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Biomedical subjects

G Ligtenberg

Publications and source records attributed to G Ligtenberg.

16 recordsLinked to original sources
PubMed2006

Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial.

Until recently, intravenous cyclophosphamide pulses with oral corticosteroids were regarded standard therapy for proliferative lupus nephritis (LN). Azathioprine, a less toxic alternative, was never proven to be inferior. In the first Dutch lupus nephritis study (enrollment between 1995 and 2001), we randomized 87 proliferative LN patients to either cyclophosphamide pulses (750 mg/m(2), 13 pulses in 2 years) combined with oral prednisone (CY) or to azathioprine (2 mg/kg/day in 2 years) combined with intravenous pulses of methylprednisolone (3 x 3 pulses of 1000 mg) and oral prednisone (AZA). After a median follow-up of 5.7 years (interquartile range 4.1-7.2 years), doubling of serum creatinine was more frequent in the AZA group, although not statistically significant (relative risk (RR): 4.1, with 95% confidence interval (95% CI): 0.8-20.4). Relapses occurred more often in the AZA group (RR: 8.8, 95% CI: 1.5-31.8). Creatinine and proteinuria at last visit did not differ between the two treatment arms. Moreover, 88.4% of the patients in the AZA arm were still free of cyclophosphamide treatment. During the first 2 years, the frequency of remission was not different, but infections, especially herpes zoster virus infections (HZV) were more frequent in the AZA group. Parameters for ovarian function did not differ between the two groups. In conclusion, in this open-label randomized controlled trial, cyclophosphamide was superior to azathioprine with regard to renal relapses and HZV. At last follow-up, there were no differences in serum creatinine or proteinuria between the two groups. However, since our study lacked sufficient power, longer follow-up is needed to reveal putative differences.

Administration, Oral↗
PubMed2003

Health-related quality of life in patients with systemic lupus erythematosus: development and validation of a lupus specific symptom checklist.

Reliable and sensitive measures are needed to evaluate the quality of life (QoL) in patients with systemic lupus erythematosus (SLE). No lupus specific questionnaires are available. This study describes the development and validation of a disease-specific questionnaire for lupus patients, which assesses the presence and burden of 38 disease- and treatment-related symptoms: the SLE Symptom Checklist (SSC). Reliability and reproducibility were tested in respectively 87 and 28 stable SLE patients. The internal consistency (Cronbach's alpha coefficients 0.89) and test-retest reliability (Pearson product-moment correlation coefficient between 0.67 and 0.87) were satisfactory. Concurrent validity was supported by significant, but moderate correlations with other measures of subjective well-being and functional status. Responsiveness was measured in 17 patients with lupus nephritis treated with cyclophosphamide, at start of therapy and 1 year thereafter. A significant change in number of symptoms and total distress level was found. It is concluded that the SSC has satisfactory psychometric properties and appears suitable for both clinical and research purposes.

Female↗
PubMed2001

Mechanisms and consequences of arterial hypertension after renal transplantation.

The high incidence of hypertension after renal transplantation contributes to the risk of cardiovascular morbidity and mortality in renal transplant recipients. Although cyclosporine has been influential in the improvement of transplant outcome, it has emerged as a major cause of hypertension after organ transplantation. The underlying pathophysiological mechanisms of cyclosporine-induced hypertension include enhanced sympathetic nervous system activity, renal vasoconstriction, and sodium/water retention. Hypertension is also significantly associated with reduced graft survival and thereby requires aggressive treatment intervention. Calcium channel blockers may offer some advantages over angiotensin-converting enzyme inhibitors for the treatment of hypertension in stable renal transplant recipients. Nevertheless, selection of the most appropriate antihypertensive agent should take into account the possibility of pharmacokinetic interactions with immunosuppressive agents. There is evidence to suggest that the use of tacrolimus-based immunosuppression induces less hypertension compared with cyclosporine. Not only do patients receiving tacrolimus tend to require less antihypertensive therapy, but converting patients from cyclosporine to tacrolimus has been shown to result in significant reductions in blood pressure. Thus, tacrolimus may be associated with an improved cardiovascular risk profile in renal transplant recipients.

Antihypertensive Agents↗
PubMed1999

Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure.

BACKGROUND: Inhibition of angiotensin-converting enzyme (ACE) reduces the risk of cardiovascular problems in patients with chronic renal failure. This effect may be due in part to a decrease in sympathetic nervous activity, but no direct evidence of such an action is available. METHODS: We studied muscle sympathetic-nerve activity in 14 patients with hypertension, chronic renal failure, and increased plasma renin activity before, during, and after administration of the ACE inhibitor enalapril. Ten other patients with similar clinical characteristics were studied before and during treatment with the calcium-channel blocker amlodipine. Normal subjects matched for age and weight were included in both studies. RESULTS: At base line, mean (+/-SD) muscle sympathetic-nerve activity was higher in the group of patients who received enalapril than in the control subjects (35+/-17 vs. 19+/-9 bursts per minute, P=0.004). The baroreflex curve, which reflects changes in muscle sympathetic-nerve activity caused by manipulations of blood pressure with sodium nitroprusside and phenylephrine, was shifted to the right in the patients, but baroreflex sensitivity was similar to that in the control subjects (-2.1+/-1.9 and -2.7+/-1.3 bursts per minute per mm Hg, respectively; P=0.36). A single dose of the sympatholytic drug clonidine caused a greater fall in blood pressure in the patients than in the control subjects. Treatment with enalapril normalized blood pressure and muscle sympathetic-nerve activity (at 23+/-10 bursts per minute) in the patients and shifted the baroreflex curve to the left, reflecting normal blood-pressure levels, without significantly changing sensitivity (-2.3+/-1.8 bursts per minute per mm Hg, P=0.96). In the patients who received amlodipine, treatment also lowered blood pressure but increased muscle sympathetic-nerve activity, from 41+/-19 to 56+/-14 bursts per minute (P=0.02). CONCLUSIONS: Increased sympathetic activity contributes to hypertension in patients with chronic renal disease. ACE inhibition controls hypertension and decreases sympathetic hyperactivity.

Amlodipine↗
PubMed1999

Preoperative evaluation of living renal donors with gadolinium-enhanced magnetic resonance angiography.

BACKGROUND: Preoperative evaluation of living renal donors includes an intra-arterial digital subtraction angiography (DSA). Inasmuch as this technique is invasive, uses radiation and an iodine-containing contrast medium, an alternative technique would be preferable. The purpose of this study was to determine the accuracy of gadolinium-enhanced magnetic resonance (MR) angiography in the visualization of renovascular anatomy for the preoperative evaluation of renal donors. METHODS: Twenty-four consecutive potential renal donors underwent gadolinium-enhanced MR angiography before the standard of reference, intra-arterial DSA. Both modalities were evaluated in a blinded manner. The results were correlated with the surgical findings. RESULTS: Three MR angiograms were technically unacceptable because of inadequate breath-hold. The remaining 21 donors had 47 renal arteries, including 5 accessory renal arteries, which were all visualized by MR angiography. MR angiography failed to visualize one case of subtle fibromuscular dysplasia in the distal part of a renal artery. In one donor, a small accessory renal artery, which had not been visualized on DSA, was encountered during nephrectomy. CONCLUSION: Gadolinium-enhanced MR angiography is an accurate minimally invasive method for the detection of accessory renal arteries in the preoperative evaluation of potential renal donors. The accuracy for excluding stenosis in general is high; however, the depiction of stenosis that are located far distally, or in the branch vessels, is less accurate. Advantages of gadolinium-enhanced MR angiography over the currently used method, intra-arterial DSA, are the minimal invasive nature, lower costs, and superiority in detecting venous anomalies, renal cysts, and tumors.

Adult↗
PubMed1999

Regulation of blood pressure in chronic renal failure: determinants of hypertension and dialysis-related hypotension.

Regulation of blood pressure is of crucial importance in the management of patients with chronic renal failure. In the predialysis phase, hypertension is common. Apart from volume overload and an inappropriately activated renin-angiotensin system, overactivity of the sympathetic nervous system appears to play a role as well. Sympathetic outflow may be enhanced by elevated Angiotensin II levels. Maintenance treatment with angiotensin converting enzyme inhibition normalizes sympathetic overactivity in hypertensive patients with chronic renal failure. In view of the unfavourable role of increased sympathetic activity in cardiovascular disease and prognosis, normalization of sympathetic outflow may be a new treatment goal. Hemodialysis is often complicated by sudden hypotension, causing considerable distress and morbidity. Reduction of blood volume causes sympatho-excitation, vasoconstriction and tachycardia. Sudden hypotension, however, is accompanied by acute withdrawal of sympathetic activity, vasodilation and relative bradycardia, also known as the Bezold-Jarisch reflex. Subtle fluctuations in vasomotor tone in hypovolemic conditions can elicit this reflex. In a series of experiments we showed that reduction of blood volume plays a pivotal role in the pathogenesis of hypovolemic hypotension. Autonomic neuropathy and dysfunction of the central opioid system have been proposed as causative mechanisms in dialysis-related hypotension. We, however, could not confirm a pathogenetic role for either mechanism.

Angiotensin II↗
PubMed1998

Presyncope during progressive hypovolaemia simulated by lower body negative pressure is not prevented by high-dose naloxone.

BACKGROUND: The haemodynamic response to progressive hypovolaemia, whether simulated by lower body negative pressure (LBNP) or head-up tilt, or induced by haemorrhage or haemodialysis, has a typical biphasic pattern: a first, sympathoexcitatory, phase of vasoconstriction, tachycardia, and stable blood pressure, and a second, sympathoinhibitory, phase of vasodilatation, bradycardia, and hypotension. The opioid system is involved in this response, since animal studies showed that opioid antagonism by naloxone can attenuate hypovolaemic hypotension. In humans, this finding could not be confirmed. We hypothesized that this could result from inadequate dosing. METHODS: Six healthy subjects underwent LBNP at -45 mmHg until presyncope before and after administration of naloxone 2 mg/kg. During the study, blood pressure, heart rate, vascular resistance, cardiac output, and plasma beta-endorphin were measured. RESULTS: LBNP caused an immediate increase in vasoconstriction and heart rate, resulting in stable blood pressure. After 12 +/- 3.5 min, vasodilatory hypotension followed, accompanied by a modest increase in plasma beta-endorphin. Naloxone did not alter the first or the second phase of the circulatory response, and tolerance to LBNP even tended to decrease (hypotension after 7.5 +/- 2.0 min, NS). Pre-LBNP plasma beta-endorphin as well as hypotensive levels were increased after naloxone. CONCLUSIONS: Our results suggest that naloxone, in a sufficient dose to interfere with the opioid system, does not influence the circulatory response to simulated hypovolaemia in humans is not influenced by naloxone. Given the mechanistic resemblance of LBNP hypotension to dialysis-induced hypotension, we propose that high-dose naloxone is not useful to treat the latter form of hypotension.

Adult↗
PubMed1998

Hemodynamic response during lower body negative pressure: role of volume status.

Sudden dialysis-related hypotension is characterized by paradoxical vasodilation, suggestive of sympathoinhibition. A similar hypotensive reaction can be evoked by lower body negative pressure (LBNP), which thus allows the study of the numerous factors involved in dialysis hypotension separately. This article examines the influence of changes in volume status on the hemodynamic response to LBNP (45 mmHg up to the iliac crest, maximum 60 min) in 12 healthy subjects. LBNP caused a decrease in cardiac index and pulse pressure, and an increase in heart rate and total peripheral resistance, most of which developed within the first 3 min of LBNP. Six subjects developed sudden hypotension characterized by vasodilation after 9 +/- 4 min of LBNP. After saline expansion (25 ml/kg), which increased blood volume by approximately 8%, five subjects endured LBNP for the full 60 min. However, after 60 min of LBNP, the circulatory parameters suggested a similar critical situation as that observed before presyncope in their first experiment. The other six subjects endured the full 60 min of LBNP. After furosemide-induced volume reduction associated with 1.6 +/- 0.2 kg weight loss and approximately 7% blood volume reduction, five of them developed vasodilatory presyncope after 17 +/- 5 min of LBNP. Comparison of presyncopal and nonpresyncopal experiments within subjects, as well as between subjects, showed that the early (3 min) response to LBNP was different: Despite similar decreases in cardiac index, the values for systolic pressure, pulse pressure, peripheral resistance, and stroke volume were lower, and the heart rate was higher in the experiments ending in presyncope. It is concluded that the volume status is a determinant of the tolerance to LBNP, probably by affecting the vasoconstrictive response. By inference, this study suggests that the vasoconstrictive response to the hemodynamic stress of hemodialysis is also influenced by the volume status.

Adult↗
PubMed1997

Cold stress provokes sympathoinhibitory presyncope in healthy subjects and hemodialysis patients with low cardiac output.

BACKGROUND: Sudden hypotension in progressive hypovolemia or during hemodialysis is attributed to sudden inhibition of sympathetic activity. Critical ventricular underfilling seems responsible for this paradox, but it is unknown why the transition from sympathoactivation accompanying hypovolemia to sympathoinhibition is so abrupt. We studied whether brief fluctuation of sympathetic activity induced by cold pressor test (CPT) evokes sympathoinhibition if applied during low cardiac output. METHODS AND RESULTS: Fourteen healthy subjects underwent CPT, lower-body negative pressure (LBNP; -45 mm Hg for 60 minutes), or the combination thereof. CPT alone caused vasoconstriction and increased muscle sympathetic nerve activity, followed by uneventful relaxation. When applied during reduced cardiac output, tachycardia, and vasoconstriction induced by prior LBNP for 6 minutes, CPT again caused vasoconstriction, now followed by acute hypotension in 10 subjects, and was associated with vasorelaxation, relative bradycardia, and fall in muscle sympathetic nerve activity. Eight subjects also experienced acute LBNP-induced hypotension in the absence of CPT, but not until 17 +/- 6 minutes of LBNP. We also performed CPT before and in the final phase of hemodialysis in 8 patients. Before dialysis, the patients tolerated CPT uneventfully, but during hemodialysis, CPT provoked acute hypotension in 5 cases, showing similar withdrawal of vasoconstriction. CONCLUSIONS: This is the first study showing that brief cold stress, tolerated well in normal circulatory conditions, can provoke sudden sympathoinhibition and hypotension when applied during decreased cardiac output induced by LBNP or hemodialysis. We suggest that during conditions of a decreased cardiac output, subtle sympathetic relaxation such as follows cold stress triggers self-enhancing relaxation that cannot be controlled.

Adult↗
PubMed1996

No change in automatic function tests during uncomplicated haemodialysis.

Uraemic autonomic dysfunction is reckoned to participate in dialysis hypotension, but a clear relationship has not been established. However, autonomic function is usually tested at rest, and possibly autonomic dysfunction arises or worsens during dialysis. We therefore performed easily repeatable tests of efferent sympathetic function, that is static exercise test and parasympathetic function, that is heart rate variability during Valsalva manoeuvre and deep breathing, at successive stages of a standard haemodialysis session; before dialysis, 20 min after dialysis without ultrafiltration, after 3 h of dialysis combined with ultrafiltration, and 20 min after dialysis. Studies were performed in 22 patients on chronic haemodialysis on a cuprophane dialyser. The mean ultrafiltration volume was 2.2 +/- 0.61. We found that blood pressure elevation upon static exercise, and heart rate variability during Valsalva or deep breathing test remained unaltered at the various stages of dialysis. On past performance the patients were divided into hypotension prone (n = 6) or resistant (n = 16). Hypotension prone patients showed a greater blood pressure drop during dialysis, but also showed an appropriately enhanced heart rate acceleration. The occurrence of autonomic dysfunction was not elevated in this group, nor did such dysfunction develop along dialysis. Predialysis parasympathetic function tests were abnormal in 10 patients. These patients also showed an augmented intradialytic blood pressure decrease, but no enhanced acceleration in heart rate. Their parasympathetic dysfunction did not worsen during dialysis. Based upon the predialysis exercise test, low responding patients (blood pressure increase 5 +/- 2 mmHg, n = 11) were distinguished. These subjects were not characterized by a greater blood pressure decrease or different heart rate acceleration. Generally, the responses upon exercise, whether low or high, remained unaltered during dialysis. we conclude that haemodialysis has no systematic effect on autonomic function. Hypotension-prone patients are not distinguished by a disturbed predialytic or intradialytic autonomic blood pressure control.

Adult↗
PubMed1993

Erysipelas: not always innocent.

The case histories of two patients with the "toxic-strep" syndrome are presented. This syndrome consists of a Streptococcus pyogenes group A infection, complicated by multi-organ failure. In our patients renal failure necessitating haemodialysis was present. General characteristics of the syndrome and long-term follow-up are presented.

Acute Kidney Injury↗