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PubMed2002

Liver abnormalities in rheumatic diseases.

Abnormalities of LFTs and liver function occur not infrequently in patients with rheumatic conditions, and many diagnostic possibilities exist. Systemic inflammation that is related to uncontrolled rheumatic disease and periods of disease remission have been described as a cause for fluctuations in levels of serum aminotransferases. Although these benign extra-articular manifestations of rheumatic disease are the most common manifestations, more serious hepatic involvement, including vasculitis, nodular regenerative hyperplasia, and primary biliary cirrhosis, have been observed in specific rheumatic diseases. The cause of rheumatic disease is unclear. Occult HCV infection and associated cryoglobulinemia can mimic rheumatic disease. HCV infection should be suspected routinely in patients with mixed cryoglobulinemia, especially because antiviral therapy may be beneficial. The medical management of rheumatic disease involves medications that are often hepatotoxic. Routine laboratory monitoring, imaging studies, and, if necessary, biopsy examination in situations in which serum aminotransferases remain abnormal, are recommended.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

A deletion mutation in region V of the cytomegalovirus DNA polymerase sequence confers multidrug resistance.

A patient with AIDS and cytomegalovirus (CMV) retinitis received ganciclovir and foscarnet for 20 and 5 months, respectively, with evidence of periodic disease progression. After this therapy, a CMV isolate from the patient was resistant to ganciclovir, foscarnet, and cidofovir. Sequence analysis showed a known ganciclovir resistance mutation in the viral UL97 phosphotransferase (L595F) and a new mutation in conserved region V of the DNA polymerase gene (pol) sequence (codons 981-982 deleted). The pol mutation was transferred to a laboratory CMV strain (Towne) by homologous recombination and selection with either ganciclovir or foscarnet. Recombinant viruses containing this deletion showed a 6-8-fold increased ganciclovir resistance and a 3-5-fold increased resistance to both foscarnet and cidofovir, compared with the wild-type CMV. A single mutation in region V of CMV pol can, therefore, confer multiple drug resistance in a clinical isolate.

Acquired Immunodeficiency Syndrome↗
PubMed1999

An overview of the management of papillary and follicular thyroid carcinoma.

Long-term survival rate for papillary and follicular carcinoma is more than 90%, but this varies considerably among subsets of patients. About 30% of patients, however, develop tumor recurrence, depending on the initial therapy. Two-thirds of the recurrences occur within the first decade after therapy, but the others may appear years later. We found that among patients with recurrent cancer, 30% could not be fully eradicated and another 15% died of disease. Tumor recurred outside the neck in 21% of our patients, most commonly in the lungs (63%), which resulted in death in about half the patients. Mortality rates are lower when recurrences are detected early by radioiodine scans rather than by clinical signs. We believe that the best treatment for most patients with differentiated thyroid carcinoma is near-total thyroidectomy followed by 131I ablation of the thyroid remnant, which in our experience reduces the recurrence rate, improves survival and facilitates follow-up. A long delay in initiating this therapy has an adverse and independent effect on prognosis, more than doubling the 30-year cancer mortality rate. If only partial lobectomy has been performed, it is best to consider completion thyroidectomy for lesions 1 cm or larger because of the high rate of residual carcinoma in the contralateral lobe. Completion thyroidectomy and 131I whole-body scanning allows for the diagnosis and treatment of unrecognized carcinoma and when performed early, results in significantly fewer lymph node and hematogenous recurrences and enhances survival. A large and growing number of studies demonstrates decreased recurrence of papillary carcinoma and decreased disease-specific mortality attributable to 131I therapy. On the basis of our observations and other studies, we believe that an aggressive approach to initial management and follow-up may render nearly 90% of the patients permanently free of disease. Periodic follow-up should be done with whole-body scanning and serum thyroglobulin (Tg) measurements, performed either during thyroid hormone withdrawal or by recombinant human thyrotropin (TSH)-stimulated scanning and Tg measurement. A scheme for follow-up management is presented.

Adenocarcinoma, Follicular↗
PubMed2005

A quantitative determination of multi-protein interactions by the analysis of confocal images using a pixel-by-pixel assessment algorithm.

MOTIVATION: Recent advances in confocal microscopy have allowed scientists to assess the expression, and to some extent, the interaction/colocalization of multiple molecules within cells and tissues. In some instances, accurately quantifying the colocalization of two or more proteins may be critical. This can require the acquisition of multiple Z plane images (Z stacks) throughout a specimen and, as such, we report here the successful development of a freeware, open-source image analysis tool, IMAJIN_COLOC, developed in PERL (v. 5.8, build 806), using the PERLMagick libraries (ImageMagick). Using a pixel-by-pixel analysis algorithm, IMAJIN_COLOC can analyze images for antigen expression (any number of colors) and can measure all possible combinations of colocalization for up to three colors by analyzing a Z stack gallery acquired for each sample. The simultaneous (i.e. in a single pass) analysis of three-color colocalization, and batch analysis capabilities are distinctive features of this program. RESULTS: A control image, containing known individual and colocalized pixel counts, was used to validate the accuracy of IMAJIN_COLOC. As further validation, pixel counts and colocalization values from the control image were compared to those obtained with the software packaged with the Zeiss laser-scanning microscope (LSM AIM, version 3.2). The values from both programs were found to be identical. To demonstrate the applicability of this program in addressing novel biological questions, we examined the role of neurons in eliciting an immune reaction in response to viral infection. Specifically, we successfully examined expression of the chemokine RANTES in measles virus (MV) infected hippocampal neurons and quantified changes in RANTES production throughout the disease period. The resultant quantitative data were also evaluated visually, using a gif image created during the analysis. AVAILABILITY: PERL (ActivePerl, version 5.8) is available at activestate.com; the PERLMagick libraries are available at imagemagick.org, and IMAJIN_COLOC, the source code and user documentation can be downloaded from http://www.fda.gov/cber/research/imaging/imageanalysis.htm.

Algorithms↗
PubMed1995

The need for quality assurance for a better compliance and increased quality of life in chronic schizophrenic patients.

In many places in the world community care facilities for chronic schizophrenic patients are insufficient, leading to a series of complications which can even be fatal. The lack of facilities contributes to a decrease in patients' compliance. The establishing of a good community care programme for the whole disease period will also considerably increase the efficacy of relapse prevention and give the patient an acceptable quality of life, and hopefully increase the patient's compliance. There is urgent need for therapy standards to be assured and monitored according to strict evaluation criteria to produce a better interplay between the schizophrenic patient and psychiatric staff.

Community Mental Health Services↗
PubMed2005

Phase II trial of weekly paclitaxel in patients with advanced melanoma.

New therapies are needed to improve the prognosis of patients with metastatic melanoma. This study evaluates the safety and efficacy of weekly paclitaxel in patients with metastatic melanoma. Patients received paclitaxel at 80 mg/m over 1 h, weekly for 3 weeks, followed by a 1-week rest period. Disease status was assessed every other cycle. Treatment was continued until patients experienced either disease progression or unacceptable toxicity. Twenty-seven patients were enrolled in this phase II clinical trial. Of these patients, two were subsequently determined to be ineligible. All patients, however, were considered to be evaluable for toxicity and all patients were included for response assessment in an intention-to-treat analysis. Patients received paclitaxel for a median of two cycles (range, <1-8). None of the 27 patients showed a response to treatment. Eight patients had stable disease. The median progression-free survival was 1.8 months (95% confidence interval, 1.7-2.5 months) and the median survival was 7.6 months (95% confidence interval, 4.7-9.7 months). The most common grade 3 toxicity was neutropenia (four patients) and one patient had grade 4 neutropenia. Other treatment-related grade 3 toxicities included hypersensitivity reaction (one patient) and diarrhoea (one patient). Of note, five patients had peripheral neuropathy; however, in each case, the neuropathy was only grade 1. Weekly paclitaxel is relatively well tolerated and can maintain disease stability for some metastatic melanoma patients. Unfortunately, the anti-tumour activity of this single-agent therapy is low and additional treatment innovations are needed.

Adult↗
PubMed1999

Estimation of the basic reproduction number of BSE: the intensity of transmission in British cattle.

The basic reproduction number, R0, of an infectious agent is a key factor determining the rate of spread and the proportion of the host population affected. We formulate a general mathematical framework to describe the transmission dynamics of long incubation period diseases with complex pathogenesis. This is used to derive expressions for R0 of bovine spongiform encephalopathy (BSE) in British cattle, and back-calculation methods are used to estimate R0 throughout the time-course of the BSE epidemic. We show that the 1988 meat and bonemeal ban was effective in rapidly reducing R0 below 1, and demonstrate that this indicates that BSE will be unable to become endemic in the UK cattle population even when case clustering is taken into account. The analysis provides some insight into absolute infectiousness for bovine-to-bovine transmission, indicating maximally infectious animals may have infected up to 400 animals each. The relationship between R0 and the early stages of the BSE epidemic and the requirements for additional research are also discussed.

Animal Feed↗
PubMed1998

Group B streptococcal bacteraemia in the elderly.

The aim of this retrospective study was to determine the clinical spectrum of group B streptococcal (GBS) bacteraemia in patients over 70 years old. Sixty-six adults with GBS bacteraemia were reviewed over a 5-year period. Disease characteristics, clinical diagnoses and underlying disease were compared in 33 older patients (mean age 82.4 years) and 33 younger patients (mean age 54.2 years). The older patients were also compared with a control group (mean age 81.3 years). Urinary tract infection (39%), skin infection (33%) and pneumonia (24%) were the most frequent clinical diagnoses in older patients. Urinary tract infection (39% versus 6%) was significantly more frequent in older than in younger patients. One underlying disease and one condition were more frequent in elderly patients: congestive heart failure (39% versus 6%) and being bedridden (36% versus 0%). A comparison with the older control group showed that being bedridden was highly associated with GBS bacteraemia and was an important mortality factor amongst older patients (10% versus 30%). In conclusion, GBS disease in the elderly was found to be a severe clinical problem with a high mortality despite appropriate treatment.

Adult↗
PubMed2004

Is there any relationship between Chlamydophila pneumoniae infection and juvenile idiopathic arthritis?

The role of Chlamydophila pneumoniae in the development and exacerbation of juvenile idiopathic arthritis (JIA) was investigated. Blood samples were taken from 60 JIA patients during an active disease period and for 4 weeks after. Synovial fluid samples were obtained from 20 of the 60 patients. In addition, 22 patients with familial Mediterranean fever (FMF) during the active period and 35 healthy children were included in the study as control groups. Synovial fluid samples were also obtained from three children with FMF. IgG, IgM and IgA levels against C. pneumoniae in serum samples were studied by immunofluorescence and IgG antibody and PCR studies were performed for C. pneumoniae DNA in synovial fluid samples. Twenty-nine (48.3 %) patients with JIA, 18 (81.8 %) patients with FMF and 22 (62.8 %) healthy children were found to be pre-infected with C. pneumoniae. Pre-infection with C. pneumoniae among FMF patients was found to be significantly higher than among those with JIA. We did not find a significant difference between JIA patients and healthy children. Chronic C. pneumoniae infection was observed only in six JIA patients, one FMF patient and two healthy children. Synovial fluid antibodies were found at higher than 1/512-fold dilution in one JIA patient and four times higher than normal serum in three JIA patients. C. pneumoniae DNA was not detected in any synovial fluid sample from FMF or JIA patients by PCR. In conclusion, C. pneumoniae infection does not have a triggering or a progressive effect on the clinical situation in JIA aetiopathogenesis, as a result of a multifactorial aetiology. New, extensive and serial studies (especially PCR studies of synovial tissue) are needed in order to confirm the indirect results.

Adolescent↗
PubMed2006

Cellular adhesion molecules in chronic urticaria: modulation of serum levels occurs during levocetirizine treatment.

BACKGROUND: Some antihistamines are capable of reducing levels of adhesion molecules in wealing tissues of patients with chronic urticaria (CU). OBJECTIVES: To determine if 6 weeks of therapy with levocetirizine 5 mg once daily would also induce any decrease in serum levels of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial leucocyte adhesion molecule-1 (ELAM-1) or P-selectin in subjects with CU and chronic autoimmune urticaria. METHODS: Thirty-six patients with CU (18 with positive and 18 with negative autologous serum skin test) were studied, together with 10 control healthy subjects. All patients received levocetirizine 5 mg daily. Serum soluble cellular adhesion molecule (CAM) levels were determined by immunoenzymatic assay before and after the end of the study period. Disease activity was recorded according to the EAACI/GA(2)LEN/EDF scoring system. RESULTS: After levocetirizine therapy CAM levels decreased in patients with CU, significantly in the cases of ELAM-1 and P-selectin. Patients' clinical scores improved during regular antihistamine therapy. CONCLUSIONS: Levocetirizine 5 mg daily demonstrated a broad anti-inflammatory effect in patients with CU. The significant decrease in serum levels of ELAM-1 and P-selectin might reflect the inhibitory activity on neutrophil rolling and extravasation towards inflamed skin.

Adolescent↗
PubMed2006

Serum substance P and calcitonin gene-related peptide levels in Behçet's disease and their association with disease activity.

BACKGROUND: Substance P (SP) and calcitonin gene-related peptide (CGRP) are neuropeptides that have a role in several cutaneous diseases and inflammations. Aim. To evaluate SP, CGRP and serum interleukin (IL)-8 levels in Behçet's disease (BD) and to explore the relationship of these peptides with BD activity. METHODS: The study group comprised 30 patients with BD, and 30 healthy individuals acted as controls. Serum levels of SP, CGRP and IL-8 were determined by micro-ELISA test during the active and inactive disease periods of patients with BD. These data were compared with each other and controls. Active and inactive periods of BD were established. RESULTS: The mean +/- SD serum CGRP (ng/ml) and IL-8 levels (pg/ml) in inactive BD (5.87 +/- 2.49 and 0.62 +/- 0.24, respectively) were significantly higher than the control group (4.74 +/- 1.17 and 0.46 +/- 0.11) (P < 0.05 for both). The difference between serum CGRP and IL-8 levels in active BD were also significantly higher than in inactive BD (P < 0.05 for both). Serum SP values (ng/ml) in active BD (18.27 +/- 5.38) were significantly higher than in inactive BD (15.26 +/- 5.74) and controls (12.6 +/- 4.45) (P < 0.05 for all), whereas the difference between the serum SP values in inactive BD and the control group was not statistically significant (P > 0.05). CONCLUSION: Serum SP and CGRP may have a role in the pathogenesis of BD. In addition, serum IL-8, SP and CGRP levels can be used as laboratory parameters indicating activity in BD.

Adult↗
PubMed1987

Lens autofluorescence in diabetes compared with the level of glycosylated hemoglobin A1c.

The autofluorescence of the crystalline lens has been measured by an ocular fluorophotometer in two comparable groups of patients with insulin-dependent diabetes mellitus. One group has had a high level of HbA1c since the onset of diabetes (mean 10.1 per cent) and the other group a very low level (mean 6.5 per cent). The group with low HbA1c during the disease period showed a significantly lower lens fluorescence than the group with high HbA1c.

Diabetes Mellitus, Type 1↗
PubMed1999

Demonstration of bronchial eosinophil activity in seasonal allergic rhinitis by induced plasma exudation combined with induced sputum.

BACKGROUND: Patients with seasonal allergic rhinitis may develop bronchial hyperresponsiveness during the active disease period. Eosinophil activation may occur in the bronchial mucosa and may be reflected by increased sputum levels of eosinophil cationic protein (ECP), especially when ECP binding proteins such as alpha 2-macroglobulin pass through the lamina propria and across the epithelium into the airway lumen. A study was therefore undertaken to determine histamine airway responsiveness (FEV1) and bronchovascular responsiveness (exudation of alpha 2-macroglobulin) to histamine in subjects with seasonal allergic rhinitis, and to explore whether sputum ECP levels are increased by the use of induced exudation followed by induced sputum. METHODS: Eleven patients with seasonal allergic rhinitis were examined before and during a birch pollen season. Sputum was induced by inhalation of 4.5% saline twice before and twice during the pollen season. Histamine inhalations were given before the second of each pair of sputum inductions at increasing concentrations until FEV1 was reduced by 20%. Sputum levels of alpha 2-macroglobulin and ECP were determined as indices of bronchial exudation of plasma and activation of bronchial eosinophils, respectively. RESULTS: Bronchomotor responsiveness increased during the pollen season (median difference in the reduction of FEV1 9% (95% confidence interval (CI) -3 to 26)) but histamine induced exudation of plasma was not increased. Baseline sputum levels of alpha 2-macroglobulin and ECP did not increase. Histamine induced exudation of alpha 2-macroglobulin was associated with increased sputum levels of ECP exclusively during the pollen season (median difference 8.2 ng/ml (95% CI 0.4 to 562.0)). CONCLUSION: Bronchial hyperresponsiveness in seasonal allergic rhinitis may not be associated with bronchovascular exudative hyperresponsiveness. Sputum levels of ECP were increased only during the season, and only after induced exudation (potentially moving ECP to the mucosal surface). It is suggested that the combined method of induced exudation and induced sputum may significantly improve the yield of some markers of inflammation in sputum samples.

Adult↗
PubMed2002

Glomerular expression of alpha2(IV) and alpha5(IV) chains of type IV collagen in patients with IgA nephropathy.

IgA nephropathy (IgAN) frequently accompanies glomerular basement membrane (GBM) alterations. To clarify the compositional changes of the GBM in IgAN, we examined the glomerular expression of alpha2(IV) and alpha5(IV) chains of type IV collagen in 36 patients with IgAN. Increased expression of the alpha2(IV) chain was observed in the expanded mesangium, and there were segmental sclerotic lesions of glomeruli in which the expression of the alpha5(IV) chain in the GBM was reduced. These lesions were found in 11 out of the 36 patients (30.6%). The patients with these lesions had more proteinuria, lower creatinine clearance and severer histological changes than the patients without them. On the other hand, a partial reduction of alpha5(IV) chain in normal-appearing GBM was observed in 15 out of the 36 patients (41.7%). The patients with this lesion had a longer disease period before biopsy than the patients without it. No other clinical and histological parameters were related to the partial reduction of alpha5(IV) in the GBM. In conclusion, an imbalance of glomerular alpha2(IV) and alpha5(IV) chain expression occurred in IgAN. This may be associated with the morphological changes of glomerular sclerosis and GBM alterations in IgAN. Further studies are required to understand the pathogenesis of the abnormal expression of type IV collagen chains.

Adult↗
PubMedDate not supplied

Thyroid function in Kuwaiti subjects with Down's syndrome.

OBJECTIVE: To investigate the thyroid function of individuals with Down's syndrome (DS). METHODS: Thyroid function and antithyroid antibodies were measured in 58 Kuwaitis with DS who resided at a residential facility or attended rehabilitation centers. RESULTS: Twenty-six subjects (45%) were euthyroid and 32 (55%) had thyroid dysfunction. One patient had previously been diagnosed with thyroid failure whereas the other 31 patients had newly discovered disease: 9 patients had primary hypothyroidism (T(4) 9.95 +/- 1.1 pmol/l and TSH 15.15 +/- 11.93 mU/l), 19 subclinical hypothyroidism (TSH 6.47 +/- 2.57 mU/l), 1 secondary hypothyroidism, 1 hyperthyroidism, and the remaining 1 subclinical hyperthyroidism. Antithyroid antibodies were found in 52% of the total subjects and in 59% of those with thyroid dysfunction. CONCLUSIONS: Thyroid dysfunction is common in Kuwaiti subjects with DS and is presumably the consequence of autoimmune thyroid disease. Periodic thyroid function testing is recommended in individuals with DS, which is best done through a national program.

Adolescent↗
PubMedDate not supplied

Understanding novel therapeutic agents for multiple myeloma.

Multiple myeloma, a B cell malignancy of the plasma cells, remains incurable. Advances in high-dose chemotherapy and stem cell transplantation have improved overall survival and event-free disease periods, but relapses are inevitable. New therapeutic agents have shown promising clinical use in patients with relapsed or refractory multiple myeloma. This article discusses the therapeutic applications of these novel agents with a focus on immunomodulatory drugs, proteasome inhibitors, and arsenic compounds.

Adjuvants, Immunologic↗
PubMed2006

Randomized double-blind trial of estrogen replacement therapy versus placebo in stage I or II endometrial cancer: a Gynecologic Oncology Group Study.

PURPOSE: To determine the effect of estrogen replacement therapy (ERT) on recurrence rate and survival in women who have undergone surgery for stage I or II endometrial cancer. PATIENTS AND METHODS: After surgery, eligible patients were allocated to therapy with ERT or placebo after undergoing hysterectomy with or without pelvic and aortic nodal sampling. Planned duration of hormonal versus placebo treatment was 3 years, with an additional 2 years of follow-up. RESULTS: The median follow-up time for all 1,236 eligible and assessable patients was 35.7 months. Stage, grade, histologic subtype, and percentage of patients receiving adjuvant therapy were similarly distributed between the groups. The median age at diagnosis for the 618 patients randomly assigned to ERT was 57 years (range, 26 to 91 years). Two hundred fifty-one patients (41.1%) were compliant with ERT for the entire treatment period. Disease recurrence was experienced in 14 patients (2.3%). Eight patients (1.3%) developed a new malignancy. There were 26 deaths (4.2%), and five deaths (0.8%) were a result of endometrial cancer. The median age at diagnosis for the 618 patients in the placebo group was 57 years (range, 30 to 88 years). Twelve patients (1.9%) experienced disease recurrence. Ten patients (1.6%) developed a new malignancy. There were 9 deaths (3.1%) in the placebo group, and four deaths (0.6%) were a result of endometrial cancer. CONCLUSION: Although this incomplete study cannot conclusively refute or support the safety of exogenous estrogen with regard to risk of endometrial recurrence, it is noteworthy that the absolute recurrence rate (2.1%) and the incidence of new malignancy were low.

Adenocarcinoma↗
PubMed2005

Molecular study of FMF patients in Armenia.

Familial Mediterranean Fever (FMF, MIM 249100), or Periodic disease, is a recessively transmitted and ethnically restricted condition prevalent in population from the Mediterranean decent. FMF notoriously has been hard to diagnose until mutations in the MEFV gene have been identified and as a tremendous help are used for the diagnosis of difficult cases. Since FMF can be controlled by medication, it is extremely desirable to have a firm diagnosis. The aim of this study was to establish the frequency of the most common mutations and genotypes in Armenian population. Molecular analysis of MEFV gene mutations in 3000 Armenian patients has demonstrated direct correlation between the clinical severity and the molecular diagnostic criteria of the disease, including the development of renal amyloidosis with MEFV genotypes. MEFV genotyping performed in the framework of a genetic counseling may reveal and identify affected individuals in presymptomatic phase, providing the possibility of a precocious start of the therapy.

Adult↗