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Biomedical subjects

M R Ogborn

Publications and source records attributed to M R Ogborn.

At least 37 records · Page 2Linked to original sources
PubMed1994

Early dietary protein restriction slows disease progression and lengthens survival in mice with polycystic kidney disease.

The objective of these studies was to examine the effects of early dietary protein restriction on disease progression and survival in the DBA/2FG-pcy (pcy) mouse model of polycystic kidney disease. Male pcy mice of 70 days of age were fed either a normal protein (NP, 25% casein) or a low-protein (LP, 6% casein) diet for 105 days. At the end of the dietary treatment, kidney weight, kidney weight relative to body weight and kidney water contents were almost 50% lower, and relative renal phospholipid and triglyceride contents were almost 50% higher, in mice fed the LP diet, indicating a marked reduction in the progression of cystic disease. Morphometric analyses also revealed a lower total and percent cyst area in kidneys derived from mice on the LP compared with the NP diet. There were no significant differences in final body weight, urine volume and osmolality, GFR, proteinuria, or plasma levels of protein and urea between these two groups. In a second study, it was found that all mice fed an NP diet from 70 days of age onward had died by 310 days of age, compared with a 42% survival rate in LP-fed mice at this age. Overall, the mean lifespan for pcy mice on the LP diet was 24% longer than that for those mice on the NP diet (310 +/- 20 versus 251 +/- 16 days; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Renal tubule Na,K-ATPase polarity in glucocorticoid-induced polycystic kidney disease.

Cyst formation in polycystic kidney disease (PKD) involves proliferation of cyst lining epithelial and changes in trans-epithelial fluid and electrolyte transport. In vitro studies have suggested that mislocation of Na,K-ATPase to the apical tubular surface may be an important component of cyst fluid transport. We undertook in vivo studies of Na,K-ATPase location using the "threshold" murine model of glucocorticoid-induced PKD (GIPKD). Using histological, immunohistochemical, and densitometric techniques, we compared cyst formation and the cellular location of Na,K-ATPase in suckling C3H (low threshold for GIPKD) and DBA (high threshold) mice given an inducing dose of 200 mg/kg methylprednisolone acetate. As expected, C3H mice demonstrated greater cyst formation as measured by proportion of section area occupied by the tubule lumen (26.7% vs 15.5%; p < 0.001). Cyst formation was associated with increased Na,K-ATPase staining and increased apical Na,K-ATPase location. MPA treatment in C3H mice resulted in apical staining that exceeded basolateral staining (35.3% of reference window vs 29.8%; p < 0.001). The relatively GIPKD-resistant DBA mice did not show such change in Na,K-ATPase location. These immunohistochemical studies suggest a role for Na,K-ATPase in renal cyst formation.

Animals↗
PubMed1993

Na-K ATPase activity in murine glucocorticoid induced polycystic kidney disease in vivo.

The prevalence and severity of polycystic kidney disease (PKD) induced by glucocorticoids in mice can be predicted by a mathematical "threshold" model. We studied the relationship between Na-K ATPase activity and cyst formation in C3H (low threshold for PKD) and DBA mice (high threshold). There was no difference in Na-K ATPase induction by 200 mg/kg methyl prednisolone acetate (MPA) (C3H; 97.4 nmol NADH/min/mg protein: DBA; 94.2 nmol NADH/min/mg protein). C3H mice demonstrated greater cyst formation than DBA animals as measured by area (20.1% relative area vs 13.9%, p < 0.05) or by calculated volume (7.4% relative volume vs 2.3%, p < 0.001). Significant relationships were seen between Na-K ATPase activity and logarithmically transformed area data in C3H animals and with cyst volume in both strains. Na-K ATPase activity is related to cyst formation in glucocorticoid induced PKD, but the level of Na-K ATPase activity is not a determinant of the threshold for glucocorticoid induced PKD.

Animals↗
PubMed1992

The use of a eutectic mixture of local anesthetic in pediatric renal biopsy.

Eight children undergoing percutaneous renal biopsy had eutectic mixture of local anesthetic (EMLA) cream substituted for dermal infiltration of local anesthetic. Five children reported no sensation of the initial skin puncture and only one child reported feeling a sharp object. EMLA cream may form a useful part of pediatric renal biopsy.

Administration, Topical↗
PubMed1992

Pediatric renal biopsy in the ambulatory care environment.

The use of pediatric ambulatory care facilities to perform invasive procedures that have low morbidity is increasingly popular. Over a 2-year period, 46 pediatric renal biopsies were performed in an ambulatory care setting at the Winnipeg Children's Hospital, with the patient discharged the same day. There was no serious complications and adequate tissue was obtained in 45 cases. Renal biopsy may be safely performed on an outpatient basis on carefully selected patients by experienced operators in properly equipped facilities.

Adolescent↗
PubMed1992

Effects of dietary protein restriction and oil type on the early progression of murine polycystic kidney disease.

A paucity of research data exists on the potential for early dietary modification to directly retard cystic growth and proliferation in polycystic kidney disease (PKD). We have therefore examined the relative effects of dietary protein levels and oil type on the progression of disease in a murine model of PKD. In the first study, weanling DBA/2FG-pcy (pcy) mice were fed either a normal (NP), 25%, or low (LP), 6%, casein diet with 10% of either sunflower seed oil (SO) (containing n-6 fatty acids), or fish oil (FO) (containing n-3 fatty acids), in a 2 x 2 design. At the end of the dietary treatment, kidney weight relative to body weight was higher in mice on the NP diets. In addition, kidney phospholipid to kidney weight (mumol/g) was lower in pcy mice on NP diets, indicating that the increased kidney size was largely due to increased cyst development. Replacement of dietary SO with FO resulted in alterations in renal phospholipid fatty acid compositions: 18:2 n-6, 20:4 n-6, and 22:5 n-6 were lower, and 20:5 n-3, 22:5 n-3, and 22:6 n-3 were higher in FO-fed animals. No effect of dietary lipid type on disease progression was noted, however. In a second study, morphometric analysis revealed an 11% lower percentage cyst area and a 46% lower total cyst area (mm2) in kidney sections derived from mice on LP diets compared to NP diets. These results indicate that early dietary protein restriction in PKD prior to clinical manifestation of symptoms of the disease may have a significant impact on the pathogenesis of PKD.

Animals↗
PubMed1991

Glucocorticoid teratogenesis in the developing nephron.

Although the induction of polycystic kidney disease by neonatal glucocorticoid treatment has been extensively documented, there are no data on induction of polycystic kidney disease with fetal exposure to glucocorticoids. We injected groups of pregnant Swiss Webster albino mice subcutaneously with 250 mg/kg of hydrocortisone acetate on individual days from days 1 to 19 of gestation. A control group received an equal volume of saline. Histologic analysis of 1,522 kidneys from the offspring of these animals revealed no evidence of polycystic kidneys in the control group or in offspring of animals injected before day 11 of pregnancy. A bimodal distribution of cystic kidney disease was noted in the remaining animals, with highest prevalence after injection on day 12 (50.8%) and day 17 (34.3%). We conclude that 250 mg/kg of glucocorticoids may induce polycystic kidney disease in utero, but possibly only during critical periods of metanephric development.

Animals↗
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

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

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↗
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↗