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Biomedical subjects

K A Kirk

Publications and source records attributed to K A Kirk.

At least 55 records · Page 3Linked to original sources

Spectrum of glomerular and tubulointerstitial renal lesions associated with monotypical immunoglobulin light chain deposition.

The purpose of this study was to characterize the spectrum of renal lesions associated with plasma cell dyscrasias from a population of patients who had renal disease identified by kidney biopsy. Thirty-six patients (2.6% of 1361 kidney specimens examined over 6 years) had evidence of monotypical light chain with or without concomitant heavy chain deposition. A variety of lesions was found, including (a) AL-amyloid and glomerular nonamyloid light chain deposition manifesting as nodular, membranoproliferative, mesangioproliferative, and "minimal-change" glomerulopathies; (b) fibrillary glomerulopathy; (c) tubulointerstitial lesions (cast nephropathy, acute tubular necrosis, and tubulointerstitial nephritis); and (d) vascular (arterioles and small and medium-sized arteries) lesions. AL-amyloid was the most common renal lesion (39%), nonamyloid deposition occurred second most commonly (33%), and cast nephropathy ("myeloma kidney") was third most frequent (14%). Clinical and laboratory manifestations of a plasma cell dyscrasia were frequently subtle. Immunoelectrophoresis of both serum and urine did not demonstrate a monotypical light chain or immunoglobulin in almost 35% of this population. Thus, the correct diagnosis was not considered in the majority of these patients before biopsy. Progressive deterioration of renal function was common with all of the lesions, except for proximal tubule injury, which tended to improve over the period of study. Renal biopsy with careful examination for monotypical light chain with or without associated heavy chain deposition using immunofluorescence or immunoelectron microscopy was crucial in identifying and characterizing the varied lesions associated with lymphoplasmacytic disorders.

Amyloid↗

Accuracy of digital Holter monitoring of extent and duration of ischemic episodes compared to analog recording.

Analog amplitude-modulated Holter devices are in widespread use for arrhythmia detection, but their reliability remains questioned for ST-segment analysis. In contrast, recently developed digital Holter devices immediately digitize and analyze the electrocardiogram (ECG) on-line and may therefore be more reliable for ST-segment analysis. To test this hypothesis, the results of digital, on-line, 2-channel ST-segment analysis were directly compared to those of analog amplitude-modulated recordings in identical leads (CM5 and CM3), using a stripchart recorder meeting the American Heart Association specifications as the standard. Thirty-five patients (25 with coronary artery disease and 10 control subjects) underwent graded treadmill exercise testing. The reference ECG mean value for ST-segment depression in CM5 was -1.4 +/- 1.2 mm and in CM3 -0.5 +/- 1.2 mm. For digital analysis, the mean values and correlation coefficients for CM5 were -1.5 +/- 1.1 mm (r = 0.97) and for CM3 -0.8 +/- 1.3 mm (r = 0.93). For analog recording, the results for CM5 were -2.1 +/- 1.7 mm (r = 0.88) and for CM3 -1.3 +/- 1.9 mm (r = 0.85). The mean duration of ST-segment depression with the reference ECG was 7.1 +/- 4.1 minutes. Digital Holter showed a significantly better agreement (7.4 +/- 4.4 min, r = 0.97) than analog Holter (9.6 +/- 5.6 min, r = 0.84). Because analog amplitude-modulated Holter recordings overestimated the degree and duration of ischemic episode, digital, on-line and full disclosure devices should be preferred to assess myocardial ischemia.

Algorithms↗

Evaluation of a risk scoring system as a predictor of preterm birth in an indigent population.

A risk scoring system designed to predict spontaneous preterm birth was implemented in a large, indigent population as part of a multicenter trial of preterm birth prevention. A total of 7478 women with singleton gestations were screened and followed up prospectively at the Birmingham project center. Patients who had an indicated preterm delivery or a fetal anomaly were excluded from the study population. Analysis by assigned risk score and parity showed that, whereas the sensitivity and positive predictive value were better in multiparous women than in nulliparous women, overall the values were low. Logistic regression analyses of the multiparous and nulliparous populations showed independent sets of significant (p less than or equal to 0.05) risk variables. A history of preterm delivery and a low prepregnancy weight were the most predictive risk factors in the multiparous and nulliparous models, respectively. We conclude that the clinical usefulness of a risk scoring system to predict spontaneous preterm birth in an indigent population is limited.

Age Factors↗

Evidence for a central site of action to explain the negative chronotropic effect of atropine: studies on the human transplanted heart.

The chronotropic response to atropine is biphasic; low doses cause slowing of the sinus rate and high doses cause acceleration. Although it is accepted that atropine functions as a competitive antagonist at high doses, the mechanism of the negative chronotropic response at low doses is controversial. Specifically, it is unclear whether the effect is mediated centrally or peripherally. Since at the time of cardiac replacement all central nervous system connections to the heart are severed, the transplanted heart is a unique model for separating these effects. Graded doses of atropine sulfate (0.5, 1.0, 2.0, 4.0, 8.0 and 40.0 micrograms/kg body weight) were administered to 12 human heart transplant recipients to test the hypothesis that the bradycardiac effect of low dose atropine is centrally mediated. The baseline sinus cycle lengths of the decentralized donor and innervated native sinus nodes were 694 +/- 20 and 733 +/- 27 ms, respectively. At the 0.5 and 1.0 microgram/kg doses, the cycle lengths of the native sinus node increased by 29.1 +/- 13.5 and 23.1 +/- 14.2 ms, respectively. At the 2.0 micrograms/kg dose the sinus cycle length again shortened to control. At the maximal dose of atropine the sinus cycle length shortened by 138.3 +/- 29.7 ms compared with control. In contrast, the decentralized donor sinus node exhibited a flat dose response to atropine. High dose atropine (40 micrograms/kg) caused no change in the donor heart's atrial effective refractory period, corrected sinus node recovery time, or sinoatrial conduction time measured by either the Strauss or the Narula method.(ABSTRACT TRUNCATED AT 250 WORDS)

Atropine↗

Renal insufficiency in treated essential hypertension.

We analyzed the clinical courses of 94 patients with treated primary hypertension and initially normal serum creatinine concentrations (less than or equal to 133 mumol per liter [less than or equal to 1.5 mg per deciliter]) who were followed for a mean (+/- SD) of 58 +/- 34 months (range, 12 to 174) to determine the frequency with which renal function deteriorated and the factors associated with deterioration. Fourteen patients (15 percent) had an increase in serum creatinine concentrations (greater than or equal to 35 mumol per liter [greater than or equal to 0.4 mg per deciliter]); in 16 percent of the 61 patients with apparently good control of blood pressure, the serum creatinine concentration rose 59 +/- 33 mumol per liter (0.67 +/- 0.38 mg per deciliter). Despite good control of diastolic blood pressure (less than or equal to 90 mm Hg), black patients were twice as likely as white patients to have elevations in serum creatinine (23 percent vs. 11 percent). Stepwise discriminant function analysis showed that a significant rise in the serum creatinine concentration was most likely to occur in association with older age, black race, a higher number of missed office visits, and employment as a laborer. We conclude that although renal function was preserved in 85 percent of patients with treated hypertension, it may deteriorate in some patients despite good blood-pressure control. Our observations may partly explain why hypertension, particularly among black persons, remains a leading cause of renal disease in the United States.

Black People↗

Control of serum potassium during fasting in patients with end-stage renal disease.

In order to evaluate internal potassium balance in patients with end-stage renal disease (ESRD), epinephrine (0.015 micrograms/kg/min) was infused intravenously into normal control (N = 9) and ESRD subjects (N = 7) after a 26 hour fast. Hyperkalemia developed in ESRD patients after 16 hours of fasting, as compared with control subjects (P = 0.02). The hemodynamic response to epinephrine was similar in the two groups. During epinephrine infusion for one hour, the serum potassium decreased in normal subjects, from 4.3 +/- 0.2 mEq/liter to 3.9 +/- 0.1 mEq/liter, but did not change in ESRD patients (P = 0.005). Serum CO2 declined in ESRD, but not in control subjects, while glucose levels were not different in the two groups. Plasma aldosterone was significantly higher in fasting ESRD patients and failed to decrease during epinephrine infusion as compared to controls. Plasma insulin levels remained low in both groups even though serum glucose levels increased. These results demonstrate that hyperkalemia occurs during fasting in ESRD probably as the result of insulinopenia, and suggest that a diminished response to epinephrine may contribute to hyperkalemia.

Adult↗

Baroreflex function in lifetime-captopril-treated spontaneously hypertensive rats.

The effects of lifetime oral captopril treatment on baroreflex control of heart rate and lumbar sympathetic nerve activity were measured in 19-21-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The sensitivity of baroreflex control of heart rate and lumbar sympathetic nerve activity were determined by the slopes of the relation between the change in mean arterial pressure (MAP) (mm Hg) versus the change in pulse interval (msec/beat) and the change in MAP versus the percent change in nerve activity, respectively. Untreated SHR had significantly higher MAP than WKY (157 +/- 3 vs. 115 +/- 3 mm Hg, p less than 0.001) and exhibited a decreased baroreflex control of heart rate. Lifetime treatment with captopril prevented the development of hypertension in SHR (MAP = 110 +/- 5 mm Hg) and increased the sensitivity of baroreflex function. The gains of the baroreflex control of heart rate for captopril-treated SHR and control SHR when MAP was raised or lowered by phenylephrine or nitroprusside were 2.38 +/- 0.49 vs. 1.10 +/- 0.33 msec/mm Hg (p less than 0.05) and 0.74 +/- 0.20 vs. 0.54 +/- 0.09 (NS) msec/mm Hg, respectively. The sensitivity of the baroreflex control of lumbar sympathetic nerve activity was greater in captopril-treated SHR than in control SHR when MAP was increased or decreased (-1.03 +/- 0.26 vs. -0.38 +/- 0.11, p less than 0.05; -0.84 +/- 0.2 vs. -0.04 +/- 0.58 (NS) mm Hg-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Corcoran lecture: the case for or against salt in hypertension. Arthur Curtis Corcoran, MD (1909-1965). Tribute and prelude to Corcoran Lecture of 1988.

Salt intake in excess of body needs has long been considered a factor in the genesis and maintenance of human hypertension; the mechanism is salt retention due to faulty renal excretory efficiency. This discussion reviews clinical studies that make a case either for or against the salt hypothesis. Included is a summary of recent experiences with 4 days of salt depletion and 3 days of salt loading in 96 normotensive control subjects and 40 hypertensive patients. These studies were done to test the hypothesis that salt-sensitive blood pressure changes are quantitatively related to sodium balance. However, we found no statistically significant relation between arterial pressure changes and sodium lost during salt depletion or retained during salt loading. The failure of that hypothesis prompted a study of the known factors that control arterial pressure by using multidimensional response surface modeling for changes produced by salt loading. The analysis indicated that in these experiments salt-sensitive blood pressure changes of hypertensive patients were controlled differently than those of normotensive subjects. In the hypertensive group, the changes were highly predictable by combinations of variables, which featured plasma aldosterone, norepinephrine, and epinephrine. In the normotensive group, the changes were less predictable; fewer of the factors were involved, and plasma renin activity was the featured variable. These findings and results of studies done over the past 50 years indicate that salt-dependent hypertension is controlled by many factors and is not a strict correlate of salt intake.

Aldosterone↗

Brain angiotensin II and baroreceptor reflex function in spontaneously hypertensive rats.

We examined whether the increase in baroreceptor reflex function previously reported in lifetime - captopril-treated spontaneously hypertensive rats (SHR) was due to an inhibition of brain angiotensin II mechanisms. Pregnant and lactating SHR were given oral captopril (100 mg/kg/day). After weaning, pups were maintained on captopril (50 mg/kg/day) until the study (19-21 weeks). Control rats received tap water. One week before study captopril-treated and control SHR were given an intracerebroventricular infusion of angiotensin II (7.5 ng/hr, osmotic pump) or vehicle (artificial cerebrospinal fluid). Baroreceptor reflex control of heart rate was assessed by the slope of the relation between the change in mean arterial pressure (mm Hg) versus the change in pulse interval (msec beat-1). Arterial pressure was raised or lowered by intravenous bolus injections of phenylephrine or nitroprusside, respectively. Central infusion of angiotensin II had no significant effect on mean arterial pressure in captopril or control SHR (captopril-angiotensin II 125 +/- 4 vs. captopril-vehicle 121 +/- 2; control-angiotensin II 169 +/- 5 vs. control-vehicle 173 +/- 7 mm Hg), but it produced a significant rise in basal heart rate (captopril-angiotensin II 371 +/- 10 vs. captopril-vehicle 323 +/- 8, p less than 0.0002; control-angiotensin II 338 +/- 7 vs. control-vehicle 312 +/- 8 beats/min, p less than 0.0183) and in daily water intake (captopril-angiotensin II 20.7 +/- 2.2 vs. captopril-vehicle 9.8 +/- 0.7, p less than 0.0426; control-angiotensin II 33.1 +/- 3.8 vs. control-vehicle 9.0 +/- 0.6 ml/100 g body wt, p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Myocardial calcification and cardiac dysfunction in chronic renal failure.

PURPOSE: Myocardial calcium content may have clinical importance in end-stage renal disease (ESRD), but it is difficult to detect during life. Our goal was to assess the effect of myocardial calcium content on left ventricular ejection fraction (LVEF) in uremic patients undergoing dialysis. PATIENTS AND METHODS: Energy subtraction radiography of the chest was used to measure myocardial calcium content in 43 patients undergoing dialysis, in 32 control subjects, and in nine patients with advanced cardiomyopathy. LVEF and left ventricular end-diastolic dimension were measured by two-dimensional echocardiography. The concentration of parathyroid hormone was measured by radioimmunoassay; calcium-phosphorus product, alkaline phosphatase, and serum bicarbonate were also assessed. RESULTS: Patients undergoing dialysis had a greater myocardial calcium content than control subjects [262 +/- 15.4 (mean +/- SE) versus 187 +/- 8 mg/cm2, p less than 0.05]. Ten patients with the highest myocardial calcium content (Group I) had the lowest LVEF values and highest left ventricular end-diastolic dimension. Significant inverse linear associations between LVEF and myocardial calcium content (r = -0.425, p = 0.013) and between parathyroid hormone concentration and LVEF (r = -0.352, p = 0.047) were noted. There was no association between parathyroid hormone concentration and myocardial calcium content. Stepwise regression analysis showed a strong positive correlation between myocardial calcium content and calcium-phosphorus product, vascular calcification, race (black), and parathyroidectomy. Similar analysis shows that LVEF was significantly associated with myocardial calcium content, lung calcium, calcium-phosphorus product, and race (black). CONCLUSION: We suggest that increased myocardial calcium content results from poor calcium and phosphorus control and may be enhanced by parathyroid hormone hyperactivity. Increased myocardial calcium content is strongly associated with myocardial dysfunction in patients undergoing dialysis.

Adult↗

Results of coronary artery bypass grafting in end-stage renal disease.

We examined the results of coronary artery bypass grafting (CABG) in patients with end-stage renal disease and symptomatic ischemic heart disease who had significant arteriosclerotic narrowing of one or more coronary vessels between 1970 and 1984. Twenty-four such patients underwent bypass grafting, 20 dialysis patients and four who had been transplanted. Bypass grafting completely or partially relieved symptoms in 83%. The hospital mortality associated with this surgery for the 20 dialysis patients was 20% compared with a lower overall hospital mortality for bypass grafting in nondialysis patients of 1.3%. Greater hospital mortality was noted for patients over age 60 undergoing bypass grafting, 33.3% v 1.9% in nondialysis patients. In this study, the most significant factor associated with mortality was older age. We conclude that bypass grafting has an acceptable mortality in younger end-stage renal disease patients anticipating or having had renal transplantation, but it is associated with a high hospital mortality in older dialysis patients.

Age Factors↗

Relationship of sodium balance to arterial pressure in black hypertensive patients.

To investigate the quantitative importance of sodium balance to arterial pressure changes produced by changes in sodium intake, we studied normotensive white and black subjects and hypertensive black patients with two protocols. Protocol 1 used a 3-day control period with a 150 mEq sodium intake/day followed by 4 days of salt depletion (SD) with a diet providing 9 mEq/day of sodium and furosemide, 1 mg/kg, given the first day and then 3 days of salt loading (SL), during which 25 mL/kg of isotonic sodium chloride solution was given intravenously each day (3.88 mEq sodium/kg/day). In protocol 2, the sequence of sodium intake changes was reversed. For both protocols, sodium balance was calculated by subtracting urinary sodium excretion from sodium intake and expressed in mEq/kg, either positive or negative. In protocol 1, the hypertensives had statistically significant changes in arterial pressure with changes in salt intake, and they also lost more sodium than normotensives during SD. In protocol 2, blacks, both normotensives and hypertensives, had statistically significant pressure changes with both SL and SD, and black hypertensives retained less sodium during SL than either normotensive group. Spearman correlations showed no relationship between sodium balance and mean arterial pressure, suggesting that salt-sensitive hypertension results not from the magnitude of sodium retention, but from the pressor mechanisms evoked.

Adult↗

Sympathetic function in spontaneously hypertensive rats after chronic administration of captopril.

The cardiovascular effects of electrical stimulation of the posterior hypothalamus, intravenous administration of norepinephrine (NE), and direct sympathetic nerve stimulation (SNS) were compared in spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) given captopril (osmotic minipump, 1.25 micrograms/h icv) or vehicle for 4 wk beginning at age 7 wk. Mean arterial pressure (MAP) and renal and mesenteric flows (pulsed Doppler flow probes) were monitored in anesthetized rats. Following chronic administration of captopril the MAP was 141 +/- 4 mmHg in SHR receiving captopril and 183 +/- 6 mmHg in SHR receiving vehicle. Posterior hypothalamic stimulation, intravenous NE, and SNS resulted in lesser increases in MAP and renal and mesenteric vascular resistances in SHR treated with captopril. Response curves were shifted to the right, and the initial slopes and rate of change of slopes of the curves were less in captopril-treated SHR than vehicle-treated rats. The decrease in sensitivity to posterior hypothalamic stimulation was greater than the decrease in response to NE or SNS. The decrease in vascular reactivity in captopril-treated SHR was not due to increased sensitivity of the baroreflex for control of vascular resistance nor to a decrease in arterial pressure per se. WKY treated with captopril also showed lesser increases in MAP and renal and mesenteric vascular resistances in response to posterior hypothalamic stimulation, intravenous NE, and SNS. The depressor effects of intracerebroventricular captopril in SHR may be due, in part, to an attenuation in sympathetic vasoconstrictor tone. This attenuation involves both a decrease in vascular smooth muscle responsiveness to NE as well as a decrease in central stimulation of sympathetic outflow.

Animals↗

Renal autoregulation and pressure natriuresis during ANF-induced diuresis.

We examined the autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR) in the anesthetized dog during selective renal arterial infusion of two different synthetic atrial natriuretic factor (ANF) analogues. Rat atriopeptin II (5 X 10(-8) M in renal arterial blood) caused increases in sodium and water excretion but left RBF and GFR unchanged. A similar response was seen with rat 8-33 atrial natriuretic peptide (ANP) (10(-9) M), but a twofold higher dose of this peptide produced a transient increase in RBF and a sustained 16% increase in GFR. The normal pattern of RBF autoregulation in response to decreases in renal perfusion pressure was not altered by either peptide. GFR was also efficiently autoregulated during ANF infusion; however, there was a threefold increase in the slope of the relationship between sodium excretion and arterial pressure (pressure natriuresis) during 8-33 ANP infusion (control 1.11 +/- 0.39, 8-33 ANP 4.00 +/- 0.86 mu eq/mmHg, P less than 0.01). We conclude that ANF-induced diuresis can be sustained without detectable changes in either the autoregulation-responsive or autoregulation-independent components of renal vascular resistance. Factors other than GFR, which are highly responsive to renal perfusion pressure, are important in modulating the natriuresis caused by ANF. The augmentation of pressure natriuresis within the GFR autoregulatory range suggests an influence of ANF on the magnitude of arterial pressure-induced changes in tubular sodium reabsorption.

Animals↗

Effect of dietary NaCl on chloride uptake in rat collecting duct segment.

To explore further the mechanism of the effect of dietary NaCl intake on collecting duct (CDS) chloride uptake, we compared late distal chloride delivery to and urinary 36Cl recovery (the latter as an index of unidirectional efflux) from the CDS in four groups of male Sprague-Dawley rats. Groups were prepared for 7-10 days as follows: group 1, drinking 0.15 M NaCl; group 2A, regular diet; group 2B, regular diet plus deoxycorticosterone (2 mg im) (at 24 and 2 h before micropuncture); and group 3, low-NaCl diet. To increase tubule fluid flow rate and produce natriuresis without chloruresis, 0.15 M NaHCO3 at 5% body wt/h was infused in all groups except group 3, in which an infusion of 150 mM Na+, 55 mM Cl-, and 85 mM HCO3- was required to maintain a plasma chloride concentration equal to that in other groups. Plasma chloride concentration and arterial pH did not differ between groups before infusion. Urinary 36Cl recovery increased in parallel with dietary NaCl content (P = 0.0001). By analysis of multiple covariances, neither tubule fluid chloride concentration nor chloride delivery to the CDS correlated with urinary 36Cl recovery within any of the groups or for all animals studied. High doses of mineralocorticoid did not alter chloride uptake in group 2. These data suggest that progressive restriction of dietary NaCl enhances chloride uptake in the CDS of the rat unrelated to changes in plasma chloride concentration or chloride delivery from the superficial late distal tubules.

Animals↗

Dialysis-associated ischemic heart disease: insights from coronary angiography.

We reviewed the records of 44 dialysis patients who had undergone one or more coronary angiograms to determine the frequency with which symptomatic ischemic heart disease (IHD) and significant coronary artery narrowing coincided and to determine those factors which were associated with the coronary atherosclerotic process. Thirty-four patients were catheterized for angina pectoris or myocardial infarction. Of this group, 53% were found to have significant narrowing of coronary arteries. This group was older than the group with trivial or no coronary artery occlusion and their duration of dialysis was shorter. All the patients with significant coronary occlusion were white and the majority were adult males. Discriminant function analysis revealed that the presence of significant coronary artery occlusion could be predicted with high sensitivity and specificity by the following variables: older age, white race, male sex, the presence of symptomatic IHD prior to the onset of dialysis, increased total serum cholesterol, abnormal left ventricular wall motion, and reduced alkaline phosphatase. We also found that the occurrence of symptomatic IHD far exceeded the presence of significant atherosclerotic coronary artery narrowing. We suggest that this may result from several dialysis-associated alterations in oxygen delivery and myocardial oxygen consumption.

Adult↗