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Biomedical subjects

C Ha

Publications and source records attributed to C Ha.

14 recordsLinked to original sources

Why are manual workers at high risk of upper limb disorders? The role of physical work factors in a random sample of workers in France (the Pays de la Loire study).

OBJECTIVE: To investigate the reasons for the excess risk of upper limb musculoskeletal disorders among manual workers compared with other workers in a random sample of 2656 French men and women (20-59 years old) participating in a study on the prevalence of work related upper limb disorders conducted by France's National Institute of Health Surveillance. METHODS: Prevalence ratios (PR) of physician-diagnosed musculoskeletal disorders of the shoulder, elbow, wrist, and hand (any of six leading disorders, rotator cuff syndrome, carpal tunnel syndrome) in manual versus non-manual workers were calculated using Cox regression models with a constant time of follow up and robust variance. RESULTS: 11.3% of men and 15.1% of women were diagnosed with an upper limb disorder. The risk was especially high in manual workers (PRs: 1.40 to 2.10). Physical work factors accounted for over 50% of occupational disparities overall, 62% (men) to 67% (women) for rotator cuff syndrome, and 96% (women) for carpal tunnel syndrome. The authors calculated that under lower levels of physical work exposures, up to 31% of cases among manual workers could have been prevented. CONCLUSIONS: In working men and women, upper limb musculoskeletal disorders are frequent. Physical work exposures, such as repetitive and forceful movements, are an important source of risk and in particular account for a large proportion of excess morbidity among manual workers.

Adult↗

Linkage disequilibrium maps constructed with common SNPs are useful for first-pass disease association screens.

To develop an efficient strategy for mapping genetic factors associated with common diseases, we constructed linkage disequilibrium (LD) maps of human chromosomes 5, 7, 17, and X. These maps consist of common single nucleotide polymorphisms at an average intermarker distance of 100 kb. The genotype data from these markers in a panel of American samples of European descent were analyzed to produce blocks of markers in strong pair-wise LD. Power calculations were used to guide block definitions and predicted that high-level LD maps would be useful in initial genome scans for susceptibility alleles in case-control association studies of complex diseases. As anticipated, LD blocks on the X chromosome were larger and covered more of the chromosome than those found on the autosomes.

Black or African American↗

Prognostic factors for disease progression after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for recurrent or refractory Hodgkin's lymphoma.

Our purpose was to study the risk factors associated with disease progression after high-dose chemotherapy followed by autologous stem cell transplantation in patients with recurrent or refractory Hodgkin's lymphoma (HL). We analyzed the long-term outcome of 184 patients with recurrent or refractory HL who underwent autologous hematopoietic stem cell transplantation. At the time of transplantation, 82 patients were in first relapse or second remission, 46 patients were refractory to the primary induction chemotherapy, and 56 patients were beyond first relapse or second remission. In 64 patients, the disease had proved refractory to the chemotherapy regimen administered immediately prior to transplantation. The median follow-up of patients who were alive and free of disease at the time of this report was 8.9 years (range, 0.1-19.0 years). At 10 years, the overall and disease-free survival rates were 34% (95% CI 27-42) and 29% (95% CI 22-36) respectively. The major cause of treatment failure was disease relapse. Chemotherapy resistance prior to transplantation, advanced stage, and higher number of chemotherapy regimens administered prior to transplantation were adverse prognostic factors for disease progression. We conclude that autologous transplantation is an effective salvage treatment for recurrent HL.

Acute Disease↗

CD56(+dim) and CD56(+bright) cell activation and apoptosis in hepatitis C virus infection.

CD3- CD56(+dim) natural killer (NK) cells, which are cytotoxic against virally infected cells, may be important in hepatitis C virus (HCV)-infected patients who are successfully treated with pegylated interferon (PEG-IFN)-alpha. We used flow cytometry to enumerate activated (CD69+) and apoptotic (annexin-V+) dim (CD3- CD56(+dim)) and bright (CD3- CD56(+bright)) NK cells obtained from HCV-infected patients before treatment (n=16) and healthy controls (n=15) in the absence and presence of pegylated interferon (PEG-IFN)-alpha-2b. A subset of HCV-infected patients, subsequently treated with PEG-IFN-alpha-2b in vivo, was determined to have a sustained virological response (SVR, n=6) or to not respond (NR) to treatment (n=5). In the absence of IFN, activated dim (CD3- CD56(+dim) CD69+) NK cells were significantly decreased (P=0.04) while activated apoptotic dim (CD3- CD56(+dim)CD69+ annexin-V+) NK cells tended to be increased (P=0.07) in SVR patients compared with NR patients. Activated bright (CD3-CD56(+bright)CD69+) and activated apoptotic bright (CD3- CD56(+bright)CD69+ annexin-V+) NK cells were significantly correlated (P=0.02 and P=0.01, respectively) with increasing hepatic inflammation. These findings suggest that in the absence of PEG-IFN, activated dim (CD3- CD56(+dim)CD69+) NK cell turnover may be enhanced in SVR compared with NR patients and that activated bright (CD3- CD56(+bright)CD69+) NK cells may play a role in liver inflammation.

Adult↗

Homology-driven assembly of a sequence-ready mouse BAC contig map spanning regions related to the 46-Mb gene-rich euchromatic segments of human chromosome 19.

Draft sequence derived from the 46-Mb gene-rich euchromatic portion of human chromosome 19 (HSA19) was utilized to generate a sequence-ready physical map spanning homologous regions of mouse chromosomes. Sequence similarity searches with the human sequence identified more than 1000 individual orthologous mouse genes from which 382 overgo probes were developed for hybridization. Using human gene order and spacing as a model, these probes were used to isolate and assemble bacterial artificial chromosome (BAC) clone contigs spanning homologous mouse regions. Each contig was verified, extended, and joined to neighboring contigs by restriction enzyme fingerprinting analysis. Approximately 3000 mouse BACs were analyzed and assembled into 44 contigs with a combined length of 41.4 Mb. These BAC contigs, covering 90% of HSA19-related mouse DNA, are distributed throughout 15 homology segments derived from different regions of mouse chromosomes 7, 8, 9, 10, and 17. The alignment of the HSA19 map with the ordered mouse BAC contigs revealed a number of structural differences in several overtly conserved homologous regions and more precisely defined the borders of the known regions of HSA19-syntenic homology. Our results demonstrate that given a human draft sequence, BAC contig maps can be constructed quickly for comparative sequencing without the need for preestablished mouse-specific genetic or physical markers and indicate that similar strategies can be applied with equal success to genomes of other vertebrate species.

Animals↗

Nasal-type T/NK lymphomas: a clinicopathologic study of 13 cases.

Natural Killer (NK) cell lymphomas, which include the nasal and the "nasal type" varieties, are defined as angiocentric lymphomas in the revised European American Lymphoma (R.E.A.L.) classification. This group of diseases is rare in the United States and Europe but is more common in Asia and Central America. It is associated with the Epstein-Barr virus (EBV) and its response to treatment and prognosis are usually very poor. The aim of this study was to describe our experience with 13 patients with angiocentric lymphomas seen at The University of Texas M. D. Anderson Cancer Center (UTMDACC) over the last 14 years. Thirteen patients with a diagnosis of nasal NK cell lymphoma were treated at UTMDACC from 1987 to 1999. Eleven patients were treated initially with doxorubicin based chemotherapy with or without radiotherapy. One patient received interferon (IFN)-alpha and vitamin A and another methotrexate, vincristine, L-Asparaginase, and radiotherapy. The median age was 44 years (range 15-76); there were four women and nine men. All patients presented with local disease involving the sinonasal region. Typical immunophenotypes expressing CD2+, CD3- and CD56+ surface markers as well as non rearrangement of T-receptors were present in all patients. Eight patients (62%) responded to therapy; six (46%) with complete response (CR) and two (16%) with partial response (PR). Five patients (38%) were alive, four with no evidence of disease (NED) at 1, 2, 3, and 9 years after treatment, and one patient was alive with disease (AWD) at the time of publication. One patient died while in CR from complications from allogeneic bone marrow transplant. Six patients had disease progression to extranodal sites including: testis (2), central nervous system (2), lung (1), bone marrow (2), liver (2), peripheral blood (2), and skin (2). In conclusion, the response to doxorubicin-containing regimens is inferior to that of patients with other non-Hodgkin's lymphomas and similar prognostic factors. Because the disease is associated with EBV virus in 90%-100% of the cases and the prognosis is poor, innovative therapies should be tried including immunotherapy that targets the expression of EBV by the tumor with or without myeloablative procedures.

Adolescent↗

Expression of a human serum albumin fragment (consisting of subdomains IA, IB, and IIA) and a study of its properties.

Site-directed mutagenesis and a yeast expression system were used to synthesize a human serum albumin (HSA) fragment (amino acids 1-297). The HSA fragment (half HSA) was evaluated with a number of biophysical techniques and found to be similar to the corresponding region in wild-type HSA. Specifically, the circular dichroism spectra of half HSA and wild-type HSA were superimposable, indicating that the highly alpha-helical secondary structure of wild-type HSA is preserved in half HSA. Additionally, half HSA was partially reactive with a polyclonal antibody against authentic HSA. Half HSA, which contains subdomain IIA, had an affinity for thyroxine and several thyroxine analogs, similar to that observed previously for wild-type HSA. This study suggests that the production of recombinant HSA fragments will be useful for the study of HSA ligand interactions.

Biophysical Phenomena↗

Low albumin gradient ascites complicating severe pseudomembranous colitis.

Pseudomembranous colitis (PMC) is a frequently severe, sometimes fatal iatrogenic disease that is antibiotic-associated in almost all cases. The most common clinical features of PMC include abdominal pain, watery diarrhea, fever, leukocytosis, hypoalbuminemia, and hypovolemia. Ascites, not considered a well-known feature of PMC, is fairly common, based on a review of the English language literature but has not been characterized fully. This case report describes 5 patients with PMC who presented with low serum-ascites albumin gradient (SAAG) and neutrocytic ascites, without evidence of infectious, malignant, or inflammatory peritoneal disease, which has not been reported previously. In 1 patient, massive low SAAG ascites was the presenting manifestation of PMC, a feature also not reported previously. Three of the 5 (60%) patients had acquired immunodeficiency syndrome. The characteristics of the fluid specimens in these 5 patients and the possible pathogenetic mechanisms are proposed. The findings suggest that PMC should be included in the differential diagnosis of low SAAG ascites, especially in patients with acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

The reliability of optimization under dose-volume limits.

PURPOSE: An optimization algorithm improves the distribution of dose among discrete points in tissues, but tolerance depends on the distribution of dose across a continuous volume. This report asks whether an exact algorithm can be completed when enough points are taken to accurately model a dose-volume constraint. METHODS AND MATERIALS: Trials were performed using a 3-dimensional model of conformal therapy of lung cancer. Trials were repeated with different limits placed on the fraction of lung which could receive > 20 Gy. Bounds were placed on cord dose and target dose inhomogeneity. A mixed integer algorithm was used to find a feasible set of beam weights which would maximize tumor dose. Tests of feasibility and optimality are introduced to check the solution accuracy. RESULTS: Solutions were optimal for points used to model tissues. An accuracy of 3-4% in a volume condition could be obtained with models of 450-600 points. The error improved to 2% with 800 points to model the lung. Solution times increased six-fold at this level of accuracy. CONCLUSION: The mixed integer method can find optimum weights which respect dose-volume conditions in usually acceptable times. If constraints are violated by an excessive amount, the optimization model should be rerun with more points.

Algorithms↗

Enhancement by perflusion emulsion (Oxygent) and carbogen breathing of the tumor growth delay of the FSaIIC fibrosarcoma after treatment with antitumor alkylating agents.

Many anticancer drugs require oxygen to be cytotoxic, or are selectively cytotoxic toward cells under oxygenated conditions. The effects of the dilute perfluorochemical emulsion Fluosol-DA with a wide variety of chemotherapeutic agents have been explored; however, it has not been possible to determine the optimal level of circulating perfluorochemical emulsion with anticancer drugs because the volume of Fluosol that may be administered in limited. Using a concentrated 90% Perflubron emulsion, Oxygent, a wide range of perfluorochemical emulsion doses have been examined in combination with melphalan, cyclophosphamide and BCNU in a murine solid tumor model. When Oxygent was administered by injection i.v. just prior to the injection of melphalan (10 mg/kg), the greatest tumor growth delays were obtained with Oxygent levels between 4 and 12 g PFC/kg. With each of these drugs the greatest tumor growth delays were obtained when the drug was prepared in the emulsion and the combination injected i.v. In each case, each dose of drug was followed by 6 h. of breathing carbogen.

Alkylating Agents↗

The effect on minimum tumor dose of restricting target-dose inhomogeneity in optimized three-dimensional treatment of lung cancer.

An examination was made of the effect upon the minimum tumor dose of a limit placed on the variation of dose across target. If the required level of target dose uniformity is slightly relaxed, a substantial improvement in the minimum tumor dose might appear. It was conjectured that this effect could be seen with treatments optimally planned and evaluated in three-dimensions. A model of advanced carcinoma of the lung treated with a computer controlled accelerator was used to test this hypothesis. A mathematical program for optimizing beam weights was used to determine the largest minimum tumor dose possible. In the six cases tested, a minimum tumor dose of greater than 80 Gy could be delivered if a 20% inhomogeneity limit was accepted. The minimum tumor dose fell to the range 44-64 Gy when the inhomogeneity limit was tightened to 13-17%. The results imply a need to examine the choice of a required level of dose uniformity from the range of values suggested in the 2-dimensional planning literature. If a strict bound-on-dose uniformity is preserved, mechanisms--such as formal optimization--which can reduce target dose inhomogeneity will be valuable.

Dose-Response Relationship, Radiation↗

The effect of vitamin B6 deficiency on cytotoxic immune responses of T cells, antibodies, and natural killer cells, and phagocytosis by macrophages.

The effect of vitamin B6 on cytotoxic immune responses of T cells, natural killer (NK) cells, cytotoxic antibody production, and macrophage phagocytosis was assessed in 5-week-old female C57B1/6 mice. Mice were fed 20% casein diets with pyridoxine (PN) added at 7, 1, 0.1, or 0 mg/kg diet, which represents 700, 100, 10, and 0% of requirement, respectively. Compared to mice fed 7 or 1 mg PN diet, animals fed 0 or 0.1 mg PN diet showed significantly reduced primary splenic and peritoneal T-cell-mediated cytotoxicity (CMC). Animals fed 0 mg PN diet also showed significantly depressed secondary T CMC of splenic and peritoneal lymphocytes against P815 tumor cells. Complement-dependent antibody-mediated cytotoxicity against P815 cells, phagocytosis of SRBC by macrophages, and native and interferon-induced NK cell activities against YAC cells were not affected by the level of vitamin B6 intake. The percentage of macrophages present in the peritoneal exudate cells was increased in animals fed the 0 mg PN diet. The immune responses were not enhanced or altered by the excess intake of vitamin B6 (7 mg PN). It appears that vitamin B6 is an essential nutrient for maintenance of normal T-cell function in vivo.

Animals↗

The effect of vitamin B-6 deficiency on host susceptibility to Moloney sarcoma virus-induced tumor growth in mice.

The effect of vitamin B-6 deficiency on in vivo host susceptibility to primary Moloney sarcoma virus (MSV)-induced tumor growth and to secondary challenge with MSB sarcoma cells was examined in mice. Female C57BL/6 mice, 6 weeks of age, were fed 20% casein diets with pyridoxine (PN) added at 1, 0.5, 0.1 or 0 mg/kg diet for 21 weeks. After 4 weeks of dietary treatment the mice were challenged with MSV. Vitamin B-6 deficiency resulted in an enhancement of tumor susceptibility as well as an increase in tumor size and regression time. The animals resistant to both MSV and MSV-transformed tumor cells ( MSB ) challenge showed splenic tumor development at necropsy 51 days after MSB challenge. Total incidence of MSV/ MSB /splenic tumors was 2/11, 2/11, 4/10 and 8/11 in animals fed PN 1, 0.5, 0.1 and 0 diets, respectively. Since MSV-induced tumors regressed spontaneously in immunocompetent hosts, the increased susceptibility to MSV oncogenesis in vitamin B-6-deficient animals suggests that reactivity of T cells and/or other effector cells is impaired in vitamin B-6-deficient animals suggests that reactivity of T cells and/or other effector cells is impaired in vitamin B-6 adequacy.

Animals↗