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Biomedical subjects

S B Miller

Publications and source records attributed to S B Miller.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effects of growth hormone and insulin-like growth factor I on renal growth and function.

Polypeptide growth factors regulate kidney development, growth, and function and participate in the repair processes after renal injury. The use of one or more growth factors as therapeutic agents in the settings of acute and chronic renal failure has been proposed. Insulin-like growth factor I (IGF-I) accelerates the restoration of kidney function and the normalization of structure and reduces mortality rates in animal models of acute renal injury. The mechanisms by which IGF-I acts in acute renal failure include stimulation of anabolism, maintenance of glomerular filtration, acceleration of tubular regeneration, and increased expression of ischemia-induced renal genes. It has been safely used in persons at risk of having acute renal failure and in patients with end-stage chronic renal failure, in whom it increases the glomerular filtration rate. Further studies to determine the role of IGF-I as a therapeutic agent for acute renal failure and its utility as a medical therapy for chronic renal insufficiency are required.

Acute Kidney Injury↗
PubMed1997

The use of growth factors to increase glomerular filtration rate in chronic renal failure patients.

Insulin-like growth factor-1 has been safely administered to humans with chronic renal failure in an attempt to increase glomerular filtration rate. The results of short-term studies have been encouraging. Further studies will be required to better define the role of this or other growth factors in increasing glomerular filtration rate in patients with chronic renal failure.

Glomerular Filtration Rate↗
PubMed1997

Whole body leptin kinetics and renal metabolism in vivo.

Leptin metabolism was investigated in male Sprague-Dawley rats by use of 125I-labeled leptin plasma kinetic and arteriovenous balance studies. When conscious rats received bolus venous injections of 125I-leptin, intact (precipitable) leptin quickly disappeared from circulation in a biexponential manner during the 2-h experimental period. After substantial delay, most of the injected radioactivity appeared in the urine. The data were described by a two-compartment model, which postulated that plasma leptin exchanged with a nonplasma pool and that all of the tracer cleared from plasma appeared in urine or in a degraded form in plasma. The half-life of leptin was 9.4 +/- 3.0 min, and the leptin production rate was 3.6 +/- 1.2 ng 100 g fat-1.min-1. The left kidney extracted 21 +/- 1.5% of intact arterial 125I-leptin 5 min after femoral venous injection. Endogenous arterial leptin was reduced 21 +/- 8 and 18 +/- 12%, respectively, in simultaneously sampled left and right renal veins. Renal elimination appears to be the major elimination mechanism for leptin in normal rats, and the kinetic studies suggest that uptake of leptin by renal tissue rather than glomerular filtration is the predominant elimination mechanism.

Adipose Tissue↗
PubMed1997

Insulin-like growth factor I preserves renal function postoperatively.

Deterioration of renal function, which can lead to postoperative renal failure, is a complication of surgery involving the suprarenal aorta and surgery involving the renal arteries. Fifty-four patients who were at risk for developing this complication were enrolled in a double-blind, randomized, placebo-controlled trial of insulin-like growth factor (IGF-I) as a therapeutic agent to prevent the decline in renal function. The primary end point was the incidence of renal dysfunction, defined as a reduction of the glomerular filtration rate (creatinine clearance) at each of three measurements over 72 h. IGF-I (100 microg/kg subcutaneously every 12 h for 6 doses) or placebo was administered on admission to the intensive care unit immediately postoperatively. IGF-I- and placebo-treated groups were well matched for sex, age, type of surgery, renal ischemic time during surgery (ischemic index), baseline creatinine clearance, and baseline serum creatinine. No patient in the study developed acute renal failure postoperatively. IGF-I was well tolerated. A smaller proportion of patients in the IGF-I group had a postoperative decline in renal function (22%) than in the placebo-treated group (33%). There were no significant differences in levels of serum creatinine at time of discharge, length of hospital stay, length of intensive care unit stay, length of intubation, or incidence of dialysis or death. Our findings establish the feasibility and potential utility for the use of IGF-I to reduce the incidence of postoperative renal dysfunction in high-risk patients.

Aged↗
PubMed1997

Control of cytomegalovirus-associated morbidity in renal transplant patients using intensive monitoring and either preemptive or deferred therapy.

The objective of this randomized, prospective study was to compare preemptive to deferred treatment of cytomegalovirus (CMV) infection in high-risk renal transplant recipients. Conducted at a university-affiliated transplant center, the study included 36 renal allograft recipients with donor or recipient CMV-seropositivity who received anti-thymocyte induction therapy. Ganciclovir was administered intravenously for 21 days upon detection of CMV viremia (preemptive, N = 15) or detection of CMV viremia associated with a CMV syndrome (deferred, N = 21). Shell vial culture, conventional culture, and polymerase chain reaction (PCR) were performed upon buffy-coat specimens weekly for 12 to 16 wk. CMV and non-CMV-associated charges were calculated. The comparative sensitivities of PCR, shell vial culture, and conventional culture were 91%, 44%, and 47%, respectively. A delay in specimen processing of > 24 h severely compromised the sensitivity of culture techniques but not that of PCR. Preemptive therapy tended to decrease symptomatic CMV episodes (0.4 versus 0.6 episodes per patient randomized; P = 0.22). One patient in each group had organ involvement, and no patient died. Allograft function and survival were similar. Ganciclovir use was increased in the preemptive group (1.2 versus 0.6 courses per patient randomized; P = 0.02). CMV-associated charges were $10,368 (preemptive) versus $5,752 (deferred); P = 0.13. PCR is superior to conventional monitoring to detect CMV viremia. Culture cannot be considered the "gold standard" for detection of CMV viremia, especially when transport of specimens over distances results in processing delays. Preemptive therapy may reduce symptomatic CMV infections in renal transplant recipients. It was associated with higher CMV-related charges but equivalent overall charges versus deferred treatment with intensive monitoring. Either strategy can achieve control of CMV infection after renal transplantation.

Adult↗
PubMed1996

Dimensions of hostility and cardiovascular response to interpersonal stress.

Emerging research suggests that hostility is a multidimensional construct with different dimensions conferring different cardiovascular disease risk. This study examined two dimensions of hostility, expressive and neurotic, and their hemodynamic response patterns upon exposure to interpersonal stress. Fifty-seven male undergraduates were categorized into high and low expressive hostility (HiEH, LoEH) and high and low neurotic hostility (HiNH, LoNH) groups based on their Buss-Durkee Hostility Inventory scores. Subjects engaged in a mathematical subtraction task, with half of the subjects harassed through anger-provoking statements. Separate analyses were conducted for the expressive and neurotic hostility groupings. For expressive hostility, results indicated that HiEH/harassed subjects exhibited greater systolic blood pressure, heart rate, and cardiac output responses than did HiEH/nonharassed subjects or LoEH subjects irrespective of harassment. Neurotic hostility analyses revealed elevated forearm blood flow in HiNH/harassed subjects as compared to HiNH/nonharassed subjects or LoNH subjects in either harassment condition. The hemodynamic response pattern of expressive hostiles is consistent with their risk for heart disease. The response pattern of neurotic hostiles may indicate risk for hypertension, though this remains to be established.

Adult↗
PubMed1996

Estradiol, progesterone and cardiovascular response to stress.

The present study examined the relationship between endogenous estradiol and progesterone levels and cardiovascular activity at rest and during stress in healthy young women. Subjects were tested in both the follicular and luteal phases of the menstrual cycle. Results indicated that, during the luteal phase, higher levels of estradiol were associated with lower levels of cardiac output responses to the combined video game and speech tasks, and lower levels of heart rate and systolic blood pressure responses to the cold pressor; estradiol levels were also associated positively with PEP responses to the cold pressor but only under high levels of progesterone. Additionally, during the luteal phase, higher levels of progesterone were associated with higher TPR and lower stroke volume responses to the cold pressor. In contrast, during the follicular phase, higher levels of progesterone were associated with lower vascular resistance responses to the cold pressor. Consistent with data from studies using exogenous estrogens, these results suggest that estradiol may contribute to a lowering of cardiovascular responses to stress.

Adolescent↗
PubMed1996

Insulin-like growth factor-I attenuates delayed graft function in a canine renal autotransplantation model.

BACKGROUND: Insulin-like growth factor-I (IGF-I) has been shown to accelerate recovery in animal models of ischemic or toxic acute renal injury. Ischemic renal injury is frequently encountered after cadaveric transplantation manifested as delayed graft function. This study was performed to determine whether perfusion of kidneys with preservation solution supplemented with IGF-I would improve the course of renal injury in a canine autotransplantation model of delayed graft function. METHODS: Dogs underwent unilateral nephrectomy with kidneys perfused and stored in Euro-Collins solution supplemented with vehicle (n = 11) or IGF-I (n = 8). After 24 hours of kidney preservation, a contralateral nephrectomy was performed and the stored kidney was autotransplanted. Renal function was examined for 5 days after the transplantation, and an inulin clearance was obtained at the time of death. RESULTS: Compared with dogs that received kidneys preserved in the vehicle, dogs receiving the IGF-I preserved kidneys had significantly lower daily serum creatinine and blood urea nitrogen levels during the course of 5 days after transplantation. Inulin clearance at death was nearly double in the IGF-I treated animals compared with the vehicle-treated controls (1.37 +/- 0.16 ml/min/kg versus 0.77 +/- 0.13 ml/min/kg; p < 0.05). CONCLUSIONS: Perfusion and storage of kidneys with preservation solution supplemented with IGF-I can attenuate the course of delayed graft function in a canine renal autotransplantation model. IGF-I may have potential for use in cadaveric human renal transplantation.

Animals↗
PubMed1996

Altered EGF expression and thyroxine metabolism in kidneys following acute ischemic injury in rat.

To define the relationship between renal epidermal growth factor (EGF) expression and thyroid hormones in acute renal failure, we performed an analysis of the renal thyroid hormone-EGF axis following acute ischemic renal injury in rats. Levels of mature EGF extractable from kidney were elevated 24 h postinjury, and levels of membrane-associated EGF precursor were reduced. Administration of triodothyronine (T3) to rats, either prior to or immediately following the induction of injury, did not further increase levels of extractable EGF. Levels of EGF mRNA in kidneys were reduced 24 h following acute ischemic damage and not affected by administration of T3. Enhanced production of mature EGF from EGF precursor occurred in membranes isolated from kidneys of rats 24 h postinjury compared with production in membranes from kidneys of normal rats. In addition, levels of thyroxine 5'-deiodinase activity in renal membranes were increased 24 h following injury. Levels of circulating total thyroxine (T4), free T4, and free T3 were reduced postischemic injury. Total T3 was unchanged. The administration of T3 to normal rats increased renal 5'-deiodinase activity and EGF precursor cleavage. Administration of propylthiouracil to rats inhibited renal 5'-deiodinase activity and prevented the increase in extractable EGF postischemic injury. We conclude that the increase in levels of mature EGF extractable from kidneys of rats postischemic injury results from enhanced activity of the serine protease that cleaves the EGF precursor. This activity may be stimulated by T3 produced in kidney. These alterations in renal T4 metabolism and EGF expression could serve to facilitate recovery of renal function following ischemia.

Acute Disease↗
PubMed1995

Severe anemia as the presenting manifestation of giant cell arteritis.

Giant cell (temporal, cranial) arteritis (GCA) is usually confirmed in patients presenting with classic features. Those who present with atypical features often undergo prolonged evaluations until a diagnosis is established. Severe anemia as an initial manifestation of GCA has rarely been described. We describe herein 2 patients with biopsy-proven GCA who presented with severe anemia and significant weight loss, which corrected after corticosteroid therapy.

Aged↗
PubMed1995

Zaprinast accelerates recovery from established acute renal failure in the rat.

Atrial natriuretic factor (ANF) has been demonstrated to be effective in the treatment of acute renal failure (ARF) in both rat and humans. The biological effects of ANF are presumed to be mediated by the generation of intracellular 3',5'-cyclic guanosine monophosphate (cGMP). Therefore, the current investigation examined whether zaprinast (M&B 22948), a guanosine 3',5'-cyclic monophosphate (cGMP)-specific phosphodiesterase inhibitor, would be effective in the treatment of established acute renal failure in the rat. Acute renal failure was induced by 60 minutes of bilateral renal artery clamping. Twenty-four hours after the ischemic insult, rats received either vehicle (5% Dextrose), zaprinast (0.03 or 0.3 mg/kg/min) or ANF24 (0.2 micrograms/kg/min) intravenously for four hours. Renal function, as measured by daily serum creatinine (days 1 to 7) and day 2 inulin clearances, was dramatically improved by zaprinast but not ANF treatment. Forty-eight hours post-renal ischemia, glomerular filtration rate (GFR) was 0.14 +/- 0.04 (ml/min/100 g body wt) in the vehicle and 0.94 +/- 0.29 in the zaprinast treated animals. To evaluate the mechanism by which zaprinast accelerated renal recovery, we measured regional blood flow in the postischemic rat kidneys during drug treatment with a laser doppler flowmeter. Both high and low dose zaprinast significantly increased cortical (17%) and outer medullary blood flow (40% and 60%), an effect not seen with ANF. In summary, zaprinast is effective in the treatment of established ischemic ARF. The mechanism by which zaprinast accelerates renal recovery is due to its unique ability to stimulate regional renal blood flow and increase intracellular cGMP in the setting of tissue ischemia.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1995

Growth factor gene expression in tubular epithelial injury.

In animal models of acute renal injury, administration of epidermal, insulin-like or hepatocyte growth factor accelerates restoration of kidney function and normalization of histology, and reduces mortality. Mechanisms for such action include stimulation of anabolism, maintenance of glomerular filtration, and enhancement of tubular regeneration. Further studies are needed to establish the utility of growth factors as therapeutic agents for acute renal failure in humans.

Acute Kidney Injury↗
PubMed1995

Triiodothyronine stimulates renal epidermal growth factor expression in adult rat.

To define the role that thyroid hormones play in regulation of renal epidermal growth factor (EGF) production, we characterized the effect of triiodothyronine (T3) administration on renal EGF expression in adult rats. The action of T3 to regulate EGF production was examined under one condition in which renal EGF expression is known to be diminished, posthypophysectomy, and in pituitary-intact rats. Levels of mature EGF, EGF precursor, and EGF mRNA, reduced in kidneys of hypophysectomized rats compared with pituitary-intact animals, increased significantly following the administration of T3 to hypophysectomized rats. Thus replacement of thyroid hormone alone was sufficient to enhance renal EGF expression. Induction of a hyperthyroid state in normal rats by injection of T3 for 4 days increased levels of extractable immunoreactive mature EGF, EGF precursor present in renal membranes, and EGF mRNA measured in kidneys. Levels of EGF in circulation were undetectable under all experimental conditions. We conclude that T3 enhances the renal synthesis of EGF in both hypopituitary and pituitary-intact rats. Enhancement of renal EGF expression is one mechanism that must be considered to explain the actions of thyroid hormones on kidney.

Animals↗
PubMed1995

Parental history of hypertension and cardiovascular response to stress in Black and White men.

White offspring of hypertensives typically exhibit an elevated cardiovascular response to stress. Studies of Black offspring of hypertensives have been fewer, with inconsistent results. This may be due, in part. to incomplete characterizations of hemodynamic responses. This study examines cardiovascular reactivity in Black and White offspring of hypertensives with a particular focus on vascular resistance responses. A total of 62 healthy normotensive men, 41 with a parental history of hypertension (PH+: 21 Blacks, 20 Whites), and 21 without parental hypertension (PH-: 7 Blacks, 14 Whites) engaged in a series of laboratory tasks. Both Black and White PH+ participants exhibited elevated diastolic blood pressure (DBP) responses, but to different patterns of stressor tasks. Familial differences in total peripheral resistance response were also obtained for Black and White participants in a comparison across all tasks, but were particularly evident in tasks when PH+ participants had elevated DBP responses. These results suggest that a parental history of hypertension is an important moderator of cardiovascular, and in particular peripheral vascular, responses to stress in Black and White individuals.

Journal Article↗
PubMed1995

Analytical artifacts in hematocrit measurements by whole-blood chemistry analyzers.

Compact analyzers suited to near-patient testing estimate hematocrit by measuring the conductivity of undiluted blood. We evaluated the accuracy of hematocrit determination of one such analyzer (Instrumentation Laboratory BGE analyzer) against an automated cell counter (EPC) and packed cell volume (PCV) microhematocrit. When specimens (n = 34) from outpatient and ward patients were analyzed with all three methods, the BGE analyzer correlated well with both EPC and PCV hematocrit determinations (BGE = 1.00 PCV + 0.3%, S(y)/x = 2.0%), suggesting that all three methods are similar in performance for most patients. However, a patient with increased plasma osmolality showed significant decreases in BGE and PCV hematocrits relative to the EPC method. The differences in hematocrit measurements could be reproduced by adding solutes to blood in vitro or by modifying the plasma osmolality of rats in vivo. Samples from patients undergoing cardiac surgery, whose blood had large changes in protein concentration, showed discrepancies between hematocrits by conductivity and other methods; similar effects could be produced by changes in protein concentration or in vitro addition of polyethylene glycol. We conclude that conductivity measurements provide accurate hematocrit results for physiologically normal subjects but not for some intensive-care and surgical patients.

Animals↗
PubMed1994

Effects of IGF-I on renal function in end-stage chronic renal failure.

To determine whether insulin-like growth factor I (IGF-I) affects kidney function in patients with end-stage chronic renal failure, we administered recombinant human IGF-I (rhIGF-I) (100 micrograms/kg body wt subcutaneously twice daily) to nine individuals with baseline inulin clearances below 21 ml/min/1.73 m2. Four patients were treated for four days (short-term treatment) and five for periods between 13 and 27 days (long-term treatment). Administration of rhIGF-I increased inulin clearance, p-aminohippurate (PAH) clearance and the percent tubular reabsorption of filtered phosphate, and decreased plasma creatinine, blood urea nitrogen (BUN) and plasma phosphate during short-term administration. Kidney volume was unchanged in patients receiving the growth factor. rhIGF-I did not cause weight gain, proteinuria or hypoglycemia. Inulin clearance was not increased significantly above baseline after 13 or 20 days of IGF-I administration. PAH clearance remained elevated after 13 days, but not after 20 days of IGF-I. Levels of total circulating IGF-I were elevated above basal levels during the entire course of long-term IGF-I administration. In contrast, levels of circulating IGF binding protein 3 (IGFBP3) declined over time. Side effects related to IGF-I forced discontinuation of its use in two of five patients undergoing long-term treatment, and side-effects possibly related to IGF-I prompted discontinuation of its use in two others. We conclude that rhIGF-I can enhance glomerular filtration rate and renal plasma flow when administered short-term to humans with end-stage chronic renal renal failure. Further studies will be required to define its efficacy and usefulness long-term.

Adult↗