Biomedical subjects

T Karrison

Publications and source records attributed to T Karrison.

70 records · Page 4Linked to original sources

PubMed1986

The limitations to and valid use of C-peptide as a marker of the secretion of insulin.

The accuracy with which the secretion rate of insulin can be calculated from peripheral concentrations of C-peptide was investigated in conscious mongrel dogs. Biosynthetic human C-peptide and insulin were infused intraportally and their concentrations measured in the femoral artery. During steady-state infusions of C-peptide, the peripheral concentration changed in proportion to the infusion rate and the metabolic clearance rate (5.2 +/- 0.3 ml/kg/min) remained constant over a wide range of plasma concentrations. Application of a two-compartment mathematical model, in which the model parameters were estimated from analysis of C-peptide decay curves after intravenous bolus injections, allowed the intraportal infusion rate of C-peptide to be derived from peripheral C-peptide concentrations, even under non-steady-state conditions. Estimates of the intraportal infusion rate based on this model were 102.4 +/- 2.6% of the actual infusion rate as it was increasing and 102.3 +/- 5.5% of this rate as it was falling. The peripheral C-peptide: insulin molar ratio was influenced by the rate at which equimolar intraportal infusions of C-peptide and insulin were changed. The baseline C-peptide: insulin molar ratio (4.1 +/- 0.9) increased to peak values of 8.2 +/- 0.6, 10.3 +/- 2.0, and 14.9 +/- 1.3 when the infusion rate was increased and then decreased rapidly. Peak values of only 5.7 +/- 1.2 were found if the intraportal infusion rate was changed slowly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

A controlled trial of extended radical mastectomy.

One hundred twenty-three women younger than 70 years of age and at clinical Stages I or II were enrolled in a randomized clinical trial of radical versus extended radical mastectomy. The 5-year survival rates in the radical and extended radical groups were 75 +/- 6.7% and 80 +/- 6.7%, respectively. (Cox P value for comparison of survival curves = 0.32.) 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 5-year survival rates for the radical and extended radical groups were 71 +/- 7.6% and 85 +/- 6.2%, respectively (P = 0.09). For patients from this subgroup with central or medial tumors, the 5-year survival rates were 66 +/- 10% and 88 +/- 8.2%, respectively (P = 0.06). For patients with lateral tumors, the 5-year survival rates were nearly equal: 79 +/- 11% and 81 +/- 9.7%, respectively. The findings in a nonrandomized series of similar patients were comparable. The results are not definitive, but suggest an advantage of extended radical mastectomy over radical mastectomy for patients with central or medial tumors. Continued follow-up of the randomized series may lead to more conclusive results.

Adult↗

PubMed1985

Developmental changes in internal structure of chick heart plasma membrane.

Although changes in electrophysiologically measurable membrane properties of chick embryo cardiac plasma membrane have been repeatedly documented during embryonic development, ultrastructural techniques were heretofore too insensitive to detect developmental changes in internal structure of this membrane. We report here significant structural changes detected by applying the quantitative analysis of Kordylewski, Karrison, and Page (Amer. J. Physiol. 245, H992-H997, 1983 and 248, H297-H304, 1985) to stereo imaged electron microscopic negatives of glutaraldehyde-fixed chick embryo hearts, freeze fractured and photographed with a goniometer stage. Between Hamburger-Hamilton stages 12+ (about 48 hr incubation) and 24 (about 96 hr incubation), plasmalemmal P-face particle density of ventricular myocytes increased from 2228 +/- 139 to 3063 +/- 109 (P less than 0.01); thereafter, measurements at stages 30, 37, 40, and 45 (7, 11, 15, and 19 days incubation) showed a slower significant linear increase which gave a least-squares line with a slope of 41 +/- 13 particles/day (P less than 0.01). Just before hatching, (stage 45) the value of 3762 +/- 234 was similar to, though slightly smaller than, the values of 4122 +/- 153 (8 days after hatching) and 4281 +/- 218 (adult chicken). These results indicate striking stage-dependent changes in the population of integral membrane proteins (channels, carriers, receptors, etc.), especially marked during early embryogenesis.

Animals↗

PubMed1985

Measurements on the internal structure of freeze-fractured cardiac plasma membrane.

We describe a quantitative analysis of the internal structure of cardiac plasma membranes freeze fractured in situ, including the P-face particle density (lambda), the P-face particle diameter (d), the percent of fracture face area occupied by particles (Ap), and the spatial distribution of particles (random, clustered, or ordered). This analysis has been applied to seven sheep hearts to compare the plasmalemmal internal structures in ventricular and atrial myocytes and Purkinje strands of the same hearts and also to myocytes of frog, chicken, rabbit, and rat ventricles (to compare internal plasmalemmal structure of different vertebrate classes). Measurements were made on tissues conventionally prepared for freeze fracture by glutaraldehyde fixation and cryoprotection. We found that, in the same sheep hearts, lambda and Ap for ventricular plasmalemma significantly exceeded those for atrial plasmalemma and that the distribution of atrial P-face particles was more clustered than that for ventricle. d and Ap for frog ventricular plasmalemmal P-face significantly exceeded values for some of the other vertebrates.

Animals↗

PubMed1985

Saxitoxin binding and "fast" sodium channel inhibition in sheep heart plasma membrane.

We compared specific [3H]saxitoxin (STX) binding to isolated sheep ventricular sarcolemmal vesicles with inhibition of maximal action potential upstroke velocity (V max) by STX and tetrodotoxin (TTX) in sheep trabeculae carneae. In sarcolemmal vesicles purified 30 to 40 times over cardiac homogenate, STX binding at 0 degrees C in Na-free solution exhibited both high-affinity sites (KD = 0.22 +/- 0.05 nM, n = 85 +/- 13 fmol/mg protein) and low-affinity sites (KD = 11 +/- 4 nM, n = 360 +/- 42). The STX-inhibition constant for V max in Tyrode solution at 37 degrees C was 280 nM. TTX was approximately 10% as effective as STX in displacing bound [3H]STX and inhibiting V max. Allowing for different experimental conditions during [3H]STX binding and V max measurements, we suggest that the low-affinity sites are physiologically relevant "fast" Na+ channels of myocardial cells. Combining morphometric data for plasmalemmal area of mammalian cardiac myocytes with n for low-affinity sites, we estimate 3.6-7.6 fast Na+ channels/micron2 plasmalemma.

Action Potentials↗

PubMed1985

Folate binding protein and the estrogen receptor in breast cancer.

Folate binding protein (FBP) and estrogen receptor (ER) content were determined in primary breast cancers of 48 patients. The mean FBP level was significantly higher in ER-negative tumors than in ER-positive tumors and largely independent of the degree of tumor involvement or menopausal status. FBP correlated negatively with ER and this was most marked for tumors from postmenopausal women. Since FBP may decrease available intracellular folate the present data support clinical findings that chemotherapeutic agents may be more effective for ER negative tumors.

Breast Neoplasms↗

PubMed1984

C-peptide and insulin secretion. Relationship between peripheral concentrations of C-peptide and insulin and their secretion rates in the dog.

Estimation of the insulin secretory rate from peripheral C-peptide concentrations depends upon the following characteristics of C-peptide kinetics: (a) equimolar secretion of insulin and C-peptide by pancreatic beta cells; (b) negligible hepatic extraction of C-peptide; (c) constant metabolic clearance rate (MCR) of C-peptide over a physiological and pathophysiological range of plasma levels; and (d) proportional changes in the secretion rate of C-peptide and its peripheral concentrations under varying physiological conditions. In the present experiments, the relationship between a variable intraportal infusion of C-peptide and its concentration in the femoral artery was explored in 12 pancreatectomized dogs. As the infusion of C-peptide was rapidly increased, the magnitude of its peripheral concentration initially increased less than the infusion rate by 20-30%. After an equilibration period of approximately 30 min, however, further increases and decreases in the intraportal infusion were accompanied by nearly proportional changes in its peripheral concentration. Estimates of the amount of C-peptide infused during the experiment based on the steady state C-peptide MCR and its peripheral concentration were within 20% of the amount of C-peptide actually infused. These experiments demonstrate that the portal delivery rate of C-peptide can be calculated from its MCR and peripheral concentration in the dog. They also provide a basis for testing the validity of more complicated models of insulin secretion based on peripheral C-peptide concentrations in the dog as well as other species, including man. Finally, we have shown that the hepatic extraction of endogenously secreted C-peptide is negligible in the basal state (3.1 +/- 6.1%), and does not change after oral glucose ingestion. The MCR of exogenous dog C-peptide was similar whether measured by constant peripheral intravenous infusion (12.3 +/- 0.7 ml/kg per min), constant intraportal infusion (13.4 +/- 0.6 ml/kg per min), or analysis of the decay curve after a bolus injection (13.5 +/- 0.7 ml/kg per min).

Animals↗

PubMed1983

Freeze-fractured cardiac gap junctions: structural analysis by three methods.

In isolated rat left ventricles perfused at 37 degrees C with control, Ca2+-loading, and Ca2+-depleting solutions (pH 7.3-7.4), we have investigated freeze-fractured gap junctional membrane by three quantitative techniques designed to correlate changes in junctional permeability with changes in membrane ultrastructure, i.e., 1) optical diffraction, 2) direct measurement of center-to-center spacings and particle diameters, and 3) statistical analysis of the spatial distribution of P-face particles based on analysis of nearest neighbor center-to-center distances. Junctions fixed either with glutaraldehyde or by quick freezing were compact, with closely packed rather than dispersed membrane particles even in the permeable state. Analysis of variance for all three methods indicated that replication was a major variability source limiting structural discrimination. Discrimination between random, regular, and clustered distributions depended critically on particle diameter and particle density. The results differ from published data of others on mammalian ventricular gap junctions and from measurements by our laboratory on sheep cardiac Purkinje fibers (J. Ultrastruct. Res. 75: 195-204, 1981).

Animals↗

PubMed1983

P-face particle density of freeze-fractured vertebrate cardiac plasma membrane.

P-face particle density of freeze-fractured cardiac plasmalemma provides an estimate of the total population of membrane channels, carriers, and receptors that insert into or traverse unit area of lipid bilayer. We have determined the size of this population of integral membrane protein assemblies by counting the number of P-face particles per square micron of plasmalemma in freeze-fractured hearts, using stereoimaged replicas tilted with a goniometer stage in the electron microscope. Particle numbers per square micron were 4,525 +/- 231, 4,799 +/- 235, 4,122 +/- 153, 4,281 +/- 218, and 5,848 +/- 300 for ventricular myocyte plasmalemmas of rat, rabbit, 8-day chick, adult chicken, and frog, respectively. These values are at least two times greater than published values, in which stereo imaging was not used. Published ligand-binding studies indicate that only the surface density of the Na+-K+ pump sites can account for a significant fraction of P-face particles; the rest so far lack functional correlates. Particle density of frog heart plasmalemma significantly exceeded particle densities of chicken and mammalian plasma membranes.

Aging↗

PubMed1982

The pathological findings of breast cancer in patients surviving 25 years after radical mastectomy.

The authors report the findings in 107 women who are known to have survived 25 years from among a population of 746 consecutive patients who underwent radical mastectomy for breast carcinoma at the University of Chicago Hospitals and Clinics from 1929 to 1955. Of these patients, 103 had invasive carcinomas, two had intraductal carcinomas, and two had subareolar papillomatosis. Six patients had to be excluded because of inadequate pathologic material. The pathologic findings in 93 cases were compared with those in an equal number of control cases dying within a comparatively short period (median, 3.4 years; range 0.9-9.9 years) after radical mastectomy. These were matched for age, tumor size, and number of positive nodes. Only two of our patients suffered recurrences, and none died of her original tumor; however, 12 developed second primaries in the opposite breast, and four died from them. Compared with all patients who underwent radical mastectomy in this period, the 25-year survivors were younger (69 versus 43% were younger than age 50 years), had smaller tumors (39 versus 26% less than 2 cm in diameter), and a larger number (60 versus 39%) had negative nodes. Nonetheless, 12% of the survivors had tumors larger than 5 cm in diameter and 11% had four or more positive nodes. Histologically, 19% of the 25-year survivors had medullary, mucoid, infiltrating lobular, tubular or lipid rich carcinomas, whereas there was only one lobular and one apocrine carcinoma in the control group. Compared with controls, the survivors had a higher percentage of Grade I tumors and a lower incidence of lymphatic and vascular invasion in the breast. Only one 25-year survivor compared with 16 controls had blood vessel invasion. A surprising 63% of the 25-year survivors had lymphatic or vascular invasion within the tumor, or lymph node metastases compared with 82% of controls. While our studies confirm the importance of these well-known prognostic indicators, it also shows that some patients with pathologically unfavorable lesions, i.e., large tumors of high grade with extensive lymphatic invasion and many positive nodes, treated by radical mastectomy may survive for 25 years. However, we could not accurately predict, among the cases we studied, who would be expected to survive 25 years or who would die within four years.

Adult↗

PubMed1982

Staging of breast cancer and survival rates. An assessment based on 50 years of experience with radical mastectomy.

The correlation of staging criteria for mammary carcinoma with the curability of primary and recurrent local and regional lesions was assessed by follow-up after 1,259 consecutive radical mastectomies performed in women under age 70 between 1927 and 1978. Using a staging scheme revised in the light of our experience, the incidence of recurrence by 20 years was 34% +/- 2.7% for pathological stage I, 65% +/- 2.6% for stage II, and 83% +/- 2.5% for stage III. Recurrence after 20 years was observed in one of 178 patients. After treatment of local recurrence, three of 51 patients survived 20 years. By restriction of entry into clinical or pathological stages I and II, currently employed revisions of staging criteria appear to increase survival in all stages, while placing patients with possibly curable lesions in stages III and IV.

Adult↗

PubMed1982

A statistical analysis of the loss of muscle strength in Duchenne's muscular dystrophy.

We have confirmed that the loss of muscle strength in 12 boys with Duchenne's muscular dystrophy, as measured by manual muscle testing, approximates a linear decay model, but we have also found that it fits as well a first order decay model. The strength in the same eight muscles was measured over time. Results of an analysis of 111 examinations are reported here. An arbitrary numerical scale for grading muscle strength was used, such that normal was 13 units, and no movement was zero. The maximal sum, if all 8 muscles were normal, would be 104 units. Pooling all measurements, the linear decay rate in this sum was -0.189 +/- 0.023 (estimate +/- standard error) arbitrary muscle strength units . month-1. The corresponding first order fractional decay rate was -0.0034 +/- 0.0004 month-1. However, a more detailed statistical analysis indicated that decay rates in muscle strength were not homogeneous, i.e. muscle strength decayed faster in some patients than others. The decay constants in 11 of the 12 subjects spanned a 10-fold range, and in one subject increased the spread to 40-fold. The distribution frequency of decay rates appears to be bimodal. In these assessments, the muscle strength at time zero was not known. Therefore, an estimate of muscle strength at 10 years was made. This varied from 34 to 71 units. The group mean was 53.0 units using the exponential model, i.e. on average, only 51% (= 53.0/104 X 100) of the normal muscle strength remained in the 8 muscle groups assessed at age 10 years. In conclusion, a quantitative characterization of muscle strength deterioration is reported, which emphasizes the heterogeneity in this disease. This approach may eventually allow quantitative distinctions between Duchenne's and Becker's varieties of muscular dystrophy.

Adolescent↗

PubMed1981

Data editing in a clinical trial.

In clinical research and, particularly, in multicenter clinical trials, data are collected onto study forms designed to minimize errors in the recorded data. Nevertheless, errors of various kinds must be anticipated, and it is necessary to devise means to detect, review, and correct erroneous values. General requirements of a data editing system and methods for accomplishing these tasks are presented. A general computer program for error detection and a method for updating the data base that leaves an "audit trail" of the original data and subsequent corrections are described.

Clinical Trials as Topic↗

PubMed1981

Prognostic significance of immunological tests in lung cancer.

We performed a battery of tests on peripheral blood samples from 94 patients with lung cancer to determine the extent to which immunological depression was due to abnormal lymphocyte function, as compared to changes in the number of lymphoid cells in the peripheral blood or in the efficiency of purification of cells in Ficoll-Hypaque gradients in preparation for testing. The percentage of lymphocytes in the gradient-derived cell suspension (%LG) was the most informative test. It decreased significantly with advancing stage of cancer and could predict survival of patients with uniform stage. The %LG correlated with survival better than any other test when multivariate analyses of all test combinations were performed. Low values of %LG reflected both the depressed lymphocyte counts and the altered buoyant density of the leucocytes of many patients with advanced cancer. A large proportion of the depression in other immune function tests was statistically attributed to changes in %LG. We concluded that this simple measurement provides valuable information about patients with lung cancer.

Carcinoma, Bronchogenic↗

PubMedDate not supplied

Racial differences in prostate-specific antigen levels in patients with local-regional prostate cancer.

Prostate cancer is a significant health problem for blacks. The incidence and mortality rates are higher in blacks than in whites; blacks often present with a higher stage. Prostate-specific antigen (PSA) is a very useful serum marker in prostate cancer. We analyzed data from a cohort of 161 patients to determine whether there were any racial differences in PSA levels prior to treatment in local-regional prostate cancer. The immunoradiometric method was used to determine the PSA values. The mean PSA levels were significantly higher in blacks than in whites (P = 0.022), and the difference remained significant in multivariate analysis after adjusting for stage and grade (P = 0.020). However, when analyzed further, the difference was statistically significant in one hospital (P = 0.001) and not in another (P = 0.493). Thus, our results are not unequivocal, but our data do suggest that racial differences in PSA levels not accounted for by tumor stage or grade may exist. Assuming that the data truly reflect a racial difference, the cause(s) of this difference remains to be determined. It may exist because, within each clinical stage, blacks are presenting with a higher tumor cell burden, or it may be indicative of more aggressive biological behavior. The possibility that racial differences are due to socioeconomic factors was considered by estimating median income level from zip code of residence; although a correlation between socioeconomic status and PSA level was found, racial differences remained borderline significant (P = 0.055) after adjusting for income level (in addition to stage and grade).

Black or African American↗

PubMedDate not supplied

Hospital utilization patterns and costs for adult sickle cell patients in Illinois.

OBJECTIVES: To determine population size, demographic characteristics, hospital utilization patterns, the specialties of physicians providing care, and costs for hospitalized adult sickle cell patients in Illinois. METHODS: A statewide, administrative dataset for the two-year period from january 1992 through December 1993 was analyzed retrospectively. RESULTS: There were 8403 admissions among 1189 individual sickle cell patients for the two-year period. Eighty-five percent of patients resided in the Chicago metropolitan area. The median age of the 1189 patients was 29; two-thirds had Medicaid or Medicare coverage. Emergency departments were the primary source of admissions (85.7%). The most common admitting diagnosis was painful crisis (97.4%), and average length of stay was four days. The median number of admissions per patient was three; most patients (85%) used only one or two hospitals. A small group used more than four hospitals and accounted for 23% of statewide admissions. Primary care physicians cared for most patients, and total hospitalization charges were more than $59 million. CONCLUSIONS: In Illinois the adult sickle cell population is concentrated in major urban centers, primarily the Chicago metropolitan area. These patients accounted for approximately 8400 admissions and more than $59 million in hospital charges during the two-year study period. A small group of patients used multiple hospitals and accounted for more than 23% of total hospitalization charges. This study shows the necessity of and provides a useful framework for developing targeted programs for adult sickle cell patients as well as for training physicians to efficiently provide comprehensive health care services for this population.

Adolescent↗