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Biomedical subjects

M Adams

Publications and source records attributed to M Adams.

At least 19 recordsLinked to original sources

A multicenter study of the treatment of childhood chronic idiopathic thrombocytopenic purpura with anti-D.

We evaluated the effects of the intravenous administration of anti-D, an immune globulin directed at the D antigen on erythrocytes that is purified from plasma from sensitized persons, on patients with idiopathic thrombocytopenic purpura. To determine the most effective dose, the duration of response, and the side effects of this therapy in children, we performed a multicenter cohort study of escalating doses of intravenously administered anti-D in children aged 1 to 18 years with chronic idiopathic thrombocytopenic purpura, defined as idiopathic thrombocytopenic purpura persisting for more than 6 months with a platelet count of less than 50 x 10(9) cells/L. Twenty-five Rh-positive children received increasing doses of anti-D as follows: day 1, 25 micrograms/kg; day 2, 25 micrograms/kg; day 7, 35 micrograms/kg; day 14, 45 micrograms/kg; and day 21, 55 micrograms/kg. Administration of anti-D was stopped after day 21 or when the platelet count rose to greater than 150 x 10(9) cells/L or the hemoglobin level was 100 gm/L. Platelet count was less than 50 x 10(9) cells/L in all children before treatment. A response was defined as an increase in the platelet count to more than 50 x 10(9)/L and a doubling of the pretreatment platelet count. Of 25 children, 23 (92%) had responses by day 7 of the initial treatment protocol. Eighteen children (72%) had platelet counts greater than 150 x 10(9) cells/L by day 7 after two doses of anti-D. Median duration of response was 5 weeks (range 1 to 24 weeks). Average drop in hemoglobin level was 13.7 gm/L; in one child (a nonresponder) hemoglobin value fell to less than 100 gm/L. No other untoward side effects were seen. Of the 23 children who responded, 21 were retreated with one dose of anti-D when platelet counts returned to baseline values of less than 50 x 10(9) cells/L; all but three of the children who underwent retreatment showed a response the second time. Sixteen children continued to receive intermittent anti-D therapy after completion of the study, and all continued to have excellent responses. We conclude that anti-D is a safe, effective, and relatively inexpensive therapy for childhood chronic idiopathic thrombocytopenic purpura.

Adolescent

Functional properties of a novel mutant thyroid hormone receptor in a family with generalized thyroid hormone resistance syndrome.

OBJECTIVE: We wished to ascertain whether a mutation in the thyroid hormone receptor beta gene was present in a family with generalized thyroid hormone resistance syndrome and to characterize the functional properties of this mutant receptor. DESIGN: Blood samples were obtained from family members for hormone assays and genomic DNA was isolated from leucocytes for genetic analyses. PATIENTS: Three members (B,C,E) of a family with possible thyroid hormone resistance and two normal family members (A,D) were studied. MEASUREMENTS: Basal thyroid function tests together with serum sex hormone binding globulin (SHBG) levels were measured. The thyroid hormone receptor beta gene was amplified using the polymerase chain reaction and the receptor mutation identified by sequence analysis. The ability of mutant receptor to bind T3, interact with a specific DNA sequence and to modulate target gene expression was tested. The effects of mutant receptor on co-expressed wild type receptor action were determined. RESULTS: Patients with resistance had raised levels of T4 and T3 together with inappropriately normal serum TSH and SHBG whereas unaffected individuals had a normal hormone profile. A single nucleotide substitution corresponding to a glycine to serine mutation at codon 340 (G340S) in the hormone binding domain was identified in one of the two beta receptor gene alleles in patients with resistance, but not in the normal family members. When expressed in vitro, this receptor protein (G340S), as well as a related (G340R) mutant identified in another family, retained the ability to bind to a specific DNA sequence but were unable to bind ligand or to activate or repress target gene expression. In addition both receptor mutants were capable of inhibiting the function of wild type thyroid hormone receptor in a co-expression assay but differed in their inhibitory potential. CONCLUSIONS: We report a second type of mutation (Gly to Ser) in codon 340 of hTR beta in a family with generalized thyroid hormone resistance. Mutations at this site eliminate T3 binding, causing a loss of hormone-stimulated receptor function. However, the mutant receptors retain the ability to block normal receptor action. The occurrence of different mutations at the same site suggests that alterations in this region of the receptor may be important for generating the clinical phenotype of this disorder.

DNA Mutational Analysis

Genetic characterization of Legionella pneumophila serogroup 1 associated with respiratory disease in Australia.

Techniques were developed for genetic characterization of Legionella pneumophila serogroup 1 by using restriction fragment length polymorphism analysis. Allozyme analysis provided an index of the discrimination achieved by restriction fragment length polymorphism. Isolates from human cases of legionellosis were examined by both methods, and their profiles were compared with reference strains of L. pneumophila serogroup 1 obtained from the American Type Culture Collection. Eighteen distinct clones were evident among the isolates examined. Both methods could be used to trace the source of an outbreak of legionellosis caused by L. pneumophila serogroup 1.

Australia

Effect of tamoxifen on cell lines displaying the multidrug-resistant phenotype.

We examined the effect of tamoxifen (Tmx), verapamil, and daunorubicin (DNR) in two cell lines that displayed the multidrug-resistant (MDR) phenotype and used laser flow cytometry to quantitate intracellular DNR content. In the vinblastine-resistant human lymphoblastic lymphoma cell line CEM-VBL, simultaneous incubation of DNR with Tmx 10 mumol/L or Tmx 50 mumol/L increased intracellular DNR fluorescence in a dose-dependent manner and demonstrated an uptake pattern similar to that seen with DNR and verapamil. Similar results were obtained in the vincristine-resistant human myeloid leukemia cell line HL-60/RV+. Cellular retention of DNR was also measured in both cell lines and results suggested that continuous exposure of the cells to Tmx resulted in higher intracellular DNR content compared with cells resuspended in fresh medium. No effect of Tmx or verapamil was observed in the drug-sensitive parent cell lines CEM or HL-60. Clonogenic experiments were then performed to determine whether Tmx was itself inhibitory to cell growth or whether Tmx potentiated DNR cytotoxicity. Tmx 10 mumol/L did not significantly inhibit either CEM-VBL or HL-60/RV+ cells after a 3-hour exposure followed by culture in methylcellulose. Tmx 50 mumol/L was significantly more inhibitory in both cell lines. However, cells that had been incubated with DNR and Tmx 10 mumol/L demonstrated a marked increment in growth inhibition compared with cells that had been incubated with DNR alone or Tmx 10 mumol/L alone. Based on the data presented here, we suggest that clinical testing of Tmx and DNR be pursued in the setting where MDR may play a role.

Cell Division

Information and education across the phases of cancer care.

Providing information to the cancer patient, is important but it is only one facet of patient education. Cancer patients also need to be taught new skills and shown new ways to cope. Patients who are not only informed, but are also educated and have more knowledge about their disease, are more likely to cooperate with treatment regimens and experience less stress and anxiety. One approach to identifying the content of cancer patient education is to focus on the various phases of cancer care. This approach provides a way for the patient and family to learn those aspects that are critical to coping with and adapting to the impact of the disease and its treatment. A number of researchers have begun to build the knowledge base important in identifying the appropriate educational content, methods for teaching, and approaches to evaluating teaching effectiveness. Future studies will continue to provide the scientific foundation for this most important aspect of cancer care.

Adult

Use of the SEER Cancer Registry for technology assessment.

The Surveillance, Epidemiology, and End Results (SEER) cancer registry contributed to technology assessment by providing population-based samples for detailed case-control studies, by serving as the control group in comparisons with various experimental groups, by allowing an assessment of selection bias in clinical trials, and by facilitating evaluations of classification and coding systems.

Databases, Factual

White cell depletion of red cell and pooled random-donor platelet concentrates by filtration and residual lymphocyte subset analysis.

This study comparing the relative white cell (WBC)-depleting efficiency of single and double filtration used two filters and new, sensitive, and reliable methods for performing WBC counts on WBC-depleted blood products. A single filtration of red cell (RBC) concentrates with a cotton-wool filter reduced WBC content by 98.64 percent, but the range of residual WBCs was wide, and many filtered units still contained more than the theoretical immunizing dose of 5 to 10 x 10(6) WBCs. A second filtration, however, always produced RBC units that had less than 5 x 10(6) WBCs. Although the degree of WBC depletion observed after a single filtration of a 6-unit pool of random-donor platelet concentrates was greater with a polyester filter than with the cotton-wool filter (98.92 vs. 98.14% reduction, respectively, when mean prefiltration WBC count was less than 600 x 10(6], in both cases, 25 percent of filtered products still contained greater than 5 x 10(6) WBCs; a second filtration (with the cotton-wool filter), however, produced units that were always below the immunizing dose. All double-filtered platelet concentrates had less than 10(6), and one-half had less than 10(4) residual WBCs. Platelet loss was similar with both filters (+/- 16% loss with one filtration). The effectiveness of the filters in producing products that were WBC-depleted below the immunizing dose was dependent on the prefiltration WBC content (but not on the age of the units), and it may be worthwhile to employ methods to ensure that total prefiltration WBC count of the product is less than 400 x 10(6).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD

Absence of HIV-1 DNA in high-risk seronegative individuals using high-input polymerase chain reaction.

Evidence of frequent HIV-1 infections in antibody-negative, high-risk individuals (so-called 'silent' infections) remains controversial. To evaluate whether these discrepant results may be the consequence of intermittent detection of rare infected cells (low viral load) preceding seroconversion, we developed a modification of the polymerase chain reaction (PCR) technique which enabled analysis of 10-fold greater amounts of cellular DNA per reaction than standard PCR (2 x 10(6) rather than 0.2 x 10(6) input cells). This technique allowed consistent detection of HIV-1 provirus in two seropositive individuals who had repeatedly tested negative by standard-input PCR. However, results were negative when high-input PCR was applied to 51 specimens from 39 selected high-risk seronegative individuals. These results suggest that variations in viral load preceding or in the absence of seroconversion probably do not explain discrepant evidence regarding silent HIV-1 infection.

Cohort Studies

Cardiopulmonary function during long-term central venous catheterization.

A prospective study was performed in an ambulatory group of infants, children, and young adults with neoplastic disorders to determine the prevalence of significant cardiopulmonary complications during long-term central venous catheterization. A cohort of 20 consecutive patients who had central venous catheters in situ for a mean of 13.5 months underwent pulmonary function testing, chest radiography, ventilation perfusion lung scintigraphy, electrocardiography, and echocardiography. No significant complications were seen. Specifically, there was no evidence of localized thrombus formation or pulmonary emboli, and no indirect evidence of pulmonary hypertension. In addition, we reviewed retrospectively the autopsy reports of 15 patients who died with central venous catheters in place. Three of these patients had superficial endocardial reactions. One patient had a right atrial mural thrombus related to the catheter, but two other patients were noted to have left atrial mural thrombi. This study demonstrates that central venous catheters can be used safely on a long-term basis in ambulatory patients requiring frequent venous access for treatment of their neoplastic disorders.

Adolescent

Life events, depression, and perceived problem solving alternatives in adolescents.

The association between negative life events and depression may be mediated by adolescents' sense of competency in solving problems. This study investigated (a) the relationship between troublesome life events and level of depression and (b) the association between level of depression and adolescents' perceived problem solving alternatives, in 135 tenth graders. The specific life events of "unemployment of a family member", "starting at a new school", and "breaking up with a boy/girlfriend", were associated with higher levels of depression. In addition, higher levels of depression were associated most consistently with the perceived alternatives of getting intoxicated and of isolating oneself in response to a variety of problems. Further research is needed to clarify both the extent to which depression influences adolescents' responses to negative life events and leads to poorer problem solving choices, and the degree to which negative life events and the lack of constructive problem solving alternatives increase the risk of depression.

Adaptation, Psychological

Graphical analysis of single-case time series data.

This article outlines the major principles for constructing good graphs and visual displays. Several methods for exploring time series data with graphical techniques are given: these include procedures for summarizing the central tendency of data, plotting linear and non-linear trend, and displaying variability and change in variability over time. We emphasize the need to explore single-case data thoroughly in order to highlight various components. Graphical analysis should be conducted in tandem with statistical analysis.

Data Display

Anticoagulants, iliopsoas hematoma and femoral nerve compression.

A case of bilateral compression femoral neuropathy due to iliopsoas muscle hematomas during anticoagulant therapy is described. Diagnosis was confirmed with computed tomographic scan. The right hematoma was larger than the left and caused a more severe femoral neuropathy. The hematoma on the right side was surgically evacuated, and the left-sided one was treated conservatively. The patient had a complete recovery.

Anticoagulants

Cardiovascular risks: among Black and White rural-urban low income women.

The purpose of this descriptive comparative pilot study was to determine if there are rural-urban and racial differences in the prevalence of four modifiable risk factors (blood pressure, serum cholesterol, diabetes and smoking) for cardiovascular disease among low income Black and White women. Of the 163 low income women who participated in the study, it was found that Black women had a significantly higher prevalence of elevated blood pressure and serum cholesterol levels than White women. The observed rates for smoking and diabetes were highest among rural White women. Implications for health education and continued research are presented.

Adult

Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia. The San Francisco community prophylaxis trial.

BACKGROUND AND METHODS: Pneumocystis carinii pneumonia (PCP) is the most frequent life-threatening opportunistic infection associated with human immunodeficiency virus (HIV) infection. To assess the possible value of aerosolized-pentamidine prophylaxis in different doses, a controlled clinical trial was begun in 1987 with 408 subjects at 12 treatment centers. The participants were randomly assigned to receive 30 mg of pentamidine every two weeks, 150 mg every two weeks, or 300 mg every four weeks. RESULTS: Eighteen months after randomization, the subjects in the 300-mg arm had had 8 confirmed episodes of PCP while receiving treatment, as compared with 22 in the 30-mg arm (P = 0.0008). The 150-mg arm had intermediate results but ones not significantly different from those of the 300-mg arm. Participants with previous episodes of PCP and CD4-cell counts less than 200 per cubic millimeter were at the highest risk for PCP. CONCLUSIONS: Aerosolized pentamidine was effective for prophylaxis against PCP in patients infected with HIV, according to the dose and schedule of administration. It and zidovudine were well tolerated together and had independent prophylactic benefits.

Adult

A cohort study of summary reports of controlled trials.

Substantial numbers of clinical trials continue to be reported only in summary reports that present insufficient methodological details to permit informed judgments about the likely validity of the conclusions. Using a cohort of 176 controlled trials reported in summary form, we tested the hypotheses that they would be more likely to be followed by full reports if, on the basis of the information provided in the summary report, (1) the trial was judged to be methodologically sound, (2) the results favored the test treatment, and (3) the sample size was relatively large. The results of univariate and multivariate analyses provided support for only the third of these hypotheses. Investigators, as well as those who fund and sanction the conduct of clinical research, should make greater efforts to ensure that clinical trials are reported properly.

Clinical Trials as Topic