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Biomedical subjects

L Carlson

Publications and source records attributed to L Carlson.

At least 19 recordsLinked to original sources

Efficacy of a tart cherry juice blend in preventing the symptoms of muscle damage.

BACKGROUND: Numerous antioxidant and anti-inflammatory agents have been identified in tart cherries. OBJECTIVE: To test the efficacy of a tart cherry juice blend in preventing the symptoms of exercise induced muscle damage. METHODS: This was a randomised, placebo controlled, crossover design. Fourteen male college students drank 12 fl oz of a cherry juice blend or a placebo twice a day for eight consecutive days. A bout of eccentric elbow flexion contractions (2 x 20 maximum contractions) was performed on the fourth day of supplementation. Isometric elbow flexion strength, pain, muscle tenderness, and relaxed elbow angle were recorded before and for four days after the eccentric exercise. The protocol was repeated two weeks later with subjects who took the placebo initially, now taking the cherry juice (and vice versa). The opposite arm performed the eccentric exercise for the second bout to avoid the repeated bout protective effect. RESULTS: Strength loss and pain were significantly less in the cherry juice trial versus placebo (time by treatment: strength p<0.0001, pain p = 0.017). Relaxed elbow angle (time by treatment p = 0.85) and muscle tenderness (time by treatment p = 0.81) were not different between trials. CONCLUSIONS: These data show efficacy for this cherry juice in decreasing some of the symptoms of exercise induced muscle damage. Most notably, strength loss averaged over the four days after eccentric exercise was 22% with the placebo but only 4% with the cherry juice.

Adolescent↗

Scavenging of As from acid mine drainage by schwertmannite and ferrihydrite: a comparison with synthetic analogues.

Ochreous precipitates containing 5.5-69.8 g/kg As were isolated from mine drainage in Finland and were composed of schwertmannite, ferrihydrite, and goethite. Schwertmannite formation was favored at pH 3-4, but its structure was degraded at high As levels. A series of coprecipitates were therefore prepared from mixed iron arsenate/sulfate solutions to define the limits of schwertmannite stability. Schwertmannite was replaced as the dominant phase by a poorly crystalline ironIII hydroxy arsenate (FeOHAs) when As/Fe mole ratios exceeded 0.15. The FeOHAs gave an X-ray diffraction pattern similar to that obtained from an "amorphous" ironIII arsenate (As/Fe = 1.0) with broad peaks at 0.30 and 0.16 nm. The FeOHAs possessed a magnetic hyperfinefield of 41.9T at 4.2 K that was intermediate to those of schwertmannite (46.1 T) and the ironIII arsenate (24.8 T). These data indicate a strong disruptive effect of arsenate on magnetic ordering and structure development in schwertmannite. Equilibration of 0.01 M arsenate solutions with freshly prepared schwertmannite and 2-line ferrihydrite at pH 3.0 for up to 60 d gave sorbed As contents of 175 and 210 g/kg, respectively. Arsenate sorption degraded the host schwertmannite and ferrihydrite, perhaps due to the formation of an FeOHAs surface phase.

Adsorption↗

The experts speak: the critical ingredients of strengths model case management.

This study assessed the level of agreement among expert's opinion of the critical ingredients of the strengths model of case management. Twenty-eight experts rated the "significance" to the model of 72 elements/behaviors thought to be important and 8 distracter elements. There were also five open-ended questions asking for opinions on agency structure, service delivery, etc. The results found an extremely high agreement among the experts on virtually all items.

Case Management↗

Comparative study of cefepime versus ceftazidime in the empiric treatment of pediatric cancer patients with fever and neutropenia.

BACKGROUND: In view of the recent trend toward monotherapy in the treatment of bacterial infection, we evaluate the clinical efficacy and safety of cefepime vs. ceftazidime for the empiric treatment of febrile episodes in neutropenic pediatric cancer patients. METHODS: In a single site, open label study, 104 neutropenic pediatric cancer patients [96% with absolute neutrophil count (ANC) of <500 neutrophils/mm3] with a median age of 6 years were randomized (1:1) to receive either intravenous cefepime or ceftazidime (50 mg/kg/dose every 8 h; < or = 6 g/day) for empiric treatment of fever (temperature >38.0 degrees C occurring at least twice in 24 h, or single >38.5 degrees C). Febrile episodes were classified as either microbiologically or clinically documented infection or fever of unknown origin. Therapy continued until the ANC was > or = 1,000 neutrophils/mm3 or there was an increasing ANC in low risk patients (maximum duration of treatment, 8 weeks). The primary efficacy endpoints assessed were clinical and microbiologic response to assigned drug therapy. Secondary outcome measures were rate of early discontinuation of study drug and use of concomitant antibiotic therapy to modify initial study drug regimen. RESULTS: Of 68 patients who could be evaluated for efficacy, 74% (26 of 35) of cefepime-treated patients and 70% (23 of 33) of ceftazidime-treated patients responded to treatment. The small number of study patients precluded statistical analysis of results. In a modified intent-to-treat analysis, 59% of the patients treated with cefepime and 47% of ceftazidime-treated patients responded to therapy. Cefepime patients developed fewer new infections than ceftazidime patients (9% vs. 21%, respectively) and early discontinuation of study drug therapy occurred slightly more often in the ceftazidime group. Further, the use of concomitant systemic antimicrobial therapy (mostly vancomycin) occurred less often in the cefepime-treated patients, as compared with the ceftazidime group [35% [17 of 49] vs. 44% (24 of 55), respectively]. No deaths or serious adverse events were considered to be related to study therapy. The most frequent adverse event was rash that was moderate in severity, and it occurred equally in both groups. CONCLUSION: Cefepime appears to be safe and effective compared with ceftazidime for initial empiric therapy of febrile episodes in neutropenic pediatric cancer patients.

Adolescent↗

Vascular function and blood pressure in GH transgenic mice.

Acromegaly is associated with cardiovascular disease. We studied vascular function and mean arterial blood pressure in transgenic mice overexpressing bovine GH. Mean arterial blood pressure was measured in conscious, unrestrained male and female bovine GH and littermate control mice during normal as well as high salt intake using telemetric devices. Structure in artificially perfused maximally dilated hindquarter vascular beds and vascular reactivity and endothelial function in small mesenteric vessels were studied in female bovine GH and control mice. Mean arterial blood pressure was increased in female bovine GH transgenic (126 +/- 3 mm Hg) and male bovine GH transgenic (129 +/- 4 mm Hg) compared with female (109 +/- 3 mm Hg, P < 0.05) and male (111 +/- 3 mm Hg, P < 0.05) controls respectively. Increased salt intake had no effect on mean arterial blood pressure. Perfusion studies showed a significant decrease in the average diameter of the female bovine GH transgenic hindquarter vascular bed (P < 0.05). The responses of isolated resistance arteries to nor-epinephrine, potassium-induced depolarization, acetylcholine, or sodium-nitroprusside did not significantly differ between bovine GH transgenic and control mice. We conclude that the phenotype of the bovine GH transgenic mice includes a salt-resistant form of hypertension. Furthermore, the increase in mean arterial blood pressure is accompanied by a significant structural narrowing of the resistance vasculature without changes in vascular reactivity or endothelial function. The results imply that hypertension in bovine GH transgenic mice is maintained mainly by a structurally based increase in peripheral vascular resistance.

Animals↗

Physical functioning and health-related quality-of-life changes with exercise training in hemodialysis patients.

The Renal Exercise Demonstration Project was designed to test the effects of two different approaches to exercise programming on the levels of physical activity, physical functioning, and self-reported health status in hemodialysis patients. Two hundred eighty-six patients were recruited for participation. Intervention patients were given individually prescribed exercise for 8 weeks of independent home exercise, followed by 8 weeks of incenter cycling during dialysis. Physical performance testing was performed at baseline and after each intervention using gait speed, sit-to-stand test, and 6-minute walk. The Medical Outcomes Study Short Form 36-item (SF-36) questionnaire was used to assess self-reported health status. The intervention group showed increased participation in physical activity. There were significant differences between the intervention and nonintervention groups in change over time in normal and fast gait speed, sit-to-stand test scores, and the physical scales on the SF-36, including the physical component scale. The intervention group improved in these test results, whereas the nonintervention group either did not change or declined over the duration of the study. It is clear that improvements in physical functioning result from exercise counseling and encouragement in hemodialysis patients. Because self-reported physical functioning is highly predictive of outcomes in hemodialysis patients, more attention to patients' levels of physical activity is warranted.

Activities of Daily Living↗

Low-functioning hemodialysis patients improve with exercise training.

The Renal Exercise Demonstration Project provided two different approaches to exercise programming to a group of hemodialysis patients. Physical functioning and self-reported health-related quality of life were measured at baseline, after 2 months of independent exercise, and again after 2 months of in-center cycling. This study compares the responses to intervention of patients who initially scored low (<34) on the Physical Component Scale (PCS) on the Medical Outcomes Study Short-Form 36 questionnaire to those who initially scored higher (>34) on the same scale. The high-PCS group scored higher on all physical function tests (normal gait speed, fast gait speed, and sit-to-stand test) at each testing time than the low-PCS group. The high-PCS group improved only on the sit-to-stand test, whereas the low-PCS group improved in all three physical function tests. There were significant differences between the groups in change over time in all the physical scales and the PCS over time, with the low-PCS group showing improvements in response to the intervention and the high-PCS group showing no change over time. No differences in change over time were noted between the groups on the mental scales in either group. We conclude that low-functioning hemodialysis patients can benefit from exercise counseling in both objective measures of physical functioning and self-reported physical functioning. The impact of such interventions seems to be more profound in the lowest functioning patients.

Analysis of Variance↗

Quantitative abductor pollicis brevis strength testing: reliability and normative values.

We conducted this study to establish reliability and normative values for abductor pollicis brevis strength. A portable microprocessor-controlled hand-held device was used for testing. Twelve healthy subjects were used for intrarater and interrater reliability testing. Intraclass correlation coefficients were 0.92 for intrarater testing and 0.89 for interrater reliability. Normative values for abductor pollicis brevis strength are presented by gender and age from the test results of 297 volunteers (121 men and 176 women; age range, 20-59 years) with at least 30 subjects in each subgroup. Abductor pollicis brevis strength was significantly greater in the men than in the women in all age groups. No significant differences were found related to age, side, or dominance. The results suggest that quantitative muscle testing produces consistent values for abductor pollicis brevis strength that remain fairly constant in patients aged 20 to 59 years.

Adult↗

Distinct activities of p52/NF-kappa B required for proper secondary lymphoid organ microarchitecture: functions enhanced by Bcl-3.

Mice rendered deficient in p52, a subunit of NF-kappa B, or in Bcl-3, an I kappa B-related regulator that associates with p52 homodimers, share defects in the microarchitecture of secondary lymphoid organs. The mutant mice are impaired in formation of B cell follicles and are unable to form proper follicular dendritic cell (FDC) networks upon antigenic challenge. The defects in formation of B cell follicles may be attributed, at least in part, to impaired production of the B lymphocyte chemoattractant (BLC) chemokine, possibly a result of defective FDCs. The p52- and Bcl-3-deficient mice exhibit additional defects within the splenic marginal zone, including reduced numbers of metallophilic macrophages, reduced deposition of the laminin-beta 2 chain and impaired expression of a mucosal addressin marker on sinus-lining cells. Whereas p52-deficient mice are severely defective in all of these aspects, Bcl-3-deficient mice are only partially defective. We determined that FDCs or other non-hemopoietic cells that underlie FDCs are intrinsically impaired in p52-deficient mice. Adoptive transfers of wild-type bone marrow into p52-deficient mice failed to restore FDC networks or follicles. The transfers did restore metallophilic macrophages to the marginal zone, however. Together, the results suggest that p52 carries out functions essential for a proper splenic microarchitecture in both hemopoietic and non-hemopoietic cells and that Bcl-3 is important in enhancing these essential activities of p52.

Adjuvants, Immunologic↗

Unusual amino acid usage in the variable regions of mercury-binding antibodies.

Monoclonal antibodies (mAb) specific for mercuric ions were isolated from BALB/c mice injected with a mercury-containing, hapten-carrier complex. The antibodies reacted by enzyme-linked immunosorbent assay with bovine serum albumin-glutathione-mercuric chloride (BSA-GSH-HgCl) but not with BSA-GSH without mercury. Nucleotide sequences from polymerase chain reaction products encoding six of the antibody heavy-chain variable regions and seven light-chain variable regions revealed that all the antibodies contained an unpaired cysteine residue in one hypervariable region, which is unusual for murine antibodies. Mutagenesis of the cysteine to either tyrosine or serine in one of the Hg-binding antibodies, mAb 4A10, eliminated mercury binding. However, of two influenza-specific antibodies that contain cysteine residues at the same position as mAb 4A10, one reacted with mercury, although not so strongly as 4A10, whereas the other did not react at all. These results suggested that, in addition to an unpaired cysteine, there are other structural features, not yet identified, that are important for creating an appropriate environment for mercury binding. The antibodies described here could be useful for investigating mechanisms of metal-protein interactions and for characterizing antibody responses to structurally simple haptens.

Amino Acid Sequence↗

A phase II trial of CI-958 in patients with hormone-refractory prostate cancer.

PURPOSE: To assess the antitumor activity of the benzothiopyranoindazole CI-958 ¿5-[(2-aminomethyl)amino]-2-[2-(diethylamino)ethyl]-2H- [l]benzothiopyrano[4,3,2-cd]-indazol-8-ol trihydrochloride¿ in hormone-resistant prostate carcinoma, using an intravenous dose of 700 mg/m(2) every 3 weeks. PATIENTS AND METHODS: Patients eligible for this study had advanced prostate carcinoma that had failed hormonal treatment. Changes in an initially elevated prostate-specific antigen (PSA) level and regression of objectively measurable disease were used as response criteria. RESULTS: All 33 patients enrolled were evaluated. Of 30 with elevated PSA levels, 6 had a >50% decline maintained for >30 days; response durations ranged from 105 to 623 days. Eleven patients had objectively measurable disease; two had partial responses (lasting 316 and 461 days) consisting of shrinkage of retroperitoneal nodes and of masses surrounding the rectum and bladder. The survival of all responding patients ranged from 366 days to 709 days and the median survival of all patients was 12 months (range 1-23 + months). Neutropenia was common, but thrombocytopenia was not. Nonhematologic side effects included nausea, vomiting, anorexia, asthenia, and chills, but were usually mild. The drug caused phlebitis when given into peripheral veins and central venous administration is recommended. No consistent reductions in cardiac function were documented by sequential assessment of left ventricular ejection fractions. CONCLUSIONS: CI-958 has modest but definite antitumor activity in hormone-resistant prostate carcinoma. Its toxicities include neutropenia, nausea, vomiting, anorexia, asthenia, chills and phlebitis.

Adult↗

Staff responsibility to exercise.

Recent attention has been focused on the importance of exercise for improving the physical functioning of renal patients. The involvement of the dialysis staff in encouragement and implementation of programs is critical to the success of patient efforts in improving physical functioning. Staff responsibility initially consists of various developmental steps that are focused on gaining staff support and developing a plan that matches the needs and the resources available to the unit. Each staff member plays a critical role in the development, implementation, and evaluation of the exercise program. A concerted effort from all staff to incorporate exercise as a routine part of the patient care will enhance the potential of success and patient participation.

Exercise Therapy↗

Mice deficient in nuclear factor (NF)-kappa B/p52 present with defects in humoral responses, germinal center reactions, and splenic microarchitecture.

p52 is a subunit of nuclear factor (NF)-kappa B transcription factors, most closely related to p50. Previously, we have shown that p52, but not p50 homodimers can form transactivating complexes when associated with Bcl-3, an unusual member of the I kappa B family. To determine nonredundant physiologic roles of p52, we generated mice deficient in p52. Null mutant mice were impaired in their ability to generate antibodies to T-dependent antigens, consistent with an absence of B cell follicles and follicular dendritic cell networks in secondary lymphoid organs, and an inability to form germinal centers. Furthermore, the splenic marginal zone was disrupted. These phenotypes are largely overlapping with those observed in Bcl-3 knockout animals, but distinct from those of p50 knockouts, supporting the notion of a physiologically relevant complex of p52 homodimers and Bcl-3. Adoptive transfer experiments further suggest that such a complex may be critical in accessory cell functions during antigen-specific immune reactions. Possible roles of p52 and Bcl-3 are discussed that may underlie the oncogenic potential of these proteins, as evidenced by recurrent chromosomal translocations of their genes in lymphoid tumors.

Adoptive Transfer↗

Toxicity, pharmacokinetics, and in vitro hemodialysis clearance of ifosfamide and metabolites in an anephric pediatric patient with Wilms' tumor.

PURPOSE: We evaluated the in vitro hemodialysis ratio and subsequent toxicity and pharmacokinetics of ifosfamide in an anephric patient with Wilms' tumor. METHODS: An in vitro model was used to determine the extraction ratio of ifosfamide by dialysis. The toxicity and plasma concentrations of ifosfamide, chloroacetaldehyde, and 4-hydroxyifosfamide were then determined over 24 h after a single 1.6 g/m2 dose of ifosfamide. Plasma concentrations were also measured before and after ten dialysis sessions during four courses of ifosfamide therapy. RESULTS: The in vitro hemodialysis model showed that ifosfamide was cleared with an extraction ratio of 86.7+/-0.5% and remained constant even at low concentrations of drug. The mean decrease in vivo following hemodialysis for ifosfamide, chloroacetaldehyde, and 4-hydroxyifosfamide were 86.9%, 77.2%, and 36.2%, respectively. The pharmacokinetic parameters for ifosfamide using model-independent methods were calculated: Vd = 0.23 l/kg, t1/2 = 4.8 h, and ClT = 3.30 l/h per m2. Ifosfamide-associated neurotoxicity was noted within hours of drug administration and improved rapidly following hemodialysis. CONCLUSIONS: The results of our study suggest that the pharmacokinetics of parent ifosfamide may not be substantially altered in patients with renal failure. Hemodialysis was shown to remove ifosfamide, chloroacetaldehyde, and 4-hydroxyifosfamide from the blood stream. Hemodialysis was also shown to reverse ifosfamide-related neurotoxicity.

Antineoplastic Agents, Alkylating↗

Preparing health care professionals for quality improvement: the George Washington University/George Mason University experience.

Seventy-seven medical, physician assistant, nurse practitioner, and health services management students were provided training in quality improvement, community-oriented primary care, and teamwork. These students were then formed into 13 interdisciplinary teams to apply their knowledge in underserved areas ("service learning") under a community and faculty preceptor.

Clinical Clerkship↗

Moderate wine consumption is associated with decreased odds of developing age-related macular degeneration in NHANES-1.

OBJECTIVE: To determine the association between alcohol intake and the risk of developing age-related macular degeneration (AMD). DESIGN: Case control study. PARTICIPANTS: The sample consisted of 3072 adults 45 to 74 years of age with macular changes indicative of AMD who participated in a nationally representative sample of the first National Health Nutrition and Examination Survey (NHANES-1) between 1971 and 1975: (a) the ophthalmology data set and (b) the medical history questionnaire. MAIN OUTCOME MEASURES: Alcohol intake and the risk of developing AMD were measured. AMD was determined by staff at the National Eye Institute by fundoscopy examination using standardized protocol. RESULTS: Overall, 184 individuals (6%) had AMD. We observed a statistically significant but negative association between AMD and the type of alcohol consumed in a bivariate model (OR 0.86; 95% CI 0.73, 0.99). In the same model, age maintained a consistently strong association with AMD (OR 1.08; 95% CI 1.06-1.11; P < .001). Among the different types of alcohol consumed in NHANES-1 (beer, wine, and liquor), the effect of wine, either alone (OR 0.66; 95% CI 0.55-0.79) or in combination with beer (OR 0.66; 95% CI 0.55-0.79) or liquor (OR 0.74; 95% CI 0.63-0.86), dominated the negative association observed between AMD and alcohol type. Additionally, a statistically significant and negative association between wine and AMD was noted after adjusting for the effect of age, gender, income, history of congestive heart failure, and hypertension (OR 0.81; 95% CI 0.67-0.99). CONCLUSION: Moderate wine consumption is associated with decreased odds of developing AMD. Health promotion and disease prevention activities directed at cardiovascular disease may help reduce the rate of AMD-associated blindness among older people. The nature and pathophysiology of this association warrant further investigation.

Age Factors↗

Requirement for NF-kappaB in osteoclast and B-cell development.

NF-kappaB is a family of related, dimeric transcription factors that are readily activated in cells by signals associated with stress or pathogens. These factors are critical to host defense, as demonstrated previously with mice deficient in individual subunits of NF-kappaB. We have generated mice deficient in both the p50 and p52 subunits of NF-kappaB to reveal critical functions that may be shared by these two highly homologous proteins. We now demonstrate that unlike the respective single knockout mice, the p50/p52 double knockout mice fail to generate mature osteoclasts and B cells, apparently because of defects that track with these lineages in adoptive transfer experiments. Furthermore, these mice present markedly impaired thymic and splenic architectures and impaired macrophage functions. The blocks in osteoclast and B-cell maturation were unexpected. Lack of mature osteoclasts caused severe osteopetrosis, a family of diseases characterized by impaired osteoclastic bone resorption. These findings now establish critical roles for NF-kappaB in development and expand its repertoire of roles in the physiology of differentiated hematopoietic cells.

Animals↗

Critical roles for the Bcl-3 oncoprotein in T cell-mediated immunity, splenic microarchitecture, and germinal center reactions.

Chromosomal translocations of bcl-3 are associated with chronic B cell lymphocytic leukemias. Previously, we have shown that Bcl-3, a distinct member of the I kappa B family, may function as a positive regulator of NF-kappa B activity, although its physiologic roles remained unknown. To uncover these roles, we generated Bcl-3-deficient mice. Mutant mice, but not their littermate controls, succumb to T. gondii owing to failure to mount a protective T helper 1 immune response. Bcl-3-deficient mice are also impaired in germinal center reactions and T-dependent antibody responses to influenza virus. The results reveal critical roles for Bcl-3 in antigen-specific priming of T and B cells. Altered microarchitecture of secondary lymphoid organs in mutant mice, including partial loss of B cells, may underlie the immunologic defects. The implied role of Bcl-3 in maintaining B cells in wild-type mice may related to its oncogenic potential.

Animals↗