Mucosal features and granulocyte–monocyte-apheresis in steroid-dependent/refractory ulcerative colitis

BACKGROUND: Mucosa-infiltrated granulocyte neutrophils are an early characteristic of inflammation and the main histological feature of active ulcerative colitis. Mucosal healing has recently been indicated as an important tool in the evaluation of response to treatment. While several studies have stressed the efficacy of granulocyte-monocyte-apheresis in inducing clinical remission in active ulcerative colitis, few data are available on mucosal features. AIM: Aim of this study was to assess the effects of granulocyte-monocyte-apheresis on clinical and mucosal features in patients with ulcerative colitis, dependent upon or refractory to steroids. MATERIAL AND METHODS: From April 2004 to April 2005, 12 patients (5 females, 7 males, mean age 49 years, range 33-71 years), with mild-moderate ulcerative colitis (six left colitis, six pancolitis) dependent/refractory upon steroids were enrolled. Each patient was treated for a 5-week period with five cycles of granulocyte-monocyte-apheresis. Patients were evaluated at baseline and 1 week after the last apheresis by means of Global Physician Assessment, quality of life features, laboratory tests (erythrocyte sedimentation rate, CRP, full blood count, faecal calprotectine), endoscopy and histology. RESULTS: At week 6 of follow-up, complete mucosal healing was observed in 3 out of 12 patients, partial mucosal healing in 8 patients and no change in 1 patient. Clinical response was complete in 8 out of 12 patients. CONCLUSIONS: These data suggest that granulocyte-monocyte-apheresis induces an improvement both in clinical and mucosal lesions in steroid-dependent/refractory ulcerative colitis. Of note, the reduction in granulocyte infiltration and the improvement in mucosal lesions are accompanied by a reduction in faecal calprotectine.     

Bone disease in primary biliary cirrhosis: Lack of association with distal renal tubular acidosis

Background and Aims: Primary biliary cirrhosis (PBC) might be complicated by osteoporosis, whose etiology remains unknown but seems to be multifactorial. Prevalence rates of 30% to 60% for distal renal tubular acidosis (DRTA) have been reported in PBC patients, generally as incomplete DRTA. Although it is undisputed that a reduced bone mineral density (BMD) is the expected outcome among patients who have been suffering from longstanding chronic metabolic acidosis, it is unclear if incomplete DRTA is also associated with metabolic bone disease in PBC patients. The present study was undertaken to compare the BMD of PBC patients with and without DRTA.
Methods: The BMD of 23 PBC patients (11 with DRTA and 12 without), all with normal clearance of creatinine, was assessed by dual energy radiograph absorptiometry. The diagnosis of DRTA was made if the urine pH was above 5.4 in all samples after the oral acid overload, showing tubular inability to acidify urine in the presence of test-induced systemic metabolic acidosis.
Results: Densitometric signs of osteoporosis were found in 82% of DRTA cases and in 83% of patients without DRTA (difference not significant). There were no significant differences in BMD measurement, T and Z scores of patients with and without DRTA.
Conclusions: The present study could not support a correlation between the presence of DRTA and the bone loss observed in PBC patients.     

老年性痴呆的病理特征与防治对策

老年痴呆症的发生与AB以及Tau蛋白的错误折叠密切相关，是蛋白质折叠相关的疾病，早期诊断是预防老年痴呆症的首要任务，而综合治疗是人类对抗老年痴呆症的必然举措。     

Effect of short daily home haemodialysis on quality of life, cognitive functioning and the electroencephalogram.

BACKGROUND: End-stage renal disease patients have a poor quality of life (QoL), suffer from impaired cognitive functioning, and their electroencephalogram (EEG) shows abnormalities. Conventional haemodialysis (CHD) only partially restores these disorders. Short daily haemodialysis (SDHD) has been reported to improve QoL, but effects on cognitive functioning and EEG have yet to be described. METHODS: Of the 13 patients (11 male, 2 female, age 45.5 +/- 8.1 years), 11 completed the Kidney Disease Quality of Life and Affect Balance Scale questionnaires, 10 underwent neuropsychological testing, and all 13 underwent EEG examination. For the neuropsychological assessments, nine patients (six male, three female, age 45.4 +/- 12.6) who remained on the CHD schedule, served as controls. The dialysis schedule of thrice-a-week for 4 h was changed in the experimental group to six times a week for 2 h (SDHD) over a period of 6 months and back to thrice a week for 4 h. RESULTS: When on SDHD, patients rated several dimensions of health-related QoL as being improved. After resuming CHD, one of these dimensions again decreased and several others worsened even lower than baseline. Cognitive functioning did not change when compared with control data. On the EEG, alpha peak frequency increased slightly when on SDHD but decreased significantly after resuming CHD. CONCLUSIONS: SDHD improves health-related QoL, but has no clear effects on cognitive functioning and EEG. Resumption of CHD after SDHD decreases aspects of QoL and EEG alpha peak frequency but has no effect on cognitive functioning.     

Disappointing results and low tolerability of photodynamic therapy with topical 5-aminolaevulinic acid in psoriasis. A randomized, double-blind phase I/II study

BACKGROUND: Based on good results in the treatment of superficial skin tumours, since the early 1990s topical photodynamic therapy with aminolaevulinic acid (ALA PDT) has been used for disseminated, inflammatory dermatoses including psoriasis. However, there is still a lack of well-documented trials. OBJECTIVE: A prospective randomized, double-blind phase I/II intrapatient comparison study was conducted in 12 patients to investigate whether topical ALA PDT is an effective treatment for chronic plaque-type psoriasis. METHODS: In each patient three psoriatic plaques were randomly treated with a light dose of 20 J/cm(2) and 0.1%, 1% and 5% ALA, respectively. Treatment was conducted twice a week until complete clearance or for a maximum of 12 irradiations. Therapeutic efficacy was assessed by weekly determination of the psoriasis severity index (PSI). RESULTS: The mean percentage improvement was 37.5%, 45.6% and 51.2% in the 0.1%, 1% and 5% ALA-treated groups, respectively. Irradiation had to be interrupted several times because of severe burning and pain sensation. CONCLUSION: Topical ALA PDT did not prove to be an appropriate treatment option for plaque-type psoriasis due to disappointing clinical efficacy, the time-consuming treatment procedure and its unfavourable adverse event profile.     

Pathological and biochemical studies on a case of Pick disease with severe white matter atrophy

We report on a male patient with Pick disease who had shown severe white matter atrophy and dilatation of the lateral ventricle in the frontal lobe from an early stage. Upon admission to our hospital 2 years after disease onset, the patient showed apathy, and MRI revealed severe atrophy of the cortex and white matter of the frontal lobe. He died at age 74, 11 years after disease onset. Autopsy revealed severe atrophy of the frontal and temporal lobes, severe loss of white matter in the frontal lobe, dilatation of the lateral ventricles, and cortical thinning. Histopathological examination showed severe loss of myelinated fibers in the frontal white matter and severe neuronal loss with gliosis in the frontal and temporal cortices. Many Pick bodies were seen. Our patient had a rare case of Pick disease predominantly affecting the frontal lobe with severe involvement of the white matter from an early stage. This case suggests that myelinated fibers in the white matter as well as cerebral neurons are primarily affected in Pick disease.     

Hemiballismus from a parietal stroke in a Parkinson patient.

Stroke-induced hemiballismus (HB) has been reported to improve motor function in people with Parkinson's disease (PD). We report on a patient who developed HB from a parietal infarct. The HB was improved by very low-dose clozapine but the HB did not improve the parkinsonism. This suggests that HB itself, whether from a lesion in the subthalamic nucleus or elsewhere, is not what improves motor function in PD; instead, the physiological function of the damaged structure is the determining factor.     

Epstein-Barr virus DNA in Reed-Sternberg cells of Hodgkin''s disease is frequently associated with CR2 (EBV receptor) expression

We studied 44 cases of Hodgkin's disease for the presence of Epstein-Barr virus (EBV) DNA, its localization and the expression of the EBV receptor on the tumour cells. EBV DNA was found in 52% (16/31) of the Hodgkin's lymphomas using the polymerase chain reaction. With a very sensitive non-radioactive DNA in situ hybridization technique in combination with immunohistochemistry for CD 30 or CD 15 antigens, EBV DNA was localized to Reed-Sternberg cells and its mononuclear variants. The relationship between the presence of EBV DNA and the expression of the EBV-receptor CR2 (CD 21) on Reed-Sternberg cells was studied using the same techniques and two different monoclonal anti-CD 21 antibodies. CR2 could be detected on a substantial number of the Reed-Sternberg cells in EBV DNA positive Hodgkin's lymphomas (9/12; 75%), whereas in EBV negative cases positivity with anti-CD 21 was rare (1/13; 8%). The results indicate that CR2 expression on Reed-Sternberg cells and the presence of EBV DNA sequences are frequently associated in Hodgkin's lymphomas.     

Ethyl-EPA in Huntington disease—Potentially relevant mechanism of action

The pathomechanisms involved in the neuronal dysfunction in Huntington disease (HD) are still unresolved and may be heterogeneous. One potential mechanism might be related to the induction of mitochondrial dysfunction in the CNS. This might lead firstly to neuronal dysfunction and finally to the activation of apoptotic pathways. Several compounds, which should alleviate mitochondrial dysfunction, have been tested in preclinical models as well as in clinical trials of different scale. Recently we reported the efficacy of Ethyl-eicosapentaenoic acid (Ethyl-EPA) in patients with HD. Ethyl-EPA is a polyunsaturated fatty acid from the n − 3 group, which is in clinical development for HD and melancholic depression. In our trial with Ethyl-EPA in HD responding patients could be characterized by either a lower CAG repeat number or a chorea-predominant clinical expression of the disease. Here we would like to describe some evidence on the potential mechanism of action of Ethyl-EPA in HD. We specifically focus on pathways, which are known to be influenced in HD and are modified by Ethyl-EPA and which points to an involvement of mitochondrial function as a common target. Some attention is given to the NF-kappa B pathway and the c-Jun amino-terminal kinases (JNK) pathway, which both may lead to an activation of the antiproliferative factor p53 and consequently mitochondrial dysfunction. Further the effects of EPA or Ethyl-EPA in preclinical models of HD are described. The evidence from these studies led to the design of phase III clinical trials, which are ongoing.     

Kawasaki Disease in a Father and Son

The pathogenesis and etiology of Kawasaki disease are unknown, but some studies suggest increased genetic susceptibility. The case is presented of an infant with Kawasaki disease whose father suffered from the same illness 21 years previously. The A, B and C loci of the HLA antigens were examined.