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Biomedical subjects

D M Alscher

Publications and source records attributed to D M Alscher.

At least 19 recordsLinked to original sources
PubMed2006

Hepatic expression of galectin-3 and receptor for advanced glycation end products in patients with liver disease.

BACKGROUND: Advanced glycation end products (AGEs) are a heterogeneous group of glycosylated proteins (of which carboxymethyl-lysine (CML) is the most common) which accumulate during ageing processes and play an important role in the pathogenesis of a variety of chronic diseases. Impaired hepatic function might result in elevated levels of AGEs, as the liver represents the major site of AGE metabolism. The actions of AGEs are mediated by various receptors, among which the AGE-receptor complex (including galectin-3 as an essential part) is thought to have a cytoprotective effect, and receptor for advanced glycation end product (RAGE) a cytotoxic effect. AIM: To assess the relationship between CML and expression of galectin-3 and RAGE in different histological structures in biopsy specimens from patients with varying degrees of liver impairment. METHOD: Immunohistochemical staining of 164 biopsies from patients with varying degrees of liver impairment was performed to determine the levels of CML, galectin-3 and RAGE in hepatocytes, Kupffer cells and bile ducts by a semiquantative score. RESULTS: Independent of diagnosis, CML and RAGEs were detected in hepatocytes, whereas galectin-3 was present only in hepatocytes of cirrhotics. By contrast, CML and galectin-3 were highly expressed in Kupffer cells (well correlating levels, highest scores in cholestasis) whereas expression of RAGEs was not significant. All three assessed biochemical markers showed their highest levels of expression/detection in bile ducts. CONCLUSION: These findings indicate an increased susceptibility of hepatocytes to the detrimental effects of AGEs and underline the protective function of Kupffer cells. Furthermore, the biliary system seems to play an important role in the disposition of AGEs.

Bile Ducts, Intrahepatic↗
PubMed2006

[Disturbances in volume and electrolytes with intestinal and kidney diseases].

The intestines and kidney are the most important excretion organs. Both organ systems are key players in keeping the homeostatic balance regarding hydration and electrolytes. Disturbances of function can lead to enormous and sometimes life-threatening complications. Intestinal diseases lead often to diarrhoea, which can be associated with fluid loss of up to 20 l per day. The accompanying electrolyte disturbances can be hypo- or hypernatremia in combination with hypokalemia. The therapy is substitution guided by knowledge of the pathophysiology. Kidney diseases lead to excessive volume and electrolyte balances, depending on the underlying molecular or pathological defect, but deficiencies can also be found. In case of kidney impairment with 30-50% total loss of function, calcium and phosphate metabolism is impaired.

Humans↗
PubMed2005

[Untreated homocystinuria in adulthood].

HISTORY: Pronounced osteoporosis was discovered in a 44-year-old man presenting with an herniated intervertebral disk. He reported severe myopia, incomplete dislocation of the lenses and retinal detachment. He did not know of any thrombembolic events in the past. On physical examination Marfan-like appearance and a funnel chest were noted. Because of these findings Marfan syndrome was suspected. INVESTIGATIONS: Considering the findings of the x-rays, homocystinuria was suspected as a cause of osteoporosis, despite apparently normal cognitive functions. This diagnosis was confirmed by greatly increased values of serum homocysteine and a positive test for urinary homocystine. Since methionine and homocystine were both elevated, the diagnosis of cystathionin-beta-synthase deficiency was established. DIAGNOSIS, TREATMENT AND COURSE: After taking folate and vitamin B6, the homocysteine level decreased moderately. Betaine and subsequently vitamin B12 were added. Homocysteine values declined markedly on this therapeutic regimen. Two years later the patient was admitted again because of atypical angina. Coronary heart disease could be excluded by coronary angiography. CONCLUSION: Diagnosis of premature osteoporosis should prompt consideration of homocystinuria even in adults. Premature arteriosclerosis, thrombembolic diseases, dislocation of the lens and retinal detachment may give further clues.

Adult↗
PubMed2001

Sustaining continuous ambulatory peritoneal dialysis after herniotomy.

Controversy still exists as to whether peritoneal dialysis (PD) treatment can be safely continued after herniotomy. Many nephrologists withhold PD treatment for several weeks after herniotomy for fear of dialysate leakage and hernia recurrence. Here, we report on 9 patients (2 women, 7 men) in whom herniotomy was performed for umbilical (n = 3), inguinal (n = 5), or cicatricial hernia (n = 2), or for open processus vaginalis (n = 2). Surgery was performed according to the Lichtenstein method with insertion of a polypropylene mesh and ligation of the hernia sac. In all patients, PD treatment was paused for the day of surgery and for 1-3 days postoperatively, depending on residual renal function. Over the next several days, low-volume (1.0-1.5 L), high-frequency (6 per day) exchanges were started. The patient's original PD regimen was gradually reinstated over the next 2-4 weeks. All patients recovered rapidly, with no uremia or dialysis-related complications. Particularly, no leakage and no hernia recurrence could be observed 3 months thereafter. None of the patients had to be hemodialyzed intercurrently. In conclusion, continuing a modified regimen of CAPD treatment after herniotomy seems to be safe, with excellent patient comfort.

Adult↗
PubMed2000

Stimulated IFNgamma and IL-10 secretion of blood mononuclear cells in patients on renal replacement therapies show different secretion patterns.

Infection is still a leading cause of morbidity and mortality in patients on renal replacement therapy (RRT). Although the role of the immune system is of great importance, little is known about the influence of the mode of RRT to the preferential excretions of regulator cytokines of mononuclear cells. Therefore, we investigated the stimulated IFNgamma (Th1) and IL-10 (Th2) secretions of mononuclear cells from patients on RRT. Blood was drawn from 10 controls, 15 patients on hemodialysis (HD), 15 on peritoneal dialysis (PD), and 10 after kidney transplantation (Tx). The cells were separated, and phytohemagglutinine (PHA) was added for stimulation. After 0, 6, and 24 h, IFNgamma and IL-10 (pg/ml) were measured by enzyme-linked immunosorbent assay. IFNgamma secretion was significantly enhanced 6 (p < 0.001) and 24 h (p = 0.002) after stimulation in all groups (in mean +/- SEM). The analysis of the subgroups 6 h after adding PHA showed significant differences (p = 0.0239) with the lowest IFNgamma in Tx (16 +/- 5) and the highest in PD (79 +/- 30). For IL-10, secretion was enhanced in all groups 6 h after stimulation (p < 0.0116). The lowest secretions were seen in HD (18 +/- 8) and controls (27 +/- 9); the highest secretions were in Tx (98 +/- 20) and PD (57 +/- 12). The differences between HD and Tx (p < 0.01) and HD versus PD (p = 0.05) were significant. The stimulated cytokine secretion of blood mononuclear cells is preserved with RRT. The modes of RRT could influence the pattern of cytokine secretion. Surprisingly, the cells from patients on PD showed enhanced IL-10 secretion compared to HD. Presumably, this is due to the chronic contact of peritoneal dialysis fluids with monocytes and the lymphatic system in PD.

Adult↗
PubMed2000

A new lactate-based, plasticizer-free, neutral peritoneal dialysis fluid provided in a two-compartment system: effect on peripheral leukocyte function.

BACKGROUND: A new neutral peritoneal dialysis fluid (PDF; Balance) provided in a two-compartment bag (pH 7.4, no plasticizers, minimal glucose degradation products - GDP) was investigated in comparison with a neutral control (Hanks' balanced salt solution with gelatin 0.1%) and other PDFs with standard properties and plasticizers (Andy plus, pH 5.2, GDP), plasticizer free (stay safe, pH 5.2, GDP), and in addition plasticizer free after sterile filtration instead of heat sterilization (pH 5.2) regarding the function of peripheral blood leukocytes. METHODS: Blood was drawn from 12 volunteers, and blood monocytes (MN) and polymorphonuclear leukocytes (PMNL) were collected. The cells were incubated for 30 min in control medium and the PDFs: glucose 1.5% (83 mmol/l) and 4.25% (238 mmol/l). Respiratory burst of cells was evaluated by chemiluminescence and superoxide (SO) generation after stimulation with phorbol myristate acetate. RESULTS: In comparison with the control medium, incubation of MN in the two-compartment PDF showed preservation of respiratory burst. In contrast, the incubation of MN in standard PDF and plasticizer-free PDF showed impaired functions. The same was found for PMNL. SO anion measurement in MN and PMNL after incubation in the new two-compartment PDF also showed preservation of cell function in comparison with the control medium. The incubation of PMNL in standard PDF and plasticizer-free PDF with a high glucose content showed depressed SO anion generation. CONCLUSIONS: These in vitro data demonstrate a better preservation of in vitro phagocyte function with adaptation of pH and reduction of glucose, GDP, and plasticizers in PDFs. The best results are achieved with the two-compartment, lactate-based neutral PDF.

Adult↗
PubMed1999

Phthalic acid is the main metabolite of the plasticizer di(2-ethylhexyl) phthalate in peritoneal dialysis patients.

Di(2-ethylhexyl) phthalate (DEHP) is the most commonly used plasticizer in polyvinyl chloride (PVC) plastics, and is therefore a major constituent of continuous ambulatory peritoneal dialysis (CAPD) bags. Because DEHP is not chemically bound, it leaches out of the plastic matrix. Recently, we found that leukocyte function in vitro is impaired by a mixture of metabolites of DEHP. In the present study, we investigated the metabolism of DEHP in patients on CAPD. The study group consisted of 10 stable patients, on CAPD for at least 6 months, using a plasticizer-containing PVC PD system [ANDY Plus (Fresenius Medical Care, Bad Homburg, Germany)]. Effluent dialysate and urine samples were collected over 24 hours, and a 10 mL blood sample was drawn. Concentrations of DEHP and its metabolites mono(2-ethylhexyl) phthalate (MEHP), phthalic acid (PA), and 2-ethylhexanol (2-EH) were determined in urine, dialysate, and serum using gas chromatography/mass spectrometry. Additionally, the degree of glucuronidation of the phthalic acid esters in urine were determined. In serum, dialysate, and urine, PA was the predominant metabolite of DEHP (0.205 +/- 0.067 mg/L, 0.284 +/- 0.180 mg/L, and 1.34 +/- 1.00 mg/L, respectively), but concentrations of MEHP were low (0.0100 +/- 0.0056 mg/L, 0.022 +/- 0.008 mg/L, 0.011 +/- 0.0064 mg/L, respectively). Urinary MEHP was glucuronidated to approximately 15%. PA was 35% eliminated as a glucuronide. Unlike healthy subjects, PD patients do not eliminate DEHP mainly in the form of MEHP or MEHP metabolites. They further break these compounds down to PA. The fact that concentrations of PA in urine exceed by far the respective serum concentrations indicates that PA is secreted by the kidney. Further research on the toxicological aspects of plasticizers in uremic patients should take these findings into account.

Chromatography, Gas↗
PubMed1998

[Cervical actinomycosis in systemic lupus erythematosus, nephrocalcinosis and distal renal tubular acidosis (type I-RTA)].

HISTORY AND CLINICAL FINDINGS: A 25-year-old woman presented with a painful soft-tissue swelling in the right neck, which made it impossible to assess the right cervical lymph nodes, while other lymph nodes were unremarkable on palpation. For 9 years she had been known to have polyarthritis. All joints were freely mobile and were without deformity or inflammatory signs. Flexion of the left elbow was slightly painful but freely mobile. There was no skin rash. INVESTIGATIONS: Erythrocyte sedimentation rate was 44 mm/h, there was a leucocytosis of 16,000 granulocytes/ml. There was hypokalaemia (3.5 mEq/l) and a metabolic hyperchloremic acidosis with a pH of 7.27 and a urinary pH of 6.5. Antinuclear and anti-ds-DNA antibodies were raised (ANA: 3.9 multiple of cutoff point [MOC; normal: 0-1.0]; anti-ds-DNA antibodies: 4.0 [normal: 0-1.0])-Fine needle aspiration cytology from the swelling revealed erythrocytes, double-refractory horny lamellae, cellular debris and only a few inflammatory cells. Abdominal ultrasound showed nephrocalcinosis. Microbiological cultures were negative. DIAGNOSIS, TREATMENT AND COURSE: Assuming a bacterial cause of the swelling antibiotic treatment with Phenoxymethylpenicillin (4 MU/d) was initiated. The local findings rapidly improved and the inflammatory parameters regressed to normal. 16 weeks after the initial admission the abscess recurred and biopsy now revealed actinomycetes with typical granules, confirming cervical actinomycosis. The other symptoms indicated autoimmune disease and, together with previous findings, established the additional diagnosis of lupus erythematodes, which caused the type 1 distal tubular acidosis. CONCLUSIONS: This case illustrates the basic approach of establishing an all-encompassing diagnosis that brings together seemingly isolated findings. It is especially in systemic disease that such diagnostic strategy will frequently lead to its recognition.

Acidosis, Renal Tubular↗
PubMed1997

[Therapy of hepatitis C].

The purpose of this review is an update of the therapy of hepatitis C especially with Interferon-alpha. From the large number of publications on this topic the established facts were worked out. Taking these facts as a base guidelines for the therapy in practical use were defined. In addition the aspects of therapeutic strategies of chronic hepatitis C which until now can not definitely be judged are discussed. In the relatively few patients in whom hepatitis C is diagnosed already in the acute phase, Interferon-alpha-treatment (3 x 3 million units 3 times a week) for 3 to 4 months increases the percentage of patients in whom HCV-RNA in the serum is eliminated. In patients with chronic hepatitis C, after decision finding for treatment, a standard scheme is recommended which consists of a monotherapy with recombinant Interferon-alpha. The dosage of Interferon-alpha is in the first 12 to 16 weeks 5 up to 6 million units given 3 times a week. For the further therapy 3 million units 3 times a week seems to be appropriate. The recommended duration of Interferon-alpha-therapy is 12 months. A long-term benefit of about 20% can be achieved in unselected groups of patients when judged on the permanent normalisation of serum transaminases and elimination of HCV-RNA in the serum. Important factors which may influence the probability of a sustained response, like HCV genotype, virus titer in serum, duration of the disease, high hepatic iron content and the presence of cirrhosis, are discussed. Up to now there exist no reliable guidelines in the case of a "no change" situation and for patients with a flare-up of inflammatory activity during or after therapy. Combination therapy of Interferon-alpha with other drugs like analogous of nucleotides (for example ribavarin), non steroidal antirheumatic drugs and ursodesoxycholic acid (UDCA) have still to be evaluated in controlled clinical trials.

Dose-Response Relationship, Drug↗
PubMed1995

Detection of hepatitis C virus antibodies and hepatitis C virus RNA in patients with alcoholic liver disease.

The prevalence of hepatitis C virus (HCV) antibody was determined in 130 patients with alcoholic liver disease using a second-generation anti-HCV enzyme immunoassay (ELISA 2) and confirmed by a sensitive polymerase chain reaction procedure measuring HCV RNA. Hepatic disease was evaluated by clinical and biochemical studies and, whenever possible, by liver biopsy. Seventy-one patients were diagnosed as having cirrhosis, and 59 alcoholic hepatitis (n = 33) or fatty liver (n = 26). The prevalence of anti-HCV in the total group was 9.2% and did not differ significantly in the cirrhotics (11.3%) as compared with the non-cirrhotics (6.8%). HCV RNA was detected in six out of eight cirrhotics and three out of four non-cirrhotics who were ELISA 2 positive. A positive test for antibodies to hepatitis core antigen (anti-HBc) was more frequent in anti-HCV-positive patients (75%) than in the anti-HCV-negative group (14%, P < 0.001). Anti-HBc was also found more frequently in the cirrhotics (25.4%) than in the alcoholics without cirrhosis (11.9%). However, the prevalence of hepatitis B surface antigen was equally low in both groups (cirrhotics 1.4%, non-cirrhotics 1.7%). No correlation was observed between the prevalence of anti-HCV antibodies and the severity of liver dysfunction. These results indicate that HCV, and especially HCV-viraemia, is less frequent in alcoholics in southern Germany than suspected in previous studies, and that the prevalence of HCV markers in alcoholics has been overestimated by ELISA 1 used alone.

Adult↗