The present and future disease burden of hepatitis C virus infections with today's treatment paradigm - volume 3.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.

Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II).

BACKGROUND: Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. AIM: To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection. METHODS: Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy. RESULTS: A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension. CONCLUSIONS: Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens.

Computed tomographic features of feline sino-nasal and sino-orbital aspergillosis.

Feline upper respiratory tract aspergillosis (URTA) occurs as two distinct anatomical forms, namely, sino-nasal aspergillosis (SNA) and sino-orbital aspergillosis (SOA). An emerging pathogen, Aspergillus felis, is frequently involved. The pathogenesis of URTA, in particular the relationship between the infecting isolate and outcome, is poorly understood. In this study, computed tomography was used to investigate the route of fungal infection and extension in 16 cases (SNA n = 7, SOA n = 9) where the infecting isolate had been identified by molecular testing. All cases had nasal cavity involvement except for one cat with SNA that had unilateral frontal sinus changes. There was a strong association between the infecting species and anatomic form (P = 0.005). A. fumigatus infections remained within the sino-nasal cavity, while cryptic species infections were associated with orbital and paranasal soft-tissue involvement and with orbital lysis. Cryptic species were further associated with a mass in the nasal cavity, paranasal sinuses or nasopharynx. Orbital masses showed heterogeneous contrast enhancement, with central coalescing hypoattenuating foci and peripheral rim enhancement. Severe, cavitated turbinate lysis, typical of canine SNA, was present only in cats with SNA. These findings support the hypothesis that the nasal cavity is the portal of entry for fungal spores in feline URTA and that the route of extension to involve the orbit is via direct naso-orbital communication from bone lysis. Additionally, a pathogenic role for A. wyomingensis and a sinolith in a cat with A. udagawae infection are reported for the first time.

Sensing and transmission characteristics of a rocking filter fabricated in a side-hole fiber with zero group birefringence.

We report on sensing and transmission characteristics of rocking filters fabricated in a silica side-hole fiber with group birefringence changing its sign at certain wavelength (λ(G = 0)), which corresponds to parabolic-like spectral dependence of beat length. Unusual birefringence dispersion of the side-hole fiber is induced by an elliptical germanium doped core located in a narrow glass bridge between two holes. Rocking filters fabricated in such a fiber have two resonances of the same order located on both sides of λ(G = 0). The sensitivity of both resonances has an opposite sign, which makes it possible to double the response of the rocking filter by applying the differential interrogation scheme. We demonstrate that in this way a pressure sensitivity of the rocking filter can be enlarged to 132 nm/MPa. We also show that by fabricating the rocking filter with a period close to maximum beat length a coupling between polarization modes can be obtained in a broad band reaching 240 nm.

Sensing characteristics of the rocking filters in microstructured fibers optimized for hydrostatic pressure measurements.

We report on the sensing characteristics of rocking filters fabricated in two microstructured fibers with enhanced polarimetric sensitivity to hydrostatic pressure. The filter fabricated in the first fiber shows a very high sensitivity to pressure ranging from 16.2 to 43.4 nm/MPa, depending on the resonance order and features an extremely low cross-sensitivity between pressure and temperature 28 ÷ 89 × 10(3) K/MPa. The filter fabricated in the second fiber has an extreme sensitivity to pressure ranging from -72.6 to -177 nm/MPa, but a less favorable cross-sensitivity between pressure and temperature of 1.05 ÷ 3.50 × 10(3) K/MPa. These characteristics allow using the rocking filters for pressure measurements with mbar resolution.

Massive haematoma formation associated with proximal popliteal artery haemangioendothelioma in a dog.

A mixed breed dog presented with diffuse unilateral hind limb swelling, which ultrasound and cytology confirmed to be caused by severe haematoma formation. Multi-detector computed tomography (MDCT) angiography allowed distinct visualisation of an anomalous segment of the proximal popliteal artery, the presumed origin of the self-sustaining haematoma. Histopathology classified the malformed vessel as a haemangioendothelioma, a neoplasia of intermediate malignancy. Considering this as differential diagnosis to a neoplastic vascular alteration of high malignancy (such as haemangiosarcoma) might alter choice of treatment in future cases with similar clinical and imaging findings.

Medial radio-carpal arthrodesis in three cats with a 2.0 mm locking maxillofacial plate system.

The medical records of three cats that were presented with severe carpal injury requiring radiocarpal arthrodesis were reviewed. Medial plating using the Compact 2.0 LOCK™ system was performed in all three cases. Although screw positioning may be difficult because of the large distance between the holes of the plate and the relatively large size of screws, plate loosening or metacarpal fractures did not occur. Long-term clinical and radiographic follow-up (6 months to 4.5 years) revealed excellent outcome in two cats. In the third cat, the radiocarpal joint did not undergo complete fusion. At four and a half years following surgery, recurrence of forelimb lameness was associated with breakage of the plate.

Bilateral iatrogenic [corrected] maxillary fractures after dental treatment in two aged horses.

This clinical report describes two horses with bilateral maxillary fractures following dental treatment. The fractures occurred during dental treatment by a veterinarian, and both had rostral, transverse, and complete bilateral maxillary fractures with instability and minimal displacement. The fractures were repaired using bilateral intraoral wiring with the patients under general anesthesia. The postoperative period was without complications and the fractures healed as expected. Maxillary fractures during or after routine dental treatment are rare, but can occur, especially in older horses. Appropriate sedation and, if necessary, regional nerve blocks might reduce the risk of iatrogenic fractures of the maxilla. General anesthesia must be considered for tooth extraction in horses that are difficult to restrain.

Pulmonary artery thrombosis in experimental Angiostrongylus vasorum infection does not result in pulmonary hypertension and echocardiographic right ventricular changes.

BACKGROUND: Dogs experimentally inoculated with Angiostrongylus vasorum develop severe pulmonary parenchymal lesions and arterial thrombosis at the time of patency. HYPOTHESIS: A. vasorum-induced thrombosis results in arterial hypoxemia, pulmonary hypertension (PH), and altered cardiac morphology and function. ANIMALS: Six healthy Beagles experimentally inoculated with A. vasorum. METHODS: Thoracic radiographs and arterial blood gas analyses were performed 8 and 13 weeks postinoculation (wpi) and 9 weeks posttherapy (wpt). Echocardiography was done before and 2, 5, 8, 13 wpi and 9 wpt. Invasive pulmonary artery pressure (PAP) measurements were obtained 8 wpi. Two untreated dogs were necropsied 13 wpi and 4 treated dogs 9 wpt. RESULTS: All dogs had patent infections at 7 wpi and clinical respiratory signs at 8 wpi. Moderate hypoxemia (median PaO2 of 73 and 74 mmHg) present at 8 and 13 wpi had resolved by 9 wpt. Echocardiographically, no evidence of PH and no abnormalities in cardiac size and function were discernible at any time point. PAP invasively measured at 8 wpi was not different from that of control dogs. Severe radiographic pulmonary parenchymal and suspected thrombotic lesions at 13 wpi were corroborated by necropsy. Most histopathologic changes had resolved at 9 wpt, but focal inflammatory, thrombotic, and fibrotic changes still were present in all dogs. CONCLUSION: In experimentally infected Beagles, pulmonary and vascular changes induced by A. vasorum are reflected by marked radiographic changes and arterial hypoxemia. These did not result in PH and echocardiographic changes in cardiac size and function.

[Megaesophagus secondary to an esophageal leiomyoma and concurrent esophagitis]. / Megaösophagus infolge eines ösophagealen Leiomyoms und Osophagitis beim Hund.

A 13-year-old male intact Golden Retriever was presented for chronic regurgitation and vomitus. The only clinical abnormality was halitosis, a neurological examination was normal. Thoracic radiography revealed a moderately distended, air-filled esophagus and a presumptive diagnosis of idiopathic megaesophagus was made. No other disorder causing abnormal esophageal motor function could be identified. As supportive and anticholinergic therapy failed to improve the dogs condition and ongoing regurgitation worsened, owners opted for euthanasia. Postmortem examination revealed a small (1.5 cm diameter) mass in the terminal esophagus. Microscopically a leio-myoma with mild multifocal mixed-cell esophagitis was diagnosed. This report illustrates how a potentially curable disease such as leiomyoma can clinically mimic acquired idiopathic megaesophagus and emphasizes that additional diagnostic procedures (contrast study, esophagoscopy) can be indicated in individual cases.

Fungal colonization of the esophagus in alcoholic liver disease.

OBJECTIVES: Little is known about the fungal colonization of the esophagus. Since alcoholic liver disease (ALD) patients are prone to fungal esophagitis, we have investigated the esophageal fungal colonization of this patient group. METHODS: One hundred consecutive ALD patients were enrolled in this prospective study. 22 patients with dyspeptic symptoms acted as controls. After taking an oropharyngeal swab, patients underwent an upper gastrointestinal endoscopy and surface material was obtained from the esophagus for direct smears and culture. RESULTS: In the ALD group pseudohyphae were found in 21.5% and yeast forms in 6.4% of the direct smears. The culture was positive in 40.8% of the ALD patients, the isolated strains were: 30 C. albicans, 2 C. kefyr, 2 C. krusei, 1 C. zeylanoides and in 3 cases the species could not be identified. 41.9% of ALD patients and 13.6% of control patients (p = 0.013) had fungi in their esophagus. Significantly more ALD patients had fungal esophagitis than in the control group (19.3% vs. 0%, p = 0.021), the rate of fungal colonization was also higher, but the difference was not significant (22.5% vs. 13.6%). A significantly higher rate of fungal esophagitis and esophageal colonization was found in patients with fungi in their oropharyngeal swabs (p = 0.00001). CONCLUSIONS: Fungal colonization of the esophagus is frequent in ALD patients. Its presence might have clinical significance in the case of liver transplantation.

Distribution of T-lymphocyte subpopulation in blood and spleen of normal cattle and cattle with enzootic bovine leukosis.

Immunocytochemical and flow cytometry techniques were used to examine T-lymphocyte subpopulations in peripheral blood lymphocytes (PBLs) and spleen from cases of enzootic bovine leukosis (EBL) in adult cattle, and from normal cattle (adult and young), with a panel of monoclonal antibodies against bovine leucocyte differentiation molecules. Both in PBLs and spleen, the percentages of T-lymphocyte subpopulations (CD3+, CD4+, CD8+, and WC1 + gamma delta T lymphocytes) of EBL-affected and normal adult cattle were significantly lower than those of normal young cattle. The percentages of these T-lymphocyte subpopulations in the PBLs of adult cattle with EBL were lower than those of normal adult cattle, but the converse was true in the spleen. It is suggested that tumour immunity occurred in the spleen. Histological examination revealed no follicular hyperplasia in the spleen, and the proliferation of neoplastic cells began in the red pulp. It is concluded that the spleen is not the organ initially responsible for the transformation of EBL lymphoma and that neoplastic cells migrating from peripheral blood are metastatic.

Hemorrhagic enteritis associated with Clostridium perfringens type A in a dog.

A female Shetland sheep dog died suddenly with hemorrhagic diarrhea and vomitting, and was examined pathologically and microbiologically. Gross pathological change was restricted to the intestinal tract. The intestine contained watery, blood-stained fluid. Histopathologically, the principal intestinal lesion was superficial mucosal hemorrhagic necrosis at the jejunoileum. Many Gram-positive bacilli were found adhering to the necrotic mucosal surface in parts of the intestinal tract. Clostridium perfringens in pure culture were isolated from jejunal contents by anaerobic culture. These results suggested that the typical lesion of this case coincided with canine hemorrhagic enteritis and enterotoxemia due to C. perfringens infection could be the cause of sudden death.

[The comparison of self-concept and self-acceptance in patients with paranoid schizophrenia and neurotic disorder]. / Porównanie obrazu wlasnego ja i samoakceptacji u chorych na schizofrenie paranoidalna i nerwice.

Self-acceptance as a correlation between real and ideal self-concept distinguishes neurotic patients from paranoid schizophrenic patients. This fact may support the hypothesis that these groups of patients are characteristic of different personality traits.

Comparison of single-dose and 7-day fluconazole treatment of fungal esophagitis in alcoholic liver disease.

The aim of the study was to assess the effectiveness of a single-dose fluconazole treatment of fungal esophagitis in patients with alcoholic liver disease. Twenty-two alcoholic liver disease patients with fungal esophagitis were randomly assigned to receive either a single-dose of 150 mg fluconazole or a 7-day treatment of daily 50 mg fluconazole. Control esophagoscopy was performed in both groups on days 9-11. Direct smears and cultures on Sabouraud's medium were performed at both endoscopies. Patients' sera were tested for Candida antigens and for antibodies against Candida albicans on days 1, 8 and 15. Twenty patients (18 C. albicans, 1 C. tropicalis, 1 C. pseudotropicalis) completed the study, there were two drop-outs from the single-dose group. Antibodies against C. albicans were found in four cases, Candida antigens in five. There were no significant differences in the treatment outcome between the two groups, clinical cure was recorded in eight out of nine patients in the single-dose group and nine out of eleven patients in the 7-day group, mycological eradication in four out of nine, and in three out of eleven, respectively. Single-dose fluconazole treatment seems to be an effective therapy of fungal esophagitis in alcoholic liver disease patients.

[Diagnostic and therapeutic experiences with purulent meningitis in adults]. / Diagnosztikus és terápiás tapasztalatok felnöttkori gennyes agyhártyalobban.

The authors reviewed data of 137 patients with purulent meningitis treated in the period of 10 years. Attention was paid to the frequency of predisposing and associated diseases, to the factors helping and delaying the diagnosis and to those altering the prognosis. The importance of effective supportive care, particulary covering pressure of the CNS as well as specific therapy was stressed. The circumstances and the conditions of management depending on the condition of the patient was emphasized. Thirty eight of patients (27%) has died.

[Prevention of rabies (experience of the past, possibilities of the future)]. / A rabies prevenciója (a múlt tapasztalatai és a jövö lehetöségei).

The authors review the history of rabies prevention, the current national and international data. Neurologic adverse effects of the Hempt vaccine are discussed. Medical histories of two patients are demonstrated, one suffered of serious complication of the vaccine; the other died of rabies. Indications of vaccine Rabivac and issues about it's administration are outlined. The possibilities of the therapy are discussed in brief.

[Acute intermittent porphyria simulating encephalitis]. / Encephalitis gyanúját keltö acut intermittens porphyria.

The authors present the case of a patient suffering from acute intermittent porphyria presenting as encephalitis. The differential diagnostics, the causes and the therapy of the porphyria attack are discussed in detail.