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Biomedical subjects

K Carlson

Publications and source records attributed to K Carlson.

At least 55 records · Page 3Linked to original sources

Effects of exercise on fatigue, aerobic fitness, and disease activity measures in persons with rheumatoid arthritis.

The effects of 12 weeks of low-impact aerobic exercise on fatigue, aerobic fitness, and disease activity were examined in a quasi-experimental time series study of 25 adults with rheumatoid arthritis (RA). Measures were obtained preintervention, midtreatment (after 6 weeks of exercise), end of treatment (after 12 weeks of exercise), and at a 15-week follow-up. ANOVAS for repeated measures showed that those subjects who participated more frequently reported decreased fatigue, while those who participated less frequently reported an increase in fatigue. All subjects, on average, showed increased aerobic fitness and increased right and left hand grip strength, decreased pain, and decreased walk time. There were no significant increases in joint count or sedimentation rate. Significant improvements in measures at the 15-week follow-up also were found. Findings indicate that persons with RA who participate in appropriate exercises may lessen fatigue levels and experience other positive effects without worsening their arthritis.

Adult↗

Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective case-matched study from the European Group for Blood and Marrow Transplantation.

A retrospective case-matched analysis was performed comparing 189 myeloma patients treated with allogeneic bone marrow transplantation (allo-BMT) with an equal number of patients who received autologous stem cell transplantation (ASCT). Matching was performed with respect to gender and number of treatment lines before transplantation. The groups were comparable with the exception of median age (43 years for allo-BMT v 49 years for ASCT, P = .0001) and median posttransplant follow-up (46 months for allo-BMT v 30 months for ASCT, P = .0003). The overall survival was significantly better for ASCT than for allo-BMT, with a median survival of 34 months and 18 months, respectively (P = .001). However, this survival advantage was only observed in men, but not in women. The statistically significant survival advantage for ASCT was seen in most subgroups, ie, chemotherapy-responsive patients, patients who had received two or more treatment lines before transplantation, patients in partial remission, patients with an IgG-subtype, patients older than 46 years of age, patients with stage II disease, and patients with a low or high serum-beta-2-microglobulin at diagnosis. The main reason for the poorer survival in allo-BMT patients was higher transplant-related mortality (41% v 13% for ASCT, P = .0001), which was not compensated for by a lower rate of relapse and progression. However, in patients alive at 1 year posttransplant, there was a trend for better long-term survival (P = .09) and significantly better progression-free survival (P = .02) for allo-BMT as compared with ASCT. We conclude that the median survival is superior for ASCT. However, allo-BMT has a lower relapse rate, which results in a similar long-term outcome for both approaches, but a longer follow-up is needed to assess the final outcome.

Acute Disease↗

Perception of breast cancer risk among women in breast center and primary care settings: correlation with age and family history of breast cancer.

BACKGROUND: A great deal of information about breast cancer risk is available to the public. The accuracy of impressions formed from this information is unknown. METHODS: A total of 750 women attending a breast center and 112 women attending a primary care office completed written surveys of their perceptions of average population risk, personal lifetime risk, and personal 10-year risk of getting breast cancer. Data sufficient to apply the Gail model were obtained, and a calculated estimate of risk was generated. Ratios of perceived to calculated risk were correlated with the respondent's age, family history of breast cancer, and location in a breast center or primary care office. RESULTS: Women in both practice settings overestimated population risk by more than twofold. Eighty percent overestimated personal lifetime risk by more than 50% and 35% by more than fivefold. Only 7% significantly underestimated risk. Ten-year risk estimates were even more inaccurate, with 69% overestimating risk by more than fivefold, 46% by more than 10-fold, and 17% by more than 20-fold. Results from a primary care population were nearly identical. Women at the extremes of age were most inaccurate in estimating risk. It was surprising that family history had little impact on perception of personal risk. CONCLUSIONS: Women in both breast center and primary care settings have a fals:ly high perception of both short-term and long-term breast cancer risk. Health care providers should recognize these misconceptions and be aware that many women may benefit from risk counseling.

Adult↗

Short-range and long-range context effects on coliphage T4 endonuclease II-dependent restriction.

Synthetic sites inserted into a plasmid were used to analyze the sequence requirements for in vivo DNA cleavage dependent on bacteriophage T4 endonuclease II. A 16-bp variable sequence surrounding the cleavage site was sufficient for cleavage, although context both within and around this sequence influenced cleavage efficiency. The most efficiently cleaved sites matched the sequence CGRCCGCNTTGGCNGC, in which the strongly conserved bases to the left were essential for cleavage. The less-conserved bases in the center and in the right half determined cleavage efficiency in a manner not directly correlated with the apparent base preference at each position; a sequence carrying, in each of the 16 positions, the base most preferred in natural sites in pBR322 was cleaved infrequently. This, along with the effects of substitutions at one or two of the less-conserved positions, suggests that several combinations of bases can fulfill the requirements for recognition of the right part of this sequence. The replacements that improve cleavage frequency are predicted to influence helical twist and roll, suggesting that recognition of sequence-dependent DNA structure and recognition of specific bases are both important. Upon introduction of a synthetic site, cleavage at natural sites within 800 to 1,500 bp from the synthetic site was significantly reduced. This suggests that the enzyme may engage more DNA than its cleavage site and cleaves the best site within this region. Cleavage frequency at sites which do not conform closely to the consensus is, therefore, highly context dependent. Models and possible biological implications of these findings are discussed.

Bacteriophage T4↗

Mutations in the homologous ZDS1 and ZDS2 genes affect cell cycle progression.

The Saccharomyces cerevisiae ZDS1 and ZDS2 genes were identified as multicopy suppressors in distinct genetic screens but were found to encode highly similar proteins. We show that at semipermissive temperatures, a yeast strain with a cdc28-1N allele was uniquely deficient in plasmid maintenance in comparison with strains harboring other cdc28 thermolabile alleles. Quantitative analysis of plasmid loss rates in cdc28-1N strains carrying plasmids with multiple replication origins suggests that a defect in initiating DNA replication probably causes this plasmid loss phenotype. The ZDS1 gene was isolated as a multicopy suppressor of the cdc28-1N plasmid loss defect. A zds1 deletion exhibits genetic interactions with cdc28-1N but not with other cdc28 alleles. SIN4 encodes a protein which is part of the RNA polymerase II holoenzyme-mediator complex, and a sin4 null mutation has pleiotropic effects suggesting roles in transcriptional regulation and chromatin structure. The ZDS2 gene was isolated as a multicopy suppressor of the temperature-sensitive growth defect caused by the sin4 null mutation. Disruption of either ZDS1 or ZDS2 causes only modest phenotypes. However, a strain with both ZDS1 and ZDS2 disrupted is extremely slowly growing, has marked defects in bud morphology, and shows defects in completing S phase or entering mitosis.

Adaptor Proteins, Signal Transducing↗

Outcome for patients with leukemia, multiple myeloma and lymphoma who relapse after high dose therapy and autologous stem cell support.

Relapses after autologous transplantation are a serious clinical problem in patients with haematological diseases. The decision making for handling of such patients is difficult and the aim of this retrospective analysis of posttransplant relapses was 1) to obtain information of practical importance for the management of future relapses and 2) to evaluate the basis for clinical phase I-II trials of salvage therapy combined with biological modifiers. Included in the study were 283 patients with acute leukemia, multiple myeloma and malignant lymphoma who relapsed after autologous transplantations during a five year period from 1989 to 1994. Chemo- and radiotherapy was given to 229 patients after relapse or due to progressive disease and the response evaluated after 90 days. Fifty four patients (24%) obtained a complete remission and 44 patients (19%) partial responses. The overall median survival from relapse was 5 months. In the group given salvage treatment the median survival was 7 months and in the 54 patients who obtained remission the median survival was 15 months. So far 6 of 14 patients in continuous complete remission have a remission time after relapse longer than the time in remission after transplantation. Survival after relapse depended upon the time from transplantation to relapse, primary disease and if salvage therapy was given. In conclusion posttransplant relapses can be treated but the strategy has to be evaluated in future clinical trials.

Adolescent↗

Autologous stem cell transplantation in multiple myeloma: results of the European Group for Bone Marrow Transplantation.

Autologous hematopoietic stem cell transplantation was used for treatment of 384 patients with multiple myeloma in 37 centers during the years 1986-1994. An analysis of prognostic factors was performed in 207 of these patients. One hundred forty one were males and 66 females, and median age was 49 years (range, 24-68). Actuarial survival at 78 months is 45%. Factors associated with a good prognosis were: response on chemotherapy immediately pretransplant, administration of only one treatment regimen, a low serum-beta 2-Microglobulin value at diagnosis and the use of a conditioning regimen including melphalan. In a multivariate analysis, response status pretransplant, age < 45 years, melphalan conditioning and non-TBI conditioning were independently predictive for longer survival, while transplantation after only one line of primary treatment and isotype other than light-chain were of borderline significance. Post-transplant alpha-interferon treatment was associated with improved survival in responsive patients. Eighteen patients treated in one center (Huddinge) passed a double autograft program, and 14 are in continuous complete remission ([CR]; n = 10) or good partial remission (n = 4) at a median time of 17 months after the first transplant (range, 2-38). In five CR patients, polymerase chain reaction (PCR)-analysis of the clone-specific immunoglobulin-rearrangement was performed, and four are PCR-negative up to 33+ months after the first transplantation. We conclude that autografting in myeloma is most effective when applied early in the course of disease in younger, chemotherapy-reponsive patients. Alpha-interferon maintaince treatment seems to be beneficial with respect to improved survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Regional and arterial localization of radioactive microparticles after local delivery by unsupported or supported porous balloon catheters.

Catheter-mediated intramural delivery of pharmaceutical agents after angioplasty is a potential method to reduce postangioplasty restenosis. The efficacy of such delivery has been limited both by an incomplete initial intramural deposition of delivered agents and by rapid diffusion of soluble agents from the site of delivery. The local delivery of microparticulate agents results in prolonged retention of material at the delivery site. Accordingly this study was designed to evaluate the complementary issue of the initial delivery efficiency and pattern of localization of microparticles after local catheter-mediated delivery with two types of porous balloons. These two types were a "standard" porous balloon (PB) in which hydraulic pressure both inflated the balloon and infused the agents and a porous balloon with a mechanical undergirding that permitted mechanical expansion (PB/ME) before agent infusion. Radioactive cerium 141-labeled microparticles (11.4 microns diameter) were locally delivered into atherosclerotic rabbit femoral arteries after angioplasty to test the hypothesis that use of the PB/ME apparatus would yield enhanced intramural particle deposition and decreased systemic administration by increased balloon-wall contact before microparticle infusion. Six animals underwent infusion with the PB catheter, and seven animals underwent infusion with the PB/ME catheter. An image of the in vivo particle distribution was obtained with a gamma camera during infusion, immediately after infusion, and 1, 3, and 7 days after infusion. Tissue samples from the artery, periadventitia, thigh, calf, and foot musculature, and liver were obtained at animal death, and retained radioactivity was measured with a well counter.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗

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Emergency Nursing↗

MR imaging of multiple myeloma in tumour mass measurement at diagnosis and during treatment.

The bone marrow of the spine, pelvis and proximal femora was examined with MR imaging at diagnosis in 30 cases of multiple myeloma (MM), and during treatment on 69 occasions. The MR pattern was normal, focal or diffuse and correlated to stage. A tumour mass index (TMI) was calculated by estimating the total myeloma mass visualised at MR imaging. The TMI correlated significantly with stage, lytic bone lesions, serum calcium, serum beta-2-microglobulin and survival. No abnormalities were seen at MR investigation in 4 of 6 patients classified as stage II because of osteoporosis only. Therapy efficacy evaluation with MR imaging corresponded to clinical evaluation on 54 of the 69 occasions. MR examination of bone marrow in MM patients can be used for tumour mass assessment, both at diagnosis and during follow-up. Valuable information can be obtained when the tumour mass is difficult to estimate using clinical criteria, e.g. in non-secretory MM or when osteoporosis is the only variable indicating an increase in the tumour mass.

Aged↗

Acute effects of high-dose chemotherapy followed by bone marrow transplantation on serum markers of bone metabolism.

There is an interplay between the cells in the bone marrow and the surrounding bone tissue, but little is known about the effects of myeloablative treatment followed by bone marrow transplantation on bone metabolism. We have therefore investigated 24 patients undergoing bone marrow transplantation (14 autologous, 10 allogeneic) for hematological malignancies. Serum concentrations of parathyroid hormone (PTH), albumin-modified calcium, and biomarkers for bone turnover--osteocalcin, bone alkaline phosphatase (B-ALP), and carboxyterminal cross-linked telopeptide of type I collagen (ICTP)--were measured. The samples were collected before myeloablative treatment, on the day of bone marrow infusion and 1, 2, 3, and 12 weeks thereafter. A serum PTH peak was consistently seen the day after total body irradiation, but no long-term effects on PTH/calcium homeostasis were observed. Bone formation as reflected by serum osteocalcin and B-ALP decreased, with nadir levels 2 to 3 weeks after marrow infusion. A simultaneous increase in bone resorption (increased S-ICTP) occurred. Pretreatment values were not completely regained 12 weeks after transplantation. The findings indicate that bone tissue is affected by myeloablative treatment, and the changes in biomarkers imply a net loss of bone over the study period.

Adolescent↗

A late exclusion of bacteriophage T4 can be suppressed by Escherichia coli GroEL or Rho.

A litCon mutation in Escherichia coli TU6 results in exclusion of bacteriophage T4 during the late, morphogenetic stage of its development at low temperatures. DNA was synthesized continuously in the infected cells, but less than 10% of the DNA made by 90 min after infection was packaged into DNAase-resistant particles, few viable phage were formed, and the cells lysed poorly. The exclusion could be relieved by conditions leading to elevated levels, determined immunologically, of the E. coli Rho protein (believed to be involved in regulation of T4 transcription), or chromosomally encoded E. coli GroEL (a chaperone known to be involved in phage assembly), or by supplying GroEL in trans from a plasmid. The two suppressing proteins appeared to act independently of each other. GroEL-suppression restored packaging to normal levels, perhaps by preventing GP23 from activating the host Lit protein; in addition DNA synthesis was delayed and reduced and cell lysis enhanced, demonstrating involvement of GroEL in both these processes. Rho suppression was less efficient. Since both transcription-termination-proficient and transcription-termination-deficient Rho suppressed, the results raise the possibility that Rho has a role during T4 development not directly involving transcription regulation.

Bacterial Proteins↗

Prognostic factors in autologous stem cell transplantation for multiple myeloma: an EBMT Registry Study. European Group for Bone Marrow Transplantation.

Autologous bone marrow- and blood progenitor cell transplantation was performed in 130 patients with multiple myeloma in 16 European centers between 1986 and 1993. At the time of follow-up, 77 patients were alive and 53 were dead. Complete remission after transplantation was obtained in 47% of all patients. The actuarial survival at 65 months was 28%. The median duration of relapse-free survival among patients who were in complete remission after transplantation was 29 months. The following factors were predictive for longer survival and freedom of progression in a univariate analysis: Male sex, age less than 45 years, a low serum-beta-2-microglobulin value at diagnosis, prior administration of only one treatment regimen, response on conventional chemotherapy immediately pretransplant and the use of a preparative regimen including melphalan. The last factor, in addition to stage I disease at diagnosis, male sex and responsive disease immediately pretransplant, were also demonstrated as independent predictive variables for longer survival in a multivariate analysis. Progression-free survival was significantly better for patients who were in complete remission after transplantation, as compared to those with persisting signs of disease. We conclude that high-dose chemo-radiotherapy with autologous stem cell transplantation can induce long-term responses, primarily in younger, male patients with chemotherapy-responsive early disease. High-dose melphalan, as single drug or in combination, appeared to be superior to other regimens. The chance of being persistently disease-free seemed to be greatest for patients being in complete remission already before the transplantation.

Adult↗

Subclinical disturbances in cardiac function at rest and in gas exchange during exercise are common findings after autologous bone marrow transplantation.

A study was undertaken to examine the effects of autologous bone marrow transplantation (BMT) on cardiac function at rest (n = 111) and pulmonary gas exchange during exercise (n = 110). Left ventricular cardiac ejection fraction (LVEF) was measured by radionuclide ventriculography before autologous BMT and after 6 months and 1, 3 and 5 years. Expired gas volume per oxygen consumption (VE/VO2) and transcutaneous PO2 were measured at rest and during submaximal exercise before and 6 and 12 months after autologous BMT, and the alveolar-arterial oxygen difference was calculated after 12 months. In lymphoma patients conditioned with BCNU, cyclophosphamide, etoposide and cytarabine, a long-lasting reduction in LVEF of 11 +/- 14% mean (+/- SD) was noted. The risk of cardiac deterioration was not increased by a subnormal LVEF before autologous BMT or total body irradiation (TBI). Impaired gas exchange during exercise was a common feature, but severe disturbances were uncommon. During exercise transcutaneous PO2 fell pathologically in 15% and 20% of the patients examined after 6 and 12 months, respectively, and the alveolar-arterial oxygen difference increased pathologically in 50% after 12 months. The VE/VO2 ratio increased significantly during exercise 6 months after autologous BMT in TBI-treated patients.

Adolescent↗

Pulmonary function and complications subsequent to autologous bone marrow transplantation.

Risk factors for early pulmonary complications occurring within the first 3 months after autologous bone marrow transplantation (BMT) were analysed in 158 consecutive adults. The long-term effects of autologous BMT on pulmonary function were analysed in 102 patients, who had survived free of disease for > 6 months after autologous BMT. Pulmonary function tests were performed before, at 6 and 12 months after autologous BMT and thereafter annually. The median follow-up was 12 (6-60) months. The incidence of early pulmonary complications was 16% (26 of 158). Idiopathic interstitial pneumonitis was seen in 11% of patients treated with total body irradiation (TBI). Single dose TBI was the major risk factor as regards early pulmonary complications but restrictive pulmonary disturbances and impaired diffusing capacity prior to autologous BMT were also significant risk factors. In both non-TBI and TBI-treated patients a mild restrictive ventilatory dysfunction and impaired diffusing capacity was noted 6 months after autologous BMT. In non-TBI-treated patients, these disturbances had resolved completely within 2 years whereas the lung volumes of TBI-treated patients were persistently reduced by 10% of their pre-autologous BMT values during follow-up. However, dysfunctions rarely progressed 6 months after autologous BMT. In most patients, ventilatory dysfunction was slight and had no clinical significance.

Adolescent↗

Pulmonary function after autologous bone marrow transplantation in children.

Forty-two children receiving bone marrow autografts were studied prospectively regarding acute pulmonary complications; there was no procedure-related mortality and only one case of interstitial pneumonitis. An analysis was also made of the pulmonary function tests (PFTs) of the 27 autografted children who were disease-free and had been followed up for at least 1 year (median 4.1 years, range 1.1-7.6 years). PFTs were performed before and 6, 12, 24, 36 and 60 months after autologous BMT. The mean pre-transplant values of total lung capacity (TLC), vital capacity (VC) and forced expiratory volume in one second (FEV1) were close to predicted but 6 months after autologous BMT there was a statistically significant decrease (11, 13 and 15% below baseline, respectively) in patients receiving total body irradiation in their conditioning regimen. There was some but not complete recovery with time. DLCO remained low throughout the study, irrespective of the conditioning regimen. In summary, acute pulmonary complications were few and PFTs showed only modest changes from baseline after ABMT. At the latest follow-up no respiratory symptoms had reportedly occurred in any of the children and the chest radiographs were normal. Although the results are promising so far, long-term follow-up is necessary to evaluate the final outcome in these children.

Adolescent↗

DNA determinants of restriction. Bacteriophage T4 endonuclease II-dependent cleavage of plasmid DNA in vivo.

Endonuclease II of coliphage T4 is necessary for the in vivo restriction of plasmid DNA in phage-infected cells. Double-stranded restriction cleavage at 12 sites in pBR322 commenced before 10-min postinfection with T4 at 37 degrees C and proceeded more slowly in the presence of competing phage DNA than in its absence, utilizing the same sites in both cases; in a 200-base pair segment of the plasmid, single-stranded nicks also were frequent. The plasmid sites were cleaved with a speed that varied with the site, yielding frequencies of cleavage at different sites varying between 10 and 90%, at 50-min postinfection. All sites contained good matches to a consensus, 5'-GRCCGCNTYGC-3', most frequently cleaved around the variable central base pair, generating fragments with blunt ends or 1-2-base 5' overhangs. Using the frequency of cleavage to determine a weighted consensus, a larger sequence, 5'-CGRCCGCNTTGSYNGC-3', was identified. Thus, DNA sequence elements 3' to the cut site appear important for rapid cleavage. Several models describing the sequence-dependent structure of DNA suggest structural anomalies around the cleavage sites. The endonuclease II restriction system is most similar to type II systems, although it differs from known type II systems in several respects.

Amino Acid Sequence↗