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Biomedical subjects

A Wahlländer

Publications and source records attributed to A Wahlländer.

16 recordsLinked to original sources

[Sarcoidosis--rare cause of an acute pancreatitis].

A 55-year-old patient was admitted to hospital because of acute epigastric pain which could also be felt in the thorax and the left side of the abdomen. After an examination of the lab results, the patient was diagnosed with an acute pancreatitis. In this particular case alcoholic or biliary genesis could be excluded. The pancreatitis progressed in a non-complicated interstitial form. To exclude malignoma as the cause of the pancreatitis, an endosonographic examination was performed. The endosonography showed multiple pathological lymph nodes in the mediastinum, in the region of the truncus coeliacus and the liver hilus. Endosonographic fine needle aspiration of a mediastinal lymph node was not conclusive. A gastroscopic examination excluded a carcinoma of the oesophagus or stomach. An X-ray of the thorax showed inconspicuous results without any trace of bronchial carcinoma. The CT confirmed the endosonographic findings with pathological mediastinal and double sided hilar lymph nodes which also spread to the truncus coeliacus and the hilus of the liver. In order to obtain a representative histology of these lymph nodes - as lymphoma was suspected - a mediastinoscopy was finally performed. The histopathology showed lymphadenitis and epithelioid cell granulomas pointing to sarcoidosis. In summary, sarcoidosis type I in association with an acute pancreatitis was diagnosed. Due to the spontaneous course of the disease, therapy with corticosteroids was not necessary. The patient was recommended to undergo another CT scan after 2 - 3 months.

Causality↗

Prognostic value of the intravenous 14C-aminopyrine breath test compared to the Child-Pugh score and serum bile acids in 84 cirrhotic patients.

The prognostic value of the intravenous 14C-aminopyrine breath test (ABT) in liver cirrhosis was compared to that of the well-established multiparametric Child-Pugh classification and that of serum bile acids, an endogenous parameter of liver function for which a prognostic value in patients with liver cirrhosis has been demonstrated previously. 84 patients with liver cirrhosis were studied. 32 of the patients died during the observation period. Survival was analyzed for periods of 3, 6 and 12 months after examination. For all chosen observation periods, the Child-Pugh score was of prognostic value. ABT gave prognostic information for periods of 6 and 12 months of survival, but was by far inferior to the Child-Pugh score. Serum bile acids in our population did not yield prognostic information at any time interval studied. We conclude that in our group of cirrhotic patients, the prognostic value of the Child-Pugh classification was by far superior to quantitative liver function tests in predicting survival.

Aminopyrine↗

Detoxification of soman in the perfused rat liver: quantitative uptake and stereoisomer metabolism.

The detoxification of soman (1,2,2-dimethyl-propyl methylphosphonofluoridate) was measured in rat livers, using hemoglobin-free, non-recirculating perfusion in situ. Since the detoxification processes may differ in perivenous and periportal zones of liver parenchyma, soman uptake, stereoselective metabolism and inhibition of esterases were compared in antegrade and retrograde perfusion experiments. At low concentrations of soman (up to about 10 mumol l-1 for 5 min) soman was taken up by the liver nearly quantitatively. About 5% recovery rate in the perfusate corresponded well to the intrahepatic shunt flow. Infusions of higher amounts yielded increasing recovery rates. The racemic infusion medium contained the four isomers of soman, C(-)P(-) to C(+)P(+), in nearly identical amounts, whereas in the effluent perfusate only P(-) isomers were found. Even small amounts of soman (5-120 nmol g-1 liver wet weight) caused significant inhibition of hepatic aliesterase activity. Doses higher than 200 nmol g-1 suppressed esterase activity by more than 90%. No essential differences in soman uptake, stereoselective metabolism or inhibition of esterases were found between antegrade and retrograde perfusion experiments.

Animals↗

Assessment of hepatic function. Comparison of caffeine clearance in serum and saliva during the day and at night.

Hepatic microsomal function was assessed by a caffeine clearance test at night and during the day using saliva and serum samples obtained simultaneously. In 26 patients with cirrhosis, 21 patients with noncirrhotic liver disease and 15 control subjects caffeine elimination correlated well during the day and at night (r = 0.915 for serum and 0.917 for saliva). The correlation coefficients for caffeine clearance in saliva and serum were 0.940 during the day and 0.963 overnight. In the cirrhotic patients, clearance differed significantly from noncirrhotic liver disease and controls in saliva samples overnight: 0.51 +/- 0.45 ml/min per kg versus 0.91 +/- 0.44 and 1.41 +/- 0.56, respectively. Comparable results were obtained for serum clearance overnight and clearances during the day. Serum and saliva clearances at night correlated well with the aminopyrine breath test (rs = 0.884 and 0.907, respectively). Overnight caffeine clearance in saliva might be a simple useful method for assessing progression and prognosis of liver disease.

Aminopyrine↗

[The prognostic value of liver function tests--clinical aspects, laboratory chemical parameters and quantitative function tests].

In view of increasing therapeutic possibilities interest focuses on prognosis of liver cirrhosis. Until nowadays studies on prognosis revealed significant importance only for some parameters: Ascites, encephalopathy and portal hypertension as signs of decompensation, bilirubin, albumin and prothrombin time as laboratory indices of decreasing liver function. The commonly used Child-Pugh-score is based on these parameters and allows a reasonable classification of diseased patients. Cholestasis and inflammation seem to be of minor prognostic importance. Assessment of liver function by quantitative tests is desirable (e.g. aminopyrine breath test, bile acids). The prognostic value, however, has not yet been proven in large studies. Use of these tests should therefore be restricted to studies (prognosis, therapy, indication to liver transplantation).

Hepatic Encephalopathy↗

Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers.

The effects of single oral doses of ketoconazole 400 mg and terbinafine 500 mg on the hepatic microsomal system have been investigated in 8 healthy male volunteers. Microsomal activity caffeine was assessed by following the metabolism of 3 mg/kg bodyweight i.v. administered 1 h after the drug. The inhibitory effect of terbinafine was more pronounced than that of ketoconazole: clearance was decreased from 1.34 ml.kg-1.min-1 in controls to 1.06 and 1.21 ml.kg-1.min-1, respectively, and the corresponding half-life was increased from 5.8 h in controls to 7.6 and 6.7 h, respectively. The apparent volume of distribution remained unchanged. The serum levels of the antimycotics were within the therapeutic range in each subject. Although all three substances are metabolised by microsomes, the kinetic parameters (Cmax, half-life, elimination constant) of the antimycotics were poorly if at all correlated with the elimination of caffeine.

Adult↗

Effect of dietary caffeine on airway reactivity in asthma.

The potential influence of dietary caffeine on bronchoprovocation challenges with carbachol was examined in 7 patients with asymptomatic asthma. In a double-blind fashion placebo or caffeine (6 mg/kg body weight; equivalent to approximately 4 cups of coffee) solved in orange juice was administered, and carbachol challenges were performed. The average peak serum concentration achieved 60 min after dosing was 7.6 +/- SD 2.1 mg/l. These caffeine levels did not produce any appreciable attenuation of the bronchoconstrictor response to carbachol inhalations. It thus appears that dietary caffeine is barely a cause of erroneous interpretations of bronchoprovocation challenges with carbachol.

Administration, Oral↗

High-performance liquid chromatographic determination of dimethylxanthine metabolites of caffeine in human plasma.

A normal-phase high-performance liquid chromatographic assay of caffeine and its metabolites, theophylline, theobromine and paraxanthine, in human plasma is described. The two internal standards ethyltheophylline and 1,3,7-trimethyluric acid are used simultaneously and cover the range of different polarities from caffeine to the three dimethylxanthines. Plasma (0.5 ml) in the presence of ammonium sulphate is extracted with chloroform--isopropanol (1:1, v/v). The extract is chromatographed with a LiChrosorb Si 60 5-micron column and a mobile phase of dichloromethane containing 2.5% of a formate buffer in methanol. Calibration is performed with six different calibration mixtures which take into account the large plasma concentration differences between caffeine and its metabolites in man. The method is suitable for the simultaneous determination of caffeine and its dimethylxanthine metabolites in plasma of healthy and diseased persons.

Ammonium Sulfate↗

Fasting plasma caffeine concentration. A guide to the severity of chronic liver disease.

Fasting plasma caffeine concentrations (FPCC) were measured in 86 outpatients being examined for suspected or known liver disease. Seven patients (8%) who avoided caffeine consumption had nonmeasurable FPCC; they were dropped from further consideration. The remaining 79 subjects were divided into 4 diagnostic groups: surgical shunt (n = 11); alcoholic, posthepatitic, or primary biliary cirrhosis (n = 29); miscellaneous liver disease (n = 23); and normal liver (n = 16). FPCC was highest (mean, 17.8 mumol/l) in the shunt group, followed by the cirrhosis (12.3), miscellaneous liver diseases (4.6), and normal liver (2.1) groups. FPCC seemed to reflect severity of functional impairment, further supported by highly significant correlations with quantitative liver function tests, such as aminopyrine breath test (Rs = -0.89; n = 66), indocyanine green disappearance (Rs = -0.85; n = 65), and galactose elimination capacity (Rs = -0.70; n = 75). A careful dietary history showed no significant difference in caffeine consumption among the groups. It is suggested that in regular coffee drinkers FPCC might serve as a simple and convenient guide to the severity of functional impairment in chronic liver disease.

Adult↗

Evaluation of caffeine plasma levels by an automated enzyme immunoassay (EMIT) in comparison with a high-performance liquid chromatographic method.

A new enzyme immunoassay (EMIT) for the measurement of levels of caffeine in plasma was adapted to an automated centrifugal analyzer (Cobas Bio) and compared with a high-performance liquid chromatographic (HPLC) method. Precision of the EMIT test was similar to that of the HPLC method with intraassay coefficients of variation in the range of 2.0-4.1% (EMIT) and 1.5-3.3% (HPLC), respectively, depending on the concentration range tested. Day-to-day precision ranged from 2.7 to 5.6% for EMIT and was 3% for HPLC. Comparison of 69 patient samples assayed with both methods yielded the following equation: y = 1.06x + 1.25 mumol/L, r = 0.994 (X = HPLC, y = EMIT). Evaluation of the cross-reactivity of the three main human caffeine metabolites revealed no significant interference from theobromine and theophylline; however, there was significant interference (28%) by paraxanthine at a concentration range from 2.5 to 80 mumol/L. At low caffeine concentrations, up to 10 mumol/L, the level of this metabolite may be more than twice the corresponding caffeine concentration; therefore, the latter may be falsely elevated in the EMIT test. Despite this cross-reactivity, the new EMIT test proved to be suitable for use in a drug assay laboratory, as well as in the routine screening of outpatients for liver disease.

Caffeine↗

Overnight salivary caffeine clearance: a liver function test suitable for routine use.

The feasibility of measuring caffeine clearance from saliva (SCl) was assessed in ambulatory patients with liver disease and in a control group, and the results were compared with quantitative liver function tests. For this purpose, the subjects were given 280 mg caffeine p.o. in decaffeinated coffee powder between noon and 4 p.m., and caffeine concentrations were measured in saliva (using an enzyme immunoassay) before bedtime and upon arising. In the cirrhotics (n = 29), SCl was 0.58 +/- S.D. 0.45 ml per min X kg, thus being reduced to approximately one-third of drug-free, nonsmoking controls (1.53 +/- 0.46, n = 18); although patients with noncirrhotic liver disease showed intermediate values (0.95 +/- 0.47), their reduction in SCl was significant (p less than 0.001). SCl was correlated with indocyanine green fractional clearance, galactose elimination capacity and aminopyrine breath test; however, the closest relationship (Rs = 0.80) was observed with the aminopyrine breath test. It is suggested that the measurement of SCl represents a noninvasive and innocuous procedure for quantifying hepatic microsomal function, and is suitable for routine use. Since a.m. saliva concentrations of caffeine are highly correlated (Rs = -0.94) with SCl, further simplification of the test to a single-point measurement appears possible.

Ambulatory Care↗