Search PubMed⌕ Search

Biomedical subjects

K Winkler

Publications and source records attributed to K Winkler.

At least 181 records · Page 10Linked to original sources
PubMed1983

Plasma-to-ascitic fluid transport rate of albumin in patients with decompensated cirrhosis. Relation to intraperitoneal albumin.

Albumin-kinetics and haemodynamic studies were performed in 20 patients with decompensated liver cirrhosis in order to improve the knowledge on genesis and perpetuation of hepatic ascites, especially with respect to determinants of intraperitoneal protein. A positive relationship was found between the plasma-to-peritoneal transport rate of albumin (index of 'lymph-imbalance') and the mass of intraperitoneal albumin (rlog = 0.82, P less than 0.001), indicating a significant role of 'lymph-imbalance' to sequestration of protein in the peritoneal cavity. Ascitic fluid albumin concentration was on the average 0.22 of that of plasma and directly correlated to the plasma concentration (rlin = 0.68, P less than 0.01). The hydrostatic pressure difference across the splanchnic microvasculature (assessed as wedged hepatic vein minus inferior vena caval pressure) was directly correlated to the effective (plasma minus ascitic fluid) oncotic pressure (rlin = 0.74, P less than 0.001) but significantly higher than that (P less than 0.005), indicating a 'non-equilibrium' in the splanchnic Starling forces. The results point to a multivariate genesis and perpetuation of cirrhotic ascites as laid down in the 'lymph-imbalance' theory of ascites formation, whereas a 'fluid equilibrium' theory seems to be too simple, especially with respect to explain protein sequestration in the peritoneal cavity.

Adult↗
PubMed1983

Heterogeneity of splanchnic vascular transit times in man.

A new method of quantifying the heterogeneity of transit times through vascular beds, free from corrections for effects of recirculation, is applied to data of splanchnic transit times in eight normal subjects and three patients with cirrhosis and end-to-side portocaval shunts, as obtained by Bradley's method. There is proportionality between the heterogeneity, expressed as standard deviation and the mean transit time in the eight normal subjects. The heterogeneity of plasma transit times is not appreciably larger than that of red blood cells, despite the larger volume of distribution of plasma. This may suggest that the large vessels contribute substantially to the dispersions of vascular transits in the entire splanchnic system. Pearson Type III distribution is proposed for the frequency function of the splanchnic transit times, and the power of the pre-exponential factor is deduced for plasma and for red blood cells. It is found that the initial splanchnic transits are dominated by plasma, this may be due to sequestration of red cells in the spleen. The heterogeneity of transit times in normals is not appreciably different from that in patients with cirrhosis and portocaval shunt, which suggests that the extra heterogeneity of the cirrhotic liver is of the same order as the heterogeneity of the normal extrahepatic splanchnic organs. The method may be a useful tool to describe heterogeneity of vascular transits in other organs.

Adolescent↗
PubMed1983

[Therapy of acute lymphoblastic leukemia in childhood. Multicenter prospective therapy study COALL-80].

Since 1979 in a cooperative study (COALL-80) 110 children with acute lymphoblastic leukemia (ALL) and 13 children with high grade malignant non Hodgkin's lymphoma (NHL) have been treated with a less aggressive modification of the Westberlin Study Program BFM 76/79. Asparaginase has been delayed from the initial 4 drugs regimen and interposed in between induction therapy and treatment of central nervous system (CNS). Induction therapy that way was well tolerated and realized mostly on an outpatient basis. The expected 2 1/2 years disease free survival rate for ALL is 86% and no worse than the results of the original BFM study. We were able to define by age (greater than 2, less than 7 years), initial blast count (less than 25000/mm3) and immunological typing (cALL Ag+) a great group of patients (52%) which has remained in continuous remission as a whole. For this group further reduction of therapy intensity is planned (omission of cyclophosphamide during CNS-phase and use of intermediate dose methotrexate (MTX-mHD) instead of CNS-irradiation).

Age Factors↗
PubMed1983

Ultrasonography, computed tomography, and cholescintigraphy in suspected obstructive jaundice--a prospective comparative study.

In order to compare their capacity to visualize the bile ducts, ultrasonography, computed tomography, and cholescintigraphy were performed in 56 consecutive jaundiced patients in whom extrahepatic cholestasis was clinically suspected. The predictions as to the patency of the large bill ducts were compared with the final diagnoses made on the basis of direct cholangiography together with autopsy, biopsy, operative findings, and the clinical course. Thirty-nine patients (70%) had obstructed bile ducts, and 17 (30%) had patent large bile ducts. Using a simple scoring scale with 112 points as the maximum, ultrasonography obtained 72 points, computed tomography received 56 points, and cholescintigraphy totalled 37 points. Nonsignificant trends were found in favor of ultrasonography as compared with computed tomography and of computed tomography as compared with cholescintigraphy (p greater than 0.05), whereas ultrasonography was significantly better than cholescintigraphy (p = 0.01). However, because computed tomography is expensive and may imply a higher number of secondary direct cholangiographies than ultrasonography, we recommend ultrasonography as the first choice for noninvasive bile duct visualization. Computed tomography is an alternative method, whereas cholescintigraphy cannot be recommended.

Cholangiography↗
PubMed1982

[Sonographic findings in malignant lymphoblastic T-cell lymphomas in childhood].

Lymphoblastic T-cell lymphoma is the most frequent Non-Hodgkin's lymphoma in childhood. The generalized character of this malignancy in patients without early leukemic conversion can often be shown by ultrasonography. Sonography can be performed even in the dangerously ill patients without disturbance. Beside the intraabdominal extension the consequences of the mediastinal tumor, pericardial and pleural effusions can be demonstrated. We report our findings in 6 patients with lymphoblastic T-cell lymphoma without early leukemic conversion.

Adolescent↗
PubMed1982

Hepatic elimination of endogenous gastrin in pigs.

To assess hepatic elimination of gastrin, concentrations of gastrin were determined radioimmunochemically in plasma samples collected simultaneously in six pigs from the portal vein, hepatic vein, and a peripheral artery before and after stimulation of the antrum with meat extract. The portal plasma flow and the total plasma volume were measured. During meat extract stimulation the antral release of gastrin increased significantly (p less than 0.05), from 15.9 +/- 3.4 ng/min to 35.6 +/- 5.4 ng/min, and the hepatic elimination increased significantly (p less than 0.05), from 10.4 +/- 2.8 ng/min to 25.5 +/- 5.9 ng/min (mean +/- S.E.M., six pigs). The artery to mesenteric vein concentration ratio was 1.03 +/- 0.05 in the basal and 0.97 +/- 0.10 in the stimulated period, indicating neither release nor uptake of gastrin in the intestines of five pigs. Hepatic elimination of gastrin was roughly proportional to the gastrin concentrations in portal venous plasma. The mean hepatic plasma clearance of gastrin was 148 +/- 26 ml/min and the total body clearance 268 +/- 43 ml/min. Thus extrasplanchnic gastrin removal accounted for half of total body elimination. It is concluded that in anesthetized pigs the "first-pass" effect on portal gastrin content makes the liver one of the important sites for elimination of endogenous gastrin.

Animals↗
PubMed1982

[Immunological classification of acute lymphoblastic leukemias (ALL) in childhood. Origin and clinical significance of phenotypic variability].

Leucemic cells in 54 children with ALL have been typed immunologically by conventional antisera, monoclonal antibodies and receptor tests as c-ALL (62.5%), T-ALL/NHL (18.5%), B-ALL (1.9%) and AUL (16.6%), respectively. The different subtypes showed a noteworthy heterogeneity in receptor patterns which may reflect an arrest in discrete differentiation stages within the maturation pathway of a lymphoid cell population. The characteristic set of clinical symptoms of T-cell neoplasias could once again be confirmed. Of interest is a clear trend for a less favourable outcome in AUL as compared to c-ALL and in NHL versus ALL as a whole, whereas no difference could be found between T-ALL and non T-ALL during therapy. Immunological typing of ALL is of clinical importance as entities with different biological behaviour and, correspondingly, different therapeutical requirements can be distinguished.

Adolescent↗
PubMed1982

Hepatic galactose elimination kinetics in the intact pig.

The hepatic galactose elimination kinetics was studied in eight anaesthetized pigs by hepatic vein catheterization. Galactose was given as successive constant intravenous infusions so that steady-state concentrations, ranging from 50 mumol/l to 8 mmol/l, were obtained. Concentrations were measured in a peripheral artery and in the hepatic veins. Hepatic blood flow was determined by constant infusion of indocyanine green. The elimination kinetics is described by a mathematical model which assumes that the liver sinusoids are perfused with unidirectional blood flow and that the elimination in the hepatocytes takes place according to Michaelis-Menten kinetics. This creates a decreasing sinusoidal blood concentration from the inlet to the outlet of the liver. The estimated maximal elimination rate, Vmax, was on average 0.67 mmol min-1 kg-1 liver (range 0.55-0.95) and the half saturation concentration Km 0.25 mmol/l (0.12-0.58). The estimate of Km is similar to the value found in the isolated perfused pig liver (0.23 mmol/l), whereas the estimate of Vmax is about 50% higher (0.43 mmol min-1 kg-1 liver), probably due to both extrahepatic elimination in the splanchnic area and a better function of the liver in situ than in the isolated preparation.

Animals↗
PubMed1982

Increased transvascular escape rate and lymph drainage of albumin in pigs during intravenous diuretic medication. Relations to treatment in man and transport mechanisms.

Transvascular escape rate of albumin (TERalb, i.e. the fraction of intravascular mass of albumin (IVMalb) passing to (or during steady state returning from) the extravascular space per unit time) was determined from the initial disappearance rate of i.v. injected radioiodinated serum albumin in anaesthetized pigs during control conditions and during diuretic medication (furosemide i.v. 20 mg/15 min, total 160-200 mg). During diuretic medication TERalb (mean 17.1% IVMalb X h-1, range 11.5-21, n = 6) increased significantly above the control period (mean 12.3% IVMalb X h-1, range 9.5-16.5, P less than 0.05). Pressures in artery, right atrium, hepatic and portal veins did not change significantly from control to diuretic period. TERalb equals the lymphatic return rate of albumin provided the transport mechanisms are filtrative-convective (i.e. no local back transport). Additional measurements in five pigs with proteins of different molecular size confirmed a dominating filtrative-convective transport. The increased TERalb during diuretic medication is best explained by an increased lymph drainage, which may decrease interstitial fluid pressure and thereby increase the transmural capillary pressure difference being essential for a filtrative-convective transvascular albumin transport. Increased lymph drainage may contribute to the therapeutic effect of diuretic treatment in oedema and ascites.

Albumins↗
PubMed1981

[Presentation of the cooperative study COALL-80 on treatment of childhood ALL (author's transl)].

The cooperative study COALL-80 is derived from the BFM-78-study. The aim of the study is a reduction of the initial therapy-morbidity and -mortality without loss of efficacy by omitting asparaginase from the four drug-induction regimen and interposing it between induction- and CNS-therapy phase. The expected two years disease free survival rate of a pilot study will be 82%. This finding is hitherto comparable with the BFM-study results.

Adolescent↗
PubMed1981

[On the chemotherapy of Ewing's sarcoma (author's transl)].

Because of the high incidence of pulmonary and skeletal metastases after only local treatment adjuvant systemic chemotherapy is mandatory in Ewing's sarcoma. The drugs most often used thereby are Actinomycin D, Cyclophosphamid, Anthracyclines and Vincristine. In polychemotherapeutic trials two year disease-free survival rates of 80% and more have been accomplished. The rate of local tumour control after radiotherapy is enhanced by chemotherapy but untoward reactions of bone and soft tissue are also. The extent of radiation portals and time indispensable dose of radiation therefore have to be reviewed again. But in view of debilitating side effects of radio-chemotherapy surgical procedures have to be considered individually.

Bone Neoplasms↗
PubMed1981

Increased transvascular escape rate of albumin during experimental portal and hepatic venous hypertension in the pig. Relation to findings in patients with cirrhosis of the liver.

Transvascular escape rate of albumin [TERalb, i.e. the fraction of the intravascular mass of albumin (IVMalb) passing to the extravascular space per unit time] was determined from the disappearance of i.v. injected radioiodinated serum albumin in anaesthetized pigs during control conditions and during regional venous congestion in the infradiaphragmatic area. Balloon catheters were placed in the portal vein (infrahepatic portal congestion) and in the inferior vena cava above (suprahepatic caval congestion) and below (infrahepatic caval congestion) the outlets of the hepatic veins. TERalb was on the average 13% IVMalb.h-1 under basal pressure conditions. TERalb rose significantly (p less than 0.01) during suprahepatic caval and infrahepatic portal congestion to an average of 29 and 19% IVMalb.h-1, respectively. TERalb was positively correlated to the portal pressure (r = 0.75, P less than 0.001). Only a minor increment in TERalb was found during infrahepatic caval congestion. The hepatic share of the increased TERalb during stasis above the hepatic veins was estimated to be threefold that of the extrahepatic splanchnic area. Our results point to filtration of protein, predominantely through the lining of the sinusoids and perisinusoidal space of the liver into the interstitial space around the portal vessels and further into the lymphatics, as the main mechanism of the previously demonstrated marked increase in TERalb in patients with portal venous hypertension due to cirrhosis of the liver.

Animals↗
PubMed1981

The effect of ascitic fluid hydrostatic pressure on albumin extravasation rate in patients with cirrhosis of the liver.

Overall transvascular escape rate of albumin [TERalb, i.e. the fraction of intravascular mass of albumin (IVMalb) passing to the extravascular space per unit time] was determined from the disappearance of i.v. injected radioiodinated serum albumin. Patients with tense ascites due to liver cirrhosis and pigs with posthepatic portal hypertension and intraperitoneally instilled fluid were studied before and after abdominal paracentesis in order to evaluate the effect of ascitic fluid hydrostatic pressure on the transvascular escape rate of albumin. TERalb of the ascitic patients (n = 6) were on average 7.8% IVMalb.h-1, which is somewhat higher but not significantly above normal (mean 5.6% IVMalb.h-1). After paracentesis and removal of the ascitic fluid, TERalb rose significantly to an average of 11.9% IVMalb.h-1 (P less than 0.05). The fraction of IVMalb passing into the peritoneal cavity was on average 0.21 and 0.38% IVMalb.h-1 before and after paracentesis, respectively (n = 4). In ascitic, posthepatic portal-hypertensive pigs (n = 6), TERalb averaged 15.1% IVMalb.h-1, a value not being significantly different from non-ascitic, normotensive controls (mean 16.1% IVMalb.h-1). After paracentesis, TERalb rose significantly to an average of 24.3% IVMalb.h-1. The increased albumin extravasation rate after removal of ascites is best explained by an increased sinusoidal-tissue pressure difference caused by a decreased hydrostatic fluid pressure in the liver interstitium (portal and subcapsular spaces) due to the hydrostatic effect of the removed ascitic fluid.

Abdomen↗
PubMed1981

Hemoglobin Great Lakes (beta 68 [E12] leucine replaced by histidine): a new high-affinity hemoglobin.

Hemoglobin Great Lakes, beta 68 (E12) Leu replaced by His is a new high oxygen affinity hemoglobin variant discovered in a 29-yr-old female having numerous hospitalizations for thrombophlebitis associated with mild erythrocytosis. The mutant hemoglobin has normal stability and normal electrophoretic mobility, but increased oxygen affinity (P-50 16.1 mm Hg at 37 degrees C, pH 7.4) and reduced cooperativity. The abnormal beta-chain could be separated on globin chain chromatography on carboxymethyl/cellulose in spite of the normal electrophoretic mobility of the intact hemoglobin. The leucyl residue at beta 68th position (E12) is in the middle of E-helix, which is part of the heme pocket and next to the valine (E11), which is the heme binding site. The substitution of proline for leucine in hemoglobin Mizuho resulted in the distortion of tertiary structure of the beta-chains and lead to a serious instability of hemoglobin molecule. However, the substitution of this residue by histidine in hemoglobin Great Lakes is not associated with hemoglobin instability.

Adult↗
PubMed1980

[ALL-study series of Hamburg (author's transl)].

From 1971 through 1979 145 newly diagnosed patients with ALL have been treated within a series of consecutive studies. Study I corresponds to branch A of the 1972 DAL study. In the following studies the induction therapy has been escalated stepwise with the continuation therapy remaining mostly unchanged. Thereby the disease free survival rates increased from 75 to 94% after one year and from 32 to 60% after 4 years respectively. CNS-relapse mainly occurred during the second year of treatment. Their incidence rose from 5% to more than 10% in connection with a change in the radiation portal. Since another correction of the portals with special consideration of the paramedian lower border of the skull base no more CNS-relapses have been observed until now. The actual cooperative ALL-study follows a modified BFM-protocol with postponed asparaginase in hoping to achieve reduced initial morbidity and at least equal good survival times.

Child↗