Biomedical subjects

R L Howard

Publications and source records attributed to R L Howard.

At least 37 records · Page 2Linked to original sources

PubMed1993

Effect of chronic hypertonic saline ingestion on vasopressin gene expression in the rat.

The present study was undertaken to examine vasopressin gene expression in response to a normal versus hypertonic sodium chloride (506 mOsm/kg H2O) intake for 7 days in Sprague-Dawley rats. The animals in both groups demonstrated precision in maintaining constancy of body fluid composition in spite of large differences in sodium and water intakes. Compared with the rats on a normal diet, chronic ingestion of hypertonic sodium chloride resulted in significant increases in total fluid intake (210 +/- 8 mL v 471 +/- 48 mL, P < 0.001) and total urine output (86 +/- 5 mL v 347 +/- 48 mL, P < 0.001), while glomerular filtration rate, hematocrit, serum urea nitrogen, creatinine, serum sodium, and plasma osmolality were unchanged. Without detectable changes in plasma osmolality or intravascular volume, vasopressin release from the pituitary, as measured by plasma and pituitary vasopressin concentrations (1.5 +/- 0.1 pg/mL v 5.9 +/- 1.5 pg/mL, P < 0.01 and 2.0 +/- 0.5 micrograms/pituitary v 0.86 +/- 0.1 micrograms/pituitary, P < 0.01, respectively), was increased in the animals ingesting hypertonic sodium chloride. In addition, vasopressin gene expression as measured by hypothalamic vasopressin mRNA concentrations was significantly increased 1.85-fold (P < 0.001) in the animals ingesting hypertonic sodium chloride. In summary, Sprague-Dawley rats ingesting hypertonic sodium chloride (506 mOsm/kg H2O) were able to maintain sodium and water homeostasis over a 7-day period. Yet, in these animals plasma vasopressin increased, pituitary vasopressin stores decreased, and hypothalamic vasopressin gene expression was stimulated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Vasopressin gene expression in rats with experimental cirrhosis.

Impaired ability to excrete a water load occurs in a substantial number of patients with advanced cirrhosis and in animals with experimental cirrhosis. The nonosmotic stimulation of arginine vasopressin release from the pituitary has been implicated as an important factor in the abnormal water excretion in patients and animals with cirrhosis. In this study, arginine vasopressin hypothalamic gene expression was studied in cirrhotic rats. Cirrhosis was induced by a combination of phenobarbital treatment in drinking water and weekly intragastric administration of carbon tetrachloride for 13 to 15 wk. Severe cirrhosis was confirmed by morphological analysis and the presence of ascites. Plasma arginine vasopressin was also significantly higher in rats with cirrhosis (control = 1.77 +/- 0.16 and cirrhotic rats = 4.14 +/- 0.62 pg/ml, n = 9, p < 0.002). Hypothalamic arginine vasopressin messenger RNA was also significantly higher in cirrhotic rats (control = 762.1 +/- 132.3 and cirrhotic rats = 1,834.2 +/- 271.9 pg/hypothalamus, n = 9, p < 0.005). Pituitary arginine vasopressin content was significantly lowered in cirrhotic rats (control = 3.69 +/- 0.98 and cirrhotic rats = 1.57 +/- 0.09 micrograms/pituitary, n = 9, p < 0.05). No difference was seen in hypothalamic arginine vasopressin content between the two groups (control = 4.64 +/- 0.34 and cirrhotic rats = 4.23 +/- 0.33 ng/hypothalamus, n = 9, NS). Oxytocin messenger RNA in the hypothalamus was also not significantly different between the two groups (control = 8.61 +/- 0.68 and cirrhotic rats = 9.33 +/- 0.65 unit of density, n = 9, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Short-term hypothyroidism and vasopressin gene expression in the rat.

Hypothyroidism is associated with abnormalities in renal water handling, which include a delay in excretion of an acute water load, decreased urinary concentrating ability, and increased urine volume. In the present study, we investigated the role of vasopressin in aminotriazole-induced hypothyroidism by measuring vasopressin concentration in the plasma and pituitary along with vasopressin mRNA levels in the hypothalamus. After 5 weeks of aminotriazole treatment, L-thyroxine levels were significantly lower in the experimental animals (122 +/- 8 v 26 +/- 1 nmol/L [9.5 +/- 0.6 v 2.0 +/- 0.1 micrograms/dL]; P less than 0.001). Serum sodium (148 +/- 0.5 v 144 +/- 1.2 mmol/L [mEq/L]; P less than 0.01), and plasma osmolality (311 +/- 2.5 v 304 +/- 1.8 mmol/kg [mOsm/kg] H2O; P less than 0.05) were also lower in the experimental animals. There were no differences in plasma (1.9 +/- 0.4 v 1.5 +/- 0.2 pg/mL) or pituitary (1.5 +/- 0.4 v 1.5 +/- 0.2 microgram/pituitary) vasopressin levels. In addition, steady-state vasopressin mRNA levels were not different between the two groups (1,286 +/- 210 v 1,093 +/- 138 pg/hypothalamus). One week of L-thyroxine replacement resulted in significant increases in serum thyroxine levels without changes in the other variables measured. These results indicate that short-term hypothyroidism, which has been shown to exert substantial effects on renal function, causes only a modest central alteration in the plasma vasopressin-osmolality relationship, which occurs in the absence of detectable changes in vasopressin synthesis.

Amitrole↗

PubMed1991

Urinary albumin, transferrin and iron excretion in diabetic patients.

The present study was undertaken to determine urinary and serum iron, transferrin and albumin levels in diabetic patients with varying amounts of proteinuria. A highly significant correlation was found between urinary albumin and transferrin excretion over a wide range of urinary albumin excretion (0.005 to 18 g/g creatinine) (r = 0.972). The urine/serum ratio of transferrin and albumin were identical, documenting a similar glomerular leak and tubule handling for these two proteins. In contrast to the above correlation between transferrin and albumin, there was no correlation between iron and either of these proteins until nephrotic range proteinuria had occurred, and even at that time the correlation was much weaker than that found between the proteins (r = 0.680). Urinary iron excretion increased early in the course of diabetic renal disease, being increased in 3 of 11 patients without proteinuria and in 8 of 10 patients with mild proteinuria. All patients with nephrotic range proteinuria had markedly increased urinary iron excretion (150 +/- 166 micrograms/g creatinine vs. 6.4 +/- 0.7 micrograms/g creatinine in controls) and decreased serum iron levels (592 +/- 189 micrograms/liter vs. 979 +/- 394 micrograms/liter in the control group). The iron/transferrin ratio in urine was consistently greater than the iron/transferrin ratio in plasma at all stages of proteinuria. In patients with both subnephrotic and nephrotic range proteinuria, approximately 35 to 40 micrograms Fe/g creatinine was present in the urine with an excess of transferrin. In conclusion, urinary iron excretion is increased early in the course of diabetic renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

Unifying hypothesis of sodium and water regulation in health and disease.

Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis, nephrotic syndrome, and pregnancy. Nonosmotic vasopressin release has been implicated in the water retention of these edematous disorders. The nonosmotic release of vasopressin is consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems in both experimental animals and in edematous patients. Moreover, the sympathetic nervous system has been shown to be involved in the nonosmotic release of vasopressin and activation of the renin-angiotensin system. These findings have led to our proposal that body fluid volume regulation involves the dynamic interaction between cardiac output and peripheral arterial resistance. Neither total extracellular fluid volume nor blood volume is a determinant of renal sodium and water excretion. Rather, renal sodium and water retention is initiated by a decrease in effective arterial blood volume (EABV) due to either a fall in cardiac output or peripheral arterial vasodilation. The acute response to a decrease in EABV involves vasoconstriction mediated by angiotensin, sympathetic mediators, and vasopressin. The slower response to restoring EABV involves vasopressin-mediated water retention and aldosterone-mediated sodium retention. The resultant renal vasoconstriction limits the distal tubular delivery of sodium and water, thus maximizing the water-retaining effect of vasopressin and impairing the normal escape from the sodium-retaining effects of aldosterone. The elevated glomerular filtration rate and filtered sodium load in pregnancy allows increased distal sodium and water delivery in spite of a decrease in EABV, thus limiting edema formation during gestation.

Animals↗

PubMed1990

Increased osmolal gap in alcoholic ketoacidosis and lactic acidosis.

OBJECTIVE: To determine whether an elevated osmolal gap is specific for toxic alcohol ingestion. DESIGN: Cross-sectional. SETTING: Emergency room and medical and surgical inpatient wards at a university-affiliated hospital. PATIENTS: Twenty-three patients with lactic acidosis, 19 with alcoholic ketoacidosis, and 10 randomly selected controls. MEASUREMENTS AND MAIN RESULTS: Calculated and measured serum osmolality was determined in all study participants. The osmolal gap was increased in patients with lactic acidosis (17.4 +/- 5.4 mmol/kg) and alcoholic ketoacidosis (26.9 +/- 7.6 mmol/kg) when compared with controls (-1.7 +/- 1.7 mmol/kg, P less than 0.05 for both comparisons). When ethanol was included in the calculation, the osmolal gap remained elevated in the lactic acidosis (10.3 +/- 2.0 mmol/kg) and alcoholic ketoacidosis (11.1 +/- 3.2 mmol/kg) groups (P less than 0.05 for both comparisons). CONCLUSIONS: The osmolal gap is often used as a screen for toxic alcohol ingestion. When calculating the osmolal gap, the contribution of ethanol should be considered. An elevated osmolal gap is not specific for toxic alcohol ingestion, as the osmolal gap was elevated in patients with lactic acidosis and alcoholic ketoacidosis. These two conditions should be considered when using the osmolal gap to design therapy (for example, hemodialysis) in the setting of anion gap metabolic acidosis and suspected toxic alcohol ingestion.

Acidosis↗

PubMed1990

Adult and pediatric peritonitis rates in a home dialysis program: comparison of continuous ambulatory and continuous cycling peritoneal dialysis.

We reviewed our 115-month experience with continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis (CCPD) in adult and pediatric patients to determine whether there is a difference in the incidence of peritonitis between patients performing CAPD or CCPD. Peritonitis rates were similar in patients performing CAPD or CCPD in both the adult and pediatric age groups. The overall CAPD peritonitis rate was significantly lower in adult patients when compared with pediatric patients. There was no difference in peritonitis rates for CCPD between adult and pediatric patients. When the data are divided into 3-year subgroups, the incidence of peritonitis is significantly lower in adult patients undergoing either CAPD or CCPD when compared with pediatric patients during the years 1986 to 1988. There is significant improvement over time in the incidence of peritonitis in both adult and pediatric patients performing CCPD; similarly, there is a trend toward improvement in patients performing CAPD. Staphylococcus species organisms remain the most common bacterial cause of peritonitis, except in pediatric patients under the age of 2 years or with nephrostomies, where gram-negative rod infections were more common. Peritonitis resulted in discontinuation of peritoneal dialysis in a greater number of adult patients. These results suggest that the number of catheter manipulations is not important in determining the incidence of peritonitis. Pediatric patients are more likely than adult patients to develop peritonitis with either CAPD or CCPD. Adult patients are more likely than pediatric patients to discontinue peritoneal dialysis secondary to peritonitis.

Adult↗

PubMed1990

A unifying hypothesis of sodium and water regulation in health and disease.

Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis, nephrotic syndrome, and pregnancy. In recent years, the use of a sensitive radioimmunoassay for plasma vasopressin has implicated the role of nonosmotic vasopressin release in the water retention of these edematous disorders. In experimental studies and studies in man, it has been found that the nonosmotic release of vasopressin is consistently associated with the activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. Moreover, the sympathetic nervous system has been shown to be involved in the nonosmotic release of vasopressin (carotid and aortic baroreceptors) and in the activation of the renin-angiotensin system (renal beta-adrenergic receptors). These findings have led to our proposal that body fluid volume regulation involves the dynamic interaction between cardiac output and peripheral arterial resistance. In this context, neither total extracellular-fluid (ECF) volume nor blood volume are determinants of renal sodium and water excretion. Rather, renal sodium and water retention is initiated by either a fall in cardiac output (e.g. ECF volume depletion, low-output cardiac failure, pericardial tamponade, or hypovolemic nephrotic syndrome) or peripheral arterial vasodilation (e.g. high-output cardiac failure, cirrhosis, pregnancy, sepsis, arteriovenous fistulae, and pharmacologic vasodilators). With a decrease in effective arterial blood volume (EABV). initiated by either a fall in cardiac output or peripheral arterial vasodilation, the acute response involves vasoconstriction mediated by angiotensin, sympathetic mediators, and vasopressin. The slower response to restoring EABV involves vasopressin-mediated water retention and aldosterone-mediated sodium retention. The renal vasoconstriction which accompanies those states that decrease EABV, by either decreasing cardiac output or causing peripheral arterial vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Volume↗

PubMed1990

The effect of calcium channel blockers on the cyclosporine dose requirement in renal transplant recipients.

Thirteen patients found to be hypertensive following renal transplantation were treated with either a calcium channel blocker or other antihypertensive therapy for control of blood pressure. Immunosuppression was either with cyclosporine and prednisone alone or with cyclosporine, azathioprine, and prednisone. Patients had weekly or biweekly cyclosporine whole-blood levels measured by radioimmunoassay drawn approximately 12 h after their last dose. Patients treated with cyclosporine and prednisone alone had their cyclosporine dosage adjusted to maintain their cyclosporine level between 400 and 900 ng/mL between 1 and 6 months following transplantation. Patients treated with cyclosporine, azathioprine, and prednisone had their cyclosporine level adjusted to be between 100 and 400 ng/mL during this same time period. Cyclosporine levels were significantly higher in verapamil-treated patients and significantly lower in nifedipine-treated patients as compared to controls. The dose of cyclosporine administered was significantly lower in the verapamil-treated patients and higher in the nifedipine-treated patients than controls. Normalizing the whole-blood cyclosporine level for the dose of cyclosporine, and verapamil-treated patients had a significantly greater, and the nifedipine-treated patients a significantly lower value than control patients. These data suggest the verapamil treatment results in significantly higher levels of cyclosporine whereas nifedipine therapy may actually result in lower cyclosporine levels for a given dose of cyclosporine than seen in patients not exposed to these drugs.

Adult↗

PubMed1989

Pathophysiology of vasopressin in edematous disorders.

Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis, nephrotic syndrome and pregnancy. In recent years the use of a sensitive radioimmunoassay for plasma vasopressin has implicated the role of nonosmotic vasopressin release in the water retention of these edematous disorders. In experimental studies and studies in humans it has been found that the nonosmotic release of vasopressin is consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. Moreover, the sympathetic nervous system has been shown to be involved in the nonosmotic release of vasopressin (carotid and aortic baroreceptors) and activation of the renin-angiotensin system (renal beta-adrenergic receptors). These findings have led to our proposal that body fluid volume regulation involves the dynamic interaction between cardiac output and peripheral arterial resistance. In this context neither total extracellular fluid (ECF) volume nor blood volume are determinants of renal sodium and water excretion. Rather, renal sodium and water retention is initiated by either a fall in cardiac output (e.g. ECF volume depletion, low-output cardiac failure, pericardial tamponade or hypovolemic nephrotic syndrome) or peripheral arterial vasodilation (e.g. high-output cardiac failure, cirrhosis, pregnancy, sepsis, arteriovenous fistulae and pharmacologic vasodilators). With a decrease in effective arterial blood volume (EABV), initiated by either a fall in cardiac output or peripheral arterial vasodilation, the acute response involves vasoconstriction mediated by angiotensin, sympathetic mediators and vasopressin. The slower response to restoring EABV involves vasopressin-mediated water retention and aldosterone-mediated sodium retention. The renal vasoconstriction which accompanies those states that decrease EABV, by either decreasing cardiac output or causing peripheral arterial vasodilation, limits the distal tubular delivery of sodium and water thus maximizing the water-retaining effect of vasopressin and impairing the normal escape from the sodium-retaining effects of aldosterone. The elevated glomerular filtration rate and filtered sodium load in pregnancy allows increased distal sodium and water delivery in spite of a decrease in EABV, thus limiting edema formation during gestation.

Blood Volume↗

PubMed1989