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Biomedical subjects

R B Wait

Publications and source records attributed to R B Wait.

At least 19 recordsLinked to original sources

Role of renal sympathetic nerve activity in renal failure associated with obstructive jaundice in the rat.

The propensity for renal failure associated with obstructive jaundice and liver disease may be related to enhanced vasoconstriction of the renal vascular bed with resultant decreases in renal blood flow. Renal sympathetic nervous activity may be a mediator of this effect. The increased renal production of prostaglandins which has been observed in previous models of bile duct ligation may serve to counterbalance the effects of such vasoconstricting influences. This study was undertaken to assess the effect of bile duct ligation on renal function and prostaglandin production in the rat. Furthermore, this study was designed to determine if renal sympathetic nerve activity contributes to the development of renal failure after bile duct ligation. Sprague-Dawley rats underwent either sham operation (n = 8), bilateral renal denervation (n = 10), bile duct ligation alone (n = 11), or bile duct ligation and bilateral renal denervation (n = 10). Renal function was assessed before and 4 days after operation. Bile duct ligation resulted in a 46% decrease in creatinine clearance (p less than 0.01), a 33% decrease in urinary sodium excretion (p less than 0.01), a twofold increase in urine flow (p less than 0.01), and twofold increases in urinary excretion of PGE2, 6-keto-PGF1 alpha, and thromboxane B2 (p less than 0.01). Renal denervation did not prevent the decreases in creatinine clearance and sodium excretion seen after bile duct ligation and had no effect on the changes in urine flow and prostaglandin excretion. These findings demonstrate that bile duct ligation in the rat results in impaired renal function, accompanied by increases in renal prostaglandin production. In addition, this study indicates that the perturbations in renal function and renal prostaglandin production induced by bile duct ligation are not mediated by renal sympathetic nerve activity.

6-Ketoprostaglandin F1 alpha

Effects of chronic cyclosporine administration on renal blood flow and intrarenal blood flow distribution.

Cyclosporine-induced decreases in renal blood flow (RBF) and glomerular function are well documented. Glomerular filtration and tubular function may be affected by changes in both total renal blood flow and cortical blood flow distribution (CBFD). The effect of CsA on RBF, CBFD, glomerular filtration rate, and tubular function was studied in conscious ewes receiving a mean CsA dose of 30 mg/kg/day for 28 days with mean CsA trough levels of 344 +/- 45 ng/ml. RBF and CBFD were determined by the injection of 15 microns radioactive microspheres before and after one month of treatment with CsA or its vehicle, olive oil. RBF decreased by 24% from 7.65 +/- 0.87 to 5.79 +/- 0.42 ml/min/g of kidney in CsA-treated ewes (P = 0.014), while no decrease was noted in the control group (7.92 +/- 1.10 vs. 7.62 +/- 0.71). Intracortical blood flow decreased in proportion to the fall in total renal blood flow--thus CsA treatment did not change the cortical distribution of flow. There was a 25% decrease in GFR, as determined by inulin clearance, in the CsA-treated group (80 +/- 6 vs. 62 +/- 3 ml/min; P = 0.027) while there was a nonsignificant increase in control animals (62 +/- 11 vs. 92 +/- 7 ml/min). There was no evidence of tubular dysfunction in either group. There were also no changes in urinary excretion rates of prostaglandins PGE2, 6-keto-PGF1 alpha or thromboxane B2, nor were there changes in plasma renin activity. CsA induced decreases in RBF occur red without redistribution of cortical blood flow, indicating that altered cortical distribution of blood flow is not responsible for the changes in GFR or tubular function that have been reported. The changes in renal blood flow and glomerular filtration rate are independent of changes in renal prostaglandin production, and are likely not associated with altered plasma renin activity.

6-Ketoprostaglandin F1 alpha

The relationship of urinary thromboxane excretion to cyclosporine nephrotoxicity.

Alterations in renal prostaglandin production have recently been postulated to modulate the decrease in renal blood flow associated with cyclosporine nephrotoxicity. In particular, increases in renal production of the potent vasoconstrictor thromboxane A2 have been implicated in the pathogenesis of this disorder. The present study was undertaken to explore the relationship between alterations in urinary thromboxane B2 excretion (UTxB2V) and CsA nephrotoxicity in two rat models. Male Sprague-Dawley (SD) rats were treated for 14 days with CsA 50 mg/kg/day (n = 8) or olive oil (C) (n = 9) by gavage. Creatinine clearance (Ccr), urine flow (V), and urinary excretion rates of sodium, N-acetyl-beta-D-glucosaminidase (NAG), glucose, and TxB2 were determined before and after treatment. A similar study was conducted using Fischer rats (CsA: n = 10, C: n = 13). In Fischer rats, CsA caused a 35% decrease in Ccr (P = 0.01), a 33% decrease in sodium excretion (P = 0.02), and a greater than 2-fold increase in NAG excretion (P = 0.03), while V, glucose excretion, and UTxB2V did not change. Although similar changes in sodium and NAG excretion were seen after CsA administration in SD rats, Ccr was not affected. Additional findings in SD rats included a 3-fold increase in V (P less than 0.01), a 24-fold increase in glucose excretion (P = 0.03), and a 5-fold increase in UTxB2V (P = 0.04). Thus, Fischer rats developed CsA nephrotoxicity in the absence of increased UTxB2V. In contrast, SD rats failed to develop nephrotoxicity despite a marked increase in UTxB2V. We conclude that changes in renal TxA2 production are unrelated to the development of CsA nephrotoxicity.

Acetylglucosaminidase

Incentives and their influence on appointment compliance in a teenage family-planning clinic.

The purpose of this study was to ascertain whether or not the family-planning compliance patterns of indigent adolescents could be influenced by various types of incentives. From February 1988 through January 1989, 534 postpartum inner city teenagers, aged 12-19, who delivered at a large city-county public hospital, participated. Teens were randomly assigned to two treatment groups that either offered a coupon for milk for the infant or a gift for the teenage mother if they returned for their postpartum visit 4-6 weeks after delivery. A third group, which used no incentive for appointment keeping, acted as a control. Although overall compliance was low, a significant relationship was found between type of program incentive and compliance outcome. The program using milk coupons as an incentive had the best compliance rate. This incentive appeared to be most effective with black adolescents. Such incentive programs, although not without controversy, offer a potential way to enhance postpartum contraceptive appointment-keeping compliance in a high-risk population.

Adolescent

Obstructive jaundice and renal failure in the rat: the role of renal prostaglandins and the renin-angiotensin system.

We have previously noted that bile duct ligation (BDL) in the rat results in decreased creatinine clearance (Ccr) and decreased urinary sodium excretion (UNaV) as well as increased renal prostaglandin (PG) production. This study was undertaken to assess the role of increased renal PG production in the change in renal function after BDL and to determine if these changes are mediated by the renin-angiotensin system. After baseline measurement of renal function, Sprague-Dawley rats underwent either sham operation (SO) or BDL. Four days later animals received a single intraperitoneal injection of either 0.9% saline, 0.5 ml/kg (SO, n = 10; BDL, n = 10), or indomethacin, 5 mg/kg (SO + Indo, n = 10; BDL + Indo, n = 10), and renal function was reassessed. Plasma renin activity was measured at the end of the second study period. BDL resulted in a 40% decrease in Ccr (p = 0.000), a 38% decrease in UNaV (p = 0.002), a twofold increase in urinary 6-keto-PGF1 alpha excretion (p = 0.005), and fourfold increases in urinary excretion of PGE2 (p = 0.006) and thromboxane B2 (p = 0.000). Indomethacin prevented the increase in urinary PG excretion otherwise seen with BDL and resulted in an additional 41% reduction in UNaV (p = 0.018). Further reductions in Ccr by indomethacin, however, were minimal and nonsignificant. Plasma renin activity did not differ among any of the groups. These findings indicate that the sodium retention associated with BDL is attenuated by the concomitant rise in renal PG production. This elevation in PG production, however, does not protect against the adverse effects of BDL on Ccr. Furthermore, the changes in renal function that occur after BDL do not appear to be mediated by the renin-angiotensin system.

Acute Kidney Injury

Incidence of gestational diabetes: effects of race.

A total of 2,435 pregnant women underwent glucose screening during the late second trimester or early third trimester. Of those screens, 548 (22.5%) were abnormal; from these, 154 abnormal glucose tolerance tests were recorded. This gave an overall 6.3% incidence of gestational diabetes at our institution. Eighty-two of the abnormal glucose tolerance tests were in Hispanic females, but this was not significantly higher than in other racial groups. Patients with a negative glucose tolerance test after a positive diabetic screen and obese gravidas had an 11.3% incidence of macrosomia. Of all the macrosomic infants (greater than 4,000 g) 38% of mothers weighed 200 lb (90 kg) or more.

Female

Renal failure complicating obstructive jaundice.

Postoperative acute renal failure in patients with obstructive jaundice remains a clinically significant complication. Acute renal failure occurs in approximately 9 percent of patients requiring surgery for relief of obstructive jaundice, and contributes to eventual mortality in 76 percent of those who develop it. The overall mortality rate for patients undergoing surgery for obstructive jaundice is 16 percent. Despite advances in perioperative care, these figures have changed very little over the past 25 years. This article describes the clinical association between jaundice and renal failure and reviews the studies that have contributed to the delineation of the possible underlying pathophysiologic mechanisms, as well as possible preventive measures which have been developed as a result of these investigations. With increased awareness of the potential risk of developing postoperative acute renal failure, the institution of prophylactic measures may result in an improvement in the mortality rate seen after surgery for obstructive jaundice.

Acute Kidney Injury

Effects of cyclosporine on glucose metabolism.

Cyclosporine may have deleterious effects on glucose metabolism. This study was designed to characterize more precisely cyclosporine-induced alterations in glucose homeostasis in a large animal model with hyperglycemic and euglycemic clamp studies in addition to simple bolus glucose (IVGTT) and insulin (IVITT) tolerance tests. In experiment 1, IVGTTs and hyperglycemic clamp studies were performed in eight ewes before and after 4 weeks of cyclosporine treatment. Studies were repeated 4 weeks after cessation of therapy. In experiment 2, IVITTs and euglycemic clamp studies were performed in seven ewes before and after 4 weeks of cyclosporine treatment. Fasting glucose and insulin levels were not affected by cyclosporine treatment. In experiment 1 cyclosporine did not alter IVGTTs; however, during sustained hyperglycemia, cyclosporine caused a 37% decrease in net glucose disposal (p less than 0.001) and a 39% decrease in plateau plasma insulin levels (p less than 0.05). In experiment 2 cyclosporine had no effect on IVITTs. Plateau insulin values in euglycemic clamp studies were lowered by 27% (p less than 0.05) after cyclosporine treatment. In addition, the metabolic clearance rate of insulin was increased by 25% (p less than 0.05), and the steady-state insulin clearance rate was increased by 16% (p less than 0.003). Measurements of insulin sensitivity were unchanged by cyclosporine. These experiments suggest that cyclosporine treatment results in impairment of sustained synthesis and secretion of insulin, increased insulin clearance, and unaltered insulin sensitivity.

Animals

Predominant sexually transmitted diseases among different age and ethnic groups of indigent sexually active adolescents attending a family planning clinic.

The present study analyzed a group of 113 sexually active, indigent female adolescents attending a family planning clinic, for age, ethnic, or racial trends in the recovery of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma species, and Ureaplasma urealyticum. The overall recovery rate for N. gonorrhoeae was 8/112 (7.1%), with the highest rate occurring in black patients (7/82, 8.5%). The overall recovery rate for C. trachomatis was 31/113 (27.4%), with the highest rate occurring in Hispanics (7/21, 33.3%). The isolation of C. trachomatis was evenly divided among patients grouped by reason for visit. Neisseria gonorrhoeae, on the other hand, was isolated more frequently from patients coming for a sexually transmitted disease screen than from those attending for other reasons. There was a significant (p less than 0.05) increase in isolation of Mycoplasma species from 18-19-year-old patients, but no such difference was observed for U. urealyticum when compared to younger age groups. Factors associated with venereal disease prevalence in our teenage indigent population as well as implications for the future reproductive health of such patients are discussed.

Adolescent

Variable results of calcium blockade in post-ischaemic renal failure.

The effects of three chemically dissimilar calcium-blocking drugs were studied in experimental post-ischaemic renal failure, in the rat. After 45 min unilateral clamping and contralateral nephrectomy, post-ischaemic verapamil administration protected renal function (p less than 0.025), but flunarizine, either before or after ischaemia, was not beneficial. Following 60 min bilateral renal pedicle clamping, nifedipine administration was not beneficial. Verapamil was the only calcium-blocking drug which attenuated the post-ischaemic renal dysfunction. Calcium blockers which differ in their modes of action, differ in their ability to protect the kidney from ischaemia.

Acute Kidney Injury

Renal vascular reactivity in the bile duct-ligated rat.

The renal dysfunction associated with liver disease appears to be caused by decreased renal perfusion. Altered renal vascular reactivity (RVR) may contribute to the development of decreased renal blood flow. This study was undertaken to assess the effect of bile duct ligation (BDL) on RVR to norepinephrine and angiotensin II in the rat and to evaluate the role of prostaglandins in the modulation of altered RVR. Male Sprague-Dawley rats underwent either sham operation (SO) or BDL. Four days later, isolated kidney perfusions were established. Dose-response curves to norepinephrine (SO, n = 9; BDL, n = 10) and angiotensin II (SO, n = 7; BDL, n = 9) were obtained. The perfusate was modified to contain indomethacin, 10(-6) mol/L, and dose-response curves to norepinephrine (SO, n = 10; BDL, n = 8) and angiotensin II (SO, n = 4; BDL, n = 8) were obtained as well. Baseline resistances did not differ between any of the groups. RVR to norepinephrine did not appear to be altered by BDL; however, increased RVR to norepinephrine was unmasked by inhibition of prostaglandin synthesis. BDL did not affect the RVR to angiotensin II with or without indomethacin. BDL is associated with an increase in renal vascular sensitivity to norepinephrine, which is balanced by a compensatory increase in renal prostaglandin activity in response to norepinephrine stimulation. These findings are consistent with theories that decreased renal perfusion associated with liver disease may be mediated by catecholamines.

Angiotensin II

Hispanic adolescent conception and contraception profiles. A comparison.

Marital status, contraception, desire for pregnancy, and social support relationships were analyzed by ethnicity for a group of pregnant and postpartum adolescents. Although no significant differences were found among ethnic groups for birth control information and use, the desire for pregnancy, grouped by marital status at conception, was significantly different for Hispanics. Positive evaluations of the life changes associated with pregnancy were found more frequently among Hispanic mothers. Hispanic teen mothers, however, were least likely to understand the menstrual cycle. The role of ethnic background in adolescent fertility behaviour is discussed, and potential clinical applications for more effectively serving sexually active Hispanic adolescents are presented.

Adolescent

The canine kidney in haemorrhagic shock: effect of verapamil.

Recent evidence suggests that verapamil administration reduces myocardial and small intestinal damage in canine haemorrhagic shock, and verapamil has also been shown to reduce renal dysfunction in clamp models in post-ischaemic renal failure. The effects of high-dose verapamil and hypovolaemia on renal haemodynamics and function in a canine haemorrhagic shock model were studied. Anaesthetized mongrel dogs were divided into three groups. Animals of group I (n = 5) were not subjected to shock but given a 90-min verapamil infusion (2.28 micrograms/kg); animals of group II (n = 5) were subjected to shock (mean blood pressure 40 mm Hg) for 2 h and given a 90-min 0.9% saline infusion, and animals of group III (n = 7) were both subjected to a 2-hour shock and given verapamil. The electrocardiograph was monitored, and general haemodynamic parameters were measured before shock (period 1), at the end of shock (period 2), after reinfusion of shed blood (period 3) and 1 h after shock (period 4). Total renal and cortical zonal blood flow was estimated by radioactively labelled microsphere injection during each period. Creatinine and osmolar clearance were estimated before and after shock. Verapamil administration caused heart block in groups I and III which lowered heart rate and blood pressure and exacerbated the haemodynamic effects of shock in group III. Despite this, no measurable difference in renal function was recorded between groups II and III. Total renal blood flow fell during shock, and this was exacerbated in animals given verapamil, suggesting a cumulative deleterious effect of shock and verapamil in renal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals