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Biomedical subjects

K H Rahn

Publications and source records attributed to K H Rahn.

At least 55 records · Page 3Linked to original sources
PubMed2000

Diadenosine polyphosphates cause contraction and relaxation in isolated rat resistance arteries.

The effects of diadenosine polyphosphates (APnA; n = 3-6) and adenine nucleotides on contractile reactivity of isolated rat mesenteric resistance arteries (MrA) and superior epigastric arteries (SEA), which display a dense and sparse autonomic innervation, respectively, were evaluated. All agonists examined, except adenosine and AMP, induced contractions. The rank order of potency was similar in both arteries: alpha,beta-methylene ATP (alpha,beta-meATP) > AP5A > AP6A > AP4A > ATP > ADP > AP3A. Contractions were stable during several minutes in SEA but highly transient in MrA. They were reduced after exposure to 10 microM alpha,beta-meATP and by 10 microM of the P2X antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid. During phenylephrine (10 microM)-induced contractions, the agonists induced a further contraction in SEA. In MrA, however, further contraction was followed by marked relaxation. The rank order of relaxing potency was comparable to that of the contractile potency of agonists. Also, the relaxing effects of APnA were blunted by 10 microM pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid and after exposure to alpha,beta-meATP. In vitro and in vivo sympathectomy with 6-hydroxydopamine and removal of the endothelium did not modify the effects of APnA in MrA. Thus, the contractile effects of APnA in resistance arteries 1) are due to a P2X purinoceptor-mediated stimulation of the smooth muscle; 2) depend on the length of the phosphate chain; and 3) are followed by endothelium-independent relaxing effects in MrA but not SEA, which may involve receptors that are similar to those mediating contraction. The regional heterogeneity of APnA effects cannot be attributed to a direct neurogenic influence.

Adenine Nucleotides↗
PubMed2000

Heterogenous vascular effects of AP5A in different rat resistance arteries are due to heterogenous distribution of P2X and P2Y(1) purinoceptors.

In the accompanying article, we showed that AP5A displayed heterogenous vasoactive effects in rat resistance arteries. It induced a stable vasoconstriction in the superior epigastric artery (SEA) and a transient vasoconstriction in the mesenteric resistance artery (MrA). In the phenylephrine-precontracted MrA AP5A induced a marked vasorelaxation. In this study the noncompetitive inhibition of the AP5A-induced vasoconstriction with pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid was found to be significantly stronger in MrA than in SEA. The nonselective P2 purinoceptor antagonist suramin inhibited AP5A-induced vasoconstriction in MrA only. The vasoconstriction by the P2X purinoceptor agonist alpha,beta-methylene ATP was inhibited by with pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid and suramin similarly to that induced by AP5A. Thus, the AP5A-induced vasoconstriction is due to P2X receptor activation, but two different P2X receptors seem to be operational in the two different vessels. The AP5A-induced vasorelaxation of phenylephrine-precontracted MrA was inhibited by the P2Y(1) receptor antagonist ADP3'5'. The vasorelaxation induced by ADPbetaS (P2Y(1) agonist) also was inhibited by ADP3'5'. These findings suggest that AP5A-induced vasorelaxation of MrA is caused by P2Y(1) receptor activation. The P1 (A(2)) receptor antagonist 3, 7-dimethyl-1-propargylxanthine only slightly inhibited AP5A-induced vasorelaxation at high concentrations. Adenosine and the A(2) receptor agonist CGS21680 failed to produce significant vasorelaxation. Therefore, vasorelaxation in MrA does not involve A(2) purinoceptor activation. AP5A-induced vasorelaxation was not inhibited by Ca(2+)- or ATP-dependent K(+) channel blockade with clotrimazole, apamin, or glibenclamide. These data indicate that vasoconstriction in MrA and SEA by AP5A is due to different P2X receptors, and vasorelaxation in precontracted MrA is due to P2Y(1) receptor activation.

Animals↗
PubMed1999

Effect of nitrendipine on renal function in renal-transplant patients treated with cyclosporin: a randomised trial.

BACKGROUND: Calcium antagonists such as nitrendipine reduce the effects of cyclosporin on renal haemodynamics, however, their long-term efficacy has not been established. We did a randomised trial to investigate the effects of nitrendipine on renal function in renal-transplant patients treated with cyclosporin. METHODS: 253 renal-transplant patients were recruited: 52 normotensive patients (diastolic blood pressure <90 mm Hg) were assigned placebo and 57 nitrendipine 5 mg twice daily; 71 hypertensive patients (diastolic blood pressure >90 to <115 mm Hg) were assigned placebo and 73 nitrendipine 10 mg twice daily. Nitrendipine was increased to 20 mg twice daily if the target diastolic blood pressure (<90 mm Hg) was not achieved. The patients were seen once a month for 24 months; blood pressure and serum creatinine concentration were recorded at each visit. Analysis was by intention to treat. FINDINGS: 63 patients were withdrawn (35 nitrendipine, 28 placebo). The mean serum creatinine concentration at baseline was slightly higher in the nitrendipine group (146.7 micromol/L [SE 4.42]) than in the placebo group (137.0 micromol/L [3.54]. At the 24-month endpoint or at dropout, serum creatinine concentration was significantly higher in the 123 patients in the placebo group than the 130 patients in the nitrendipine group (160.8 [7.1] vs 148.5 [5.3], p for effect of treatment=0.025, analysis of covariance in a two-way classification; 95% CI for difference -1.77 to -22.98). At study entry, the blood pressures of the placebo and the nitrendipine groups were almost identical. At 24 months, blood pressure was higher in the normotensive patients given a placebo than in those patients given nitrendipine. By contrast, blood-pressure values were similar in those hypertensive patients given a placebo and those given nitrendipine at the end of treatment. INTERPRETATION: The calcium antagonist nitrendipine has no adverse effects on kidney function in renal-transplant patients with cyclosporin. The drug has a small but significant nephroprotective effect, that is independent of the drug's antihypertensive action.

Adult↗
PubMed1999

[Kikuchi-Fusimoto disease: the differential diagnosis of cervical lymphadenitis with recurrent attacks of fever].

HISTORY AND CLINICAL FINDINGS: A 49-year-old, otherwise healthy woman had recurrent fever and lymphadenopathy with leukopenia for nineteen years. Her symptoms prompted successless antibiotic therapy and extensive evaluations of fever of unknown origin. At admission there were several enlarged cervical lymph nodes and subfebrile temperatures. INVESTIGATIONS: Neither laboratory findings nor imaging did show an infectious, rheumatologic or hematologic cause of her symptoms. Histopathological examination of an lymph node biopsy revealed histiocytic, necrotizing lymphadenitis (Kikuchi-Fusimoto disease) as the underlying disease. TREATMENT AND COURSE: After spontaneous resolution without specific therapy the patient is now symptomless and well 9 months after diagnosis. CONCLUSION: Kikuchi-Fusimoto disease is a cause of benign and usually self-limiting lymphadenopathy. Clinicians and pathologists should be aware of this uncommon differential diagnosis since early histologic recognition will minimize potentially and unnecessary evaluations and treatments.

Biopsy↗
PubMed1999

Na+ and Mg2+ contents in smooth muscle cells in spontaneously hypertensive rats.

Whereas in blood cells decreased magnesium concentrations and increased sodium concentrations in essential hypertension have often been described, only sparse data exist on cellular magnesium or sodium content and exchange in vascular smooth muscle cells. Therefore in aortic smooth muscle cells from 10 spontaneously hypertensive rats (SHR) of the Münster strain and 10 normotensive Wistar-Kyoto rats (WKY) aged 8 to 10 months, the intracellular magnesium and sodium content was measured. Electron-probe X-ray microanalysis was used to determine intracellular Mg2+ and Na+ concentrations in aortic cryosections 3 microm thick. The magnesium ion content was 0.90 +/- 0.15 g/kg dry weight in SHR versus 1.15 +/- 0.10 g/kg dry weight in WKY (means +/- SD, P < .05). Vascular smooth muscle sodium ion content was 6.66 +/- 0.39 g/kg dry weight in WKY and 12.61 +/- 0.91 g/kg dry weight in SHR (P < .01). Aortic smooth muscle cells from SHR are characterized by markedly lowered intracellular magnesium ion content and increased sodium ion concentrations in animals 8 to 10 months old, compared with normotensive cells. The results may be due to genetically determined disturbances in transmembrane magnesium and sodium ion transport.

Animals↗
PubMed1999

Flow-mediated vasodilation and distensibility in relation to intima-media thickness of large arteries in mild essential hypertension.

Whether endothelial dysfunction in essential hypertension is a cause or a consequence of structural vessel wall alterations is not known. The purpose of the present study was to compare flow-mediated vasodilation and mechanical vessel wall properties of large arteries between never treated mild essential hypertensive patients with normal intima-media thickness (IMT) and those exhibiting intima-media thickening. We measured brachial and carotid artery diameter and distension by Doppler frequency analysis of vessel wall movements in M-mode in ten essential hypertensive patients with normal carotid artery IMT (HYP1), in ten patients with increased IMT (HYP2), and in 13 normotensive control subjects (CON). Thereafter, we measured changes in brachial artery (BA) diameters during distal reactive hyperemia after 4 min of forearm occlusion. Nitroglycerin-mediated vasodilation was measured to assess endothelium-independent vasodilation, and BA blood flow was estimated using a pulsed Doppler system. Intima-media thickness of the carotid arteries was examined by high resolution B-mode ultrasound. IMT was 0.66 +/- 0.02 mm in the HYP1 group, 0.84 +/- 0.03 mm in the HYP2 group (P < .01 v HYP1, P < .01 v CON), and 0.71 +/- 0.04 mm in the CON group. Forearm occlusion was reduced in both the HYP1 group (3.4% +/- 3.6%, P < .01 v CON) and the HYP2 group (6.4% +/- 1.5%, P < .05 v CON) when compared with the CON group (16.5% +/- 2.8%). Nitroglycerin-mediated vasodilation and BA blood flow were not different between study groups. BA distension (as well as carotid artery distension) was significantly lower in the HYP1 group (52 +/- 6 microm, P < .05 v CON), but not in the HYP2 group (72 +/- 10 microm) when compared with the CON group (88 +/- 13 microm). The data suggest that endothelial dysfunction and reduced distensibility of large arteries in patients with essential hypertension occur in the absence of structural vessel wall alterations.

Adult↗
PubMed1999

Studies on diurnal blood pressure variation in kidney diseases associated with excessive salt and water retention.

Salt and water retention, a cardinal feature of nephrotic syndrome, was suggested to be an important factor leading to reduced diurnal blood pressure (BP) variation in renoparenchymal disease. Twenty-four hour BP (SpaceLabs SL 90207), 24-h urine excretion of catecholamines, plasma renin activity and plasma aldosterone concentration were therefore determined in 10 nephrotic patients with normal serum creatinine levels (group A, serum creatinine 1.0+/-0.2 mg/dl), in 10 nephrotic patients with increased serum creatinine levels (group B, serum creatinine 2.4+/-0.9 mg/dl) and in 20 controls matched in respect of age and BP. To study the direct influence of fluid volume overload, diurnal BP variation was determined before and after volume depletion by ultrafiltration in 10 patients with end-stage renal failure. Diurnal BP variation was characterised by the difference of mean BP during daytime (10 pm to 8 am) and night-time (8 am to 10 pm). In group A, the systolic and diastolic day-night difference was not changed when compared with the controls (NS). In contrast, in group B the day-night difference was significantly lower than in the controls (P < 0.01). Twenty-four hour urine catecholamine excretion and plasma aldosterone were comparable between the study groups. Plasma renin activity, however, was significantly increased in group A (P < 0.05). Nocturnal BP drop was not related to plasma renin activity in the nephrotic patients. The blunted diurnal blood pressure variation in end-stage renal failure was not influenced by ultrafiltration. The study demonstrates that the blunted diurnal BP variation in kidney disease is unaffected by marked changes in total exchangeable sodium and fluid volume, but is sensitive to changes in glomerular filtration rate.

Adult↗
PubMed1999

Studies on cardiac sympathovagal balance and large artery distensibility in patients with untreated essential hypertension.

BACKGROUND: Power spectral analysis of heart rate variability and arterial distensibility are non-invasive measures of cardiac autonomic modulation and mechanical vessel wall properties, respectively. The aim of the present study was to assess cardiac sympathovagal balance, carotid and brachial artery distensibility and a possible relation between these parameters in mildly hypertensive patients as compared to normotensive controls. METHODS: Total power (TP, 0.01 to 0.5 Hz) and spectral components (low frequency 0.04-0.15 Hz, mainly sympathetic cardiac modulation; high frequency 0.15-0.4 Hz, mainly vagal cardiac modulation) and cardiac sympathovagal balance (LF/LH ratio) of short term heart rate variability (ECG-recording) were calculated in 15 untreated essential hypertensive patients (HYP) and 15 age- and sex-matched healthy controls (CON). Brachial and carotid artery distensibility coefficient (DC) was measured with a multigate doppler system (echo-tracking). RESULTS: TP (ms2 x 10(-3)) (11.2 +/- 0.8 vs 13.6 +/- 0.9, P < 0.03), LF/HF ratio (1.07 +/- 0.08 vs 0.75 +/- 0.07, P < 0.01) and HF (ms2 x 10(-3)/%) (0.7 +/- 0.1/49 +/- 2 vs 1.3 +/- 0.2/58 +/- 2, P < 0.01/P < 0.01) were significantly reduced in HYP compared to CON subjects. LF (ms2 x 10(-3)/%) was 0.7 +/- 0.1/50 +/- 2 vs 0.9 +/- 0.1/41 +/- 2, P = 0.16/P < 0.01. Carotid artery DC (15 +/- 2 vs 26 +/- 2, P < 0.001) and brachial artery DC (4.7 +/- 0.6 vs 9 +/- 1.0, P < 0.001) were significantly reduced in HYP. There was a significant correlation between carotid DC and LF/HF (rho = -0.41, P < 0.03). CONCLUSION: The data shows reduced heart rate variability and altered cardiac sympathovagal balance as well as impaired arterial distensibility in untreated mildly hypertensive patients. The relative increase in sympathetic modulation and decreased carotid distensibility appear to be related.

Adult↗
PubMed1999

Chronic intoxication by doxycycline use for more than 12 years.

We report the clinical case of a 12-years' intoxication by doxycycline. A patient with a depersonalization and derealization syndrome took 1 g doxycycline per day. In addition to hepatocellular necrosis with cholestasis, nephrotoxicity, leukopenia, anaemia and skin hyperpigmentation he suffered from hitherto unreported adverse cardiac events as intermittent supraventricular tachycardia and sporadic Wenckebach heart block. Despite a long period of self-medication these side-effects were reversible.

Adult↗
PubMed1999

Flow-mediated vasodilation and distensibility of the brachial artery in renal allograft recipients.

BACKGROUND: Alterations of large artery function and structure are frequently observed in renal allograft recipients. However, endothelial function has not yet been assessed in this population. METHODS: Flow-mediated vasodilation is a useful index of endothelial function. We measured the diameter and distensibility of the brachial artery at rest using high-resolution ultrasound and Doppler frequency analysis of vessel wall movements in the M mode. Thereafter, changes in brachial artery diameter were measured during reactive hyperemia (after 4 min of forearm occlusion) in 16 cyclosporine-treated renal allograft recipients and 16 normal controls of similar age and sex ratio. Nitroglycerin-mediated vasodilation was measured to assess endothelium-independent vasodilation. Brachial artery blood pressure was measured using an automatic sphygmomanometer, and brachial artery flow was estimated using pulsed Doppler. RESULTS: Distensibility was reduced in renal allograft recipients (5.31 +/- 0. 74 vs. 9.10 +/- 0.94 x 10-3/kPa, P = 0.003, mean +/- sem), while the brachial artery diameter at rest was higher (4.13 +/- 0.14 vs. 3.25 +/- 0.14 mm, P < 0.001). Flow-mediated vasodilation was significantly reduced in renal allograft recipients (0.13 +/- 0.08 vs. 0.60 +/- 0.08 mm or 3 +/- 2 vs. 19 +/- 3%, both P < 0.001). However, nitroglycerin-mediated vasodilation was similar in renal allograft recipients and controls (0.76 +/- 0.10 vs. 0.77 +/- 0.09 mm, NS, or 19 +/- 3 vs. 22 +/- 2%, NS). There were no significant differences in brachial artery flow at rest and during reactive hyperemia between both groups. The impairments of flow-mediated vasodilation and distensibility in renal allograft recipients remained significant after correction for serum cholesterol, creatinine, parathyroid hormone concentrations, end-diastolic diameter, as well as blood pressure levels, and were also present in eight renal allograft recipients not treated with cyclosporine. Flow-mediated vasodilation was not related to distensibility in either group. CONCLUSIONS: The results show impaired endothelial function and reduced brachial artery distensibility in renal allograft recipients. The impairments of flow-mediated vasodilation and distensibility are not attributable to a diminished brachial artery vasodilator capacity, because endothelium-independent vasodilation was preserved in renal allograft recipients.

Adult↗
PubMed1999

Studies on structural changes of the carotid arteries and the heart in asymptomatic renal transplant recipients.

BACKGROUND: The present study was designed to characterize early structural changes of large arteries in renal transplant recipients with no clinical evidence of cardiovascular disease and normal blood pressure values, and to analyse the relationship between arterial alterations and those of the heart. METHODS: Intima media thickness and atherosclerotic plaques of the carotid arteries as well as left ventricular geometry and function were examined in 35 asymtomatic renal transplant recipients and 29 age- and sex-matched healthy controls by high resolution B-mode ultrasound and by echocardiography. RESULTS: Intima-media thickness of the carotid arteries was significantly higher in renal transplant recipients (1.21+/-0.08 mm) than in healthy controls (0.74+/-0.04 mm) (P<0.001). Atherosclerotic plaques were found in the majority of renal transplant recipients (71% vs 14% in healthy controls, P<0.001). Left ventricular mass index was significantly increased in the group of renal transplant recipients (264+/-13 g, 146+/-7 g/m2) when compared with healthy controls (155+/-8 g, 83+/-4 g/m2) (P<0.001). Multiple regression analysis in renal transplant recipients showed that intima media thickness of the carotid arteries was significantly related to left ventricular mass index (P<0.02), but not to age, blood pressure, body mass index, serum creatinine, cholesterol and lipoprotein (a) levels. In the group of healthy controls, intima-media thickness of the carotid artery was related to age (P<0.002), but not to left ventricular mass index or the other independent variables. CONCLUSIONS: The present study documents pronounced intima-media thickening in asymptomatic renal transplant recipients. Atherosclerotic lesions are present in most renal transplant recipients with no clinical evidence of cardiovascular disease. We observed a parallelism between arterial wall thickening and left ventricular hypertrophy, although blood pressure levels were normal during haemodialysis therapy and after renal transplantation.

Adult↗
PubMed1999

How to assess glomerular function and damage in humans.

In human subjects, the assessment of renal function and of its changes by interventions is limited to the measurement of glomerular filtration rate (GFR), renal blood flow and the estimation of proteinuria. In humans, GFR can be determined exactly by measuring the clearance of an ideal filtration marker, such as inulin. The classic method of measuring inulin clearance in humans includes constant intravenous infusion of the compound and timed collections of urine. In order to avoid the need for timed urine collections, a number of alternative procedures have been devised. All these methods only use determinations of inulin in plasma or serum. From these, the total body inulin clearance is obtained using pharmacokinetic calculations. In order to measure total body clearance, usually called plasma clearance, inulin is either given as a constant intravenous infusion or as a bolus infusion. Both procedures overestimate GFR because of incomplete distribution of inulin during the study periods. The error may be minimized by using model-independent pharmacokinetic calculations. Unlike inulin, creatinine is not a perfect filtration marker. This is because the substance is not only eliminated by glomerular filtration but also by tubular secretion. The extent of tubular creatinine secretion is not constant in various individuals. Serum creatinine concentration is a commonly used measure of renal function in clinical practice. This parameter is determined both by the renal elimination and by the production of the compound. Differences in creatinine production among subjects and over time in a single individual may occur because of changes in muscle mass. Radioisotopic filtration markers can easily and accurately be measured in plasma and serum. Using this method, the plasma concentration-time curve of these compounds can easily be studied after intravenous bolus injection. From the plasma concentration-time curves obtained, the total body clearance (plasma clearance) of the substances can be calculated using pharmacokinetic models. Most frequently, 125l-iothalamate, 99mTc-diethylenethiaminepenta-acetic acid and 51Cr-ethylenediaminetetra-acetic acid are used for the estimation of GFR in humans. The total body clearance of all these filtration markers overestimates GFR. The error induced by this phenomenon is particularly relevant at low levels of GFR. In recent years, iohexol has been used as a filtration marker. The substance can be measured in plasma, serum and urine using high-performance liquid chromatography. So far, good agreement has been shown for GFR determined by the classic inulin clearance and by the iohexol plasma clearance. Screening for proteinuria is commonly performed using reagent test strips. Quantitative measurements of marker proteins can be used to estimate the extent and the site of damage in the nephron. These measurements may be used to estimate the progression of renal disease and the response to therapeutic interventions. Of particular interest is the degree of albuminuria which indicates nephropathy in diabetic patients and end-organ damage in patients with hypertension.

Humans↗
PubMed1999

ACE inhibitor versus beta-blocker for the treatment of hypertension in renal allograft recipients.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to slow the progression of chronic renal failure. However, the value of ACE inhibitors for the treatment of hypertension in renal allograft recipients has not been established. ACE inhibitors dilate the efferent glomerular arteriole, an effect that may aggravate the decrease in glomerular filtration rate resulting from cyclosporine-induced vasoconstriction at the afferent glomerular arteriole. Therefore, the goal of this double-blind, randomized study was to compare the antihypertensive and renal effects of the ACE inhibitor quinapril with those of the beta-blocker atenolol in renal allograft recipients in whom hypertension developed 6 to 12 weeks after transplantation. All patients received cyclosporine as an immunosuppressant and had stable graft function (serum creatinine concentration, <220 micromol/L) at entry into the study. Twenty-nine patients who received quinapril (daily dose titrated between 2.5 and 20 mg) and 30 patients who received atenolol (daily dose titrated between 12.5 and 100 mg) completed the 24-month study. The two groups did not differ in age, sex ratio, height, and weight before entry into the study. Quinapril decreased diastolic blood pressure from 96+/-1 to 84+/-1 mm Hg (average throughout treatment period), and atenolol decreased diastolic blood pressure from 96+/-1 to 83+/-1 mm Hg. The serum creatinine concentration did not change significantly in either group after 24 months (129+/-8 micromol/L at entry and 148+/-19 micromol/L after 24 months in the quinapril group and 131+/-6 micromol/L at entry and 152+/-15 micromol/L after 24 months in the atenolol group; P=NS for both groups). After 24 months, the change in urinary albumin excretion from baseline was -10+/-15 mg/d in the quinapril group and 52+/-32 mg/d in the atenolol group (P=0.03). These results show that quinapril and atenolol are effective antihypertensive drugs when used after renal transplantation. Moreover, compared with atenolol, quinapril has no adverse effects on graft function. The relative reduction in albuminuria observed with quinapril as compared with atenolol could indicate a beneficial effect of quinapril on long-term graft function.

Adolescent↗
PubMed1999

The sympathetic nervous system in the pathogenesis of hypertension.

There are now numerous studies demonstrating that essential hypertension is accompanied by sympathetic activation. Using drugs which block cardiac sympathetic effects, it could be shown that a noticeable fraction of subjects with borderline hypertension had an increased sympathetic drive. A meta-analysis of studies on plasma noradrenaline levels as an indirect marker of sympathetic tone reported that noradrenaline concentrations were significantly elevated in patients with essential hypertension as compared with normotensive control subjects. In addition, it could be shown that the rate of noradrenaline spillover from sympathetic nerve terminals was sometimes increased in essential hypertension, particularly in young hypertensive subjects. Additional data have emerged by direct measurement of sympathetic nerve traffic to skeletal muscle circulation using a microelectrode technique. Most studies using this method have demonstrated increased sympathetic nerve activity in patients with essential hypertension. In contrast, patients with secondary hypertension did not differ from normotensive subjects. Taken together, the data available at present show that sympathetic activation is a specific feature of essential hypertension and that it may play a pathogenetic role in this disease.

Arteries↗