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T Philipp

Publications and source records attributed to T Philipp.

At least 91 records · Page 5Linked to original sources
PubMed1999

Disodium cromoglycate does not prevent terbutaline-induced desensitization of beta 2-adrenoceptor-mediated cardiovascular in vivo functions in human volunteers.

In humans, prolonged administration of the beta 2-adrenoceptor agonist terbutaline leads to a desensitization of beta 2-adrenoceptor-mediated cardiovascular responses, which can be blunted by concomitant administration of the antianaphylactic drug ketotifen. This study investigated the effect of disodium cromoglycate, another antiallergic drug, on terbutaline-induced desensitization of beta-adrenoceptor-mediated cardiovascular and noncardiovascular responses. In a double-blind, placebo-controlled, randomized design, nine healthy male volunteers received disodium cromoglycate (4 x 200 mg/day, p.o.) or placebo for 3 weeks with terbutaline (3 x 5 mg/day, p.o.) administered concomitantly during the last 2 weeks. beta 2-Adrenoceptor cardiovascular function was assessed by the increase in heart rate and reduction of diastolic blood pressure induced by an incremental intravenous infusion of the unselective beta-adrenoceptor agonist isoprenaline; beta 1-adrenoceptor cardiovascular function was assessed by exercise-induced tachycardia. Tremulousness was monitored as a beta 2-adrenoceptor-mediated noncardiovascular effect. After 2 weeks' administration of terbutaline, there was a marked and significant (p < 0.001) attenuation of isoprenaline-induced tachycardia (mean percentage attenuation, 53.3%) and of the isoprenaline-induced decrease in diastolic blood pressure (mean percentage attenuation, 55.6%). Exercise-induced tachycardia also was significantly (p < 0.001) blunted, but the magnitude of this attenuation was only very small (mean attenuation, 5.6%). Disodium cromoglycate affected neither the rightward shift of beta 2-adrenoceptor-mediated responses nor the small rightward shift in beta 1-adrenoceptor-mediated exercise tachycardia after 2 weeks' administration of terbutaline. Tremulousness observed during the first few days of terbutaline administration disappeared after 4 to 8 days, indicating development of desensitization of beta 2-adrenoceptor-mediated noncardiovascular responses. This was not prevented by disodium cromoglycate. These results confirm that long-term beta 2-adrenoceptor agonist therapy leads to a desensitization of beta 2-adrenoceptor-mediated cardiovascular and noncardiovascular effects in humans in vivo. However, unlike ketotifen, cromolyn sodium is not able to attenuate this desensitization.

Adrenergic beta-2 Receptor Agonists↗
PubMed1999

Wrist measurement of blood pressure: some critical remarks to oscillometry.

UNLABELLED: Oscillometric blood pressure measuring devices worn at the wrist are preferred by a growing part of hypertensive patients for self-measurement because of their compactness and ease of use. However, little is known about the accuracy of such instruments. The accuracy of such devices was evaluated by measuring the blood pressure at the end of a coronary angiography procedure in 27 subjects nearly simultaneously in the aortic arch, using a Statham P23 transducer, and at the wrist, using the blood pressure watch (BPW) by NAIS-Matsushita. Four replicate comparative measurements were performed in each subject. On average, the blood pressure measured by the BPW was found to be higher: systolic +1.2+/-(SD)10.2 mm Hg, diastolic +4.1+/-7.2 mm Hg. The correlation coefficient between the two methods was 0.85 for the systolic and 0.84 for the diastolic pressure, but 39% of the systolic and 22% of the diastolic differences were outside the range of +/-1 SD. There was no correlation between systolic differences and blood pressure or patients' variables, but multiple regression analysis revealed that the diastolic blood pressure differences were negatively correlated with the aortic diastolic pressure (r = 0.89, p<0.001), indicating that the BPW is less accurate to detect lower values. CONCLUSIONS: (1) Though the average systolic and diastolic deviations between both methods and the relative correlation coefficients suggest that the BPW is to be used carefully for monitoring blood pressure, the great variability of differences and the inability of the BPW to detect lower diastolic blood pressure calls for a mandatory validation test by an approved protocol before this new device can be recommended for general use. (2) On the basis of our results for wrist oscillometry with the BPW and data reported in the literature for upper-arm oscillometric devices, we recommend to use oscillometric devices only when they were validated properly. In particular, the oscillometric measurement should be employed with caution for epidemiological studies or for investigation of population groups (e.g., children or pregnant women) that are expected to display lower diastolic pressures.

Adult↗
PubMed1999

Indirect and direct simultaneous, comparative blood pressure measurements with the Bosotron 2 device.

Testing the accuracy of the automatic blood pressure measuring device Bosotron 2, we performed simultaneous, same-arm, comparative blood pressure measurements with three instruments (A, B, and C) of the device and by auscultation in the antecubital fossa by a trained observer in 24 volunteers each. The volunteers were evenly matched for age, sex, and blood pressure level. The mean systolic differences and their standard deviations (24 subjects each, n = 288 single measurements) were -1.32+/-3.8 mm Hg for instrument A, -0.99+/-3.9 mm Hg for instrument B, and -1.12+/-5.0 mm Hg for instrument C. The corresponding values for the diastolic differences were -2.71+/-4.4, -3.46+/-4.3, and -2.72+/-3.9 mm Hg, respectively. Combining the results for the three instruments, the comparison yielded a good accuracy (mean difference) and sufficient repeatability of the differences (standard deviation) for the systolic and diastolic blood pressures (systolic -1.14+/-4.3 mm Hg; diastolic -2.96+/-4.2 mm Hg). In addition to the British Hypertension Society protocol, in 33 patients with coronary artery disease the measurements using the three Bosotron 2 devices were compared with measurements within the aortic arch. The mean systolic/diastolic differences (+/-SD) were +1.45+/-4.3 and +7. 27+/-4.7 mm Hg for instrument A, +4.70+/-12.8 and +1.73+/-7.4 mm Hg for instrument B, and -3.74+/-8.0 and +5.61+/-2.6 mm Hg for instrument C. Combining the results of the three instruments, the blood pressure was determined to be only slightly higher (systolic +1.74+/-9.6 mm Hg; diastolic +4.87+/-5.6 mm Hg) by the Bosotron 2 R device as compared with the aortic arch pressure. The Bosotron 2 R device seems to be suitable for clinical use and for monitoring blood pressure during clinical-pharmacological studies.

Adolescent↗
PubMed1999

[Quality of life following transplantation. The impact ofa new immunosuppressive substance].

The improvement of quality of life is one of the major goals in the treatment of patients after renal transplantation. While immunosuppressive therapy is present in almost all of these patients, little is known about the effects of newer immunosuppressive agents. We therefore investigated the impact of tacrolimus on life quality. From November 1997 to January 1998, a questionnaire was handed out which focussed on physical and mental problems as well as sexual capacity and the attitudes towards graft, donor and transplant related side effects. 50 kidney graft recipients treated with tacrolimus were matched to 50 patients with a cyclosporine-based immunosuppression (= controls). Values are given as mean +/- standard deviation. Tacrolimus treated patients had a mean creatinine of 1.8 +/- 0.8 mg/dl, as compared to 1.6 +/- 0.7 mg/dl in controls. The overall status of health was assessed to be good in 82% of the tacrolimus group (controls: 80%). 38% were working full-time (controls: 20%). Only 14% of patients described their physical condition as poor (16% in controls). Sexual function was good in 66% (controls: 74%) and poor in 10% (controls: 12%). Mental function was assessed to be good in 92% (controls: 82%). The majority of patients felt comfortable with their physical, sexual and mental capabilities. This was independent from the immunosuppressive regimen.

Cyclosporine↗
PubMed1999

Adrenoceptors mediating the cardiovascular and metabolic effects of alpha-methylnoradrenaline in humans.

alpha-Methylnoradrenaline is a widely used tool to study alpha2-adrenoceptor function, but its selectivity for this receptor has not been validated in humans in vivo. To characterize the adrenoceptors mediating cardiovascular and metabolic effects of alpha-methylnoradrenaline in humans, we have performed graded i.v. infusions of alpha-methylnoradrenaline in a randomized, placebo-controlled crossover study in six young, healthy males in the absence and presence of the beta-adrenoceptor antagonist propranolol, the alpha1-adrenoceptor antagonist doxazosin, and the alpha2-adrenoceptor antagonist yohimbine. alpha-Methylnoradrenaline dose-dependently increased heart rate, systolic blood pressure, cardiac output, blood glucose, serum insulin, free fatty acids, and gastrin, shortened the duration of heart rate-corrected electromechanical systole, and decreased diastolic blood pressure, total peripheral resistance, and plasma noradrenaline. Propranolol completely reversed the rise in heart rate and cardiac output, the fall in peripheral resistance, the shortening of electromechanical systole, and the rise in insulin; it blunted the increase in free fatty acids and gastrin. Yohimbine did not significantly influence most parameters but significantly potentiated the rise in insulin, blunted the increase in glucose, and prevented the fall in noradrenaline. Doxazosin was largely without effect on any of these parameters. We conclude that i.v. administered alpha-methylnoradrenaline primarily acts on beta-adrenoceptors in the human cardiovascular and metabolic system, but an alpha2-adrenergic component of the response is detectable for changes of plasma noradrenaline, blood glucose, and serum insulin. Whereas alpha-methylnoradrenaline is selective for alpha2- over alpha1-adrenoceptors, beta-adrenoceptor blockade is required to unmask alpha-adrenoceptor-mediated vasoconstriction.

Adult↗
PubMed1999

Two by two hour creatinine clearance--repeatable and valid.

AIM: The purpose of this study was to determine the repeatability and validity of 2 x 2 hour creatinine clearance, and the validity of creatinine clearances estimated by equations. PATIENTS AND METHODS: In 30 patients two 2 x 2 h and two 24-h creatinine clearances were performed on consecutive days. In addition, creatinine clearances estimated by 4 different equations were calculated. Two by two hour creatinine clearance provided a measurement of GFR as valid as 24-h creatinine clearance. RESULTS: We found, that 2 x 2 h creatinine clearance was well repeatable with a mean difference between 2 repeated measurements of 0.8 ml/min and low coefficients of repeatability of 14.5 ml/min. The validity of 2 x 2 h creatinine clearance, assessed by the mean difference between 2 x 2 and 24-h creatinine clearances, was 1.2 ml/min with tight 95% limits of agreement with a range from -8.1 to 10.5 ml/min. This high degree of repeatability and validity was present over the entire range of renal function (6-141 ml/min). As 2 x 2 h creatinine clearance is more simple and rapid than 24-h creatinine clearance, results are obtained on the same day and easy, but repeatable and valid day-to-day monitoring of renal function is possible. In addition, the two times two hour clearances allow for quality control. In contrast, estimated creatinine clearances show only poor validity. CONCLUSION: Because of the high degree of repeatability and validity, 2 x 2 h creatinine clearance may replace 24-h creatinine clearance as the standard method to determine renal function in clinical practice.

Adolescent↗
PubMed1999

Continuous venovenous hemodialysis treatment in critically ill patients after liver transplantation.

BACKGROUND: Acute renal failure (ARF) in critically ill patients is associated with a high mortality rate. Continuous renal replacement therapy (CRRT) is now widely used for the treatment of ARF in these critically ill patients. We retrospectively analyzed the role of CRRT as a prognostic parameter in patients receiving a cadaveric liver graft in 1998. METHODS: We reviewed the patient records of all adult recipients of a cadaveric liver graft (N = 54) in 1998 and compared those who underwent CRRT treatment (N = 19) to those without CRRT treatment (N = 35). RESULTS: Mortality was high in the continuous venovenous hemodialysis (CVVHD) group (58%). At the time of transplantation, creatinine (1.7+/-0.4 vs. 1.0+/-0.1 mg/dl), blood urea nitrogen (40+/-13 vs. 22+/-3 mg/dl), aspartate aminotransferase (ASAT; 585+/-420 vs. 242+/-97 U/liter), and bilirubin (11.6+/-4.1 vs. 6.5+/-1.9 mg/dl) were higher in the CVVHD group than in controls, whereas hemoglobin (10.3+/-0.6 vs. 10.8+/-0.4 g/dl), white blood cells (6.3+/-0.6 vs. 7.0+/-0.8/nl), and thrombocytes (110+/-18 vs. 90+/-10/nl) were similar. After transplantation, liver graft function was impaired in the CVVHD group as compared with controls. CONCLUSIONS: The necessity for CRRT in patients after liver transplantation correlates with a high risk of death. Thus, more efforts have to be made to prevent renal failure in patients after liver transplantation.

Acute Kidney Injury↗
PubMed1998

Distinct prevalence of antibodies to the E2 protein of GB virus C/hepatitis G virus in different parts of the world.

Since the identification of the new human virus, GB virus C (GBV-C)/hepatitis G-virus (HGV), in 1995/1996, reverse transcription polymerase chain reaction remained the sole available diagnostic tool for GBV-C/HGV infection. Recently, a serologic test based on the detection of antibodies to the putative envelope protein 2 (anti-E2) has been introduced. We used this assay for a seroepidemiological survey including 3,314 healthy individuals from different parts of the world, 123 patients from Germany who were suspected to have an increased risk of acquiring GBV-C/HGV infection, 128 multiple organ donors, and 90 GBV-C/HGV RNA positive persons. In European countries, anti-E2 seropositivity ranged from 10.9% (Germany) to 15.3% (Austria). In South Africa (20.3%) and Brazil (19.5%), even higher anti-E2 prevalence rates were recorded. In Asian countries like Bhutan (3.9%), Malaysia (6.3%), and the Philippines (2.7%), anti-E2 positivity was significantly lower. GBV-C/HGV anti-E2 prevalence in potential "risk groups," i.e., patients on hemodialysis and renal transplant recipients, did not vary significantly from anti-E2 seroprevalence in German blood donors. Anti-E2 and GBV-C/HGV RNA were found to be mutually exclusive, confirming the notion that anti-E2 has to be considered as a marker of past infection.

Antibodies, Viral↗
PubMed1998

Implications of End-Stage Renal Disease on Cardiac Surgery.

End-stage renal failure requiring dialysis is considered a significant risk factor in cardiac surgery. To assess the risk we performed a retrospective analysis of 17 patients with end-stage renal failure who underwent open heart surgery during 1994 and 1995. Pre-, peri-, and postoperatively we evaluated the following factors: renal failure etiology, risk factors, concurrent diseases, previous heart diseases, complications, mortality, and long-term outcome. All patients were dialyzed on the day before surgery. Intraoperative hemofiltration was performed in each patient. The first postoperative hemodialysis was performed on the second postoperative day or earlier for hyperkalemia or pulmonary edema. Postoperative complications occurred in seven patients: three patients expired postoperatively of noncardiac and nonrenal causes and four died during follow-up. With an average follow-up of 16.5 months (range 7-30 months) NYHA class had improved by an average of 1.7 in the 10 patients who were alive and their quality of life was acceptable. Because of these acceptable short- and long-term results and relatively low operative risk, we support an approach of prompt diagnostic work-up and surgical intervention when necessary.

Journal Article↗
PubMed1998

Enhanced G protein activation in IDDM patients with diabetic nephropathy.

Genetic susceptibility contributes significantly to the risk of developing nephropathy in insulin-dependent diabetes mellitus (IDDM). The cellular substrate for this has remained enigmatic. We investigated whether afflicted IDDM patients display an enhanced activation of pertussis toxin (PTX)-sensitive G proteins, a phenomenon which has been demonstrated in patients with essential hypertension. We established immortalised B lymphoblast cell lines from 10 IDDM patients without nephropathy (DC) and 15 IDDM patients with nephropathy (DN). Nephropathy was defined as a persistent albumin excretion rate of more than 20 microg/min (DC 3.9 +/- 5.8, DN 562.3 +/- 539.0 microg/min, respectively). Subjects were matched with regard to age (DC 28.9 +/- 6.5, DN 35.9 +/- 9.9 years), diabetes duration (DC 19.3 +/- 6.9, DN 22.7 +/- 5.8 years) and HbA1c values (DC 8.5 +/- 1.4, DN 8.8 +/- 1.6%). Reactivity of PTX-sensitive G proteins was quantified by measuring platelet-activating factor (PAF)-induced Ca2+ mobilisation (fura 2 method) and by mastoparan-stimulated [35S]GTPgammaS binding. Expression of Galphai proteins was quantified by Western blot analysis. PAF-evoked Ca2+ increases above baseline averaged 77.0 +/- 52.5 nmol/l in DC and 150.7 +/- 61.5 nmol/l in DN (p = 0.005). PAF-evoked Ca2+ increases correlated with stimulated [35S]GTPgammaS binding (r2 = 0.42, p = 0.012). From Western blot analysis an overexpression of Galphai proteins could be excluded in DN. A consequence of the altered metabolic milieu in diabetes is the increased release of vasoactive and proliferative agonists which promote glomerular hyperfiltration, hypertrophy, enhanced matrix deposition, and, finally, glomerulosclerosis. Many of these auto- and paracrine agonists bind to G protein-coupled receptors. Therefore, their cellular effects are reinforced by the enhanced G protein reactivity and increase the propensity to nephropathy in IDDM.

Adult↗
PubMed1998

Hypertension accelerates the pace of chronic graft dysfunction in the rat.

In this study we compared the effects of hypertension on chronic rejection in a rat model of renal transplantation utilizing genetically normotensive (BBOK) and spontaneously hypertensive rats (SHR). SHR received either a BBOK (BBOK-->SHR) or an SHR (SHR-->SHR) kidney; normotensive isografts served as controls. Before transplantation, SHR recipients were treated with hydralazine (50 mg/kg per day). To prevent acute rejection, an anti-CD4 antibody (3 mg/kg per day for 3 weeks) in combination with cyclosporin A (3 mg/kg per day for 1 week) was given to all groups. Six weeks after transplantation, blood pressure was measured, and the kidneys removed for histological and immunohistological analysis. SHR-->SHR developed a significantly higher blood pressure than BBOK-->SHR. Blood pressure in BBOK-->BBOK was significantly lower than in the other two groups. The degree of glomerulosclerosis was similarly increased in allografted (BBOK-->SHR) and SHR-->SHR kidneys as compared with the BBOK-->BBOK kidneys (P < 0.05). Infiltration of ED-1+ monocyte/macrophages and OX19 pan-T-cells was most pronounced in allografts (BBOK-->SHR) and was also increased in SHR-->SHR as compared with BBOK-->BBOK. Our results indicate that hypertension accelerates the morphological and immunohistological changes characteristic of grafts undergoing chronic rejection. However, our findings support the hypothesis that alloantigen-dependent factors are of greater important.

Animals↗
PubMed1998

Clinical efficacy of a new AT1 blocker.

The main goal of the treatment of hypertension is to decrease cardiovascular morbidity and mortality. Since this has been demonstrated for betablocker and diuretics only, other antihypertensive agents should be recommended for initial single-drug therapy only if they demonstrate that their antihypertensive potency, and their tolerability is at least comparable to that of the other established drug classes. From this latter perspective AT1 blockers should become one of the most favored anti-hypertensive drugs, since it can be shown that their efficacy is comparable to all other classes of antihypertensive drugs and their tolerability is undoubtedly better. Candesartan seems to be the most efficient AT1 blocker with regard to molar potency. Moreover, it has been shown that Candesartan achieves an impressively long duration of action presumably due to its special receptor binding properties with a peak trough ratio of more than 0.9. An other advantage of this special AT1 blocker may be its dose response curve which demonstrates a continuous increase of efficacy between 2 and 16 mg daily.

Angiotensin Receptor Antagonists↗
PubMed1998

Hepatitis G virus infection in children on dialysis and after renal transplantation.

The aim of the present study was to use a combination of the reverse transcription-polymerase chain reaction and a new diagnostic test for antibodies against the viral envelope protein E2 to assess the prevalence of hepatitis G virus (GBV-C/HGV) infection in sera of Hungarian children on hemodialysis (HD) or peritoneal dialysis (CAPD), as well as in sera of renal transplant patients (RTx). The GBV-C/HGV RNA prevalence was significantly higher in the whole group of children with renal failure (18.5%) than in the control group (children with urinary tract infection, 2.5%). The difference between the GBV-C/HGV RNA prevalence in the RTx group (33.3%) and in the control group (2.5%) was significant (P = 0.007). Anti-E2, which is considered an indicator of a past GBV-C/ HGV infection, was detected in 10% (1/10) of HD patients, in 33.3% (4/12) of RTx patients, but in none of the children on CAPD. These differences were not significant. Children receiving a renal graft are at an increased risk of developing GBV-C/HGV infection, which may be attributed to the immunosuppressive drugs necessary to maintain the grafts.

Adolescent↗
PubMed1998

Do urinary tract infections trigger chronic kidney transplant rejection in man?

PURPOSE: Urinary tract infections are frequent after kidney transplantation but little is known about the impact on long-term survival. As chronic rejection is the major cause of graft loss in the long term, we retrospectively analyzed the role of urinary tract infections in this process. MATERIALS AND METHODS: We included in the study all adult patients who received kidney transplants at our unit between 1972 and 1991, which ensured followup of at least 5 years, and we focused on the relationship between urinary tract infections and the incidence of chronic rejection episodes. To analyze the influence of urinary tract infections on chronic rejection patients were separated into those in whom biopsy proved chronic rejection developed within the first 5 years after transplantation (chronic rejection group 225) and those without apparent signs of chronic rejection during that period (control group 351). The correlation between urinary tract infections per year and the incidence of chronic rejection was analyzed. RESULTS: Patients with chronic rejection had more urinary tract infections per year than controls. In the first year after transplantation both groups had the highest incidence of urinary tract infections but thereafter the rate of urinary tract infections per year declined. However, the incidence consistently remained higher in the chronic rejection group. This difference reached significance by year 3 after transplantation. Furthermore, a high rate of urinary tract infections correlated with an early onset of chronic rejection. CONCLUSIONS: Urinary tract infections are an important risk factor for the onset of chronic rejection, and early and intense treatment is critical.

Adult↗
PubMed1998

Influence of different transplantation methods on liver cell survival in spleens of rats.

Isolated hepatocytes, liver tissue suspensions, or liver tissue cylinders from biopsies were transplanted into the spleens of adult male rats. Donors were syngenic fetuses, syngenic or allogenic adult rats, or autologous material was obtained from the rat's own liver. The outcome of the different transplantation procedures was evaluated at 1 and 6 months after surgery. Additionally the influence of a 30% hepatectomy (HX) on the result of the transplantation was investigated. When fetal material was transplanted, the best results in sequence with respect to the number of viable hepatocytes within the spleens were obtained (1) after transplantation of syngenic fetal liver tissue suspensions, (2) syngenic fetal liver tissue cylinders and (3) syngenic fetal isolated hepatocytes. HX only improved the results with transplantation of syngenic fetal isolated hepatocytes. After transplantation of syngenic fetal liver tissue suspensions and isolated hepatocytes, but not after transplantation of syngenic fetal liver tissue cylinders, the number of hepatocytes was higher at 6 months than at 1 month after surgery. Concerning syngenic adult liver material, only transplantation of isolated hepatocytes lead to a remarkable and increasing number of surviving hepatocytes at both 1 and 6 months after surgery. These results were further improved by HX. With syngenic adult liver, the other transplantation methods yielded no or nearly no viable hepatocytes in the spleens. In comparison to the results after transplantation of syngenic fetal liver tissue suspensions, transplantation of syngenic adult isolated hepatocytes was less efficient, but still yielded more viable hepatocytes than the transplantation of syngenic fetal isolated hepatocytes. After transplantation of autologous liver tissue suspensions, autologous liver tissue cylinders or allogenic adult liver material only few surviving hepatocytes were observed. At 1 month after transplantation of syngenic fetal liver material, syngenic adult isolated hepatocytes or autologous liver tissue cylinders into the spleens 40-80% of the explants consisted of bile ducts independent from the transplantation method. At 6 months after surgery the bile ducts were much less and in some cases no longer visible. After transplantation of autologous liver tissue suspensions or allogenic adult liver material only very few bile ducts were seen, but anyhow in those cases only poor results were obtained. Thus, with respect to transplantation outcome and long-term liver cell survival, intrasplenic transplantation of both syngenic fetal liver tissue suspensions and syngenic adult isolated hepatocytes seem to be the most suitable methods and should be chosen for further investigations on explant morphology and function.

Animals↗