Search PubMed⌕ Search

Biomedical subjects

K Peterson

Publications and source records attributed to K Peterson.

At least 55 records · Page 3Linked to original sources

Binary transgenic mouse model for studying the trans control of globin gene switching: evidence that GATA-1 is an in vivo repressor of human epsilon gene expression.

To test whether human GATA-1 (hGATA-1) is involved in the transcriptional control of globin gene switching, we produced transgenic mice overexpressing hGATA-1, crossed them with mice carrying a human beta-globin locus yeast artificial chromosome (beta YAC), and analyzed globin gene expression in their progeny. Mice carrying both the hGATA-1 and the beta YAC transgenes had normal levels of gamma- and beta-globin mRNA and no distortion in the rate or in the timing of gamma-to-beta switch, indicating that hGATA-1 is not involved in the developmental control of gamma- and beta-globin genes. In contrast, mice carrying the hGATA-1 and the beta YAC transgenes had 5- to 6-fold lower expression of the human epsilon globin gene compared with beta YAC mice lacking the hGATA-1 transgene. These results provide direct in vivo evidence that hGATA-1 is a specific repressor of human epsilon gene expression. Our findings also suggest that binary transgenic mouse systems based on overexpression of transcriptional factors can be used to investigate the trans control of human globin gene switching. Systems as the one we describe here should be useful in the study of any developmentally controlled human gene for which transgenic mice are available.

Animals↗

Prospective study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing.

BACKGROUND: Paclitaxel-induced peripheral neuropathy (PN) may be severe and dose-limiting at initial doses > or = 275 mg/M2, but its neurotoxicity at doses < or = 250 mg/M2 has been incompletely characterized. The purposes of this study were to characterize and quantify paclitaxel-induced PN and to determine the utility of quantitative sensory testing (QST). METHODS: We prospectively examined clinically and by QST 37 women with metastatic breast cancer, treated with paclitaxel (200-250 mg/m2) (average number of cycles = 7.3 over an average of 20.1 weeks). QST included thermal threshold (TT) and vibration threshold (VT). RESULTS: Paresthesias appeared in 31 (84%) patients after an average of 1.7 cycles and an average cumulative dose of 371.5 mg/M2. Symptoms occurred after the first or second dose in 26 (84%) patients and then stabilized in 10 (32%), improved in 13 (42%) despite continued treatment, resolved completely in 6 (19%), and were progressive in 2 (7%). Paclitaxel was discontinued in only 1 (3%) patient because of neurotoxicity and no patient required dose reduction because of PN. Thirty-six (97%) developed signs of PN. The most sensitive QST was great toe VT but QST did not predict or identify subclinical PN in any patient. Neurologic syndromes other than PN developed in 12 (32%) patients, and 7 were due to metastatic cancer. CONCLUSIONS: 1) Paclitaxel-induced PN is mostly sensory, and begins after the first or second dose. At these doses the neuropathy is mild, and rarely dose-limiting. 2) QST quantified the neuropathy but was less sensitive than the clinical examination. 3) Knowledge of the features of paclitaxel's PN allows it to be differentiated from other neurologic syndromes which may signal tumor progression.

Adult↗

Clinical evaluation of a new orthosis, the 'walkabout', for restoration of functional standing and short distance mobility in spinal paralysed individuals.

The Walkabout orthosis is a relatively new device for assisted standing and mobility in spinal paralysed individuals. The design, with a medially-mounted single-axis hinge joint linking two knee-ankle-foot orthoses, is quite different to other currently available orthoses which have laterally positioned hip joints such as the Reciprocal Gait Orthosis or Hip Guidance Orthosis. Twenty-five spinal cord injured patients were fitted and trained with the Walkabout orthosis and followed up regularly for just under 2 years on average. Sixty percent of all the patients fitted have incorporated use of the Walkabout orthosis into their lifestyles. Maintenance of joint mobility and psychological benefits were the most important outcomes of Walkabout usage. Loss of thoraco-lumbar mobility was found to be a limiting factor in successful use of the Walkabout orthosis in patients without active hip flexion. Patient selection criteria should include demonstrated spinal stability without significant deformity, controlled muscle spasm, less than 5 degrees of hip or knee flexion contracture, achievable neutral ankle position, mobility of the thoraco-lumbar spine into lateral flexion, good upper limb strength, and motivation with realistic expectations.

Adult↗

Exercise.

Explore the source record for details and available documents.

Adolescent↗

Television viewing as a cause of increasing obesity among children in the United States, 1986-1990.

BACKGROUND AND METHODS: The prevalence of obesity among children and adolescents has increased, and television viewing has been suggested as a cause. We examined the relation between hours of television viewed and the prevalence of overweight in 1990, and the incidence and remission of overweight from 1986 to 1990 in a nationally representative cohort of 746 youths aged 10 to 15 years in 1990 whose mothers were 25 to 32 years old. Overweight was defined as a body mass index higher than the 85th percentile for age and gender. RESULTS: We observed a strong dose-response relationship between the prevalence of overweight in 1990 and hours of television viewed. The odds of being overweight were 4.6 (95% confidence interval, 2.2 to 9.6) times greater for youth watching more than 5 hours of television per day compared with those watching 0 to 2 hours. When adjustments were made for previous overweight (in 1986), baseline maternal overweight, socioeconomic status, household structure, ethnicity, and maternal and child aptitude test scores, results were similar (odds ratio, 5.3; 95% confidence interval, 2.3 to 12.1). We also found significant relations between television viewing and increased incidence and decreased remission of overweight during this 4-year period, adjusted for baseline covariates. The adjusted odds of incidence were 8.3 (95% confidence interval, 2.6 to 26.5) times greater for youth watching more than 5 hours of television per day compared with those watching for 0 to 2 hours. Estimates of attributable risk indicate that more than 60% of overweight incidence in this population can be linked to excess television viewing time. CONCLUSION: Television viewing affects overweight among youth, and reductions in viewing time could help prevent this increasingly common chronic health condition.

Body Mass Index↗

The Practice Environment Project. A process for outcome evaluation.

OBJECTIVE: Evaluating the practice environment is essential to determine if the practice environment is conducive to the delivery of quality patient care. The Practice Environment Project (PEP) was created to provide a framework for current and ongoing evaluation of the practice environment. BACKGROUND: Major changes in the delivery of patient care services have focused attention on the evaluation of the effectiveness of these changes. The extent and type of change may vary throughout an institution. The identification of core variables to assess the effectiveness of these changes sets the framework for ongoing evaluation of new unit-based models for delivery of services. METHODS: In part 1, quantitative data were collected from nursing staff members (job satisfaction, collaboration with physicians, autonomy), physicians (quality of nursing care, collaboration with nurses), and patients (satisfaction with nursing care). In part 2, focus groups were held with nursing personnel to discuss factors that affected the provision of services. Unit-based action plans were developed to manage barriers to the delivery of services. RESULTS: Patients and physicians reported a high degree of satisfaction with patient care. Physicians reported a higher level of collaboration with nurses than that reported by nurses. Nurses reported a high degree of autonomy in practice, however, in other areas of job satisfaction (development and recognition), they suggested areas for improvement. CONCLUSIONS: The PEP created a mechanism to evaluate the current state-of-the-practice environment by identifying core elements for evaluation of work redesign. It also provided a framework for managing barriers that disrupted the delivery of patient care services.

Focus Groups↗

Immune dysregulation in the aging human lung.

Aging has been associated with diminished lung function and increased susceptibility to lung infection. To determine whether changes suggestive of immune dysregulation and inflammation appear in the lungs of clinically normal individuals as a function of advancing age, we performed bronchoalveolar lavage (BAL) on discontinuous age groups (20-36, 45-55, and 65-78 yr old) of clinically normal volunteer subjects. We measured immunoglobulin (IgG, IgA, IgM), albumin, interleukin-6 (IL-6), and interleukin-10 concentrations in BAL fluid. Bronchoalveolar cell profiles, cell surface antigen expression, and superoxide anion production were also measured. A significant increase in total cell concentration, neutrophils, and BAL immunoglobulin content was observed in the oldest age group compared with the youngest age group. Mean lymphocyte subset (CD4+/CD8+) ratios were significantly increased in blood (2.6 +/- 0.4 versus 1.6 +/- 0.1; p<0.03) and to a greater degree in BAL (4.8 +/- 1.0 versus 1.9 +/- 0.2; p<0.01) for the oldest versus youngest age groups. Similarly, BAL-derived cells displayed significantly increased phorbol myristate acetate-stimulated release of superoxide anion (8.8 +/- 1.3 versus 4.5 +/- 0.7 nmol/5 x 10 5 cells/h; p<0.01) for the oldest versus youngest subject group, and mean BAL IL-6 concentrations were significantly elevated in the oldest age group (0.86 +/- 0.13 ng/ml) compared with the youngest age group (0.53 +/- 0.03 ng/ml; p<0.01). Our observations suggest that altered inflammatory cell profiles and low-grade inflammation exist in the lower respiratory tracts of many asymptomatic, clinically normal volunteers of advanced age.

Adult↗

Salvage chemotherapy for oligodendroglioma.

The authors present their experience with salvage chemotherapy for oligodendroglioma, an uncommon brain tumor that responds predictably to PCV (procarbazine, lomustine (CCNU), and vincristine) when given as initial therapy. The authors reviewed the records of patients with oligodendrogliomas who received a second, third, or fourth cytotoxic regimen prescribed to combat tumor recurrence documented by computerized tomography or magnetic resonance imaging following an initial chemotherapy program. Initial regimens were prescribed at various time points: as neoadjuvant therapy prior to radiotherapy, as adjuvant therapy in conjunction with radiotherapy, or at recurrence following radiotherapy. Response criteria were based on measurable changes in tumor size following published guidelines. Twenty-three patients (14 men and nine women) aged 25 to 58 years (median 36 years) received 33 salvage regimens. When non-PCV chemotherapy had been the prior regimen, seven (88%) of eight patients responded to salvage chemotherapy, all seven (100%) responding to PCV. Administration of PCV was effective after regimens of carmustine and CCNU but was ineffective after prior administration of PCV. When PCV had been given any time previously, only four (19%) of 21 patients responded to salvage chemotherapy; however, four (40%) of 10 patients who received etoposide (VP-16)/cisplatin (CDDP) responded. Despite the small number of patients, two noteworthy trends emerge from these data: first, PCV is a highly effective salvage treatment when used at tumor recurrence following non-PCV chemotherapy regimens, and second, the synergistic combination of VP-16 and CDDP may exert substantial anti-oligodendroglioma activity, and it warrants further evaluation.

Adult↗

Multifocal enhancing magnetic resonance imaging lesions following cranial irradiation.

Radiation necrosis is a delayed complication of cranial irradiation, typically presenting as a single intracerebral mass that is radiographically indistinguishable from recurrent tumor. We describe 6 patients with a distinct radiographic syndrome of multifocal enhancing lesions on magnetic resonance images, and their variable clinical courses: some fluctuating, some spontaneously resolving, and some demonstrating fulminant progression to frank necrosis.

Adult↗

Effects of butyrate and glucocorticoids on gamma- to beta-globin gene switching in somatic cell hybrids.

Butyrate and its analogs have been shown to induce fetal hemoglobin in humans and primates and in erythroid cell cultures. To obtain insights concerning the cellular mechanisms of butyrate action, we analyzed the effects of butyrate on human globin gene expression in hybrids produced by fusing mouse erythroleukemia cells (MEL) with human fetal erythroid cells (HFE). These hybrids initially express human fetal hemoglobin but subsequently switch to adult globin expression after several weeks in culture. We found that alpha-aminobutyric acid, a butyrate analog which does not induce terminal maturation, strikingly delays the rate of the gamma- to beta-globin gene (gamma-to-beta) switch in the HFE x MEL hybrids. The effect of butyrate on globin expression is transient, with the result that the delay of globin gene switching requires the continuous presence of this compound in culture. Furthermore, butyrate fails to induce fetal hemoglobin expression in hybrids which have switched, suggesting that the effect of this compound on gamma-globin expression is due to inhibition of gamma gene silencing rather than to induction of gamma gene transcription. Since in other cellular systems, glucocorticoids antagonize the action of butyrate, the effect of dexamethasone on the gamma-to-beta switch in HFE x MEL hybrids was examined. Dexamethasone strikingly accelerated the gamma-to-beta switch, and its effect was irreversible. The effects of dexamethasone and butyrate on the gamma-to-beta switch of the HFE x MEL hybrids appear to be codominant. These results indicate that steroids can have a direct effect on globin gene switching in erythroid cells.

Aminobutyrates↗

Medulloblastoma/primitive neuroectodermal tumor in 45 adults.

Medulloblastoma/primitive neuroectodermal tumor (PNET) is an uncommon tumor in adults. We reviewed the medical records of 45 patients, 15 years or older, with medulloblastoma/PNET. Most patients presented with symptoms referable to the posterior fossa, and 31 of 45 patients had disease limited to the posterior fossa at the time of diagnosis. Despite initial favorable response to surgical resection, radiation, and chemotherapy, one-half had recurrence 10 to 76 months after initial treatment. Only two of these patients had local recurrence; the remainder had CNS dissemination, systemic metastasis, or both. The recommended approach to medulloblastoma/PNET in adults is similar to that in children, and includes initial staging evaluation, systemic and focal therapy (ie, neuraxis irradiation with posterior fossa boost and chemotherapy), and long-term follow-up to detect late and distant recurrence.

Adolescent↗