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Biomedical subjects

J F Crocker

Publications and source records attributed to J F Crocker.

At least 37 records · Page 2Linked to original sources
PubMed1991

Deferoxamine and aluminum clearance in pediatric hemodialysis patients.

Mobilization of aluminum by deferoxamine and the subsequent clearance from plasma by hemodialysis with or without charcoal hemofiltration was studied in four pediatric patients. Deferoxamine, 10-20 mg/kg, followed by dialysis with a Travenol CA50 dialyzer produced reductions in mean plasma aluminum levels from 2433 +/- 729 nmol/l (65.5 +/- 19.6 micrograms/l) to 1727 +/- 554 nmol/l (46.5 +/- 14.9 micrograms/l) during dialysis. The use of a charcoal cartridge in the circuit resulted in a reduction in mean plasma aluminum levels 2459 +/- 591 nmol/l (66.2 +/- 15.9 micrograms/ml) to 1380 +/- 106 nmol/l (35.8 +/- 2.9 micrograms/l). In one patient, high-flux dialysis produced a reduction from 2140 nmol/l (55.6 micrograms/l) to 1134 nmol/l (29.4 micrograms/l). No patients suffered direct adverse reactions to low-dose deferoxamine, although two patients had previously exhibited potential aluminum neurotoxicity after rapid increases in plasma aluminum levels with deferoxamine in higher doses. Aluminum levels must be monitored closely during deferoxamine therapy in uremic children to minimize the risk of exacerbating aluminum neurotoxicity.

Aluminum↗
PubMed1991

Surfactant-potentiated increases in intracranial pressure in a mouse model of Reye's syndrome.

Severe encephalopathy, the usual cause of death in Reye's syndrome (RS), is characterized by cerebral edema with associated increases in intracranial pressure (ICP). In previous studies, we have shown that exposure of neonatal mice to nontoxic doses of an industrial surfactant and subsequent infection with mouse-adapted influenza B (Lee) virus result in a significant increase in mortality rate and that this is associated with several of the characteristic features of human RS. In the present study we have measured ICP in the young mice undergoing their version of the disease, and we now report that the animals treated with surfactant plus virus experience increases in intracranial pressure that are significantly in excess of those in any of the three control groups. These findings support our hypothesis that this and the other abnormal biochemical and morphological responses in RS are related in some manner to a chemically compromised host.

Animals↗
PubMed1991

Ontogeny of dexamethasone binding and sodium potassium ATPase activity in experimental murine polycystic kidney disease.

The induction of polycystic kidney disease (PKD) by glucocorticoids in newborn mice behaves as a "threshold" trait, with prevalence of PKD varying in different inbred strains after exposure to an inducing steroid. C3H mice (low threshold for PKD) demonstrated greater specific dexamethasone binding than DBA mice (high threshold) on the second day of life. Treatment with methylprednisolone acetate (MPA), a cyst-inducing steroid, down regulated dexamethasone binding earlier than in DBA mice. C3H mice demonstrated greater whole kidney homogenate Na-K ATPase activity than DBA mice within 24h of MPA injection. Specific renal glucocorticoid binding may be a regulator of threshold for murine glucocorticoid induced PKD. Our findings support in vitro evidence that glucocorticoid induced Na-K ATPase activity during critical periods of nephron development is an important regulatory point of this model.

Animals↗
PubMed1990

Plasma therapy for severe hemolytic-uremic syndrome in children in Atlantic Canada.

Clinical reports have suggested that therapy with fresh frozen plasma is a useful adjunct in the management of the hemolytic-uremic syndrome (HUS). We reviewed the charts of 36 children with severe HUS who were treated at the Izaac Walton Killam Hospital for Children, Halifax, over 10 years to assess the effectiveness of plasma therapy. All children who required specific supportive therapy for renal dysfunction, hemolysis or serious extrarenal complications were included. We compared the outcome of 18 children who received plasma therapy from 1982 to 1987 with that of 18 children who did not. The two groups were similar with regard to the severity of HUS, the length of hospital stay, the duration of renal dysfunction and the incidence of disease-related complications, such as seizures, enterocolitis and cardiomyopathy. At discharge the prevalence of hypertension was higher in the plasma therapy group than in the control group. Plasma therapy did not demonstrate any benefit that would outweigh the risk of fluid overload, hyperproteinemia and transmission of viral infection.

Acute Disease↗
PubMed1990

Glucocorticoid-induced polycystic kidney disease--a threshold trait.

Administration of hydrocortisone acetate (250 mg/kg) to newborn mice caused polycystic kidney disease (PKD) of varying proportions in each of 18 different inbred strains; none of the injected controls were affected. All kidneys were histologically examined and scored for degree of cyst formation using a semi-continuous (0 to 4+) grading scheme. Results suggested that this condition is a multifactorial threshold trait. For each strain, estimates of the mean and standard deviation of normally distributed liability were determined by maximum likelihood methods. Concomitant analyses showed: 1) a significant environmental effect related to drug source; 2) a variation in thresholds ranging from 0.94 (N = 46) for the B10.M strain to -0.71 (N = 297) for the C57B1/6J strain; and 3) three groups of strains with different susceptibility to PKD. These results are consistent with a multifactorial basis for susceptibility to PKD. Quantitative analysis of thresholds and liability distributions reveals that genetic, environmental and random elements all contribute to the expression and extent of the cystic trait.

Animals↗
PubMed1990

The microanatomy of the intrahepatic bile duct in polycystic disease: comparison of the cpk mouse and human.

The cpk mutation in mice produces a lethal recessive form of polycystic kidney disease (PKD) that, like human forms of the condition, is associated with an age-related incidence of hepatic cysts. Injection of plastic into the biliary tree of affected animals revealed that these cysts arise from focal dilatations of the epithelial lining that may enlarge to the point that they obstruct the bile ducts. This concept was supported by histological and scanning and electron microscopic studies. No evidence could be found of primary obstruction of the biliary tree. The same techniques were then employed in specimens of human liver from patients with both recessive (ARPKD) and dominantly inherited PKD (ADPKD). Similar abnormalities of the biliary tree were identified. These abnormalities were not found in control liver samples from patients without PKD. The liver of the patient with ADPKD also demonstrated many von Meyenburg complexes. These were related to some cyst development, but these complexes freely communicated with bile ducts, contrary to currently held opinion. We conclude that hepatic abnormalities in the cpk mouse and human PKD arise from changes in bile ducts that are analogous to the renal lesions.

Animals↗
PubMed1989

Nifedipine, verapamil and cyclosporin A pharmacokinetics in children.

We report two paediatric renal transplant patients in whom interaction with the calcium channel blocking agent verapamil resulted in reduced cyclosporin A (CyA) elimination. Prior therapy with another calcium channel blocking agent, nifedipine, did not affect CyA pharmacokinetics. We speculate that verapamil reduced CyA elimination in children via an effect upon the microsomal oxidase system that is independent of calcium channel activity.

Child↗
PubMed1989

The hypocalcemic effect of inorganic sulfate infusions.

Inorganic sulfate is a divalent anion that forms a soluble ion-pair complex with serum calcium, but the extent to which infusions of sulfate salts may depress the concentration of ionized calcium has never been quantitated. In a study of 9 patients who received sodium sulfate infusions as part of a standard diagnostic workup for their renal tubular acidosis, we observed a decrease in mean ionized calcium (adjusted to pH 7.40) from 1.15 +/- 0.01 to 1.04 +/- 0.02 mmol/l (p less than 0.01). The changes in ionized calcium were highly correlated with those in serum sulfate (r2 = 0.95; p less than 0.01). Quantitatively, an increase of 1 mmol/l in serum sulfate was associated with a decrease of 0.017 mmol/l in ionized calcium, a result that is in close agreement with in vitro data based on simple salt solutions. Diagnostic sulfate infusions should be used with caution in any patient predisposed to hypocalcemia.

Acidosis, Renal Tubular↗
PubMed1988

Effects of chronic phthalate exposure on the kidney.

Several investigators have reported the finding of polycystic kidney disease (PKD) at autopsy in patients who had undergone long-term hemodialysis for renal failure due to causes other than PKD. We initiated studies to determine whether the drugs or chemicals to which patients on dialysis are exposed could be responsible for these cystic changes. Adult rats were tube fed chemical residues from an artificial kidney or phthalate esters [di(2-ethylhexyl) phthalate, DEHP], which are a main component of these plastic kidneys or a control solution. Rats receiving DEHP or residues showed a significantly higher incidence of focal cysts when compared to controls. Rats receiving DEHP developed a significant decrease in kidney function as demonstrated by creatinine clearance, and these animals had the highest tissue levels of measureable DEHP. We postulate that patients receiving long-term dialysis may acquire PKD secondary to their exposure to chemicals leached from artificial kidneys.

Administration, Oral↗
PubMed1988

Effects of lithium chloride and ethacrynic acid on experimental polycystic kidney disease.

Hydrocortisone acetate is known to produce polycystic kidney disease when administered to susceptible animals in the perinatal period. To assess whether sodium and water transport mechanisms are involved in cyst pathogenesis, we administered lithium, an inhibitor of such transport in the distal nephron, and ethacrynic acid, an inhibitor of sodium transport in the Loop of Henle, to hydrocortisone acetate treated newborn rats. Hydrocortisone acetate alone resulted in significant polycystic kidney disease with the development of uremia, hypokalemia, and shortened life span. Co-administration of lithium and hydrocortisone acetate increased the severity of cystic tubular change and further compromised renal function. Ethacrynic acid reduced the degree of cyst formation induced by the combination of lithium chloride and hydrocortisone acetate but otherwise had no effect. We conclude that fluid and electrolyte disturbance plays a significant role in cyst formation, but we are unable to ascribe that effect to a single ion. We also conclude that the antinatriuretic effect of glucocorticoids is not the principal factor in glucocorticoid induced polycystic kidney disease.

Animals↗
PubMed1987

Investigation of pediatric hypertension. Use of a tailored protocol.

Using a comprehensive protocol, the efficacy of simple clinical data, including history, physical examination, and urinalysis, in the discrimination of essential or secondary hypertension was investigated by a review of 103 patients, aged 2 weeks to 18 years, consecutively referred for investigation. Essential hypertension (55/103 mm Hg) was the most common diagnosis, even in infancy, whereas various renal disorders formed the next most common diagnostic category (21/103 mm Hg). Family history and the presence of "fixed" vs "labile" hypertension were of no value in detecting secondary hypertension. Urinalysis was useful in detecting inflammatory renal lesions but not structural disorders of the kidney. This study emphasizes the need for thorough investigation, including renal imaging, of asymptomatic hypertensive children and suggests a useful protocol to achieve this end.

Adolescent↗
PubMed1987

Hepatic lipid abnormalities in a chemical/viral mouse model for Reye's syndrome.

We have examined hepatic lipid profiles in a mouse model for Reye's Syndrome (RS) in which young animals are exposed to nontoxic doses of an industrial pesticide emulsifier and subsequently are infected with sublethal doses of mouse-adapted human Influenza B (Lee) virus (FluB). The purpose of this study was to determine whether liver lipid content was altered in the mice, the time course of any changes, and whether lipid changes were consistent with liver pathology. Neonatal mice exposed dermally to the emulsifier, Toximul MP8 (Tox), had significantly elevated levels of hepatic cholesterol, with otherwise normal lipid composition. Subsequent inoculation of the mice with FluB significantly increased mortality rate. The combined Tox + FluB treatment had several significant effects on liver lipids, including a transient increase in phospholipid (PL) content, a reduction in neutral glycerides and persistently high cholesterol levels. Abnormalities in fatty acid profiles included an apparent elevation in medium chain fatty acids and increased ratios of PL arachidonic to docosahexaenoic acids. Histologically, there was no evidence of fat accumulation in the liver; however, hepatic mitochondria had severe structural abnormalities characteristic of RS. These studies demonstrate that chemical-dependent enhancement of viral virulence is associated with significant alterations of hepatic lipids. We believe that these abnormalities are related to mitochondrial structural damage in RS despite the absence of hepatic steatosis.

Animals↗
PubMed1987

RU38486 prolongs survival in murine congenital polycystic kidney disease.

The cpk/cpk mutant mouse develops a lethal infantile polycystic kidney disease that is associated with disregulation of post natal glucocorticoid production. To establish if the observed endocrine abnormality is involved in the pathophysiology of polycystic kidney disease, blockade of glucocorticoid action during the immediate post-natal period was attempted. The steroid antagonist, RU38486, when administered from day 3 to day 12 of post-natal life, prolonged survival in affected animals. This finding supports a role for steroid hormones in the pathogenesis of this form of polycystic kidney disease.

Animals↗