Biomedical subjects

R Müller

Publications and source records attributed to R Müller.

At least 73 records · Page 4Linked to original sources

PubMed2002

Suicide in children, adolescents and young adults.

As suicides of children, adolescents and young adults occur very seldom and only few case reports and more comprehensive studies are available in forensic literature, the autopsy records of the Bonn Institute of Forensic Medicine and the database of the Bonn police authorities from 1989 to 1998 were retrospectively analysed for this phenomenon. This search revealed 37 respective suicides involving 23 male (62%) and 14 female (38%) victims. The ages ranged from 10 to 21 years with the prevalence sharply increasing in adolescents and young adults. Independent from sex, the victims almost unexceptionally applied hard suicide methods like hanging, running over by a train or jump from the height. As for the psychological background, current conflicts with a sweetheart, within the family or at school on the background of mental illness or chronically disturbed family structures were encountered as prevailing factors.

Adolescent↗

PubMed2002

[Current epidemiology of carcinoma of the esophagus and cardia in Germany].

BACKGROUND AND OBJECTIVE: In the past 20-30 years the incidence of adenocarcinoma (AC) of the esophagus and the cardia has risen in western countries, while that of squamous cell carcinoma (SC) of the esophagus has largely stayed constant. Current data in the epidemiology of these cancers in Germany were analysed. METHODS AND MATERIAL: The data of the epidemiological cancer register of the Saarland (Old State of former West Germany) and the combined registers of the New States of Germany (former East Germany) and Berlin were collected. Because of the excellent registration procedures, data from the Saarland and the New States, Mecklenburg-Pommern, Brandenburg and Saxony were selected for this study. The incidence was calculated and corrected for age in relation to the world population. RESULTS: The incidence of esophageal AC among males in the Saarland rose from 0.22 per 100 000 population to 1.17 between 1986 to 1997, an increase of 432%, while in Brandenburg, Mecklenburg-Vorpommern and Saxomy it rose, between 1977 and 1998, from 0.23 to 0.8 i.e. by 248%. Esophageal SC incidence remained largely constant in both cancer registers since 1986. In 1998 it was 3.31 in the three New States of Germany and 5.05 in the Saarland. In females the incidence was markedly lower. In 1996-1998 fewer than 10% of cases of esophageal cancer were in UICC stage 1 (T 1 N 0 M 0, early carcinoma). Correspondingly the 5-year survival of all patients with esophageal carcinoma in the Saarland was less than 10% in 1971-1995. AC of the cardia also increased. In the three New States of Germany the incidence among males rose from 1.27 in 1977 to 2.18 in 1998, in females from 0.4 to 0.58. During the same period malignant tumors of the entire stomach, including the cardia, decreased in males from 29.5 to 17.1, in females from 14.3 to 9.2. CONCLUSION: In Germany, during the past 15-20 years, the incidence of esophageal AC and presumably also of AC of the cardia has increased. But the incidence of squamous cell carcinoma of the esophagus has remained largely constant. The proportion of early carcinoma and the 5-year survival with esophageal carcinoma remains under 10%.

Adenocarcinoma↗

PubMed2002

[Diagnosis of B and C viral hepatitis: new developments and relevance for general practice].

Diagnosis of hepatitis B and hepatitis C viral infections can be achieved by highly specific and sensitive primary serological screening assays. Still more costly amplification systems on the qualitative and quantitative detection of HBV-DNA and HCV-RNA are only used for answering special clinical questions. They are relevant to indicate antiviral therapy or to control the outcome of treatment. They are rarely necessary for diagnostic purposes as it may happen in immunosuppressed persons. While in hepatitis B activities of aminotransferases and liver histology usually present a good correlation this is not dependably seen in hepatitis C. Histologic evaluation still appears the only reliable diagnostic procedure for determining inflammatory activity and fibrosis progression in hepatitis C. Liver biopsy therefore is considered mandatory prior to initiation of treatment especially since only patients suffering from severe disease with progression to liver cirrhosis may benefit from today's standard treatment procedures.

Biopsy↗

PubMed2002

High-dose intravascular beta-radiation after de novo stent implantation induces coronary artery spasm.

BACKGROUND: Intracoronary brachytherapy is effective in preventing restenosis after coronary interventions. However, in vitro and animal studies have shown that irradiation produces immediate and sustained endothelial dysfunction. This study assesses the clinical relevance of impaired vasomotoric function induced by brachytherapy. METHODS AND RESULTS: We analyzed the occurrence of postradiation coronary artery spasms in 1 animal study and 2 clinical trials investigating the effects of high-dose intracoronary beta-radiation after de novo coronary artery stenting. Irradiated segments (IRSs) proximal and distal to the stent were studied by quantitative coronary angiography after stenting, after radiation, and at the end of the procedure. There was an 67% overall incidence of coronary artery spasm in the IRSs immediately after beta-radiation compared with 9% after sham treatment (P<0.001). Whereas in most cases this phenomenon was only minor or moderate, in 12 cases, 4 (22%) animals and 8 (28%) patients, severe coronary spasm (>90% diameter stenosis) with significant ECG-changes or hemodynamic instability was observed. Relief of spasms was protracted (mean time until complete relief of spasm 423+/-122 seconds) and required repetitive intracoronary administration of nitroglycerin (mean dose: 1.2+/-0.6 mg). CONCLUSIONS: Vasoconstriction is a frequent reaction of coronary arteries after high-dose intracoronary beta-radiation, necessitating repetitive administration of vasodilators.

Animals↗

PubMed2002

[Suspected acute coronary syndrome in patients without ST-elevation. Exclusion of infarction, early clinical estimation and non-coronary diagnoses].

BACKGROUND AND OBJECTIVE: Patients admitted to the hospital with suspected acute coronary syndrome (ACS) represent a collective at high risk. The NOWIS substudy aimed at evaluating 3 points: (1) Safe exclusion of myocardial infarction by history, symptoms, biochemical markers and the ECG, (2) value of the first diagnosis by the physician in the emergency room, and (3) prevalence and distribution of non-coronary leading diagnoses. PATIENTS AND METHODS: In 164 patients admitted with suspected ACS without ST-segment elevation (73 % men, median age 66 years) the cardiac markers myoglobin, troponin T and CK/CK-MB were assessed on admission and 4 h later. In 2 of the NOWIS centers, the diagnosis on admission, derived from the ECG, history and clinical symptoms, was compared with the leading diagnosis at discharge, based on coronary angiography and, if negative, on additional esophago-gastroscopy. RESULTS: (1) Myoglobin was the biochemical marker with the highest sensitivity 4 h after admission for acute myocardial infarction (classic) definition by CK-MB elevation) with 90.4 %, followed by troponin T with 84.6 %. Four h after admission, in 15.4 % of the infarction patients (prevalence 31.7 %) troponin T was normal. (2) The admission diagnosis instable angina pectoris was confirmed in 46.7 % (57 of 122), suspected acute infarction in 76.2 % (32 of 42). On the other hand, 90.4 % (57 of 63) of the patients with instable angina as leading diagnosis at discharge were correctly diagnosed on admission, but only 61.5 % (32 of 42) of the patients with infarction. (3) At discharge, 29.9 % (49 of 164) of the patients had a non-coronary leading diagnosis. Here, the most common were gastro-intestinal (55.1 %), costo-vertebral (18.4 %) and broncho-pulmonary (16.3 %). CONCLUSIONS: (1) Troponin and myoglobin are helpful in patients without ST-segment elevation; yet, 4 h after admission, a safe exclusion of myocardial infarction is not possible. (2) The clinical diagnosis on admission is important. However, it corresponds with the leading diagnosis at discharge, based on coronary angiography, in only 50 to 75 %. Patients admitted with suspected ACS should be monitored for 24 h in the hospital (chest pain units or coronary care units). (3) Nearly one third of the patients initially admitted with suspected ACS show a non-coronary leading diagnosis, thus underlining the value of further investigations and of an interdisciplinary approach.

Acute Disease↗

PubMed2002

XAFS investigation of the structure of aqueous thorium(IV) species, colloids, and solid thorium(IV) oxide/hydroxide.

X-ray absorption fine structure (XAFS) spectroscopy at the Th L3 edge is applied for the characterization of crystalline, anhydrous ThO(2)(cr), microcrystalline ThO(2).xH(2)O(s), amorphous ThO(n)(OH)(4-2n).xH(2)O(am), aqueous Th(IV) solutions, and colloidal suspensions up to p(c)H 3.7. The microcrystalline, possibly hydrated thorium dioxide, is formed at p(c)H 1.5-2.5 by precipitation from suspensions of 16-23 nm thorium dioxide colloids. The solubility data determined for this solid is several orders of magnitude lower than the values for amorphous Th(IV) hydroxide or hydrous oxide. The EXAFS spectrum of the isolated microcrystalline particles shows that their structure is different from that of anhydrous crystalline ThO(2)(cr) and amorphous ThO(n)(OH)(4-2n).xH(2)O(am) precipitated at higher pH and dried at room temperature. The solubility measured for the amorphous Th(IV) precipitate is comparable to that previously reported for a solid prepared in a similar manner. In other solubility studies with amorphous Th(IV) hydroxide or hydrous oxide, considerably higher thorium concentrations are measured at p(c)H 3.5-5. The aqueous speciation is made by EXAFS for solutions prepared by careful coulometric titration under comparable conditions (p(c)H and thorium concentration). The spectra of these solutions demonstrate the presence of a large amount of Th(IV) polynuclear species or colloids of small size, having a highly asymmetric Th-O coordination. The EXAFS spectrum of these colloids is similar to that of the amorphous solid.

Journal Article↗

PubMed2002

[Neuromuscular monitoring in a patient with hemiparesis. Resistance of the paralysed musculature to non-depolarising muscle relaxants].

The control of the neuromuscular blockade is part of the standard monitoring in general anaesthesia. However, the degree of blocking is affected by different disorders. We describe the neuromuscular monitoring in four patients suffering from central hemiplegia by stimulation of the ulnar nerve simultaneously on the paretic and the normal side. After application of non-depolarising muscle relaxants (Atracurium, Mivacurium, Rocuronium, Vecuronium) a resistance of the paretic extremity against the relaxant used was shown in all cases. A possible explanation for this observation is the spreading out of abnormal acetylcholine receptors over the surface of denervated muscle cells which could lead to a false estimation of the depth of the neuromuscular blockade. Therefore, in the clinical practice, neuromuscular monitoring must always be carried out on the normal extremity of the patient.

Adult↗

PubMed2002

Drug eluting stents: initial experiences.

Local delivery of immunosuppressive or antiproliferative agents using a drug-eluting stent is a new technology meant to inhibit in-stent restenosis providing both a biological and mechanical solution and has recently emerged as a very promising approach. Up to now several agents have been in use: Paclitaxel, Rapamycin, Actinomycin D or Tacrolimus. Evaluating these drugs regarding their release kinetics, effective dosage, safety in clinical practice and benefit, several studies have been published or are still ongoing: SCORE (Paclitaxel-derivative), TAXUS I, II, III, IV (Paclitaxel), ELUTE, ASPECT (Paclitaxel), RAVEL, SIRIUS (Sirolimus), ACTION (Actinomycin), EVIDENT, PRESENT (Tacrolimus). Paclitaxel was the first stent-based antiproliferative agent under clinical investigation providing profound inhibition of neointimal thickening, depending on delivery duration and drug dosage. The randomized multicenter SCORE trail (Quanam stent, Paclitaxel coated) enrolled 266 patients at 17 sites. At 6 month follow-up, a drop of 83% in stent restenosis using the drug-eluting stent could be achieved (6.4% drug-eluting stent vs. 36.9% control group) attributable to a remarkable decrease in intimal proliferation. Unfortunately, due to both frequent stent thrombosis and side-branch occlusions the reported 30-day MACE rate was 10.2%. The randomized TAXUS I safety trail (NIRx, Paclitaxel coated) also demonstrated beneficial reduction of restenotic lesions at 6-month FU (0% vs. 11%) but, this time, associated with the absence of thrombotic events presumably due to the lower drug dosage. The ongoing TAXUS II, III and IV trails are aimed at providing additional insight regarding the efficacy of the TAXUS Paclitaxel-eluting stent. Both the RAVEL and the SIRIUS trial have been conducted to evaluate a Sirolimus-coated stent (Bx VELOCITY stent). From the results available, the beneficial findings regarding reduction of renarrowing using a drug-eluting stent have been confirmed without any adverse effects. Although parameters like drug toxicity, optimal drug dosage or delayed endothelial healing need to be further evaluated, summarizing the today's clinical experience the strategy of drug-coated stents promises a striking benefit in interventional treatment of coronary lesions.

Angiogenesis Inhibitors↗

PubMed2002

Chemical composition of the attachment pad secretion of the locust Locusta migratoria.

This study is the first attempt to characterise the chemical composition of the secretion of the smooth pads of the locust Locusta migratoria and to relate this to the composition of the cuticle coverage of the pads and the wings. Gas-chromatography and mass-spectrometry (GC-MS) were the principal techniques used for the characterization of these materials. Secretion droplets were visualised and quantified with the aid of diverse microscopic techniques. The chemical composition of prints is shown to differ from the cuticle coverage, in particular, with respect to the fatty acid distribution: in the secretion, saturated and unsaturated fatty acids with chain lengths between C(16) and C(20) in both the free form and as glycerides predominate, whereas cuticle coverage contains waxes of long-chained fatty-acids bound to long-chain primary alcohols. The second important difference is the significant amount of glucose and other saccharides found in methanolyzates of the pad fluid. A considerable amount of the amino acids (up to 53%) was detected in the non-volatile portion of the fluid. Data obtained from the shock-freezing, carbon-platinum coating and replica preparation show that the secretory droplets contain nano-droplets on their surfaces. The results lead us to suggest that the pad secretion is an emulsion consisting of lipidic nano-droplets dispersed in an aqueous liquid. According to the chemical composition of the secretion, a high-viscosity of the fluid may be suggested. Presumably, the fluid is a kind of a coupling agent, promoting and strengthening adhesion between otherwise incompatible materials by providing the proximity of contact for intermolecular forces.

Amino Acids↗

PubMed2002

Mechanical strength of the thoracolumbar spine in the elderly: prediction from in situ dual-energy X-ray absorptiometry, quantitative computed tomography (QCT), upper and lower limb peripheral QCT, and quantitative ultrasound.

The objective of this study was to compare the ability of clinically available densitometric measurement techniques for evaluating vertebral strength in elderly individuals. Measurements were related to experimentally determined failure strength in the thoracic and lumbar spine. In 127 specimens (82 women and 45 men, age 80 +/- 10 years), dual-energy X-ray absorptiometry (DXA) was performed at the lumbar spine, femur, radius, and total body, and peripheral-quantitative computed tomography (pQCT) at the distal radius, tibia, and femur under in situ conditions with intact soft tissues. Spinal QCT and calcaneal ultrasound parameters were performed ex situ in degassed specimens. Mechanical failure loads of thoracic vertebrae 6 and 10 (T-6 and -10), and lumbar vertebra 3 (L-3) were determined in axial compression on functional three-segment units. In situ anteroposterior DXA and QCT of the lumbar spine explained approximately 65% of the variability of thoracolumbar failure. A combination of cortical and trabecular density (QCT) provided the best prediction in the lumbar spine. However, this was not the case in the thoracic spine, for which lumbar cortical density (QCT) and DXA provided significantly better estimates than trabecular density (QCT). pQCT was significantly less correlated with the strength of lumbar and thoracic vertebrae (r(2) = 40%), but was equivalent to femoral or radial DXA. pQCT measurements in the lower limb showed no advantage over those at the distal radius. Ultrasound explained approximately 25% of the variability of vertebral failure strength and added independent information to spinal QCT, but not to spinal DXA. These experimental results advocate site-specific assessment of vertebral strength by either spinal DXA or QCT.

Absorptiometry, Photon↗

PubMed2002

Experimental determination of the absorption rate of unattached radon progeny from respiratory tract to blood.

An exposure methodology was developed for the determination of the absorption rate of unattached radon progeny deposited in the human respiratory tract to blood. Twenty-one volunteers were exposed in a radon chamber during well-controlled aerosol and radon progeny conditions, with predominantly unattached radon daughters. Special efforts were made to restrict the dose to the volunteers to an absolute maximum of 0.08 mSv. Measurements of radon gas and radon progeny in blood samples of these volunteers indicated absorption half times of 20 min to 60 min. Former determinations, mainly performed with much larger aerosol particles of diameters between 100 nm and 1,000 nm, implied absorption half times around 10 h. This indicates that the absorption of radon decay products from ciliated airways into blood is dependent upon particle size and particle composition.

Absorption↗

PubMed2002

[Piezoresistive sensors for medical applications exemplified by a probe for measure pressure in the rectum].

We described a pressure sensor probe suitable for assessing dynamic rectal pressure profiles. It comprises 10 piezoresistive sensors mounted in low-temperature co-fired ceramic. To protect against corrosion, the sensors are coated with a biocompatible silicone elastomer. The ceramic measures 4.5 x 5.5 x 1.4 mm. The entire probe has a diameter of 9 mm and a length of 20 cm. A healthy test subject was submitted to rectal manometry. The experimental data and analysis of linearity, hysteresis errors, temperature dependence and reproducibility are discussed. The sensor probe extends classical anorectal manometry, in particular with regard to the diagnosis of rectal motility disorders.

Defecation↗

PubMed2001

Clustering of isochorismate synthase genes menF and entC and channeling of isochorismate in Escherichia coli.

There are two isochorismate synthase genes entC and menF in Escherichia coli. They encode enzymes (isochorismate synthase, EC 5.4.99.6) which reversibly synthesize isochorismic acid from chorismic acid. The genes share a 24.2% identity but are differently regulated. Activity of the MenF isochorismate synthase is significantly increased under anaerobic conditions whereas the activity of the EntC isochorismate synthase is greatly stimulated during growth in an iron deficient medium. Isochorismic acid synthesized by EntC is mainly channeled into enterobactin synthesis whereas isochorismic acid synthesized by MenF is mainly channeled into menaquinone synthesis. When menF or entC were separately placed onto overexpression plasmids and the plasmids introduced into a menF(-)/entC(-) double mutant in two separate experiments, the isochorismate formed was fed into both, the menaquinone and the enterobactin pathway. Moreover, in spite of a high isochorismate synthase activity menaquinone and enterobactin formation were not fully restored, indicating that isochorismate was lost by diffusion. Thus, under these conditions channeling was not observed. We conclude that in E. coli the chromosomal position of both menF and entC in their respective clusters is a prerequisite for channeling of isochorismate in both pathways.

Chorismic Acid↗

PubMed2001

Spinal neurofibromatosis without café-au-lait macules in two families with null mutations of the NF1 gene.

Spinal neurofibromatosis (SNF) is considered to be an alternative form of neurofibromatosis, showing multiple spinal tumors and café-au-lait macules. Involvement of the neurofibromatosis type 1 (NF1) locus has been demonstrated, by linkage analysis, for three families with SNF. In one of them, a cosegregating frameshift mutation in exon 46 of the NF1 gene was identified. In the present study, we report four individuals from two families who carry NF1 null mutations that would be expected to cause NF1. Three patients have multiple spinal tumors and no café-au-lait macules, and the fourth has no clinical signs of NF1. In the first family, a missense mutation (Leu2067Pro) in NF1 exon 33 was found, and, in the second, a splice-site mutation (IVS31-5A-->G) enlarging exon 32 by 4 bp at the 5' end was found. The latter mutation has also been observed in an unrelated patient with classical NF1. Both NF1 mutations cause a reduction in neurofibromin of approximately 50%, with no truncated protein present in the cells. This demonstrates that typical NF1 null mutations can result in a phenotype that is distinct from classical NF1, showing only a small spectrum of the NF1 symptoms, such as multiple spinal tumors, but not completely fitting the current clinical criteria for SNF. We speculate that this phenotype is caused by an unknown modifying gene that compensates for some, but not all, of the effects caused by neurofibromin deficiency.

Adolescent↗

PubMed2001

Multiple hybrid polyketide synthase/non-ribosomal peptide synthetase gene clusters in the myxobacterium Stigmatella aurantiaca.

Many bacterial and fungal secondary metabolites are produced by polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS). Recently, it has been discovered that these modular enzymatic systems can also closely cooperate to form natural products. The analysis of the corresponding biosynthetic machineries, in the form of hybrid systems, is of special interest for combinatorial biosynthesis, because the combination of PKS and NRPS can lead to an immense variety of structures that might be produced. During our screening for hybrid PKS/NRPS systems from myxobacteria, we scanned the genome of Stigmatella aurantiaca DW4/3-1 for the presence of gene loci that encode both the PKS and NRPS genes. In addition to the previously characterized myxothiazol system, we identified three further hybrid loci, three additional PKS and one further NRPS gene locus. These were analyzed by hybridization, physical mapping, PCR with degenerate oligonucleotides and sequencing of fragments of the gene clusters. The function of these genes was not known but it had already been speculated that one compound produced by the strain and detected via HPLC was a secondary metabolite. This was based on the observation that its production is dependent on an active copy of the phosphopantetheinyl transferase gene mtaA. We show here that one of the identified hybrid gene loci is responsible for the formation of this secondary metabolite. In agreement with the genetic data, the chemical structure resembles a cyclic polypeptide with a PKS sidechain. Our data show that S. aurantiaca has a broader genetic capacity to produce natural products than the number of compounds isolated from the strain so far suggests.

Blotting, Southern↗

PubMed2001

In vitro reconstitution of the myxochelin biosynthetic machinery of Stigmatella aurantiaca Sg a15: Biochemical characterization of a reductive release mechanism from nonribosomal peptide synthetases.

Microorganisms produce iron-chelating compounds to sequester the iron essential for growth from the environment. Many of these compounds are biosynthesized by nonribosomal peptide synthetases, some in cooperation with polyketide synthases. Myxochelins are produced by the myxobacterium Stigmatella aurantiaca Sg a15, and the corresponding gene cluster was cloned recently. We have undertaken to express heterologously the myxochelin biosynthetic machinery in Escherichia coli. To activate the involved proteins posttranslationally, they were coexpressed with the phosphopantetheinyltransferase MtaA from the myxothiazol biosynthetic gene cluster. Phosphopantetheinylation of the carrier proteins could be verified by protein mass analysis. Six active domains in proteins MxcE, MxcF, and MxcG are capable of assembling myxochelin from ATP, NAD(P)H, lysine, and 2,3-dihydroxybenzoic acid in vitro. This fact demonstrates that the condensation domain of MxcG performs two condensation reactions, creating the aryl-capped alpha-amide and the aryl-capped gamma-amide of the molecule. A previously unknown type of reductive release is performed by the reduction domain of MxcG, which alternatively uses NADPH and NADH to set free the peptidyl-carrier protein-bound thioester as an aldehyde and further reduces it to the alcohol structure that can be found in myxochelin A. This type of reductive release seems to be a general mechanism in polyketide and nonribosomal peptide biosynthesis, because several systems with C-terminal similarity to the reductase domain of MxcG can be found in the databases. Alternatively, the aldehyde can be transaminated, giving rise to a terminal amine.

Amino Acid Sequence↗

PubMed2001

Synthesis and evaluation of hydroxylated polyamine analogues as antiproliferatives.

A new means of accessing N(1)-cyclopropylmethyl-N(11)-ethylnorspermine (CPMENSPM) and the first synthesis of (2R,10S)-N(1)-cyclopropylmethyl-2,10-dihydroxy-N(11)-ethylnorspermine [(2R,10S)-(HO)(2)CPMENSPM] are described. Both of these polyamine analogues are shown to be more active against L1210 murine leukemia cell growth than either N(1),N(11)-diethylnorspermine (DENSPM) or (2R,10R)-N(1),N(11)-diethyl-2,10-dihydroxynorspermine [(2R,10R)-(HO)(2)DENSPM] after 96 h of treatment; the activity was comparable to that of (2S,10S)-N(1),N(11)-diethyl-2,10-dihydroxynorspermine [(2S,10S)-(HO)(2)DENSPM] at 96 h. Both cyclopropyl compounds reduced putrescine and spermidine pools, but less effectively than did DENSPM and its derivatives. Only CPMENSPM, and not (2R,10S)-(HO)(2)CPMENSPM, lowered spermine pools. As with DENSPM and (2R,10R)-(HO)(2)DENSPM, both cyclopropyl analogues diminished ornithine decarboxylase and S-adenosylmethionine decarboxylase activity. Unlike the hydroxylated DENSPM compounds, both cyclopropyl norspermines substantially upregulated spermidine/spermine N(1)-acetyltransferase. The most interesting effect of hydroxylating CPMENSPM is the profound reduction in toxicity compared with that of the parent drug. The same phenomenon had been observed for the DENSPM/(2R,10R)-(HO)(2)DENSPM pair. Thus, hydroxylation of norspermine analogues appears to be a way to maintain the compounds' antiproliferative activity while reducing their toxicity.

Acetyltransferases↗

PubMed2001

[Retrospective cohort study of lamivudine therapy in patients with chronic hepatitis B].

BACKGROUND AND AIMS: Lamivudine, a nucleoside analogue with specific antiviral activity against the hepatitis B virus, is now available as an alternative therapeutic option to standard interferon-alpha treatment in chronic hepatitis B. Larger studies with lamivudine treatment in chronic hepatitis B were mainly performed in North America and Asia. Data on treatment responses in European patients are sparse. Therefore, we evaluated the efficacy and safety of lamivudine therapy in Central European patients and compared the data with the results from international trials. PATIENTS AND METHODS: In this retrospective, multicenter, cohort study, 95 patients with chronic hepatitis B (median age: 40.4 years, male: 87 patients, female: 8 patients, HBeAg positive: 47 patients, anti-HBe positive: 48 patients), who were treated with lamivudine (100-300 mg/d per os) between 1997 to 1999, were enrolled. RESULTS: During lamivudine treatment a virologic response with HBeAg to anti-HBe seroconversion was achieved in 22/47 (47%) of the HBeAg positive patients. Pretreatment ALT levels (> threefold the upper limit of normal; p = 0.03) and HBV-DNA serum concentration (< or = 100 pg/ml; p = 0.08) were identified as positive predictors for virologic responses. The virologic response was sustained in six of nine patients who had a follow-up period (median 26 weeks). In anti-HBe positive patients a virologic response with undectable HBV-DNA levels was achieved in 35/48 (73%) patients during lamivudine treatment. Side effects during lamivudine therapy were generally mild and reversible. CONCLUSIONS: In this retrospective cohort study virologic end-of-treatment responses to lamivudine monotherapy in patients with chronic hepatitis B were comparable with yet reported international trials. Thus, lamivudine represents a cost-effective and well tolerable option in addition to IFN-alpha in the treatment of chronic hepatitis B.

Adult↗