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Biomedical subjects

J P Pennell

Publications and source records attributed to J P Pennell.

At least 19 recordsLinked to original sources
PubMed2001

Optimizing medical management of patients with pre-end-stage renal disease.

Patients with end-stage renal disease have reduced quality of life, high levels of morbidity, and an annual mortality of about 22%. Because the high morbidity and mortality of dialysis patients might be reduced substantially if patients were healthier at the time of initiating renal replacement therapy, this article will present treatment recommendations designed to retard the progression of chronic renal disease, to optimize the medical management of comorbid medical conditions, such as cardiovascular disease, diabetes, and lipid disorders, and to reduce the complications of renal insufficiency, including hypertension, anemia, hyperparathyroidism, and malnutrition. Given the lack of prospective clinical studies in this area, these recommendations are derived from consensus standards for managing dialysis patients or patients with cardiovascular disease, hypertension, diabetes, and lipid disorders, and from expert opinion derived from laboratory investigations of pathophysiology and relevant experimental disease models.

Anemia↗
PubMed1998

Detection of anti-hepatitis C virus antibodies in patients undergoing dialysis by utilizing a hepatitis C virus 3.0 assay: correlation with hepatitis C virus RNA.

Hepatitis C virus (HCV) infection is endemic in long-term dialysis units. We assessed the performance of a recently developed HCV 3.0 assay for the detection of HCV antibodies in patients undergoing dialysis. The study evaluated 128 patients undergoing long-term maintenance hemodialysis. Anti-HCV was detected by 2.0 and 3.0 enzyme immunoassay (EIA). Results were confirmed with recombinant immunoblot assays (RIBA 2.0 and RIBA 3.0). HCV RNA was detected by using reverse transcriptase-polymerase chain reaction (RT-PCR). Thirty-two patients (25%) were HCV EIA 2.0 positive. Of these, 1 was RIBA 2.0 negative (PCR positive), 3 were indeterminate (3 PCR positive), and 28 were positive (23 PCR positive). Thirty-five (27%) were HCV EIA 3.0 positive. One was RIBA 3.0 negative (PCR positive), 1 was indeterminate (c33c, PCR positive), and 33 were positive (27 PCR positive) by RIBA 3.0. Thus only 1 PCR-positive patient was negative with RIBA 2.0 and 3.0 assays. Two of the 3 RIBA 2.0 indeterminate samples were positive with RIBA 3.0. One remained indeterminate but was HCV RNA positive. In summary, HCV 3.0 EIA detected 4 additional viremic patients but was positive in 6 PCR-negative subjects. A high correlation of the presence of antibody to c33c with HCV RNA (28 of 34, 82%) was found, and it was found in all anti-HCV positive samples and in 1 indeterminate sample. We conclude that the HCV EIA 3.0 test with the supplemental confirmatory RIBA 3.0 test may improve the sensitivity for the detection of anti-HCV. Nevertheless, in potentially immunocompromised patients undergoing dialysis, PCR continues to be the only reliable test for detecting viremia.

Adult↗
PubMed1998

Prevalence of hepatitis C and G virus infection in chronic hemodialysis patients.

An RNA virus designated hepatitis G virus (HGV) has been recently identified in patients with acute and chronic liver disease. HGV is transfusion transmissible, it has global distribution, and it is present in the volunteer blood donor population in the United States. One hundred sixty patients undergoing maintenance hemodialysis at the University of Miami-affiliated unit were evaluated. There were 99 men and 61 women ranging in age from 22 to 80 years. Sixty percent had a history of blood transfusion, 6% had a history of drug abuse, and 9% were infected with the human immunodeficiency virus. HGV-RNA was detected by reverse-transcriptase polymerase chain reaction with amplification of two independent regions (5'-nontranslated region and NS5a coding region). Detection of digoxigenin-labeled amplification products with specific capture probes to the coding and noncoding regions was performed with the Enzymun-test DNA on an ES-300 Immunoassay System (Boehringer-Mannheim, Mannheim, Germany). Hepatitis C antibodies were measured with anti-hepatitis C virus enzyme-linked immunosorbent third-generation assays and hepatitis C virus RNA by reverse-transcriptase polymerase chain reaction. There were 32 (20%) patients with detectable HGV RNA with both primer pairs. Because of possible mutations, the HGV virus may be detectable only with one primer pair. We considered the latter as indeterminate: 12 had detectable levels to the NS5a region only, seven to the 5'-nontranslated region, and six had borderline results. Detectable and indeterminate samples were confirmed by repeat measurements in a new blood sample. Seven of 24 (29%) patients with detectable hepatitis C virus RNA had coexisting HGV with one or both HGV primer pairs (four with both and three with one). Five patients were hepatitis B surface antigen positive and HGV negative. We conclude that HGV infection is prevalent in our dialysis patients. The clinical significance of HGV infection remains to be established.

Adult↗
PubMed1988

Student evaluation of accelerated program at the University of Miami.

The University of Miami School of Medicine has an accelerated, six-year B.S.-M.D. program called the Honors Program in Medicine (HPM). In 1985 the HPM and traditional program students were surveyed at the end of their first year in medical school regarding their opinions about accelerated medical education. Eighty-seven percent of the traditional students felt that HPM students had ability equal to that of the average medical student (that is, neither more nor less ability), but 41 percent felt that the HPM students were less mature than the average class member. The traditional students felt the HPM students were required to follow a rigid collegiate curriculum (76 percent) and had an inadequate nonscience background (68 percent) and that the HPM would negatively affect both the future professional competence of HPM participants (59 percent) and the medical profession (34 percent). A larger percentage of the HPM than the traditional students (63 versus 48 percent) reported earning more than a minor in nonscience subjects, and fewer HPM than traditional students (9 versus 36 percent) felt that pressure to maintain a high grade-point average limited their selection of college courses. The HPM students felt that they were well prepared for medical school academically (82 percent) and emotionally (91 percent). The HPM students excelled academically in college and in the preclinical curriculum.

Attitude↗
PubMed1986

Endotoxemic acute renal failure in awake rats.

The sequence of changes in renal function in endotoxemic acute renal failure (ARF) and the role of hypotension and systemic hemodynamics were evaluated in awake female Sprague-Dawley rats given an intravenous bolus of Escherichia coli endotoxin (20-40 mg/kg). After endotoxin ARF was abrupt in onset as glomerular filtration rate (GFR) fell promptly and progressively by 53% within 3.5 h, whereas renal blood flow decreased by 42% and renal vascular resistance nearly doubled. Systemic hemodynamics remained stable, including mean arterial blood pressure, cardiac output, and total peripheral resistance. Early endotoxemic ARF was associated with oliguria and sodium retention, a finding consistent with intact tubular function. Three and one-half hours after endotoxin, however, fractional water and sodium excretion were significantly increased. Ultrastructural studies then demonstrated sequestration of phagocytic leukocytes and intracellular edema in the peritubular capillaries with normal glomeruli. The decrease in GFR was spontaneously reversible within 7-9 days. Extracellular fluid volume expansion with saline either before or 24 h after administration of endotoxin failed to prevent the decrease in GFR or to normalize renal function. The data suggest that endotoxin has direct renal effects. The endothelial cells may be the primary target of endotoxin in the kidney.

Acute Kidney Injury↗
PubMed1982

Water reabsorption by papillary collecting ducts in the remnant kidney.

Water transport by terminal papillary collecting ducts was examined by micropuncture of the renal papilla in 15 rats with a solitary remnant kidney (RK) and in 27 normal rats, 10 of which had undergone sham operation. Before papillary exposure, urinary osmolality was significantly (P less than 0.001) lower in RK rats (685 vs. 1,722 mosmol/kg H2O in normal rats). After papillary exposure, urinary osmolality decreased by 50% in normal rats but did not change in RK rats. In RK rats, a greater percentage of filtered water was delivered to (5.74% vs. 2.29% in normal rats, P less than 0.001) and reabsorbed by (1.94% vs. 0.94% in normal rats, P less than 0.005) the terminal millimeter of papillary collecting ducts. Fractional water reabsorption by terminal papillary collecting ducts correlated directly (r = 0.83, P less than 0.001) with fractional water delivery, suggesting load dependence of water reabsorption. Estimated absolute water reabsorption by terminal collecting ducts was equivalent for remnant and normal kidneys and increased two-to fourfold in remnant kidneys when analyzed per functioning papillary collecting duct. There was an inverse relationship between urinary osmolality and fractional water delivery to papillary collecting ducts (r = 0.65, P less than 0.001). Although the data do not exclude functional alterations of papillary collecting ducts, the events underlying the reduction of urinary osmolality in remnant kidneys appear to involve physiological processes based on a high delivery and reabsorption of water.

Absorption↗
PubMed1981

Glomerular selective permeability to macromolecular neutral dextrans in experimental diabetes.

Rats with streptozotocin-induced chronic diabetes mellitus develop a glomerulopathy functionally manifested by proteinuria. The ability of the glomerular capillary wall to retard filtration of macromolecules was examined in 5 chronically diabetic Munich-Wistar rats exhibiting excessive proteinuria (39 +/- 7 mg/24 h, mean +/- SEM) and 5 age-matched normal Munich-Wistar rats without increased proteinuria (4.7 +/- 0.2 mg/24 h). Urinary albumin excretion was not increased in the diabetic rats (2.0 +/- 0.6 mg/24 h vs 1.6 +/- 0.3 mg/24 h) suggesting that the normal net electronegative charge of the glomerular capillary wall was not altered. Fractional clearances of macromolecular neutral dextrans were similar in diabetic and normal rats throughout a wide range of molecular size (18-42 A). Glomerular filtration rate was the same in the two groups of rats (2.77 +/- 0.16 ml/min in diabetics and 2.72 +/- 0.11 ml/min in normals) suggesting that renal haemodynamic factors did not influence fractional clearances of neutral dextrans in diabetic rats. We conclude that the proteinuria exhibited by these chronically diabetic rats is not attributable to alterations of size-selective properties of the glomerular capillary wall, such as increases in the size or the number of pores.

Animals↗
PubMed1981

Adaptive changes of juxtamedullary glomerular filtration in the remnant kidney.

The participation of surviving juxtamedullary nephrons in the adaptive changes of glomerular filtration that occur in response to loss of functioning nephron mass was examined by direct micropuncture of the rat renal papilla. The solitary remnant kidney (RK) in rats with an 85% reduction of renal mass demonstrated strikingly elevated values for single nephron glomerular filtration rate (SNGFR) in both superficial (46.1 +/- 3.2 nl/min) and juxtamedullary (73.5 +/- 6.1 nl/min) nephrons in comparison to respective values observed in normal hydrophenic rats (superficial SNGFR = 15.0 +/- 1.9 nl/min, P less than 0.001, and juxtamedullary SNGFR = 30.2 +/- 3.2 nl/min, P less than 0.001). In RK rats, the proximal portions of both superficial and juxtamedullary nephrons exhibited a marked increase in absolute fluid reabsorption as well as a markedly enhanced delivery of fluid to more distal portions of the nephron. These observations indicate that similar, not preferential, functional adaptations in glomerular filtration occur concomitantly in both superficial and juxtamedullary nephrons consequent to reduction of renal mass.

Adaptation, Physiological↗
PubMed1981

Proteinuria in the acutely diabetic rat and its response to insulin treatment.

The development of proteinuria and its response to insulin therapy in acute experimental diabetes was examined in 11 female rats by sequentially measuring 24 h excretion of glucose and total protein before diabetes, during 5-37 days of acute streptozotocin diabetes, during and after 7-14 days of continuous subcutaneous insulin administration. Induction of diabetes promptly resulted in marked polyuria (78 +/- 9 ml/24 h), and glycosuria (6.6 +/- 0.7 g/24 h), while proteinuria quadrupled (from 4.7 +/- 0.7 to 18.8 +/- 1.8 mg/24 h, p less than 0.001). Concurrent with amelioration of polyuria and glycosuria by insulin treatment, proteinuria decreased strikingly (8.5 +/- 1.2 mg/24 h, p less than 0.001) Polyuria and glycosuria resumed after discontinuing continuous subcutaneous insulin, and proteinuria promptly returned to pretreatment levels (19.0 +/- 2.5 mg/24 h). Similarly decreased proteinuria (8.8 +/- 0.9 mg/24 h) recurred in five rats retreated with insulin after 100 days of diabetes. Elevated proteinuria was not associated with lysozymuria or consistent changes in glomerular filtration rate. The rapid fluctuations in proteinuria attending acute diabetes and its effective treatment suggest that metabolic aberrations of diabetes may directly effect renal handling of proteins.

Acute Disease↗
PubMed1978

Pericardial effusions in patients with end-stage renal disease.

Echocardiography has greatly increased the accurate recognition of pericardial effusion. Echocardiograms were performed prospectively on the total group of 35 stable asymptomatic patients on chronic haemodialysis to determine the incidence of pericardial effusion. Effusions were shown in 11 per cent (4/35); only 6 per cent (2/35) were estimated as greater than 100 ml. For comparison, records were reviewed retrospectively from 41 haemodialysis patients referred during a 27-month period for echocardiographic assessment of suspected pericardial effusion. These 41 patients came from a total group of 108 patients treated with chronic dialysis over this interval. Of 41 examined, 21 (51%) or 21 of 108 (19%) of the population at risk had an effusion. Of 21 with echocardiographic effusions, 15 (71%), or 15 of 41 (37%) of those with clinically suspected effusion, had more than 100 ml fluid. Gross (greater than 100 ml) pericardial effusions are infrequent in stable, asymptomatic patients with end-stage renal disease. When clinical findings suggest pericardial disease, the echocardiographic demonstration of over 100 ml pericardial fluid is indicative of new effusion, rather than coincidental pre-existing effusion.

Echocardiography↗
PubMed1976

Potassium secretion by the decending limb or pars recta of the juxtamedullary nephron in vivo.

Potassium reabsorption by the juxtamedullary nephron up to the hairpin turn was studied by the micropuncture technique in the exposed renal papilla of rats. In 18 nondiuretic rats, the fraction of filtered potassium remaining at the end of the desdending limb averaged 113 +/- 9%, indicating either that potassium is not reabsorbed by the juxtamedullary proximal tubule and descending limb or that potassium is reabsorbed and secreted in those segments. Furosemide, a drug which inhibits NaCl reabsorption in the ascending limb downstream from the descending limb, significantly decreased the potassium remaining at the end of the descending limb from 106 +/- 12 to 72 +/-11% in seven rats. Benzolamide, a drug which inhibits reabsorption of NaHCO3 and water in the proximal tubule upstream from the descending limb significantly increased the potassium remaining from 103 +/- 13 to 177 +/- 32% in eight rats. These findings support the hypothesis that in the rat, potassium is normally reabsorbed by the proximal convoluted tubule and secreted in the pars recta or descending limb of the juxtamedullary nephron.

Absorption↗
PubMed1976

Initial approach to blood access for the chronic hemodialysis patient--the bovine heterograft.

Experience with the modified bovine heterograft arteriovenous fistula for hemodialysis in 79 grafts in 73 patients over an 18 mo period is analyzed. An immediate (30 day) patency rate of 97.5%, and a 12 mo cumulative patency rate of 73.9% was observed. Early and late complication rates were acceptably low, despite early usage in 80% of cases. It is concluded that the bovine fistula provides an acceptable blood access route for the initial approach to the patient in urgent need of hemodialysis.

Animals↗
PubMed1975

The effect of urea infusion on the urinary concentrating mechanism in protein-depleted rats.

To explore the role of urea in the urinary concentrating mechanism, the contents of vasa recta, Henle's descending limbs and collecting ducts were sampled by micropuncture of the renal papilla before and after infusion of urea in 10 protein-depleted rats. Eight protein-depleted rats not given urea were similarly studied as a control group. After urea administration, osmolality and the concentrations of urea and nonurea solute of urine from both exposed and contralateral kideny increased significantly. The osmolality and urea concentration of fluid from the end of Henle's descending limb and vasa recta plasma and the tubule fluid-to-plasma inulin ratio in the end-descending limb all increased significantly after urea infusion. We interpret these observations to indicate that urea enhances urinary concentration by increasing the abstraction of water from the juxtamedullary nephron (presumably the descending limb), in agreement with the prediction of recent passive models of the urinary concentrating mechanism. However, the concentration of urea in fluid from the descending limb after urea infusion was high (261 plus or minus 31 mM) and the difference in solium concentration between descending limb fluid and vasa recta was small and statistically insignificant.

Animals↗