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Biomedical subjects

R Larson

Publications and source records attributed to R Larson.

At least 19 recordsLinked to original sources

Obesity increases the likelihood of total joint replacement surgery among younger adults.

We conducted a retrospective review of medical charts of patients, aged 18 to 59 years old, who underwent either a total knee replacement (TKR) or total hip replacement (THR) from January 2002 to December 2004. Of the 204 study subjects, 52% had a TKR while 48% had a THR. Obesity was significantly associated with the need for a TKR or THR when comparing the study group to adults of similar age in the general population (P< 0.0001). Seventy-two percent (146) of the study group was obese and 21% (42) overweight (BMI 25.0 to 29.9 kg/m(2)) compared to only 26% (596) obese and 34% (732) overweight in the general population. Patients undergoing a TKR were significantly more likely to be obese (BMI>30 kg/m(2)) than those having a THR, 83% (89) compared to 59% (57) (P< .0006). Our findings support those previously observed in the elderly population. Primary and secondary prevention programs aimed at reducing obesity are strongly recommended.

Adolescent↗

Use of bacteriophages as surrogates for mammalian viruses.

The threat of viral contamination is common to all processes using biological products of animal or human origin. Therefore, demonstration of virus clearance (i.e. validation of virus removal and/or inactivation steps) is of utmost importance to the biopharmaceutical industries. Ultimately, virus clearance studies should show that any virus removal/inactivation stage incorporated into the manufacturing process not only removes or inactivates known viruses that may be conceivably present (e.g. from cell banks and source materials), but also other viruses that may be introduced adventitiously (e.g. by addition of supplements downstream of the manufacturing process). In this paper, we outline the shared properties of mammalian viruses and similar sized bacteriophages, and factors that may influence the virus clearance process. We also present test data from filtration studies, showing similar titre reductions for both types of virus. We propose that well-characterised bacteriophage, such as PP7 and PR772 can be used as models for mammalian viruses if the virus removal mechanism is based on size exclusion.

Animals↗

Perspectives on the treatment of chronic phase and advanced phase CML and Philadelphia chromosome positive ALL(1).

Chronic myeloid leukaemia (CML) is a malignant disease of the bone marrow characterised by the presence of the Philadelphia (Ph) chromosome. About 20% of acute lymphoblastic leukaemia (ALL) patients also show this genetic abnormality. A new drug, imatinib (Glivec, Novartis Pharma AG, Basel, Switzerland, and formerly STI571) is having a profound effect on the treatment and management of all stages of CML and Philadelphia chromosome positive (Ph+) ALL. New treatment algorithms are being developed. Should imatinib replace or be combined with existing therapies? To address this question, we review the pros and cons of therapy with interferon-alpha (IFN-alpha), allogeneic transplantation, autologous transplantation, imatinib, and in the case of Ph+ ALL, chemotherapy and experimental approaches. Conservative and aggressive treatments will be discussed and new molecular methods of monitoring cytogenetic response and their significance will also be reviewed.

Antineoplastic Agents↗

Age trends in the experience of family discord in single-mother families across adolescence.

This study utilized the Family Environment Scale and the Experience Sampling Method to evaluate how overall family discord and discord in immediate family interactions were related to adolescents' age, in 101 single-mother families. Mothers' reports of overall family discord decreased across adolescence. In immediate interactions, adolescent boys reported feeling more anger towards their mothers with age, while girls reported feeling less anger with age.

Adolescent↗

Developmental expression of the Xenopus Iroquois-family homeobox genes, Irx4 and Irx5.

We have isolated and characterized the developmental expression of the Xenopus Iroquois 4 (Irx4) and Iroquois 5 (Irx5) homeodomain transcription factors. Irx4 is expressed in a subset of cells in the neural retina and the developing hindbrain and also, specifically, in the ventricle of the heart. Xenopus Irx5 is expressed in the developing midbrain, hindbrain, neural tube, and also in the retina.

Amino Acid Sequence↗

Men's work and family lives in India: the daily organization of time and emotion.

This article examines daily patterns of work and family life for a sample of middle-class men in northern India. One hundred fathers of 8th graders provided information on their hour-to-hour time use and subjective states, by means of the experience sampling method. They reported little time spent on family work but substantial amounts of time with their children and thinking about their families. At their jobs, they reported high levels of attention but more negative emotion. By contrast, the home sphere elicited lower attention, more favorable affect, and more feeling of choice. Unlike for American samples, little relationship was found between experience at work and home, including little influence of men's work emotions on the family in the evening. These findings reflect how strong traditional family roles in India shape men's daily lives.

Adult↗

Rapid presumptive diagnosis of hantavirus cardiopulmonary syndrome by peripheral blood smear review.

Hantavirus cardiopulmonary syndrome (HCPS) is a rare but frequently lethal acute zoonotic viral infection in rural North America. The rapidity of progression from febrile prodrome to cardiogenic shock and noncardiogenic pulmonary edema requiring intensive care creates high diagnostic urgency and a need for a rapid screening tool. In this retrospective cohort study, 2 pathologists scored blinded peripheral blood smears from 52 patients with HCPS and 128 seronegative patients referred for diagnosis of suspected hantavirus infection. During the prodromal phase, thrombocytopenia was the only consistent abnormality and could be used to indicate hantavirus serologic testing. After the onset of pulmonary edema detected radiographically, the presence of 4 of 5 findings (thrombocytopenia, myelocytosis, hemoconcentration, lack of significant toxic granulation in neutrophils, and more than 10% of lymphocytes with immunoblastic morphologic features) has a sensitivity for HCPS of 96% and a specificity of 99% and missed no patients with HCPS who required intensive care. While each abnormality is commonly seen, the combination of at least 4 of these CBC count data and peripheral blood smear findings can guide early treatment and patient transport decisions until rapid, specific, serologic testing becomes widely available.

Adult↗

Quality beyond compliance.

The service sector within the biopharmaceutical industry has experienced phenomenal growth over the past decade. In the highly regulated Good Laboratory Practices environment, the need for timely, high-quality service, accurate results, and on-time deliverables becomes paramount for the success and profitability of biopharmaceutical companies. The quality assurance process is a vital component of this drug product-development cycle and ensures compliance to the highest domestic and international regulatory standards. Quality-assurance professionals historically have held the role of independent auditors of the processes, who certify that results meet current standards of practice. Covance, a contract research organization that includes Good Laboratory Practices laboratories, reorganized and expanded the functional responsibilities of its quality assurance team in 1997. Auditors and quality assurance professionals have assumed roles beyond traditional compliance auditing and are forging new leadership and mentoring roles as process-improvement specialists. The results have been tangible, measurable benefits for clients and the Covance organization. This article provides an overview of this cultural change and the processes put in place to improve efficiency, productivity, and customer and employee satisfaction.

Consumer Behavior↗

The oncogenic T cell LIM-protein Lmo2 forms part of a DNA-binding complex specifically in immature T cells.

The LIM-only protein LMO2 is expressed aberrantly in acute T-cell leukaemias as a result of the chromosomal translocations t(11;14) (p13;q11) or t(7;11) (q35;p13). In a transgenic model of tumorigenesis by Lmo2, T-cell acute leukaemias arise after an asymptomatic phase in which an accumulation of immature CD4(-) CD8(-) double negative thymocytes occurs. Possible molecular mechanisms underlying these effects have been investigated in T cells from Lmo2 transgenic mice. Isolation of DNA-binding sites by CASTing and band shift assays demonstrates the presence of an oligomeric complex involving Lmo2 which can bind to a bipartite DNA motif comprising two E-box sequences approximately 10 bp apart, which is distinct from that found in erythroid cells. This complex occurs in T-cell tumours and it is restricted to the immature CD4(- )CD8(-) thymocyte subset in asymptomatic transgenic mice. Thus, ectopic expression of Lmo2 by transgenesis, or by chromosomal translocations in humans, may result in the aberrant protein interactions causing abnormal regulation of gene expression, resulting in a blockage of T-cell differentiation and providing precursor cells for overt tumour formation.

Adaptor Proteins, Signal Transducing↗

High-energy total body irradiation as preparation for bone marrow transplantation in leukemia patients: treatment technique and related complications.

PURPOSE: Bone marrow transplantation with conditioning regimens that include total-body irradiation (TBI) is widely used in patients with acute lymphoblastic and acute myelocytic leukemias. The major causes of death in this population are relapse of leukemia, infection, and treatment related complications. Our purpose was to achieve a homogenous radiation dose distribution and to minimize the dose to the lungs, liver, and kidneys so that the incidence of organ injury was reduced. METHODS AND MATERIALS: Dose to the bone marrow, midplane, and periphery was quantified by use of thermoluminescent detectors in a bone-equivalent tissue phantom. In an effort to reduce the risk of complications, we treated relapsed or refractory leukemia patients with TBI administered in fractionated, parallel opposed large fields with 24 MV photons, using tissue compensation and partial-transmission lung shielding. Tissue toxicities were then determined. RESULTS: Dose quantitation in bone-equivalent and tissue-equivalent phantoms demonstrated that backscatter and pair production interactions adjacent to bone increased the bone marrow dose by 6 to 11%. At an SSD of 400 cm and at patient diameters of 20 to 40 cm, the percent inhomogeneity across the phantom with 24 MV photons was 0 to 0.3%, compared to 4 to 6% for 6 MV photons. End-organ toxicities consisted of clinical interstitial pneumonitis in six patients, idiopathic interstitial pneumonitis in three patients, renal toxicity in seven patients, and veno-occlusive disease of the liver in one patient. Toxicities did not correlate with fractionation schedule. CONCLUSIONS: Total-body irradiation administered with 24 MV photons increases the dose deposition in bone marrow through pair production and backscatter interactions occurring in bone. Because percent depth dose increases with SSD, the 24 MV beam is more penetrating at a 400 cm distance than at 100 cm and dose homogeneity is improved with higher energies. Thus, the incidence of radiation-mediated injury to lung, liver, and kidney is reduced. This is an effective preparatory regimen for patients with high-risk leukemias requiring bone marrow transplantation.

Adolescent↗

Mortality from cancer and other causes of death among synthetic rubber workers.

OBJECTIVES: This study evaluated the mortality experience of workers from the styrene-butadiene rubber industry. Concerns about a possible association of 1,3-butadiene and styrene with lymphohaematopoietic, gastrointestinal, and lung cancers prompted the investigation. METHODS: A retrospective follow up study was conducted of 15,649 men employed for at least one year at any of eight North American styrene-butadiene rubber plants. Analyses used standardised mortality ratios (SMRs) to compare styrene-butadiene rubber workers' cause specific mortalities (1943-91) with those of the United States and Ontario general populations. RESULTS: On average, there were 25 years of follow up per subject. The standardised mortality ratio (SMR) was 87 (95% confidence interval (95% CI) 85 to 90) for all causes of death combined and was 93 (95% CI 87 to 99) for all cancers. There was an excess of leukaemia (SMR 131, 95% CI 97 to 174), restricted to hourly workers (SMR 143, 95% CI 104 to 191). For causes of death other than leukaemia, SMRs were close to or below the null value of 100. Results by work area (process group) were unremarkable for non-Hodgkin's lymphoma, multiple myeloma, and stomach cancer. Maintenance workers had a slight increase in deaths from lung cancer, and certain subgroups of workers had more than expected deaths from cancer of the large intestine and the larynx. CONCLUSION: This study found an excess of leukaemia that is likely to be due to exposure to butadiene or to butadiene plus other chemicals. Deaths from non-Hodgkin's lymphoma, multiple myeloma, and stomach cancer did not seem to be related to occupational exposure. The excess deaths from lung cancer among maintenance workers may be due in part to confounding by smoking, which was not controlled for, and in part to an unidentified occupational exposure other than butadiene or styrene. Increases in cancer of the large intestine and larynx were based on small numbers, did not seem to be due to exposure to butadiene or styrene, and may be chance observations.

Butadienes↗

Developmental patterns and gender differences in the experience of peer companionship during adolescence.

Adolescents in fifth through eighth grade (N = 218) carried electronic pagers for 1 week and completed self-report forms in response to signals received at random times. Four years later, the sample underwent the same procedure. Results indicate that thinking about the opposite sex occurs at an earlier age than spending time with the opposite sex alone and that both increase over time. Results also indicate little change in same-sex companionship over time. Girls spent more time with the opposite sex and spent more time thinking about opposite- and same-sex peers. Time with the opposite sex alone was experienced as very positive, whereas time spent thinking about the opposite sex was associated with less positive states as adolescents became older.

Adolescent↗