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Biomedical subjects

D M McCarthy

Publications and source records attributed to D M McCarthy.

At least 91 records · Page 5Linked to original sources

Renin secretion by the spontaneously diabetic rat.

Renal function studies and measurements of in vivo plasma renin activity (PRA), kidney renin content, and renin secretion by isolated, perfused kidneys were performed in spontaneously diabetic and nondiabetic BioBreeding/Worcester (BB/W) rats. Diabetic animals evidenced hyperglycemia, glycosuria, and plasma volume expansion. After dietary sodium deprivation, plasma volume fell to levels equivalent to those of sodium-deprived, nondiabetic rats. Dietary sodium deprivation evoked a larger proportional increase in PRA among diabetic than nondiabetic animals, although PRA before sodium restriction was equivalent in the two groups. Basal renin release (RR) was higher from isolated, perfused kidneys from diabetic rats than from nondiabetic kidneys. Diabetic kidneys, moreover, displayed increased kidney renin content (KRC). By contrast, while isoproterenol (10(-5) M) stimulated a nearly fivefold increment in RR from nondiabetic, perfused kidneys, a negligible effect was observed in diabetic kidneys. The dose-response curve of renin secretion (as a proportion of total renal content) in response to isoproterenol was shifted downward. Hence, while KRC and spontaneous RR by isolated, perfused kidneys were increased, the increment in PRA with salt depletion and the renin-secretory response to isoproterenol in vitro were impaired. We propose that specific defects in renin secretion, in particular, the response to beta-adrenergic stimulation, may be operative in diabetes.

Animals↗

Cryptosporidiosis in immunocompetent patients.

The intestinal protozoan cryptosporidium is known to cause diarrhea in immunocompromised patients, but few cases have been reported in detail in immunocompetent persons. During a 12-month period, we identified cryptosporidium in the stools of 43 immunocompetent patients. The numbers of cases were increased in those under 4 years old and in those from 30 to 39 years old. Of 30 index cases, 23 (77 per cent) were diagnosed in the late summer or the fall. Fifteen of the 43 patients (35 per cent) had other gastrointestinal pathogens, of which only Giardia lamblia was statistically associated with cryptosporidium. In the 28 patients in whom other gastrointestinal pathogens were not identified, the clinical manifestations were predominantly watery, nonbloody diarrhea and, less commonly, abdominal discomfort, anorexia, fever, nausea, and weight loss. The infection was self-limited in all 43 patients. Clustering of cases occurred in a day-care center and in two families. These clinical observations confirm worldwide findings and suggest that cryptosporidium is a relatively common nonviral cause of self-limited diarrhea in immunocompetent persons in the northeastern United States.

Adolescent↗

Accuracy of left ventricular ejection fraction using the nuclear stethoscope in left ventricular aneurysm.

Although the nuclear stethoscope, a nonimaging probe, accurately determines left ventricular (LV) ejection fraction (EF), its reliability in patients with LV aneurysm has not been established. Accordingly, LVEF was determined using the nuclear stethoscope and compared with that determined by equilibrium gated blood pool scanning in 29 patients, 1 studied on 2 separate occasions, for a total of 30 patient studies. Patient studies were separated into 2 groups. Patients in group I (n = 20) had no gated blood pool evidence for aneurysm, and those in group II (n = 10) had discrete focal akinesia or dyskinesia. Nineteen patients (13 in group I and 6 in group II) had 2 separate nuclear stethoscope acquisitions. In group I, EF determined by gated blood pool scanning (53 +/- 4%, mean +/- standard error) did not differ from that determined by nuclear stethoscope (51 +/- 4%). EF determined using either gated blood pool scanning (32 +/- 6%) or nuclear stethoscope (35 +/- 5%) was significantly lower in group II than in group I, although nuclear stethoscope and gated blood pool scanning did not differ. Reproducibility was excellent (r = 0.96). Overall, nuclear stethoscope and gated blood pool EFs correlated closely (r = 0.93), and the correlation coefficients were similar in groups I (r = 0.92) and II (r = 0.92). The slopes of the regression curves for group I (0.97) and group II (0.92) were not statistically different. These results confirm the accuracy and reproducibility of LVEF determination by nuclear stethoscope and specifically demonstrate its reliability in patients with LV aneurysm.

Adult↗

Sources of variability in quantitative thallium analysis.

Nineteen patients undergoing exercise thallium scanning had two separate redistribution 40 degree LAO acquisitions obtained; the gamma camera was repositioned between the views. Data were analyzed by generating 60-point circumferential profile curves for each of the 38 images and the variability of individual points and 18 degrees and 36 degrees segments was determined. Intraobserver variability, assessed by reanalyzing the scans one week later, was approximately 5.0%. The interobserver variability was of similar magnitude (approximately 6%). The total reimaging variability was, however, significantly larger (approximately 13%). It is concluded that quantitative image analysis is highly reproducible with low intra- and interobserver variabilities, but the act of repositioning and reimaging introduces significant additional variability. This may limit the ability of quantitative thallium scanning to document changes in the size of defects.

Adult↗

Gastric secretion and hormonal interactions in multiple endocrine neoplasia type I.

Results of preparathyroidectomy and postparathyroidectomy studies in a patient with multiple endocrine neoplasia type I and gastrinoma suggest that hyperparathyroidism unmasks occult gastrinoma and related secretory abnormalities. Three of four diagnostic findings were later obscured by parathyroidectomy and normalization of serum calcium concentration. Basal acid output, basal acid output/maximal acid output ratio, and serum gastrin concentration were decreased from values consistent with gastrinoma to normal. The secretin stimulation test, though still positive, was attenuated. These observations suggest that in multiple endocrine neoplasia type I, normal values for serum gastrin concentration, gastric secretion, and secretin stimulation may not exclude gastrinoma. The investigations clarify the interpretation of a voluminous but confusing literature on the interrelationship between hyperparathyroidism and altered gastric function in the presence or absence of Zollinger-Ellison syndrome.

Adenoma↗

Effect of myocardial ischemia and type I antiarrhythmic drug therapy on exercise QT intervals.

Direct measurement of the QT interval during exercise is the preferred method to assess duration of this interval with changes in heart rate. The influence of exercise induced ischemia or type I antiarrhythmic drugs on the exercise QT interval has not been well studied. Exercise electrocardiograms and thallium scintigraphy were performed in three groups-normals, patients with coronary artery disease, and patients taking type I antiarrhythmic drugs. The change in QT interval with heart rate increases during exercise was compared among the three groups. The QT interval shortened progressively in the normal group. Demonstrable myocardial ischemia (positive thallium scan) had no effect on the QT interval. Type I antiarrhythmic drugs prolong the QT interval at rest compared to normals, but the interval shortened to the same degree as in normals during exercise. Thus, normal values can be used to compare QT intervals in patients with coronary artery disease. These values do not apply to patients receiving type I antiarrhythmic drugs.

Anti-Arrhythmia Agents↗

Multiple-hospital survey of ejection-fraction variability using a cardiac phantom.

A dynamic cardiac phantom was used to provide identical input data at 11 different nuclear medicine laboratories throughout the Philadelphia area, and the variability in the resulting calculations of ejection fraction (EF) was assessed. The variability observed between different operators using the same computer system averaged 3 EF units, which was similar to that between different observers using different types of computers. In the range of low ejection fractions, however, there was a suggestion that EFs calculated with an MDS computer were slightly lower than those from a DEC computer.

Cardiac Output↗

Genomic alterations involving the c-myc proto-oncogene locus during the evolution of a case of chronic granulocytic leukaemia.

In a patient with Ph-positive chronic granulocytic leukaemia who had 3 separate episodes of promyelocytic transformation associated with new cytogenetic and genetic changes DNA from the peripheral-blood leucocytes obtained during the second episode of transformation showed an 8-fold to 16-fold amplification of cellular myc proto-oncogene (c-myc) sequences, and rearrangement of these sequences. There was no amplification or rearrangement of c-myc sequences in DNA from leucocytes collected during the chronic phase, nor were these sequences amplified in DNA from leucocytes collected during the third episode of transformation. These observations show that new clones of cells that proliferate during the evolution of a myeloid leukaemia can carry genetic changes in addition to any recognisable karyotypic changes. Such genetic changes might underlie the progression of the disease.

Adult↗

Bayesian analysis using Fourier transforms of thallium-201 scintiscans to predict the presence of coronary artery disease.

Bayes' theorem of conditional probability was applied to the diagnosis of coronary artery disease (CAD) using thallium-201 scintigraphy as the testing procedure. Thallium-201 scintiscans were evaluated with a discriminant function previously developed using the amplitude coefficients of the Fourier transforms of the scans. The technique was applied prospectively to a population of 100 patients undergoing diagnostic coronary arteriography and thallium-201 scintigraphy, including 83 patients with CAD (70% or greater stenosis of luminal diameter) and 17 control subjects. A pretest probability of CAD was determined for each patient from the patient's age, sex and anginal symptoms. The pretest probability was combined with the patient's discriminant score to determine a posttest probability for CAD. For patients with CAD, the mean posttest probability was 0.85. Moreover, 57 of 83 patients (69%) had posttest probabilities exceeding 90%, including 40 patients (48%) with posttest probabilities exceeding 99%. For control subjects, the mean posttest probability was 0.19, with 11 of 17 (65%) having a posttest probability of less than 10%. Overall, 68 subjects had a posttest probability either less than 10% or more than 90% of which 63 were correctly classified (93%). Using a 50% posttest probability as a cutoff for classification, the technique has an 89% sensitivity, an 82% specificity and an overall accuracy of 88%. Therefore, this method objectively distinguishes patients with CAD from control subjects and provides a measure of the certainty of diagnosis. In addition, the discriminant function avoids the problem of inter- and intraobserver variability in visually interpreting thallium-201 scans.

Adult↗

A role for 1,25-dihydroxyvitamin D3 in control of bone-marrow collagen deposition?

It is suggested that 1,25-dihydroxyvitamin D3 (1,25-[OH]2D3), the active hormonal metabolite of vitamin D3, inhibits the formation of fibrous tissue (mainly collagen) in bone-marrow and also increases its degradation. 1,25-(OH)2D3 inhibits the proliferation of megakaryocytes which normally promote collagen synthesis. The hormone also directly antagonises collagen synthesis. Degradation of fibrous tissue is mediated by monocytes and macrophages, which contain collagenase, and the number and activity of these cells is increased by 1,25-(OH)2D3. Thus the various actions of this hormone contribute collectively to a reduction in collagen content; conversely a deficiency of 1,25-(OH)2D3 may allow abnormal accumulation of collagen in the marrow.

Bone Marrow↗

Changes in surface antigens of HL-60 cells during differentiation in vitro.

We have examined the pattern of binding of monoclonal antibodies OKM 1, FMC 10, FMC 12, FMC 13, FMC 17 and FMC 33 to human promyelocytic leukaemia (HL-60) cells. We found that the expression of antigens detectable with FMC 17 and FMC 33 (specific for monocytes and macrophages) was increased by exposure of HL-60 cells to 1,25-dihydroxyvitamin D3 but not by exposure of HL-60 cells to 12-tetradecanoyl phorbol-13-acetate (TPA). The antigen detected with the OKM 1 antibody was highly induced by TPA. The expression of granulocyte-specific antigens detected by FMC 10 and FMC 13 was increased during induction of granulocytic maturation; these antigens were retained during monocyte-macrophage differentiation of HL-60 cells. We conclude that in some cases the expression of particular antigens during maturation of malignant cells proceeds normally while in other cases antigenic differences between leukaemic and normal cells at equivalent levels of maturation can be detected.

Antibodies, Monoclonal↗

Fragments of prosomatostatin isolated from a human pancreatic tumour.

Six peptides from an extract of a human pancreatic tumour were purified to homogeneity by HPLC. Amino acid composition and chemical properties indicated probable structures the same as somatostatin-14, somatostatin-28 (1-12), [Met(O)8]somatostatin-28 (1-12), [Met(O)8]somatostatin-28 (1-10), somatostatin-25 (1-9) and [Met(O)5]somatostatin-25 (1-9). The structure of somatostatin-14 was confirmed by sequence analysis. The isolation of these peptides provides insight into the processing of prosomatostatin in the tumour cells.

Amino Acid Sequence↗