[Quality of life and depression in hearing-impairment : A German survey]. / Lebensqualität und Depression bei Hörminderung : Eine deutsche Bedarfsanalyse.

BACKGROUND: Hearing-impairment can lead to a reduced quality of life and thus represents a vulnerability factor for mental disorders. OBJECTIVE: This study represents the first psychiatric analysis of subjective quality of life and depression in people with hearing-impairment in Germany. MATERIALS AND METHODS: The patient group included 30 hearing-impaired participants (27 women, 3 men) with a current or previous mental disorder and/or psychiatric/psychotherapeutic treatment (age: mean, M = 49.67 years; standard deviation, SD = 13.54 years). The control group consisted of 22 hearing-impaired participants (16 women, 6 men) without mental disorders or treatment (age: M = 52.41 years, SD = 17.30 years). Besides sociodemographic variables, we registered onset/extent of the various hearing-impairments and hearing aid provision. Both groups underwent extensive diagnostic assessment comprising subjective functional impairment (Sheehan Disability Scale, SDS), health-related quality of life (SF-36 Health Survey), and depressive symptoms (Beck Depression Inventory, BDI-II). RESULTS: Groups did not differ significantly in terms of sociodemographic variables such as age, gender, or intelligence. Participants of the patient group had a significantly greater subjective impairment, a lower quality of life, and more pronounced symptoms of depression. The invasiveness of the hearing aid (i. e., cochlear implant) as well as the timepoint of hearing-impairment onset (postlingually) appear to serve as vulnerability factors for mental health problems in this group. CONCLUSION: Our results indicate that besides delivering high-quality acoustic care, practitioners should continuously check patients' requirements for psychosocial treatment due to a loss of quality of life. The development of a specific psychotherapeutic treatment for hearing-impaired clients requires additional research focused on protective and vulnerability factors which may influence the emergence of mental disorders in these patients.

[Clinical evaluation of PFNA® and relationship between the tip-apex distance and mechanical failure]. / Klinische Evaluation des PFNA® und Zusammenhang zwischen Tip-Apex-Distanz und mechanischem Versagen.

The incidence of trochanteric fractures is increasing in Europe, and the economic impact and mortality is high. The aim of the study was to evaluate the PFNA® (proximal femoral nail antirotation) with respect to its clinical use and mechanical complications.All patients with a trochanteric fracture who had been treated with a PFNA® between 12/2004 and 12/2007 were identified and analysed regarding complications and radiological findings. The study included 195 patients; 61.2% of the patients were classified as Singh I und II. The mean duration of surgery was 57 min. In ten cases (5.1%) the blade migrated, four cases (2.1%) showed blade cut out and in one case the nail broke (0.5%). The mean TAD was 26.7 mm, in cases of cut out 41.3 mm and in blade migrations 38.6 mm. No failure could be documented when the TAD was less then 30 mm. There is a strong relationship between increasing TAD and mechanical failure (P<0.001); 84.6% of the patients have been followed up, and 30.2% died in the follow-up period.The PFNA® is an easy-to-use implant for the treatment of stable and instable proximal femur fractures. Mechanical failure depends on the TAD.

Communicative reprogramming non-curative hepatocellular carcinoma with low-dose metronomic chemotherapy, COX-2 inhibitor and PPAR-gamma agonist: a phase II trial.

Systemic therapy for advanced hepatocellular carcinoma (HCC) is still challenging. A biomodulatory therapy approach targeting the communicative infrastructure of HCC, including metronomic low-dose chemotherapy with capecitabine, pioglitazone and rofecoxib, has been evaluated in patients with non-curative HCC. Altogether 38 patients were evaluable in this one-arm, multicenter phase II trial. The primary endpoint, median progression-free survival was 2.7 months (95% CI: 1.6-3.79) for all evaluable patients and 8.4 months (95% CI: 0-18.13) for patients ≥ 6 weeks on protocol. Median overall survival (OS) was 6.7 months (95% CI: 4.08-9.31) and 9.4 months (95% CI: 4.82-13.97), respectively. Most common adverse events were edemas grade 3, which were commonly related to the advanced stage, with 66% of the patients suffering from liver cirrhosis. Exploratory data analyses showed significant impact of ECOG performance status grade 0 versus 1 and CLIP score 0/1 versus > 1 on OS, 9.8 months (95% CI: 4.24-15.35) versus 2.7 months (95% CI: 1.03-4.36; P = 0.002), and 9.8 months (95% CI: 3.23-16.37) versus 4.4 months (95% CI: 3.14-5.66; P = 0.009), respectively. Preceding tumor surgery had significant beneficial impact on survival, as well as maximal tumor diameter of < 5 cm. The correlation of C-reactive protein decrease with significantly improved OS underlines the close link between inflammation and tumor control. Biomodulatory therapy in advanced HCC may be a low toxic, efficacious treatment and principally demonstrates that such approaches should be followed further for treatment of advanced HCC.

Ragged-red fibres detected in paraffin sections by a monoclonal antibody to inner mitochondrial membrane.

An immunohistochemical method is reported using the M-II68 monoclonal antibody, which detects mitochondrial accumulations ("ragged-red fibres") in routinely processed (formalin-fixed, paraffin-embedded) muscle tissue. Ten cases with electron-microscopically and histochemically proven mitochondrial myopathy featured 4% to 24% ragged-red fibres. In a series of 50 muscle biopsies without mitochondrial myopathy, scattered ragged-red fibres (less than 0.1%) were present in a few normal and pathological muscles. The immunohistochemical method is specific for mitochondria, does not require frozen tissue and permits rapid examination of large areas.

Basement membrane proteins and type III procollagen in murine schistosomiasis.

The livers of female CBA mice were examined 9 to 10 weeks after subcutaneous infection with Schistosoma mansoni. Cryostat liver sections and isolated liver cells were examined by indirect immunofluorescence using specific antibodies against basement membrane proteins (laminin, fibronectin and type IV collagen and type III collagen precursor. Liver cells were isolated by collagenase digestion, purification on Percoll density gradients and centrifugal elutriation to yield enriched fractions of hepatocytes, endothelial and Kupffer cells (Fractions I, II, III respectively). Infected animals yielded more than three times the control number of non-parenchymal cells; electron microscopy revealed that the increase in Fraction II was due mainly to eosinophilic leucocytes and in Fraction III due to Kupffer cells and macrophages from the schistosomal granulomata. Studies of cryostat liver sections showed that the schistosomal granulomata contained dense deposits of type III collagen precursor and fibronectin in the distribution of the reticulin fibres but laminin and type IV collagen were conspicuous only in new vessels in the periphery of the granuloma. Isolated liver cells showed fibronectin on their surface. Immunofluorescence studies could not be performed on Kupffer and endothelial cell fractions because of marked non-specific fluorescence. These experiments indicate that centrifugal elutriation is a useful method for isolating the constituent cells of murine schistosomal granulomata.

Cognitive function in adult epileptic patients established on anticonvulsant monotherapy.

A battery of psychometric tests was administered to 110 patients with epilepsy and to 24 non-epileptic controls. Eighty-four patients had been established on treatment with a single anticonvulsant drug (35 carbamazepine (CBZ), 30 sodium valproate (VPA), 19 phenytoin (PHT)) at unaltered dosage for the previous 3 months. The remaining 26 patients were untreated at the time of study. No individual test discriminated between the groups. Tests were converted to standard scores and summated to give overall psychomotor, memory and side-effect assessments. There were no important differences between the performances of untreated epileptic patients and non-epileptic controls. The CBZ-treated patients had poorer psychomotor scores than both control groups and the VPA-treated patients (all P less than 0.05). The PHT patients scored less well on the composite memory scale than did VPA patients and non-epileptic controls (both P less than 0.05). There were no significant differences in subjective side-effects among the groups. This study demonstrated that anticonvulsant monotherapy has little effect on overall cognitive function in patients tolerating treatment. Psychomotor performance appeared to be selectively influenced by CBZ and memory impaired by PHT. VPA may be the drug to chose when cognitive function is an important consideration. Different cognitive modalities can be affected by different first-line anticonvulsants and this should be taken into account when choosing the most appropriate drug for an individual patient.

The effects of muscle tension on cerebral circulation in blood-phobic and non-phobic subjects.

This study aimed to assess whether (1) a muscle tensing procedure which has been found to be useful in the treatment of blood-phobic patients produces an increase in heart rate and cerebral blood flow and (2) whether this increase is greater than that produced by mental effort alone. Subjects were 17 volunteers with a history of fainting in response to blood-injury stimuli, (12 were phobic) and 8 volunteers with no fainting history. They were required to (a) rest, (b) do mental arithmetic, and (c) repeatedly tense and release their arm and leg muscles. It was found that Ss, heart rate and cerebral blood flow velocity were significantly greater during the muscle tensing procedure than during mental arithmetic or resting conditions. The increased cerebral blood flow produced by muscle tensing may enable blood phobic patients to prevent fainting during exposure treatment.

Parameters predicting response to alpha-interferon treatment in chronic hepatitis C.

BACKGROUND/AIMS: Sustained response to alpha-interferon treatment for chronic hepatitis C is seen in only 25% of cases. Therefore, it is desirable to define pretreatment factors predicting responders. MATERIALS AND METHODS: Forty-nine patients with chronic hepatitis C were treated with a standard alpha-interferon regimen (3 x 3 MU s.c./week). Demographic, biochemical and immunological parameters, and HCV genotypes were obtained prior to initiation of treatment and evaluated for their value in predicting response to alpha-interferon therapy. RESULTS: Response, as defined by normalization of ALT, was 71% during interferon therapy and sustained response after discontinuation of interferon 24.5%. Patients infected with HCV-genotype 1b had significantly more often "community-acquired" disease. Their outcome was worse with a response rate of 44% during therapy and a sustained response of 12.5%, as compared to 87% and 27% respectively in patients infected with genotypes other than 1b. On multivariate analysis, absence of cirrhosis, HCV-genotype other than 1b, higher ALT levels and higher numbers of CD8 positive liver infiltrates were found to be predictors of response during alpha-interferon therapy. CONCLUSION: Response to alpha-interferon therapy seems to be influenced both by viral virulence factors and by the intensity of the host immune response to HCV.

[Recurrent intrahepatic cholestasis of pregnancy and chain-like choledocholithiasis in a female patient with stop codon in the ABDC4-gene of the hepatobiliary phospholipid transporter]. / Rezidivierende Schwangerschaftscholestase und perlenschnurartige Choledocholithiasis bei einer Patientin mit Stoppcodon im ABCB4-Gen des hepatischen Phospholipidtransporters.

We report the case of a 40-years-old female patient with recurrent cholestatic liver disease who presented twice with severe intrahepatic cholestasis of pregnancy and pronounced choledocholithiasis between pregnancies. Bile duct stones were removed endoscopically and a laparoscopic cholecystectomy was performed after the second pregnancy. Liver histology revealed intrahepatic cholestasis with portal inflammation and fibrosis, resembling progressive familial intrahepatic cholestasis (PFIC). Molecular genetic studies identified the heterozygous mutation c.957C > T in the ABCB4 gene encoding the hepatobiliary phospholipid transporter. This is the first report of this mutation that introduces a stop codon in an index patient with intrahepatic cholestasis of pregnancy and multiple bile duct stones. In addition, we detected the ABCB11 polymorphism V 444A, which is associated with a decreased expression of the bile salt export pump. Whereas homozygous carriers of the ABCB4 mutation develop PFIC type 3, the heterozygous ABC transporter mutations represent genetic risk factors for cholelithiasis and recurrent cholestatic hepatitis upon challenge with oral contraceptives or during pregnancy. Of note, the patient presented with normal serum gamma-glutamyltranspeptidase activities during pregnancy-associated cholestatic episodes but normal liver enzymes after delivery, whereas choledocholithiasis was associated with high gamma-glutamyl transpeptidase levels. It is unknown whether ursodeoxycholic acid prevents cholestasis or gallstones in patients with ABCB4 deficiency.

Safety, tolerability and efficacy of peginterferon alpha-2a and ribavirin in chronic hepatitis C in clinical practice: The German Open Safety Trial.

The combination treatment of peginterferon alpha-2a (PEG-IFN alpha-2a; Pegasys) plus ribavirin (RBV) is recommended as a standard care for HCV infections. Side effects and aspects of efficacy and safety have to be balanced. This study evaluates clinical practice data on safety and efficacy of HCV treatment with PEG-IFN in combination with RBV over 24 and 48 weeks. This study was a phase III, multi-centre, open-label study with two treatment groups: PEG-IFN in combination with RBV for 24 or 48 weeks. The allocation to the treatment groups was at the discretion of the investigator; 309 patients entered active treatment: 90 patients received PEG-IFN plus RBV for 24 weeks and 219 patients PEG-IFN plus RBV for 48 weeks. A sustained virological response (SVR) was achieved in 48.9% of all patients. Genotype 1 patients with a 48-week combination treatment achieved an SVR of 39.9%. In the 48-week group a low baseline viral load was associated with a higher SVR rate (47.0% vs. 32.4%). For genotype 2 or 3 patients, the SVR was 67.9%. For these patients there was no relevant difference between patients with low and high viral loads; 97.7% of the patients experienced at least one adverse event. The incidence of serious adverse events was distinctly lower in the 24-week group (4.4% vs. 10.5%). This investigation confirms the well-known risk-benefit ratio found in controlled studies in a clinical practice setting. The safety profile is similar and shows the highest incidence of adverse events in the first 12 weeks of treatment.

[Pathogenesis and clinical aspects of primary liver cell carcinomas]. / Pathogenese und Klinik der primären Leberzellkarzinome.

The hepatocellular carcinoma is the most frequent primary liver cell carcinoma. On account of its geographical distribution with preferential occurrence in China, SE Asia and South Africa, exogenic causes are thought to be mainly responsible for its aetiopathogenesis. Besides mycotoxins, the hepatitis B virus infection (HBV) is particularly important. Integration of HBV-DNS into the hepatic cell DNS is considered to be an initiatory step in hepatocarcinogenesis. Clinically the tumour usually becomes manifest by upper abdominal complaints. Curative treatment can be promising only with very small tumours which can be detected most safely via ultrasound examination and alpha-1-fetoprotein determination.

[Methotrexate in the therapy of primary biliary cirrhosis]. / Methotrexat in der Therapie der primären biliären Zirrhose.

In a pilot study 5 females with primary biliary cirrhosis (PBC), histological stages I-III, were treated with methotrexate (7.5-15.0 mg by mouth weekly) for 15 months. Pruritus and fatigue decreased in 3 patients and cholestyramine could be reduced or discontinued. The concentration of alkaline phosphatase decreased significantly until the 6th month of treatment (P less than 0.002), but only after the methotrexate dosage had been increased to 15 mg weekly. However, the improvement in cholestasis parameters persisted until the end of the period of observation in only 3 patients in stages I and II. In only one case, initially in stage III with increased serum bilirubin concentration of 3.5 mg/dl, was there a change in the histological stage, to stage IV, after treatment. These preliminary results indicate that methotrexate can influence the symptoms and cholestasis enzymes in the early stages of PBC. Controlled studies should therefore only be conducted on anicteric patients in an early stage of the disease.