First-order wedge wetting revisited.

We consider a fluid adsorbed in a wedge made from walls that exhibit a first-order wetting transition and revisit the argument as to why and how the pre-filling and pre-wetting coexistence lines merge when the opening angle is increased approaching the planar geometry. We clarify the nature of the possible surface phase diagrams, pointing out the connection with complete pre-wetting, and show that the merging of the coexistence lines lead to new interfacial transitions. These occur along the side walls and are associated with the unbinding of the thin-thick interface, rather than the liquid-gas interface (meniscus), from the wedge apex. When fluctuation effects, together with the influence of dispersion forces are included, these transitions display strong non-universal critical singularities that depend on the opening angle itself. Similar phenomena are also shown to occur for adsorption near an apex tip.

Effect of 5-diazouracil on the catabolism of circulating pyrimidines in rat liver and kidneys.

The inhibitory effect of 5-diazouracil on the catabolism of circulating uracil and 5-fluorouracil was examined in the rat in vivo. Measurements of the activity of the entire enzymatic pathway of uracil catabolism in the cytosolic supernatant of different rat organs as well as the determination of the total amount of 5-fluorouracil catabolites, accumulated in these tissues, served to clarify their role in the complete systemic breakdown of uracil or 5-fluorouracil. The activity of the enzymatic pathway involved in uracil catabolism was estimated from the 14CO2 produced from [2-14C]uracil in the cytosolic supernatants. Complete degradation of uracil was detected only in the liver and, at a much lower rate, in the kidneys. Fifteen min after the i.p. injection of a tracer dose of 5-fluoro[6-14C]-uracil, more than 90% of the total radioactivity in blood plasma was associated with 5-fluorouracil catabolites. The relative amount of the major catabolite alpha-fluoro-beta-alanine and of dihydrofluorouracil in blood plasma was considerably suppressed after a pretreatment with 5-diazouracil inversely correlated with a 27-fold increase in the absolute amount of unchanged 5-fluorouracil. Control animals accumulated by far the highest amount of total acid-soluble radioactivity from 5-fluoro[6-14C]uracil in liver and kidneys. Total radioactivity in all other organs was much lower and was comparable to the amount of label in blood plasma. In liver and kidneys, the sum of total acid-soluble catabolites including dihydrofluorouracil, alpha-fluoro-beta-ureidopropionic acid, and alpha-fluoro-beta-alanine made up more than 98% of the label correlating with minimal salvage utilization of the base analogue in both organs. Injection of 5-diazouracil 2 h before a tracer dose of 5-fluoro[6-14C]uracil strongly inhibited the accumulation of labeled catabolites in liver and kidneys causing a fall in total acid-soluble radioactivity in both tissues by 75 and 66%, respectively. In blood plasma and all other organs, however, pretreatment with 5-diazouracil was followed by a 2-fold enhancement of the radioactivity contents, mostly due to the appearance of unchanged 5-fluorouracil. Under these conditions, there was a 2.6- to 4-fold increase in the relative proportion of cis-diol group-containing anabolites of 5-fluorouracil in liver and in kidneys. Within 2 h, 12.7% of the administered radioactivity from 5-fluorouracil was excreted into bile. 5-Diazouracil lowered the biliary excretion of radioactivity to 2% of the injected dose.(ABSTRACT TRUNCATED AT 400 WORDS)

The glutamine analog acivicin as antipyrimidine. Studies on the interrelationship between pyrimidine and urea synthesis in liver.

The inhibition of cytosolic carbamoyl-phosphate synthetase II by acivicin was used to study the role of the cytosolic carbamoyl phosphate pool as the exclusive substrate source for de novo pyrimidine synthesis in rat hepatocytes. De novo pyrimidine synthesis was stimulated: 1. by uridine triphosphate deficiency (incubation with D-galactosamine) leading to a stimulation of cytosolic carbamoyl phosphate synthesis, and 2. by accumulation and efflux of mitochondrial carbamoyl phosphate (incubation with ammonium ions and L-norvaline). The stimulated orotate formation from cytosolic carbamoyl phosphate in UTP depleted cells was completely blocked by acivicin. It was not influenced by an inhibition of mitochondrial carbamoyl phosphate synthesis mediated by 4-pentenoate, since mitochondrial carbamoyl phosphate did not participate in cytosolic pyrimidine synthesis even in the presence of ammonium ion concentrations maintaining physiological rates of urea synthesis. An excess of ammonium ions led to an artificial accumulation and efflux of mitochondrial carbamoyl phosphate, which could be avoided by 4-pentenoate. The non-regulated stimulation of pyrimidine synthesis from surplus mitochondrial carbamoyl phosphate was not inhibited by acivicin. Utilization of mitochondrial carbamoyl phosphate for de novo pyrimidine synthesis presumably does not occur under physiological conditions because mitochondrial CP efflux depends on the accumulation of this metabolite in the mitochondria under experimental or pathological circumstances. Acivicin inhibition of CPS II thus cannot be bypassed by mitochondrial CP. It is suitable as inhibitor of the physiological de novo pyrimidine synthesis.

First clinical experiences with a selective chemotherapy of hepatocellular carcinoma with 5-fluorouridine in combination with other antipyrimidines.

Sixteen unselected patients with non-resectable hepatocellular carcinoma were treated in a phase I study with 261 cycles of D-galactosamine and 6-azauridine prior to 5-fluorouridine. Thirty % of the patients survived for more than one year without signs of tumor progression and with an unchanged performance status. The compatibility of this chemotherapeutical method was quite satisfactory. The only extrahepatic side effect was a leucopenia and/or thrombocytopenia which was reversible upon reduction of the 5-fluorouridine dose. The heterogeneity of the 16 patients treated to date does not allow a definite statistical evaluation of the reported clinical observations and results. A final decision about the clinical applicability of this concept of a selective chemotherapy of hepatocellular carcinoma requires further experience.

[Prospective study of the incidence of ultrasound detectable liver hematomas after laparoscopically controlled liver puncture with the Silverman needle]. / Prospektive Studie zur Häufigkeit von sonographisch nachweisbaren Leberhämatomen nach laparoskopisch gezielter Leberpunktion mit der Silverman-Nadel.

BACKGROUND: A high incidence of hepatic haematomas detected at sonography following percutaneous liver biopsy and laparoscopy-guided liver biopsy has recently been reported. PATIENTS AND METHODS: Prompted by this report, we carried out a prospective study on 71 patients aged between 20 and 79 years (median age: 51 years). The patients were examined by ultrasound prior to and following laparoscopy-guided biopsy with the Silverman needle. RESULTS: Only two of the 71 patients (3%) had a hepatic haematoma after biopsy. The haemangiomas had a maximum diameter of 2.6 cm, caused no pain, and disappeared again within ten days at the latest. No therapeutic measures were required. CONCLUSION: The results of this study indicate that laparoscopy-guided liver biopsy with the Silverman needle is associated with relatively few complications.

[Incidence of ultrasound detectable liver hematomas after ultrasound controlled fine needle puncture with the 0.95 mm cutting biopsy cannula in comparison with percutaneous liver biopsy with the 1.4 mm Menghini needle]. / Inzidenz sonographisch nachweisbarer Leberhämatome nach ultraschallgezielter Feinnadelpunktion mit der 0,95-mm-Schneidbiopsiekanüle im Vergleich zur perkutanen Leberbiopsie mit der 1,4-mm-Menghini-Nadel.

BACKGROUND: Recently, a high incidence of ultrasound-detected hepatic hematomas due to percutaneous liver biopsy has been reported. Until yet, little is known about the incidence of asymptomatic hepatic hematomas following sonographically guided fine-needle biopsy. PATIENTS AND METHODS: For that reason, we carried out a prospective study with sonographic examinations before and after liver biopsy in 160 patients. 51 patients, aged 50 to 83, median 67 years, with focal liver lesions had ultrasound-guided liver biopsy using the 0.95 mm-cut biopsy-needle, in 109 patients (17 to 80, median 49 years) with diffuse liver disease percutaneous liver biopsy with the 1.4 mm-needle of Menghini was performed. RESULT: After fine-needle biopsy none of the 51 patients with focal liver lesions displayed liver hematoma on ultrasonography. In the group of patients who underwent percutaneous Menghini biopsy a liver hematoma, sized up to 12 x 5 cm in diameter, occurred four times (3.7%). CONCLUSION: The results of this study indicate that fine-needle biopsy of the liver is a particularly safe diagnostic procedure, when compared with percutaneous Menghini biopsy.

[Treatment of cholestatic hepatic diseases: more than the substitution of fat soluble vitamins?]. / Therapie cholestatischer Lebererkrankungen: Mehr als Substitution fettlöslicher Vitamine?

The clinical-biochemical syndrome of cholestasis is characterized by an alteration in bile constituents. As a consequence, the concentrations of bilirubin, bile acids, phospholipids and cholesterol are elevated. The main clinical symptoms of cholestasis are icterus and pruritus, and in severe cases xanthelasma and xanthoma. Primary intrahepatic cholestasis, caused by impaired bile secretion in the liver, should be separated from the extrahepatic secondary cholestasis which is a consequence of a biliary obstruction. This paper evaluates the therapy of liver diseases which developed as consequence of a primary disturbance in bile secretion.

[Value of the brief neuropsychological tests for detection of acquired cognitive deficits. Exemplified by the Lehrl and Fischer c.I. (cerebral insufficiency) test]. / Zur Brauchbarkeit leistungspsychologischer Kurztests für den Nachweis erworbener Hirnleistungsminderungen. Dargestellt am Beispiel des c.I.-Tests von Lehrl und Fischer.

The aim of the study was to find whether the c.I. test is useful for the exclusion and the demonstration of acquired cognitive deficits. In all, 195 patients with brain damage and 68 neurotic patients were examined with the c.I. test and with a comprehensive number of neuropsychological tests. The hit rate of the c.I.-test for the whole group was 67% and lay lower than the base rate of 74% brain damaged patients respectively only unessentially higher than the base rate of 64% patients with unambiguous acquired cognitive deficits. There were very low hit rates especially in patients with absent (46%) or low-grade cognitive deficit (54%) and with low (55%) or with high premorbid mental abilities (55%). Both the low correlations between the c.I. test and the validity criterion as well as the considerable overlapping of the c.I. test raw score distributions, grouped by grades of cognitive deficits, indicate serious deficiencies in the test. The extremely brief c.I. test possesses an inadequate grade of difficulty and cannot detect low- and medium-grade acquired cognitive deficits, and its orientation to ability-related global syndromes means that partial, multifactorial and general cognitive deficits are neglected. The c.I. test is therefore not useful as a screening method for the diagnosis of acquired cognitive deficits.

[Comparison of psychodiagnostic methods for dementia and deterioration]. / Vergleich psychodiagnostischer Verfahren zur Demenz- und Abbaudiagnostik.

Several cognitive impairment/dementia diagnostic methods were examined concerning their results: (a) in the differentiation of accidental and pathological ability changes; (b) in the demonstration/exclusion of cognitive impairment; and (c) the degree of dementia. Sixty-five patients suffering from brain damage were examined with five accepted methods of diagnosing dementia (Syndrom-kurztest, KAI-MWT-Methode, Demenz-Test, Mini-Mental-Status-Test, Wurzer-Methode) and a comprehensive performance test battery as an external criterion for valid determination of the degree of dementia and definite differentiation of accidental and pathological performance changes. The five methods of diagnosing dementia differ appreciably in determining the degree of severity (r = 0.44). They are effective in registering accidental performance changes in comparison with the outer criterion, but pathological changes are inaccurately registered (hit rate 88%/53%); the results concerning the degree of cognitive impairment are identical: between 25 and 43% (r = 0.43). High rates (58%) of false-negative diagnoses are especially apparent in the range of slight and intermediate cognitive impairment. The methods examined are only useful for the demonstration and not for the exclusion of severe cognitive impairment (dementia) and in no circumstances for the registration of slight/intermediate cognitive impairment. Valid diagnosis of cognitive impairment/dementia necessitates the use of test batteries that differentiate functions including the premorbid performance level.

[The risk of liver biopsy]. / Zur Frage des Risikos von Leberbiopsien.

Complications have been reported to occur in 0.14 through 0.29% of all patients undergoing liver biopsy. The total incidence of complications is lower in laparoscopically guided biopsy when compared with percutaneous liver biopsy. On the other hand fatal complications appear to be more frequent with laparoscopy (0.038%) than with percutaneous biopsy (0.009-0.017%). Nevertheless, laparoscopic biopsy should be preferred particularly in patients with suspected liver cirrhosis, since laparoscopy is more sensitive for this diagnosis. Until now, the significance of the type of biopsy needle used has not definitively been clarified. The results that are available however indicate, that biopsy with the Tru-cut needle is accompanied by a particularly high bleeding risk. Regarding the results of retrospective studies concerning needle diameter, less serious complications appear to occur after fine needle biopsy when compared with standard needles. Thus, fine needle biopsy should be preferred in patients with focal liver lesions, since the bleeding risk is assumed to be higher in these cases.

[Biochemical and pathophysiological aspects of hyperammonaemia (author's transl)]. / Biochemische und pathophysiologische Aspekte der Hyperammoniämie

1. Ammonia liberated continuously in large amounts in muscle, kidney and brain is used immediately for the synthesis of mainly glutamine because of the toxic effects of elevated ammonia concentrations. After glutamine hydrolysis in the liver ammonia serves as substrate for the urea biosynthesis. In ureotelic animals urea is the quantitatively most important product for the elimination of surplus nitrogen. 2. The rate of urea biosynthesis depends on the amount of surplus nitrogen and acts as regulatory factor for the nitrogen balance of the adult organism. 3. Urea cycle abnormalities in liver diseases or inborn enzymatic defects are important factors leading to hyperammonaemia in patients. 4. The hyperammonaemia induces an increase of the rate of hepatic pyrimidine nucleotide biosynthesis as a consequence of an ineffective feedback inhibition of the glutamine-dependent carbamoyl phosphate synthetase. 5. The distribution of ammonia between intra- and extracellular space and the amount of ammonium ions excreted in the urine depend on the pH value. An alkalosis induces an intracellular ammonia load and inhibits the urinary ammonium ion excretion, which is increased in acidosis as one mechanism of protein elimination. 6. The ammonia-induced inhibition of the citric acid cycle by an alpha-ketoglutarate deficiency is one important reason for the neurotoxicity of ammonia, which is the main point in the pathogenesis of hepatic coma.

[Non-cardiac chest pain]. / Der nicht-kardiale Thoraxschmerz.

Non-cardiac chest pain is caused in 50% by esophageal disorders. About 30% of such esophageal chest pain is induced by gastroesophageal reflux. 2/3 of esophageal chest pain is related to various esophageal motility disorders, which can be differentiated by manometry. Diagnostic procedures for esophageal dysfunction (endoscopy, radiology, long-term pH-metry) have been evaluated. Therapy of gastroesophageal reflux disease has been proven effective; maintenance therapy should be evaluated in further controlled randomized trials. Treatment of esophageal motility disorders, unsatisfactory so far, needs to be improved and standardized.

De novo pyrimidine biosynthesis in isolated rat hepatocytes. Quantitative aspects of the regulation by UTP.

Quantitative aspects of de novo pyrimidine biosynthesis in rat hepatocytes were monitored. A reduction of intracellular UTP contents by different concentrations of D-galactosamine led to a dose-dependent increase of 14CO2 incorporation into the sum of all acid-soluble uracil nucleotides. In controls the rate of de novo synthesis which was calculated from the incorporation rate of 14CO2 into the sum of all acid-soluble uracil nucleotides was 0.014 mumol X h-1 X g-1 compared to 0.056 mumol X h-1 X g-1 wet weight of liver in situations of a maximally stimulated de novo synthesis. Incubation of hepatocytes with uridine led to a dose-dependent reduction of 14CO2 incorporation to less than 25% of the amount incorporated in the controls. Alterations of the CTP content had no influence on the 14CO2 incorporation. In the presence of high D-galactosamine concentrations the increase of the total amount of acid-soluble uracil nucleotides exceeded the rate of the de novo synthesis derived from the incorporation of 14CO2 into the sum of the acid-soluble uracil nucleotide pool. It was also greater than the increase of the total amount of intra- and extracellular orotate after acidic hydrolysis--even in the presence of 6-azauridine, which stimulated de novo pyrimidine biosynthesis by itself.