Search PubMedSearch

Biomedical subjects

M McCormick

Publications and source records attributed to M McCormick.

At least 19 recordsLinked to original sources

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

Reconstitution of an operon from overlapping fragments: use of the lambda SV2 integrative cloning system.

We have used the lambda SV2 system [Howard and Gottesman. In Gluzman (Ed.), Eukaryotic Viral Vectors. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1982, pp. 211-216; in Inouye, M. (Ed.) Experimental Manipulations of Gene Expression. Academic Press, New York, 1983, pp. 137-153] to reconstitute the Salmonella typhimurium his operon from overlapping fragments. lambda SV2 can be propagated as an autonomously replicating plasmid or as a prophage integrated in the Escherichia coli chromosome at the lambda attachment site; our reconstitution was accomplished in the integrated state. We first inserted a portion of the his operon into lambda SV2 and integrated the resulting plasmid by site-specific recombination into the E. coli chromosome. This was achieved by brief induction of a resident prophage. The lysogen was then transformed with DNA from a lambda SV2 clone carrying the remainder of the his operon on an overlapping DNA fragment. The second plasmid was forced to integrate into the first by homologous recombination. When this recombination occurs at the his overlap, a lysogen carrying two lambda SV2 prophages is produced. One prophage carries the entire his operon and the other carries the his overlap region. The latter is removed by site-specific recombination, permitting further contiguous sequences to be sequentially added to the remaining prophage. This method should be applicable for the reconstitution and maintenance of large genes or gene clusters in the E. coli genome.

Alleles

Hürthle cell tumors: a twenty-five-year experience.

During a 25-year period (1959 through 1983), 54 patients with Hürthle cell tumors were treated and monitored at the University of Chicago Medical Center. Thirty percent were men and 70% were women; mean age at diagnosis was 46.7 +/- 13.2 years (range: 19 to 69 years). Tumors were grouped into three categories at the time of initial diagnosis: group 1, grossly malignant (four patients, or 7.5%); group 2, intermediate (partial capsular and/or subcapsular vascular invasion) (10 patients, or 18.5%); and group 3, benign appearing (40 patients, or 74%). Twenty-one (39%) of the patients had a history of low-dose, external radiation to the head and neck in childhood (including three of four grossly malignant lesions). A separate non-Hürthle cell thyroid carcinoma was found within the thyroid gland in 22 (50%) of the patients--79% were papillary and 21% were follicular carcinomas. In half of these, there was a history of childhood irradiation. During a mean follow-up period of 8.4 years (range, 22 days to 35 years), three additional Hürthle cell tumors were recognized as malignant after metastases were discovered--two were originally classified as intermediate lesions and one was in the benign-appearing group. Thus, seven of 54 of our patients (13%) had Hürthle cell carcinomas. One of the seven patients died of widespread metastases after 35 years, and the other six are currently free of disease. We believe that therapy of these lesions should be individualized. Total thyroid ablation (surgical procedure followed by radioiodine therapy) is appropriate for frankly malignant Hürthle cell cancers, for all Hürthle cell tumors occurring in patients who received low-dose childhood irradiation, for associated papillary or follicular carcinomas, and in those patients who exhibit partial capsular or subcapsular vascular invasion. On the other hand, single, well-encapsulated, benign-appearing Hürthle cell tumors may be treated by lobectomy and careful follow-up, since the chance that they will later exhibit malignant behavior is low (2.5% in our series and 1.5% among patients described in the recent literature).

Adenoma

Graves' disease and thyroid cancer.

The relationship between Graves' disease or its therapy and carcinoma of the thyroid remains uncertain. We studied 20 patients found to have thyroid cancer in glands previously treated for Graves' disease between 1961 and 1986 at the University of Chicago Medical Center. Sixteen (80%) occurred in women and four (20%) occurred in men. The mean age at operation was 37 years (range, 19 to 69 years) and did not differ by sex. Fifteen of the 20 cancers (75%) were papillary while five (25%) were follicular. Six individuals (30%) had a history of external radiation to the head and neck as an infant, child, or young adult. Two others had received radioiodine (RAI) therapy for Graves' disease 1 and 19 years earlier. Patients were divided into three groups: group I: four patients (20%) had a neck mass 4, 14, 20, and 41 years after having had a subtotal thyroidectomy (STT) for Graves' disease; three of four had a history of external irradiation therapy. These tumors behaved aggressively, resulting in the death of two of the four patients. group II: 11 patients (55%) had diffusely enlarge toxic goiters without a nodule. A carcinoma was diagnosed intraoperatively on frozen section in only two of these patients. The others received STT. After recognition on permanent section, those carcinomas that were 4 mm or greater in diameter received postoperative RAI. One recurrence occurred and was treated successfully with further RAI. group III: Five patients (25%) had Graves' disease and a palpable thyroid nodule. None of them had had a prior thyroidectomy for Graves' disease, as in group 1. Thyroid carcinoma was diagnosed in all patients preoperatively or intraoperatively, and a total thyroidectomy was performed. Each patient is alive and well with a mean follow-up of 5 years. Between 1971 and 1981, 194 patients had surgery for Graves' disease, and 10 (5.2%) were found to have an associated carcinoma; six patients (3.1% of the total) did not have a nodule or any other suspicion of malignancy before surgery. During the same time, 303 patients received RAI therapy for Graves' disease and one (0.3%) has subsequently developed thyroid carcinoma. Thyroid cancer associated with Graves' disease is found more commonly in surgically treated patients than in patients after RAI therapy. The greatest risk factor in our patients was previous external radiation to the head and neck. Such individuals should be treated with total thyroid ablation rather than the usual STT, since they are at risk of developing aggressive thyroid cancers if thyroid remnants are left.

Adult