Uwe Ritzel

Release of glucagon-like peptide-1 (GLP-1) by carbohydrates in the perfused rat ileum

Abstract The effect of various carbohydrates on glucagon-like peptide-1 (GLP-1) release was studied in the in vivo perfused rat ileum. GLP-1 concentrations in the mesenteric venous effluent increased significantly after luminal perfusion with substrates of a sodium/glucose cotransporter (d-glucose, d-galactose, methyl-αd-glucoside, and 3-O-methyl-d-glucose). d-Fructose induced a sodium-independent release of GLP-1. Carbohydrates like 2-deoxy-d-glucose and N-acetyl-d-glucosamine, which are not substrates of a luminal sodium/glucose or fructose transporter, did not affect GLP-1 release. Since methyl-αd-glucoside is not a substrate of the basolateral glucose transport mechanism and 3-O-methyl-d-glucose is not metabolized within intestinal cells, it is concluded that intracellular metabolism of carbohydrates and intracellular removal are not essential to induce GLP-1 secretion in rats.

Simvastatin in primary biliary cirrhosis: effects on serum lipids and distinct disease markers

BACKGROUND/AIMS Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver with inflammation of small and middle-sized bile ducts. Serum lipids are frequently elevated, but the use of a lipid lowering drug therapy in PBC is still a matter of debate. Application of an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in hypercholesterolemic PBC patients was therefore the subject of the present study. METHODS Six female patients (aged 46.5 (32-61) years; median (range)) were treated with the HMG-CoA reductase inhibitor simvastatin (5 or 20 mg/day). Levels of serum total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were determined prior to and after 2 months of treatment. Concentrations of serum markers of cholestasis, antimitochondrial antibodies (AMA), and immunoglobulins A, G and M were also assessed. RESULTS Simvastatin significantly (P<0.05) reduced serum levels of total cholesterol, LDL cholesterol, alkaline phosphatase, -glutamyltransferase, and immunoglobulin M (by 19, 26, 12, 37 and 14%, respectively). CONCLUSIONS The lipid lowering potency of the HMG-CoA reductase inhibitor simvastatin was confirmed in hypercholesterolemic patients with PBC. The drug might also prove useful as modulator of cholestasis and of immune response in this disease.

The sentinel lymph node concept

From the contents: General Part: Definition and Basic Principles Main Techniques of Sentinel Lymph Node Labeling Different Aspects on Type and Localization of the Primary Basic Strategies in Sentinel Node Detection and Verification of Cancer Metastasis into the Regional Node PET: Significance for Preoperative N-Staging Detection and Radiological Imaging of SLN Lymphatic Drainage to the SLN.- Special Part: The Sentinel Lymph Node Concept Related to Main Tumor Types and Subtypes, Applicability in Daily Routine Work: Breast Cancer Thyroid Cancer Cancers of the Face, Nose Pharynx, and Oral Cavity Lung Cancer Malignant Melanoma Esophageal and Gastrointestinal Cancer SLN Staging in Carcinoide and Neuroendocrine Tumors The Sentinel Lymph Node Concept in Cancers of the Female Genitalia Cancers of the Male Genitalia Prostate Cancer: an Overview Cancers of the Urinary Tract Closing Remarks Therapy Regimens Used in Adjuvant and Neoadjuvant Treatment of the Tumor Types Discussed.

Metformin-assoziierte Lactatazidose mit akutem Nierenversagen bei Diabetes mellitus Typ 2

ZusammenfassungFallbericht: Eine 83-jährige Patientin wurde mit gastrointestinalen Symptomen, zunehmender Verwirrtheit und verwaschener Sprache notfallmäßig stationär aufgenommen. In der Vorgeschichte waren ein Diabetes mellitus Typ 2, weshalb die Patientin Metformin einnahm, und eine grenzwertig eingeschränkte Nierenfunktion bekannt. Bei Aufnahme fanden wir eine soporöse Patientin mit Kussmaulscher Atmung, die mit einer Körpertemperatur von 32.1°C deutlich unterkühlt war. Die Kreislaufverhältnisse waren bei einem Blutdruck von 80/30 mm Hg und einer Herzfrequenz von 86/min instabil. Laborchemisch fiel bei Aufnahme eine Lactatazidose mit einem pH-Wert von 6,71, einem Base Excess von −30, einem Standardbicarbonat von 4,0 mmol/l und einem Lactatwert von 24,4 mmol/l auf. Zudem bestand ein akutes Nierenversagen mit einem Serumkreatinin von 10,6 mg/dl und einem Harnstoff-N von 134 mg/dl. Die Elektrolyte lagen im Normbereich, die Blutglucose war mit 147 mg/dl erhöht. Aufgrund von Anamnese, klinischer Symptomatik und typischer Laborkonstellation konnte sofort die Verdachtsdiagnose Metformin-assoziierte Lactatazidose mit akutem Nierenversagen gestellt werden. Ein bei Aufnahme deutlich erhöhter Metforminwert im Serum bestätigte später diese Diagnose. Es wurde schnellstmöglich eine Bicarbonathämodialyse eingeleitet. Nach insgesamt 8-stündiger Hämodialyse war der Säure-Basen-Haushalt nahezu normwertig. Der Vigilanzzustand der Patientin normalisierte sich unter dieser Therapie rasch. Im Folgenden waren keine weiteren Hämodialysen mehr notwendig, die Nierenfunktion normalisierte sich unter ausreichender Flüssigkeitszufuhr fast vollständig. Die Patientin wurde auf eine Insulintherapie umgestellt. Schlussfolgerungen: Die Metformin-assoziierte Lactatazidose ist keine seltene Nebenwirkung bei Patienten mit zunehmender Niereninsuffizienz. Um eine frühzeitige Diagnose stellen zu können, sollten Ärzten und Patienten die klinischen Symptome einer Metforminintoxikation gut bekannt sein. Zur Normalisierung des Säure-Basen-Haushalts ist die Bicarbonathämodialyse Therapie der Wahl, da hierdurch auch Metformin effektiv eliminiert werden kann. Natriumbicarbonatinfusionen erscheinen dagegen wenig erfolgversprechend. Um dieser Nebenwirkung von Metformin vorzubeugen, sollten die Nierenfunktion regelmäßig überwacht und bei Verschlechterung Metformin abgesetzt werden.AbstractCase Report: An 83-year-old patient was admitted to our hospital because of gastrointestinal symptoms, mental confusion and dysarthria. The patient suffered from type 2 diabetes mellitus and was taking metformin. A mild renal insufficiency was known. On admission, we found impaired consciousness, Kussmaul breathing, a body temperature of 32.1°C, and hemodynamic instability. Laboratory testing revealed lactic acidosis (pH 6.71, base excess −30, standard bicarbonate 4.0 mmol/l, lactate 24.4 mmol/l) and acute renal failure with a creatinine of 10.6 mg/dl and blood urea nitrogen of 134 mg/dl. Electrolytes were not altered; the blood glucose was elevated (147 mg/dl). According to history, physical examination, and laboratory testing the diagnosis metformin-induced lactic acidosis with acute renal failure was made. This diagnosis was confirmed by an elevated level of metformin. As soon as possible a bicarbonate hemodialysis was initiated. After 8 hours of hemodialysis the acid-base metabolism was almost balanced and the vigilance of the patient normalized. No further sessions of hemodialysis were needed and insulin therapy was started. Conclusions: Metformin-induced lactic acidosis is a common side effect in patients with renal insufficiency. For an early diagnosis, clinical symptoms of intoxication should be well known by physicians and patients. First-line therapy for correction of lactic acidosis and effective elimination of metformin is bicarbonate hemodialysis. Sodium bicarbonate infusions are not able to correct the acid-base metabolism sufficiently. For prevention the renal function should be monitored closely and metformin therapy should be stopped, if a deterioration of renal function is observed.

Detection of circulating albumin-mRNA by RT-PCR does not indicate metastasizing hepatocellular carcinoma.

ZusammenfassungHepatozelluläre Karzinome (HCC) weisen nach primärer Resektion bzw. orthotoper Lebertransplantation eine hohe Rezidivrate auf. Ein Grund hierfür sind möglicherweise im peripheren Blut zirkulierende Hepatomzellen. Der Nachweis von HCC-Zellen im Blut könnte das therapeutische Vorgehen entscheidend beein-flussen und als Nachweis einer hämatogenen Mikrometastasierung dienen. In der vorliegenden Studie wurde humane Albumin-mRNA als spezifischer Marker für zirkulierende Hepatozyten mittels RT-PCR im peripheren Blut von Patienten mit hepatozellulärem Karzinom verifiziert. Albumin-spezifische PCR-Produkte ließen sich im peripheren Blut aller untersuchten HCC-Patienten nachweisen. Ebenso fanden sie sich im Blut von gesunden Probanden. Die Ergebnisse der vorliegenden Arbeit lassen Albumin-mRNA nicht als geeigneten Marker für eine hämatogene und nicht als geeigneten Marker für eine hämatogene Metastasierung erscheinen.AbstractHepatocellular carcinomas (HCC) frequently recur after partial liver resection or orthotopic liver transplantation, possibly because of the presence of a small number of hepatoma cells in the peripheral blood. Detection of circulating HCC cells might improve therapeutic options and could predict disease recurrence resulting from a metastasizing disease. In the present study, human albumin-mRNA was detected by RT-PCR in the peripheral blood of patients with hepatocellular carcinoma. Circulating albumin-specific PRC products were detected in each patient with HCC, but also in healthy volunteers. It is concluded that albumin-mRNA is not specific to circulating hepatoma cells and therefore does not indicate metastasizing disease.

Circulating human hepatic lipase mRNA in patients with hepatocellular carcinoma and healthy controls

OBJECTIVE To evaluate circulating human hepatic lipase mRNA as an indicator of circulating hepatoma cells by reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with hepatocellular carcinoma (HCC). DESIGN Prospective study SETTING University hospital, Germany. SUBJECTS 15 patients with hepatocellular carcinoma and 8 healthy volunteers. INTERVENTIONS Peripheral venous blood was obtained and total RNA was extracted from the lymphocytic layer by caesium chloride gradient centrifugation. The mRNA was reverse transcripted, and hepatic lipase cDNA was amplified by hepatic lipase specific primers with PCR. The integrity of isolated RNA was confirmed by RT-PCR with beta-actin specific primers. Amplificates were visualised by agarose gel electrophoresis and ethidium bromide staining. MAIN OUTCOME MEASURES Detection of hepatic-lipase-specific RT-PCR products in peripheral blood. RESULTS Circulating hepatic lipase-specific PCR products were detected in all patients with HCC and in all healthy controls. CONCLUSION Detection of circulating human hepatic lipase-mRNA by RT-PCR does not indicate metastasising HCC.

Ultrasonographic guided laser-induced interstitial thermotherapy (LITT) of hepatic metastases

Background: In patients with unresectable hepatic metastases or primary liver tumors therapeutic options are limited. Laser-induced thermotherapy could be a minimal invasive option for palliative treatment of hepatic metastasized tumors. Thereby, absorption of laser light energy induces denaturation of proteins and thermocoagulation of tumor cells. Methods: Laser coagulation was performed by using a neodymium-yttrium alum/n/urn garnet (Nd:YAG) laser (Dornier MediLas fibertom 4100) with a scattering-dome light emitter and a water-cooled application catheter (Somatex). On the basis of ex vivo experiments 36 patients with unresectable hepatic tumors (15 colorectal carcinomas, 7 pancreatic adenocarcinomas, 4 gastric carcinomas, 4 metastasized midgut carcinoids, 5 hepatocellular carcinomas, 1 cholangiocellular carcinoma) were treated with LII3. After local anesthesia and intravenous sedation with midazolam laser probes were placed percutaneously under ultrasonographic guidance. Up to 5 metastases were treated per session. Results: During laser light emission uitrasonographic imaging showed a marked signal enhancement that allowed estimation of the coagulation zone. Percutaneous LITT was performed without any side effects such as bleeding, infection or liver injury. The 30 day mortality was zero. Patients left the hospital within 3 days after LITT. A significant tumor reduction was demonstrated by abdominal CT or MRT. Conclusions: It can be concluded that percutaneous LITT can be safely performed under ultrasonngraphic guidance in patients with malignant liver tumors. LITI induces significant destruction of tumor mass as verified by abdominal CT or MRT.

7005 Evaluation of a minilaparoscopical technique in the diagnosis of liver diseases.

INTRODUCTION: Explorative laparoscopy combined with guided liver biopsy offers many advantages in the diagnosis and staging of liver diseases. Its use might be limited by the invasivity of the technique and the development of non-invasive diagnostic imaging techniques, respectively. In the present publication we report about a minilaparoscopic technique that uses miniaturized scopes to reduce the risc of trauma. PATIENTS AND METHODS: Between April 1999 and Novembre 1999 30 patients (6 females and 24 males) underwent diagnostic assessment for chronic liver disease by minilaparoscopy. The mean age was 56 years in the female patients (range:27 to 73 years) and 43 years in the male patients (range: 20 to 72 years). Minilaparoscopy was performed in local anesthesia and weak sedation using a 1.9 mm optical instrument, which was inserted through the same 2.75 mm trocar as the Veress needle used for inflating the pneumoperitoneum. The minilaparoscop was connected to a video converting system that enabled monitoring on a video scope. Liver specimens were obtained under laparoscopical sight through an additional 2.3 mm trocar. RESULTS: Minilaparoscopy could be performed in all 30 patients without any severe complications. In one of the initial cases liver biopsy was not performed because of technical difficulties. In all other patients it was performed without any limitations. Macroscopic evaluation of the liver revealed a steatosis in 4 cases (histological diagnosis idem), acute hepatitis in 2 cases (histological diagnosis idem), cirrhosis in 7 cases (agreement with histological diagnosis in 6 cases), and no sighns of cirrhosis in 16 cases (histological diagnosis idem). In one patient a disseminated peritoneal carcinosis was found that appeared histologically as a low differenciated adenocarcinoma. CONCLUSIONS: The minilaparoscopical technique allows macroscopic and histological diagnosis of liver diseases with a minimum of invasiveness. It is tolerated excellent by the patients and is a safe technique. It is concluded that explorative minilaparoscopy is a useful technique in the diagnosis of liver diseases and peritoneal carcinosis.