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Biomedical subjects

R Zachoval

Publications and source records attributed to R Zachoval.

At least 19 recordsLinked to original sources
PubMed2003

[Hepatitis of unknown origin with protracted liver failure in a 48-year-old patient with significantly increased pANCA titer].

In spite of intense diagnostic testing, no cause for the chronically aggressive hepatitis of a 48-year old male patient was found. Evidence for an autoimmune process, however, could be derived from a high titer of pANCA. Only according to the revised criteria of the working group on autoimmune hepatitis, but not to the first version, it was possible to classify this as an autoimmune hepatitis. Despite of high-dose steroid treatment and accelerated preparation for liver transplantation the patient died of the complications of rapid liver failure. Thus, in case of unclear rapid progressive hepatitis, the revised criteria of autoimmune hepatitis should be reviewed early and with high priority and consequent high-dose steroid therapy and preparation for liver transplantation should be initiated. The prognostic impact of a high titer of pANCA in patients with autoimmune hepatitis remains to be established.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2002

Increased ratio of serum cortisol to cortisone in acute-phase response.

BACKGROUND/OBJECTIVES: 11beta-Hydroxysteroid dehydrogenase (11beta-HSD) enzymes convert cortisol into inactive cortisone and vice versa. While 11beta-HSD type 2 (mainly localized in the kidney) unidirectionally inactivates cortisol to cortisone, type I isoform (mainly localized in the liver) acts bidirectionally and can thus potentially restore cortisone to active cortisol. The aim of this pilot study was to investigate whether the serum cortisol:cortisone ratio is altered during the acute-phase response, possibly due to altered modulation of 11beta-hydroxysteroid dehydrogenase isoforms. METHODS: Using liquid chromatography electrospray tandem mass spectrometry, cortisol and cortisone were measured in the serum of hospitalized patients with normal and abnormal CRP concentrations, the latter indicating acute-phase response. Fifteen unselected samples were analyzed, all with a CRP concentration within one of the following ranges to cover a wide range of CRP concentrations evenly: <5, 5-20, 21-50, 51-100, 101-200, and >200 mg/l. RESULTS: In the heterogeneous study population, increased CRP concentrations significantly correlated with an increased cortisol:cortisone ratio (p < 0.001; r = 0.65, Spearman correlation coefficient). This correlation was independent of increased serum cortisol concentrations found by multivariate regression analysis. The median ratio was 6.4 (interquartile range 5.5-7.4; n = 30) in patients with a CRP concentration < or =20 mg/l, and 11.2 (interquartile range 8.8-13.9; n = 60) in patients with CRP >20 mg/l (p < 0.01). CONCLUSION: The balance between serum cortisol and cortisone is altered during acute-phase response with a shift towards active cortisol, suggesting that 11beta-HSD isoenzymes play a role in the modulation of systemically available cortisol during acute illness.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2001

Isolate KAV: a new genotype of the TT-virus family.

A novel DNA sequence belonging to a new genotype of TT virus (TTV) was detected by long-distance PCR in the serum of a chronically HCV-infected patient. The isolate was designated KAV according to the patient's initials. Extending the sequence to full length revealed a 3705-nt viral genome, which is about 100 nucleotides shorter than the other TT-viruses. KAV showed common features with the TTV family, such as the organization of open reading frames and conserved noncoding regions. The largest open reading frame of KAV (ORF 1) was about 40 aa shorter than that of other TT-viruses. Overall sequence homology with known TTV isolates was less than 66%. Phylogenetic analysis poses KAV in one major group with three recently published TTV sequences. So KAV can be considered as a new genotype of the TTV family (provisionally designated genotype 28).

Base Sequence↗
PubMed2001

Hepatitis C virus-specific CD4+ T cell response after liver transplantation occurs early, is multispecific, compartmentalizes to the liver, and does not correlate with recurrent disease.

The role of hepatitis C virus (HCV)-specific CD4+ T cells in recurrent HCV infection after orthotopic liver transplantation (OLTx) is unclear. In parallel, 73 intrahepatic and 73 blood-derived T cell lines were established from 34 patients. At a single cell level, virus-specific interferon (IFN)-gamma production to various HCV proteins was determined by ELISPOT assay: 45 (62%) of 73 liver- or blood-derived T cell lines produced IFN-gamma in response to one of the HCV antigens. HCV specificity was detected mainly in the liver (47% vs. 23% in the blood; P<.05, chi(2) test) and was detectable earlier (< or =6 months) significantly more often than later (>6 months) after OLTx (78% vs 49%; P<.05, chi(2) test). Histology, histologic activity index, liver enzymes, and virus load did not correlate with the occurrence of HCV-specific CD4+ T cells. Despite strong immunosuppressive treatment, OLTx recipients can develop an early, multispecific, preferentially intrahepatic CD4+ T cell response that decreases over time, making it a potential candidate target for novel therapeutic approaches in the transplant setting.

Antibody Formation↗
PubMed2001

Serum cortisol/cortisone ratio after Synacthen stimulation.

OBJECTIVES: 11beta-Hydroxysteroid dehydrogenase (11beta-HSD) enzymes interconvert active cortisol and inactive cortisone. There is growing evidence that local tissue concentrations of cortisol are generally modulated by site specific different 11beta-HSD actions. While 11beta-HSD type 2 unidirectionally inactivates cortisol, type 1 isoform acts bidirectionally. 11beta-HSD type 1 is mainly localized in the liver and may thus restore circulating biologically inactive cortisone to active cortisol thereby modulating systemic glucocorticoid action; such a mechanism might be of importance in stressful situations. To study this hypothesis we investigated the influence of exogenous ACTH on serum cortisol/cortisone ratio. DESIGN AND METHODS: Paired serum samples that were submitted for routine analysis of cortisol before and 1 h after stimulation with 250 microg ACTH (1-24) (Synacthen) were collected prospectively if the routine tests indicated normal adrenal function; 40 patients were included in the study, 29 patients were female, 11 male, median age was 31 yr (range 14-70). Serum cortisol and cortisone were determined using LC-ESI/MS/MS with an online sample extraction system and tri-deuterated cortisol as the internal standard. RESULTS: While mean serum cortisol increased by 109% (mean basal concentration 373 nmol/L (SD 151 nmol/L), stimulated 781 nmol/L (SD 194 nmol/L)), mean serum cortisone significantly decreased after ACTH administration by 31% (p < 0.001, paired t-test for differences). Mean serum cortisone was 70 nmol/L (SD 16 nmol/L) before and 48 nmol (SD 16 nmol/L) after ACTH administration; decrease in serum cortisone was observed in 34 (85%) of the patients. The ratio of serum cortisol/cortisone increased in all subjects (mean 5.4 (SD 1.9) before ACTH, and 16.2 (SD 6.2) after ACTH; p < 0.001). CONCLUSIONS: The data of our observational study suggest a modulation of peripheral metabolism of cortisol by ACTH with a stimulation of systemic 11beta-HSD type 1 activity, leading to restoration of inactive cortisone to biologically active cortisol.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2001

Short-term effects of statin therapy in patients with hyperlipoproteinemia after liver transplantation: results of a randomized cross-over trial.

BACKGROUND/AIMS: Hyperlipoproteinemia is frequent following liver transplantation and may lead to atherosclerosis. Lipid-lowering agents may be useful, but could interfere with the function of the transplanted organ and with immunosuppression. We therefore evaluated in a prospective, randomized, open-labeled cross-over trial the effect of two frequently used 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (pravastatin 10 mg d(-1) and cerivastatin 0.1 mg d(-1)) in hyperlipoproteinemic patients after liver transplantation. METHODS: Sixteen patients (6.3 +/- 2.0 years post-transplantation, cyclosporine n = 11, tacrolimus n = 5) with hyperlipoproteinemia (cholesterol 246 +/- 42, triglycerides 191 +/- 87, low-density lipoprotein (LDL)-cholesterol 161 +/- 35, high-density lipoprotein (HDL)-cholesterol 44 +/- 11 mg d(-1)) were included. Treatment periods of 6 weeks were separated by a 4-week washout period. RESULTS: Both medications were tolerated well, no effects on serum concentrations of liver enzymes or immunosuppressive agents were observed. Cerivastatin and pravastatin decreased (P < 0.001) cholesterol by 21 +/- 10% and 15 +/- 10%, LDL-cholesterol by 27 +/- 14% and 17 +/- 15%, respectively, while triglyceride and HDL-cholesterol concentrations did not change significantly. LDL/HDL-cholesterol markedly improved (P < 0.001) by 29 +/- 16% (cerivastatin) and 16 +/- 16% (pravastatin). Cerivastatin was more potent than pravastatin in patients receiving cyclosporine A, while there was no significant difference in patients receiving tacrolimus. CONCLUSIONS: Low-dose cerivastatin and pravastatin significantly improve lipid profiles following liver transplantation without affecting liver function or immunosuppression.

Aged↗
PubMed2001

Treatment of benign ureterointestinal anastomotic strictures with permanent ureteral Wallstent after Camey and Wallace urinary diversion: long-term follow-up.

BACKGROUND AND PURPOSE: Ureterointestinal anastomotic stricture follows urinary diversion in 4% to 8% of patients and may lead to a progressive deterioration of renal function. There are problems with all current management techniques: surgical revision, endourologic incision, nephrostomy drainage, external ureteral stents, and dilation with a high-pressure angioplasty balloon. The authors present their long-term results with permanent ureteral Wallstents for the treatment of benign ureterointestinal stricture. PATIENTS AND METHODS: Eight patients with 10 strictures were treated by placement of self-expanding permanent indwelling stents via percutaneous nephrostomy between September 1993 and January 1998. The mean age of the group was 59.2 years. Development of strictures occurred a mean of 20.9 months after urinary diversion. There were seven complete and three partial strictures. Of 49 patients treated by the Camey procedure, 7 patients (14%) developed 9 (18%) strictures. Of 28 patients having the Wallace procedure, 1 patient (3.5%) developed one stricture. After recanalization of the distal ureter by a Terumo guidewire and dilation with a high-pressure angioplasty balloon, a Wallstent was placed across the stricture via a percutaneous approach. RESULTS: The endourologic placement of the Wallstent was well tolerated by all patients. The hospital stay averaged 2 days. Seven patients with nine strictures after the Camey procedure are doing well with a follow-up of 7 to 68 months (mean 22.4 months). One major complication was observed in one patient necessitating an additional procedure (lithotripsy) because of stone formation at the lower part of the stent extending into the neobladder in order to maintain patency after 68 months. The other patient, who had a Wallace procedure, is doing well 1 year 8 months afterward. CONCLUSION: An endourologic ureteral Wallstent approach to ureterointestinal stricture is a successful alternative, providing satisfactory management of the problem in most patients. No complication such as stent migration, hematuria, pain, or recurrent stricture was observed.

Aged↗
PubMed2001

Potential lack of specificity using electrospray tandem-mass spectrometry for the analysis of mycophenolic acid in serum.

The remarkably strong formation of the mycophenolic acid molecular ion from mycophenolic acid glucuronide during electrospray atmospheric pressure ionization in patients' serum samples is described. It is concluded that because of this effect appropriate chromatographic separation prior to tandem-mass spectrometric analysis and correct peak detection and integration of the respective multiple reaction monitoring traces is mandatory probably in all cases where conjugate drug metabolites are present in post-dose samples.

Chromatography, High Pressure Liquid↗
PubMed2001

Prostate-specific antigen: current status.

PSA is the most important of all tumor markers because it has significant applications in all aspects of the management of men with prostatic disease. Certainly, the most important utilization of PSA is for early detection of this most ubiquitous of all human neoplasms. In this article the authors describe the molecular forms of PSA and their characteristics, the factors influencing values of serum concentration of PSA, the problems of screening, and particularly the possibility to use PSA for detection of prostate carcinoma. A big problem in prostate carcinoma detection is the low specificity of PSA at the concentrations between 4-10 ng/ml, the so-called diagnostic gray zone, where the incidence of prostate carcinoma is only 25%. The authors evaluate the methods which make it possible to increase the sensitivity and/or specificity of PSA detection, such as PSA density, PSA density of the transition zone, PSA velocity, PSA doubling time, age-specific PSA, free PSA and, prospectively, the use of the RT-PCR technique.

Biomarkers, Tumor↗
PubMed2000

Association of hepatitis C virus-specific CD8+ T cells with viral clearance in acute hepatitis C.

CD8+ T lymphocytes play a major role in antiviral immune defense. Their significance for acute hepatitis C is unclear. Our aim was to correlate the CD8+ T cell response with the outcome of infection. Eighteen patients with acute hepatitis C and 19 normal donors were studied. Hepatitis C virus (HCV)-specific CD8+ T cells were identified in the enzyme-linked immunospot assay by their interferon-gamma (IFN-gamma) production after specific stimulation. The highest numbers of IFN-gamma-producing HCV-specific CD8+ T cells were found in patients with acute hepatitis C and a self-limited course of disease during the first 6 months after onset of disease, but these numbers dropped thereafter to undetectable levels. The differences in responsiveness between patients with self-limited disease versus patients with a chronic course were statistically significant (P<.001). Our data show that the number of IFN-gamma-producing HCV-specific CD8+ T cells during the first 6 months after onset of disease is associated with eradication of the HCV infection.

Acute Disease↗
PubMed2000

Cytokine profile of liver- and blood-derived nonspecific T cells after liver transplantation: T helper cells type 1/0 lymphokines dominate in recurrent hepatitis C virus infection and rejection.

Orthotopic liver transplantation (OLT) is a successful treatment in patients with hepatitis C virus (HCV)-associated end-stage liver disease worldwide. T lymphocytes and their cytokines are believed to have a pivotal role in the defense against HCV and in allograft rejection. An immunosuppressive drug regimen may cause a cytokine imbalance toward a T helper (TH) cell type 2 profile that is associated with the persistence of infection and acceptance of the graft. The aim of this study is to assess whether cytokine imbalances toward a TH1- or TH2-type response may have a role in recurrent HCV infection and rejection after OLT. Twenty-one intrahepatic T-cell lines of 15 patients with recurrent HCV infection after OLT (group A) and 15 lines of 11 patients with rejection (group B) were studied. Both patient groups had received liver allografts because of HCV-associated end-stage liver disease. Patients with HCV-induced liver disease who did not undergo OLT served as controls: 17 patients with chronic hepatitis C (CH-C) and 8 patients with cirrhosis. At the time of liver biopsy, 14 blood-derived T-cell lines of 12 patients with recurrent HCV infection, 7 of 10 patients with rejection, and 18 of 18 control patients were also investigated. Regardless of the underlying disease (recurrent HCV infection, rejection, HCV-induced hepatitis, and cirrhosis), all liver tissue-derived T-cell lines produced interferon-gamma; some additionally produced interleukin-4 (IL-4), but none produced IL-10, indicating that the TH0/1 cytokine profile dominates. T-cell lines showing a TH1 cytokine profile derived from intrahepatic T cells could be established significantly more often in recurrent HCV infection and rejection than in controls with CH-C (Fisher's exact test, P <.05). The cytokine profile of intrahepatic T cells did not differ from that obtained in peripheral blood. TH0/1 cytokine profile dominates the intrahepatic and blood-derived immune response in recurrent HCV infection and rejection after OLT regardless of the mode of immunosuppression. The lymphokine profile of immunocompromised patients with recurrent HCV infection or rejection does not differ principally from that of patients with HCV-induced hepatitis and cirrhosis, but seems to show a TH1 profile significantly more often.

Cytokines↗
PubMed2000

Erythrocyte protoporphyrins in hepatitis C viral infection.

OBJECTIVES: Protoporphyrin is the immediate precursor of the heme molecule. Due to a spillover from hemaotopoietic tissue it is regularly found in small amounts in erythrocytes and excreted into the bile. In hereditary erythropoietic protoporphyria excess protoporphyrin accumulates and can cause severe liver damage both by crystallization and induction of oxidative stress. The aim of this investigation was to study protoporphyrin concentrations in other liver disorders. DESIGN AND METHODS: Erythrocyte protoporphyrin and zinc protoporphyrin concentrations were studied in 50 patients with chronic hepatitis C infection and various degrees of liver damage. High-performance liquid chromatographic analysis with fluorescence detection was used. RESULTS: Erythrocyte protoporphyrin was increased in 32% of the patients studied; in 12 patients up to two-fold higher than the maximum of the reference range, in 4 up to three-fold higher (median concentration 98 nmol/L, interquartile range 68-142; maximum 379 nmol/L (reference range: <125 nmol/L)). In 6 of the 10 patients in the subgroup with signs of severe liver dysfunction (decreased serum albumin and prolonged thromboplastin time, elevated serum bilirubin), protoporphyrin was elevated. Erythrocyte zinc protoporphyrin was increased in 7 cases out of all 50 studied; in these seven cases, erythrocyte protoporphyrin was also elevated (median concentration of zinc protoporphyrin in the whole study group: 232 nmol/L, interquartile range 182-342; maximum 827 nmol/L (reference range <464 nmol/L). CONCLUSIONS: Elevated erythrocyte protoporphrin levels are frequently found in patients with advanced chronic hepatitis C infection. Because protoporphyrin is well known to be hepatotoxic, these findings warrant further investigation.

Adult↗
PubMed2000

[Lower urinary tract function and its disorders].

The lower urinary tract provides two modes of operation--storage and elimination of urine. The normal function results in the coordination of contraction and relaxation of muscles of the urinary bladder and urethral sphincters. Disorders of these activities or their interaction lead to the development of lower urinary tract dysfunctions. The nervous system plays an essential role in the regulation of the functions. The control of micturition is coordinated by several regious of the central nervous system. Afferents and efferents of the peripheral nervous system carry signals from and to the lower urinary tract. The reflex circuitry controlling micturition consists of five components: spinal efferent neurons, peripheral efferent neurons, primary afferent neurons, spinal interneurons and neurons in the brain. Preganglionic neurons located in the sacral parasympathetic nucleus and lumbar sympathetic nucleus excite the peripheral efferent neurons innervating smooth muscles of the urinary bladder and urethra. Motoneurons of sacral Onuf's nucleus excite the striated muscle of the external urethral sphincter. Myelinated and unmyelinated afferent axons transmit information from the lower urinary tract to the lumbosacral spinal cord. Three receptor types of the lower urinary tract are present: tension receptors, volume receptors and "silent receptors", which become nociceptors following the sensitization. Afferent pathways terminate on spinal interneurons. Spinal interneurons relay information to the brain or to other regions of the spinal cord. Because micturition reflexes are mediated by disynaptic or polysynaptic pathways, interneuronal mechanisms are of crucial importance in the regulation of lower urinary tract. Central pathways involved in micturition reflexes are located in spinal and supraspinal areas. Micturition reflexes can be modulated at the level of the spinal cord by viscero--bladder and somato--bladder reflexes. Supraspinal areas have a more complicated organization: critical component of the micturition reflex is the pontine micturition center and the periaqueductal gray. Inhibitory and excitatory areas in the pontomedullary and hypothalamic systems and the brain play an important role in the regulation of micturition reflexes.

Humans↗
PubMed1999

Virus-specific lymphokine production differs quantitatively but not qualitatively in acute and chronic hepatitis B infection.

Cytokines that are secreted as a response to viral antigen not only have direct antiviral properties but also crucially influence immune reactions determining the outcome of infection. As an advantageous alternative to the study of cytokines present in the supernatants of antigen-specific T cell clones and lines, we have used ELISPOT assays to determine the number of interferon-gamma (IFN-gamma)- and IL4-producing cells generated by peripheral blood mononuclear cells from patients with acute hepatitis B (AHB) and chronic hepatitis B (CHB) infection in response to HBcAg in a short-term culture (48 h). In response to HBcAg IFN-gamma was predominantly produced. In contrast to the results obtained in acute hepatitis B, the typical lymphokine pattern in CHB was characterized by a weak or absent antigen-specific IFN-gamma production. A predominance of IL-4-producing cells was not observed in either AHB or CHB. A significant number of IFN-gamma-producing cells was usually detectable during phases of viral elimination and the quality of the lymphokine response seemed to be epitope independent. Comparison of the results obtained in proliferation assays and ELISPOT assays clearly shows that lymphokine production upon stimulation with viral protein is totally independent of T cell proliferation and more sensitively reflects antiviral reactivity.

Acute Disease↗
PubMed1999

Erdheim-Chester disease: a case report and literature overview.

Erdheim-Chester (EC) disease belongs to the group of lipoid granulomatosis. Symmetric sclerosis of the meta- and diaphysis of long tubular bones are pathognomonic radiologic changes. Additionally, other skeletal segments can be affected. Extraskeletal manifestations can occur in almost all organs; lungs, pericardium, retroperitoneum, skin, and orbita play particularly important roles. The last case of 38 cases of Erdheim-Chester disease with an extraordinary mediastinal and perirenal involvement is described. For the second time following the initial description by Chester, an axial skeletal pattern of eburnated vertebra is shown.

Aged↗