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Biomedical subjects

D Ellis

Publications and source records attributed to D Ellis.

At least 181 records · Page 10Linked to original sources
PubMed1986

Partial characterization and ontogeny of renal cytosolic glucocorticoid receptors in mouse kidney.

The glucocorticoid receptor (GR) was partially characterized in mouse renal cytosol. A sensitive and reproducible [3H]dexamethasone binding assay suitable for use with small quantities of cytosolic protein, was developed. Studies defined the optimal equilibrium binding conditions, metabolism of [3H]dexamethasone in adult renal cytosol, specificity of binding of the GR, and molecular weight of the GR-[3H]dexamethasone complex by gel filtration chromatography. The assay was subsequently used to measure the renal GR during different stages of foetal and postnatal development, as well as in glomerular and renal tubular preparations from adult mice. An almost linear increase in GR occurred from day 13 to day 18 of gestation with levels rising from 100 to 201 fmol/mg cytosol protein; this was followed by a sharp rise in receptor concentration just after birth to 343 fmol/mg cytosol protein. Adult levels, 410-433 fmol/mg cytosol protein, were reached by 2 weeks after birth. The equilibrium dissociation constants (Kd) of the [3H]dexamethasone-receptor complex were similar in adult and in embryonic cytosols (range, 2.8-11.8 nM; mean +/- SD = 6.5 +/- 2.9 nM). Specific binding was assessed to be 3- to 5-fold greater in tubular than in glomerular preparations. These data on the localization and ontogeny of GR during murine metanephric development provide a basis for study of glucocorticoid-mediated effects on various models of congenital and acquired renal disease.

Aldosterone↗
PubMed1986

Renal failure in children with hepatic failure undergoing liver transplantation.

Over a 3 1/2 year period, 133 children with hepatic failure underwent orthotopic liver transplantation (OLT) at our center. Renal failure (creatinine clearance less than 20 ml/min/1.73 m2) was present in 19 (14.3%) of these children. In seven of the 19 children, renal failure was present before OLT, and in the other 12 after OLT. The causes of renal failure included hepatorenal syndrome in seven, postischemic acute tubular necrosis in five, severe prerenal azotemia in five, and cyclosporine nephrotoxicity in two. Eight other patients died of renal failure while awaiting emergency transplantation. Of the total of 31 deaths among 133 children who underwent OLT, nine occurred in the 19 patients with renal failure. Thus patients with OLT and renal failure had a significantly higher mortality than other patients with transplants (P less than 0.025). Dialysis was not associated with improved survival. The majority of deaths in patients with renal failure were related to severe hemorrhage, thromboembolic events, and systemic fungal infections. Our experience suggests that renal failure is common in children with hepatic failure and is associated with reduced patient survival after OLT.

Acute Kidney Injury↗
PubMed1986

Renal failure and dialysis therapy in children with hepatic failure in the perioperative period of orthotopic liver transplantation.

Severe renal failure (GFR less than or equal to 20 ml/min/1.73 m2) complicated the clinical course in 27 of 146 children (18.5%) admitted for orthotopic liver transplantation (OLT). Hepatorenal syndrome (HRS) was the cause of renal failure in 12 of 15 patients in whom renal failure preceded OLT while acute tubular necrosis, pre-renal factors and cyclosporine nephrotoxicity were the major causes of renal failure post-OLT. Eight patients died from hemorrhage, infection or other complications of hepatic failure before OLT could be performed. Survival in the remaining 19 patients undergoing OLT was significantly lower compared to 114 patients with OLT and no renal failure (53% vs 81%, p less than 0.025). Dialysis therapy in 13 of the 27 patients with renal failure (10 hemodialysis and 3 peritoneal dialysis) was frequently complicated by severe gastrointestinal hemorrhage and hypotension, and directly contributed to the death of two patients prior to OLT. Among the 19 patients with renal failure who were actually transplanted, the survival rate was similar whether dialysis was used or not (5/10 vs 5/9) even though the mean GFR was significantly lower in dialyzed patients (p less than 0.05). However, although small patient numbers precluded meaningful statistical analysis, dialysis appeared to be beneficial for the subgroup of 12 patients with HRS, 4 of whom had complete recovery of renal function after successful OLT. We conclude that, renal failure is common in children with advanced liver failure; dialysis in such patients may increase morbidity and does not improve overall mortality; and dialysis support may improve survival in the subgroup of patients with HRS.

Acute Kidney Injury↗
PubMed1985

Renal function and somatic growth in pediatric cadaveric renal transplantation with cyclosporine-prednisone immunosuppression.

The posttransplantation courses of 28 consecutive patients (age range, 0.8 to 16 years) who received cadaveric renal allografts and combined cyclosporine-low-dose prednisone immunosuppression were analyzed. The mean follow-up time was 16.5 months (range, four to 42 months). There was one death and the actuarial one-year graft survival was 59%. At follow-up, the group mean (+/- SD) serum creatinine concentration in 14 patients with functioning grafts was nearly double the expected mean value for normal children of similar age and sex (1.13 +/- 0.38 vs 0.61 +/- 0.07 mg/dL), and the mean +/- SD glomerular filtration rate was 76.5 +/- 20.0 mL/min/1.73 sq m (range, 40 to 115.5 mL/min/1.73 sq m). Although rejection accounted for 11 (79%) of 14 graft losses, failure of immunosuppression could be implicated in only four of these patients. Among eight preadolescent patients with good renal function for one year posttransplantation, somatic growth was poor in four and suboptimal in three patients; catch-up growth occurred in one patient. In such patients, the weight-for-height index increased, reflecting the development of obesity after transplantation. We conclude that cyclosporin-low-dose prednisone offers little or no advantage in terms of cadaveric renal allograft survival or stimulation of somatic growth when compared with conventional therapy.

Adolescent↗
PubMed1985

Na-Ca exchange in cardiac tissues.

Our awareness of the importance of Na-Ca exchange in cardiac muscle has progressed from early observations of Na-Ca antagonism in the activation of contractile force. This was followed by demonstrations of actual Na-Ca ion countertransport across cell membranes and later functional studies in which manipulation of intracellular and extracellular Na and Ca concentrations has permitted a better characterization of the exchange process and its contribution to contractile force. The recent development of vesicle preparations from cardiac sarcolemmal membranes has, despite some drawbacks, produced useful information on the electrogenicity of the exchange mechanisms and on the relative affinity of the exchange carrier compared to the ATPase-driven Ca pump. These studies confirmed earlier estimates of the approximate exchange ratio of the Na-Ca countertransport system and have demonstrated its large maximum transport rate capabilities. The application of ion-sensitive microelectrodes in recent years has enabled measurements of the actual ion-activity gradients across the sarcolemmal membrane. These activity gradients together with the membrane potential control the rate and direction of the Na-Ca exchange. Despite the wide range of techniques employed to tackle the problem, the exchange ratio of Na to Ca movement is still in some doubt, with most estimates ranging between 5:2 and 4:1.

Animals↗
PubMed1985

Growth factor requirements of organogenesis in serum-free metanephric organ culture.

In order to define humoral growth factors which may regulate mammalian renal development, the growth requirements of fetal metanephric organogenesis were studied in serum-free murine organ culture. Metanephric growth, determined by cell proliferation and protein content, and metanephric differentiation, determined morphometrically as epithelial glomerular formation, were compared and contrasted following 144 hours of organ culture incubation in basal medium, basal medium supplemented with 10% fetal bovine serum, and basal medium supplemented with various combinations of growth factors. The basal medium was composed of equal volumes of Dulbecco's modified Eagle's medium and Ham's F-12 medium. Five humoral growth factors were studied in the following concentrations: selenium, 6.8 X 10(-9) M; insulin, 8.3 X 10(-7) M; triiodothyronine, 2 X 10(-9) M; transferrin, 6.2 X 10(-8) M; and prostaglandin E1, 7.1 X 10(-8) M. Results showed that transferrin and prostaglandin E1 were necessary for optimal growth in the system and that prostaglandin E1 was necessary for maximal metanephric differentiation. Such data provide guidelines for the creation of serum-free medium for future fetal renal cell and tissue culture systems, and provide insight into the factors which may regulate normal and abnormal renal embryogenesis and the reparative processes of renal hyperplasia and hypertrophy which follow renal injury.

Alprostadil↗
PubMed1985

Use of a lighted stylet for guided orotracheal intubation in the prehospital setting.

Management of the airway in acutely injured patients demands special skills of the emergency physician. A technique of light-guided orotracheal intubation has been described in the literature and was performed under protocol by resident physicians in an urban mobile intensive care system. The method utilizes a flexible lighted stylet to provide a guide to correct placement through transillumination of the soft tissues of the neck. During the 12-month period of the study, 24 intubations were attempted in 21 patients using this technique. Twenty-one attempts (88%) were successful. The average time for intubation was 20 seconds, with none requiring more than 45 seconds. Fourteen intubations (67%) were successful on the first attempt. Of the three unsuccessful procedures, two were attempted in bright sunlight, and all three patients had vomited prior to the attempts. Trauma to the soft tissues in one successfully intubated patient was the only complication reported with the technique. The advantages of this method, including rapidity of intubation, ability to intubate without manipulation of the head or neck, and the apparently few complications, make it particularly attractive to emergency personnel. We conclude that guided orotracheal intubation using a lighted stylet is an effective and safe method of emergency intubation, even in the adverse prehospital environment.

Critical Care↗
PubMed1985

Sodium-potassium ATPase activity mediates cyst formation in metanephric organ culture.

To study the possible role of altered transtubular transport in renal tubular cyst formation, the ontogeny of renal Na-K ATPase was studied during glucocorticoid-induced cystic metanephric tubular development in serum-free, murine organ culture (SFMOC). Utilizing an enzyme-linked kinetic microassay, a developmental profile of total ATPase and specific Na-K ATPase activity was established for control (CON) and glucocorticoid-induced cystic organ culture (CY) explants. During 120 hr of CON and CY organ culture nephrogenesis total Na-K ATPase activity, specific Na-K ATPase activity, and the Na-K ATPase: total ATPase ratio progressively increased, simulating normal in vivo murine enzyme development. However, from 48 to 120 hr of organ culture, CY showed significant increases in Na-K ATPase activity when compared to CON at similar stages of development. Na-K ATPase activity (expressed as nmoles . min-1 . mg protein -1, mean +/- SD) was, at: 48 hr, CY 13.1 +/- 0.7 vs. CON 11.0 +/- 0.9 (P less than 0.01); 72 hr, CY 16.4 +/- 1.1 vs. CON 12.2 +/- 0.7 (P less than 0.001); 96 hr, CY 35.4 +/- 4.9 vs. CON 13.7 +/- 0.4 (P less than 0.001); and 120 hr, CY 26.1 +/- 1.4 vs. CON 16.3 +/- 0.9 (P less than 0.001). The initial differences in CY enzyme activity preceded the earliest ultrastructural evidence of cyst formation by 18 to 24 hr, while subsequent increases in Na-K ATPase activity in CY paralleled progressive tubular cyst formation. Tubular cyst formation in CY could be largely prevented by daily incubation of explants with ouabain, 0.2 mM (final concentration) X 120 min, without deleterious effects on overall metanephric development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Sodium-dependent control of intracellular pH in Purkinje fibres of sheep heart.

Intracellular pH (pHi) of Purkinje fibres from sheep heart was recorded with pH-sensitive glass micro-electrodes. The cells were acidified by one of three methods: (1) exposure to and subsequent removal of NH4Cl, (2) exposure to solutions containing 5% CO2 or (3) exposure to an acidic Tyrode solution. The pHi recovery from these acidifications was studied. The time constant of recovery from an acidification induced by NH4Cl was almost twice as long as that from one induced by CO2 or acid extracellular pH. Following an acidification induced by exposure to CO2 the time constant of pHi recovery was not changed when the cell was depolarized to -40 mV (by replacement of some Na+ by K+). An intracellular acidification was produced when extracellular Na+ was removed and replaced by quaternary ammonium ions or K+. Such Na+-free solutions also inhibited pHi recovery from an acidification. A 50% inhibition of the rate of recovery was produced by lowering the [Na+]o to 8 mM. When used as a Na+ substitute, Li+ could permit recovery. Tris (22 mM) changed pHi in the alkaline direction. Amiloride (1 mM) or a decrease in temperature slowed the recovery from an acidification (Q10 = 2.65). There was no effect of SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid disodium salt; 100 microM) on the recovery. Na+-sensitive glass micro-electrodes were used to measure the intracellular Na+ activity when [Na+]o was lowered to levels used in our pHi recovery experiments. From these data we have calculated the apparent Na+ electrochemical gradient at different values of [Na+]o. If this gradient is responsible for H+ efflux from the cell then, by applying thermodynamic considerations, it can be shown that only low concentrations (1-2mM) of extracellular Na+ are required. Solutions containing a very low [Ca2+]o (less than 10(-8) M, buffered with EGTA) were used to prevent large rises of [Ca2+]i which may occur on removal of external Na+. Under these conditions pHi recovery is still dependent upon [Na+]o, and the apparent inhibition of pHi recovery by removal of Na+ is not simply due to rises in [Ca2+]i. The intracellular acidification which occurs on removal of Na+ does not occur when [Ca2+]o is very low (less than 10(-8) M).(ABSTRACT TRUNCATED AT 400 WORDS)

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1985

Effects of stimulation and diphenylhydantoin on the intracellular sodium activity in Purkinje fibres of sheep heart.

The effects of stimulus frequency on the intracellular Na+ activity (aiNa) of Purkinje fibres from sheep hearts have been investigated using ion-sensitive micro-electrodes. aiNa increased by approximately 44% at 3 Hz and approximately 6.5% at 0.2 Hz. The size of the increase was very variable between preparations and did not appear to be related to the initial level of aiNa before stimulation. During stimulation, the rise of aiNa was exponential and gave a new steady-state level within about 15 min. The time constant of this rise was independent of the frequency of stimulation. The recovery of aiNa following a period of stimulation also appeared to be exponential but the time constant was dependent upon the extent to which aiNa had been raised during stimulation, with shorter time constants following larger rises. The effects of stimulation on aiNa were compared to inhibition of the Na+-K+ pump using high concentrations of cardioactive steroids. The influence of diphenylhydantoin (DPH) on the Na+ permeability of the cell membrane was assessed by measuring the rate of rise of aiNa following Na+-K+-pump inhibition. DPH decreased the rate of rise of aiNa by approximately 37% at concentration of 10(-4) M. The decrease of Na+ permeability produced by DPH is probably responsible for the observed reduction of aiNa in quiescent preparations. DPH also produced substantial decreases of aiNa in stimulated preparations. These results are discussed in relation to its known anti-arrhythmic effects.

Action Potentials↗