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Biomedical subjects

M McCormick

Publications and source records attributed to M McCormick.

At least 19 recordsLinked to original sources

An empirical evaluation of the placebo run-in.

A prerandomization placebo run-in period is often used in an attempt to exclude potential clinical trial participants who are likely to be poor adheres. It is assumed that potential participants who are poor adherers during the run-in will be less likely to take medication during the trial. This assumption was tested in the Cholesterol Reduction in Seniors Program (CRISP), by prescribing placebo for a 3-week period, but not using the results of the run-in as an entry criterion. The CRISP study was a pilot study designed to compare the effects on lipids and the safety of two doses of lovastatin and placebo in persons 65 years of age and older. After general entry criteria were satisfied, each participant was prescribed placebo for a 3-week period. At the end of the 3-week period, all participants were randomized to one of the three treatment groups, regardless of their adherence to the placebo. Of the 431 participants in the study, 66 (15%) who took less than 80% of the prescribed placebo or who failed to return their unused placebo pills were classified as poor run-in adherers. Poor run-in adherence was associated with lower educational attainment. At 3 and 6 months of follow-up mean adherence was 89.3% and 83.4% among all participants. Exclusion of poor run-in adherers would have increased these means to 90.9% and 85.5%, respectively. Treatment effect as measured by fall in LDL cholesterol would have increased by 2.9 mg/dl in the 40 mg/day dose group at 3 months of follow-up with the addition of a placebo run-in. We conclude that a placebo run-in would have had little effect on the outcome of the CRISP study and would have substantially increased recruitment difficulties. Lower educated persons were more likely to be excluded by a placebo run-in, but the effect of the run-in on follow-up adherence was stronger in less educated participants. More research about the role of a placebo run-in is needed in order to determine the appropriate role of this method in clinical trials.

Aged

Initial symptoms as predictors of esophageal injury in alkaline corrosive ingestions.

The predictive value of initial clinical evaluation in the management of alkaline corrosive ingestion remains unclear. This multicenter study was designed to determine if specific clinical signs and symptoms following ingestion of alkaline corrosives could predict significant esophageal injury. Alkaline corrosives were defined by a pH greater than or equal to 12. Signs and symptoms previously suggested as predictive of significant esophageal injury were documented on a standardized data form. Esophagoscopy reports were reviewed blinded to initial symptoms. Three hundred thirty-six alkaline-corrosive ingestions were analyzed. The mean number of symptoms reported in patients who did not have esophagoscopy was 1.2, in patients who had esophagoscopy was 3.0, and in patients that had visualized second or third degree esophageal burns was 4.8. Of 88 patients who had esophagoscopy, 63 (72%) had both the esophagoscopy report and initial symptom assessment available. Esophagoscopy was positive, defined as second or third degree esophageal burns, in 18 of 63 cases (29%). All patients with significant burns were symptomatic. No single or group of initially reported signs and symptoms could identify all patients with potentially serious esophageal burns.

Abdominal Pain

As time goes by: children's early understanding of growth in animals.

Beliefs about naturally occurring transformations were examined in children aged 3 to 6 years in 4 experiments. Experiment 1 tested children's understanding that animals (but not artifacts) predictably get larger over time. Experiment 1a examined whether the results obtained in the first experiment could be attributed to an added memory component on the artifact task. Experiment 2 further examined beliefs about the aging of artifacts. In Experiment 3, color and shape (metamorphosis) changes of animals were investigated. At all ages, children appeared to understand that animals get larger and not smaller with age. While older children and adults allowed for rather dramatic changes in the size and shape of animals over the life span if the alternative involved decreasing in size with age, preschool children were less willing to accept these changes. Taken together, the results of these studies suggest that even young preschool children have 2 conceptual insights about natural transformations: that they are lawful and nonrandom, and that they are domain and mechanism specific. Further, children as young as age 3 are able to go beyond the perceptual appearance of animals in making judgments about transformations caused by growth. Implications for children's understanding of personal and species identity are discussed.

Animal Population Groups

Blood lead, calcium status, and behavior in preschool children.

To determine if calcium status is associated with blood lead levels and behavior, 64 black urban children aged 18 to 47 months were studied. Twenty-seven controls (blood lead levels, less than 1.45 mumol/L) were compared with 37 cases (blood lead levels, greater than or equal to 1.45 mumol/L) with respect to four calcium measures (calcium intake, serum calcium level, 1,25-dihydroxyvitamin D level, and bone densitometric findings) and three behavioral scores. Levels of 25-hydroxyvitamin D provided a measure of vitamin D sufficiency. As expected, blood lead level was associated with pica scores. However, none of the calcium measures differed between cases and controls. Controlling for four confounders (season, pica score, maternal education, and sex), yielded no significant differences between the two groups in the mean values of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D level. There was no interaction between blood lead level and the four covariates. No relationship could be demonstrated between calcium status and the pica scores.

Bone Density

Comparison of RA 131I treatment protocols for Graves' disease.

The efficacy of 131I therapy in achieving euthyroidism has been studied in a group of 264 patients followed for up to 10 yr. One hundred and eighty-six were given a dose adjusted for thyroid size and radioactive iodine uptake (Protocol 1), and a second group received the same dosage followed by antithyroid drug therapy plus potassium iodide for 15 days (Protocol 2). At 10-yr follow-up, 50-60% of patients were euthyroid. 25-29% of patients required 2 doses of 131I, and 4-5% required 3 doses. Fewer patients became hypothyroid when their pretreatment FTI was above the average value. More patients became hypothyroid, if their pretreatment test for antimicrosomal antibodies was positive. Patients who required a second dose of radioactive iodide had a significantly greater chance of having worsening of their ophthalmopathy than those who became hypothyroid after the first dose. Treatment with radioactive iodide under either protocol appears to achieve euthyroidism at 10 yr with an incidence higher than that achieved by antithyroid drugs and comparable to that reported for subtotal thyroidectomy.

Combined Modality Therapy

Natural history, treatment, and course of papillary thyroid carcinoma.

We have analyzed the course of papillary thyroid carcinoma in 269 patients managed at the University of Chicago, with an average follow-up period of 12 yr from the time of diagnosis. Patients were categorized by clinical class; I, with intrathyroidal disease; II, with cervical nodal metastases; III, with extrathyroidal invasion; and IV, with distant metastases. Half of the patients had a history of thyroid enlargement known, on the average, for over 3 yr. In 15% of patients given thyroid hormone, the mass decreased in size. The peak incidence of cancer was when subjects were between 20-40 yr of age. Tumors averaged 2.4 cm in size; 21.6% had tumor capsule invasion, and 46% of patients had multifocal tumors. Sixty-six percent of the patients had near-total or total thyroidectomy. The overall incidence of postoperative hypoparathyroidism was 8.4%, but the incidence was zero in 83 near-total or total thyroidectomies carried out by 1 surgeon. Twenty-five percent of the patients had continuing or recurrent disease, and 8.2% died from cancer. Deaths occurred largely in patients with class III or IV disease. Cervical lymph nodes were associated with increased recurrences, but not increased deaths. Extrathyroidal invasion carried an increased risk of 5.8-fold for death, and distant metastases increased this risk 47-fold. Age over 45 yr at diagnosis increased the risk of death 32-fold. Tumor size over 3 cm increased the risk of death 5.8-fold. Surgical treatment combining lobectomy plus at least contralateral subtotal thyroidectomy was associated, by Cox proportional hazard analysis, with decreased risk of death in patients with tumors larger than 1 cm and decreased risk of recurrence among all patients, including patients in classes I and II, compared to patients who underwent unilateral thyroid surgery or bilateral subtotal resections. By chi 2 analysis, 131I ablation of residual thyroid tissue after operation was associated with decreased risk of recurrence in tumors larger than 1 cm and decreased risk of death in patients in classes I and II with tumors more than 1 cm in size. The data strongly support the use of more extensive initial surgery in class I and II patients with tumors more than 1 cm in size as well as postoperative radioactive 131I ablation of thyroid remnant tissue.

Age Factors

Regulation of the metastatic phenotype by the E1A gene of adenovirus-2.

We have previously demonstrated that rat embryo cells transformed by the ras oncogene alone are both tumorigenic and highly metastatic when injected into nude mice. In contrast, rat embryo cells transformed with the ras oncogene and the adenovirus 2 (Ad2) Ela gene are tumorigenic but either fail to metastasize, or exhibit a very low metastatic potential. Here we demonstrate that transfection of the Ad2 Ela gene into several of the ras transformed rat embryo cell lines results in a dramatic reduction in metastatic potential relative to the parental cell line. Transfection of cDNAs for the 12S and 13S Ela transcripts showed that both gene products are capable of reducing the metastatic potential of the ras transformed cell lines, however the 12S cDNA was more effective. This effect is specific to the Ad2 Ela gene as ras transformed cell lines expressing the Ad12 Ela gene or the human N-myc gene maintained their high metastatic potential. We hypothesize that the Ad2 Ela gene may regulate the expression of one or more cellular genes that contribute to the metastatic phenotype.

Adenovirus Early Proteins

Effect of cardiac index and hematocrit changes on oxygen consumption in resuscitated patients.

Oxygen consumption (Vo2) has been found to depend on oxygen delivery (Do2) following resuscitation from hemorrhage in both humans and animals. The relative influence of blood flow and arterial oxygen (O2) content, the components of Do2, has not been separately assessed. To determine the relative contribution of content and flow, we determined Do2 and Vo2 while making systematic changes in cardiac index (CI) and hematocrit (HCT). Fourteen patients were studied within 36 hr of hypotension from which they were resuscitated to a HCT of 27.9 +/- 0.4% (mean +/- SEM). Following initial hemodynamic measurements, CI was manipulated by changing end expiratory pressure by increments of +/- 5 cm H2O and measurements were repeated. Patients were then transfused overnight to raise their HCT to 36.7 +/- 0.5% and measurements were repeated, varying CI in the same manner. The increase in HCT resulted in significant (P less than 0.05) increases in O2 delivery (+ 130 +/- 33 ml/min/m2), arterial O2 content (+ 3.9 +/- 0.3 vol%), and mixed venous O2 content (+ 3.7 +/- 0.4 vol%). O2 extraction decreased by 6 +/- 1% from 30 +/- 2%. The change in HCT did not alter Vo2 (143 +/- 7 ml/min/m2), CI (3.6 +/- 0.2 L/min/m2), or intrapulmonary shunt (18.1 +/- 1.7%). However, as CI was changed at both levels of HCT, there were changes in Vo2 directly dependent on Do2. We conclude that oxygen consumption in patients resuscitated from hemorrhage may be influenced by oxygen delivery and that this influence is related more to flow than to arterial content.

Adult

The E1a gene of adenovirus type 2 reduces the metastatic potential of ras-transformed rat embryo cells.

We have previously demonstrated that second-passage rat embryo cells transformed by the ras oncogene alone are both tumorigenic and highly metastatic when injected into nude mice. In contrast, rat embryo cells cotransformed with the ras oncogene and the adenovirus type 2 (Ad2) E1a gene are tumorigenic but either fail to metastasize or exhibit a very low metastatic potential. In this report, we demonstrate that transfection of the Ad2 E1a gene into four independent ras-transformed rat embryo cell lines results in a dramatic reduction in metastatic potential relative to that of the parental cell line. Transfection of cDNAs for the 12S and 13S E1a transcripts showed that the 12S cDNA was highly effective in reducing the metastatic potential of ras-transformed cell lines, while the 13S cDNA showed an effect in only one of the two cell lines tested. This effect is specific to the Ad2 E1a gene, since ras-transformed cell lines expressing the Ad12 E1a gene maintained their high metastatic potential. We hypothesize that the Ad2 E1a gene may regulate the expression of one or more cellular genes that contribute to the metastatic phenotype.

Adenovirus Early Proteins

Sib selection.

Isolation of a particular clone from a library by sib selection is based on fractionating the library and choosing a positive subfraction which is consequently enriched for the clone of interest. The goal is to repeat this cycle until the enrichment process results in purification. As discussed in this chapter, particular patterns of fractionating are more efficient than others depending on the relative abundance of the clone, and the size of the original library. Importantly, sib selection is an isolation process that can be used in conjunction with any assay system. In particular, it may be used to isolate a gene from a library where there is an assay for the gene product, but no selection or sequence information available.

Animals

Factors predicting response of end stage squamous cell carcinoma of the head and neck to cisplatinum.

Cisplatinum significantly prolongs survival in end stage head and neck cancer but only 30-40% of patients respond. Many receive chemotherapy with little or no benefit and it would obviously be advantageous to determine in advance those patients likely to benefit. In 2 phase III trials of chemotherapy in end stage disease, 129 patients have been treated with cisplatinum, either alone or in 2-drug combination with bleomycin, methotrexate or 5-fluorouracil. Factors analysed in the entire group were age, sex, site, previous treatment, performance status and the use of cisplatinum in combination. A high albumen and oro- or nasopharyngeal site were significantly favourable, while a hypopharyngeal, middle ear, skin or paranasal site were all significantly unfavourable. In the separate analysis of the subgroup with recurrent disease, site of recurrence and time to recurrence were analysed in addition to the factors named above. Although similar trends to those in the entire group were observed none reached significant levels. In the subgroup with advanced previously untreated disease, histological grade was analysed in addition to the above factors. Good performance status emerged as significantly favourable. The emerging trends provide some insight regarding outcome but are not sufficiently clearcut to allow a decision to be made on who should and who should not be treated.

Antineoplastic Combined Chemotherapy Protocols

The 5'-flanking sequences of human globin genes contribute to tissue specific expression.

The specificity of expression of the isolated 5'-flanking sequences of the human beta- and epsilon-globin genes was examined in the K562 human erythroleukemia cell line, the murine erythroleukemia (MEL) cell, and in nonerythroid cell lines CV-1, HeLa-S3, and WI-38. Globin flanking sequences were active only in the erythroid K562 and MEL cell lines. Furthermore, the upstream sequence of the adult, beta-globin gene was active in MEL cells which express adult globin and not in K562 cells which express embryonic and fetal globins suggesting that tissue specificity resides in these upstream sequences. No expression was observed in K562 cells which have an embryonic-fetal hemoglobin phenotype.

Acetyltransferases