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Biomedical subjects

I Kingma

Publications and source records attributed to I Kingma.

At least 55 records · Page 3Linked to original sources

Effect of recombinant human erythropoietin therapy on ambulatory blood pressure in normotensive and in untreated borderline hypertensive hemodialysis patients.

The effect of recombinant human erythropoietin (r-HuEPO) on ambulatory blood pressure (ABP) was studied in 13 anemic hemodialysis patients. Eight patients were normotensive and five patients had untreated borderline systolic hypertension. Mean hemoglobin increased from 82 +/- 3 g/L to 114 +/- 3 g/L (P < .01) after 3 to 4 months of r-HuEPO therapy (30 to 40 U/kg) administered subcutaneously three times weekly. Mean 24-h systolic and diastolic ABP measurements were significantly increased by 16 +/- 4 mm Hg and 10 +/- 2 mm Hg, respectively (P < .01 for both). Blood pressure was increased in all but one patient. In six patients, the mean 24-h systolic and diastolic ABP measurements were more than 160 mm Hg or 90 mm Hg at the end of the study. The increase in ABP was slightly but not significantly greater during the waking period as compared with the sleeping period and the circadian blood pressure pattern was not modified by r-HuEPO treatment. The blood pressure load (percentage of ABP reading exceeding 140/90 mm Hg during the waking period and 120/90 mm Hg during the sleeping period) was significantly increased (P < .05) after r-HuEPO therapy. Nine of the 13 patients failed to show the expected reduction in blood pressure during the sleeping period and were defined as "nondippers"; the others were defined as "dippers." During r-HuEPO therapy, the increase in ABP was similar in both dippers and nondippers. This suggests that the nondipper condition is not a risk factor for the development of hypertension during r-HuEPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of push handle height on net moments and forces on the musculoskeletal system during standardized wheelchair pushing tasks.

The aim of this investigation was to analyze the external forces and biomechanical loading on the musculoskeletal system during wheelchair pushing, in relation to different push handle heights. In addition, recommendations for wheelchair pushing in accordance with push handle height are made. Eight young, female subjects carried out three different wheelchair transport tasks at five different push handle heights in a standardized laboratory setting. Five pushing heights were selected as a percentage of the subjects shoulder height (61, 69.5, 78, 86.5 and 95%). All three wheelchair transport tasks investigated required higher pushing handles in order to minimise net shoulder moments and external vertical forces on the hands. When pushing a wheelchair on to a pavement, net moments around wrists, elbows, shoulders compression and shear forces at L5-S1 and external vertical forces were lower using higher pushing heights. When low pushing handles are used, elderly female attendants are at risk of L5-S1 low back pain when lifting and pushing the wheelchair on to a pavement. A recommendation is made to reconsider height and position of the pushing handles of attendant propelled wheelchairs. For the investigated tasks, a pushing height of 86.5% (1.191 +/- 0.034 m) was most favourable.

Activities of Daily Living↗

The evaluation of a practical biomechanical model estimating lumbar moments in occupational activities.

To estimate the mechanical load on the low back in manual materials handling, the Static Strength Prediction Model (SSPM, University of Michigan) is widely used in the occupational field. It requires (for practical reasons) only a small number of input variables (five body segment angles, standing height, total body mass, external load on the hands) on which basis the moment at the lumbo-sacral intervertebral joint (beside other parameters) is computed. The dynamic character of the activities is ignored in the calculations. To evaluate the validity of the SSPM in various situations, lumbar moments in lifting/lowering activities at different lifting techniques and speeds obtained by the SSPM, were compared with those obtained by a more comprehensive dynamic model (DM). An analysis of variance showed significant effects (p = 0.001) of the biomechanical model applied and the lifting speed used on the peak lumbar moment values. No effects of lifting technique were found. The differences in results from the SSPM and DM were dependent on the lifting speed: the SSPM peak lumbar moments were on average 9% (not significant), 21% (significant at p = 0.005) and 42% (p = 0.0001) smaller compared to the DM moments in the slow (mean velocity in a complete lifting/lowering cycle, 0.2 m s-1), normal (0.4 m s-1) and fast (0.8 m s-1) speed condition respectively. The results indicate that the static/dynamic difference between the models is a major source for the different lumbar moments, while other differences between the SSPM and DM are of minor importance.

Adult↗

Plasma endothelin levels and blood pressure in hemodialysis and in CAPD patients. Effect of subcutaneous erythropoietin replacement therapy.

We investigated plasma endothelin (ET) concentration and blood pressure in 44 patients with end stage renal failure chronically treated with either hemodialysis (n = 24) or continuous ambulatory peritoneal dialysis (CAPD) (n = 20). Half of the subjects were on chronic erythropoietin (r-HuEPO) replacement therapy (30-60 U/kg) subcutaneously, 3 times weekly. The mean plasma ET level of the whole group was about five fold higher than the normal range. Plasma ET concentration and mean blood pressure were higher in hemodialysis than in CAPD patients (33.3 +/- 2.1 vs 24.8 +/- 1.2 pg/ml, p < 0.01, and 101 +/- 2.4 vs 91 +/- 3 mmHg, p < 0.025). There was a significant correlation between plasma ET levels and systolic blood pressures in both groups (r = 0.45, p < 0.05). Patients (hemodialysis and CAPD) receiving subcutaneous r-HuEPO had higher mean blood pressure (99 +/- 3 vs 85 +/- 4 mmHg, p < 0.01), while their plasma ET levels were similar to untreated patients independent of the dialysis mode. However, a statistically significant correlation between plasma ET and systolic blood pressure was present only in the r-HuEPO treated group (r = 0.46, p < 0.05 vs r = 0.29, N.S., for the untreated group). These results show that plasma ET levels are markedly increased on both dialysis mode, but the values are lower in CAPD patients. Plasma ET concentrations significantly correlated with systolic blood pressures in the whole group of patients, and also in those receiving r-HuEPO replacement therapy.

Adult↗

An innovative technical approach for repetitive intratracheal instillation without anesthesia in small animals.

Intratracheal instillation in small laboratory animals often involves repeated anesthesia and upper airway intubation. To facilitate this approach, we developed an indwelling system for repeated intratracheal administrations that was assembled from widely available simple components. Its installation can be considered a minor surgical procedure and is done under sterile surgical conditions. This system allows repeated intratracheal administration of substances in the lungs in unanesthetized animals, with the possibility to increase the frequency of instillations and lower the dose. Thoracic radiography was performed to document the reliability of this permanent instillation system. Furthermore, a potent toxic nitrosamine (NNK; N-nitrosamine 4-[nitrosomethylamino]-1-[3-pyridil]-1-butanone) was used to demonstrate appreciable pulmonary toxicity at low dosage but with repetitive administration. This simple technique brings a significant simplification and improvement to small animal studies that require repeated bronchoalveolar administration of substances.

Anesthesia↗

Glomerular capillary pressures in long-surviving rat renal allografts.

Many renal transplants undergo gradual deterioration in structure and function in the months or years after transplantation. The processes that underlie this progressive decline have not been defined, and may include immunological and nonimmunological mechanisms. The present experiments were designed to investigate the glomerular capillary hydrostatic pressure in long-surviving rat renal transplants with or without chronic rejection. Stop-flow glomerular pressures were measured in F344 renal allografts with chronic rejection, syngeneic F344 grafts, and long-surviving syngeneic and allogeneic LEW grafts without chronic rejection; control measurements were done in nontransplanted intact animals or after subtotal renal ablation. Renal ablation or transplantation resulted in increased glomerular pressure in F344 but not LEW kidneys; the glomerular pressure in syngeneic F344 grafts was not different from that in allogeneic F344 grafts. There was no correlation between the mean arterial pressure and the glomerular capillary pressure. Our data suggest that the glomerular capillary pressure is determined by local intrarenal factors. The glomerular capillary pressure in allotransplanted kidneys resembles that of the donor kidney after subtotal renal ablation. The importance of increased glomerular pressure in the progressive decline of graft function of chronic rejection remains to be established.

Animals↗

Different methods to estimate total power and its components during lifting.

A more fundamental understanding about the act of manual lifting can be provided by the assessment of the total production of power and the power generated in joints. The present study is concerned with the validity of the estimations of these parameters. Four subjects lifted an 18.8 kg load while they were filmed and ground reaction forces were measured. The total generated power was calculated in three ways: (1) by summation of joint powers, (2) on the basis of the rate of change of the summed energy contents of human body segments, and (3) on the basis of the rate of change of the body energy estimated from ground reaction forces. The results were compared. Furthermore, at a segmental level the power supplied to or absorbed from a segment was compared to the rate of change of its energy content. The resulting instantaneous power curves from the three different methods showed a high level of agreement, which supports their validity. However, some minor discrepancies were observed. The major cause of the observed difference between the rate of change of the summed segmental energy contents and the summed joint powers was found at a segmental level. It was observed that segmental link lengths (i.e. distances between proximal and distal markers) changed during movement, which yielded discrepancies between the power flow to or from a segment and the rate of change of its energy content.

Adult↗

The effect of nitroglycerin on pulmonary vascular capacitance in dogs.

In this study we investigated the hypothesis that the decrease in pulmonary vascular pressures observed after administration of nitroglycerin is in part due to a shift in the pulmonary vascular pressure-volume relationship. The experiments were done in six closed-chest dogs anesthetized with pentobarbital, in which pulmonary, cardiac, and intestinal relative blood volumes were determined by equilibrium blood pool scintigraphy. Nitroglycerin (30 micrograms/kg/min) caused 7% (p less than 0.02) and 12% (p less than 0.02) reductions in pulmonary and total cardiac blood volume, respectively, and a 7% (p less than 0.01) increase in intestinal blood volume. This shift of blood from the heart and the pulmonary circulation to the systemic (intestinal) circulation was accompanied by reductions in mean pulmonary artery pressure from 16 +/- 2 mm Hg to 12 +/- 1 mm Hg (p less than 0.01), in mean pulmonary capillary wedge pressure from 11 +/- 2 mm Hg to 6 +/- 1 mm Hg (p less than 0.01), and in mean portal pressure from 9 +/- 1 mm Hg to 8 +/- 1 mm Hg (p less than 0.01). The position of the pulmonary vascular pressure-blood volume relationship was unaffected by nitroglycerin, whereas the portal pressure-intestinal blood volume relationship was shifted to the left and upward. These changes suggest that pulmonary vascular tone remained unchanged, whereas intestinal vascular tone decreased during administration of nitroglycerin. In conclusion, nitroglycerin decreased pulmonary vascular pressures through a passive emptying of the pulmonary circulation as a result of increased systemic (intestinal) vascular capacitance.

Animals↗

Cyclosporine-associated reduction in systolic myocardial function in the rat.

The cardiotoxic effect of cyclosporine in the inbred rat was investigated in the isolated perfused heart model. Diastolic and systolic function was studied in 5 groups of (Lewis x Brown Norway) F1 rats treated with different doses of cyclosporine for different time intervals and in a group which received the vehiculum cremophor. Of the cyclosporine-treated rats, one group was studied four weeks after drug discontinuation to assess reversibility of the effect. To control for the nephrotoxic side effects of cyclosporine, a group of animals that had undergone 1.5-1.75 renal ablation was included. Left ventricular pressures were measured with a balloon catheter; stepwise increases in preload were obtained by small increments in the balloon volume. Over the range of left ventricular volumes studied, no differences were found in diastolic pressure between the groups. Peak systolic pressures were significantly lower in hearts obtained from cyclosporine treated rats which had received 15 or 7.5 mg/kg/24 h subcutaneously for three weeks (P less than 0.05). Our results indicate that cyclosporine treatment resulted in a reversible decrease in myocardial contractile force apparently unrelated to decreases in renal function or to changes in mean arterial pressure.

Analysis of Variance↗

Left and right ventricular diastolic function during acute pericardial tamponade.

The aim of the study was to determine the effect of acute pericardial tamponade on left (LV) and right ventricular (RV) intracavitary and transmural pressure-volume (P-V) relations and to assess the effect of changing blood volume during tamponade on LV and RV volumes. The experiments were done in 11 acutely instrumented anaesthetized dogs in which LV and RV volumes were determined by computed tomography (CT) (n = 5) and LV and RV diameters by sonomicrometry (n = 6). Pressures were measured in the pericardium (balloon transducer), in the aorta and in the ventricles. Incremental pericardial infusion (up to 180 ml) caused a progressive left and upward shift of the LV and the RV intracavitary P-V relationship. This shift was entirely due to increased pericardial pressure (PP). The induction of tamponade caused no change in the LV and RV transmural P-V relationship. During tamponade with ventricular filling pressures above 10-15 mmHg, blood volume expansion caused only minimal increase in LV and RV volumes. In conclusion, pericardial tamponade shifted the LV and the RV intracavitary diastolic P-V relation by increasing PP. However, there was no change in the transmural P-V relationship, indicating unchanged myocardial compliance. Volume loading caused only minimal increase in LV and RV volumes during tamponade.

Animals↗

Human papillomavirus type 16 associated with oral squamous carcinoma in a cardiac transplant recipient.

Human papillomavirus type 16 (HPV 16) has been associated with a variety of squamous carcinomas, particularly those involving the anogenital tract. The authors report the development of an oropharyngeal carcinoma in a 43-year-old man approximately 20 months after cardiac transplantation while he was on a maintenance regimen of cyclosporine A and prednisone. The carcinoma was resistant to treatment, and he died of complications related to metastatic disease 3 years posttransplantation. Molecular biologic studies using nonisotopic-labeled viral DNA probes were done. In situ hybridization demonstrated the presence of HPV 16 DNA in the tumor cells. DNA dot blot analysis confirmed the presence of multiple copies of HPV 16 DNA within the tumor cells and their absence from adjacent normal-appearing tissue. Southern blot analysis suggested that the HPV 16 DNA was integrated into the tumor cell genome. With increasing recognition of the carcinogenicity of HPV type 16 infection, a role for this virus in the development of squamous cell malignancies in immunosuppressed organ transplant recipients is likely to be noted with increasing frequency.

Adult↗

The dependence of the time constant of left ventricular isovolumic relaxation (tau) on pericardial pressure.

The purpose of this study was to investigate the dependence of tau, the time constant of left ventricular (LV) isovolumic relaxation, on pericardial pressure and to compare values of tau as determined by the methods of previous investigators and by a standard exponential curve fit. All of the more recent methods involve an additional parameter--the pressure to which the exponential relaxation finally declines (PB, the pressure intercept in the method of Craig and Murgo and the asymptote in the exponential fits). An additional purpose of the study was to determine the relation of these parameters to pericardial pressure. In eight closed-chest anesthetized dogs, tau was calculated from intracavitary (Plv) and transmural LV pressure (Plv = Plv-Pper) by each method as pericardial (Pper) and LV end-diastolic pressure were changed by pericardial infusion and intravenous volume loading. The time constant determined by the method of Weiss et al was dependent on pericardial pressure; the time constants determined by the other methods were not. PB and the asymptotes were found to be similar and to increase almost equally with pericardial pressure. When pericardial pressure was zero, these values were approximately -20 mm Hg. Thus, both these parameters seem to indicate the same baseline pressure, a pressure that increases pari passu with pericardial pressure. Reported changes in the value of tau calculated from intracavitary LV pressure by the method of Weiss et al may reflect factors other than changes in LV diastolic function.

Animals↗

Increased pulmonary vascular capacitance with beta-adrenergic receptor stimulation: an experimental study of the effect of isoproterenol on the pulmonary vascular volume-pressure relationship.

The present study is an investigation of the effect of beta-adrenergic receptor stimulation by isoproterenol on pulmonary vascular capacitance. The experiments were done in six intact-chest, anaesthetized dogs in which pulmonary and cardiac blood volumes were assessed by blood pool scintigraphy. Isoproterenol (0.150 microgram.kg-1.min-1) significantly (p less than 0.005) lowered pulmonary capillary wedge pressure (PPCW) and pulmonary artery pressure (PPA) but did not significantly change pulmonary blood volume (PBV). Left ventricular end-diastolic pressure and total cardiac volume both significantly (p less than 0.005) decreased. Pulmonary vascular volume-pressure (V-P) relationships before and during isoproterenol were described by means of blood transfusions and hemorrhage. In individual dogs the PBV-PPCW and the PBV-(PPCW + PPA)/2 relationships were significantly shifted upward by isoproterenol (p less than 0.05 or less); slope changes were variable. Pooled data from all dogs also showed a significant (p less than 0.001) upward shift in the pulmonary vascular V-P relationship regardless of which measure of distending pressure was used. These results suggest that beta-receptor stimulation by isoproterenol increases pulmonary vascular capacitance by increasing the unstressed volume.

Adrenergic beta-Agonists↗

Left ventricular external constraint: relationship between pericardial, pleural and esophageal pressures during positive end-expiratory pressure and volume loading in dogs.

Left ventricular (LV) diastolic filling is limited by the constraining effects exerted by the pericardium (PE) and the lung/chest wall. The aim of the present study was to assess the validity of various estimates of external cardiac constraint, compared to pericardial surface pressure (Ppe) measured lateral to the LV myocardium. In nine anesthetized dogs we measured Ppe, pleural surface pressure (Ppt) (lateral to the pericardium) and esophageal pressure (Pes) under conditions of volume loading and positive end-expiratory pressure (PEEP). We measured Ppe and Ppl with flat, liquid-containing silastic rubber balloons and Pes with an air-containing cylindrical balloon. After instrumentation, the chest was resealed and continuous suction (-5 mm Hg, 1 mm Hg = 0.133 kPa) was maintained. Volume loading with incremental intravenous infusions of saline was used to increase LV end-diastolic pressure to 20-25 mm Hg. PEEP of 0, 10 and 20 mm Hg were applied at baseline and after each increment of volume loading. At low volume, increases in PEEP caused simultaneous increases in LV end-diastolic pressure (P less than 0.01) and in Ppe (P less than 0.0001) but a reduction in transmural LV pressure (P less than 0.0005). Ppl and Pes both increased with PEEP (P less than 0.001 and P less than 0.01, respectively). However, Ppe always exceeded Ppl, while Pes remained at only approximately 1/3 Ppl throughout. Volume loading caused a significant increase in Ppe (P less than 0.0001) and a smaller, but significant increase in Ppl (P less than 0.05). Pes remained unchanged during volume loading. Thus external cardiac constraint increased markedly during volume loading and PEEP as evidenced by a marked elevation of Ppe. Both Ppl and Pes markedly underestimated this increase. Therefore, calculation of transmural LV pressure by subtracting pleural or esophageal pressure from intracavitary pressure can lead to overestimation of LV preload. The decrease in cardiac output during PEEP occurs secondary to decreased preload, i.e. decreased transmural pressure and end-diastolic dimension. Analysis of performance using cardiac function curves does not suggest a change in contractility with PEEP.

Animals↗

Modulation of vascular capacitance by angiotensin and nitroprusside: a mechanism of changes in pericardial pressure.

The aim of the present study was to test the hypothesis that vasoactive drugs may modify left ventricular diastolic function by shifting blood between the systemic vascular bed and the heart, thereby changing pericardial and left ventricular pressure. The experiments were done in 10 open-chest, anesthetized, previously splenectomized dogs in which changes in pericardial surface pressure in response to intravenous sodium nitroprusside and angiotensin were related to changes in blood volume in the abdominal region. Blood volume was determined by blood pool scintigraphy (99mTc) and regions of interest were drawn in the liver and in the mesenteric area. Angiotensin was infused at rates that were adjusted to increase mean aortic pressure by 20 and 30 mm Hg, and nitroprusside was infused at rates to decrease mean aortic pressure by 30 and 50 mm Hg. Angiotensin increased pericardial pressure by 3 and 5 mm Hg at the respective doses and there were increments in left ventricular end-diastolic pressure (LVEDP) and left ventricular diameter (sonomicrometry). Angiotensin decreased blood volume in the mesenteric region by 14% and 17%, but did not significantly change blood volume in the liver region. Angiotensin increased portal venous pressure and decreased mesenteric blood volume, suggesting decreased mesenteric venous compliance. Nitroprusside had opposite effects: pericardial pressure was decreased by 5.5 and 6.5 mm Hg by the respective doses. The doses of nitroprusside increased blood volume in the mesenteric region by 14% and 20%, but did not significantly change blood volume in the liver region.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Transseptal pressure gradient and diastolic ventricular septal motion in patients with mitral stenosis.

Previous studies from our laboratory have shown that the position of the ventricular septum relative to the two ventricles at end-diastole is determined by the instantaneous transseptal pressure gradient (TSG) defined as left ventricular minus simultaneous right ventricular pressure. Since patients with mitral stenosis often have exaggerated leftward (paradoxic) motion of the ventricular septum during early diastole, we studied seven patients with mitral stenosis undergoing cardiac catheterization to determine if position (and therefore motion) of the ventricular septum was determined by TSG throughout diastole. M Mode echocardiograms derived from a two-dimensional parasternal short-axis view were recorded with simultaneous micromanometer measurements of left ventricular and right ventricular pressures. Six of seven patients demonstrated abnormal early diastolic leftward motion of the ventricular septum in at least one cardiac cycle. TSG measured at intervals throughout diastole ranged from -2.5 to +20 mm Hg, with abnormal TSG observed in most of the 40 cardiac cycles selected for analysis. The intracardiac position of the ventricular septum, defined as the distance from the right ventricular epicardium (RVEpi) to the left surface of the ventricular septum normalized for total cardiac dimension (RVEpi-VS), was plotted against left ventricular pressure, right ventricular pressure, and TSG. Linear regression of pooled data from all patients (164 observations) demonstrated a highly significant correlation between the instantaneous TSG and the relative intracardiac position of the ventricular septum (RVEpi-VS = 1.52 TSG + 42.7; r = .79, p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗