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Current guidelines advocate no treatment for patients with histologically mild hepatitis C virus (HCV) infection. This was a UK multicentre randomized controlled trial comparing alpha-interferon (3 MU thrice weekly) + ribavirin (1000-1200 mg/day) for 48 weeks with no treatment in treatment naive, adult patients with histologically mild chronic HCV infection. The aim was to compare benefits, safety and efficacy of combination therapy with alpha-interferon 2b and ribavirin for 48 weeks with no treatment (current standard management) in this patient group. In the treatment group 32 of 98 (33%) patients achieved a sustained virological response (SVR). Patients infected with genotype 1 had a lower SVR than those infected with genotype non-1 (18% vs 49% P = 0.02). No patients who failed to achieve a 2-log drop in viral load at 12 weeks achieved SVR. Improvements in quality of life 24 weeks postcessation of therapy compared with baseline using the SF-36 questionnaire measures were observed in the treated group. For patients with mild HCV infection with viral genotype non-1, the results are sufficiently good to suggest that therapeutic decisions should no longer be biopsy-driven. For patients infected with genotype 1, a liver biopsy is still indicated as the low chance of SVR is outweighed by an unacceptable burden of side-effects. Patients who fail to respond by 12 weeks of therapy should have their treatment curtailed early.

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A 25-year-old woman with Hallopeau-Siemens recessive dystrophic epidermolysis bullosa had generalized blistering, scarring and milia since birth. In the course of the disease, acral pseudosyndactyly developed, and the patient suffered from corneal erosions, oesophageal strictures, malabsorption, recurrent severe pneumonias and nephrotic syndrome. In addition, she had severe anaemia, sideropaenia, hypocalcaemia, heavy proteinuria and hypoalbuminaemia. A rapidly growing skin squamous cell carcinoma developed on the neck that spread to axillary and cervical lymph nodes. Recurrent hypocalcaemic tetanic convulsions and dyspnoea and a pneumonia refractory to antibiotics led to the premature demise of the patient. Autopsy revealed extensive amyloidosis of the renal, hepatic and splenic tissues. AA type amyloid deposits were detected in the renal glomeruli and in the lung, explaining the patient's unusually severe pulmonary infections. In essence, the patient had severe recessive dystrophic epidermolysis bullosa, complicated by squamous cell carcinoma, recurrent pneumonias and nephrotic syndrome due to secondary amyloidosis of the kidney and lung. The possibility of secondary pulmonary amyloidosis should be considered in severe dystrophic epidermolysis bullosa patients with recurrent pulmonary infections.

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Isolated hepatocytes represent a relevant model of the liver and are highly required both for research and therapeutic applications. However, sources of primary liver cells from human beings and from some animal species are limited. Therefore, cryopreservation of hepatocytes could greatly facilitate advances in various research areas. The aim of this study was to evaluate whether cryopreserved primary woodchuck hepatocytes could be used for woodchuck hepatitis B virus (WHV) infection studies, and whether they could maintain their regenerative potential in vivo after thawing. Critical steps for good quality of cryopreserved hepatocytes included the use of University of Wisconsin (UW) solution as a main component of the freezing medium, stepwise reduction of dimethylsulfoxide (DMSO) to avoid osmotic shock, and maintenance of low concentrations of DMSO in the culture medium. After cryopreservation, cell viability was still high (70% to 80%), and 50% to 60% of thawed cells attached to the plates. The appearance of covalently closed circular (ccc)DNA and of WHV-replicative forms a few days after in vitro infection demonstrated that thawed woodchuck hepatocytes were still susceptible to viral infection, thus proving maintenance of a very high hepatocyte-specific differentiation status. Furthermore, transplantation of woodchuck hepatocytes into the liver of urokinase-type plasminogen activator (uPA)/recombination activation gene-2 (RAG-2) mice, a model of liver regeneration, demonstrated that cryopreserved cells retained the ability to divide and to extensively repopulate a xenogenic liver. Notably, in vivo susceptibility to infection with WHV and proliferative capacity of frozen/thawed woodchuck hepatocytes in recipient mice were identical to those observed by transplanting fresh hepatocytes.

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Mice containing livers repopulated with human hepatocytes would provide excellent in vivo models for studies on human liver diseases and hepatotropic viruses, for which no permissive cell lines exist. Here, we report partial repopulation of the liver of immunodeficient urokinase-type plasminogen activator (uPA)/recombinant activation gene-2 (RAG-2) mice with normal human hepatocytes isolated from the adult liver. In the transplanted mice, the production of human albumin was demonstrated, indicating that human hepatocytes remained functional in the mouse liver for at least 2 months after transplantation. Inoculation of transplanted mice with human hepatitis B virus (HBV) led to the establishment of productive HBV infection. According to human-specific genomic DNA analysis and immunostaining of cryostat liver sections, human hepatocytes were estimated to constitute up to 15% of the uPA/RAG-2 mouse liver. This is proof that normal human hepatocytes can integrate into the mouse hepatic parenchyma, undergo multiple cell divisions, and remain permissive for a human hepatotropic virus in a xenogenic liver. This system will provide new opportunities for studies on etiology and therapy of viral and nonviral human liver diseases, as well as on hepatocyte biology and hepatocellular transplantation.

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We report a case of Costello syndrome, which is an uncommon multisystemic condition with cutaneous manifestations on the palms and soles. In the literature there are 29 cases described, all the studies are published in the genetic literature with a few exceptions. We add a further case associated with impaired glucose tolerance. The diagnostic clinical signs are impressive, and highly characteristic. Cutaneous manifestations are: loose skin of the hands and feet "washer woman's hand", hyperkeratosis palmoplantaris, curly or sparse hair, acanthosis nigricans, papillomata nasi. Coarse, progeroid facial features with a bulbous nose, feeding difficulties in infancy, cardiac involvement with cardiomyopathy or conduction defect, and in our case impaired glucose tolerance also presented. Postnatal growth retardation, mental retardation, and a distinctive friendly personality is characteristic. Hyperextensible fingers with broad distal phalanges and joint contractures were observed, and peroneal hypertonicity required treatment by Achilles tendon lengthening. The decreased glucose tolerance is interesting in the view of the acanthosis nigricans. No storage disease and no chromosomal abnormality were observed. Only in one case is a balanced translocation described in the literature.

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The palmoplantar keratodermas (PPK) are a heterogeneous group of conditions, most frequently inherited in autosomal dominant fashion. A few are well-documented autosomal recessive disorders; other are acquired in association with certain metabolic disorders and malignancies. Recently different point mutations of the keratin 9 (K9) gene have been identified in unrelated families with epidermolytic palmoplantar keratoderma (EPPK). We investigated two unrelated Hungarian families with EPPK. In one, a mutation consisting of a G-->A transversion at nucleotide position 551, which changes codon arginine to glutamine at codon 162 (R162Q), was found. In the other, we observed a novel mutation at nucleotide position 571, which changes codon 169 lysine (AAG) into the amber stop codon (TAG) (K169X). Each found mutation is present in the highly conserved coil 1A region of the rod domain. In the case of a stop codon type of mutation, it is questionable whether it really results in a clinical phenotype, but segregation analysis revealed cosegregation of the PPK phenotype with the mutant allele.

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UNLABELLED: Early detection of oligosymptomatic gluten-sensitive enteropathy (GSE) may contribute to the prevention of late complications, such as malignancy. Family members of known GSE patients are at higher risk of being affected. To evaluate the frequency and clinical significance of multiple occurrence, we routinely offered an antiendomysium antibody (EmA)-based non-invasive screening to affected families. Among 997 family members of 396 GSE patients, we identified 89 subjects with EmA positivity and/or severe jejunal villous atrophy. In 83 cases GSE has been verified, four patients refused the biopsy and two subjects are under further observation for latent celiac disease. Prevalence of GSE was 8.5% (80/943) among the first-degree relatives, with significantly higher values in the siblings (13.8%) and offsprings (12.0%) than in the parents (4.2%) of the probands (p < 0.001). In 55 families (13.9% of the families studied) two, in ten families (2.5%) three, in one family four and in one other family six members were affected. Combinations of the clinical presentations of index and screening-detected cases were highly variable, with a high percentage of silent and atypical forms in the relatives. GSE cases presenting both with and without dermatitis herpetiformis occurred in 15 families. Six GSE cases with atypical or mild dermatitis herpetiformis were detected in consequence of the screening. CONCLUSIONS: EmA-assisted family screening resulted in the detection of a clinically significant number of additional GSE patients.

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Cefaclor is an oral cefalosporin for a wide range of gram-positive and gram-negative infection. A retrospective study of cefaclor toxicoderma cases at the Department of Dermatology of Heim Pál Children's Hospital found 11 cases. After the administration of the drug, serum sickness like syndromes were observed. The characteristic symptoms were: erythema multiforme like urticaria, polyarticular swelling and oedema of joints and fever. Laboratory findings were: arised activity of the liver enzymes. After the acute symptoms urticaria factitia appeared.

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The authors give a short overview about the background of the organisation of the liver transplantation and about the process of the "liver alarm". One of the most important work of the coordinator is to increase the number of organ donation. The other part of the preparation of liver transplantation is to create the recipient waiting list. The organisation of the "liver alarm" needs the work of two coordinators. The donor coordinator keeps contact with the donor hospital, harmonizes the travel of different transplant teams and organizes the organ explantation. In the same time, the recipient coordinator prepares the liver recipient for the liver transplantation and keeps contact with the donor coordinator in the donor hospital. If the donor liver macroscopically seems good for transplantation, the patient can be send to the operating room and the work of the anaesthesiologists and the surgeons starts.

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Authors carried out a comparative study on freeze--dryers of one--and two chamber-systems. Samples containing dextran and mannitol were used for the control of process-uniformity. Moisture content of the products were monitored during the sublimation process and after closing the ampules by colouring of the CoCl2 labelled samples. They put forward proposals for the combined measurement of barometric vapor pressure and product temperature in order to improve safety.

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The aim of the present study was to assess in vitro the heat generated within the implant body when preparing titanium implants of the ITI Dental Implant System to estimate the potential risk of tissue damage of individual abutment preparation. The speed and the pressure were applied according to routine clinical procedures used in the patient's mouth. Much attention was paid to ensure optimal cooling at the point where the implant and secondary part were being cut. For each of 3 preparations the change from the original temperature was measured over a period of 40 s. Each type of preparation was repeated on 5 implants fitted with temperature probes. Three different preparatory procedures performed with rotating diamond burs and stainless steel finishing burs under cooling with spray from the dental unit may result in a maximal increase in temperature of 10 degrees, 7 degrees and 3 degrees measured coronally, both at the implant shoulder and at the coronal extent of the plasma-sprayed surface after 10 s. The use of additional spray and pressured air significantly reduced this maximal increase to 5 degrees C, 5 degrees C and 4 degrees C, respectively at 10 s. At the 30-s and 40-s time points, all the measured temperatures were significantly lower. Preparation of implants or abutments does not lead to detrimental effects on peri-implant tissues provided that adequate cooling with spray is used. However, without cooling, extreme overheating could be provoked, reaching the critical temperature that would lead to irreversible bone damage within only a few seconds.

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These are the preliminary data of an open multicenter trial of antihypertensive treatment with isradipine as monotherapy (dose, 4.55 +/- 0.56 mg twice daily; n = 11) or isradipine (7.5 +/- 0.63 mg twice daily) in combination with bopindolol (1.16 +/- 0.12 mg once daily; n = 30) administered for 3 years to patients with essential hypertension (WHO classification I or II). Blood pressure was significantly decreased in both treatment groups and there was no indication of resistance to therapy. Plasma levels of total cholesterol and triglycerides were decreased by the end of the second year of treatment, and there was a tendency toward increase in plasma levels of high-density lipoprotein cholesterol (HDL2 or HDL3). The atherogenic index (ratio between total cholesterol and HDL2 plus HDL3) was also decreased. Blood glucose levels remained unchanged in both normoglycemic patients and those with non-insulin-dependent diabetes mellitus (NIDDM) during 3 years of therapy. It is concluded that isradipine is safe and effective when administered long-term in the treatment of hypertensive patients with either hyperlipidemia or NIDDM.

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The hypothesis that plasma lipids may modulate the antihypertensive effect of the calcium antagonist isradipine was tested in 85 patients who had essential hypertension. Significant linear correlations were found between the antihypertensive effect of isradipine and plasma levels of total cholesterol and high-density lipoprotein (HDL2 or HDL3) in normotriglyceridemic (n = 63), but not in hypertriglyceridemic (n = 22), patients. From this, we conclude that normal levels of plasma lipids may modulate the function of calcium channels and their interaction with calcium antagonists.

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The aim of this study was to assess the effects of long-term (9-month) treatment with isradipine, alone or combined with bopindolol, on blood pressure, left ventricular hypertrophy (LVH), and diastolic function. Thirty-five hypertensive patients with LVH and supine diastolic blood pressures (DBPs) greater than or equal to 100 and less than or equal to 120 mm Hg received increasing doses of isradipine (1.25, 2.5, and 5 mg twice daily); if blood pressure was not controlled, bopindolol (0.5-2 mg once daily) was added to the treatment. Clinical and laboratory investigations were carried out after placebo for baseline values, and after 5 and 9 months of isradipine treatment alone (n = 11) or combined with bopindolol (n = 24). At the end of the study, blood pressure was significantly decreased while heart rate did not change with isradipine alone, but decreased significantly after the addition of bopindolol. Although the DBP was normalized (less than or equal to 90 mm Hg) in 28 patients (80%), complete reversal of the left ventricular mass index (LVMI) was seen in only 7 patients (20%). The ratio of early to atrial filling did not change, but the deceleration time was significantly decreased after 9 months. No laboratory abnormalities or important side effects were observed. Although isradipine alone or combined with bopindolol was effective in controlling blood pressure and significantly reduced the LVMI after 5 months, improvement in diastolic function was seen only after 9 months of active treatment.

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The objective of the study was to investigate the efficacy of different dose levels of bopindolol monotherapy in hypertension. This potent nonselective beta-adrenergic receptor blocker has intrinsic sympathomimetic activity and long duration of action. Forty-four patients with essential hypertension of mild (n = 40) or moderate (n = 4) severity (90 less than DBP less than or equal to 115 mmHg at the end of the placebo period) entered and completed the single-blind, placebo-controlled trial. The study lasted 14 weeks: 2 weeks on placebo, and 12 weeks on active treatment during which the initial dose of bopindolol, 1 mg daily, was augmented up to 1.5 mg, then to 2 mg at four-week intervals until BP normalized or a maximum dose of 2 mg/day bopindolol was reached. The bopindolol was administered once a day in the morning. Patients were seen every other week in the morning before drug taking, when BP and heart rate, supine and standing, a twelve lead ECG and side-effects were recorded. Compared with placebo, supine BP was significantly reduced by bopindolol: from 169 +/- 2/103 +/- 1 mmHg to 148 +/- 3/92 +/- 1, 144 +/- 3/90 +/- 1 and 136 +/- 2/85 +/- 0.6 mmHg at the end of 4, 8 and 12 weeks of treatments, respectively (P less than 0.01 for each). BP changes during standing were similar. Bopindolol lowered the supine heart rate from 84 +/- 2 to 75 +/- 1, 74 +/- 1, 72 +/- 1 beats/min (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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