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Biomedical subjects

T Karrison

Publications and source records attributed to T Karrison.

At least 55 records · Page 3Linked to original sources
PubMed1991

Increased all-cause and cardiac morbidity and mortality associated with the diagonal earlobe crease: a prospective cohort study.

PURPOSE: To ascertain whether the diagonal earlobe crease (ELC) is associated prospectively with future death or cardiac events over 8 years of follow-up in two sets of patients: those with known coronary artery disease (CAD) and those without evidence for CAD. PATIENTS AND METHODS: We performed a prospective, observational study of 108 patients in four cohorts (each matched for age, sex, and race, but differing in the presence or absence of both a diagonal ELC and CAD in 1979 to 1982). Follow-up information was gathered by telephone interviews, and dates and causes of death were determined by reference to death certificates (n = 48), hospital records (n = 9), or attending physician statements (n = 1). RESULTS: During 8 to 10 years of follow-up, 58 of the patients had died. Patients with ELCs had poorer survival rates than those without creases, by stratified log-rank test (p = 0.006 for the cohorts thought not to have CAD, and p = 0.058 for those with CAD). Cardiac death rates (due to acute myocardial infarction, "sudden cardiac death," or heart failure) were also higher for patients with ELCs: 8.0 versus 0.9 cardiac deaths per 100 patient-years (p less than 0.001) in patients without CAD at entry, and 11.7 versus 3.7 cardiac deaths per 100 patient-years (p = 0.008) in patients with CAD in 1979 to 1982. Cardiac event rates (cardiac death, nonfatal myocardial infarction, or coronary artery bypass surgery) were also higher in those with ELCs: 10.4 versus 1.4 events per 100 patient-years (p less than 0.001) for those without known CAD, and 15.8 versus 5.7 events per 100 patient-years (p = 0.009) for those with CAD. CONCLUSION: These results suggest that a diagonal ELC is associated with increased all-cause and cardiac morbidity and mortality. Patients with ELCs may be at higher risk for coronary events, and might be especially cautioned to control or reduce other cardiac risk factors, even if currently without diagnostic evidence of CAD.

Aged↗
PubMed1991

Efficacy of daily routine chest radiographs in intubated, mechanically ventilated patients.

OBJECTIVE: To determine the efficacy of daily routine chest radiographs in intubated, mechanically ventilated patients. DESIGN: With approval of our Institutional Review Board, data were collected prospectively to compare bedside clinical assessment of the patient with the routine chest radiograph in determining the occurrence of new findings. Before review of the daily chest film, patients underwent careful evaluation of clinical and physiologic variables by critical care physicians, who then documented the new findings and the diagnostic and therapeutic interventions required. These results were compared with the interpretations of the daily chest film by radiologists blinded to the clinical assessment. Correlations were made of the new major (requiring immediate intervention) and new minor (abnormal but not requiring immediate intervention) findings noted by clinical assessment and chest radiography. SETTING: This study was conducted in a ten-bed medical/surgical ICU admitting 650 to 750 patients/yr, a majority of whom require intubation and mechanical ventilation. PATIENTS: Seventy-seven episodes of intubation and mechanical ventilation in 74 patients were evaluated. Only patients with translaryngeal intubation and a requirement for mechanical ventilation beyond 24 hrs were considered for inclusion in this study. Major admitting diagnoses included malignancy, aspiration pneumonia, sepsis, liver failure, chronic obstructive pulmonary disease, and adult respiratory distress syndrome. INTERVENTIONS: Specific interventions were not made by study design; instead, clinical practice with and without the routine chest radiograph was compared. MEASUREMENTS AND MAIN RESULTS: The measure of comparison between the chest radiograph and clinical assessment was the correlation between the two for a number of major and minor findings defined in advance. A total of 538 chest radiographs were examined; of these, 354 (65.8%) did not disclose either new major or new minor findings as defined. One hundred sixty-three radiographs disclosed only new minor findings, 40.5% of which were anticipated by bedside assessment. However, in 13 (17.6%, 95% confidence interval 9% to 26%) of our 74 patients, new major findings were discovered only by chest radiography. CONCLUSIONS: These data demonstrate that, while a large percentage of radiographs will not disclose new findings, routine daily studies have a substantial impact on the management of intubated, mechanically ventilated patients in the ICU. These findings support the use of daily chest radiographs in critically ill patients.

Adolescent↗
PubMed1989

Heterogeneity of O6-alkylguanine-DNA alkyltransferase activity in peripheral blood lymphocytes: relationship between this activity in lymphocytes and in lymphoblastoid lines from normal controls and from patients with Hodgkin's disease or non-Hodgkin's lymphoma.

We determined O6-alkylguanine-DNA alkyltransferase (AGT) activity in the peripheral blood lymphocytes (PBLs) of normal controls and patients with Hodgkin's disease or non-Hodgkin's lymphoma and compared these values with those of Epstein-Barr virus (EBV)-transformed cell lines prepared from the same PBL samples. PBLs have an AGT level characteristic of the individual from whom the cells were obtained. The AGT activity of lymphoblastoid cell lines obtained from a control group of PBLs was significantly correlated with the activity of the PBLs from which they were derived (r = 0.742). There was no significant correlation between PBLs and EBV-transformed lines derived from these PBLs in Hodgkin's disease/non-Hodgkin's lymphoma patients (r = 0.407, -0.225, and 0.270 for patients prior to, during, or after therapy, respectively). The lack of significant correlation between lines and PBLs was not due to random fluctuations in AGT activity, because multiple lines prepared from the same PBL sample were found to be highly correlated in AGT activity. In order to account for these results, we suppose that PBLs from a given individual are a heterogeneous population with respect to AGT activity. In normal individuals, the AGT activity of early passages of the multi-clonal EBV-transformed cell lines reflect the AGT activity of the PBLs from which they were derived. Malignancy and/or treatment with chemotherapeutic agents may selectively affect those lymphocytes which are targets for EBV-transformation so that the resultant cell line is no longer representative (with respect to AGT activity) of the total PBL population. Long-term culture of lymphoblastoid cell lines results in changes in AGT activity in some but not all cell lines suggesting that with time in culture, subsets with different AGT activities may be selected. There appears to be no growth advantage of low AGT activity and only rarely have we obtained lines with no measurable AGT activity, even after long periods in culture.

Cell Transformation, Viral↗
PubMed1989

A controlled trial of extended radical versus radical mastectomy. Ten-year results.

In view of increasing debate over possible benefit of more complete surgery compared to conservative procedures, a randomized controlled trial contrasting the then standard Halsted radical (RDL) operation with the more complete extended radical (EXT) mastectomy was initiated in 1973. Between November 1973 and July 1982, 123 women younger than 70 years of age and at clinical Stages I and II were enrolled. Of the total series, 112 were treated by the same surgeon and confirmed pathologically as having invasive mammary carcinoma. In this more homogeneous subgroup, the 10-year survival rates (and standard errors) were for RDL, 60% (+/- 7%) and for EXT, 74% (+/- 6%) (P value for comparison of survival curves = 0.13). In patients from this subgroup with central-medial tumors, comprising 62% of the total, survival after RDL at 10 years was 60% (+/- 8%), and after EXT 86% (+/- 6%) (P = 0.025). In the remaining patients with lateral tumors, survival rates were unaffected by treatment: 58% (+/- 13%) and 56% (+/- 11%), respectively (P = 0.62). Comparison of a nonrandomized series of 266 RDL and 124 EXT patients treated between 1960 and 1978 found differences consistent with those of the randomized study, although not statistically significant.

Aged↗
PubMed1989

Chromosomal sensitivity of lymphocytes from individuals with therapy-related acute nonlymphocytic leukemia.

A small fraction of those individuals exposed to cytotoxic chemotherapy or radiation for the treatment of a primary malignant disease will develop a second malignancy some time later. Although exposure to the cytotoxic agents is believed to be the causative factor, the reason only certain individuals develop the second malignancy is unknown. Some studies have suggested that these individuals might be predisposed to cancer because of an inherent sensitivity to the alkylating agents used in cancer therapy. We have reported that these individuals with therapy-related acute nonlymphocytic leukemia (t-ANLL) have reduced endogenous levels of the repair protein O6-alkylguanine alkyltransferase (AGT). To further investigate the etiology of this disease, alkylation-induced sister-chromatid exchange (SCE) formation in individuals who developed second malignancies, was compared to other patient groups and normal controls. Peripheral blood lymphocytes from patients with (1) t-ANLL, (2) primary forms of acute nonlymphocytic leukemia (ANLL de novo), (3) patients with primary malignancies at risk of developing secondary disease, and (4) unexposed, healthy controls were treated in vitro with N-methyl-N'-nitro-nitrosoguanidine or mitomycin C. Baseline and mutagen-induced frequencies of SCEs were determined. These studies failed to detect any increased sensitivity in those patients who developed second malignancies as compared to controls or patients with de novo forms of the same disease. Also, no correlation between sensitivity to the alkylating agent N-methyl-N'-nitro-nitrosoguanidine and endogenous levels of the AGT repair protein was found. These results suggest that t-ANLL patients are not sensitive to SCE induction by either MNNG or MMC.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1988

Low O6-alkylguanine DNA alkyltransferase activity in the peripheral blood lymphocytes of patients with therapy-related acute nonlymphocytic leukemia.

Chemotherapeutic agents such as procarbazine, which produce methylated bases in DNA, are used to treat many Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) patients. A small proportion of such patients develop secondary malignancy. We examined the possibility that those patients who develop secondary malignancy have low endogenous levels of O6-alkylguanine DNA alkyltransferase (AGT) activity and are therefore more sensitive to the mutagenic and carcinogenic effects of their treatment. We assayed AGT activity in peripheral blood lymphocytes from patients with HD, NHL, acute nonlymphocytic leukemia (ANLL) de novo, and therapy-related ANLL, as well as a group of normal control subjects. Studies in normal controls showed that at least over a short term of 1 week, individuals have characteristic AGT levels, although some individuals sampled repeatedly over several months showed high variation. Mean AGT activities +/- SE for the various groups studied were (fmol/micrograms of DNA): normal control group, 7.05 +/- 0.36; HD and NHL patients (prior to treatment), 4.97 +/- 0.42; HD-NHL patients receiving procarbazine, 3.88 +/- 0.44; ANLL de novo, 7.78 +/- 1.72; and therapy-related ANLL, 4.30 +/- 0.58. AGT activity decreased in the peripheral blood lymphocytes of some individuals taking procarbazine. The mean AGT activity in the procarbazine-treated patients was low, as was the activity for the therapy-related ANLL patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Dose-dependent effects of oral and intravenous glucose on insulin secretion and clearance in normal humans.

Insulin secretion and clearance were studied in 2 groups of 7 normal subjects who each received 25, 50, and 100 g of glucose either orally or intravenously (iv) on separate occasions. Insulin secretion rates were calculated during a 1-h base line and for 5 h after glucose administration from a two-compartmental analysis of peripheral C-peptide concentrations using individual kinetic parameters derived after iv bolus injections of biosynthetic human C-peptide. Incremental glucose areas after oral or iv glucose increased as a function of the glucose dose (P = 0.0001). Incremental insulin secretion increased with increasing doses of both oral and iv glucose (P = 0.0001). The metabolic clearance rate (MCR) of endogenous insulin was calculated as the ratio of the total area under the insulin secretion rate curve and the simultaneous peripheral insulin concentration curve. The basal MCR was 1,879.5 +/- 110.5 ml/min (mean +/- SE). The poststimulatory MCR decreased with increasing doses of both oral and iv glucose concomitant with the greater insulin secretory response (P = 0.0014). This decrease in insulin clearance was not significantly different between oral and iv administration of glucose (P = 0.495). In conclusion diminished insulin clearance may be seen after marked stimulation of insulin secretion with larger doses of oral and iv glucose.

Administration, Oral↗
PubMed1988

Quantitative study of insulin secretion and clearance in normal and obese subjects.

The secretion and hepatic extraction of insulin were compared in 14 normal volunteers and 15 obese subjects using a previously validated mathematical model of insulin secretion and rate constants for C-peptide derived from analysis of individual decay curves after intravenous bolus injections of biosynthetic human C-peptide. Insulin secretion rates were substantially higher than normal in the obese subjects after an overnight fast (86.7 +/- 7.1 vs. 50.9 +/- 4.8 pmol/m2 per min, P less than 0.001, mean +/- SEM), over a 24-h period on a mixed diet (279.6 +/- 24.2 vs. 145.8 +/- 8.8 nmol/m2 per 24 h, P less than 0.001), and during a hyperglycemic intravenous glucose infusion (102.2 +/- 10.8 vs. 57.2 +/- 2.8 nmol/m2 per 180 min, P less than 0.001). Linear regression analysis revealed a highly significant relationship between insulin secretion and body mass index. Basal hepatic insulin extraction was not significantly different in the normal and obese subjects (53.1 +/- 3.8 vs. 51.6 +/- 4.0%). In the normal subjects, fasting insulin did not correlate with basal hepatic insulin extraction, but a significant negative correlation between fasting insulin and hepatic insulin extraction was seen in obesity (r = -0.63, P less than 0.02). This finding reflected a higher extraction in the six obese subjects with fasting insulin levels within the range of the normal subjects than in the nine subjects with elevated fasting insulin concentrations (61 +/- 3 vs. 45 +/- 6%, P less than 0.05). During the hyperglycemic clamp, the insulin secretion rate increased to an average maximum of 6.2-fold over baseline in the normal subjects and 5.8-fold in the obese subjects. Over the same time, the peripheral insulin concentration increased 14.1-fold over baseline in the normals and 16.6-fold over baseline in the obese, indicating a reduction in the clearance of endogenously secreted insulin. Although the fall in insulin clearance tended to be greater in the obese subjects, the differences between the two groups were not statistically significant. Thus, under basal, fasting conditions and during ingestion of a mixed diet, the hyperinsulinemia of obesity results predominantly from increased insulin secretion. In patients with more marked basal hyperinsulinemia and during intense stimulation of insulin secretion, a reduction in insulin clearance may contribute to the greater increase in peripheral insulin concentrations that are characteristic of the obese state.+

Blood Glucose↗
PubMed1988

2-[(Aminopropyl)amino] ethanethiol-mediated reductions in 60Co gamma-ray and fission-spectrum neutron-induced chromosome damage in V79 cells.

The radioprotector 2-[aminopropyl)amino] ethanethiol (WR1065), which has been reported to reduce the cytotoxic and mutagenic effects of low LET radiation, was investigated for its ability to protect against low LET (60Co gamma ray) and high LET (fission-spectrum neutron)-induced chromosome damage in V79 cells. Cells were irradiated in G2 phase in the presence or absence of 4 mM WR1065 and were harvested and analyzed 2 h later for chromatid-type aberrations. Irradiation of G2-phase V79 cells in the presence of WR1065 resulted in a 30 to 50% reduction in the frequency of gamma-ray and neutron-induced chromatid-type breaks and exchanges. The effects were found only after exposures of greater than 200 cGy gamma-ray or 50 cGy neutron irradiation. The radioprotector was effective at reducing neutron-induced aberrations after exposures at dose rates of both 10 and 43 cGy/min. Thus the radioprotector WR1065 is an effective anti-clastogenic agent in V79 cells, protecting against both 60Co gamma-ray and fission-spectrum neutron-induced aberrations, when present during irradiation.

Animals↗
PubMed1987

Assessment of tumor cell kinetics by immunohistochemistry in carcinoma of breast.

Cell proliferation was assessed in 33 invasive breast carcinomas by an immunoperoxidase procedure using the monoclonal antibody, Ki-67, which reacts with a nuclear antigen in proliferating cells. The antibody labeled a variable proportion of tumor cells ranging from 3% to 60%. High numbers of Ki-67-positive cells were found in tumors with high mitotic rates, high nuclear grade, high histologic grade, and in premenopausal women. Tumors with low and intermediate Ki-67 labeling rates often had high estrogen receptor content, whereas tumors with high Ki-67 labeling rates were usually estrogen receptor negative. These correlations are similar to those previously reported for other measurements of cell cycle kinetics such as thymidine labeling index and suggest that immunohistochemical staining of invasive breast carcinoma for the Ki-67 epitope may provide cell cycle information not otherwise readily available to the clinician and may be useful in assessing prognosis in carcinoma of the breast.

Adult↗
PubMed1986

Developmental changes in P-face and E-face particle densities of Xenopus cardiac muscle plasma membrane.

P- and E-face particle densities (PPD and EPD) were measured in electron micrographs of freeze-fractured cardiac sarcolemma from eight developmental stages of Xenopus laevis (stages 33/34 (33 post-otic somite embryos) to 66 (fully metamorphosed juvenile toad], using stereo-imaged replicas. We found striking progressive increases in PPD and EPD, most rapid between stages 33/34 and 37/38; that PPD was significantly greater than EPD at all stages; that both PPD and EPD of stereo-imaged replicas were about X2 greater than corresponding values not stereo-imaged; and that sarcolemmal PPD of late anuran embryonic and post-metamorphosis hearts were significantly greater than our previously determined PPD values for chick late embryo and adult mammalian sarcolemma. We suggest that PPD and EPD depend on how membrane particles segregate during freeze-fracture and on the relative contributions of membrane-spanning and non-membrane-spanning integral membrane protein complexes to each fracture face.

Aging↗
PubMed1986

Functional equality of coordinating centers in a multicenter clinical trial. Experience of the International Mexiletine and Placebo Antiarrhythmic Coronary Trial (IMPACT).

The International Mexiletine and Placebo Antiarrhythmic Coronary Trial (IMPACT) included clinical centers in both Europe and North America. The clinics were monitored by two Regional Coordinating Centers: one located in Baltimore, Maryland, for North American clinics; the other in Lyon, France, for European clinics. These coordinating Centers were in turn monitored by an independent Data Audit Center located in Chicago, Illinois. This article describes how computer systems and operational procedures were developed to allow the three IMPACT centers to exchange processed files for a common analysis by the two Regional Coordinating Centers. The problems encountered and the advantages of this organization are described and discussed.

Arrhythmias, Cardiac↗
PubMed1986

Histologic features associated with long-term survival in breast cancer.

Three basic cytologic variants were identified among cases of infiltrating ductal carcinoma of the breast (NOS). These variants were found to have different distributions among patients surviving 25 years after mastectomy, compared with matched short-lived control subjects. Multivariate analyses indicated that recognition of these cytologic variants enhanced the prognostic value of tumor grade and blood vessel invasion. Patients with tumors designated here as histologic type C, which others have called invasive cribriform carcinoma, appear to have a higher probability of long-term survival than patients with other histologic subtypes. Since they account for approximately 20 per cent of 25-year survivors, they should be distinguished from patients with other types of infiltrating ductal carcinoma (NOS).

Adult↗
PubMed1986

Radiation-resistant and repair-proficient human tumor cells may be associated with radiotherapy failure in head- and neck-cancer patients.

Inherent cellular radioresistance and repair of x-ray damage was studied in 19 early-passage squamous cell carcinoma lines derived from head- and neck-cancer patients with known clinical results following radiotherapy. Human tumor cells that were radioresistant and/or proficient in accumulation/repair of x-ray damage were cultured from patients unsuccessfully treated with radiotherapy. Thus, the presence of radiation-resistant and repair-proficient tumor cells was associated with clinical radiation failure, suggesting the possibility of a predictive assay based on in vitro radiobiological parameters.

Carcinoma, Squamous Cell↗
PubMed1986

Effects of long-term therapy with oral ibopamine on resting hemodynamics and exercise capacity in patients with heart failure: relationship to the generation of N-methyldopamine and to plasma norepinephrine levels.

N-Methyldopamine (epinine), one of the few modifications of the dopamine (DA) molecule that retains agonist activity at the DA1 receptor, was administered orally as the diisobutyric ester, ibopamine (100, 200, and 300 mg), to 15 patients with congestive heart failure. An increase in cardiac index and decline in systemic vascular resistance was observed with each dose, and these hemodynamic effects persisted for 3 to 6 hr. Small transient increments in right atrial and pulmonary capillary wedge pressures occurred 0.5 hr after ingestion of 200 and 300 mg of ibopamine, but these pressures returned to baseline or lower levels within 30 min. Heart rate and mean arterial pressure were unchanged. Plasma concentrations of epinine peaked 0.5 hr after administration of drug and then declined to minimal levels at 3 hr. Ten patients enrolled in a trial to evaluate the efficacy of long-term therapy with ibopamine; after 8 weeks of treatment, the initial hemodynamic responses to the drug were attenuated and no significant improvement in oxygen uptake at peak exercise was observed. A decline in plasma norepinephrine concentrations, which could be attributed to activation of alpha 2-adrenoceptors and/or DA2 receptors on sympathetic nerves, was observed after initial administration of ibopamine and persisted after long-term drug ingestion; no long-term hemodynamic benefit could be ascribed to the reduction in sympathetic activity.

Administration, Oral↗
PubMed1986

Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients.

We undertook this study to examine the accuracy of plasma C-peptide as a marker of insulin secretion. The peripheral kinetics of biosynthetic human C-peptide (BHCP) were studied in 10 normal volunteers and 7 insulin-dependent diabetic patients. Each subject received intravenous bolus injections of BHCP as well as constant and variable rate infusions. After intravenous bolus injections the metabolic clearance rate of BHCP (3.8 +/- 0.1 ml/kg per min, mean +/- SEM) was not significantly different from the value obtained during its constant intravenous infusion (3.9 +/- 0.1 ml/kg per min). The metabolic clearance rate of C-peptide measured during steady state intravenous infusions was constant over a wide concentration range. During experiments in which BHCP was infused at a variable rate, the peripheral concentration of C-peptide did not change in proportion to the infusion rate. Thus, the infusion rate of BHCP could not be calculated accurately as the product of the C-peptide concentration and metabolic clearance rate. However, the non-steady infusion rate of BHCP could be accurately calculated from peripheral C-peptide concentrations using a two-compartment mathematical model when model parameters were derived from the C-peptide decay curve in each subject. Application of this model to predict constant infusions of C-peptide from peripheral C-peptide concentrations resulted in model generated estimates of the C-peptide infusion rate that were 101.5 +/- 3.4% and 100.4 +/- 2.8% of low and high dose rates, respectively. Estimates of the total quantity of C-peptide infused at a variable rate over 240 min based on the two-compartment model represented 104.6 +/- 2.4% of the amount actually infused. Application of this approach to clinical studies will allow the secretion rate of insulin to be estimated with considerable accuracy. The insulin secretion rate in normal subjects after an overnight fast was 89.1 pmol/min, which corresponds with a basal 24-h secretion of 18.6 U.

Adult↗
PubMed1986

Calculation of the systemic delivery rate of insulin in normal man.

The accuracy with which the systemic delivery rate of insulin can be estimated from peripheral insulin concentrations was investigated in eight normal men. Endogenous insulin secretion was suppressed by somatostatin, and insulin was infused exogenously via a peripheral vein. The infusion rate was progressively increased and then decreased to stimulate the changes in insulin secretion that occur after a secretory stimulus. The infusion rate of insulin was then estimated by analyzing peripheral insulin concentrations using both single and two-compartment mathematical models and was compared with the actual infusion rates. Model parameters were measured in each subject by analysis of the insulin decay curve after a bolus injection. Estimated infusion rates based on the single compartment model were 84.3 +/- 3.0% (mean +/- SE) of the actual infusion rate as it was increasing and 110.3 +/- 3.7% of the infusion rate as it was decreasing. The mean overall absolute percent error associated with this approach was 14.1 +/- 1.0% (range, 10.2-18.8%), and model estimates of the total amount of insulin infused over the duration of the experiment were 97.1 +/- 3.2% of the quantity actually infused (range, 85.4-110.7%). Estimates of the infusion rate based on a two-compartment model represented 90.3 +/- 3.1% of the actual infusion rate as it was increasing and 98.2 +/- 3.2% of the actual rate as it was falling. The area under the derived infusion rate curve was 94.8 +/- 2.8% of the area under the actual curve. The overall error associated with the use of the two-compartment model was 12.9 +/- 1.1% (range, 8.8-18.6%). Differences between the single and two-compartment models were minor and not statistically significant. These data demonstrate that under euglycemic conditions, changes in the plasma insulin concentration within the physiological range are not associated with changes in the clearance kinetic rate constants of the hormone. Furthermore, the systemic delivery rate of insulin can be accurately derived from peripheral insulin concentrations using either a single or two-compartmental model if model parameters are accurately measured in individual subjects by analysis of insulin decay curves.

Humans↗