Kidney biopsy in patients with glomerulonephritis: is the earlier the better?

BACKGROUND: Interventional diagnostic procedures are established for several diseases in medicine. Despite the KDOQI guideline recommendation for histological diagnosis of kidney disease to enable risk stratification, its optimal time point has not been evaluated. We have therefore analyzed whether histological diagnosis of glomerulonephritis (GN) at an early stage of chronic kidney disease (CKD) is associated with different outcome compared to diagnosis at a more advanced stage. METHODS: A cohort of 424 consecutive patients with histological diagnosis of GN were included in a retrospective data analysis. Kidney function was assessed by glomerular filtration rate (GFR) estimation at the time point of kidney biopsy and after consecutive immunosuppressive therapy. Censored events were death, initiation of dialysis or kidney transplantation, or progression of disease, defined as deterioration of CKD stage ≥ 1 from kidney biopsy to last available kidney function measurement. RESULTS: Occurrence of death, dialysis/transplantation or progression of disease were associated with GFR and CKD stage at the time of kidney biopsy (p < 0.001 for all). Patients with CKD stage 1 and 2 at kidney biopsy had fewer endpoints compared to patients with a GFR of <60 ml/min (p < 0.001). CONCLUSION: Kidney function at the time point of histological GN diagnosis is associated with clinical outcome, likely due to early initiation of specific drug treatment. This suggests that selection of therapy yields greatest benefit before renal function is impaired in GN.

CT-guided transforaminal epidural injections with local anesthetic, steroid, and tramadol for the treatment of persistent lumbar radicular pain.

BACKGROUND: A substantial number of patients with persistent lumbar radicular pain are treated with a multimodal spectrum of conservative therapies without lasting effect. The duration of pain is certainly a risk factor for chronification. There is evidence that guided periradicular infiltrations are a valid option in the treatment of radiculopathies. Usually a combination of local anesthetic and/or corticosteroid is injected. Tramadol is being used for perioperative analgesia and has been shown to provide effective, long-lasting pain relief after epidural administration. OBJECTIVE: The aim of this pilot study was to evaluate the efficacy of serial CT-guided transforaminal nerve root infiltrations with a supplement of tramadol for patients with persistent, radicular pain. STUDY DESIGN: Interventional cohort study. SETTING: Outpatient department for interdisciplinary pain medicine. METHODS: 37 patients who had radicular leg pain for over 9 weeks received up to 3 CT-guided transforaminal nerve root infiltrations at intervals of 2 weeks as long as their level of pain was over 3 on a numerical rating scale from 0 to 10. 50 mg of Tramadol were added to a combination of local anesthetic (Ropivacain, 2 mg) and corticosteroid (Triamcinolon, 40 mg). Evaluations were carried out 24 hours after the Infiltration as well as 2 weeks, 3 and 6 months after the treatment series. The intensity of their radicular pain was measured by a numerical rating scale (NRS). Pain reduction of at least 50% was defined as successful outcome. RESULTS: In total, 65 infiltrations were carried out with pain relief in more than 90% of the patients within 24 hours and an average pain reduction of 64%. Six months post-injection 23 of 34 patients available for follow-up (67.6%) had a successful pain reduction of 84% on average. No adverse effects ascribable to the use of tramadol were noted. LIMITATIONS: Due to the lack of a control group we cannot make any statement if tramadol improves short-term pain reduction. CONCLUSION: Fast and lasting pain relief is the key to optimize rehabilitation for patients with radicular pain. There is a physiological rationale that the opioid receptors at the spinal level could be used to optimize the analgetic effect of guided periradicular injections. In our case series, serial CT-guided selective nerve root infiltrations with the supplement of tramadol were found to be highly effective in the treatment of persistant radiculopathies. Randomized controlled trials will be necessary to clarify the possible benefit of the supplement of an opioid.

Exercise training lowers plasma visfatin concentrations in patients with type 1 diabetes.

CONTEXT: Exercise training exerts beneficial effects on metabolic and vascular risk factors in patients with type 1 diabetes mellitus (T1DM). It is unknown whether training also influences concentrations of visfatin, a novel insulin-mimetic adipocytokine. OBJECTIVES: In this study, we have investigated whether plasma visfatin concentrations are altered by training in patients with T1DM. DESIGN AND PATIENTS: Fasting plasma visfatin concentrations and metabolic parameters were measured in 18 patients with T1DM who participated in a supervised aerobic exercise program for 4 months. Three subjects discontinued training prematurely after 2 months. Samples were obtained before and during training and 8 months after the end of regular exercise. Fourteen healthy young subjects served as controls. RESULTS: At baseline, patients with T1DM had higher visfatin concentrations than controls (64.1 +/- 12.0 vs. 1.3 +/- 0.0 ng/ml, P < 0.01). Exercise reduced visfatin after 2 and 4 months to 27.8 +/- 2.6 (n = 18) and 17.5 +/- 3.4 ng/ml (n = 15), respectively (P < 0.001 for n = 15 subjects who participated in all visits, ANOVA). This effect was maintained 8 months after cessation of training, with visfatin concentrations of 19.7 +/- 5.0 ng/ml (n = 15). Metabolic parameters were not affected by the training program. CONCLUSION: Elevated visfatin concentrations in patients with T1DM can be lowered by regular physical exercise. It is unknown whether glucose tolerance is affected by changes in visfatin concentrations.

Aerobic capacity, muscle strength and health-related quality of life before and after orthotopic liver transplantation: preliminary data of an Austrian transplantation centre.

OBJECTIVE: Patients before orthotopic liver transplantation usually show a reduced physical performance status, which impacts on their daily life and social participation. This pilot study aimed to evaluate endurance capacity, muscle strength, and quality of life before and after orthotopic liver transplantation in patients in an Austrian transplantation centre. SUBJECTS: Fifteen patients (male/female = 10:5) were included in the pilot study. METHODS: Exercise testing, strength testing of knee extensor muscles and of handgrip, and quality of life (SF-36 health survey) were assessed before and after orthotopic liver transplantation (after 1-2 months). RESULTS: The oxygen uptake at the anaerobic threshold (VO2AT) and isokinetic strength testing of quadriceps femoris muscle did not change significantly from baseline, before transplantation to follow-up after orthotopic liver transplantation. Before orthotopic liver transplantation, quality of life was hampered concerning functional status, emotional role, vitality, and general health perception. Significant improvements of social functioning (p=0.032), vitality (p=0.006), mental health (p=0.004) and general health perception (p=0.002) could be found for this study population after orthotopic liver transplantation. CONCLUSION: The results of this pilot study including a population of an Austrian transplantation centre indicate deficits of physical performance as well as reduced quality of life in patients before and after orthotopic liver transplantation.

Cross-cultural adaptation of the JPF-Questionnaire for German-speaking patients with functional temporomandibular joint disorders.

OBJECTIVES: Clinical research related to the management of the syndrome of temporomandibular joint pain and dysfunction would be facilitated enormously between researchers in different locations around the world if a small number of patient-oriented questionnaires were to achieve wide acceptance. It would make comparison of therapeutic results possible. For this reason, a cross-cultural version of the Jaw Pain and Function (JPF)-Questionnaire was developed and validated for use in German-speaking patients with functional temporomandibular disorders. MATERIAL AND METHODS: The scale was translated from the English into the German language and translated back into English again, pretested and reviewed by a committee. The German version of the JPF-Questionnaire was tested on 137 patients with temporomandibular disorders. Reliability and concurrent construct validity were assessed using Pearson's correlation coefficients. RESULTS: The concurrent validity was assessed by evaluating the relation of the questionnaire's summary score (the internal criterion) to data on maximum interincisal distance (the external criterion). Spearman's and correlation coefficients were statistically significant for the comparison of the summary score with maximal mouth opening (r=-0.213; p=0.036). Test-retest reliability for the JPF-Questionnaire was also assessed by Spearman's correlation coefficients: at first admission at the clinic (time a, mean=20.23+/-16.42, median=16), then at the time of administration 1 day later at home (time b, mean=17.98+/-16.29, median=13), and 7 days later at home (time c, mean=17.90+/-15.77, median=13). They were r=0.91 (p=0.0001) for the initial administration with the repetition 1 day later, r=0.90 (p=0.0001) for the initial administration with the repetition 1 week later, and r=0.93 (p=0.0001) for the correlation between the two repetitions. Test - retest reliability measured by mean-against-difference graphs was not satisfactory for time (a) versus time (b) and time (a) versus time (c) but there was a good test-retest reliability for time (b) versus time (c). CONCLUSION: The use of this instrument can be recommended in future clinical trials, as the German version of the JPF-Questionnaire seems to be valid and--under the same test-retest conditions--reliable for the assessment of temporomandibular joint disorders.

Regular physical exercise normalizes elevated asymmetrical dimethylarginine concentrations in patients with type 1 diabetes mellitus.

INTRODUCTION: Levels of the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) are elevated in patients with type 1 diabetes mellitus (DM1) and may contribute to vascular complications. In this study we tested the hypothesis that elevated ADMA in patients with DM1 can be reduced by regular physical exercise. METHODS: Plasma samples for analysis of L-arginine, ADMA, symmetrical dimethylarginine (SDMA) and metabolic parameters were obtained from 11 patients with DM1 who participated in a supervised aerobic exercise program for four months. Samples were collected before the training began, at two and four months after initiation, and eight months after cessation of regular training. Fifteen age- and sex-matched healthy persons who did not exercise regularly were examined once as controls and did not participate in the training program. RESULTS: The patients with DM1 had higher ADMA levels than the controls before the training program began (0.54 +/- 0.02 vs. 0.44 +/- 0.03 micromol/l; P < 0.05). After two and four months of exercise, ADMA concentrations in the patients decreased to those seen in healthy persons (0.42 +/- 0.02 and 0.43 +/- 0.03 micromol/l; P < 0.001 and P < 0.05 compared with ADMA levels before training began). Eight months after cessation of the exercise program, ADMA levels in the patients reverted to those observed before the start of training. The L-arginine-to-ADMA ratio increased slightly after two months; L-arginine, symmetrical dimethylarginine, blood lipids and HbA1c were not affected by the training program. CONCLUSIONS: Elevated ADMA levels in patients with DM1, who have a high risk for developing cardiovascular disease, can be lowered to those of healthy persons by regular physical exercise. This favorable effect on ADMA is not sustained when training is discontinued.

Cross-cultural adaption of the Manniche questionnaire for German-speaking low back pain patients.

OBJECTIVE: To develop and validate a cross-cultural version of the Manniche Low Back Pain Rating Scale (MRS) for use in German-speaking low back pain patients. BACKGROUND: Clinical intervention research in back pain would be enormously facilitated if a small number of relevant, patient-centred questionnaires became internationally used. MRS seems to be particularly suitable for cross-cultural adaptation due to its coverage of multidimensional back pain-specific health domains. METHODS: MRS was translated and back-translated, pretested and reviewed by a committee. The German version was tested in 126 patients with low back pain from all countries of German-speaking Europe. Reliability (subsample n = 20), dimensionality and construct validity was assessed. Single-dimensionality, higher correlations of MRS with the physical scales compared with the mental scales of the MOS SF-36, a moderate to good correlation with the Roland Morris Questionnaire and a low correlation with the Finger Floor Distance were hypothesized. RESULTS: Spearman's Rho for test-retest reliability was 0.98 (p < 0.001); Cronbach's alpha 0.95. Factor analysis revealed only 1 factor with an Eigenvalue >1 [3.25]. MRS was strongly correlated with the Roland Morris Questionnaire (r = 0.91), and slightly correlated with the Finger Floor Distance (r = 0.23). Correlations of MRS with domains of the SF-36 "Physical Functioning", "Role Physical" and "Bodily Pain" were higher (r -0.66 to -0.72) than with "Role Emotional", "Mental Health" and "Social Functioning" (r -0.34 to -0.61). CONCLUSION: The German version of the MRS seems to be reliable, uni-dimensional and construct valid for the assessment of functional status in German-speaking low back pain patients.

Exercise training improves vascular endothelial function in patients with type 1 diabetes.

OBJECTIVE-Impaired endothelial function of resistance and conduit arteries can be detected in patients with type 1 diabetes. We studied whether a persistent improvement of endothelial function can be achieved by regular physical training. RESEARCH DESIGN AND METHODS-The study included 26 patients with type 1 diabetes of 20 +/- 10 years' duration and no overt angiopathy; 18 patients (42 +/- 10 years old) participated in a bicycle exercise training program, and 8 patients with type 1 diabetes (33 +/- 11 years old) served as control subjects. Vascular function of conduit arteries was assessed by flow-mediated and endothelium-independent dilation of the brachial artery and of resistance vessels by the response of ocular fundus pulsation amplitudes to intravenous N(G)-monomethyl-L-arginine (L-NMMA) at baseline, after 2 and 4 months of training, and 8 months after cessation of regular exercise. RESULTS-Training increased peak oxygen uptake (VO(2max)) by 13% after 2 months and by 27% after 4 months (P = 0.04). Flow-mediated dilation (FMD) of the brachial artery increased from 6.5 +/- 1.1 to 9.8 +/- 1.1% (P = 0.04) by training. L-NMMA administration decreased fundus pulsation amplitude (FPA) by 9.1 +/- 0.9% before training and by 13.4 +/- 1.5% after 4 months of training (P = 0.02). VO(2max), FMD, and FPA were unchanged in the control group. Vascular effects from training were abrogated 8 months after cessation of exercise. CONCLUSIONS-Our study demonstrates that aerobic exercise training can improve endothelial function in different vascular beds in patients with long-standing type 1 diabetes, who are at considerable risk for diabetic angiopathy. However, the beneficial effect on vascular function is not maintained in the absence of exercise.

Hypertrophic osteoarthropathy caused by PGE1 in a patient with congestive heart failure during cardiac rehabilitation.

Continuous chronic drug infusion with PGE1 via a portable pump and neuromuscular electrical stimulation (NMES) help to improve the quality of life in patients with severe chronic heart failure waiting for a donor heart, as both treatments can be performed at home. We report a 56-year-old woman suffering from severe chronic heart failure, who was referred for a cardiac rehabilitation program because of progressive muscle weakness and weight loss. Due to her underlying heart disease she was unable to perform voluntary exercise. NMES of both knee extensor muscles was started. Under simultaneous chronic drug infusion with PGE1 via a portable pump the patient developed clinical signs of hypertrophic osteoarthropathy, which prevented her from continuing the rehabilitation program. X-ray examinations and bone scans concurred with the diagnosis of secondary hypertrophic osteoarthropathy. After the PGE1 dose had been reduced, the clinical signs of the osteoarthropathy resolved and the patient was able to continue the rehabilitation program with no difficulty. This case report underlines the importance of being aware of the potential side effects of modern cardiac drugs in the complex treatment of patients waiting for a donor heart.

Regular physical exercise improves endothelial function in heart transplant recipients.

BACKGROUND: Impaired endothelial function is detectable in heart transplant (HTX) recipients and regarded as risk factor for coronary artery disease. We have studied whether endothelial function can be improved in HTX patients participating in a regular physical training program as demonstrated in patients with chronic heart failure, hypertension and coronary artery disease. METHODS: Male HTX patients and healthy, age-matched controls were studied. Seven HTX patients (age: 60 +/- 6 yr; 6 +/- 2 yr of HTX) participated in an outpatient training program, six HTX patients (age: 63 +/- 8 yr; 7 +/- 1 yr of HTX) maintained a sedentary lifestyle without regular physical exercise since transplantation. A healthy control group comprised six subjects (age: 62 +/- 6 yr). Vascular function was assessed by flow-mediated dilation of the brachial artery (FMD). Systemic haemodynamic responses to intravenous infusion of the endothelium independent vasodilator sodium nitroprusside (SNP) and to NG-monomethyl-L-arginine (L-NMMA), an inhibitor of constitutive nitric oxide synthase, were also measured. RESULTS: Resting heart rate was significantly lower (p < 0.05) in healthy controls (66 +/- 13) than in the HTX training group (83 +/- 11) and in non-training HTX patients (91 +/- 9), baseline blood pressure also tended to be lower in healthy subjects and in the training HTX patients. FMD was significantly higher (p < 0.05) in the control group (8.4 +/- 2.2%) and in the training group (7.1 +/- 2.4%), compared with non-training HTX patients (1.4 +/- 0.8%). The response of systolic blood pressure (p = 0.08) and heart rate (p < 0.05) to L-NMMA was reduced in sedentary HTX patients compared with healthy controls and heart rate response to SNP was also impaired in sedentary HTX patients. DISCUSSION: Regular aerobic physical training restores vascular function in HTX patients, who are at considerable risk for developing vascular complications. This effect is demonstrable in conduit and systemic resistance arteries.