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R J Carroll

Publications and source records attributed to R J Carroll.

At least 73 records · Page 4Linked to original sources

Conditional regression models for transient state survival analysis.

Survival models are important tools for the analysis of data when a disease event occurs in time and subjects are lost to follow-up. Many models, however, can also be adapted for use when an event is characterized by transitions through intermediate states of disease with increasing severity. In this presentation, such adaptations will be demonstrated for a class of conditional regression models for the analysis of transient state events occurring among grouped event times. The type of conditioning that will be described is useful in providing comparisons of specific disease states and an assessment of transition-dependent risk factor effects. An example will be given based on the Framingham Heart Study.

Adult↗

Urinary enzyme concentrations in healthy horses.

Urinary concentrations of gamma glutamyl transferase (GGT), alkaline phosphatase (AP), aspartate aminotransferase (AsAT), and alanine aminotransferase (AAT) were measured in 32 healthy horses (16 geldings and 16 females) at the same time on 2 consecutive days. The subjects were divided into 4 ages groups, each comprising 8 horses (4 of each sex). In 10 of the geldings, urine was collected continuously for 72 hours, with catheterized samples being obtained at 0800, 1400 and 2000 hours, and an aliquot of the pooled urine being taken every 24 hours. Urinary enzyme activity was found to be unrelated to serum concentrations of the same enzymes. There was no diurnal variation in the activity of the urinary enzymes. Neither the sex of the horses nor their age influenced urinary enzyme activity regardless of whether it was expressed in absolute terms or in reference to creatinine excretion Normal values of GGT and AP were determined to be 3.3 +/- 3.0 IU/L, (2.5 +/- 3.4 IU/g Cr); and 10.2 +/- 4.0 IU/L (6.7 +/- 3.9 IU/g Cr) respectively. Neither AAT or AsAT were present in detectable levels. The mean urine creatinine concentration of all horses was 1.56 +/- 0.42 g/L with no significant age or sex variation being evident.

Alanine Transaminase↗

Combination chemotherapy for multiple myeloma with BCNU, cyclophosphamide, vincristine, melphalan, and prednisone (M-2 protocol).

54 consecutively referred, previously untreated patients with stage II and III multiple myeloma have been treated with the M-2 protocol. 50% of patients had a performance status of less than 50%. 13% were stage II and 87% stage III. In 50 of 54 patients (90%), and objective response according to the Myeloma Task Force was achieved; 10% of the responses have been complete (9+, 15+, 17+, 18+ and 66+ months). Remissions now range from 1 to 86+ months. The actuarial median survival determined from the initiation of therapy will exceed 4 years. Toxicity was acceptable with mild myelosuppression. These results confirm the efficacy of the M-2 protocol in multiple myeloma with regards to response rate and survival.

Adult↗

Modification by the Hancock T6 process of calcification of bioprosthetic cardiac valves implanted in sheep.

The effectiveness of the T6 process (surfactant treatment) to decrease calcification of porcine aortic valvular (PAV) and bovine pericardial (BPV) bioprostheses was investigated. Morphologic and biochemical studies were made of standard and T6-treated PAVs and BPVs that had been implanted for a mean of 20 weeks in the tricuspid position in young sheep. Gross, radiographic, histologic and ultrastructural observations showed that the calcific deposits were less severe in T6-treated (n = 9) than in standard PAVs (n = 7), but were similar in severity in T6-treated (n = 6) and standard BPVs (n = 7). This was confirmed by results of quantitative analyses for calcium in half of each cusp of each explanted valve. Because these results showed large differences in standard deviations in the 4 groups of sheep, natural logarithmic and square-root transformations were used for statistical comparisons. The mean calcium content (milligrams of calcium per gram of dry tissue) of standard PAVs (111 +/- 53) was greater than that of T6-treated PAVs (11 +/- 3) (p = 0.0037). The calcium content of T6-treated PAVs was lower than that of T6-treated BPVs (96 +/- 26) (p = 0.031). However, the calcium content of standard BPVs (35 +/- 13) was not different from that of T6-treated BPVs or standard PAVs. Thus, under conditions of relatively short-term implantation in the sheep model, the T6 process is useful for decreasing the extent of calcification in PAVs, but not in BPVs.

Animals↗

DNA synthesis in rat atrial myocytes as a response to left ventricular infarction. An autoradiographic study of enzymatically dissociated myocytes.

An autoradiographic study was performed on enzymatically isolated atrial muscle cells to examine the DNA synthetic response of atria to left ventricular infarction. DNA synthesis was studied in left and right atrial myocytes and nonmyocytes of: young Sprague-Dawley rats 11 days after ligation of the left coronary artery; rats subjected to a sham surgical procedure without coronary artery ligation; unoperated rats. Each animal received a series of ten injections of tritiated thymidine at 12-h intervals, beginning on the fifth post-operative day; cells were isolated 36 h after the last injection. In infarcted animals, 37.1% of the left atrial myocytes were labeled and binucleated, and 6.5% were labeled and mononucleated; 13% of the right atrial myocytes were labeled and binucleated, while 12.7% were labeled and mononucleated. For both the left and right atria, the incidence of tritiated thymidine label in myocytes of the sham-operated group was similar to that of the unoperated controls, indicating that the surgical procedure did not stimulate DNA synthesis in atrial myocytes. In both left and right atria of the infarcted group, non-muscle cells were labeled to a greater extent (49.9% and 47.1%) than in the sham-operated group (22% and 20.8%), which in turn showed labeling to a greater extent than did the unoperated control group (10.9% and 11.6%), indicating that DNA synthesis was stimulated in non-myocytes of the atria by the sham operation and was further stimulated by experimental infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Interpreting multiple logistic regression coefficients in prospective observational studies.

Multiple logistic models are frequently used in observational studies to assess the contribution of a risk factor to disease while controlling for one or more covariates. Often, the covariates are correlated with the risk factor, resulting in multiple logistic coefficients that are difficult to interpret. This paper highlights the problem of assessing the magnitude of a multiple logistic coefficient and proposes a supplemental procedure to the usual logistic analysis for describing the relationship between a risk factor and disease. An example is given, along with results that are not apparent when the multiple logistic coefficient is considered alone. Conclusions that are presented are important in biologic studies if describing the effect of a risk factor is influenced by correlation with a covariate.

Coronary Disease↗

Changes in DNA content, number of nuclei and cellular dimensions of young rat atrial myocytes in response to left coronary artery ligation.

Studies of enzymatically isolated myocytes from atria of young male Sprague-Dawley rats at 11 days after left coronary artery ligation show that a major response of atrial myocytes to ventricular infarction is binucleation. In sham-operated animals, 23.2% of left and 15.5% of right atrial myocytes were binucleated, compared to 77.8% of left and 40.5% of right atrial myocytes of infarcted animals. Examination of 150 g and 250 g unoperated control animals indicate that this response is occurring at a time when a small but significant amount of binucleation is also occurring as a normal part of growth. Using a Feulgen-acriflavine-SO2 method for cytofluorometry, a significant increase in ploidy was seen in left atrial myocytes of infarcted animals over those of sham or control animals. The number of left atrial myocytes in infarcted animals having a ploidy level above 3C was 10.8% above sham values. The mean length of binucleated myocytes of left atrium was significantly greater in infarcted animals (119.8 microns) than in sham-operated animals (97 microns) and the mean length of mononucleated myocytes was greater in infarcted animals (104.1 microns) than in sham-operated animals (77 microns). Thus, cardiac myocytes are capable of a substantial response to a stressful situation by increases in cell length, number of nuclei and ploidy. Study of a model system such as the rat atrium may yield an understanding of the mechanisms involved in the induction of these nuclear changes.

Animals↗

Turbulent blood flow in the ascending aorta of dogs.

A conical hot film anemometer probe was used to measure instantaneous velocities in the ascending aorta of anaesthetised, open-chest dogs. The probe was mounted on a saddle which allowed traversal of the aorta in 1 mm increments 4 cm above the aortic valve. From these point measurements, the radial distribution of velocity was obtained by averaging ten cardiac cycles. The contractile state of the heart was increased by sequential intravenous infusions of isoprenaline. The absolute peak centreline velocity in the baseline state ranged from 28 to 56 cm x s-1 and, in 20 micrograms x min-1 isoprenaline infusion, from 39 to 112 cm x s-1. Two major effects of isoprenaline on blood flow were noted: 1) isoprenaline dramatically increased peak centreline velocity, and 2) disturbances resembling turbulence appeared as peak velocity increased. With isoprenaline infusion disturbances existed throughout the deceleration portion of the aortic blood flow. Analysis of the frequency components of the velocity wave was performed, and significantly higher frequency components up to 100 Hertz were found in the turbulent cases compared to the laminar ones. Turbulent flow or disturbed flow is found when the ratio of Reynolds number to Womersley number is above 200. In general the hot film measurements showed that both laminar and disturbed velocity profiles tended to be flat throughout the cardiac cycle, with the sharp velocity gradient confined to the region of the wall. Turbulent normal stress during the deceleration portion of aortic blood flow were found in the orders of 15 to 30 dynes x cm-2 and the wall shear stresses were found to be from 10 dynes x cm-2 at the baseline condition to 50 dynes x cm-2 during the 20 micrograms x min-1 isoprenaline infusion.

Animals↗

Conversion of proinsulin to insulin: involvement of a 31,500 molecular weight thiol protease.

A lysed crude secretory granule fraction from rat islets of Langerhans was shown to process endogenous proinsulin to insulin with a pH optimum of 5.0--6.0. The converting activity in the lysed fraction was not inhibited by serine protease inhibitors (diisopropyl fluorophosphate, soybean trypsin inhibitor, and aprotinin) or metalloprotease inhibitors (EDTA and o-phenanthroline) but was inhibited by some thiol protease reagents (p-chloromercuribenzenesulfonic acid, antipain, and leupeptin) but not by others (N-ethylmaleimide and iodoacetamide). N alpha-p-Tosyl-L-lysyl chloromethyl ketone only mildly inhibited at higher concentrations, whereas L-alanyl-L-lysyl-L-arginyl chloromethyl ketone was a powerful inhibitor. L-Alanyl-L-lysyl-L-arginyl chloromethyl ketone was [125I]iodotyrosylated and used as an affinity labeling agent for the converting activity. Because the crude granule preparation contained contaminating lysosomes the affinity labeling of the granule preparation proteins was compared with that in liver lysosomes purified from rats injected with Triton WR1339. In the crude granule fraction the affinity label bound in a cysteine-enhanced manner to a single 31,500 molecular weight protein, but in purified liver lysosomes the major affinity-labeled protein had a molecular weight of 25,000 and minor 31,500 and 35,000 molecular weight proteins were also labeled. Evidence suggests that these proteins are thiol proteases and that in islets the 31,500 molecular weight thiol protease is involved in the conversion of proinsulin to insulin.

Affinity Labels↗

The joint associations of multiple risk factors with the occurrence of nosocomial infection.

To compare nosocomial infection rates estimated in different time periods or in different hospitals, it is necessary to control for differences in the distribution of factors that substantially influence a patient's susceptibility to infection. To evaluate the associations of multiple risk factors with the occurrence of infection at each of four major sites and to develop composite measures for use in controlling for differences in the distribution of risk among groups of patients, we used a multivariate categorical data analysis technique to study the infection experience of 169,518 patients admitted in 1970 to the 338 hospitals studied in the Study on the Efficacy of Nosocomial Infection Control (SENIC, Project). The relative importance of risk factors and their complex interactions varied by site. The factors found to be highly important for one or more sites were duration of urinary catheterization, the patients' intrinsic risk as reflected in their diagnoses and types of surgical procedures, duration of preoperative hospitalization, duration of operation, anatomic location of surgical procedure, previous infection and steroid or immunosuppressive therapy. Site-specific risk strata and estimates of each patient's probability of acquiring infection were developed from these data for use in future SENIC analyses.

Age Factors↗

Identification of prosomatostatin in pancreatic islets.

A 12.5-kilodalton protein not related to insulin or glucagon was detected in pulse-chase-labeled rat islets of Langerhans. Although this protein reacted poorly with various somatostatin antisera, analysis of two-dimensional peptide maps showed that it contains all of the tryptic fragments of somatostatin, which is located at its COOH terminus. Proteolytic conversion of the putative prosomatostatin, which took place parallel to the processing of proinsulin and proglucagon in pulse-chase experiments, coincided with the appearance of newly synthesized somatostatin and proceeded without the apparent involvement of major intermediate forms.

Amino Acid Sequence↗

Identification and processing of proglucagon in pancreatic islets.

Immunoprecipitation and tryptic peptide analysis of newly synthesized proteins from rat islets have identified an 18,000 molecular weight (MW) protein as proglucagon. Conversion of this precursor was kinetically similar to the conversion of proinsulin and resulted in the formation of both pancreatic glucagon and a 10,000-MW protein lacking this hormonal sequence.

Animals↗

Detection and kinetic behavior of preproinsulin in pancreatic islets.

Newly synthesized rat islet proteins have been analyzed by polyacrylamide slab gel electrophoresis and fluorography. A minor component having an apparent molecular weight of 11,100 was identified as preproinsulin by the sensitivity of its synthesis to glucose, the pattern of NH2-terminal leucine residues, and the rapidity of its appearance and disappearance during incubation of islets or islet cell tumors. A small amount of labeled peptide material which may represent the excised NH2-terminal extension of preproinsulin or its fragment was also detected. The kinetics of formation and processing of the preproinsulin fraction were complex, consisting of a rapidly turning over component having a half-life of about 1 min and a slower minor fraction that may have bypassed the normal cleavage process. The electrophoretic resolution of the preproinsulin and proinsulin fractions into two bands each is consistent with the presence of two closely related gene products in rat islets rather than intermediate stages in the processing of these peptides.

Adenoma, Islet Cell↗

Dopaminergic stimulation of cyclic AMP accumulation and parathyroid hormone release from dispersed bovine parathyroid cells.

The effects of dopaminergic agonists and antagonists have been studied in dispersed bovine parathyroid cells. Dopaminergic agonists caused a transient 20- to 40-fold increase in cellular cyclic AMP and a 2- to 3-fold increase in parathyroid hormone release. Dose-response relationships were similar for cyclic AMP accumulation and hormone release, whether studied by increasing agonist concentration or by increasing concentration of antagonist with constant agonist. The effects on the dopamine receptor could be differentiated from those of the previously characterized beta-adrenergic receptor by specific inhibitors. These results appear to represent proof with a homogeneous cell population that dopaminergic receptors linked to adenylate cyclase can regulate a secretory process mediated by cyclic AMP. This system should be useful in further studies on dopamine receptors and should provide a valid tool for determining interactions of radiolabeled ligands with such receptors.

Adrenergic beta-Agonists↗

Mitral valve prolapse in coronary artery disease.

Mitral valve motion, left ventricular segmental contraction and severity of arterial stenosis were analyzed in 92 patients with coronary artery disease and 28 patients with "atypical chest pain" and normal coronary arterio-rams. Mitral valve motion was evaluated for the presence or absence of leaflet prolapse. Segmental contraction was evaluated by calculating the percent shortening of six chords of the left ventricle measured from right anterior oblique ventriculograms. The severity of disease in each coronary vessel (left anterior descending, left circumflex and right coronary) was graded on a scale of 1 (0 to 30 percent stenosis) to 5 (complete occlusion). Mitral valve prolapse was not suspected clinically but observed angiographically in 15 of 92 patients with coronary artery disease and in 5 of 28 patients with normal coronary arteriograms. In nine patients with coronary artery disease, the prolapse was restricted to the posterior leaflet, in five it was in both the anterior and the posterior leaflets and in one patient in the anterior leaflet only. Mitral regurgitation was noted in seven patients with coronary artery disease; it was mild in six and moderate in one. Among the patients with coronary artery disease, 12 of the 15 (80 percent) with mitral valve prolapse had left ventricular asynergy compared with 63 of the 77 (82 percent) without valve prolapse. The mean scores for severity of disease in the left anterior descending, circumflex and right coronary arteries were, respectively, 4.2, 2.5 and 3.2 in the patients with valve prolapse and 4.2, 2.2 and 3.5 in those without prolapse. In summary, there was no significant correlation between mitral valve prolapse and distribution of coronary arterial obstructions or abnormal patterns of left ventricular segmental contraction. There was a high frequency of mitral valve prolapse in patients with severe coronary artery disease and in those with normal coronary arteriograms and atypical chest pain.

Adult↗

Retrograde coronary artery flow in aortic valve disease.

Retrograde coronary artery flow was observed angiographically in 43 patients with aortic stenosis and/or regurgitation. In the 24 patients with pure or predominant aortic stenosis, retrograde flow was seen in all 24 during end-systole. In the eight patients with pure aortic regurgitation, retrograde flow was seen mainly during end-diastole (6/8). Among the 11 patients with stenosis and regurgitation, retrograde flow was both end-systolic and enddiastolic. Dominant left coronary arteries were seen in 13 patients; 13 showed retrograde flow in the dominant arteries. Dominant right coronary arteries were seen in 25 patients: all 25 showed retrograde flow equally in the right and left coronary. Five of the 43 patients could not be evaluated for dominance because of coronary artery occlusions. The severity of retrograde flow did not correlate with usual clinical, hemodynamic or tension-stress parameters: angina, electrocardiographic abnormality, end-diastolic pressure or volume, end-systolic pressure or volume, ejection fraction, severity of aortic regurgitation, peak or mean valve gradient, aortic valve area, myocardial tension and stress calculations, or DPTI:SPTI. In summary, retrograde coronary artery flow was seen in all 43 patients with severe aortic valve disease. The time in the cardiac cycle when retrograde flow occurred was related to the type of valve disease. Retrograde flow was seen mainly in the coronary arteries supplying the left ventricle and may result from increased regional myocardial stresses.

Adult↗