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PubMed2001

A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis.

BACKGROUND & AIMS: Ursodeoxycholic acid (UDCA) is used for the treatment of cholestatic liver diseases including primary biliary cirrhosis (PBC) for which it has a positive effect on laboratory values, may delay the development of liver failure and prolong the transplant-free disease period. Standard doses of UDCA (8-15 mg/kg daily) have been shown to be ineffective in the treatment of primary sclerosing cholangitis (PSC). We report on the findings (clinical, biochemical, histological, and cholangiographic) and side effects of a 2-year double-blind placebo-controlled preliminary study of high-dose UDCA in PSC patients. METHODS: Twenty-six patients with PSC were randomized to high-dose (20 mg/kg daily) UDCA or placebo. Cholangiography and liver biopsy were performed at entry and after 2 years. Symptoms, clinical signs, and liver biochemical tests were recorded at 3 monthly intervals. RESULTS: High-dose UDCA did not influence symptoms, but there was a significant improvement in liver biochemistry (serum alkaline phosphatase, P = 0.03; gamma-glutamyl transferase, P = 0.01) and a significant reduction in progression in cholangiographic appearances (P = 0.015) and liver fibrosis as assessed by disease staging (P = 0.05). In the treatment group, a significant increase in total bile acids and saturation with UDCA >70% confirmed patient compliance. No significant side effects were reported. CONCLUSIONS: High-dose UDCA may be of clinical benefit in PSC, but trials with a larger number of participants and of longer duration are required to establish whether the effect of high-dose UDCA on liver biochemistry, histology, and cholangiography in patients with PSC is translated into improved long-term survival.

Adult↗
PubMed2003

[Effects of Bakumondo-to (Mai-Men-Dong-Tang) on cough sensitivity to capsaicin in asthmatic patients with cough hypersensitivity].

UNLABELLED: Some patients with bronchial asthma have increased cough sensitivity. In such patients coughing may be an inducer of wheeze. The aim of the present study was to investigate the effect of Bakumondo-to on the cough sensitivity and respiratory tract inflammation in asthmatic patients with increased cough sensitivity. In addition influences of intensity of respiratory tract inflammation, gender, type of asthma, and disease period on the effect of Bakumondo-to on the cough sensitivity were examined. Twenty-one bronchial asthmatics whose cough thresholds to capsaicin were less than 3.9 microM were examined. METHODS: Cough thresholds to capsaicin (concentration of inhaled capsaicin solution causing 5 or more coughs) was measured before and after 2 months or more treatment with Bakumondo-to (9 g/day, TJ-29). Number of eosinophils in peripheral blood, sputum eosinophil ratio, and ECP level in the serum were also measured before and after treatment. RESULTS: Bakumondo-to significantly increased the cough threshold. Although respiratory tract inflammation was not significantly improved, number of eosinophils in peripheral blood, sputum eosinophil ratio and ECP level in the serum were remarkably decreased more than the half. And Bakumondo-to was more effective in asthmatic subjects with severe airway inflammation. Furthermore, a greater effect of it was observed in women. A greater effect was also observed in patients having a disease duration of less than 1 year. CONCLUSION: Our results suggest that Bakumondo-to may be an effective therapeutic preparation for coughing in asthmatic patients with cough hypersensitivity.

Adolescent↗
PubMed1993

Assessment of cerebrovascular disease in the Cardiovascular Health Study.

The Cardiovascular Health Study (CHS) is a longitudinal population-based study of coronary heart disease and stroke in men and women 65 years and older. The initial CHS cohort consisted of 5201 men and women recruited from a random sample of the Health Care Financing Administration (HCFA) Medicare eligibility lists in four communities in the United States. Extensive historical, physical, and laboratory evaluations were performed at the baseline examination in 1989 to 1990 to identify risk factors and subclinical disease. Periodic contacts are carried out to ascertain and verify incident cardiac and stroke events and their sequelae. Since only a short time has passed since entry of all the patients into the study, data are not available on time trends in the mortality rate of stroke, but we expect to contribute in this area in the years ahead. This article then is a description of the CHS, of methods of assessing stroke in the CHS cohort, and of prevalence of stroke and transient ischemic attacks at the initial examination.

Aged↗
PubMed1991

An unexpected periodicity among the prevalences of human age-related, mortal diseases.

A periodic pattern was discovered among the relative number of deaths per year for the major age-related diseases in humans. This pattern was observed among 178 causes-of-death composed of male and female. White (U.S.A.), Black (U.S.A.) and Japanese (Japan) populations. Both descriptive (Fourier transform) and statistical analysis procedures revealed evidence that the pattern resulted from the presence of an underlying power progression between disease prevalences, with a factor of approximately 2.0 between sizes. This periodicity was highly unlikely to have occurred by chance (P much less than 0.01). The presence of such a power progression suggests that the sizes of the various fractions of the total population, that are afflicted with these mortal diseases, are determined by forces intrinsic to the population and probably result from a common mechanism.

Age Factors↗
PubMed2000

Activation of nuclear factor-kB in the spinal cord of experimental allergic encephalomyelitis.

The DNA-binding activity of nuclear factor (NF-kB) was found to be induced in the spinal cord of rats with experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), from the onset of the disease. This activation of NF-kB persisted throughout the disease period and decreased thereafter in the recovery phase. Supershift analysis of NF-kB DNA-binding activity in nuclear extracts of spinal cords showed that RelA/p65 and p50 subunits but not c-Rel/p75, RelB/p68 and p52 subunits were involved in DNA binding. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kB activation, markedly inhibited the in vivo activation of NF-kB in the spinal cord of EAE rats and attenuated the clinical symptoms of EAE. These studies suggest that activation of NF-kB plays an important role in the pathogenesis of EAE and inhibitors of NF-kB activation may have therapeutic importance in MS.

Animals↗
PubMed2006

Covariation of corticospinal efficiency and silent period in motoneuron diseases.

For a better understanding of the changes affecting the cortically induced silent period (SP) in motoneuron disease, the excitatory and inhibitory effects of transcranial magnetic stimulation were explored repeatedly in 8 patients with amyotrophic lateral sclerosis (ALS), 3 patients with Kennedy's disease (KD), and 10 healthy subjects. In KD, the background electromyogram (EMG) and the motor evoked potential (MEP) area were both enhanced. However, neither the corticospinal efficiency (MEP gain, the ratio between MEP and background EMG) nor the duration of the SP differed from healthy subjects. In ALS patients, the MEP gain and the SP duration decreased conspicuously with time. We conclude that use of the MEP gain improves detection of corticospinal dysfunction in ALS patients. Part of the SP shortening in ALS seems to reflect the reduced activation of cortical or spinal inhibitory networks by the abnormal corticospinal pathway.

Adult↗
PubMed2001

Village poultry production systems in the central highlands of Ethiopia.

Participatory rural appraisal (PRA), supported by checklists and intensive case studies on individual households, was carried out in three villages at three different altitudes in the central highlands of Ethiopia. The chicken production system in each village is described and the problems are discussed. More than 60% of the families kept chickens, and in most cases the women owned and managed the birds and controlled the cash from the sales. The production systems followed were mainly low-input and small-scale, with 7-10 mature birds per household, reared in the back yards with inadequate housing, feeding and health care. The average egg production per clutch was 15-20, with 3-4 clutches per year. The mean number of eggs set per bird was 12.9 +/- 2.2 (n = 160), depending on the size of the bird and season, and the hatching rate was 80.9% +/- 11.1%, range 44%-100% (n = 160). Poultry meat and eggs were generally accepted and appreciated in all three villages. In addition to the small amount of cash income they provide, scavenging chickens have nutritional, cultural and social functions. The flock composition, price of poultry and poultry products, disease outbreaks and hatching of chicks were strongly affected by season. Disease was cited as the most important problem by most of the members of the community, followed by predation, lack of feed, poor housing, insufficient water and parasites. Disease periodically decimated the flocks, and consequently, about 50% of the eggs produced were incubated in order to replace the birds that had died. The major source of loss in the system was the high mortality of chicks (61%) that occurred between hatching and the end of brooding at 8 weeks of age. The system was characterized by no or few inputs and a low output level. The major input was the cost of foundation stock, but after that virtually no cost was involved. The major source of feed for the birds was from the scavenging feed resource base, which comprised table leftovers, small grain supplements and anything edible from the immediate environment.

Animal Feed↗
PubMed2006

Adjuvant local irradiation for Merkel cell carcinoma.

OBJECTIVES: To determine the effect of adjuvant local irradiation on (1) disease recurrence and (2) survival rates in Merkel cell carcinoma (MCC). DATA SOURCES: An Ovid MEDLINE search (January 1966-May 26, 2004) was performed using the following criteria: group 1, "Merkel cell OR trabecular OR neuroendocrine skin OR APUDoma skin OR primary small cell skin OR primary undifferentiated skin OR endocrine skin OR neuroepithelial" AND group 2, "carcinoma OR tumor OR cancer" with mapping modifiers "-title, -abstract, -keyword, -subject heading." The search yielded 843 citations. STUDY SELECTION: The Ovid set was then searched using the following criteria: "surgery OR radiation OR radiotherapy," which yielded 242 discrete citations. Reports from all 242 citations were reviewed. For the remaining 601 citations, abstracts (when available) were reviewed to assess the level of relevance for potential inclusion; reports from 63 of these citations were reviewed. An additional 28 secondary references were reviewed, for a total of 333 reports. DATA EXTRACTION: The following criteria for inclusion were applied to each potential patient: (1) a histopathologic diagnosis of MCC; (2) a single, primary tumor arising on the skin, for which (3) the primary treatment was surgical excision (local excision, wide excision, or Mohs surgery) with or without the use of adjuvant irradiation (to the tumor bed); (4) following surgery, negative (clear) surgical margins were obtained; (5) during the postoperative follow-up period, disease recurrence, progression, and survival and/or duration of event-free interval was documented with (6) a minimum follow-up of 1 month. A total of 1254 patients were included in the analysis. RESULTS: Statistically significant reductions in local (hazard ratio [HR], 0.27; P < .001) and regional (HR, 0.34; P < .001) recurrence were observed among patients treated with combination therapy compared with surgery alone. Similar rates of distant metastasis were observed between treatment groups (HR, 0.79; P = .31). Overall survival rates were 87% (1 year) and 49% (5 years). Cause-specific survival rates were 90% (1 year) and 62% (5 year). In general, differences in overall (HR, 0.78; P = .16) and cause-specific (due to MCC: HR, 0.72; P = .14) survival rates between treatment groups did not reach statistical significance. A subgroup analysis that excluded single-patient case reports and studies of only 1 treatment group revealed a significant overall (HR, 0.63; P = .02) and cause-specific (HR, 0.62; P = .04) survival advantage after treatment with combination therapy. CONCLUSIONS: Surgery plus local adjuvant irradiation was associated with significantly lower rates of local and regional recurrence of MCC than surgery alone. Prospective investigation is needed to clarify the presence of a survival benefit from combination therapy.

Adult↗
PubMed1986

Rapid emergence of novel antigenic and genetic variants of equine infectious anemia virus during persistent infection.

Previous results from our laboratory have demonstrated that equine infectious anemia virus displays structural variations in its surface glycoproteins and RNA genome during passage and chronic infections in experimentally infected Shetland ponies (Montelaro et al., J. Biol. Chem. 259:10539-10544, 1984; Payne et al., J. Gen. Virol. 65:1395-1399, 1984). The present study was undertaken to obtain an antigenic and biochemical characterization of equine infectious anemia virus isolates recovered from an experimentally infected pony during sequential disease episodes, each separated by intervals of only 4 to 8 weeks. The virus isolates could be distinguished antigenically by neutralization assays with serum from the infected pony and by Western blot analysis with a monoclonal antibody against the major surface glycoprotein gp90, thus demonstrating that novel antigenic variants of equine infectious anemia virus predominate during each clinical episode. The respective virion glycoproteins displayed different electrophoretic mobilities on sodium dodecyl sulfate-polyacrylamide gels, indicating structural variation. Tryptic peptide and glycopeptide maps of the viral proteins of each virus isolate revealed biochemical alterations involving amino acid sequence and glycosylation patterns in the virion surface glycoproteins gp90 and gp45. In contrast, no structural variation was observed in the internal viral proteins pp15, p26, and p9 from any of the four virus isolates. Oligonucleotide mapping experiments revealed similar but unique RNase T1-resistant oligonucleotide fingerprints of the RNA genomes of each of the virus isolates. Localization of altered oligonucleotides for one virus isolate placed two of three unique oligonucleotides within the predicted env gene region of the genome, perhaps correlating with the structural variation observed in the envelope glycoproteins. Thus these results support the concept that equine infectious anemia virus is indeed capable of relatively rapid genomic variations during replication, some of which result in altered glycoprotein structures and antigenic variants which are responsible for the unique periodic disease nature observed in persistently infected animals. The findings of envelope specific differences in isolates of visna virus and of human T-cell lymphotropic virus III (acquired immune deficiency syndrome-related virus) suggest that this variation may be a common characteristic of the subfamily Lentivirinae.

Animals↗
PubMed2002

Peritubular capillary regression during the progression of experimental obstructive nephropathy.

Injury to the renal microvasculature may be a major factor contributing to the progression of renal disease. Although severe disruption of peritubular capillaries (PTC) could lead to marked tubulointerstitial scarring, elucidation of that process remains incomplete. This study investigated the morphologic changes in PTC and their likely regulation by vascular endothelial growth factor (VEGF) during the progression of tubulointerstitial injuries. Unilateral ureteral obstruction was induced in Wistar rats by ligation of the left ureter, and the kidneys were then collected at selected times. PTC lumina and the expression of VEGF and its receptor Flk-1 were immunohistochemically detected. Morphologic changes in PTC endothelial cells were examined by using Ki67 staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling, and electron-microscopic studies. In the first week of the disease period, immunohistochemical labeling of tubular VEGF intensified, with accompanying deformation and dilation of adjacent thrombomodulin (TM)-positive PTC lumina; an angiogenic response of endothelial cells was demonstrated with Ki67 and TM double-staining. During the subsequent 2 wk, tubular VEGF labeling decreased until it was virtually absent, an effect confirmed by Western blotting. Concomitantly, labeling of the VEGF receptor Flk-1 in PTC endothelial cells decreased and PTC lumina began to regress, demonstrating endothelial cell apoptosis (as detected in terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling and electron-microscopic studies). By the end of week 4, the numbers of TM-positive PTC lumina were significantly decreased in areas of marked tubulointerstitial scarring. These results suggest that PTC regression, involving an early, unsustained, angiogenic response followed by progressive endothelial cell apoptosis, could be a potential factor contributing to tubulointerstitial scarring in this unilateral ureteral obstruction model.

Animals↗
PubMed1971

Muscle silent period in Parkinson's disease.

The muscle silent period was measured in 11 patients with moderate to severe rigidity associated with Parkinson's disease. The determinations were made under conditions of maximum disability for each patient, since all medications had been withdrawn before testing. The duration of the EMG silence, produced by small and large electrical twitch contractions of the adductor pollicis muscle, fell within a range of values previously determined for normal individuals. Major alleviation of the rigidity and bradykinesia with chronic oral l-dopa therapy was not accompanied by any change in the silent period. It was concluded that in untreated Parkinsonism, and also after its treatment with l-dopa, the functioning of the muscle spindles and local inhibitory reflexes remains normal.

Aged↗
PubMed2005

[Autologous transplant (AT) with peripheral-blood stem-cell rescue for multiple myeloma. A clinical experience].

BACKGROUND: Multiple myeloma is rarely curable. Advances in high dose chemotherapy and stem cell transplantation have improved overall survival and event-free disease periods, but relapses are inevitable. AIM: To report our experience with AT in multiple myeloma, between 1994 and 2003. MATERIAL AND METHODS: Retrospective analysis of 20 patients (12 women), with a mean age of 51.1 years. VAD (vincristine, doxorubicin and dexamethasone) was used as initial therapy in 19 patients. High dose cyclophosphamide (11 patients) and variations of VAD regimen (7) associated with granulocyte colony stimulating factor were used for peripheral-blood stem cell harvest. The conditioning regimen consisted of melphalan 200 mg/m2 followed by the reinfusion of peripheral-blood stem cells 24 hours later. The median number of CD34 cells infused was 3.3x10(6)/kg. Three patients were subjected to a second auto graft and one to a non-myeloablative transplant. Mean follow up was 35.5 months. RESULTS: Mucositis and febrile neutropenia were common complications. The median number of days for neutrophil engraftment was 9 (range 8-11) and for platelets, 10 (range 7-13). No patient died. Complete remission was obtained in 60% (12/20), progression-free survival was 30 months and overall median survival, 47 months. CONCLUSIONS: The AT with high-dose melphalan is a safe procedure in our hospital, without mortality and engraftment in all the patients. Complete remission and progression free survival were similar to those reported abroad but the overall median survival was lower.

Adult↗
PubMed1985

Plasma exchange in six patients with advanced cancers of the head and neck.

Six patients with advanced squamous cell cancers of the head and neck, with serum IgA greater than or equal to 400 mg/dl and IgE less than or equal to 1000 IU/ml, underwent a trial of six 2-liter plasma exchanges over a 2-3-week period. Disease progressed in patients 1, 2, and 4, who died on days 44, 72, and 159. The tumor in patients 3 and 6 regressed significantly, repeatedly in patient 3 over each of four courses of apheresis. Tumor recurred in both patients after cessation of treatment, and they died at days 420 and 79. Patient 5, with inoperable disease, received full-dose radiotherapy immediately following the course of apheresis, and showed complete response in the primary lesion and a major response in the extensive lymph node metastases, dying on day 421 of apparently unrelated causes. Serum IgE in the three patients experiencing tumor regression rose paradoxically during plasmapheresis. Only patient 3 had an elevated level of soluble E-receptor suppressor factor prepheresis; the serum of patient 6 was lymphocytotoxic prepheresis but this activity decreased or disappeared during each of the exchanges studied. Controlled trials are now indicated.

Aged↗
PubMed1983

Myelin basic protein and multiple sclerosis.

Myelin basic protein (BP) has the capacity to induce experimental allergic encephalomyelitis (EAE) in animals as well as to prevent and suppress EAE. Immunoreactive BP or BP fragments appear in cerebrospinal fluid (CSF) in persons with multiple sclerosis in acute disease periods and in individuals with acute damage to central nervous system myelin. Humoral and cellular immune responses, especially in the CSF, may occur but are of uncertain effect in the etiology and pathogenesis of MS. Attempts to use BP to suppress MS have disclosed no therapeutic benefit.

Animals↗
PubMed2005

Scleroderma associated with ANCA-associated vasculitis.

We have recently reported on two cases of scleroderma patients with ANCA-associated vasculitis for the first time in Korea. In order to explore the nature of this disease combination, we pooled together all the previously known cases and statistically analyzed them. Out of the 50 selected cases, survival analysis was done for comparison of the scleroderma disease period and the clinical factors associated with ANCA-associated vasculitis (AAV). Kaplan-Meier analysis revealed that patients having anti-topoisomerase antibody (anti-Scl-70) and, probably, PR-3 ANCA are at a higher risk for developing AAV than patients without both anti-topoisomerase antibody and anti-centromere antibody (ACA), and patients with MPO-ANCA. Multivariate Cox regression analysis revealed having anti-topoisomerase antibody as a risk factor for developing AAV [OR 3.1 (95% CI 1.11-8.55), P=0.031]. We suggest that having anti-topoisomerase antibodies may play a role among scleroderma patients in developing AAV.

Adult↗
PubMed1996

Multiple sclerosis: prospective analysis of TNF-alpha and 55 kDa TNF receptor in CSF and serum in correlation with clinical and MRI activity.

The possibility of antagonizing tumor necrosis factor-alpha (TNF-alpha) in vivo with antibodies or soluble TNF receptor has focused much interest on the role of this cytokine in the natural course of MS. We studied nine patients prospectively and serially for one year (14 time points, 131 observations). TNF-alpha and the 55 kDa soluble TNF receptor were measured every 4 weeks in the serum and at defined time points in the CSF. Each value was correlated to clinical symptoms and to MRI measurements obtained on the same day. All patients with relapsing-remitting disease showed periodic increases of TNF concentrations. Overall, the association between serum TNF-alpha levels and bursts of Gd-DTPA enhancement on cranial MRI was not sufficiently tight to reach statistical significance. However, serum TNF levels > 50 pg/ml and measurable CSF levels were always associated with Gd-DTPA enhancing MRI lesions. Isolated high serum TNF peaks were noted during episodes of infection, hay fever or psychic stress. After treatment with glucocorticoids, TNF levels were suppressed for several months, whereas new Gd-DTPA enhancing lesions continued to appear. The concentrations of the soluble 55 kDa TNF receptor did not show marked fluctuations. These results are consistent with an active role of TNF-alpha in MS during periods of disease activity and provide further support for the clinical evaluation of anti-TNF therapies.

Adult↗
PubMed2004

Bone mineral acquisition in adolescents with type 1 diabetes.

OBJECTIVE: To track bone mineral acquisition in adolescents with type 1 diabetes (DM). STUDY DESIGN: Subjects were adolescents, ages 12 to 18 years, with DM (n=42) and a healthy regional reference (n=199). Measurements of tibia bone characteristics by peripheral quantitative computed tomography (pQCT) and spine and whole body (WB) by dual-energy x-ray absorptiometry (DEXA), anthropometrics, and lifestyle questionnaires were obtained during a 12-month period. Disease duration, insulin dose, renal function, and glycosylated hemoglobin (HbA1c) values for the previous 12 months were recorded. RESULTS: Body size and maturation were similar between groups. DM had lower tibia, spine, and WB bone characteristics but greater muscle mass (LBM) and lower bone mineral content (BMC)/LBM at baseline and 12 months. Annual gains for tibia cortical bone and WB BMC/LBM were lower and inversely related to HbA1c levels (R=-0.36 to -0.51), whereas spine area and density and WBLBM were greater and were predicted by pubertal-driven growth. Overall, the DM cohort had 8.5% less WB BMC/LBM, suggesting that bone mineral deposition was not adequately adapted to muscle gains. CONCLUSIONS: Adolescents with type 1 diabetes continue to have smaller bone mass and bone size despite normal growth and maturation. Poor metabolic control appears to negatively influence bone mineral acquisition.

Absorptiometry, Photon↗
PubMed2006

Kidney transplantation in patients receiving dialysis treatment for more than 10 years.

In the present single center study, we analyzed 277 kidney transplant patients (procedures performed between February 1984 and February 2006) to determine the impact of long-term dialysis on kidney transplant outcomes. Forty-four had been treated prior to renal transplantation with dialysis for more than 10 years (range, 10.0-32.5 years, average, 16.6 years; Group I), while the remaining 233 recipients showed an average end-stage renal disease period of 2.8 years (range, 0-9.8 years; Group II). There were no significant differences in patient survivals between the 2 groups: 97.3% vs 97.4% at 1 year; 85.7% vs 92.4% at 5 years; 85.7% vs 90.7% at 10 years (P = .2347). Five Group I patients died: 2 from infections, 2 from liver dysfunction, and 1 from cerebral bleeding. These causes of death were similar to those among Group II patients. Graft survival was not significantly different between the 2 groups: 95% vs 88.8% at 1 year; 75.5% vs 76.5% at 5 years; 75.5% vs 65.5% at 10 years (P = .6264). Our results suggested that dialysis treatment for more than 10 years did not have negative effects on posttransplantation patient and graft survival.

Adult↗