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Biomedical subjects

J D Walker

Publications and source records attributed to J D Walker.

At least 91 records · Page 5Linked to original sources
PubMed1992

Evaluation of the integrity of the blood-brain barrier after meningeal trauma.

RATIONALE AND OBJECTIVES: The authors used magnetic resonance imaging (MRI) techniques to examine the effect of meningeal trauma produced by cisterna magna puncture on the integrity of the blood-cerebrospinal fluid barrier (BCB) in a rat model. METHODS: Intravenous gadolinium-DTPA (Gd-DTPA), a relaxation rate modifier which normally does not cross the BCB, was used as a probe to follow leakage of fluid across the BCB. After Gd-DTPA injection, cerebrospinal fluid (CSF) serial samples were obtained through the needle used to create the experimental trauma. These samples were subsequently examined in vitro by MRI to obtain their T1 relaxation rates and assayed by mass spectrometry for gadolinium and elemental iron concentrations. RESULTS: The iron levels reflected the severity of puncture-related subarachnoid hemorrhage. Rats with ongoing meningeal damage showed significantly higher CSF levels of gadolinium and significantly higher CSF T1 relaxation rates than controls at all samples times over 1 hour after the puncture. Blood in the CSF could not explain these changes because the CSF iron levels did not significantly differ from control levels. CONCLUSIONS: Intravenously administered Gd-DTPA can gain access to the subarachnoid space through minor defects in the BCB and cause significant increases in CSF T1 relaxation rates.

Animals↗
PubMed1992

Na+/H+ antiport activity and cell growth in cultured skin fibroblasts of IDDM patients with nephropathy.

IDDM patients with incipient and overt nephropathy have been found to exhibit an overactivity of RBC sodium-lithium countertransport. To explore the physiological relevance of this finding, we measured the activity of Na+/H+ antiport in serially passaged cultured skin fibroblasts from IDDM patients with and without nephropathy and from normal, nondiabetic control subjects. Na+/H+ antiport activity (measured as the rate of amiloride-sensitive Na+ influx at pHi = 6.4, extracellular pH = 8.0, and [Na+] = 1 mM) was elevated significantly in IDDM patients with nephropathy compared with IDDM patients without nephropathy and nondiabetic control subjects (13.35 +/- 3.8 vs. 8.54 +/- 2.0 vs. 7.33 +/- 2.3 nmol Na+.mg protein-1.min-1; P less than 0.006 and P less than 0.001, respectively). A kinetic analysis of Na+/H+ antiport activity showed that the raised activity in IDDM patients with nephropathy was caused by an increased Vmax for extracellular Na+. Km values were similar in the three groups. pH-stimulated amiloride-sensitive Na+ influx also was higher under baseline conditions and after serum stimulation in cells from IDDM patients with nephropathy. pHi values were significantly higher, both during active proliferation and after 10-min exposure to serum, in cells from IDDM patients with nephropathy, compared with IDDM patients without nephropathy and nondiabetic control subjects. Serum-stimulated incorporation of [3H]thymidine into DNA was greater in IDDM patients with nephropathy than in the other two groups (35.7 +/- 18.9- vs. 17.4 +/- 7.5- vs. 11.9 +/- 8.7-fold stimulation above baseline; P less than 0.01 for both.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Chemical selection by the Interagency Testing Committee: use of computerized substructure searching to identify chemical groups for health effects, chemical fate and ecological effects testing.

Since 1977, the Interagency Testing Committee has convened over 300 meetings, issued 27 semi-annual reports to the Administrator of the US Environmental Protection Agency, screened about 26,000 chemicals, reviewed about 4,500 chemicals and recommended between 5000 and 7600 health effects, chemical fate or ecological effects tests for 114 chemicals and 27 chemical groups. The Committee has used three chemical selection processes to screen and identify chemicals for priority testing consideration. From 1977 to 1980, the Committee's processes consisted of examining large lists of chemicals and designating chemical categories that satisfied generic definitions. From 1980 to 1989, the Committee used sequential exposure and biological scoring processes followed by in-depth review. Since 1989, the Committee has used computerized processes to identify chemical groups that are associated with potentials to cause adverse health or ecological effects or that are likely to involve occupational or environmental exposure and that have common substructures, uses, testing information deficiencies, risk assessment uncertainties, etc. This paper focuses on use of the computerized processes to identify chemical groups containing common substructures that are associated with potentials to cause adverse ecological effects. The purpose of this paper is to describe how: (i) chemical substructures are selected, (ii) substructures are used to identify chemical groups, (iii) groups are processed, and (iv) reliability of the processes that were used to select chemical substructures are being assessed.

Animals↗
PubMed1991

Implications of microalbuminuria in diabetes.

Microalbuminuria is defined as small elevations of urinary albumin excretion not detected by conventional tests. It is associated with elevated arterial pressure, proliferative retinopathy, lipoprotein abnormalities and left ventricular hypertrophy and is predictive of later diabetic nephropathy. Improved glycaemic control and antihypertensive treatment lower urinary albumin excretion but it is not known whether these manoeuvres affect long-term outcome.

Albuminuria↗
PubMed1990

Sodium-lithium countertransport activity in red cells of patients with insulin dependent diabetes and nephropathy and their parents.

OBJECTIVE: To determine whether there are familial and genetic aspects of sodium-lithium countertransport activity in red cells in diabetic nephropathy. DESIGN: Case-control study. SETTING: Teaching hospital diabetic clinic. SUBJECTS: 40 Patients with insulin dependent diabetes, both of whose parents were alive: 20 with persistent proteinuria and 20 with normal albumin excretion matched for age, duration of diabetes, and body mass index. All 80 parents. MAIN OUTCOME MEASURES: Sodium-lithium countertransport activity in red cells and arterial blood pressure. RESULTS: Sodium-lithium countertransport activity in red cells was higher in the patients with proteinuria than in the patients with normoalbuminuria (mean (95% confidence interval) 0.47 (0.39 to 0.54) v 0.33 (0.28 to 0.38) mmol/l red cells/h respectively, p = 0.0036; mean difference 0.14 (0.04 to 0.22)). The mean countertransport activity for the two parents of each patient was calculated, and from this the mean value for each group of parents was calculated; the value was higher in the parents of the patients with proteinuria than in the parents of the patients with normoalbuminuria (0.40 (0.32 to 0.48) v 0.30 (0.26 to 0.33) mmol/l red cells/h respectively, p = 0.016; 0.10 (0.02 to 0.19)). Twenty-eight of the parents of the patients with proteinuria compared with 12 of the parents of the patients with normoalbuminuria had a countertransport activity that was above the median value in all 80 parents (p less than 0.001). Mean arterial blood pressure in the parents of the patients with proteinuria was related to that of their offspring (r = 0.46; p less than 0.01). There was a positive correlation between the sodium-lithium countertransport activity in red cells in the parents and their offspring when all parents and patients were considered (r = 0.37; p less than 0.001). CONCLUSIONS: Increased sodium-lithium countertransport activity in red cells in the parents of diabetic patients with nephropathy provides further evidence that familial, and possibly genetic, factors related to a predisposition to arterial hypertension have a role in the susceptibility of diabetic renal disease.

Adolescent↗
PubMed1990

Sodium-lithium countertransport in microalbuminuric insulin-dependent diabetic patients.

A familial predisposition to arterial hypertension has recently been suggested as one important component of the susceptibility to diabetic kidney disease. Sodium-lithium countertransport activity, a marker of risk for essential hypertension, has been found to be increased in diabetic patients with overt nephropathy. We have measured red blood cell sodium-lithium counter-transport activity in 36 microalbuminuric insulin-dependent diabetic patients, a group at high risk of progression to clinical nephropathy and cardiovascular disease, and compared it with that of a matched group of 36 normoalbuminuric diabetic patients. Sodium-lithium countertransport was higher in the microalbuminuric (0.43 [95% confidence interval (CI) 0.38-0.47] mmol/l red blood cells [RBC]/hr) than in the normoalbuminuric diabetic patients (0.29 [0.25-0.33] mmol/l RBC/hr, mean difference 0.14 [0.08-0.20]; p less than 0.0001). Microalbuminuric patients had a higher frequency of parental hypertension than normoalbuminuric diabetic patients (56% vs. 28%, p less than 0.05). Sodium-lithium countertransport was related to mean arterial pressure in the microalbuminuric patients (r = 0.54, p less than 0.001) and to daily insulin requirements in both groups (microalbuminuric patients r = 0.39, p less than 0.05; normoalbuminuric patients r = 0.42, p less than 0.01). In a subset of patients in whom lipoproteins were measured, sodium-lithium countertransport activity was related to total and very low density lipoprotein triglycerides (r = 0.41, p less than 0.05 and r = 0.48, p less than 0.05) and to apolipoprotein B (r = 0.56, p less than 0.05), independently of body mass index, albumin excretion rate, glycemic control, and insulin dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Restriction of dietary protein and progression of renal failure in diabetic nephropathy.

In a study of the effect of a low-protein diet on the progression of renal disease 19 insulin-dependent diabetic patients with persistent clinical proteinuria were observed for 12-39 (mean 29) months while they were on a normal-protein diet (1.13 [0.06] g/kg per day), then for 12-49 (mean 33) months on a low-protein diet (0.67 [0.03] g/kg per day). The low-protein diet had no adverse effect on nutrition or glycosylated haemoglobin concentration. Mean supine blood pressure (BP) fell slightly on the low-protein diet and was probably due to the start or modification of antihypertensive medication in 9 patients. The mean rate of decline in glomerular filtration rate fell from 0.61 (SEM 0.14) ml/min per month with the normal-protein diet to 0.14 (0.08) with the low-protein diet, and this effect remained highly significant after adjustment for blood pressure, energy intake, and glycosylated haemoglobin. The rise in the fractional clearance of albumin during a normal-protein diet stopped with the low-protein diet, and there was a significant fall in albumin excretion from 467 (95% CI 234-895) micrograms/24 h on the normal-protein to 340 (138-719) on the low-protein diet. Thus, a low-protein diet, with its reduction in protein and possibly other dietary components such as phosphate or fat, seems to retard the rate of decline of glomerular filtration rate in diabetic nephropathy independently of blood pressure changes and glycaemic control.

Adult↗
PubMed1989

Survival after rupture of the oesophagus and subsequent candidal endocarditis: use of new serological methods in management.

The prognosis following both spontaneous rupture of the oesophagus (Boerhaave's syndrome) and candidal endocarditis is poor. Antifungal treatment for the latter has, in the past, been empirical. A patient who survived both these conditions is described, his case demonstrating some of the major risk factors for candidal endocarditis. Management of his antifungal treatment was guided by newly developed serological methods. Close liaison between microbiologist and clinician is essential for the management of this serious condition.

Adult↗
PubMed1989

Patterns of hyperinsulinaemia in type 1 diabetic patients with and without nephropathy.

The prevalence and patterns of insulinaemia in five groups of patients with Type 1 diabetes have been reinvestigated using a free insulin assay which minimizes in vitro redistribution of the free and antibody-bound insulin components. In 18 diabetic patients managed by conventional insulin injection treatment and 19 patients treated by continuous subcutaneous insulin infusion (CSII), the mean 24-h serum free insulin level exceeded a non-diabetic reference range in 78% (injections) and 68% (CSII). Twenty-four-hour profiles showed that hyperinsulinaemia occurred in the basal state before meals and at night, but not immediately post-prandially. The serum free insulin concentration at 0800 h, 1200 h, and 1600 h was significantly (p less than 0.001) correlated with mean 24-h free insulin in injection-treated and CSII patients, and samples at one of these time-points may thus provide a simple, single measure of integrated insulinaemia for population studies. There was no significant difference in 24-h mean free insulin levels in 7 patients randomly crossed-over between injection treatment and CSII, but the profiles had a more physiological pattern during CSII, with a mean post-prandial serum free insulin level which was significantly higher on CSII than injections (mean +/- SE = 37.2 +/- 3.1 vs 26.9 +/- 2.5 mU l-1, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Effect of tilting disk, heart valve orientation on flow through a curved aortic model.

The influence of tilting disk valve orientation on pulsatile flow through a curved tube model of the human aorta was studied. Simultaneous, two-component laser Doppler velocimeter measurements were made in a tube having a 22 mm diameter and 41 mm radius of curvature which simulated the average dimensions of the adult aorta. The blood analog fluid had a viscosity of 3.0 cp and matched the refractive index of the glass model aorta. Results at mid-arch showed low turbulence levels in early systole and no influence of valve orientation. During mid-systole, fluid from the ventricle reached mid-arch exhibiting strong influence of valve orientation and increased turbulence levels. With the major orifice of the valve adjacent to the inner curved wall, the peak turbulent shear stress was 307 dynes/cm2 at mid-arch during mid-systole. When the major orifice was rotated 180 degrees, the peak value was reduced to 91 dynes/cm2 at the same location and time. At the exit of the curved section, the flow was independent of the valve orientation and the turbulent shear the flow was independent of the value orientation and the turbulent shear stress levels were an order of magnitude lower than the peak value at the inlet. This study demonstrated that orienting the major orifice of a tilting disk valve adjacent to the outer curved wall minimized turbulent shear stress levels.

Aorta↗