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Biomedical subjects

U Leonhardt

Publications and source records attributed to U Leonhardt.

At least 19 recordsLinked to original sources

Serum procalcitonin and proinflammatory cytokines in a patient with acute severe leptospirosis.

Leptospirosis is a zoonosis, with clinical manifestations ranging from the imperceptible to severe, potentially fatal renal and liver failure accompanied by haemorrhage and jaundice. In this case report of a patient with severe leptospirosis, serum levels of procalcitonin decreased ahead of any obvious clinical improvement, and thus may be useful as a prognostic marker. Levels of soluble IL-2 receptor were very high and correlated well with the clinical course.

Acute 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.

Biomarkers, Tumor↗

Immunoreactive leptin and leptin mRNA expression are increased in rat hypo- but not hyperthyroidism.

In this study, plasma leptin concentrations were measured in rats artificially rendered hyper- or hypothyroid by administration of thyroxine or TRH, by administration of methimazole, or by thyroidectomy. Compared with those in untreated controls, leptin immunoreactivity was not affected in the hyperthyroid state, but was significantly increased in hypothyroid animals. Methimazole administration for longer time periods caused a stepwise increase in plasma leptin immunoreactivity. Greatest leptin concentrations were seen after 28 days of methimazole. Seven days after withdrawal of the methimazole, leptin concentrations no longer differed from those observed in control animals. In hypothyroid animals, expression of leptin mRNA was increased in both retroperitoneal and epididymal adipose tissue, whereas no difference was seen for subcutaneous or mesenteric fat. Incubation of rat leptin with plasma of eu- or hypothyroid rats and subsequent HPLC analysis of leptin plasma peaks gave no indication of an altered hormone stability. We conclude that, in hypothyroid rats, leptin concentrations may be increased as a result of stimulated leptin synthesis in retroperitoneal and epididymal adipose tissue.

Adipose Tissue↗

Hyperphagia in children with craniopharyngioma is associated with hyperleptinaemia and a failure in the downregulation of appetite.

Patients with craniopharyngioma frequently suffer from severe obesity. Leptin induces an inhibition of appetite via hypothalamic receptors. This study was undertaken to investigate whether a relationship exists between serum leptin levels and pituitary/hypothalamic lesions in craniopharyngioma patients. Serum leptin levels were evaluated by RIA in 14 patients (age 7-21 years; 7 females, 7 males) after they had undergone neurosurgical treatment for craniopharyngioma. Normal controls had a positive correlation between leptin levels and body mass index (BMI) with higher levels in the females than in the males. Significantly elevated leptin levels with respect to BMI were found in 11 craniopharyngioma patients who had been affected by a suprasellar tumour, whereas 3 patients with an intrasellar tumour had lower, almost normal serum leptin levels. Our data suggest that craniopharyngioma patients develop hypothalamic obesity because their hypothalamic structures are insensitive to endogenous leptin. The elevated serum leptin concentrations found only in patients with a suprasellar tumour may be explained by a disturbed feedback mechanism from the hypothalamic leptin receptors to the adipose tissue.

Adolescent↗

Serum leptin levels in hypo- and hyperthyroidism.

Leptin, the product of the ob gene, is an important circulating signal for the regulation of body weight. In the present study the role of immunoreactive leptin (leptin-IR) was investigated in functional thyroid disease. Serum leptin-IR levels of 23 hypothyroid and 19 hyperthyroid patients were compared with 21 controls. Leptin-IR was quantified by a specific RIA. In hyperthyroid patients, leptin-IR was not different from controls. Serum leptin-IR levels were significantly increased in hypothyroid patients (21.0 +/- 2.7 micrograms/l vs controls 10.8 +/- 2.1 micrograms/l, P = 0.0044). When serum leptin of hypothyroid patients was compared with euthyroid controls of the same body mass index the difference was still significant (P = 0.0333 by paired Student's t-test). This might indicate that elevation of the serum leptin level does not merely reflect changes in body weight secondary to hypothyroidism, but might be increased to overcome the gain of body weight caused by hypothyroidism.

Body Mass Index↗

A synthetic glucagon-like peptide-1 analog with improved plasma stability.

Glucagon-like peptide-1 (GLP-1) is the most potent endogenous insulin-stimulating hormone. In the present study the plasma stability and biological activity of a GLP-1 analog, [Ser]GLP-1(7-36)amide, in which the second N-terminal amino acid alanine was replaced by serine, was evaluated in vitro and in vivo. Incubation of GLP-1 with human or rat plasma resulted in degradation of native GLP-1(7-36)amide to GLP-1(9-36)amide, while [Ser]GLP-1(7-36)amide was not significantly degraded by plasma enzymes. Using glucose-responsive HIT-T15 cells, [Ser]GLP-1(7-36)amide showed strong insulinotropic activity, which was inhibited by the specific GLP-1 receptor antagonist exendin-4(9-39)amide. Simultaneous i.v. injection of [Ser]GLP-1(7-36)amide and glucose in rats induced a twofold higher increase in plasma insulin levels than unmodified GLP-1(7-36)amide with glucose and a fivefold higher increase than glucose alone. [Ser]GLP-1(7-36)amide induced a 1.5-fold higher increase in plasma insulin than GLP-1(7-36)amide when given 1 h before i.v. application of glucose. The insulinotropic effect of [Ser]GLP-1(7-36)amide was suppressed by i.v. application of exendin-4(9-39)amide. The present data demonstrate that replacement of the second N-terminal amino acid alanine by serine improves the plasma stability of GLP-1(7-36)amide. The insulinotropic action in vitro and in vivo was not impaired significantly by this modification.

Animals↗

[Doppler sonographic short- and long-term studies of portal hemodynamics following transjugular intrahepatic portasystemic shunt (TIPSS)].

Shunt insufficiency due to shunt occlusion or stenosis is frequent after TIPS (about 50% after one year). Controversially discussed is whether Doppler sonography is effective in detecting shunt stenosis or whether regular angiographies are required. The experience with a noninvasive method of surveillance primarily based on Doppler sonography is reported here. 58 patients (35 men, 23 women, mean age 55 years, range 33-82 years) were treated by TIPS because of complications of portal hypertension (43 x gastroesophageal bleeding, 14 x refractory ascites, 1 x venoocclusive disease). Liver cirrhosis (alcoholtoxic etiology in 63%) was present in 55 cases, according to Child-Pugh's classification 23 patients = A, 19 patients = B and 13 patients = C. Within a mean observation period of 14 months, Doppler sonography was performed in three months intervals, endoscopy in six months intervals and angiography only when shunt insufficiency was suspected by Doppler sonography and/or because of clinical events, e.g. recurrent bleeding. Immediately after TIPS, maximal flow velocity and flow volume in the portal vein increased by 116% and 115%, respectively. Three months later, a significant increase of portal vein diameter of about 15% was measured. Shunt flow was initially 2.700 ml/min (one week after TIPS) and decreased progressively by about 30% within the first nine months of follow-up. Correspondingly, angiographically proven shunt insufficiency was present in 22 patients (33 episodes). A total of twelve bleeding episodes recurred in seven patients (rebleeding rate of 16% after one year and 19% after two years). In the remaining 15 patients (68%; 21 episodes) shunt insufficiency could be corrected prior to complications because of detection by Doppler sonography (19x) and endoscopy (2x). Therefore, Doppler sonography is an effective diagnostic tool for the detection of shunt insufficiency and should be performed at three months intervals for at least 18 months. In this context it appears allowable to avoid routine angiographies.

Adult↗

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

Hepatocellular 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 PCR 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.

Carcinoma, Hepatocellular↗

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

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 co-transporter (D-glucose, D-galactose, methyl-alpha D-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-alpha D-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.

3-O-Methylglucose↗

[Individual therapeutic procedure in metastatic carcinoid of the small intestine].

Actually, the therapeutic goal in a metastasized carcinoid tumor is rather symptomatic than curative. Here we report the case of a 53 year old woman with a hepatic and pulmonal metastasized carcinoid tumor of the small intestine. We will discuss current therapeutic options and the approach to the individual patient. After treatment with the standard therapeutics Octreotide and Interferon alpha we could achieve a remarkable and persistent remission by applying the rather unusual drug Dacarbacine in this patient. This is an example for the frequently occurring clinical situation in the treatment of patients with rare tumors requiring the application of individually modified therapeutic regimens. Furthermore, the potency of Dacarbacine in the treatment of carcinoid tumors seems to be underestimated up to now.

Carcinoid Tumor↗