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Biomedical subjects

H Hartmann

Publications and source records attributed to H Hartmann.

At least 37 records · Page 2Linked to original sources
PubMed1998

In vitro reactivity of cryoglobulin IgM and IgG in hepatitis C virus-associated mixed cryoglobulinemia.

BACKGROUND/AIMS: Mixed cryoglobulinemia is frequently associated with chronic hepatitis C virus infection. We aimed to clarify the mechanism, kinetics and participating proteins in cryoprecipitate formation, which are still being debated. METHODS: Eighteen patients with cryoglobulinemia were studied. Isolated serum cryoprecipitates and purified cryoglobulin IgM and IgG fractions were analyzed in vitro by turbidimetry for temperature-dependent complex formation. Immunoglobulin reactivity, i.e. in cryoprecipitates and in cryoglobulin-free sera, was studied using immunoblot and enzyme immunoassays. HCV RNA was detected by reverse transcriptase/polymerase chain reaction. RESULTS: By turbidimetry, purified cryo-IgM precipitated (in the absence of HCV RNA) with cryo-IgG as well as with non-cryoglobulin IgG and with IgG Fc or F(ab')2 fragments. In contrast, purified cryo-IgG did not precipitate with non-cryoglobulin IgM. Anti-HCV IgG reactivity was found in cryoglobulin-free sera, in cryoprecipitates and in purified cryoglobulin IgG fractions. The respective titers were similar. Purified cryo-IgM did not react to HCV-encoded proteins. Binding of cryo-IgM to heterologous IgG was inhibited by intact IgG (up to a mean of about 52%) as well as by IgG Fc (33%) and F(ab')2 fragments (17%). Binding of cryo-IgM to IgG was enhanced at low temperature (4 degrees C vs. 37 degrees C), particularly for type III cryoglobulin IgM. CONCLUSIONS: In hepatitis C virus-associated cryoglobulinemia the in vitro precipitate formation depended on cryo-IgM, while IgG appeared to act as an unspecific antigenic partner. Hepatitis C viral particles were probably not required. Cryo-IgM binding occurred primarily to intact IgG. Anti-HCV reactivity of either cryo-IgM or cryo-IgG was not necessary for precipitate formation. Regarding the pathogenesis, a direct hepatitis C virus protein-dependent stimulation of B-cells producing cryo-IgM seems to be unlikely.

Cryoglobulinemia↗
PubMed1998

Mouse insulin-like growth factor binding protein-6: expression, purification, characterization and histochemical localization.

The mitogenic and metabolic activities of insulin-like growth factors (IGF) are modulated by a family of six high affinity IGF binding proteins (IGFBPs). This study describes the expression of the mouse IGFBP-6 which is unique among IGFBPs in its preferential binding of IGF II, in insect cells using the baculovirus system. The purified, O-glycosylated IGFBP-6 was functional as shown by IGF binding and by inhibition of IGF II-stimulated DNA synthesis in human fibroblasts. Specific antibodies generated in chicken against the recombinant IGFBP-6 were used for Western blotting analysis and immunohistochemistry. Strong immunoreactivity was found in ossifying bones of the cranial base, in cell clusters of the pancreas anlage, in the trigeminal ganglion, on myoblasts, on motoneurons of the spinal cord of embryonic mice. In tissues of adult mouse, strong IGFBP-6 immunostaining was present in epidermal and peridermal layers of the skin, in meningeal layers, in long-striated skeletal muscle, and in the Langerhans' islets of the pancreas. No immunopositive staining was observed in lung and liver indicating that sites of synthesis and IGFBP action are different.

Animals↗
PubMed1998

Characterization of the insulin-like growth factor axis in a human hepatoma cell line (PLC).

The insulin-like growth factors (IGF-I and -II) are structurally related peptides participating in the regulation of metabolism, growth and cellular differentiation. In the present study, the human hepatoma cell line PLC was studied for the expression of individual components of the IGF axis. Northern blot analysis using IGF-I and -II coding cDNAs failed to detect IGF-I- or -II-specific transcripts in total RNA from PLC cells. Biosynthesis of type I and II IGF receptors was demonstrated by northern blotting and binding studies as well as cross-linking of the respective radiolabeled ligand. Both IGF-I and -II stimulated [3H]-thymidine incorporation dose-dependently. The mitogenic activity of exogenously added IGFs was reduced by the presence of IGF-binding proteins of 24, 30, 34, 41 and 45 kDa in supernatants of PLC cells identified as IGFBP-4, -1, -2 and -3, respectively, by [125I]IGF-I ligand-, immuno- and northern blotting. Biosynthesis of IGFBP-3 was stimulated dose-dependently by IGF-I and -II, while IGFBP-1, -2 and -4 were not affected. The increase of IGFBP-3 in response to IGF-I and -II was due to a stimulation of IGFBP-3 specific mRNA as well as to an inhibition of IGFBP-3 endocytosis. Proteolytic activity for rhIGFBP-3 was detected in media from PLC cells at acidic pH that was inhibited by the aspartyl protease inhibitor pepstatin A as well as after immunodepletion of cathepsin D from media of PLC cells. Thus, a role of cathepsin D for the regulation of IGFBP-3 bioavailability via endocytosis in acidic prelysosomal compartments was suggested. The susceptibility of PLC for IGF-I and -II was restricted by their ability to increase the abundance of inhibitory IGFBPs and to decrease the level of IGF-I receptor expression. The present data point to the IGF axis as a complex regulatory system that self limits the mitogenic activity of exogenous IGFs.

Blotting, Northern↗
PubMed1998

Transjugular intrahepatic portosystemic stent-shunt after orthotopic liver transplantation in a patient with early recurrence of portal hypertension of unknown origin.

A 65-year-old italian patient developed complicated portal hypertension immediately after orthtopic liver transplantation (OLT) necessitating shunt creation. One to five weeks after OLT, massive ascitic fluid losses of up to 121/day developed. Vascular and major hepatic-parenchymal abnormalities were excluded by duplexsonography, angiography and initial histology, respectively. A peritoneovenous shunt (Denver-shunt) on day 31 after OLT reduced (by about 50%) but did not stop ascitic fluid losses. Furthermore, three variceal bleedings occurred after implantation of the Denver-shunt. Direct portography on day 45 after OLT revealed portal hypertension (pressure gradient of 26 mmHg) requiring the implantation of a transjugular intrahepatic portosystemic stent-shunt (TIPS) leading to a reduction of the pressure gradient to 13 mmHg. Subsequently, ascites resolved within ten days and esophageal varices improved. Liver function parameters normalized inspite of recurrence of HCV infection with detection of HCV RNA in serum already in the fifth week after OLT. During follow-up, histological findings deteriorated from mild changes to extended fibrosis at day 61 after OLT, which might have contributed to the maintenance of portal hypertension. The deterioration of liver histology was accompanied by an improvement/normalization of liver graft function. There was no evidence for additional viral liver infections, e.g. hepatitis B or cytomegalovirus infection. This case illustrates an etiologically unclear syndrome developing directly after OLT and reaffirms the effectiveness of TIPS in the treatment of complicated portal hypertension even after liver transplantation.

Aged↗
PubMed1998

[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↗
PubMed1997

[Refractory hydrothorax in primary biliary cirrhosis: successful treatment with transjugular intrahepatic portosystemic stent shunt].

HISTORY AND CLINICAL FINDINGS: A 55-year-old woman with known primary biliary cirrhosis (PBC) was hospitalized because of increasing dyspnoea. A year before she had for the first time experienced a right-sided pleural effusion which had to be drained every 4 weeks. Physical examination revealed dullness on percussion and greatly decreased breath sounds on auscultation over the entire right thorax. In addition there were signs of moderate ascites and leg oedema. INVESTIGATIONS: Chest radiograph showed a homogeneous shadowing of the right thorax without mediastinal shift. Diagnostic thoracocentesis produced a serous effusion, a transudate on chemical analysis, comparable to the composition of the ascitic fluid. Bacteriological and cytological tests on both fluids were unremarkable. TREATMENT AND COURSE: The right pleural effusion was presumed to be due to a hydrothorax from the ascites caused by portal hypertension associated with the PBC. Despite continuous diuretic treatment and thoracocentesis with albumin substitution every 3 days there was no improvement and implantation of a transjugular intrahepatic portosystemic stent shunt (TIPSS) was performed. This effectively lowered portal pressure and markedly improved the patient's condition so that further thoracocentesis were no longer necessary. 3 weeks after TIPSS implantation she was discharged in good condition. Radiography 3 weeks later demonstrated continued reduction in the hydrothorax. CONCLUSION: Hydrothorax is a rare complication of liver cirrhosis. TIPSS implantation can provide lasting resolution and corresponding clinical improvement of a hydrothorax, especially in those conditions which are refractory to diuretic treatment and thoracocentesis.

Diuretics↗
PubMed1997

[Extrahepatic manifestations of HBV and HCV infection].

Acute as well as chronic infections by HBV and HCV can be associated with extrahepatic disease. As in liver disease of non-viral etiology, several extrahepatic manifestations can be observed that are non-specific for HBV or HCV, e.g. those clinical signs and symptoms frequently encountered when cirrhosis of the liver is present. In addition, distinct clinical conditions have been described in which the unterlying liver disease is specifically due to HBV or HCV infection. In chronic HBV infection, glomerulonephritis (of the membranous and of the membranoproliferative type) and polyarteritis nodosa have been observed. The pathogenesis of both conditions involves the deposition of circulating immune complexes. Although controlled trials are lacking, interferon therapy appears to be beneficial. The use of immunosuppressive drugs and of plasmapheresis should probably be limited to the initial phase of treatment. In chronic HCV infection, mixed cryoglobulinemia (and ensuing systemic vasculitis) is a frequent extrahepatic manifestation. The clinical presentation might include the presence of purpura, arthralgias, weakness and renal involvement. Nowadays, HCV can be regarded as the etiological agent of a form of mixed cryoglobulinemia formerly considered to be 'essential'. In addition, an association to lymphoma has been postulated recently. Interferon alpha has been used for treatment with similar response rates as those observed in HCV-infected patients without cryoglobulinemia. Interestingly, the antiviral activity of interferon, e.g. normalization of transaminases and loss of serum HCV RNA, was closely related to the beneficial effect on cryoglobulinemia. An association of Sjögren's syndrome and of porphyria cutanea tarda to HCV infection (though claimed before) remains questionable. Serological markers of autoimmunity, e.g. antinuclear antibodies or anti-LKM-1, are present in many patients with chronic HCV infection. The clinical relevance of this latter observation appears low however, particularly since the decision for interferon treatment is hardly influenced by their presence.

Autoimmune Diseases↗
PubMed1997

Neuronal localization of presenilin-1 and association with amyloid plaques and neurofibrillary tangles in Alzheimer's disease.

Mutations in the presenilin-1 (PS1) gene is a cause of early- onset familial Alzheimer's disease (AD). Endogenous PS1 is associated with the endoplasmic reticulum in the cell body of undifferentiated SH-SY5Y neuroblastoma cells. At early stages of neuronal differentiation in rat hippocampal culture, PS1 appears in all neuritic processes and in growth cones. In mature differentiated neurons, PS1 is concentrated in the somatodendritic compartment but is also present at lower levels in axons. A similar localization of PS1 is observed in vivo in neurons of the adult human cerebral cortex. In sporadic AD, PS1 appears in the dystrophic neurites of mature amyloid plaques and co-localizes with a subset of intraneuronal neurofibrillary tangles (NFTs). About 30% of hippocampal NFTs are labeled with a highly specific antibody to the PS1 C-terminal loop domain but not with an antibody to the PS1 N terminus. This observation is consistent with a potential association of the PS1 C-terminal fragment with NFTs, because PS1 is constitutively cleaved to N- and C-terminal fragments in neurons. These results suggest that PS1 is highly expressed and broadly distributed during early stages of neuronal differentiation, consistent with a role for PS1 in neuronal differentiation. Furthermore, the co-localization of PS1 with NFTs and plaque dystrophic neurites implicates a role for PS1 in the diverse pathological manifestations of AD.

Alzheimer Disease↗
PubMed1997

Developmental regulation of presenilin-1 processing in the brain suggests a role in neuronal differentiation.

Most cases of early-onset familial Alzheimer's disease are caused by mutations in the presenilin genes. Presenilin-1 (PS1) is subject to proteolytic cleavage resulting in the accumulation of N- and C-terminal fragments. In this report, we show that the proteolytic cleavage of PS1 is developmentally regulated in the brain. Low levels of full-length PS1 and higher levels of 30-kDa N-terminal and 20-kDa C-terminal fragments are identified at all developmental stages in the rat brain. However, in the adult brain, additional 36-kDa N-terminal and 14-kDa C-terminal fragments appear and become major PS1 species. Alternative N-terminal PS1 fragments also appear in the adult human brain, but are more heterogenous than in the rat brain. The alternative PS1 fragments are not detected at significant levels in rat or human peripheral tissues that express PS1. The alternative cleavage of PS1 is also detected in primary cultures of rat hippocampal neurons, but not in astrocytes, and is induced by neuronal differentiation. Furthermore, alternative PS1 cleavage is detected in rat PC12 cells and human neuroblastoma SH-SY5Y cells following induction of neuronal differentiation. These results suggest that an alternative pathway of PS1 proteolytic processing is induced in the brain by neuronal differentiation. PS1 may therefore play an important role in brain development and neuronal function, which may relate to the brain-specific pathological effects of PS1 mutations.

Aging↗
PubMed1997

[Quality assurance in rheumatology. Evaluation of a team work model between general practitioners and a rheumatologist].

The intention of the project was to heighten the theoretical and practical skills of general practitioners in the care of patients with musceloskeletal problems. Six general practitioners and a rheumatologist participated. The rheumatologist joined the general practitioners at two health centres, which he visited on two occasions with an interval of six months. The patient and case history were presented by the local physician, and an additional historical and physical examination was performed by the rheumatologist. The physicians were trained in relevant examination techniques. The study was evaluated by means of questionnaires to the doctors and interviews with six patients. The theoretical knowledge of the general practitioners increased by an average of 23%. Both general practitioner and rheumatologist observed improvement in examination techniques. This parameter was not specifically evaluated. The patients appreciated the way in which they were treated. They found that the first and second line health care served as a smooth-working team. The cost of this project was low. The model is being continued at the request of the general practitioners.

Clinical Competence↗
PubMed1997

[TIPSS in the Budd-Chiari syndrome with portal vein thrombosis].

HISTORY AND CLINICAL FINDINGS: A 41-year-old woman, known for 10 month to have polycythaemia vera, developed severe right upper abdominal pain. The abdomen was tense from marked ascites and the liver enlarged by 18 cm in the mid-clavicular line. INVESTIGATIONS: Serum bilirubin was slightly elevated to 2.2mg/dl, liver synthesis being much reduced (recalcifying time minimally 23%, albumin minimally 2.8 g/dl). Doppler sonography detected no flow in the right and middle hepatic veins, indicating Budd-Chiari syndrome. Portal vein flow was diminished. TREATMENT AND COURSE: Heparin treatment had to be stopped because of heparin-associated type II thrombocytopenia and hirudin was substituted. Attempted lysis with a total of 100 mg r-tPA failed. As the patient's condition deteriorated a TIPSS was implanted to provide portal decompression. Incomplete portal vein thrombosis was demonstrated and worsened during the procedure until nearly complete occlusion. Local lysis treatment for 2 days with urokinase, 50,000-60,000 U/h, and two shunt revisions finally succeeded in completely dissolving the thrombus. Portocaval pressure fell from 32 to 21 mm Hg, and the size and function of the liver became almost normal and the ascites disappeared. Anticoagulation with a coumarin derivative was started and hydrocarbamide again given for recurrent thrombocytosis. The patient remained largely symptom-free one year after TIPSS. CONCLUSION: This case demonstrates the effectiveness of TIPSS in Budd-Chiari syndrome, even in complicated portal vein thrombosis.

Adult↗
PubMed1997

Analysis of histopathological manifestations of chronic hepatitis C virus infection with respect to virus genotype.

Hepatitis C virus (HCV) causes acute and often chronic hepatitis. On the basis of variations in nucleotide sequence, at least six genotypes and several subtypes have been identified. Histopathologically, chronic HCV infection is characterized by relatively mild hepatic inflammatory activity and a low degree of fibrosis, but hepatic lesions might be accompanied by bile duct damage, intraportal lymphoid aggregates, steatosis, or a combination of these manifestations. The histopathological lesions thus appear quite heterogeneous. To address the question of whether distinct histopathological manifestations are related to particular genotypes of HCV, 90 patients with chronic HCV infection were analyzed regarding histopathological features, biochemical liver parameters, demographic data, and virus genotype. The results revealed a significantly higher prevalence of both steatosis and bile duct lesions among patients infected by HCV type 3a compared to patients infected by types 1a or 1b. Furthermore, the data suggest interrelationships between virus genotype, patient's age, and a history of intravenous drug abuse. However, none of the histopathological manifestations were found to be related to a history of drug abuse. The data further corroborate the relationship of HCV type 1b infection to age, duration of disease, and the degree of fibrosis, respectively. Irrespective of HCV genotype, elevated serum ALT activity was shown to be associated with pronounced inflammatory activity or pronounced steatosis as well. Thus, the current data support the hypothesis that distinct genotypes of HCV appear to be associated with distinct manifestations of disease.

Adult↗
PubMed1997

Interferon-alpha treatment of hepatitis C virus-associated mixed cryoglobulinemia.

BACKGROUND/AIMS: Chronic hepatitis C virus infection is frequently associated with mixed cryoglobulinemia. The efficacy of interferon-alpha treatment in the presence of cryoglobulinemia, particularly the rate of sustained responders, has not yet been well defined. METHODS: Fifty-nine consecutive patients with chronic HCV infection were studied prospectively with regard to the presence of cryoglobulinemia and their biochemical and virological response to interferon-alpha2a therapy. RESULTS: Cryoglobulins were detected in sera of 23 patients. For this latter group of patients, significant differences were found compared to the 36 patients without cryoglobulinemia, i.e. the prevalence of female sex was higher, the duration of liver disease was longer and distinctive laboratory abnormalities, e.g. higher rheumatoid factor activity, were noted as well as a higher prevalence of cirrhosis. The distribution of HCV genotypes and serum HCV RNA titers was similar in the two groups. Interferon-alpha treatment regimens were not different regarding mean cumulative dose and mean duration of therapy. The response to therapy was almost identical, i.e. 35% of patients with cryoglobulinemia showed a sustained response compared to 22% of patients without cryoglobulinemia. The percentages of patients showing a relapse or breakthrough were similar in both groups. Pre-treatment viremia levels were higher in non-responders compared to sustained responders. Non-responders appeared to be more frequent among patients infected with genotypes 1a and 1b, especially among male patients without cryoglobulinemia. CONCLUSIONS: The presence of cryoglobulinemia per se in chronic HCV-infected patients does not adversely affect the outcome of interferon-alpha therapy, including the rate of sustained response.

Adult↗
PubMed1997

Clinical, biochemical, and histological changes in hepatitis C virus infection-associated cryoglobulinemia.

The most common extrahepatic manifestation of HCV infection is mixed cryoglobulinemia (MC). 62 unselected patients with chronic HCV infection were prospectively evaluated for the presence of cryoglobulinemia and associated clinical and biochemical parameters. Furthermore, a putative relationship between the HCV genotypes and cryoglobulinemia was tested. Histological features typical for HCV infection were comparatively analyzed in cases with and without cryoglobulinemia. Whether an intrahepatic Th2-response is responsible for the strong antibody production causing cryoglobulinemia was also examined. Cryoglobulins were detected in sera of 30 patients (approximately equal to 48%). Patients with cryoglobulinemia were on the average elder, showed an apparent longer duration of infection, and suffered more frequently from arthralgia, accompanied by a significant increase of total serum IgM concentration and rheumatoid factor activity. The HCV genotype distribution among patients with cryoglobulinemia was not different from that found in patients without cryoglobulinemia. In cases with cryoglobulinemia, an increased activity of chronic hepatitis and a higher grade of liver fibrosis was noted. The prevalence of HCV-typical histological lesions among all patients were: Portal lymphocytic aggregates (40%), bile duct damage (35%), steatosis (47%), and intracellular acidophilic bodies (29%). A significant correlation, however, could not be found between cryoglobulinemia and the presence of HCV-typical histological lesions. An intrahepatic Th2-response causing an increased antibody production could not be observed in cases with cryoglobulinemia.

Adult↗
PubMed1997

[Pathogenesis and diagnosis of systemic acidosis in animals with conclusions for effective forms of therapy].

Intermediary metabolism produces daily approximately 285 mmol hydrogen ions per kilogramm metabolic body weight (BWkg 0.75). If the lung fails to eliminate the volatile acid H2CO3 sufficiently and/or if the kidneys do not eliminate the also produced nonvolatile acids a retention of acids in the organism results. This way, as well as increased acid production through metabolic processes, leads to a systemic acidosis. Systemic acidosis develops after a primary dysfunction of an organ. If there is only one cause of an acid-base-disturbance, e.g. metabolic acidosis, the organism will respond with compensation by the correspondent organ, e.g. the lung, which reduces the drop in the pH. If metabolic and respiratory acidosis occur simultaneously normal compensation is impaired and the fall in the pH is greater by additive effects. This can lead to a severe, life-threatening decline in the blood-pH (< 7.00). If the pH falls from normal value of 7.40 below 7.20, buffer therapy is necessary. Most alkalinizing agents in veterinary medicine, such as bicarbonate, lactate or acetate are only effective after increased pulmonary elimination of CO2 produced in buffer reactions. These substances are not suitable and are even contraindicated in therapy of primary respiratory or mixed respiratory-metabolic acidosis. New buffer agents, e.g. an equimolar mixture of NaHCO3 and Na2CO3 (= Carbicarb) open new promising possibilities in the treatment of acidotic disorders in animals. However clinical trials to determine the efficacy of Carbicarb in animals are still to be conducted.

Acid-Base Equilibrium↗