, as determined by NaF leakage, is elevated in normoalbuminuric Type 1 diabetic patients with long-standing disease, and the excess elevation in microalbuminuric Type 1 diabetic patients is ameliorated by ACE-inhibition. Skin NaF videodensitometry seems a useful tool to document capillary permeability in intervention studies.

Albuminuria↗

Walking training for intermittent claudication in diabetes.

OBJECTIVE: Walking training (WT) is an established treatment for patients with intermittent claudication (IC). Abnormalities specific to diabetes, such as a relative preponderance of distal lesions and the contribution of microcirculatory disease, might well influence the results of WT. We compared changes in walking distance during WT in diabetic patients with those in nondiabetic control subjects. RESEARCH DESIGN AND METHODS: In consecutive patients with limiting IC and proven peripheral vascular disease, 33 patients with diabetes were compared with 136 control subjects during a half-year supervised WT program. Walking parameters were determined every 2 months, while vascular parameters were obtained at the start and end of the program. RESULTS: Of the 33 diabetic patients, 25 (76%) completed the program, as did 87 of the 136 (64%) control subjects. Thereafter, the symptom-free walking distance and the maximum walking distance (MWD) were significantly increased in diabetic patients from 142 +/- 30 to 339 +/- 57 m and from 266 +/- 39 to 603 +/- 52 m, respectively, and in control subjects from 126 +/- 8 to 400 +/- 39 m and from 292 +/- 18 to 628 +/- 36 m, respectively. The relative gain in MWD was 88% greater in those with diabetes. The vascular parameters were comparable for both groups before and after WT. CONCLUSIONS: WT is an effective treatment for IC, with a greater relative gain in diabetic patients.

Blood Pressure↗

Home blood pressure measurement: reproducibility and relationship with left ventricular mass.

OBJECTIVE: To evaluate the reproducibility and relationship with left ventricular mass index of home blood pressure in comparison with ambulatory and office blood pressures. METHODS: We measured home, ambulatory and office blood pressures of 84 previously untreated hypertensive patients, aged 60-74 years, from primary care, at baseline and after 12 weeks, without active intervention in between. Left ventricular mass index was determined echocardiographically during week 12. RESULTS: Decreases in systolic and diastolic blood pressures were found after 12 weeks for mean home and office blood pressures (P<0.05), but not for mean ambulatory blood pressure. The coefficients of reproducibility for systolic and diastolic ambulatory blood pressures were 26.4 and 16.0, respectively. Correlation coefficients for correlation of left ventricular mass index to ambulatory blood pressure (0.51 and 0.36) were higher than the correlation coefficients for home (0.31 and 0. 16) and office (0.32 and 0.21) blood pressures, for systolic and diastolic values, respectively. However, we could find no statistically significant difference among the correlation coefficients for all three types of measurements. CONCLUSIONS: Home blood pressure was considerably less reproducible than ambulatory blood pressure and no different from office blood pressure in this respect. The relationship with left ventricular mass index appeared to be stronger for ambulatory than it was for home and office blood pressures, although not statistically significant so.

Aged↗

A simple nomogram for determination of echocardiographic left ventricular geometry.

Recent data have shown that left ventricular (LV) geometry provides additional information on the simple dichotomy of presence or absence of LV hypertrophy with regard to cardiovascular risk of hypertensive patients. A "new" class of concentric remodeling was created, identifying a rather large group of hypertensive patients who do have increased risk despite no LV hypertrophy. Because determination of LV geometry is not easy, our objective was to develop a nomogram enabling determination of LV geometry in a simple way. The geometric classification is based on the combination of increased relative wall thickness and LV hypertrophy (LV mass index > or = 125 g/m2) both of which are calculated from wall thickness and end-diastolic diameter. In the nomogram the calculated cutoff lines for relative wall thickness and left ventricular hypertrophy are plotted, forming 4 quadrants that represent the geometric classes. Two nomograms are made: 1 based on Penn convention measurement calculations and 1 based on American Society of Echocardiography convention measurements. This nomogram provides a simple way to determine LV geometry, and thus a quick assessment of the additional cardiovascular risk of the hypertensive patient. This is especially important for subjects with concentric remodeling, who would otherwise not be identified as having increased risk for cardiovascular disease.

Echocardiography↗

Oral iloprost in Raynaud's phenomenon secondary to systemic sclerosis: a multicentre, placebo-controlled, dose-comparison study.

OBJECTIVE: To identify the optimal dose of oral iloprost on the basis of efficacy and tolerability in patients with Raynaud's phenomenon secondary to systemic sclerosis. DESIGN: Multicentre, randomized, parallel-group comparison of two different doses of oral iloprost and placebo. SETTING: European university hospitals. PATIENTS: A total of 103 patients with Raynaud's phenomenon secondary to systemic sclerosis. INTERVENTION: Patients received one of three treatments for 6 weeks: placebo, oral iloprost 50 microg or oral iloprost 100 microg. Each treatment was taken twice daily, giving total daily doses of iloprost of 100 and 200 microg. MEASUREMENTS: The frequency, total daily duration and severity of Raynaud's attacks were recorded in a specially designed patient diary; physician's global assessment and adverse events were recorded at visits to the clinic. Analysis was performed on an intention-to-treat population. RESULTS: A total of 103 patients were recruited, 89 completed the assessments throughout the treatment period and 82 completed an additional 6 weeks of follow-up after treatment. Thirty-five patients received placebo, 33 received iloprost 50 microg and 35 received iloprost 100 microg. The mean percentage reductions in the frequency, total daily duration and severity of Raynaud's attacks were numerically greater in the iloprost groups at the end of treatment and at the end of follow-up. At the end of treatment (6 weeks), there were significant treatment differences in the total daily duration of attacks (P = 0.03), but not in the severity (P = 0.07) or the frequency of attacks (P = 0.37). At the end of follow-up (12 weeks), there were significant treatment differences in the total daily duration of attacks (P = 0.001) and in the severity of attacks (P = 0.007), but not in the frequency of attacks (P = 0.07). Percentages of patients improved at the end of treatment as assessed by the physician were 44% placebo, 57% iloprost 50 microg and 64% iloprost 100 microg (not significant). Side-effects were reported by 80% of patients on placebo, 85% on oral iloprost 50 microg and 97% on oral iloprost 100 microg. Premature discontinuations of treatment in each group were 9, 30 and 51%, respectively, with 6, 27 and 51% being due to adverse events. CONCLUSION: The results on the daily duration of Raynaud's attacks suggest that both 50 and 100 microg oral iloprost twice daily may be effective in the treatment of Raynaud's phenomenon secondary to systemic sclerosis. The 50 microg iloprost dose was better tolerated in this patient group.

Administration, Oral↗

Effects of low-dose dopamine on renal and systemic hemodynamics during incremental norepinephrine infusion in healthy volunteers.

OBJECTIVES: To assess the effects of low-dose dopamine on norepinephrine-induced renal and systemic vasoconstriction in normotensive healthy subjects. DESIGN: On separate days, either a low-dose dopamine (4 microg/kg/min) or a placebo (5% glucose) infusion was added in a single, blinded, randomized order to incremental norepinephrine infusions of 40, 80, and 150 ng/kg/min over a 60-min period each. SETTING: Outpatient clinic of a university-affiliated hospital. SUBJECTS: Normotensive healthy volunteers. INTERVENTIONS: Infusions of norepinephrine and dopamine. MEASUREMENTS AND MAIN RESULTS: Blood pressure and heart rate were measured with a semiautomated device, and glomerular filtration rate and effective renal plasma flow were determined with constant infusions of 125I-iothalamate and 131I-hippurate, respectively. Norepinephrine alone progressively increased mean arterial pressure to pressor levels, whereas this effect was attenuated by the addition of dopamine (p < .05 vs. norepinephrine alone). Glomerular filtration rate increased during lower norepinephrine doses and did not decrease at the highest norepinephrine dose. Addition of dopamine further increased glomerular filtration rate. Effective renal plasma flow decreased with each norepinephrine alone infusion step, but this decrease was completely prevented by concomitant dopamine infusion (p < .01 vs. norepinephrine). Sodium excretion tended to decrease with norepinephrine, but increased two- to three-fold after addition of dopamine (p < .01 vs. norepinephrine alone). CONCLUSIONS: In healthy man, norepinephrine causes a large decrease in renal plasma flow but not in glomerular filtration rate. Concomitant dopamine administration prevents this decrease in renal plasma flow, increases sodium excretion, and also attenuates the norepinephrine-induced systemic blood pressure increase. These findings warrant further clinical evaluation of the effect of concomitant low-dose dopamine and norepinephrine administration in critically ill patients.

Adrenergic alpha-Antagonists↗

Effect of quinapril and triamterene/hydrochlorothiazide on cardiac and vascular end-organ damage in isolated systolic hypertension.

We compared, in a prospective double-blind randomized study, the effect of the angiotensin-converting enzyme inhibitor quinapril (QUI) with that of triamterene/hydrochlorothiazide (THCT) treatment on cardiovascular end-organ damage in subjects with untreated isolated systolic hypertension (ISH). End-organ damage measurements, performed initially and after 6 and 26 weeks of treatment, included echocardiographic determination of left ventricular mass index (LVMI) and of diastolic function and measurement of aortic distensibility and peripheral vascular resistance. Blood pressure was significantly reduced in the 44 subjects (21 QUI, 23 THCT) completing the study. Both LVMI and aortic distensibility had changed at 6 weeks, with comparable improvements in both groups. LV diastolic function showed overall no significant changes, although patterns of early filling did differ between the two drug groups. Peripheral vascular resistance appeared to increase between 6 and 26 weeks in THCT subjects only, along with a decreased aortic distensibility. Blood pressure and LV mass were rapidly and markedly reduced in both treatment groups of ISH subjects, paralleled by an improvement of aortic distensibility. In interpreting these results, the pathophysiologic alterations in ISH need to be taken into account, because these differ strongly from those in diastolic hypertension. Results of LV diastolic function and peripheral vascular resistance were less clear but appear to show less favorable changes in the THCT subjects treatment group.

Aged↗

Exogenous norepinephrine induces an enhanced microproteinuric response in microalbuminuric insulin-dependent diabetes mellitus.

Exogenous norepinephrine (NE) increases intraglomerular pressure in animal experiments, but it is unknown whether NE induces a microproteinuric response in humans. Moreover, it has not been studied whether possible microproteinuric and renal hemodynamic changes induced by NE are altered in insulin-dependent diabetes mellitus (IDDM) complicated by microalbuminuria. Therefore, the microproteinuric and renal hemodynamic responses to exogenous NE infusions were measured in eight matched normoalbuminuric IDDM patients (group D1), microalbuminuric IDDM patients (group D2), and control subjects (group C). As anticipated, mean arterial pressure (MAP)-NE dose-response curves were significantly shifted leftward in groups D1 and D2 compared with group C (P < 0.05), indicating a higher systemic NE responsiveness in IDDM. On separate days, NE or placebo was infused at individually determined NE threshold doses (T; delta MAP = 0 mmHg), 20% pressor doses (20% P; delta MAP = 4 mmHg), and pressor doses (P; delta MAP = 20 mmHg), with measurement of urinary albumin (UalbV), IgG excretion (UIgGV), GFR (by 125I-iothalamate), and effective renal plasma flow (by 131I-hippurate). At NE pressor dose, UalbV and UIgGV rose in all groups (P < 0.05 to 0.01), whereas urinary beta 2-microglobulin was unchanged. The increases in UalbV and UIgGV were more pronounced in the microalbuminuric group than in the other groups (P < 0.05). An NE dose-dependent fall in effective renal plasma flow and rise in filtration fraction were found in all groups (P < 0.05 to 0.001 for all), whereas GFR did not change significantly. The renal hemodynamic dose-response relationship was similar in the groups. In conclusion, exogenous NE acutely promotes glomerular protein leakage, and it is plausible that intraglomerular NE effects contribute to this phenomenon. The microproteinuric response is enhanced in microalbuminuric IDDM despite unaltered renal hemodynamic responsiveness, which may reflect a specific NE response or a general effect of vasopressor stimuli to promote glomerular protein leakage in patients with a preexistent defect in glomerular permselectivity.

Adult↗

The assessment of autonomic function in patients with systemic amyloidosis: methodological considerations.

Autonomic neuropathy is a well-known and prognostically important feature of systemic amyloidosis. In other conditions, autonomic function is commonly assessed by cardiovascular reflex tests, described by Ewing, but the feasibility of these tests has not been investigated in patients with systemic amyloidosis. We studied autonomic function in amyloidotic patients using cardiovascular tests and assessed their feasibility. Patients with AA, AL and ATTR amyloidosis participated. In all patients, cardiovascular reflex testing (mental arithmetic stress test and head-up tilting, besides the Ewing-tests) was performed. Of the 46 patients included, only 28 patients could perform all 4 Ewing-tests. In particular, patients with AA amyloidosis secondary to rheumatoid arthritis could not perform standing up and the isometric handgrip test. However, when the mental stress test replaced the handgrip test and head-up tilting replaced standing up, in 45 of the 46 patients, autonomic function could be assessed with cardiovascular reflex tests. Half of the patients with AA amyloidosis had signs of autonomic neuropathy--which was more than expected. We propose to replace the isometric handgrip test with the mental arithmetic stress test and standing up with head-up tilting if a patient is not able to perform these tests.

Adolescent↗