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Biomedical subjects

R M Hurley

Publications and source records attributed to R M Hurley.

At least 19 recordsLinked to original sources

Neonatal hypertension. Incidence and risk factors.

To determine the incidence and risk factors for neonatal hypertension we studied the entire population of 3179 infants admitted to our neonatal intensive care unit over a 6-year period. We report a 0.81% (26/3179) incidence of hypertension in this population. In 13 patients (50%) the hypertension was renal in origin. In four patients (15.4%), the etiology of hypertension could not be determined. Significant risk factors for neonatal hypertension included: bronchopulmonary dysplasia (5.9% in affected infants v 0.5% in unaffected infants, P less than .001); patent ductus arteriosus (3.07% in affected v 0.5% in unaffected infants, P less than .001); intraventricular hemorrhage (2.89% in affected infants v 0.56% in unaffected infants, P less than .001); and umbilical arterial catheterization (8.8% v 0.2% in infants with and without catheterization, respectively, P less than .001).

Bronchopulmonary Dysplasia

Elevated lead levels in a patient with sickle cell disease and inappropriate secretion of antidiuretic hormone.

A five-year-old girl with known sickle cell disease presented with severe hyponatremia and findings compatible with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). She was found to have lead levels in the Class III category. By exclusion, we postulated that the SIADH was in some way related to the high lead levels, since this was the only abnormality the patient exhibited. The toxic lead levels and the elevated vasopressin levels rapidly responded to dimercaprol and calcium EDTA chelation therapy.

Anemia, Sickle Cell

Glycosuria and maternal licking in rats.

Maternal anogenital licking (MAGL) has been studied to understand the mechanism of maternal behaviour. The present study showed that rats had glycosuria at the concentration of 18-20 mg/dl and glucose was the preference of postpartum rats. MAGL increased on suckling rats separated for 24 h. However, wiping anogenital region attenuated the increase of MAGL. Therefore, glucose preference of postpartum rats may be involved in MAGL.

Animals

Diltiazem treatment of endotoxic shock in suckling rats.

Gram-negative sepsis septic shock continues to produce significant mortality and therefore remains a major medical problem. Vasodilators have been studied in the treatment of circulatory shock. However, the effectiveness of calcium channel blockers in the treatment of newborn endotoxic shock has not been well documented. In the present study, diltiazem, a calcium channel blocker, and nitroprusside, a vasodilator, were used for the treatment of endotoxic shock in 10-day-old rats. Mortality rate, hemodynamics, and glucose metabolism were monitored. Diltiazem at a dose of 0.3 mg/kg attenuated the hypotension, bradycardia, hypoglycemia, and lactacidemia in newborn endotoxic shock. Diltiazem treatment resulted in reduced 24-hour mortality. However, 0.6 mg/kg diltiazem enhanced the hypotension, bradycardia, and lactacidemia in endotoxic shock. Nitroprusside blunted the hypoglycemia and decreased the mortality rate among rats with endotoxic shock. Afterload reduction may be responsible for the beneficial effects of 0.3 mg/kg diltiazem and nitroprusside. Diltiazem at a dose of 0.3 mg/kg reduced the lactacidemia of endotoxic shock more than nitroprusside. Therefore the effects of diltiazem may be due not only to afterload reduction but also to inhibition of cellular calcium influx. We conclude that 0.3 mg/kg diltiazem and 1.0 mg/kg nitroprusside are beneficial for the treatment of endotoxic shock in newborn rats.

Animals

Altered glucose transporter mRNA abundance in a rat model of endotoxic shock.

To better understand molecular mechanisms of glucose transport in shock, we studied glucose transporter isoform mRNA abundance after injection of S. enteritidis endotoxin (40 mg/kg) or saline. Six to 8 hours after injection, endotoxin-treated animals compared to controls became hypoglycemic (44 +/- 6 vs. 111 +/- 4 mg/dl) and lactacidemic (5.9 +/- 0.5 vs. 1.3 +/- 0.1). At such times, tissue RNA was isolated and hybridized to Riboprobes for GLUT1 (erythrocyte), GLUT2 (liver), and GLUT4 (muscle/fat) glucose transporter isoforms and expressed as percent of control. GLUT1 mRNA abundance was increased in fat (660%, p less than .05), soleus muscle (314%, p less than .05), and liver (871%, p less than .001) of endotoxin-treated rats. Soleus muscle GLUT4 mRNA levels were increased (+33%, p less than .02), while liver GLUT2 mRNA levels were markedly decreased (-58%, p less than .01). The overall increase in GLUT1 mRNA abundance accompanied by lowered liver GLUT2 mRNA levels may either cause or reflect profoundly altered glucose transport.

Adipose Tissue

A comparison of two common clinical methods with high-pressure liquid chromatography for the measurement of creatinine concentrations in neonates.

The accurate measurement of low serum creatinine levels is necessary for estimating clinically useful creatinine clearances in the pediatric population. This study compares two routine clinical methods: the kinetic Jaffé with the newer Kodak enzymatic method against our reference method, high-pressure liquid chromatography, for the measurement of serum and urine creatinine levels in neonates. One hundred and twenty-five serum and 59 urine creatinines and 56 absolute creatinine clearances were measured in neonates ranging from 23 to 46 weeks (mean 32 weeks) post-conceptional age and weighing 480-4398 g (mean 1650 g). Urine creatinine levels, and serum creatinine levels greater than 0.8 mg/dl were equivalent for both clinical methods. However, the enzymatic method was much more accurate (P less than 0.001) than the kinetic Jaffé method for serum creatinine measurements of less than or equal to 0.8 mg/dl. We conclude that the enzymatic methodology is a better clinical choice for the accurate measurement of serum creatinine levels when using these values for the determination of neonatal renal function.

Child, Preschool

Effect of intraosseous saline infusion on hematologic parameters.

STUDY OBJECTIVE: To examine the effects of intraosseous saline infusion on hematologic parameters. DESIGN AND SETTING: Eight New Zealand White rabbits were anesthetized with intramuscular ketamine. An initial blood sample was withdrawn from a earlobe vein on induction of anesthesia. An 18-gauge intraosseous needle was then inserted into the rabbit's proximal tibia, and 10 mL/kg of normal saline was infused over one minute. Two additional blood samples were obtained 15 and 30 minutes after the intraosseous infusion. MEASUREMENTS: Complete blood counts were performed on the blood samples. RESULTS: Significant differences were found in monocytes, basophils, and nucleated RBCs from samples drawn before and after intraosseous infusion. The microscopic examination of the peripheral blood smear revealed an increase in the number of burr cells, schistocytes, and polychromasia in the postinfusion samples. CONCLUSION: We advocate caution in the interpretation of hematologic studies performed on blood samples obtained shortly after an intraosseous infusion.

Animals

Cepharanthine (biscoclaurine alkaloid) treatment in endotoxic shock of suckling rats.

Gram-negative sepsis/septic shock causes significant mortality in newborns. However, there has been no established method for newborn endotoxic shock treatment. Prostaglandins play a role in endotoxic shock. Cepharanthine is a biscoclaurine alkaloid that primarily inhibits phospholipase A2. Therefore, the effects of cepharanthine have been studied on endotoxic shock in newborn rats. Cepharanthine decreased the 24 h mortality of endotoxic shock in a dose-related manner. At the dose of 0.2 mg kg-1 it effectively reduced the mortality from 90 to 21% in newborn rats. It also induced hyperglycaemia in control rats and blunted the hypoglycaemia of endotoxic shock. Cepharanthine did not suppress body weight gain nor did it delay death as seen with glucocorticoid treatment. We conclude that cepharanthine is beneficial in the treatment of newborn endotoxic shock.

Alkaloids

Prophylaxis and treatment of newborn endotoxic shock with anti-lipid A monoclonal antibodies.

The newborn is very susceptible to gram-negative sepsis/septic shock. The mortality of newborn endotoxic shock continues to be high. Since lipid A is responsible for the toxic effects of lipopolysaccharide, anti-lipid A antibodies may prevent endotoxic shock in the newborn. This study showed that both anti-lipid A monoclonal IgG (A78S1) and anti-lipid A monoclonal IgM (A523) decreased the mortality of endotoxic shock in 10 day old rats. Prophylactic administration of A78S1 and A523 to the pregnant rat decreased the mortality of endotoxic shock in their 0-day-old offspring. Prophylaxis was due to transplacental passage of A78S1 treatment. The mechanism of prophylaxis remains unclear in A523 treatment.

Animals

Mortality, temporal substrate and insulin responses to endotoxic shock in zero, ten and twenty-eight day old rats.

Neonatal sepsis is a significant health problem. However, to our knowledge, the temporal substrates and insulin response to endotoxin have not been characterized in the young animal to guide the investigations of glucoregulation in septic shock in the newborn. We characterized the temporal response to endotoxin in the developing rat. Sprague-Dawley rats were given intraperitoneal Salmonella enteritidis endotoxin in high and low lethal doses to zero, ten and 28 day old rats. Mortality, temporal glucose, lactate, hepatic glycogen and insulin were monitored. Mortality experiments show the ten day old rat is 300 times as sensitive to endotoxin as the 28 day old rat. Plasma glucose concentration increased in the high mortality groups by 120 minutes in the zero and ten day old rats (102 +/- 4 milligrams per deciliter, 119 +/- 6 milligrams per deciliter, respectively, and by 60 minutes in the 28 day old rats (223 +/- 12 milligrams per deciliter). The plasma glucose level decreased to 52 +/- 3 milligrams per deciliter by 240 minutes in the ten day old and by 180 minutes to 99 +/- 8 milligrams per deciliter in the 28 day high mortality groups. Peak lactic acid levels in the high lethality groups were zero day 2.8 +/- 0.2 millimoles per liter in zero day old rats, 3.3 +/- 0.2 millimoles per liter in 28 day old rats. Glycogen in the liver decreased rapidly by 120 minutes in all age groups. Plasma insulin concentration did not elevate significantly in zero and ten day old rats. In the 28 day old rat, insulin concentration increased by 120 minutes to 52 +/- 17 microunits per milliliter. Insulin glucose ratios were also elevated in the 28 day old endotoxin treated rat, indicating hyperinsulinemia. Thus, temporal substrates and insulin responses to endotoxin differ with animal age.

Age Factors

Effects of cytarabine on glucoregulation in suckling rats.

The effects of cytarabine (beta-cytosine arabinoside) on glucose metabolism is not well known. The present study showed that 5 mg/kg of cytarabine decreased plasma glucose level in 10 day old rat 4 hours after ip injection. Hepatic glycogenolysis decreased 4 hours after cytarabine injection. Thus, cytarabine alters newborn glucoregulation.

Animals

Enuresis: the difference between night and day.

The differentiation between night and day wetting allows the application of practical developmental and behavioral approaches to the diagnosis, evaluation, and therapy of each problem. Wetting the bed is mainly a developmental issue, and wetting the pants is a behavioral one.

Child

Dexamethasone and indomethacin treatment during endotoxicosis in the suckling rat.

Gram negative sepsis/septic shock continues to be a major cause of morbidity and mortality in newborns. We studied the effects of anti-inflammatory drugs, indomethacin (IND) and dexamethasone (DX), on glucoregulation, body weight, and mortality in 10-day-old suckling rats administered Salmonella enteritidis lipopolysaccharide (LPS). IND (1.5 mg/kg) or DX (4 mg/kg) was intraperitoneally (ip) administered immediately after highly lethal LPS injection. Both IND and DX attenuated the LPS-induced hypoglycemia and lactacidemia, and decreased the mortality, IND did not alter body weight changes in rats with septic shock. DX continued a catabolic state and reduced their body weights. In rats fasted for 24 hr before LPS injection, DX, but not IND, increased the mortality. We concluded that IND and DX improved the LPS-induced glucose dyshomeostasis and decreased the mortality of endotoxic shock in 4-hr-fasted 10-day-old rats. Per contra, DX was detrimental in 24-hr-fasted 10-day-old endotoxic rats.

Animals

Renal lesions in young rats induced by Salmonella enteritidis endotoxin.

Sepsis in newborns and infants is a major pediatric problem often associated with renal dysfunction. The present report deals with changes in renal tissue induced by Salmonella enteritidis endotoxin in 10- and 28-day-old Sprague-Dawley rats. Our studies revealed a 90% lethality within 24 h of 0.1 mg/kg and 35 mg/kg S. enteritidis endotoxin injection in 10- and 28-day-old rats, respectively. The 10- and 28-day-old animals received a single intraperitoneal injection of the 90% lethality dose and were sacrificed at different intervals for histopathological evaluation of kidneys by light and electron microscopy. The glomeruli showed visceral epithelial and endothelial cell swelling and polymorphonuclear leukocyte and platelet accumulation in the capillary lumina. Cortical and medullary tubules showed edematous separation, mild focal epithelial cell damage and focal intertubular hemorrhage. Renal sections of 28-day-old experimental rats showed increased numbers of polymorphs in the glomerulus and enlarged mesangial matrix. These sections also showed an increase in the number of hemorrhagic foci in 10 x field compared with the 10-day-old experimental rats. Endothelial cells of renal vasculature showed cytoplasmic swelling, vacuolization, autophagic vesicle formation and presence of secondary lysosomes. Changes in the endothelial cells of peritubular microvasculature were extensive, resulting in focal degeneration and partial loss of endothelial lining. These studies show that infant rats are extremely sensitive to S. enteritidis endotoxin requiring 1/350 the dose given to young adults to induce histopathological changes in kidney; the endothelial cells of microvasculature appear to be the primary targets of endotoxic injury irrespective of age.

Animals

Bromate poisoning.

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Acute Kidney Injury

Microvascular endothelium: a major target site of endotoxin induced injury in 10 day old rat.

We have studied the effects of two endotoxins, S enteritidis and E coli on liver, pancreas, intestine, lung and kidney of 10 day old Sprague Dawley rat at light and electron microscope levels. One group of experimental animals (N = 31) received a single intraperitoneal injection of 0.1 mg/kg of S enteritidis endotoxin. The second experimental group (N = 34) received multiple intraperitoneal injections of 5 to 10 mg/kg of E coli endotoxin at 15 minute intervals over a period of 75 minutes. Within four hours of injections, histopathologic evaluation of all the tissues revealed interstitial edema, widening of blood capillary lumina, accumulation of polymorphonuclear leukocytes and platelets in capillary lumina and marked swelling, vacuolization and focal desquamation of endothelial cells in microvasculature. Hepatocytes showed loss of glycogen, vacuolization and degeneration in the centro-portal region. Islet cells of pancreas also revealed swelling and vacuolization. In the small intestine, hemorrhagic pools of blood were frequently seen in lamina propria and the apical portion of villi showed degeneration and breakdown. Lungs showed focal hemorrhage, collapse of alveolar architecture and swelling of endothelium in larger artereoles. Based on these studies, we suggest that endothelial cells of microvasculature in various tissues of 10 day old rat are extremely sensitive to endotoxins, irrespective of source, and cells derived from reticuloendothelial system may play an important role in the endotoxicosis.

Animals

Prophylactic immunotherapy in newborn rat endotoxicosis.

The incidence and mortality of gram negative sepsis/septic shock remains high in newborns. In this paper, we postulated that prophylactic immunotherapy may be beneficial in newborn endotoxicosis. Lipopolysaccharide (LPS) tolerant rats were produced by serial Salmonella enteritidis LPS injections, and their sera were used for immunotherapy. Antiserum cotreatment blunted hypoglycemia and lactacidemia in S. enteritidis endotoxicosis and decreased the mortality. In 0-day-old rats, antiserum cotreatment groups had a decreased mortality when injected with S. enteritidis LPS (P less than .001), S. typhosa LPS (P less than .005), and Escherichia coli LPS (P less than .05). This global protection suggested that antibody to S. enteritidis LPS could be due to a common LPS antigen. Prophylactic antiserum administration to pregnant rats on the 18th day of gestation decreased the mortality of S. enteritidis endotoxicosis in 0-day-old rats (P less than .001). The prophylactic effects of antiserum was achieved by transplacental passage to the conceptus. We conclude that prophylactic as well simultaneous immunotherapy was beneficial in newborn rat endotoxicosis.

Animals