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Biomedical subjects

R E Pecoraro

Publications and source records attributed to R E Pecoraro.

34 records · Page 2Linked to original sources

Ascorbic acid metabolism in diabetes mellitus.

Competition for membrane transport between glucose and ascorbic acid (AA) has been shown in vitro in human lymphocytes, granulocytes, and fibroblasts. Therefore, we examined the effects of acute administration of i.v. glucose on AA levels in mononuclear (MNL) and polymorphonuclear leukocytes (PMN) and on leukocyte chemotaxis. Plasma glucose and AA, MNL AA, PMN AA, and chemotaxis by MNL and PMN were measured before and after i.v. glucose in fasted normal male volunteers. A decline in AA occurred in PMN as well as MNL, but decreases in AA induced acutely by transient hyperglycemia were not associated with changes in chemotaxis. However, under conditions of prolonged hyperglycemia maintained by a glucose clamp technique, significant changes (p less than 0.01) in chemotaxis by both PMN and MNL were observed after 210 and 240 min, with changes in chemotaxis to several chemoattractants significantly correlated with decreases in intracellular AA after 240 min (p less than 0.05). These results are consistent with the hypothesis that chronic hyperglycemia may be associated with intracellular deficits of leukocyte AA, an impaired acute inflammatory response, and altered susceptibility to infection and faulty wound repair in patients with diabetes.

Adult↗

Influenza vaccination and warfarin anticoagulation.

Because influenza vaccine can markedly depress hepatic cytochrome P450 activity and may have caused an extreme prolongation of the prothrombin time in one patient receiving warfarin, we studied the effect of influenza vaccine on anticoagulation in 21 male outpatients receiving chronic warfarin therapy. Prothrombin times measured three to five times in the month after vaccination were in the therapeutic range as often as those measured before vaccination. Mean changes in prothrombin times measured after vaccination were not significantly different from those on the day of vaccination or in the 3 months before vaccination. The size of this study assured an 80% chance that any deviation from the observed mean prothrombin times would not exceed 2.1 s. No patient had any bleeding or thromboembolic problems. Thus, influenza vaccination of patients anticoagulated with warfarin appears to be safe.

Aged↗

Seeding efficiency, plating efficiency, and population doublings of human skin fibroblastlike cells: results of replicate testing.

Using skin fibroblastlike cells from 10 healthy volunteers, 12 to 54 yr old, we measured, in replicates, seeding efficiency (SE), plating efficiency (PE), and population doublings (PD) during 2 wk of growth and the cumulative replicative life span (CRLS). We determined the effects of donor age and of in vitro cell age on the test results and test precision. We found that (a) On the average, SE was 82% +/- 24 SD, PE was 12% +/- 9 SD, PD was 7.3 doublings +/- 2.5 SD, and CRLS was 31.1 doublings +/- 9.6 SD. (b) Plating efficiency and PD correlated well with each other and with CRLS whereas SE did not correlate with PE, PD, or CRLS. (c) Plating efficiency and PD were affected negatively by increasing passage levels and by donor ages, but the influence of age was evident only for cells from early passages. Seeding efficiency was not affected by either of the two variables. (d) Variations in PD from early passages explained half of the donor-to-donor variation in CRLS whereas PD from later passages had little or no predictive power. (e) Of the two short term tests, PD had better precision than PE. For replicate runs with cells from early passages the coefficient of variation was 44% for PE and 15% for PD. The results show that PD for cells from early passages in mass culture give rapid results, which express the in vitro replicating potential of cells from different donors with greater precision than do measurements of CRLS.

Adolescent↗

Hyperglycemia-induced intracellular depletion of ascorbic acid in human mononuclear leukocytes.

It has recently been reported that glucose and its analogues inhibit in vitro ascorbic acid transport across the cell membrane of polymorphonuclear leukocytes and fibroblasts. We have studied the effect of in vivo hyperglycemia on the intracellular ascorbic acid level of mononuclear leukocytes in normal and diabetic human subjects. Administration of an intravenous glucose load resulted in a prompt decrease of mononuclear leukocyte ascorbic acid level in the normal subjects. The rate of its decline correlated closely with the rate of change of plasma glucose. Among the NIDDM subjects in the fasting state, the plasma glucose was high and the leukocyte ascorbic acid level was low when compared with that of the normal subjects. The decrease in the leukocyte ascorbic acid level during disposition of the i.v. glucose load was not statistically significant in the diabetics. The hyperglycemia-induced intracellular depletion of ascorbic acid could be clinically important and requires further evaluation.

Adult↗

Screening for noncompliance among patients with hypertension: is self-report the best available measure?

The substantial prevalence of noncompliance with drugs in populations of patients with treated hypertension suggests that a reliable, clinically applicable screening test for this behavior is needed. Among employed white males, patient response to a nonjudgmental clinician inquiry has been reported to be highly predictive of noncompliance when positive but relatively insensitive (40 per cent). We assessed the performance of patient self-report in a demographically different population and confirmed the generalizability of prior observations. A compound decision rule combining blood pressure and verbal inquiry observations, however, had higher sensitivity (83 per cent) for noncompliance in our population than self-report alone (55 per cent) and could be considered for use when the prevalence of noncompliance among uncontrolled hypertensives is sufficiently high. Because 40 per cent of well-controlled hypertensives in our test population were noncompliant by pill-count, a question is raised regarding the need for "stepping down" drug therapy in some individuals under treatment for high blood pressure.

Female↗

Variations in patient compliance with common long-term drugs.

An indirect measure of adherence to drug regimens was developed from pharmacy records of prescription refills. This measure was validated by demonstrations of significant relationships between compliance with hydrochlorothiazide and propranolol and expected physiologic effects of these drugs (decreased blood pressures and decreased pulse rates, respectively). The measure was used to survey compliance with 20 common drugs prescribed to 419 outpatients for long-term administration on regular schedules. Eight of the study drugs showed very low levels of compliance, suggesting "take-as-needed" (PRN) use, in spite of medical record, pharmacy record, and label instructions for regular administration. For the whole survey population, 12 truly "non-PRN" drugs showed showed a considerable gradient in mean compliance rates, ranging from digoxin (76.6 per cent) to hydralazine (50.4 per cent). Within-patient differences in mean compliance with different drugs were shown (e.g., hydrochlorothiazide 61.2 per cent versus potassium chloride 41.2 per cent mean compliance, p < 0.001). Correlations between compliance rates with different drugs in a single regimen were sometimes strikingly low. We conclude that 1) chart and prescription directions for regular administration are not sufficient to identify "non-PRN" drugs in compliance studies; 2) when compliance is an outcome measure in health care trials, drug mix is an important confounding variable; 3)in outpatient clinical settings, it may be appropriate to be inherently more suspicious of noncompliance with some drugs than others; and 4) patients may comply at different rates with individual drug components of a single regimen.

Angina Pectoris↗

Effects of a self-administered health history on new-patient visits in a general medical clinic.

Self-administered health history questionnaires (SAHHQs) are widely used in ambulatory care settings to save provider time and to assure completeness of the clinical data base. A controlled, prospective study was undertaken in a general medical clinic to evaluate the impact of an extensively pretested, highly reliable, 120-item self-administered health history questionnaire developed for new patient visits. Seventy-seven patients were randomly assigned to the SAHHQ or control groups. Time analyses were performed on audiotapes of the encounters. Patients' charts were scored on explicit criteria for data completeness. Problem recognition was determined by comparison of pre-encounter and postencounter problem lists. SAHHQ and control visits did not differ significantly in total encounter time (44.7 versus 48.3 minutes, respectively). Less time was spent in SAHHQ encounters on data base questions (2.5 versus 3.9 minutes, p = .003). Chart data were more complete for SAHHQ patients (p less than .001). The completeness of senior staff charts was more affected by the presence of the SAHHQ than residents' charts (p = .03). Physicians tended to recognize more new problems in SAHHQ visits. Mutual (physician and patient) recognition of problems occurred more often in the SAHHQ visits (p = .05). Carefully designed SAHHQs increase recorded data base completeness and may increase problem recognition, but do not result in major time savings.

Attitude of Health Personnel↗

Comparison of a colorimetric assay for glycosylated hemoglobin with ion-exchange chromatography.

Because levels of glycosylated hemoglobin (GHb) are increased in diabetes and reflect the previous metabolic control, clinicians and clinical investigators are finding increasing applications for measurements of GHb in diabetic patients. We report the characterization of a colorimetric assay procedure for GHb and compare its performance with that of a commonly used assay by ion-exchange chromatography. Although results of GHb determination by both methods correlate highly (r = 0.946, P less than 0.001), the two procedures estimate different glycosylated fractions. The colorimetric procedure is nonstoichiometric, requiring careful standardization of assay conditions, including the concentration of total hemoglobin in the assayed aliquot, to achieve precision and permit comparison of results. We characterized the effect of storage of hemolysates or packed erythrocytes on the subsequent determination of GHb by both methods. Determinations of GHb by the colorimetric method, but not by column chromatography, are reproducible on hemolysates or packed erythrocytes on the subsequent determination of GHb by both methods. Determinations of GHb by the colorimetric method, but not by column chromatography, are reproducible on hemolysates or packed erythrocytes stored frozen for at least 5 mo. A unique advantage of the colorimetric procedure is the capability to estimate GHb levels when variant hemoglobins, including fetal and sickle hemoglobins, are present.

Chromatography, Ion Exchange↗

Validity and reliability of a self-administered health history questionnaire.

A self-administered, health history questionnaire devised for routine use in a general medical clinic is completed without the assistance of clinic personnel and used, unedited, by the providers. The reliability and validity of the responses of 23 patients to this questionnaire were tested statistically. In our setting, more than 90 percent of the patients referred for care are capable of completing the questionnaire. The 23 patients averaged 32 minutes to complete the questionnaire. An average of 34 minutes of encounter time is required to obtain the same historical data by interview. Test-retest reliability of patients' responses to the questionnaire was 90 percent. More than 92 percent of the patients' written responses to health history items agreed with the data obtained in a blinded fashion by internists in the traditional interview. The questionnaire accurately obtains items of history frequently missing from the recorded ambulabory care data base, and in some instances obtains items of history more effectively than the interviewing physician. The study results showed a low incidence of false positive (1.8 percent) and false negative (2.8 percent) responses to questionnaire items.

Adult↗

Relationship of patient request fulfillment to compliance, glycemic control, and other health care outcomes in insulin-dependent diabetes.

Patients' perceptions of the extent to which their health care needs have been met may affect compliance with prescribed health behaviors and related health outcomes. The authors examined the relationships of "patient request fulfillment" to patient compliance, glycemic control, and several other health care outcomes in 51 adult outpatients with insulin-dependent diabetes mellitus. On average, patients retrospectively cited 4.5 long-term requests, of which over three-fourths were fulfilled. Fulfillment of these requests was significantly associated with patient satisfaction, perceived health status, fewer insulin reactions, and greater insulin injection time reliability (p less than 0.05), but not with several other measures of compliance. Higher patient request fulfillment at single visits was correlated, as hypothesized, with subsequent reduction in glycosylated hemoglobin, but this association was not statistically significant. These results suggest that patient request fulfillment is associated with several aspects of health behavior and health status in adults with insulin-dependent diabetes. Further studies are needed to confirm these observations and determine whether strategies to enhance patient request fulfillment can enhance health care outcomes.

Adult↗

Factors affecting staphylococcal colonization among NIDDM outpatients.

Because colonization with Staphylococcus aureus probably predisposes to staphylococcal infections, we examined several factors that may be associated with staphylococcal carriage in outpatients with non-insulin-dependent diabetes mellitus and in nondiabetic controls. Nose and skin carrier rates for 59 diabetic patients were significantly greater (30.5%) than for 44 controls (11.4%) (P = .02), but rates did not differ significantly between diabetic patients who injected insulin (31.0%) and those who did not (30.0%). Among the diabetic patients, staphylococcal colonization was not significantly correlated (P greater than .05) with recent antibiotic treatment, age, race, or clinical duration of diabetes but was inversely correlated (P less than .03) with glycemic control, as measured by fasting plasma glucose and glycosylated hemoglobin levels. Hospitalization in the previous year was also associated with staphylococcal colonization, and it was significantly more common among the diabetic patients than the controls; however, this did not account for the increased colonization rates observed. Our results in a well-characterized population confirm an increased rate of staphylococcal colonization among diabetic as compared with nondiabetic outpatients but demonstrate that neither injections of insulin nor various pertinent demographic factors explain this finding.

Adolescent↗

Insulin, pancreatic polypeptide, and glucagon antibodies in insulin-dependent diabetes mellitus.

To assess the possible value of the use of high-purity pork insulin (HPPI) in the United States, the serum insulin (I), pancreatic polypeptide (PP), glucagon (G), and somatostatin (SRIF) antibody binding characteristics have been determined in 90 conventional insulin-treated diabetic subjects and related to their degree of metabolic control, as assessed by glycosylated hemoglobin (HbA1) concentration. All diabetic subjects had antibodies to insulin, but there was no relationship between any of the antibody binding characteristics and HbA1 level: 47% possessed PP antibodies; mean +/- SEM HbA1 in these patients was 14.5 +/- 0.3%, identical to those without PP antibodies (14.5 +/- 0.4%); 10% had G binding antibodies with HbA1 levels of 14.6 +/- 0.8%, similar to those without G antibodies. No subject possessed SRIF antibodies. This lack of correlation between antibody characteristics and metabolic control makes it unlikely that, in the majority of patients, treatment with a less immunogenic insulin (HPPI) versus conventional insulin will result in improved diabetic control.

Adult↗

Glycosylated hemoglobin and fasting plasma glucose in the assessment of outpatient glycemic control in NIDDM.

Interpreting measurements of fasting plasma glucose (FPG) and glycosylated hemoglobin (GHb) is subject to inherent limitations. The time course of change in GHb cannot be reliably specified in the individual patient, nor do single measurements of GHb convey any information regarding recent change or stability in glycemic control. To evaluate whether the clinical utility of these measurements may be extended, sequential measurements of FPG and GHb were examined from 16 outpatients with NIDDM followed over periods of 12 successive weeks or longer, including intervals following cessation of prior therapy or initiation of new hypoglycemic therapy with glipizide. In some individuals as well as groups of patients, changes in GHb followed patterns previously described by mean changes among groups of patients. Differing from those patterns, however, other individuals demonstrated prompt improvement in GHb following substantial improvement in FPG, confirming that patterns of change described from group means do not apply to all circumstances of changing glycemic control, though they may represent the most common. By using measurements of both FPG and GHb obtained on a single occasion to calculate a third parameter, called the glycosylated hemoglobin index (GHb-1), accurate information could be obtained regarding changes in glycemic control which occurred over intervals of 1-4 wk prior to the measurements. By this approach the utility of GHb measurements in the management of outpatients with NIDDM may be extended beyond retrospective description of the "average" prior metabolic control to include assessment of recent changes in glycemia, either deterioration or improvement.

Aged↗

Comparative clinical reliability of fasting plasma glucose and glycosylated hemoglobin in non-insulin-dependent diabetes mellitus.

Because accurate determination of glycosylated hemoglobin (GHb) is difficult and relatively expensive in comparison with the modest cost and ready availability for tests of fasting plasma glucose (FPG), we examined the reliability of repeated measurements of FPG and GHb in typical diabetic outpatients taken in the usual clinical setting. We determined FPG and GHb concurrently on three separate occasions spanning 4 wk in 41 patients with non-insulin-dependent diabetes mellitus (NIDDM) and, for contrast, 5 with insulin-dependent diabetes mellitus (IDDM). Most of the NIDDM subjects were obese, with initial FPG levels ranging from 93 to 355 mg/dl. The reliability of each test was estimated by calculating two measures: the intraclass correlation coefficient (rho I) and the coefficient of variation (CV) for the repeated test values. For NIDDM patients treated with diet or oral hypoglycemic agents (OHA), rho I for FPG, log(FPG), and GHb were very similar. For insulin-treated NIDDM patients, rho I for FPG was somewhat lower than the coefficient in other treatment groups, and the reliability of FPG by this measure did not match the reliability of GHb within the limits of statistical significance. By analyzing the CV of test values repeated within subject, the reliability of FPG did not differ from GHb in any of the NIDDM treatment groups. Although patients were recruited sequentially to minimize sample selection bias, caution must be exercised in the interpretation of the statistical analyses of reliability with either rho I or CV due to limitations imposed by small sample size.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Overview article: basal lamina of epidermis, muscle fibers, muscle capillaries, and renal tubules: changes with aging and in diabetes mellitus.

Using autopsy material from 14 diabetics and 10 controls (8-84 years old), the authors measured the thickness of basal lamina (BL) in skeletal muscle capillaries, renal tubules, skeletal muscle fibers, and epidermis to determine whether BL accumulation is a generalized phenomenon or limited only to certain anatomic structures. The four structures were selected because earlier experiments in animals have shown that in two (muscle capillaries and renal tubules) BL accumulates as a by-product of cell renewal while in the other two (muscle fibers and epidermis) it does not. In human tissues we found that BL accumulates in muscle capillaries and renal tubules but not in muscle fibers and epidermis, in muscle capillaries and in renal tubules it accumulates in controls and in diabetics as a function of aging, more BL in both anatomic structures accumulates in diabetics than in controls, and the extent of BL accumulation in muscle capillaries and renal tubules does not correlate with duration of diabetes mellitus. In addition to the fact that BL does not accumulate in all anatomic structures in which BL is normally present, the observations indicate that diabetes alone is not responsible for BL accumulation, diabetes exaggerates age-dependent accumulation of BL, and accumulation of BL in man is probably a by-product of cell renewal.

Adolescent↗