Treatment of severe lichen planus with mycophenolate mofetil

Lichen planus (LP) is an inflammatory skin disorder with a wide range of clinical appearances. The treatment of disseminated and especially erosive forms of LP is often difficult and disappointing. Activated T cells are important in the pathogenesis of LP as indicated by the dermal lymphocytic infiltrate leading to keratinocyte destruction and lesion formation. Similar histologic findings are present in graft-versus-host disease. Since T cells are key players in the development of both disorders and mycophenolate mofetil has been successfully introduced in the treatment of graft-versus-host disease, we have examined the therapeutic potential of this agent in 3 patients suffering from disseminated and erosive LP. Mycophenolate mofetil was well tolerated and induced complete remission in 2 patients, and substantial improvement in the third patient.     

Kidney transplant in children weighing less than 15 kg: donor selection and technical considerations

BACKGROUND: Small children represent a challenging patient group in kidney transplantation (KTx). The aim of this study was to analyze patient and donor data influencing outcome in children that weighed <15 kg. METHODS: Sixty-eight kidneys were transplanted in 64 children that weighed <15 kg. In 44 cases, kidneys came from cadaveric donors (CAD) and in 24 cases from living-related donors (LRD). Grafts were placed transperitoneally via midline incision (n=16) or extraperitoneally to the iliac fossa (n=52). Vascular anastomoses were routinely performed to the aorta and vena cava even when the extraperitoneal approach was used. RESULTS: Vascular thrombosis was observed in two (3%), urinary leaks in five (7%), and stenosis in four (6%) patients. In six children receiving organs from adults to the iliac fossa, wound closure was performed using an absorbable mesh to avoid organ compression. Initial graft function occurred in 60 cases (88%). Frequency of initial graft function was significantly higher after KTx from LRD (100%) compared with CAD (82%). The 1-, 5-, and 10-year patient survival was 93%, 91%, and 91%, respectively, and the 1-, 5-, and 10-year graft survival was 92%, 85%, and 85%, respectively. There was no significant difference in patient and graft survival when KTx from LRD and CAD were compared. Within the CAD group, graft survival was improved using kidneys from donors >12 years compared with younger donors. CONCLUSION: Despite size discrepancy between recipients and grafts, KTx is feasible in children that weigh <15 kg by using an improved surgical technique even when adult organs are placed to the iliac fossa.     

Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes

Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes and 702 control subjects aged 0-34 years. GADAs were associated with HLA-DQ2 in young but not in older patients (P = 0.009). Autoantibodies to insulin were negatively associated with age (P < 0.0001) but positively associated with DQ8 (P = 0.03) and with INS VNTR (P = 0.04), supporting possible immune tolerance induction. ICA512/IA-2 were negatively associated with age (P < 0.0001) and with DQ2 (P < 0.0001) but positively associated with DQ8 (P = 0.04). Males were more likely than females to be negative for GADA (P < 0.0001), autoantibodies to islet cells (P = 0.04), and all four autoantibody markers (P = 0.004). The CTLA-4 3' end microsatellite marker was not associated with any of the autoantibodies. We conclude that age and genetic factors such as HLA-DQ and INS VNTR need to be combined with islet autoantibody markers when evaluating the risk for type 1 diabetes development.     

Cost-utility analysis of interferon beta-1B in secondary progressive multiple sclerosis using natural history disease data

OBJECTIVES: Different cost-effectiveness analyses have been presented for interferon beta-1b (IFNB) in the treatment of secondary progressive multiple sclerosis (SPMS). All studies have used modeling techniques since any effect on progression of disability achieved during a clinical trial will last beyond the trial. Different approaches to extrapolation have been taken, but generally they have been based on disease progression and relapse rates in clinical trials. The problem with this approach is that the population in clinical trials is a selected group of patients, which has the potential to bias results. A better method for extrapolation is to use epidemiologic data. The objective of this study is to incorporate natural history data for MS into a previously presented cost-utility model and to compare the two methods of extrapolation. METHODS: Clinical trial data were used to model disease progression during the first 3 years in the model. To extrapolate beyond the trial (10 years), data on progression of disability were available from a geographically based epidemiologic study of the natural history of MS in Canada. There were 568 patients who had converted to SPMS during the follow-up that were included in the data set. Mean costs and utilities for each Markov state were calculated from a population-based cross-sectional study in Sweden. RESULTS: The extrapolation using clinical trial data appears to have underestimated the progression of disability in the long term and thus also the potential benefit of treatment. Using the epidemiologic data, the incremental cost per QALY is SEK 257,000 (US $25,700; US $1 = SEK 10; November 2000) when all costs (direct, informal care, and indirect) are included (discounted 3%). This compares to SEK 342,000 in the previous model. The lower cost-effectiveness ratio is mostly due to a larger QALY gain with treatment than in the previous model (0.217 compared with 0.162). CONCLUSIONS: Cost-effectiveness analysis in SPMS requires that the effect of treatment beyond clinical trials be included. The method of extrapolation clearly affects the results, and when available, epidemiologic data should be used. Using the longitudinal data from Canada, the cost-utility ratios for IFNB-1b in the treatment of SPMS appear well within the acceptable range.     

Experiments on effects of an intermittent 16.7-Hz magnetic field on salivary melatonin concentrations, rectal temperature, and heart rate in humans

OBJECTIVES: The present experiments concerned the hypothesis that an intermittent, strong and extremely low frequency magnetic field reduces salivary melatonin levels and delays consecutively the nadirs of rectal temperature and heart rate. METHODS: Twelve healthy young men (18-25 years) participated in three randomly permuted sessions, which were performed as constant routines. The participants kept a strict bed rest over 26 h, air temperature was 20 degrees C, illumination < 30 lx, and sound level < 50 dBA. Salivary melatonin levels were determined hourly, rectal temperature and heart rate were registered continuously throughout. An intermittent magnetic field was administered in one session from 6 p.m. to 2 a.m. at 16.7 Hz, 0.2 mT and alternating on/off-periods of 15 s. This situation was compared with a control session without any additional stress. Another session was performed to determine the participants' ability to respond to a well-known melatonin-suppressing stress, namely bright light (1,500 lx, 10 p.m.-2 a.m.). RESULTS: Bright light inhibited melatonin synthesis in all 12 participants and delayed the nadirs of rectal temperature and heart rate. The only significant alteration that was associated with exposure to the magnetic field was a delay in the heart rate nadir, which was not mediated by an accordingly altered melatonin profile. CONCLUSION: The fact that the circadian rhythm of only the heart rate was altered indicates an internal dissociation which might constitute a health risk in the long run and needs to be investigated more extensively.     

Anti-prostate cancer and anti-breast cancer activities of two peptides derived from alpha-fetoprotein

A chemically synthesized 34-amino-acid peptide and a select analog have been studied to determine their activities against the growth of prostate and breast cancer tumors. It was of interest to determine if the peptide has anti-prostate cancer activity. Previously, the peptide was shown to inhibit the growth of breast cancer tumor cells. The peptide inhibited the growth of both breast and prostate tumors. A novel experimental design for the peptide was in a study in which a time-release pellet was used to give daily peptide doses to mice that were subjected to a breast cancer tumor. The peptide was effective in inhibiting the growth of tumors in the mice. The 2 C-->2 A analog peptide, in which the two cysteines were replaced by alanines, was also active in inhibition of the growth of prostate and breast cancer cell lines and in an in vivo assay against breast cancer. A scrambled amino acid sequence of the peptide was used as a control in these tumor studies, and it had virtually no anti-cancer activity.     

Nuclear matrix protein alterations associated with colon cancer metastasis to the liver.

PURPOSE: The development of colon cancer markers that can detect liver metastases early and predict which patients are at risk to develop liver metastases would have a major impact on this disease. We have previously identified G. Brunagel, et al., Cancer Research, 62:2437-2442, 2002, nuclear matrix proteins (NMPs), which are associated with colon cancer. The objective of this study is to identify the existence of a specific NMP "fingerprint" for human liver metastasis from colon cancer. Experimental Design: Using high-resolution two-dimensional gel electrophoresis, we analyzed the NMP expression of 12 matched liver metastases and adjacent normal samples and three normal donor liver samples. These were compared with colon cancer NMP patterns, along with several primary cell systems and lines. RESULTS: Analysis of multiple gels for each sample revealed three proteins present in all liver metastases, which are not present in normal liver tissue and normal hepatocytes. These three proteins were also present in colon cancer samples. CONCLUSION: Data provided here demonstrate that the NMP composition is able to differentiate liver metastases from normal liver tissue and normal hepatocytes and that these proteins are also expressed in colon cancer. These results further show that the adjacent normal liver tissue changes its NMP pattern of expression. Development of an assay to detect these specific NMPs in tissue and/or serum specimens is a promising modality for early detection of liver metastases from colon cancer or potentially as a prognostic tool. In addition the functional characterization of these proteins will significantly enhance our understanding of the development of liver metastases of this disease.     

Patients' Satisfaction with Psychiatric Treatment: Comparison Between an Open and a Closed Ward

The study compared patients' satisfaction with psychiatric inpatient treatment between an open and a closed ward. During a six-month period, all voluntarily participating patients on two wards of a psychiatric University hospital were investigated anonymously at admission and/or before discharge. A self-rating questionnaire (SATQ-98) was used to assess satisfaction with several domains of psychiatric inpatient treatment. In total, 135 questionnaires were received (retrieval rate 49%). The general level of satisfaction with treatment was high. General satisfaction, satisfaction with medication, ward equipment, visiting opportunities, and regulations for going out were significantly lower at discharge on the closed ward. Dissatisfaction with medication was related to low actual mood, and to low satisfaction with the frequency of psychotherapeutic interventions, visiting opportunities, and with the treating doctor. The results thus far strongly support the need for patients' satisfaction with treatment to be taken into account in order to improve psychiatric inpatient services, particularly on closed wards.     

Serum nerve growth factor concentration and its role in the preclinical stage of dementia

OBJECTIVE: Nerve growth factor is important for the development and function of the cholinergic basal forebrain. The authors examined the hypothesis that the concentration of nerve growth factor is lower than normal in the preclinical phase of neurodegenerative dementia, especially Alzheimer's disease. METHOD: The serum nerve growth factor concentration of subjects from the Berlin Aging Study and the Berlin Memory Clinic who later developed Alzheimer's disease were compared with those of subjects who were free of dementia and subjects who were already suffering from Alzheimer's disease. RESULTS: There were 17 subjects in each group, matched for age and sex. The three groups differed in log-10-transformed mean nerve growth factor concentrations: 1.62 (SD=0.59) for the healthy comparison subjects, 0.92 (SD=0.30) for the subjects with preclinical dementia, and 1.44 (SD=0.61) for the subjects with Alzheimer's disease. CONCLUSIONS: These results support the hypothesis of disturbed nerve growth factor regulation in the serum of patients with preclinical Alzheimer's disease. Mechanisms by which these disturbances appear are unclear, but they may reflect the situation in the preclinical Alzheimer's disease brain.