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H Hartmann

Publications and source records attributed to H Hartmann.

At least 91 records · Page 5Linked to original sources

[Diagnostic and pathophysiological aspects of the determination of kidney function in animals].

Early diagnosis of loss in renal function (< 60-70%) is not possible either by resorting to the parameters of plasma urea and creatinine concentrations (responsive to functional loss by > 75% or by reference to urine concentration capacity (urine density: sensitive to concentrations > 60%). However, clearance techniques for determination of the glomerular filtration rate (GFR) have proved suitable for quantitative assessment of renal function. Endogenous creatinine clearance is one of the most common clinical approaches in GFR determination. Criticism of results obtainable from endogenous creatinine clearance appears to be justified by pharmacokinetic aspects of creatinine as an indicator, as well as by some of its analytical peculiarities. The tediousness of the procedure is another counterproductive aspect pertaining to large-scale use of endogenous creatinine clearance in veterinary medicine. Total blood-plasma clearance of exogenous creatinine (T-Clexo.Creatinine) would provide vets with an accurate (diagnostic validity) and practical method for carrying out clinical kidney-function diagnostics. However, more research on a number of related issues will be required before the general introduction of the procedure.

Animal Diseases↗

Cryoglobulinemia in chronic hepatitis C virus infection: prevalence, clinical manifestations, response to interferon treatment and analysis of cryoprecipitates.

Chronic hepatitis C virus infection can be associated with mixed cryoglobulinemia and systemic vasculitis. The pathogenesis remains poorly understood. 55 consecutive patients with chronic HCI infection (anti-HCV- and serum HCV RNA-positive) were studies prospectively. Cryoglobulinemia was detected in 28 patients (51%) with a mean cryocrit level of 2.2%. Clinical symptoms of vasculitis were encountered in six patients. Compared to those HCV-infected patients without cryoglobulinemia the following distinctive features were observed in the presence of cryoglobulinemia: increased age (p<0.02), female preponderance (p<0.002), longer-lasting HCV infection (mean of 10.7 vs. 4.7 yrs), higher prevalence of cirrhosis (42.8 vs. 0%), increased serum concentration of IgM and increased rheumatoid factor activity, decreased concentration of serum C4 (each p<0.05). The response to interferon treatment was similar in patients with and without cryoglobulinemia. When cryoprecipitates were analyzed by immunofixation, type II cryoglobulinemia was present in 1/3 and type III in 2/3 of patients. By SDS-PAGE four different proteins were demonstrable in cryoprecipitates each identified by immunoblotting as IgG and IgM heavy or light chains respectively. Cryoprecipitate IgGs were shown to react with HCV structural as well a non-structural proteins in a recombinant immunoblotting assay (RIBA). In contrast, cryoprecipitate IgMs reacted only to the HCV core protein c22-3. HCV RNA was detected in cryoprecipitates without a significant enrichment when compared to the corresponding serum or supernatant HCV RNA content. Given the monoclonality of some cryoprecipitate IgM and their reactivity to HCV core, a cross-reactivity to IgG was postulated. In fact, when performing a computer-assisted search for sequence homology, a motif within the core protein (EGLGWAGWL, conserved in HCV genotypes) was identified homologous to a sequence of IgG heavy chains. Thus, temperature-dependent affinity changes of IgM anti-HCV core (nonapeptide) and ensuing complex formation with IgG via binding to the homologous IgG sequence could be a mechanism of cryoprecipitate formation.

Adult↗

[Nitric oxide in therapy of pulmonary hypertension after correction of congenital single atrium].

We report on a 19-month-old boy with congenital single atrium. Cardiac catheterization preceding the surgical repair revealed an elevated pulmonary artery pressure of 60/15 mmHg (mean pressure 40 mmHg). Pulmonary flow was 8.4 l/min.m2 and systemic flow was 5.5 l/min.m2. Pulmonary arteriolar resistance was elevated to 4.2 U.m2 with 64% left-right shunt and 25% right-left shunt. Arterial O2-saturation varied around 90%. After surgical repair (insertion of a Goretex patch), the patient required mechanical ventilation with 100% oxygen for adequate oxygenation. Cardiac catheterization was repeated on the first postoperative day. No residual shunts were found. The pulmonary artery pressure was 66/40 mmHg (mean pressure 50 mmHg), systemic arterial pressure was 85/62 mmHg (mean pressure 68 mmHg). Cardiac index was 2.8 l/min.m2, pulmonary vascular resistance was 12 U.m2. After administration of prostacyclin a significant decrease of pulmonary artery pressure was observed, but without changing the ratio between pulmonary and systemic pressure. The AaDO2 varied between 400 and 580 mmHg and the oxygenation-index (PaO2/FiO2) was less than 1.0. In this situation, an attempt with inhaled nitric oxide (NO) was performed. After adding 20 ppm NO to the inspired gas, the AaDO2 decreased significantly from 580 to 270 mmHg and the oxygenation-index (OI) rose from 0.9 to 1.5. The inspired fraction of oxygen could be reduced quickly to 60%. During the next days, the concentration of NO was reduced stepwise to 1 ppm. Finally, the AaDO2 was within the normal range (25-65 mmHg) and the OI rose to a level about 4.0. The FiO2 could be reduced to 30% and nitric oxide therapy could be stopped and the child could be extubated.

Administration, Inhalation↗

Apolipoprotein E and cholesterol affect neuronal calcium signalling: the possible relationship to beta-amyloid neurotoxicity.

Besides the neurotoxic properties of beta-amyloid (beta A4), apolipoprotein E polymorphism seems to play an important role in the pathogenesis of sporadic Alzheimer's disease (AD). The calcium amplifying effect of beta A25-35 (the neurotoxic sequence of beta A4) in dissociated mouse brain neurons and human lymphocytes was nearly abolished by cholesterol (100-500 mumol/l). This effect may be related to the membrane stabilizing properties of cholesterol which could be confirmed by measurements of membrane fluidity. ApoE did not affect the Ca2+ amplifying effect of beta A25-35, but amplified the neuronal Ca2+ response significantly in a very low concentration (100nmol/l). The findings suggest a possible link between AD pathology and ApoE polymorphism by the calcium amplifying effect of ApoE itself as well as by the modulation of beta A4 neurotoxicity by cholesterol.

Amyloid beta-Peptides↗

Similar age-related changes of free intracellular calcium in lymphocytes and central neurons: effects of Alzheimer's disease.

Several studies suggest that alterations of cytosolic free calcium concentration ([Ca2+]i) are involved in the pathophysiology of aging and Alzheimer's disease (AD). However, only few data are presently available giving detailed information about specific characteristics of age-related or AD-specific changes in cellular Ca(2+)-homeostasis. To allow a comprehensive evaluation of age-related changes in [Ca2+]i we performed parallel investigations in central mouse brain cells and mouse spleen lymphocytes of young and aged animals and also in human lymphocytes and granulocytes of young and aged donors and additionally of AD patients. In aged animals, basal [Ca2+]i was decreased in brain cells but increased in spleen lymphocytes. No age-related alterations in baseline [Ca2+]i was found in human lymphocytes or granulocytes. However, comparison of activation-induced rise in [Ca2+]i revealed parallel age-related changes in the different cell-types investigated. The increase in [Ca2+]i after depolarization of mouse brain cells with KCl and after stimulation of mouse lymphocytes with phytohaemagglutinin (PHA) was significantly impaired in aged animals. Moreover, activation of human lymphocytes with PHA also revealed a reduced increase in [Ca2+]i in cells of aged donors. In lymphocytes of AD-patients there was a tendency to higher basal [Ca2+]i compared to their aged matched controls, but no specific alterations in [Ca2+]i could be found after stimulation with PHA. Also no age-related or AD-specific changes were found in granulocytes after stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Disturbances of the neuronal calcium homeostasis in the aging nervous system.

Maintenance of the cellular calcium homeostasis plays an important role for neuronal cell function and interneuronal cell to cell communication. Therefore, alterations of the neuronal Ca2+ homeostasis may play a crucial role for brain aging in general and for age-related deficits in cognitive functions particularly. Numerous studies indicate various disturbances of the Ca2+ homeostasis on different levels like Ca2+ channel properties, 45Ca2+ uptake, or Ca2+ binding proteins. Investigations on alterations of the free intracellular calcium concentration ([Ca2+]i) in presynaptic synaptosomal preparations led to inconsistent results reporting increased or unchanged [Ca2+]i in aged animals. Postsynaptic alterations of [Ca2+]i have been investigated mainly indirectly by electrophysiological methods and revealed prolonged Ca(2+)-dependent afterhyperpolarization or prolonged Ca2+ spike duration. By using acutely dissociated mouse brain cells it was possible for the first time to evaluate age-dependent alterations of postsynaptic [Ca2+]i directly. In neurons of aged mice basal [Ca2+]i was reduced and depolarization-induced rise in [Ca2+]i was also reduced, probably as a result of increased activation of Ca(2+)-dependent mechanisms terminating Ca(2+)-influx. Depolarization-induced, Ca(2+)-mediated inositolphosphate accumulation was also increased in aged animals. This leads to the conclusion that Ca(2+)-dependent intracellular processes become more sensitive during aging. Investigations about the effect of beta-amyloid on the Ca2+ homeostasis in the same system revealed a small but consistent destabilizating effect of this peptide on K(+)-induced rise in [Ca2+]i which may result in chronically increased neuronal vulnerability. Together with increased Ca2+ sensitivity during aging this might be one of the reasons for the increasing prevalence of Alzheimer's disease (AD) with aging.

Aging↗

Alterations of intracellular calcium regulation during aging and Alzheimer's disease in nonneuronal cells.

Because of its function as an intracellular messenger in many cells, calcium plays an important role in signal transduction. Changes in intracellular free calcium concentration occur in central neurons during aging and Alzheimer's disease (AD). It is possible that similar changes in peripheral cells could mirror or, at least parallel, similar abnormalities in the brain. Assuming that manifestations of the aging process and AD are also present outside the central nervous system, nonneuronal tissues like lymphocytes could be used to search directly for abnormalities in cellular calcium regulation in man. Consistent with observations of reduced depolarization-induced Ca2+ rises in dissociated neurons of aged mice, corresponding age-related changes of reduced mitogen-induced Ca2+ responses were observed both in mouse lymphocytes and, more importantly, in circulating human lymphocytes. With respect to AD, Ca2+ responses after stimulation were unaltered (compared to normal controls). In addition, freshly prepared human lymphocytes showed elevated mitogen-induced Ca2+ responses after exposure to beta-amyloid, the main component of senile plaques in AD. These findings again parallel our observations that this peptide amplifies the K(+)-induced Ca2+ rise in acutely dissociated mouse brain cells. Thus, the lymphocyte seems to be a valuable model to study the effects of beta-amyloid in man. In a preliminary study with AD-patients, sensitivity of the lymphocytes to beta-amyloid's effects on Ca2+ rise was reduced, an observation which was entirely unexpected. Nevertheless, such studies indicate lymphocytes may represent a promising candidate for a peripheral marker of AD and can contribute to the understanding of the disease process.

Aging↗

Influence of gender on the monoethylglycinexylidide test in normal subjects and liver donors.

The objective of this study was to investigate the effect of gender on monoethylglycinexylidide (MEGX) formation in normal subjects and cadaveric liver donors. The study included 92 male and female healthy volunteers < 45 years of age and 98 age- and sex-matched liver donors from a previous study, whose livers were used for transplantation. Women < 45 years not taking contraceptives showed significantly lower MEGX concentrations 30 min after lidocaine administration than men [median (16-84th percentile)]: 59 micrograms/L (41-70 micrograms/L) versus 81 micrograms/L (58-98 micrograms/L)]. The lowest MEGX 30 min values were observed in women taking contraceptives: 39 micrograms/L (25-48 micrograms/L). Intraindividual variability of serial MEGX tests was moderate (median: 17.8%, n = 8) when measured in female subjects taking no contraceptives and males. Cadaveric liver donors showed significantly higher MEGX 15 and 30 min values compared with normal subjects (p < or = 0.0001). There was no statistically significant difference between MEGX values obtained in male and female cadaveric donors. The urinary excretion of MEGX was similar in male and female normal subjects. Our results suggest that sex-related differences in MEGX formation as well as the influence of contraceptives have to be taken into account when test results from living related liver donors and patients with less advanced chronic liver disease are evaluated. In cadaveric liver donors, however, sex-related differences do not affect MEGX formation.

Adult↗

Negative extrathoracic pressure ventilation in central hypoventilation syndrome.

Nine patients with central hypoventilation syndrome (CHS) were treated with negative extrathoracic pressure ventilation (VNEP). Treatment with VNEP was started between 20 days and 57 months of age, which was two days to 47 months after diagnosis. The equipment to provide VNEP utilised a new system with a latex neck seal and Perspex chamber allowing easy access to the child. Seven patients are managed with VNEP at home by their parents. They did not have a tracheostomy when VNEP was started at ages of 22, 24, 31, 38, and 75 days, 5 and 57 months. They have continued to be successfully managed with VNEP and without tracheostomy. Short periods of intubation and positive pressure ventilation were required on 10 occasions (median duration 7 days, range 4 to 21 days) in four subjects during respiratory tract infections. Three patients required periods of continuous positive airway pressure (CPAP) via a nasal mask or a nasopharyngeal airway during sleep to overcome upper airway obstruction. In three patients the hypoventilation improved and two of these do not require regular ventilatory support at 1.3 and 3.4 years of age. Six of these seven patients are developing normally. In two patients with long term tracheostomies, VNEP could not be established at an age of 29 and 52 months because of tracheal obstruction after temporary removal of their tracheostomy cannula. VNEP is an effective, non-invasive, treatment in infants with CHS if initiated before tracheostomy. It may improve the children's quality of life during the daytime. If upper airway obstruction is a problem in the first year of life, it may be combined with nasal mask CPAP.

Child Development↗

Essential mixed cryoglobulinemia (EMC) in a case of chronic hepatitis C--successful treatment with interferon alpha.

Chronic hepatitis C virus infection has previously been shown to be associated in some cases with an immunologic disorder called "Essential Mixed Cryoglobulinemia" (EMC). In this report a case of transfusion-associated chronic hepatitis C will be demonstrated. During patient's follow-up over a period of fifteen years the woman developed symptoms consistent with the clinical triad of EMC: general weakness, polyarthralgias and purpura. Laboratory chemical values support the presence of mixed cryoglobulins. Application of different therapeutic strategies revealed an improvement of both clinical and biochemical findings during interferon-alpha treatment. Results suggest that during chronic hepatitis C virus infection interferon-alpha therapy may represent the elective choice of treatment for typical symptoms of EMC.

Biopsy↗

Hereditary pancreatitis--a case report.

A female patient with hereditary chronic pancreatitis is described. She presented initially at the age of 18 years with abdominal pain due to acute pancreatitis. Predisposing etiological factors were not recognized. During the ensuing years she had recurrent episodes of abdominal pain and chronic pancreatitis with extensive pancreatic calcifications was finally demonstrated. Six other family members within three generations were affected by chronic pancreatitis suggesting an autosomal dominant mode of transmission. None of the affected patients showed signs of diabetes mellitus, aminoaciduria or hyperparathyroidism.

Adult↗

[Current therapeutic strategies in hepatocellular carcinoma, Part 1].

Hepatocellular carcinoma (HCC) is the most frequent primary malignancy of the liver, most prevalent in Asia and Africa but also showing a rising incidence worldwide. Chronic hepatitis B and C virus infection is the most important risk factor for HCC. More than half of the patients suffer from underlying liver cirrhosis. The prognosis is determined by tumor stage and residual capacity of the liver, the median survival being 0.9 to 12.8 months for patients receiving no specific treatment. In the East, early detection has been improved by screening programs which seem to be less valuable in the Western world.

Carcinoma, Hepatocellular↗

[Evaluation of hypoxic conditions in calves using the erythrocyte density test (EDT)].

The erythrocyte density separation test (EDT) divides the red blood cells into two groups: younger (less dense) and older (more dense) erythrocytes. Using this test enables veterinarians to assess the erythropoiesis in calves on the basis of the percentage of less dense (younger) red blood cells. Anemic calves, as well as those with pneumonic infections show higher proportions of less dense red blood cells in the EDT than healthy ones. This testing procedure makes it possible to estimate the effects of an oxygen deficiency condition, such as hypoxemia, anemia, shock etc. on the peripheral tissues. So the EDT represents a valuable complement to existing hematological laboratory methods. Carrying out the EDT is very simple and suitable in routine clinical testing.

Anemia↗

[Current therapeutic strategies for hepatocellular carcinoma, 2].

Therapeutic decisions depend on the tumor stage and the functional reserve of the tumor-free liver since most HCC are found in cirrhotic livers. Prospective randomized trials are not available, as is a uniform stage-adapted therapeutic concept. The only potentially curative therapy is surgical. Only 15-30% of patients are suitable for liver resection; localized but anatomically or functionally irresectable tumors can be treated by liver transplantation. Both methods have shown a high recurrence rate; controlled studies on adjuvant therapy are missing. Percutaneous ethanol injection therapy is an alternative in early stages resulting in survival rates comparable to surgical resection. More advanced tumors can be treated by transarterial chemoembolization using Lipiodol. Chemotherapy is little successful, the standard substance Adriamycin achieving remission rates of about 20%. To improve the results of chemotherapy, a combination of cytostatic agents with Lipiodol in non-metastasized tumors has been proposed. Among new therapeutic options such as treatment with cytokines, hormone antagonists, lipiodol or antibodies coupled with radioactivity no definite results have been published so far. Therefore, all patients with HCC should be treated in prospectively controlled, randomized studies.

Carcinoma, Hepatocellular↗

[Portal hypertension--pathophysiology and therapeutic approaches].

The following review article describes pathophysiological aspects of portal hypertension in its first part, especially the topographic variety of the vascular collateral system creating the danger of variceal bleeding. The second part discusses different forms of therapy including pharmaco- and sclerotherapy as well as operative and interventional procedures. Beta-blocker-therapy preferentially serves for the primary and secondary prevention of variceal bleeding. Sclerotherapy appears as the dominant therapeutic tool for the management of acute variceal bleeding. New chances of therapy include variceal banding and the implantation of a transjugular intrahepatic portosystemic stent-shunt (TIPSS). Operative procedure loose their significance more and more by the wide-spread use of sclerotherapy and the chance of a definite therapy of portal hypertension (liver transplantation) and the use of nonoperative interventional procedure (TIPSS or TIPS) which are still under clinical investigation.

Adrenergic beta-Antagonists↗

[Diagnostic and pathophysiological aspects of the determination of kidney function in animals].

Early diagnosis of loss in renal function (< 60-70%) is not possible either by resorting to the parameters of plasma urea and creatinine concentrations (responsive to functional loss by > 75% or by reference to urine concentration capacity (urine density: sensitive to concentrations > 60%). However, clearance techniques for determination of the glomerular filtration rate (GFR) have proved suitable for quantitative assessment of renal function. Endogenous creatinine clearance is one of the most common clinical approaches in GFR determination. Criticism of results obtainable from endogenous creatinine clearance appears to be justified by pharmacokinetic aspects of creatinine as an indicator, as well as by some of its analytical peculiarities. The tediousness of the procedure is another counterproductive aspect pertaining to large-scale use of endogenous creatinine clearance in veterinary medicine. Total blood-plasma clearance of exogenous creatinine (T-Clexo.Creatinine) would provide vets with an accurate (diagnostic validity) and practical method for carrying out clinical kidney-function diagnostics. However, more research on a number of related issues will be required before the general introduction of the procedure.

Animals↗

Rapid quantification of C3a and C5a using a combination of chromatographic and immunoassay procedures.

Monoclonal antibodies were isolated which reacted specifically with the complement cleavage products C3a, C3adR, C5a, and C5adR but not with the parent molecules C3 or C5. In both cases the mAbs showed a higher affinity towards the desArg forms. These mAbs were used as capture antibodies in immunoassays for C3a/C3adR and C5a/C5adR. The immunoassays are based on the ABICAP technology which ensures for a rapid measurement. Due to the large binding capacity and the very short diffusion pathways in the gel-matrix the binding equilibrium between capture antibodies and the antigen is reached whilst the sample is flowing through the column. Therefore this test represents an endpoint assay offering the possibility of using a single calibration curve for a large number of measurements. With the C3adR assay concentrations down to 16 ng/ml C3adR can be detected. The lower detection limit of the C5adR assay is 1 ng/ml C5adR. The tests for C3a/C3adR, and C5a/C5adR can be performed in 20 to 25 min and this rapid processing of plasma samples should permit the application of these parameters for diagnostic purposes and patient management.

Amino Acid Sequence↗