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Biomedical subjects

T Philipp

Publications and source records attributed to T Philipp.

At least 19 recordsLinked to original sources
PubMed1995

[Tuberous sclerosis: typical complications of a hereditary disease and therapeutic options].

BACKGROUND: Tuberous sclerosis is an autosomal-dominant hereditary disease (incidence and prevalence 1:10,000) which is characterized by hamartomas in various organs. PATIENTS AND METHODS: We demonstrate three patients with different and partly atypical manifestations: All had facial angiofibroma. No patient was mentally retarded and epilepsy was observed only intermittently. In all cases periventricular calcifications were noted and renal angiomyolipomas were found. Two patients requested dialysis after nephrectomy. One patient suffered from severe complications of the rare pulmonary lymphangioleiomyomatosis. RESULTS: Therapy of this multiorgan disease is only symptomatic. Operations should be considered as second line treatment. In one case, successful renal transplantation is described. CONCLUSIONS: Genetic counselling is warranted in this disease with high penetrance, particularly the broad spectrum of manifestations should be taken into account.

Adult↗
PubMed1995

[Type I cryoglobulinemia].

HISTORY AND CLINICAL FINDINGS: For 2 years a 52-year-old man had repeated bouts of purpura, arthralgia and fever. He was known to have abnormal monoclonal gammaglobulins, type IgG-lambda and vasculitis when he had another bout with acute renal failure and necrotizing ulcers in the legs. TESTS: Several laboratory tests were abnormal: erythrocyte sedimentation rate (122 mm), haemoglobin level (9.1 g/dl), white cell count (32,000/microliters), platelet count (562,000/microliters), creatinine level (4.1 mg/dl) and liver enzyme activities. He also had proteinuria (4.5 g daily) and nephritic urinary sediments. The immunoglobulin was subtype IgG3, and a cryoglobulinaemia was also present. Total complement level (CH 50) was not measurable. Bone marrow aspirate revealed plasmocytoma infiltration, and renal biopsy demonstrated necrotizing arteritis, as well as granular subendothelial deposits of IgG and complement. TREATMENT AND COURSE: After three plasma separations and initiation of the first treatment cycle with a four-day infusion of vincristine, doxorubicin and dexamethasone the creatinine concentration fell to within the normal range and the necroses healed slowly. No cryoglobulin activity has been demonstrable over the past 24 months.

Acute Kidney Injury↗
PubMed1995

Recovery by splenectomy in patients with relapsed thrombotic thrombocytopenic purpura and treatment failure to plasma exchange.

Thrombotic thrombocytopenic purpura is a serious, potentially fatal disease, and conventional plasma exchange appears to be the best initial therapy. Following this approach, survival in 90% of patients is available. In patients with relapse and treatment failure to plasma exchange, splenectomy is recommended. The rationale for splenectomy and the relevant pathomechanisms involved are obscure. In the present paper two patients with TTP are reported who first responded to conventional treatment strategies but later relapsed. Resumption of previous therapy was not able to continuously maintain normal platelet levels. Thus, splenectomy was considered to be indicated. In contrast to former reports, repeated cycles of conventional plasma exchanges were performed until a transient steady state (12 hrs) of the platelet counts occurred. Then splenectomy was performed immediately and, in contrast to former reports, no reinstitution of treatment was necessary after splenectomy. In addition no postoperative complications (bleeding, neurologic impairment) have been observed. This favorable outcome might be due to the strategy of repeated conventional plasma exchange procedures. The follow-up shows now event free disease for 2 years.

Adrenal Cortex Hormones↗
PubMed1995

Molecular analysis of autoantigens in hepatitis D.

In contrast to hepatitis B virus infection, autoimmunity is common in chronic hepatitis D. In 1983, microsomal autoantibodies were described that differ from the previously described liver-kidney microsomal (LKM)-1 and LKM-2 antibodies. Therefore, these were named LKM-3. In addition, autoantibodies against basal layer cells of rat forestomach (basal cell layer antibodies (BCLA)) and thymic stellate epithelial cells (stellate epithelial cell antibodies (SECA)), as well as thymic reticular (thymic reticular antibodies) and perithymocytic cells (perithymocytic cell antibodies), were reported to be specifically associated with hepatitis D. Antinuclear antibodies against nuclear membrane lamin C were also found to be specifically associated with chronic hepatitis D. A molecular identification of the nonnuclear antigens has not been achieved apart from the observation that BCLA and SECA both recognize an antigen of 46 kDa and that these antibodies are immunologically cross-reactive. After the identification of cytochrome P450 2D6 as the major LKM-1 antigen and cytochrome P450 2C9 as the LKM-2 antigen, family 1 uridine diphosphate-glucuronosyltransferases have been identified as the molecules expressing the major LKM-3 autoepitope. Future studies will have to assess the possible pathogenetic and diagnostic relevance of these autoantibodies. However, chronic hepatitis D seems to be a good clinical model for the study of virus-induced autoimmunity in man.

Animals↗
PubMed1995

Hyperviscosity syndrome: efficacy and comparison of plasma exchange by plasma separation and cascade filtration in patients with immunocytoma of Waldenström's type.

The hyperviscosity syndrome is a common problem in patients suffering from IgM paraproteinemia. In this situation cytotoxic chemotherapy alone is insufficient and additional plasma therapy is required. Until recently, conventional plasma exchange was the only plasma therapy available. While this method has proven its efficacy, it eliminates proteins unselectively. Cascade filtration, on the other hand, has been established to remove proteins as a function of their size offering the prospect of a highly selective withdrawal of macromolecules. In the work presented, the efficacy of conventional plasma exchange and cascade filtration was evaluated performing both techniques at random in cases of hyperviscosity syndrome due to immunocytoma of Waldenström's type (n = 11/group). In these patients, conventional plasma exchange decreased plasma viscosity by 48%; cascade filtration was less effective (26%), correlating with a smaller decrease of IgM (conventional plasma exchange 42% vs cascade filtration 27%). The profile of other plasma proteins studied did not change significantly with either treatment. Furthermore, we observed no differences regarding serious side-effects. In conclusion, we could not demonstrate a superior effect of cascade filtration as compared to conventional plasma exchange in the treatment of hyperviscosity syndrome.

Aged↗
PubMed1992

Alpha- and beta-adrenoceptors in hypertension: molecular biology and pharmacological studies.

Recent years have witnessed astonishing progress in our understanding of the molecular basis of adrenoceptor structure, function and regulation and revealed an unexpected heterogeneity of adrenoceptors demonstrating the existence of at least 11 subtypes. This paper discusses the implications of these advances on studies regarding a specific role of adrenoceptors in the development of genetic hypertension. The available data indicate that among the alpha-adrenoceptor subtypes the alpha 2A-adrenoceptor is the most likely candidate for an alteration specifically linked to genetic hypertension in the animal model of the spontaneously hypertensive rat and possibly in some patients. Alterations of other alpha-adrenoceptor subtypes may be specific for some forms of genetic hypertension but are unlikely to play an important role for blood pressure regulation. Most beta-adrenoceptor alterations appear to occur secondary to blood pressure elevation independently of whether hypertension has occurred on a genetic basis or not. Moreover, the mechanisms regulating alpha- and beta-adrenoceptor responsiveness upon prolonged agonist exposure may be altered in hypertension and thereby contribute to the pathophysiology of this disease.

Adrenergic alpha-Antagonists↗
PubMed1992

On the role of renal alpha-adrenergic receptors in spontaneously hypertensive rats.

We tested the hypothesis that a genetically determined increase in renal alpha-adrenergic receptor density might be a pathophysiologically important factor in the spontaneously hypertensive rat model of genetic hypertension. In a first study, we compared renal alpha 1 and alpha 2-adrenergic receptor density with systolic blood pressure in 45 rats of an F2 generation of Wistar-Kyoto x spontaneously hypertensive rat hybrids but were unable to detect significant cosegregation between either receptor density or blood pressure. In a second study, we determined renal alpha 1- and alpha 2-adrenergic receptor density in Wistar-Kyoto and spontaneously hypertensive rat kidneys that were transplanted into an F1 generation of Wistar-Kyoto x spontaneously hypertensive rat hybrids. Although Wistar-Kyoto kidneys lowered blood pressure in these animals and spontaneously hypertensive rat kidneys increased blood pressure, renal alpha-adrenergic receptor densities were similar in membranes from both types of kidneys. Since rat kidney coexpresses alpha 1A- and alpha 1B-adrenergic receptors, we also investigated whether differential regulation of these two subtypes might conceal ongoing alterations. The alpha 1A/alpha 1B-adrenergic receptor ratio, however, was similar in Wistar-Kyoto rats, spontaneously hypertensive rats, and F1 rats transplanted with a kidney from either strain. Taken together these data do not support the hypothesis that genetically determined alterations of renal alpha-adrenergic receptor numbers play an important role in the development of elevated blood pressure in the spontaneously hypertensive rat.

Animals↗
PubMed1992

Lack of oral kallikrein in lowering systemic blood pressure in primary hypertension.

Primary hypertension is associated with a lack in renal kallikrein activity which might be one of the reasons for the blood pressure elevation. Some smaller and partially uncontrolled studies suggested that an oral substitution of glandular kallikrein lowers blood pressure by a kinin-mediated vasodilation and increased natriuresis. To test this hypothesis we treated in two studies over 100 patients with untreated mild to moderate primary hypertension (WHO I-II) for 5 resp. 12 weeks in a double blind randomized and placebo controlled manner with 1800 U glandular kallikrein orally. Blood pressure measurements were performed according to the two study designs after 3 and 5 resp. 8 and 12 weeks of treatment sphymomanometrically in the day time course. No significant changes in blood pressure by kallikrein treatment could be observed at any time. Neither renal kallikrein excretion, renin and ACE-activity nor blood glucose concentration in diabetics or non-diabetics was changed. Thus, we could undoubtedly demonstrate that oral applied glandular kallikrein has no effect on primary hypertension.

Administration, Oral↗
PubMed1991

[Effect of erythropoietin therapy on alpha receptor density in chronic dialysis patients].

The effect of a six months therapy with human recombinant erythropoietin (rHu-EPO) on blood pressure and on several parameters of sympathetic nervous activity was studied in chronic haemodialysis patients in a controlled and randomized trial in order to gain further insight into the mechanism of rHu-EPO-induced blood pressure elevation. Treatment was started at a dose of 3 X 80 IE/kg/week in eleven patients aiming to increase the initial hemoglobin concentration (7.0 +/- 0.3 [SEM] g%) to 10.0 g% by dose adjustments, while another untreated eleven patients served as a control group. Diastolic arterial pressure measured before and after haemodialysis increased on rHu-EPO treatment by 7 and 8 mm Hg respectively (p less than 0.05). Plasma noradrenaline concentration was increased (p less than 0.05) after the six months treatment period in the presence of unchanged dry weights. Conversely platelet alpha 2-adrenoceptor density (3H-yohimbine binding) and the fraction of high affinity binding sites for alpha 2-agonists (3H-UK 14.304) decreased (p less than 0.01) along with a decrease in reactivity to exogenous noradrenaline (p less than 0.05). None of these parameters changed in the control group compared to pretreatment values. The results obtained demonstrate that increased plasma noradrenaline concentrations may participate in rHu-EPO induced blood pressure increases. The decrease in platelet alpha 2-adrenoceptor densities and the decrease in noradrenaline reactivity in the presence of increased plasma noradrenaline concentrations suggest an intact regulation of alpha 2-adrenoceptors in chronic haemodialysis patients on chronic rHu-EPO therapy.

Blood Platelets↗
PubMed1991

Does treatment with beta-adrenoceptor antagonists in vivo alter human adenylate cyclase responsiveness in vitro?

1. Treatment with beta-adrenoceptor antagonists in vivo can alter adenylate cyclase responsiveness in the human heart. We have determined the effects of treatment with four different beta-adrenoceptor antagonists in vivo on the responsiveness of lymphocyte and platelet adenylate cyclase in vitro in healthy volunteers. 2. Propranolol (non-selective, 4 x 40 mg day), bisoprolol (beta 1-selective, 1 x 10 mg day), and ICI 118.551 (beta 2-selective, 3 x 25 mg day) were tested as drugs without and pindolol (non-selective, 2 x 5 mg day) as a drug with intrinsic sympathomimetic activity. Adenylate cyclase stimulation by GTP, prostaglandin E1 and forskolin was determined before, after a 7 day treatment period and 7 days after drug withdrawal. 3. Neither treatment with or withdrawal of any of the beta-adrenoceptor antagonists altered adenylate cyclase responsiveness. 4. We conclude that adenylate cyclase responsiveness in circulating blood cells underlies different regulatory mechanisms than that in solid tissues such as the human heart. Our data suggest that circulating blood cells do not always reflect alterations in solid tissues.

Adenylyl Cyclases↗
PubMed1991

Influence of the calcium antagonist nitrendipine on the hepatotoxic effect of cyclosporine A.

Calcium antagonists have a protective effect on different forms of nephrotoxicity due to cyclosporine A (CsA). The objective of the present study was to examine the influence of a calcium antagonist on the liver function in CsA-treated patients after kidney transplants. Different quantitative liver function tests were performed in six patients before and 3 months after administration of the calcium antagonist nitrendipine. Indocyanine green clearance (ICG-Cl) as a marker for hepatic blood flow and excretion showed a significant increase under nitrendipine. In addition, there was an improvement of the galactose elimination capacity. Although nitrendipine and lidocaine are both metabolized by the cytochrome P system, there was no reduction in lidocaine clearance. These results suggest an improvement of liver function under nitrendipine. Whether these findings alone are the expression of an improved liver blood flow or whether there is an additional hepatoprotective characteristic of the calcium antagonist nitrendipine cannot be determined.

Cyclosporine↗
PubMed1991

Hydrochlorothiazide and verapamil in the treatment of hypertension. The Verapamil Versus Diuretic (VERDI) Trial Research Group.

The efficacy and tolerability of hydrochlorothiazide, sustained-release verapamil, and their combination was compared in patients with mild to moderate hypertension. The design was a multicenter, randomized, double-blind clinical trial with a single-blind placebo baseline period of 2 weeks. Three hundred sixty-nine patients with a diastolic blood pressure of 95-120 mm Hg were included. Treatment consisted of 12.5 mg of hydrochlorothiazide once daily, then 25 mg once daily, and finally 25 mg twice daily; the other group received verapamil at a dose of 120 mg once daily, then 240 mg once daily, and finally 240 mg twice daily. Patients not achieving target blood pressure (less than 90 mm Hg diastolic) were given the combination of hydrochlorothiazide and verapamil, that is, 25 and 240 mg once daily and twice daily. During all time points during the study patients receiving verapamil achieved target blood pressure more often than patients receiving hydrochlorothiazide (after 8 weeks, 57.7 and 42.7%; after 24 weeks, 46.8 and 26.4%; and after 48 weeks, 44.8 and 24.7%, respectively). Adding verapamil to hydrochlorothiazide was more effective in lowering blood pressure than adding hydrochlorothiazide to verapamil. The number of treatment withdrawals was essentially the same with the two drugs. Therefore, in the doses currently used in antihypertensive treatment, verapamil was more effective than hydrochlorothiazide as a single agent and in combination in mild to moderate hypertension.

Adult↗