Impact of age on viral kinetics of peginterferon alfa-2a/ribavirin in chronic hepatitis C: final analysis from the PROPHESYS cohort.

The population of patients with chronic hepatitis C viral infection is ageing; however, elderly, hepatitis C-infected patients are understudied and less frequently treated. This subanalysis of data from the multinational PROPHESYS study examined associations between age (≤65 vs >65 years), on-treatment virological response and sustained virological response (SVR) in patients treated with peginterferon alfa-2a (40KD)/ribavirin in accordance with local licences. PROPHESYS comprised three cohorts studied in 19 countries according to country-specific legal and regulatory requirements. This subanalysis includes treatment-naive HCV mono-infected patients assigned to receive peginterferon alfa-2a (40KD)/ribavirin, with 6276 individuals aged ≤65 years and 349 aged >65 years. Rapid virological response (RVR) rates by Week 4 were consistently lower in older genotype (G) 1 (21.6% vs 27.2% in younger patients), G2 (80.7% vs 85.1%) and G3 (60.0% vs 74.2%) patients. SVR rates were significantly lower (29.8% vs 43.0%) and relapse rates significantly higher (43.1% vs 26.7%) in older G1 patients (P = 0.0002 vs ≤65 years). In contrast, SVR and relapse rates were similar in G2 and G3 patients regardless of age. The positive predictive value of RVR for SVR was comparable in older and younger G1 patients (66.7% vs 68.6%, respectively) and higher in older G2 (80.7% vs 75.6%) and G3 (77.8% vs 66.8%) patients. Virological response rates are generally lower in elderly CHC patients, and RVR is a reliable positive predictor of SVR in patients >65 years.

Ictal dystonic posturing in mesial versus neocortical temporal lobe seizures.

PURPOSE: Ictal contralateral dystonic posturing is a frequently observed clinical feature in temporal lobe seizures. It is generally interpreted as the result of spread of the ictal discharge into basal ganglia structure. In previous reports, analysing ictal behavior, a precise definition and description of the upper limb ictal dystonia is often lacking or contradictory. In our study we aimed to determine whether different subtypes of dystonia and their latency from the clinical onset of seizure might be of value for the differentiation between mesial temporal lobe epilepsy (MTLE) and neocortical temporal lobe epilepsy (NTLE). METHODS: Eighty seizures (51 MTLE and 29 NTLE) and 30 patients (20 MTLE and 10 NTLE) were analyzed with regard to dystonic posturing of the upper limb. Ictal dystonia was subdivided into different subtypes according to distinct clinical features. Their frequency and latency from the clinical onset of seizure were assessed. RESULTS: Frequencies of all subtypes were similar in MTLE and NTLE. Concerning the latencies contralateral dystonic posturing characterized by sustained muscle contractions with flexion of the wrist and fist closure, a frequently appearing feature, occurred significantly earlier in NTLE than in MTLE seizures. CONCLUSIONS: This difference between the two groups may provide a differentiation between an epileptic focus of mesial from neocortical temporal lobe origin.

Roussy-Lévy syndrome is a phenotypic variant of Charcot-Marie-Tooth syndrome IA associated with a duplication on chromosome 17p11.2.

The Roussy-Lévy syndrome (MIM #180800) was described in 1926 as a disorder presenting with pes cavus and tendon areflexia, distal limb weakness, tremor in the upper limbs, gait ataxia and distal sensory loss. We report a family with affected members in four generations, showing these clinical signs of Roussy-Lévy syndrome and a partial duplication at chromosome 17p11.2. This genetic defect is commonly found in patients with the hypertrophic form of the Charcot-Marie-Tooth syndrome. Our finding provides evidence against the Roussy-Lévy syndrome as a distinct entity but suggests a close relation with the Charcot-Marie-Tooth syndrome. What causes the additional features of gait ataxia and essential tremor needs further clarification.

Gamma knife radiosurgery for hypothalamic hamartomas in patients with medically intractable epilepsy and precocious puberty. Report of two cases.

Hamartoma of the hypothalamus represents a well-known but rare cause of central precocious puberty and gelastic epilepsy. Due to the delicate site in which the tumor is located, surgery is often unsuccessful and associated with considerable risks. In the two cases presented, gamma knife radiosurgery was applied as a safe and noninvasive alternative to obtain seizure control. Two patients, a 13-year-old boy and a 6-year-old girl, presented with medically intractable gelastic epilepsy and increasing episodes of secondary generalized seizures. Abnormal behavior and precocious puberty were also evident. Magnetic resonance (MR) imaging revealed hypothalamic hamartomas measuring 13 and 11 mm, respectively. After general anesthesia had been induced in the patients, radiosurgical treatment was performed with margin doses of 12 Gy to 90% and 60% of isodose areas, covering volumes of 700 and 500 mm3, respectively. After follow-up periods of 54 months in the boy and 36 months in the girl, progressive decrease in both seizure frequency and intensity was noted (Engel outcome scores IIa and IIIa, respectively). Both patients are currently able to attend public school. Follow-up MR imaging has not revealed significant changes in the sizes of the lesions. Gamma knife radiosurgery can be an effective and safe treatment modality for achieving good seizure control in patients with hypothalamic hamartomas.

Endoscopic surgery versus medical treatment for spontaneous intracerebral hematoma: a randomized study.

A controlled randomized study of endoscopic evacuation versus medical treatment was performed in 100 patients with spontaneous supratentorial intracerebral (subcortical, putaminal, and thalamic) hematomas. Patients with aneurysms, arteriovenous malformations, brain tumors, or head injuries were excluded. Criteria for inclusion were as follows: patients' age between 30 and 80 years; a hematoma volume of more than 10 cu cm; the presence of neurological or consciousness impairment; the appropriateness of surgery from a medical and anesthesiological point of view; and the initiation of treatment within 48 hours after hemorrhage. The criteria of randomization were the location, size, and side of the hematoma as well as the patient's age, state of consciousness, and history of hypertension. Evaluation of outcome was performed 6 months after hemorrhage. Surgical patients with subcortical hematomas showed a significantly lower mortality rate (30%) than their medically treated counterparts (70%, p less than 0.05). Moreover, 40% of these patients had a good outcome with no or only a minimal deficit versus 25% in the medically treated group; the difference was statistically significant for operated patients with no postoperative deficit (p less than 0.01). Surgical patients with hematomas smaller than 50 cu cm made a significantly better functional recovery than did patients of the medically treated group, but had a comparable mortality rate. By contrast, patients with larger hematomas showed significantly lower mortality rates after operation but had no better functional recovery than the medically treated group. This effect from surgery was limited to patients in a preoperatively alert or somnolent state; stuporous or comatose patients had no better outcome after surgery. The outcome of surgical patients with putaminal or thalamic hemorrhage was no better than for those with medical treatment; however, there was a trend toward better quality of survival and chance of survival in the operated group.

Ethanol radical-induced protein-DNA crosslinking. A radiolysis study.

Aqueous solutions of double-stranded DNA from calf thymus and bovine serum albumin (BSA) were irradiated at pH 7 under N2O and N2 in the presence of 10(-1) mol dm-3 ethanol, which was partly 14C-labelled. Ethanol protects DNA from strand breakage by scavenging OH radicals, but ethanol radicals induce protein-DNA crosslinks. Ethanol radicals react readily with BSA mainly by addition. They react also with double-stranded DNA, but produce crosslinking only very slowly. Based on these results the following mechanism is proposed: ethanol radicals bind to BSA producing protein radicals which become crosslinked to DNA.

Future aspects of the presurgical evaluation in epilepsy.

Epilepsy surgery is a successful therapeutic approach in patients with medically intractable epilepsy. The presurgical evaluation aims to detect the epileptogenic brain area by use of different diagnostic techniques. In this review article the current diagnostic procedures applied for this purpose are described. The diagnostic armamentarium can be divided conceptually into three different groups: assessment of function/dysfunction, structural/morphologic imaging methods and functional neuroimaging techniques. Properties, diagnostic power and limits of all diagnostic tools used in the diagnostic evaluation are discussed. In addition, future perspectives and the diagnostic value of new technologies are mentioned. Some are increasingly gaining acceptance in the routine preoperative diagnostic procedure like MR volumetry or MR spectroscopy of the hippocampus in patients with temporal lobe epilepsy. Some, on the other hand, like MEG and 11C-flumazenil PET, still remain experimental diagnostic tools as they are technically demanding and cost intensive. Besides the refinement of established techniques, co-registration of different modalities like spike-triggered functional MRI will play an important role in the non-invasive detection of the epileptic seizure focus and may change the regimen of the preoperative diagnostic work up of epilepsy patients in the future.

Hemorheologic treatment of cerebral reversible ischemic episodes with pentoxifylline--a prospective study.

One hundred patients (49 males, 51 females) with reversible neurologic deficit due to cerebral ischemia of vascular origin in the carotid artery territory were recruited for a long-term observation to follow up recurrence of ischemic events. Fifty-eight patients (mean age sixty-four years) were treated daily with 1200 mg oral pentoxifylline in addition to basic therapy (antihypertensives, antidiabetic drugs, etc), and 42 matching patients (mean age sixty-two years) of a control group had no pentoxifylline or other hemorheologic medication. The mean observation period was fifty-six months (range thirty-six to sixty). On admission patients presented with increased platelet aggregation and/or impaired red cell filterability and with enhanced red cell aggregation. Five patients in the pentoxifylline group (8.6%) and 16 control patients (38%) suffered a relapse of an ischemic episode. These data support previous reports of a beneficial effect of pentoxifylline in the prevention of cerebral ischemic events.

[Clinical diagnosis of normal pressure hydrocephalus (author's transl)]. / Klinik und Diagnose des Normaldruckhydrozephalus.

5 patients are described in which normal pressure hydrocephalus was diagnosed. The criteria on which the diagnosis was based were a cerebrospinal fluid perfusion test and an air study. Pathological verification was additionally obtained in 2 patients. The clinical picture in all patients was characterized by dementia. 4 patients were incontinent and 3 were paraspastic.

[Occurrence of dementia and depression in an elderly Danish population]. / Forekomsten af demens og depression i en dansk aeldrebefolkning.

A community survey of all Danish speaking residents above the age of 64 in a geographically delimited area was performed. The aim of the survey was to establish the prevalence of dementia disorders and depression by the use of international screening tools: the Mini Mental State Examination for dementia and the Beck's Depression Inventory for depression. The screening was performed during the period of one year in the municipality of Karlebo and the interviews took place in the homes of the participants. Six hundred and sixty-four (66%) of the 1,008 eligible persons entered the study. Six percent were residents in nursing homes. Thirteen point seven percent were found to be suffering from dementia. Nine point six percent had symptoms of depression. These prevalences would indicate that more than 6,000 persons in Frederiksborg county suffer from dementia while more than 4,000 might be suffering from depression. The study confirms knowledge obtained in other studies, indicating that one out of seven of the elderly suffers from dementia. We do not conclude, however, that nine point six percent suffer from depression, but rather that they need further examination to make it possible to decide whether they are indeed depressed.

[Geriatric psychiatry in the regimen of community psychiatry. 2. Psychiatric consultation service at a primary care community nursing home for the physically handicapped]. / Gerontopsykiatri i distriktspsykiatrisk regi. 2. Psykiatrisk konsulenttjeneste på primarekommunale plejehjem og amtskommunale plejehjem for fysisk handicappede.

In January 1988, three gerontopsychiatric teams were established in the Copenhagen County Hospital, Nordvang. One of their rasks was to supply outpatient psychiatric service for nursing homes. The object of this investigation was to investigate how much this offer was utilised, and assessment of this service by the nursing homes in a geographically delimited region consisting of 11 primary communities. The investigation was retrospective. Where all of the patients were concerned, the following were registered: age, sex, diagnosis and residence at the conclusion of treatment. After 12 months, a questionnaire was sent to all departments in nursing homes with questions about whether they had utilised this offer and how they had assessed it. During the period from 1.1.1988 to 31.12.1988, 184 patients were referred corresponding to 7.6% of all residents in nursing homes. Two gerontopsychiatric teams had had contact with 80 out of 116 possible departments and had arranged teaching about psychiatric illness in elderly persons in 39 out of 48 nursing homes. The consultant service given included individual diagnosis and treatment and also teaching and advice to the staff. The positive assessment reflected the need for a gerontopsychiatric service in nursing homes. An offer of gerontopsychiatric service should be included in the total community psychiatric service.

[Geriatric psychiatry in the regimen of community psychiatry. 1. Community psychiatric services for patients living at home]. / Gerontopsykiatri i distriktspsykiatrisk regi. 1. Distriktspsykiatrisk funktion for hjemmeboende.

On 1.1.1988 three community psychiatric teams were established in the gerontopsychiatric fields under the Copenhagen County Hospital, Nordvang. The objects were to supervise and treat patients over the age of 65 in their own homes or in nursing homes. This article is an account of the functions of two teams concerning patients living in their own homes during the period 1st January to 31st December 1988. A total of 125 patients were referred and 31 were admitted, five of these because of lack of nursing home beds. Women and persons living alone were most frequently involved. On the initiative of the teams, it proved possible to obtain increased covering by measures in the primary community in various fields. The frequency of psychopharmacological treatment was high and this was in agreement with the observation that 33% were psychotic and that many demented patients presented secondary psychiatric symptoms requiring treatment. It is concluded that it was possible to treat these patients in their own homes to a great extent, that the psychiatric service for elderly persons is improved and that cooperation between the hospital, referring general practitioner and the primary community had increased.

[Patients' evaluation of coercion in a psychiatric department. Interview studies in psychiatric departments for adult patients at the Hillerød hospital]. / Patienternes vurdering af tvang på psykiatrisk afdeling. Interviewunders gelse på de voksenpsykiatriske afdelinger ved Hillerød Sygehus.

During an 11 month period, use of coercion was prospectively registered in a psychiatric department. Of all patients who had been subjected to coercion 36% were (n = 86) interviewed subsequently. Eleven percent of the interviewed patients did not know, that they had been submitted to coercion, 22% did not know the reason and 30% did not agree with the motivation for the decision. Forty-seven percent were satisfied with the information they had been given concerning how to complain of their treatment, 50% were satisfied with their adviser and 70% were satisfied with their overall admission. Sixty-five percent accepted that there should be a law allowing the use of coercion in psychiatry.

[The use of coercion at psychiatric departments for adults, Hillerød hospital. A descriptive study of the period 10 January 1991-31 August 1992]. / Tvangsudøvelse på de voksenpsykiatriske afdelinger, Hillerød Sygehus. En deskriptiv undersøgelse i perioden 1.10.1991-31.8.1992.

The study describes the type and amount of coercion used during 11 months of 1992. Four hundred and fourty-one cases were included. Young patients i.e. 10 to 29 years old, demented patients and patients suffering from organic psychoses were, overall, more often subjected to coercive measures. When looking at each type of coercion separately, it was found that detainment, compulsive treatment and fixation were especially used on the young and on patients suffering from schizophrenia. However, fixation used as a protective measure was mainly used on the demented and the 60 to 79 year-old patients.

[Practice-oriented control of BVD virus infection in cattle herds]. / Praxisorientierte Bekämpfung der BVD-Virusinfektion in Rinderbeständen.

The BVD-virus-infection is at present the economically most important disease of bovine animals. A control program requires to take into consideration the given epidemiological facts. Sufficient diagnostic examination procedures are available for estimation of the infection taking place in a herd. An effective preventive measure prior to the infection as well as the quick limitation of an already existing infection taking place consists in a consequent vaccination program. Pre-condition for the vaccination program is the attention to a strict indication of vaccines available, the detailed information of the animal owner as well as taking into consideration the cost-profit-proportion of the envisaged control measurements.

Absolute and relative contraindications to pegylated-interferon or ribavirin in the US general patient population with chronic hepatitis C: results from a US database of over 45 000 HCV-infected, evaluated patients.

BACKGROUND: Chronic hepatitis C (HCV) treatment with pegylated-interferon (PEG-IFN)/ribavirin (RBV) is often limited by preexisting medical, psychiatric and psychosocial contraindications. However, limited data exist in general patient populations. AIM: To evaluate the percentage of HCV-infected patients in the general US population who may have contraindications to PEG-IFN/RBV. METHODS: The General Electric (GE) Centricity dataset was used to screen the US population between 2004 and 2009 for HCV infection and contraindications to PEG-IFN/RBV. HCV diagnosis and contraindications were identified using ICD-9-CM codes or laboratory values. Only patients with an encounter 180 days prior to HCV diagnosis were included. Demographic differences were calculated using Pearson's chi-squared test. Frequencies and percentages for absolute and relative contraindications to PEG-IFN and/or RBV were determined and proportions and rates/1000 person-months were calculated. RESULTS: A total of 15 561 021 patients were screened, and 45 690 (0.3%) were HCV-positive and were evaluated. Those with contraindications were significantly younger, female, White, not currently married and receiving Medicare or Medicaid coverage (all P < 0.0001). 17.3% had at least one contraindication to PEG-IFN/RBV (5.5 events/1000 person-months); bipolar disorder (6.5%), anaemia (Hgb < 10 g/dL; 5.9%), pregnancy (1.9%) and neutropenia (neutrophils <750 cells/mm(3) ; 1.2%) were most frequently cited. CONCLUSIONS: Approximately, 17% of HCV-infected patients in the general US population had at least one contraindication to PEG-IFN/RBV. Most contraindications were relative and potentially modifiable. Clinical assessment of contraindications as relative and/or modifiable should be considered and used to determine if patients could benefit from current PEG-IFN-containing triple therapy or future PEG-IFN- or RBV-free regimens.

Hepatitis C virus therapy is associated with lower health care costs not only in noncirrhotic patients but also in patients with end-stage liver disease.

BACKGROUND: The effect of anti-viral treatment on downstream costs for hepatitis C virus (HCV)-infected patients is unknown. AIM: To evaluate follow-up costs in patients with chronic HCV, stratified by liver disease severity. METHODS: Using a US private insurance database, mean all-cause per-patient-per-month (PPPM) US (2010) medical costs were calculated for HCV-infected persons who did and did not receive anti-HCV treatment between January 2002 and August 2010. Analysis was stratified by liver disease severity [noncirrhotic disease (NCD), compensated cirrhosis (CC) or end-stage liver disease (ESLD)] defined by ICD-9 and CPT codes. RESULTS: A total of 33 309 patients were included (78% NCD, 7% CC and 15% ESLD); 4111 individuals (12%) received anti-HCV treatment during the 2-year baseline period. Mean PPPM follow-up health care costs were significantly lower among treated patients with NCD ($900 vs. $1378 in untreated patients, P < 0.001) and ESLD ($3634 vs. $5071, P < 0.001) groups but not in the CC group ($1404 vs. $1795, P < 0.071; t-test). In a multivariable model adjusted for demographic characteristics, comorbidities, index date and geographical region, incremental cost ratios for total health care costs differed significantly (P < 0.001) between treated and untreated patients in the NCD and ESLD groups but not in the CC group. From this model, mean PPPM total health care costs between treated and untreated patients were $885 and $1370 in the NCD, $1369 and $1802 in the CC, and $3547 and $5137 in the ESLD groups, respectively. CONCLUSIONS: Anti-HCV therapy was associated with lower follow-up US health care costs, and these savings were independent of baseline patient comorbidities and stage of disease.

Fine-tuning of substrate architecture and surface chemistry promotes muscle tissue development.

Tissue engineering has been increasingly brought to the scientific spotlight in response to the tremendous demand for regeneration, restoration or substitution of skeletal or cardiac muscle after traumatic injury, tumour ablation or myocardial infarction. In vitro generation of a highly organized and contractile muscle tissue, however, crucially depends on an appropriate design of the cell culture substrate. The present work evaluated the impact of substrate properties, in particular morphology, chemical surface composition and mechanical properties, on muscle cell fate. To this end, aligned and randomly oriented micron (3.3±0.8 µm) or nano (237±98 nm) scaled fibrous poly(ε-caprolactone) non-wovens were processed by electrospinning. A nanometer-thick oxygen functional hydrocarbon coating was deposited by a radio frequency plasma process. C2C12 muscle cells were grown on pure and as-functionalized substrates and analysed for viability, proliferation, spatial orientation, differentiation and contractility. Cell orientation has been shown to depend strongly on substrate architecture, being most pronounced on micron-scaled parallel-oriented fibres. Oxygen functional hydrocarbons, representing stable, non-immunogenic surface groups, were identified as strong triggers for myotube differentiation. Accordingly, the highest myotube density (28±15% of total substrate area), sarcomeric striation and contractility were found on plasma-coated substrates. The current study highlights the manifold material characteristics to be addressed during the substrate design process and provides insight into processes to improve bio-interfaces.