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Biomedical subjects

G Kleber

Publications and source records attributed to G Kleber.

At least 19 recordsLinked to original sources
PubMed2006

Gemcitabine, oxaliplatin and weekly high-dose 5-FU as 24-h infusion in chemonaive patients with advanced or metastatic pancreatic adenocarcinoma: a multicenter phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).

BACKGROUND: Combinations of gemcitabine-oxaliplatin, gemcitabine-5-fluorouracil (5-FU) and 5-FU-oxaliplatin have synergistic activity and nonoverlapping adverse effect profiles. This trial assessed efficacy and safety of the triple combination gemcitabine-oxaliplatin and infusional 5-FU in patients with locally advanced (n=11) or metastatic (n=32) pancreatic adenocarcinoma. PATIENTS AND METHODS: A total of 43 eligible patients were treated with intravenous infusions of gemcitabine (900 mg/m2 over 30 min), followed by oxaliplatin (65 mg/m2 over 2 h) and 5-FU (1500 mg/m2 over 24 h) on days 1 and 8 of a 21-day cycle. RESULTS: Among all 43 patients, the tumor response rate was 19% [95% confidence interval 7% to 30%]. Nine patients were nonassessable for response because they did not complete the first two cycles of chemotherapy due to rapid disease progression, early death or treatment refusal. One patient was lost to follow-up. Median time to progression and overall survival were 5.7 and 7.5 months. Principal grade III/IV toxic effects were leucopenia in 11 (2%), thrombocytopenia in 13 (2%), nausea in 13 (0%), anorexia 16 (7%) and sensory neuropathy in 18 (0%) of patients. Unexpected cardiotoxicity was observed in this trial. CONCLUSION: Response rates and survival of the three-drug combination compare favorably with single-agent gemcitabine, but do not exceed results for doublets.

Adenocarcinoma↗
PubMed2005

Chemotherapy for advanced gastric cancer.

BACKGROUND: Gastric cancer currently ranks second in global cancer mortality. Most patients are either diagnosed at an advanced stage, or develop a relapse after apparently curative operation. Apart from supportive measures, systemic chemotherapy is the only treatment option available in this situation. OBJECTIVES: To assess the effect of chemotherapy versus best supportive care, combination versus single agent chemotherapy and different combination chemotherapy regimens in advanced gastric cancer. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE and EMBASE up to February 2004 and reference lists of articles. We also contacted pharmaceutical companies as well as national and international experts. SELECTION CRITERIA: Randomised controlled trials on systemic intravenous chemotherapy versus best supportive care, combination versus single agent chemotherapy and different combination chemotherapies in advanced gastric cancer. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. A third investigator was consulted in case of disagreements. We contacted study authors to obtain missing information. MAIN RESULTS: Chemotherapy versus best supportive care consistently demonstrated a significant benefit in terms of overall survival in favour of the group receiving chemotherapy (Hazard Ratios (HR) 0.39; 95% confidence intervals (CI) 0.28 to 0.52). Combination versus single-agent chemotherapy provides evidence for a survival benefit in favour of combination chemotherapy (HR 0.85; 95% CI 0.76 to 0.96). Numbers included in these comparisons were 184 and 1338 participants respectively. This benefit is achieved at the price of increased toxicity in the combination chemotherapy arms. When comparing 5-FU/cisplatin-containing combination therapy regimens with anthracyclines versus those without anthracyclines (HR 0.77; 95% CI 0.62 to 0.95 based on 501 participants) and 5-FU/anthracycline-containing combinations with cisplatin versus those without cisplatin (HR 0.83; 95% CI 0.76 to 0.91 based on 1147 participants), there was a significant survival benefit for regimens including 5-FU, anthracyclines and cisplatin. AUTHORS' CONCLUSIONS: Chemotherapy significantly improves survival in comparison to best supportive care. In addition, combination chemotherapy improves survival compared to single-agent 5-FU, but the effect size is much smaller. Among the combination chemotherapy regimens studied, best survival results are achieved with regimens containing 5-FU, anthracyclines and cisplatin. In this category, ECF (epirubicin, cisplatin and continuous infusion 5-FU) is tolerated best.

Anthracyclines↗
PubMed2005

Hepatic arterial doppler sonography in patients with cirrhosis and controls: observer and equipment variability with use of the ultrasonic contrast agent SHU 508A.

PURPOSE: The aims of this study on hepatic arterial Doppler sonography were to ascertain interobserver and interequipment variability, to investigate any potential artificial influence of the ultrasonic contrast agent on the Doppler measurements and to compare the results in healthy and cirrhotic subjects. METHODS: Doppler sonography of the left hepatic artery was performed in nine healthy and nine cirrhotic subjects by three independent observers using three different devices. Continuous infusion of the ultrasonic contrast agent SHU 508A and placebo were administered in a double blind fashion. Systolic, mean and end diastolic peak velocities as well as resistive and pulsatility indices were measured. RESULTS: Equipment associated variances (5.8 - 12.7 %) of the five Doppler parameters were greater than interobserver variances (0.3 - 3.6 %). No significant differences were observed between the velocities using ultrasonic contrast agent and placebo. Systolic (65.9 +/- 3.6 vs. 47.7 +/- 4.2 cm/s mean +/- SE, p = 0.02) and mean peak velocity (35.4 +/- 1.6 vs. 24.5 +/- 1.8 cm/s, p = 0.007) were significantly higher in cirrhotic than in healthy subjects whereas the resistive and pulsatility indices were not different. CONCLUSIONS: Doppler sonography of the left hepatic artery performed by various observers is reproducible as long as the same device is used. Under clinical conditions, velocities are correctly measured with the use of ultrasonic contrast agent and are elevated in patients with cirrhosis.

Adult↗
PubMed2004

[Pulmonary infiltrates in a 19 year old patient with dysuria and hypercalcemia].

A 19 year old patient presented with the typical constellation of sarcoidosis. In the presence of indefinable pulmonary infiltrates, hypercalcemia, raised angiotensin converting enzyme and even evidence of giant and epitheloid cell granulomas, cocaine abuse should be considered. Chronic inhalative cocaine abuse can cause foreign body associated granulomatosis of the lung and other organs. It is important to establish this differential diagnosis by confidential interview and systematic polarisation microscopy to detect foreign material in tissues: unnecessary therapies with potential side effects should be avoided and drug weaning with rehabilitation of the patient should be initiated. However the potential for rapid progressive respiratory failure should not be underestimated.

Administration, Inhalation↗
PubMed2003

13C-Methacetin metabolism in patients with cirrhosis: relation to disease severity, haemoglobin content and oxygen supply.

BACKGROUND: Hypoxia may contribute to impairment of liver function and thus interfere with results of liver tests. In patients with cirrhosis, cytochrome P-450 mediated metabolism of substrates is facilitated in the presence of supplemental oxygen. It has not been studied how this relates to liver function and haemoglobin content. AIM: We questioned how oxygen supplementation would influence the hepatic microsomal function as assessed by the 13C-methacetin breath test in patients with cirrhosis of different severity and different degrees of anaemia. METHODS: 13C/12C ratios in exhaled breath assessed by non-dispersive infrared spectrometry were studied in 34 patients with cirrhosis (Child A/B/C 9/17/8) after administration of 75 mg 13C-methacetin p.o. with and without oxygen inhalation (4 L/min). RESULTS: In patients breathing room air the total amount of 13C exhaled weakly correlated both with the Child-Pugh score (r = - 0.41, P < 0.02) and haemoglobin concentrations (r = 0.46; p = 0.006). Oxygen supplementation increased the total amount of 13C exhaled by 68 +/- 90% (P < 0.001). This effect was similar in Child-Pugh classes A (43 +/- 55%), B (83 +/- 80%) and C (66 +/- 123%) and not related to the Child-Pugh score. CONCLUSIONS: Our results suggest that tests of microsomal liver function are independently influenced both by oxygen delivery and the Child-Pugh score.

Acetamides↗
PubMed2000

Hepatic arterial blood flow velocities: assessment by transcutaneous and intravascular Doppler sonography.

BACKGROUND/AIMS: Doppler sonography has been used to assess hepatic arterial perfusion in a number of published reports. However, adequate validation studies are available for neither the transcutaneous nor the intravascular Doppler approach. The aim of this comparative study was to assess hepatic arterial perfusion with both methods. METHODS: In 15 patients the right hepatic artery was examined with intravascular and transcutaneous Doppler sonography after calibration of Doppler devices in vitro with a thread model. The measurements were performed simultaneously in five and separately within 24 h in 10 patients. RESULTS: In vitro, the correlations between the velocities of the thread and the velocities as determined by intravascular (r=1.0, p<0.001) and transcutaneous Doppler sonography (r=1.0, p<0.001) were excellent. In vivo, the best correlation was found for systolic peak velocities (intravascular: 58.5+/-18.1 cm/s, mean+/-standard deviation, transcutaneous: 58.2+/-25.2 cm/s, r=0.63, p=0.01). Although lower mean (intravascular: 26.5+/-7.7 cm/s, transcutaneous: 32.5+/-14.4 cm/s) and end-diastolic velocities (intravascular: 11.5+/-4.0 cm/s, transcutaneous: 18.4+/-8.6 cm/s) were found with intravascular compared to transcutaneous Doppler sonography, significant correlations were demonstrable between results obtained by both methods (r=0.63, p=0.01 for mean and r=0.57, p=0.025 for diastolic velocities). Similarly, the calculated resistive (intravascular: 0.79+/-0.07, transcutaneous: 0.68+/-0.06, r=0.65, p=0.009) and pulsatility indices (intravascular: 1.78+/-0.47, transcutaneous: 1.26+/-0.25, r=0.55, p=0.034) were somewhat higher using the intravascular device, but correlated well with the numbers obtained by the transcutaneous approach. CONCLUSIONS: The data suggest that with use of different Doppler devices, systolic velocities are the most suitable parameter for Doppler assessment of hepatic arterial perfusion.

Adult↗
PubMed1999

Hepatic arterial flow volume and reserve in patients with cirrhosis: use of intra-arterial Doppler and adenosine infusion.

BACKGROUND & AIMS: In cirrhosis, liver blood flow becomes increasingly dependent on the hepatic artery. The aim of this study was to investigate hepatic arterial blood flow volume and resistance and hepatic arterial flow reserve in relation to liver function and systemic hemodynamic alterations in patients with cirrhosis. METHODS: In 38 patients with cirrhosis, liver function, cardiac output, and systemic vascular resistance were studied, and hepatic arterial blood flow velocity, flow volume, and pulsatility index at baseline and during intra-arterial administration of adenosine (2-40 microg. min-1. kg body wt-1) were assessed by angiography combined with intravascular Doppler flowmetry. RESULTS: Hepatic arterial flow velocity was 21 +/- 11, 31 +/- 17, and 41 +/- 27 cm/s; flow volume was 266 +/- 246, 342 +/- 289, and 417 +/- 220 mL/min; and pulsatility index was 2.2 +/- 0.7, 1.7 +/- 0.6, and 1.5 +/- 0.5 in Child-Pugh classes A, B, and C, respectively (differences not statistically significant). Adenosine-induced changes in these parameters were more marked in Child-Pugh class A (68 +/- 15 cm/s, 1246 +/- 486 mL/min, and -1.14 +/- 0.5) than in class C (45 +/- 23, P < 0.05; 704 +/- 492, P = 0.02; and -0.58 +/- 0.38, P < 0.05). Using analysis of variance, cardiac index, systemic vascular resistance, and ascites, but not Child-Pugh class, were related to baseline values and adenosine-induced changes. CONCLUSIONS: Adenosine is a potent dilator of the hepatic artery in humans. The data suggest that hepatic arterial blood flow and adenosine-dependent flow reserve in patients with cirrhosis are under systemic hemodynamic or neurohormonal control.

Adenosine↗
PubMed1998

Transjugular intrahepatic portosystemic shunt for bleeding angiodysplasia-like lesions in portal-hypertensive colopathy.

Portal-hypertensive colopathy has attracted interest in recent years because such lesions can cause life-threatening hemorrhage. In contrast to upper gastrointestinal bleeding from varices, there is no established therapy for bleeding from angiodysplasia-like lesions. This case report describes the first successful use of transjugular intrahepatic portosystemic shunt (TIPS) for long-term control of bleeding from angiodysplasia-like colonic lesions in a patient with cirrhosis caused by chronic hepatitis B infection. During an 18-month course after TIPS, angiodysplasia-like lesions disappeared without any further evidence of recurrent hematochezia. TIPS may be helpful as second-line treatment in patients with recurrent portal-hypertensive bleeding from colonic angiodysplasia-like lesions who do not tolerate or are unresponsive to treatment with beta-adrenergic blockers.

Aged↗
PubMed1998

[Endoscopic therapy of cholangiolithiasis by percutaneous approach. Percutaneous gallstone therapy].

PATIENTS AND METHODS: In a retrospective study, the results of percutaneous transhepatic therapy of bile duct stones under cholangioscopic control (PTCS) were evaluated in 32 patients in which a endoscopic retrograde stone removal was impossible or failed. RESULTS: Previous gastric surgery was the most common reason for choosing the percutaneous route (22 cases). Five patients had biliodigestive anastomosis, two pyloric obstructions, and in three patients the retrograde stone removal failed. Complete stone removal was obtained after 3 to 11 (median 5) percutaneous procedures in all cases, in 28 patients by electrohydraulic lithotripsy, and in the remaining 5 cases by mechanical extraction alone. There was no complication due to cholangioscopy and lithotripsy themselves. Two cases had major complications which needed laparotomy (4%, one case had capsular bleeding from the liver, another one had catheter perforation of the duodenum). In addition, three cases (7%) had minor complications which required no therapy during the percutaneous fistula procedure. Two elderly multimorbid patients (4%) died during hospitalisation after successful stone removal not related to the performed procedure. CONCLUSION: The percutaneous transhepatic cholangioscopy (PTCS) and lithotripsy are highly effective techniques for endoscopic treatment of bile duct stones. Because of an increased rate of complications during the fistula procedures, both methods should be restricted to cases with difficult anatomic situation and high risk of surgery.

Adult↗
PubMed1995

Short-term cardiovascular effects of somatostatin in patients with cirrhosis.

Somatostatin is used to treat variceal hemorrhage in patients with cirrhosis and portal hypertension. Its systemic hemodynamic effects, however, are not yet well defined. Since cardiomyopathy or pulmonary artery hypertension may occur in patients with cirrhosis, definition of the systemic hemodynamic effects of somatostatin or its analogue octreotide is of clinical importance. The aim of this study was to evaluate the effects of somatostatin, at different doses and under different conditions of administration, on the systemic hemodynamics in 17 patients with cirrhosis. Two sets of experiments were performed. In the first, eight patients received two different bolus doses (100 and 250 micrograms) of somatostatin. The second set of experiments was designed to study the hemodynamic effects of the combination of a bolus and an infusion of somatostatin. Nine other patients received one bolus of 250 micrograms of somatostatin, followed by a 250 micrograms/h infusion for 65 min. A second bolus of 250 micrograms of somatostatin was injected in these patients after 35 min of infusion. Before and for 30 min after each bolus, systemic hemodynamics were measured. Following a bolus of somatostatin, a dose-dependent decrease in heart rate (from 77 +/- 3 to 73 +/- 5 beats/min with 100 micrograms, and from 78 +/- 4 to 68 +/- 5 beats/min with 250 micrograms, p < 0.05) and increases in systemic and pulmonary artery pressures were observed. The combination of an infusion and a bolus of somatostatin significantly reduced the increases in systemic and pulmonary artery pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Reversible hyperkinesia in a patient with autoimmune polyglandular syndrome type I.

Autoimmune polyglandular syndrome is characterized by a failure of multiple endocrine organs and the presence of circulating organ-specific autoantibodies targeted against the failing organs. Here we describe a patient with autoimmune polyglandular syndrome type I with the endocrine manifestations of hypoparathyroidism, adrenocortical insufficiency, and insulin-dependent diabetes mellitus. Long-standing hypoparathyroidism led to extensive calcification of the basal ganglia which resulted in the clinical presentation of an extrapyramidal movement disorder (choreoathetotic and hemiballistic hyperkinesia of the left extremities). Interestingly, parallel to rehydration and the initiation of cortisol replacement therapy a complete reversion of the hyperkinetic signs was achieved. This case shows a rare multiendocrine organ failure with complex metabolic interactions resulting in marked neurological signs. Furthermore, this case demonstrates for the first time that a hyperkinetic syndrome--most likely due to hypoparathyroidism-induced basal ganglia calcification--can be reversed solely by adequate treatment of the concomitant endocrine failures.

Adrenal Cortex Diseases↗
PubMed1993

Manometry of esophageal varices: comparison of an endoscopic balloon technique with needle puncture.

BACKGROUND: A noninvasive technique of pressure measurement in esophageal varices using an endoscopic balloon has been shown to be reliable in vitro. In the present study, this method was tested in vivo. METHODS: Thirty-seven pressure measurements in esophageal varices were performed in 34 patients by two independent operators (A and B) using an endoscopic balloon and compared with measurements performed by needle puncture by a third operator (C). RESULTS: Three measurements performed with the endoscopic balloon were rejected because they were noninterpretable. Measurements performed by A and B correlated well (correlation coefficient, 0.90); interobserver variability (r) was 0.88. Of 37 punctures performed for pressure measurements, 4 resulted in bleeding and 8 measurements were rejected as uninterpretable. Regression analysis showed a good correlation between the needle puncture and balloon techniques for pressure measurements performed by both operators (y = 5.3 + 1.0x, r = 0.8; y = 6.2 + 0.9x, r = 0.8), and analysis of variability showed a measurement bias of -5.3 +/- 4.1 and -4.1 +/- 3.5 cm H2O. No significant difference in variceal size measured with the endoscopic balloon or endoscopic forceps was found. CONCLUSIONS: The endoscopic balloon allows measurement of pressure in esophageal varices without hazard to the patient; in addition, it may be used to assess the varix size.

Adult↗
PubMed1993

[Recent aspects in diagnosis and therapy of esophageal varices].

Esophageal varices are of ominous significance in patients with cirrhosis. Diagnostic procedures are undertaken for evaluation of the bleeding risk. Whereas after a recent bleeding event the risk of rebleeding is high (up to 70%) and rebleeding prophylaxis is obligatory, the risk of first bleeding in patients who never bled depends on the presence of bleeding risk indicators. Endoscopy is the most powerful tool for assessment of the bleeding risk. Variceal size, the presence of the red color sign and the presence of concomitant fundic varices indicate a high risk of first bleeding. Currently used endoscopic or medical prophylaxis has a high rate of failure. On the other hand, operative measures prevent bleeding in most patients. However, the perioperative morbidity and mortality is high. Controlled studies will show whether the patients will benefit from new experimental treatment approaches (endoscopic obliteration of varices, endoscopic ligation of varices, TIPS and liver transplantation.

Esophageal and Gastric Varices↗