Biomedical subjects
Publications and source records attributed to J Singer.
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Sixty-eight patients with moderate (n = 15) or severe (n = 53) aplastic anemia were entered into a prospective, randomized, two-arm treatment study comparing antihuman thymocyte globulin (ATG), lower-dose methylprednisolone (LDM) and oxymetholone to ATG, higher-dose methylprednisolone (HDM), and oxymetholone. There were no differences between the two groups when comparing age, sex, etiology of aplasia, disease duration, severity of aplasia, or pretherapy granulocyte counts. Side effects of LDM and HDM were similar. Of the 64 patients evaluable for response to therapy, 12 of 33 (36%) who received LDM had complete, partial, or minimal responses compared with 15 of 31 patients (48%) who received HDM (P = .33). Actuarial survival at 4 years is 43% for patients in the LDM group and 47% for patients in the HDM group (P = .99). Causes of death included hemorrhage, infection, evolution to acute leukemia, and complications of subsequent bone marrow transplantation. Long-term complications included paroxysmal nocturnal hemoglobinuria (n = 3), evolution to myelodysplasia or acute leukemia (n = 6), and recurrent aplasia (n = 6). We were unable to show a significant difference in toxicity, response rate, or survival for patients treated with ATG, oxymetholone, and LDM compared with patients who received ATG, oxymetholone, and HDM.
OBJECTIVE: To compare the use of indwelling catheters and intermittent catheterization in the management of urinary retention after surgical repair of hip fractures. DESIGN: Randomized open trial. SETTING: Orthopedic unit in a general hospital. PATIENTS: Patients 60 years or more admitted to hospital for surgical repair of a hip fracture between November 1986 and December 1987. Of the 76 who were eligible and agreed to participate 5 became medically unstable, 2 died before surgery, and 2 did not have urinary retention after surgery. The remaining 55 women and 12 men were randomly assigned to one of two treatment groups. INTERVENTION: An indwelling catheter inserted preoperatively was removed 48 hours after surgery (group 1); the procedure was repeated if necessary after 24 hours. Intermittent catheterization was performed every 6 to 8 hours (group 2); the frequency was adjusted to avoid bladder distension. MAIN OUTCOME MEASURE: Pattern of return to satisfactory voiding within 5 postoperative days. RESULTS: Of the patients in group 1, 37% resumed voiding within the 5-day postoperative period, as compared with 66% in group 2 (p less than 0.025). The mean numbers of days for return to satisfactory voiding were 9.4 and 5.1 respectively (difference 4.3 days, p less than 0.01, 95% confidence interval 0.7 to 8.0 days). Urinary tract infections developed in 31% of those in group 1 and 38% of those in group 2; the difference was not significant. CONCLUSION: Satisfactory voiding resumes earlier with the use of intermittent catheterization, if begun at the onset of urinary retention and repeated at regular intervals, than with the use of an indwelling catheter in elderly patients who have undergone surgical repair of hip fractures.
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Transfusion medicine laboratories routinely perform a series of pretransfusion serological tests including: ABO grouping, Rh typing, and investigation of the recipient's serum to detect antibodies against blood group antigens (antibody screen). As a final check, most laboratories also perform a crossmatch in which the recipient's serum is incubated with the donor's red cells followed by the addition of an antiglobulin reagent (antiglobulin crossmatch). The need for the antiglobulin crossmatch when the antibody screen is negative has been questioned because there are few antibodies that are detected by this test. Such antibodies are usually directed against low incidence antigens that are not expressed on the screening cells and in many cases the clinical importance of these antibodies is uncertain. For these reasons, we performed a prospective study in which patients requiring red cell transfusion had a group and screen performed. If the antibody screen was negative the antiglobulin crossmatch was omitted. Following the transfusion of the blood, the antiglobulin crossmatch was performed to look for any potential incompatibility. All patients were monitored both serologically and clinically. Over the 2-year interval of the study 9128 patients were entered. There were 8936 patients (97.9%) with a negative antibody screen and 26.9% (2404 patients) were transfused a total of 10,899 red cell concentrates. The antiglobulin crossmatch performed after the transfusion indicated that 168 red cell concentrates (1.5%) would have been incompatible if the antiglobulin crossmatch had been performed pretransfusion. These 168 red cell concentrates were transfused to 119 patients during 130 transfusion episodes (defined as all transfusions administered within 24 h). Of the 130 transfusion episodes, 79.2% (103/130) were false positive laboratory results. There were 27 transfusion episodes where the antiglobulin crossmatch on blood transfused was positive due to an IgG antibody. Even though these transfused red cell concentrates were designated incompatible by the antiglobulin crossmatch, none of the patients receiving this blood had clinical or serological evidence of haemolysis. We concluded that the antiglobulin phase of the crossmatch can be omitted from pretransfusion testing without putting patients at risk.
BACKGROUND: Whether respiratory muscle training is of benefit to patients with chronic airflow limitation is controversial. The objective of the study was to determine the effect of resistance breathing training on physiological and functional measures in patients with chronic airflow obstruction. METHODS: The design was a randomised, double blind, controlled trial with a six month follow up. Eighty two patients with a forced expiratory volume in one second (FEV1) of less than 70% predicted, and an FEV1/vital capacity ratio of less than 0.7, were randomised to receive training for 10 minutes five times daily with progressively larger resistances through a resistive breathing device (PFLEX) as tolerated or to a sham device which gave minimal resistance. The main outcome measures, respiratory muscle strength and endurance, a progressive exercise test, a six minute walk test and physical and emotional function (chronic respiratory questionnaire) were assessed at monthly intervals. Patients in both groups were also randomised to wear or not wear nose clips during their training. RESULTS: No significant differences were observed between treatment and control groups, with or without nose clips, for any of the outcomes. Confidence intervals on the difference between treatments were narrow, excluding clinically important difference in any major outcome. CONCLUSION: This training regimen fails to strengthen respiratory muscles or improve exercise or functional capacity in patients with chronic airflow limitation.
PURPOSE: The purpose of this report was to review the Seattle experience in bone marrow transplantation (BMT) for acute myeloid leukemia (AML) during untreated first relapse. PATIENTS AND METHODS: Through 1990, 126 patients were transplanted during untreated first relapse of AML. Several preparative regimens were used, two of which involved more than 20 patients. Regimen 1 (29 patients) consisted of cyclophosphamide (CY) 120 mg/kg and 15.75 Gy of fractionated total-body irradiation (TBI) with methotrexate (MTX) given intermittently during a 102-day period to prevent graft-versus-host disease (GVHD). Regimen 2 (22 patients) consisted of the same CY and TBI treatment and a combination of MTX and cyclosporine (CSP) for GVHD prophylaxis. The remaining 75 patients were treated with 17 other transplant regimens. Outcome was compared for patients who were treated with regimen 1, regimen 2, and any other regimen. RESULTS: The 5-year probabilities of relapse-free survival (RFS), relapse, and nonrelapse mortality for 126 patients were .23, .57, and .44, respectively. With regimen 1, relapse (.26) was significantly less than for regimen 2 (.70; P = .004) or any other regimen (.76; P = .004). Regimen 1 patients developed more acute GVHD (.67) than regimen 2 patients (.26; P = .02) or patients on other regimens (.41; P = .02), and had increased nonrelapse mortality. Nevertheless, regimen 1 patients had a significantly higher 3-year RFS (.38) than those treated with regimen 2 (.18; P = .04) or any other regimen (.20; P = .05). CONCLUSIONS: For patients who received 120 mg/kg CY and 15.75 Gy TBI, relapse incidence was less and survival was better after GVHD prophylaxis with MTX alone than after a combination of MTX and CSP, despite a significantly higher incidence of acute GVHD. The results of treatment with regimen 1 justify future studies of the optimal timing of allogeneic BMT in the treatment of patients with AML.
We have isolated a 5-kilobase pair fragment of genomic DNA containing the entire coding region for the Chlamydomonas reinhardtii gene encoding the copper-repressible Cyt c6. A region comprising 2.6 kilobase pairs contains the entire transcribed region plus 852 nucleotides upstream of the Cyt c6 transcription start site and 495 nucleotides downstream of the conserved C. reinhardtii polyadenylation signal. Comparison of the genomic sequence with the cDNA sequence (Merchant, S., and Bogorad, L. (1987) J. Biol. Chem. 262, 9062-9067) revealed that the coding region is interrupted by two introns, each of which is flanked by C. reinhardtii consensus intron/exon boundaries. Primer extension and S1 nuclease protection analyses identified the 5' border of the Cyt c6 mRNA at approximately 79 base pairs upstream from the initiator methionine. Analysis of the 5' upstream region reveals no significant similarity to sequences found in upstream regions of other copper-regulated genes. Time-course studies indicate that 1) the mature Cyt c6 mRNA has a half-life of approximately 45-60 min and is completely lost within 4 h, and 2) the primary, unspliced transcript has a half-life of approximately 10 min and is completely lost within 30 min after the addition of copper ions to copper-depleted cells. These results indicate that the response to copper occurs very rapidly upon elevation of extracellular copper levels. Although this gene is unresponsive to silver ions in vivo, in contrast to the yeast copper-responsive CUP1 gene (Furst, P., Hu, S., Hackett, R., and Hamer, D. (1988) Cell 55, 705-717), it does respond to mercury ions, albeit with less sensitivity. Mercury ions cannot, however, substitute for copper in allowing the accumulation of plastocyanin in vivo.
A Tn3 derivative was constructed to make small in-frame insertions within genes. The transposon contains the URA3 gene, the tetA gene, a truncated lacZ, and phage P1 loxP recombination sites at either end. Insertions that have fused lacZ to an open reading frame are lac+ because they express the truncated lacZ. In the presence of the phage P1 cyclization recombinase cre, the transposon can delete the URA3, tetA, and lacZ genes between the two loxP sites. The remaining short imperfect palindrome contains the ends of Tn3 and a loxP site and does not contain a translational termination codon in the correct reading frame. We have analyzed several insertions within the yeast HO gene. Several insertions inactivate HO and prohibit initiation of mating-type switching. In contrast, an epitope inserted in the central portion encodes a functional HO endonuclease.
This investigation was designed to determine the impact of a brief period of cardiac rehabilitation, initiated within 6 weeks of acute myocardial infarction (AMI), on both disease-specific and generic health-related quality of life, exercise tolerance and return to work after AMI. With a stratified, parallel group design, 201 low-risk patients with evidence of depression or anxiety, or both, after AMI, were randomized to either an 8-week program of exercise conditioning and behavioral counseling or to conventional care. Although the differences were small, significantly greater improvement was seen in rehabilitation group patients at 8 weeks in the emotions dimension of a new disease-specific, health-related Quality of Life Questionnaire, in their state of anxiety and in exercise tolerance. All measures of health-related quality of life in both groups improved significantly over the 12-month follow-up period. However, the 95% confidence intervals around differences between groups at the 12-month follow-up effectively excluded sustained, clinically important benefits of rehabilitation in disease-specific (limitations, -2.70, 1.40; emotions, -4.86, 1.10, where negative values favor conventional care and positive values favor rehabilitation) and generic health-related quality of life (time trade-off, -0.062, 0.052; quality of well-being, -0.042, 0.035) or in exercise tolerance (-38.5, 52.1 kpm/min); also, return to work was similar in the 2 groups (relative risk, 0.93; confidence interval, 0.71, 1.64).(ABSTRACT TRUNCATED AT 250 WORDS)
A randomized controlled trial with 76 physicians in 16 community hospitals evaluated audit and feedback and local opinion leader education as methods of encouraging compliance with a guideline for the management of women with a previous cesarean section. The guideline recommended clinical actions to increase trial of labor and vaginal birth rates. Charts for all 3552 cases in the study groups were audited. After 24 months the trial of labor and vaginal birth rates in the audit and feedback group were no different from those in the control group, but rates were 46% and 85% higher, respectively, among physicians educated by an opinion leader. Duration of hospital stay was lower in the opinion leader education group than in the other two groups. The overall cesarean section rate was reduced only in the opinion leader education group. There were no adverse clinical outcomes attributable to the interventions. The use of opinion leaders improved the quality of care.
OBJECTIVES: To determine what treatment decisions physicians will make when faced with an incompetent elderly patient with life-threatening gastrointestinal bleeding and to identify the factors that affect their decisions. DESIGN: Survey. SETTING: Family practice, medical and geriatrics rounds in academic medical centres and community hospitals in seven countries. PARTICIPANTS: Physicians who regularly cared for incompetent elderly patients. OUTCOME MEASURE: A self-administered questionnaire containing three case vignettes. Each provided the same details on an incompetent elderly patient; however, one gave no information about the wishes of the patient and his family (no directive), the second provided a do-not-resuscitate (DNR) request, and the third included a detailed therapeutic and resuscitative effort chart (DTREC) requesting maximum therapeutic care without admission to the intensive care unit (ICU). The four treatment options were supportive care only, limited therapeutic care, maximum therapeutic care without admission to the ICU and maximum care with admission to the ICU. MAIN RESULTS: Treatment decisions varied and were systematically related to age, level of training and country (p less than 0.001). The older physicians and those in family medicine were less likely than the others to choose aggressive treatment options. Brazilian and US physicians were the most aggressive; Australian physicians were the most conservative. The DNR request resulted in a significant decrease in the number of physicians choosing aggressive options (p less than 0.001). The DTREC resulted in a move toward more aggressive treatment, as outlined in the directive (p less than 0.001). Overall, however, about 40% of the physicians chose a level of care different from what had been requested. Furthermore, over 10% would have tried cardiopulmonary resuscitation despite the DNR request. CONCLUSION: Treatment of incompetent elderly patients with life-threatening illness varies widely within and between countries. Uniform standards should be developed on the basis of societal values and be communicated to physicians.
OBJECTIVE: To determine whether there is a difference in the quality of life between elderly patients managed in a day hospital and those receiving conventional care. DESIGN: Randomized controlled trial; assessment upon entry to study and at 3, 6 and 12 months afterward. SETTING: Geriatrician referral-based secondary care. PATIENTS: A total of 113 consecutively referred elderly patients with deteriorating functional status believed to have rehabilitation potential; 55 were assessed and treated by an interdisciplinary team in a day hospital (treatment group), and 58 were assessed in an inpatient unit or an outpatient clinic or were discharged early with appropriate community services (control group). OUTCOME MEASURES: Barthel Index, Rand Questionnaire, Global Health Question and Geriatric Quality of Life Questionnaire (GQLQ). MAIN RESULTS: Eight study subjects and four control subjects died; the difference was insignificant. Functional status deteriorated over time in the two groups; although the difference was not significant there was less deterioration in the control group. The GQLQ scores indicated no significant difference between the two groups in the ability to perform daily living activities and in the alleviation of symptoms over time but did show a trend favouring the control group. The GQLQ scores did indicate a significant difference in favour of the control group in the effect of treatment on emotions (p = 0.009). CONCLUSION: The care received at the day hospital did not improve functional status or quality of life of elderly patients as compared with the otherwise excellent geriatric outpatient care.
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OBJECTIVE: To determine the effectiveness of physician probability estimates calculated on the basis of findings from history-taking and physical examination in the diagnosis of iron deficiency anemia in elderly patients. DESIGN: Prospective study. SETTING: Two community hospitals offering secondary and tertiary care. PATIENTS: A total of 259 patients over 65 years of age found to have previously undiagnosed anemia. MEASURES: Physician estimates of the likelihood of iron deficiency before (pretest probability) and after (post-test probability) the laboratory test results were available. The hemogram was available to the physicians when they made their pretest probability estimates. Because the serum ferritin level proved to be the most powerful of the laboratory test results studied, the likelihood ratios associated with the post-test estimates were compared with the ratios associated with the serum ferritin level. MAIN RESULTS: The post-test probability estimates were influenced by the serum ferritin level and the pretest estimates. The post-test estimates derived from the findings obtained through history-taking and physical examination and the laboratory test results (including the serum ferritin level) were slightly less accurate in predicting iron deficiency than the serum ferritin level alone. Nevertheless, a model in which the pretest estimates were used in addition to the serum ferritin level to predict iron deficiency proved to be more powerful than the serum ferritin level alone (p = 0.006). This indicated that the limitations of the post-test estimates were due to a misinterpretation of the serum ferritin level and that the findings from history-taking and physical examination added important diagnostic information. CONCLUSIONS: Physicians must be aware of test properties to provide optimal care to their patients. If test results are properly interpreted, pretest probabilities derived from findings obtained through history-taking and physical examination can add useful information that will lead to more accurate diagnoses.
OBJECTIVE: To determine the efficacy of tetrahydroaminoacridine (THA) in Alzheimer's disease. DESIGN: Randomized, double-blind, multiple crossover trial with three treatment periods, each consisting of 3 weeks of active drug therapy and 3 weeks of placebo administration. SETTING: Referral-based geriatric practice in a community hospital. PATIENTS: Thirty-four patients with moderate to severe Alzheimer's disease. Subjects were included if they had stage 3 to 6 disease (as determined by the Reisberg scale) and had not been taking psychotropic drugs for at least 1 month and if informed consent had been obtained from the patients and their next of kin. INTERVENTIONS: Fifty to 100 mg of THA daily and matched placebo. RESULTS: Of the initial 34 patients 14 experienced liver toxicity and 3 gastrointestinal side effects during the study; however, all 22 who completed the study were able to tolerate at least the minimum dose. For the 22 patients there was no clinically or statistically significant effect of THA on cognition, functional status or behaviour. The results for individual patients showed no subgroup of THA-responsive patients. CONCLUSION: THA has no clinically important benefits in Alzheimer's disease and is associated with appreciable toxic effects.
OBJECTIVE: To examine the mechanisms through which two bronchodilators (theophylline and salbutamol) influence dyspnea during daily activities. METHODS: Twenty-four patients with chronic airflow limitation participated in a multiple crossover, randomized, placebo-controlled trial. The effect of theophylline and salbutamol, alone or combined, on pulmonary function and dyspnea during daily activities was examined. Correlations of changes in forced expiratory volume in 1 second (FEV1) and maximum expiratory pressures (MIPs) (independent variables) and changes in dyspnea score during daily activities (dependent variable) were also examined. RESULTS: The two drugs proved to be beneficial the effects in general were additive rather than synergistic. The drugs improved the FEV1; theophylline significantly improved the MIPs. The correlation between the changes in FEV1 and those in dyspnea score, after adjustment for the changes in MIPs, was 0.55 (p less than 0.001). The correlation between the changes in MIPs and those in dyspnea score, after adjustment for the changes in FEV1, was 0.39 (p less than 0.001). CONCLUSIONS: Changes in airway calibre and in respiratory muscle strength play an independent and important role in dyspnea during daily activities in patients with chronic airflow limitation. Changes in airway calibre may be of greater importance.