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Biomedical subjects

N Muirhead

Publications and source records attributed to N Muirhead.

At least 73 records · Page 4Linked to original sources
PubMed1984

Suppression of secondary hyperparathyroidism in uraemia: acute and chronic studies.

A study was conducted evaluating the response of serum parathyroid hormone to acute hypercalcaemia and long term administration of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in patients receiving maintenance haemodialysis. During infusion of elemental calcium 4 mg/kg/h over four hours in 12 patients not receiving vitamin D the concentration of serum amino terminal parathyroid hormone fell by 31-96% (mean 74.8 (SD 17.6)%) while that of carboxy terminal parathyroid hormone changed little. There was a strong inverse correlation between baseline serum calcium concentration and percentage fall in amino terminal parathyroid hormone during infusion (r = 0.88; p less than 0.001). In seven patients who received prolonged treatment with 1,25(OH)2D3 after calcium infusion there was a positive correlation between maximum percentage fall in amino terminal parathyroid hormone during infusion and the percentage fall in amino terminal parathyroid hormone after 1,25(OH)2D3 treatment (r = 0.79; p less than 0.05). The responsiveness of the parathyroid glands to changes in calcium in acute studies may be used to predict the efficacy of long term treatment with 1,25(OH)2D3. Patients in whom calcium infusion does not suppress parathyroid hormone may have true parathyroid autonomy and require early parathyroidectomy.

Adult↗
PubMed1984

Regulation of calmodulin- and dopamine-stimulated adenylate cyclase activities by light in bovine retina.

Neural retina from most species contains 3,4- dihydroxyphenylethylamine (dopamine) receptors coupled to stimulation of adenylate cyclase activity. It has been demonstrated that release of dopamine from its neurons and subsequent occupation of dopamine receptors is increased by light. In this study, we have shown that adenylate cyclase activity in bovine retina is highly responsive to the endogenous Ca2+-binding protein, calmodulin, and that calmodulin can increase dopamine-sensitive adenylate cyclase activity in bovine retina. We further demonstrate that both dopamine- and calmodulin-stimulated adenylate cyclase activities can be regulated by alterations in light. Bovine retinas were dissected from the eye under a low-intensity red safety light, defined as dark conditions, and incubated for 20 min in an oxygenated Krebs Henseleit buffer under either dark or light conditions. The retinas were then homogenized and adenylate cyclase activity measured in a particulate fraction washed to deplete it of endogenous Ca2+ and calmodulin. Activation of adenylate cyclase activity by calmodulin, dopamine, and the nonhydrolyzable GTP analog, guanosine-5'-(beta,gamma-imido)triphosphate ( GppNHp ), was significantly (60%) greater in particulate fractions from retinas that had been incubated under dark conditions as compared to those incubated under light conditions. Basal, Mn2+-, and GTP-stimulated adenylate cyclase activities were not altered by changes in lighting conditions. Calmodulin could increase the maximum stimulation of adenylate cyclase by dopamine in retinas incubated under either dark or light conditions, but the degree of its effect was greater in retinas incubated under light conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1984

Calmodulin stimulates adenylate cyclase activity and increases dopamine activation in bovine retina.

Adenylate cyclase activity in bovine retina is highly responsive to Ca2+ and the endogenous Ca2+-binding protein, calmodulin (CaM). CaM stimulated adenylate cyclase activity in washed particulate fractions of bovine retina by 6.6-fold in a Ca2+-dependent manner. Activation of adenylate cyclase activity by CaM was maximal at 0.12 microM free Ca2+. The apparent Ka for calmodulin stimulation of adenylate cyclase was 67 nM and the apparent Vmax was 116 pmol/min/mg of protein above basal activity. Adenylate cyclase activity in bovine retina was stimulated approximately 50% by guanosine 5'-triphosphate (GTP), but the nonhydrolyzable GTP analogue, guanosine-5'-(beta, gamma-imido)triphosphate (Gpp(NH)p), was able to activate the enzyme nearly 5-fold. CaM and Gpp(NH)p appeared to be partially competitive activators of adenylate cyclase in the retina particulate fraction. Dopamine stimulated adenylate cyclase activity in the presence of GTP with an apparent Ka of 1.0 microM and an apparent Vmax of 66 pmol/min/mg of protein. Ca2+ and CaM increased the apparent Vmax of the dopamine-stimulated adenylate cyclase activity more than 2-fold to a level of 146 pmol/min/mg of protein but did not alter the apparent Ka. This suggests that CaM is an endogenous modulator of dopamine-stimulated adenylate cyclase activity in the retina. CaM-stimulated adenylate cyclase activity may be a common component to retina since we found this activity in retinas from rabbit, rat, and goldfish as well as cow.

Adenylyl Cyclases↗
PubMed1983

[Blood phosphate and calcium metabolism in bicarbonate dialysis of chronic stable hemodialysis patients].

Leucocyte count, blood pH and gases, plasma concentrations of total and ionised calcium, of phosphate and PTH were studied in 11 stable patients on chronic haemodialysis alternatively, the sequence being randomised, during acetate (AHD) and bicarbonate (BHD). Initial leucopenia and its subsequent correction were comparable with both dialysis types whereas pO2 and pCO2 transitory decreased only in AHD so that the mechanism of hypoxemia with AHD does not seem to be related to the pulmonary leucostatis but rather to the reflex hypoventilation secondary to the decrease of pCO2 into the acetate dialysis. As regards the bone metabolism, no difference was observed between HDA and HDB considering the increase of total and ionised calcium, the decrease of plasma phosphate and the absence of decrease of PTH, the initial levels of which being however only slightly elevated. However blood pH was significantly (but slightly) higher before the subsequent dialysis in the case of BHD. This more sustained correction of acidosis would be the only theoretical advantage of BHD for the prevention of bone demineralisation.

Acetates↗
PubMed1982

Loin pain and haematuria in young women: diagnostic pitfalls.

Cystoscopy, intravenous urography and urine culture frequently fail to reveal the cause of loin pain and haematuria in young women. Two such women are presented in whom renal biopsy was not only unhelpful but also misleading. Subsequent renal arteriography showed arteriovenous fistulae which were considered erroneously to be the cause of the symptoms in both patients; in fact the fistulae were traumatic post-biopsy fistulae rather than congenital malformations. These patients were probably examples of the "loin/pain/haematuria syndrome" which is thought to have a vascular basis and may have predisposed to the formation of fistulae.

Adolescent↗
PubMed1982

Long-term effects of 1,25-dihydroxy vitamin D3 and 24,25-dihydroxy vitamin D3 in renal osteodystrophy.

Twenty-three patients with end-stage renal failure on maintenance haemodialysis were treated with 1,25-dihydroxy vitamin D3 or 24-25-dihydroxy vitamin D3 for 3-32 months (total 232 patient months). Treatment with 1,25-dihydroxy vitamin D3 was marked by symptomatic, biochemical and histological improvements in the majority of patients. In contrast, treatment with 24,25-dihydroxy vitamin D3 produced no biochemical or histological improvements and such patients developed severe symptomatic bone disease. Successful renal transplantation resulted in rapid improvement in symptoms, biochemistry and bone histology in nine of 10 patients irrespective of whether prior treatment was with 1,25-dihydroxy vitamin D3, 24,25-dihydroxy vitamin D3 or both. During treatment with 1,25-dihydroxy vitamin D3 progressive reduction in dosage was required in the majority of patients because of hypercalcaemia, which was rapidly corrected by stopping treatment for a few days. Hypercalcaemia did not occur until serum alkaline phosphatase (AP) and amino terminal parathyroid hormone (N-PTH) had fallen towards normal. Treatment failure was uncommon in 1,25-dihydroxy vitamin D3-treated patients and was characterized by the early development of hypercalcaemia. Addition of 24,25-dihydroxy vitamin D3 in such patients rendered the hypercalcaemia more manageable but did not lead to any further improvement in biochemistry or bone histology. Treatment with 24,25-dihydroxy vitamin D3 was accompanied by the development of severe symptomatic bone disease in the majority of patients and a characteristic pattern of biochemical abnormalities with hypocalcaemia and rises in AP and N-PTH. Substitution of 1,25-dihydroxy vitamin D3 treatment for 24,25-dihydroxy vitamin D3 in these patients resulted in prompt improvement in clinical, biochemical and histological abnormalities. Successful renal transplantation was accompanied by rapid resolution of clinical, biochemical and histological features of renal osteodystrophy irrespective of whether previous treatment was with 1,25-dihydroxy vitamin D3 or 24,25-dihydroxy vitamin D3. Hypophosphataemia was common in the early months after renal transplantation without evidence of continuing hyperparathyroidism. The studies have confirmed that 1,25-dihydroxy vitamin D3 is effective in controlling clinical, biochemical and histological features of renal osteodystrophy while 24,25-dihydroxy vitamin D3 did not have a useful therapeutic effect in the dose used.

24,25-Dihydroxyvitamin D 3↗
PubMed1981

Effect of dihydroxylated metabolites of vitamin D3 on calcium absorption in uraemic man.

1. Peak 47Ca absorption and 7 day 47Ca retention were measured by a whole-body radioactivity counting technique in 10 haemodialysis patients before and after treatment with 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and 24,25-dihydroxycholecalciferol [24,25-(OH)2D3]. 2. Before treatment all patients had low peak 47Ca absorption and 7 day 47Ca retention. 3. After treatment with 1,25-(OH)2D3 (0 . 25-l microgram/day for 4-12 months) peak 47Ca absorption and 7 day 47Ca retention returned to normal. 4. After treatment with 24,25-(OH)2D3 (2 microgram/day for 4-12 months) peak 47Ca absorption and 7 day 47Ca retention remained at pretreatment levels. 5. It is concluded that physiological doses of 24,25-(OH)2D3 have no effect on calcium absorption or retention in uraemic man.

24,25-Dihydroxyvitamin D 3↗
PubMed1980

Comparison of 1,25(OH)2D3 and 24,25(OH)2D3 in the long-term treatment of renal osteodystrophy.

24,25(OH)2D3 has been compared with 1,25(OH)2D3 in the treatment of renal osteodystrophy. Treatment with 24, 25(OH)2D3 2 micrograms/day for 5-7 months was accompanied by deterioration in clinical, biochemical, radiological and histological features of osteodystrophy with no increase in Ca absorption. In contrast, treatment with 1,25(OH)2D3 0.25--1 microgram/day for 6-15 months resulted in rapid improvement in clinical, biochemical, radiological and histological features and a return of Ca absorption to normal. It is concluded that in the dose used 24,25(OH)2D3 alone is not an effective treatment for renal osteodystrophy.

24,25-Dihydroxyvitamin D 3↗
PubMedDate not supplied

Use of bone char as an adsorbent in preparation of water for dialysis.

Currently, deionizers (DI) and reverse osmosis (RO) are used to prepare water for dialysis. When water metal levels increase, for example, with the use of alum, the variation in metal content can reduce RO performance. Pretreatment of water with ethylenediaminetetraacetic acid or alkali can be used to reduce Al fouling. The authors examined adsorption of metal water contaminants with bone char (BRIMAC, Biolab, Oakville, Canada) as a cheaper alternative. Water treatment for the unit consists of a blend valve, 30 mu filter, 2 X 3 cu ft adsorption tanks, 5 mu filter, 30,000 grain automatic water softener, 5 mu filter, Millipore RO 1,000, 2 X 7" mixed bed DI in series, and a polysulfone ultrafilter. During 29 weeks of continuous bone char adsorption, raw water Al ranged from 0.022 to 0.298 ppm (mean, 0.097 +/- 0.075 ppm; cf. the Environmental Protection Agency's proposed drinking water standard of < 0.05 ppm). Postadsorption Al ranged from 0.002 to 0.076 ppm (0.041 +/- 0.04), a decrease of 55-91% (83.0 +/- 8.5%). Final water Al was < 0.001 at all times. No fouling of the RO membrane occurred. Residual chlorine after the first adsorption was < 0.02 to 0.09 ppm. Significant reductions in other metals, notably Pb, Cu, and Zn were noted. Bone char is a cheap, effective, and simple alternative for removing excess trace elements from water for hemodialysis. Further study to evaluate the efficacy of bone char in removing other organic and inorganic water contaminants is needed.

Adsorption↗
PubMedDate not supplied

Access type as a predictor of dialysis adequacy in chronic hemodialysis patients.

Dialysis prescription commonly exceeds the delivered dialysis dose. Tunneled hemodialysis catheters (PC) may provide less dialysis than arteriovenous fistula (AVF) and polytetrafluoroethylene grafts (GG), but the impact of access type on the discrepancy (deltaHD) between dialysis prescription and dose is unknown. This study investigates the relationship between deltaHD and vascular access type. Fifty three chronic hemodialysis patients in our unit were prospectively studied for 3 weeks with measurement of delivered single pool and prescribed Kt/V(urea). There were 25 patients with AVF, 17 with GG, and 11 with PC. Demographic characteristics did not significantly differ between groups. Mean prescribed Kt/V(urea) was 1.73 +/- 0.26, and mean delivered Kt/V(urea) was 1.61 +/- 0.26. For 10 of 53 (19%) patients, dialysis delivery was at least equal to that prescribed, and this proportion did not differ between access types. Forty six of fifty three patients (86.7% of all patients) received Kt/V(urea) > 1.3, with no difference in this proportion between access types: AVF 22 of 25 (88.0%), GG 16 of 17 (94.1%), PC 8 of 11 (72.7%). Surprisingly, prescription times for patients with PC (3.6 +/- 0.3 hr) were significantly shorter than for those with AVF (3.9 +/- 0.3 hr) and GG (3.9 +/- 0.3 hr) (p = 0.02), perhaps indicating physician bias toward patients with tunneled catheters. In summary, access type was not a significant predictor of deltaHD, although patients with arteriovenous access tended to receive more dialysis than those with tunneled catheters. While a large proportion of patients received less dialysis than prescribed, the high levels of delivered Kt/V(urea) indicate that adequate dialysis is possible even in patients who must use tunneled catheters.

Adult↗
PubMedDate not supplied

Predictors of erythropoietin responsiveness in chronic hemodialysis patients.

The impact of dialysis intensity on erythropoietin (EPO) requirements is unclear. Previous work suggests that increased dialysis is associated with increased erythropoietin responsiveness (ERSP), but average dialysis intensity has increased since those publications. We hypothesized that ERSP would be independent of delivered Kt/V(urea) at current intensities of hemodialysis. We prospectively studied 135 stable chronic hemodialysis patients who receive iron and subcutaneous EPO dosed according to current guidelines. We collected biochemical, hematologic, and single pool urea kinetics data. ERSP was expressed as units per kilogram per week of EPO administered. Simple and multiple linear regression were used to identify characteristics predictive of ERSP. The mean age of the patients was 62 +/- 17 years (range, 17-90 years); 68 of 135 (50.3%) were women, and 120 of 135 (88.9%) were Caucasian. Mean delivered Kt/V(urea) was 1.60 +/- 0.49, with 102 of 135 (75.6%) of patients with a delivered Kt/V(urea) > 1.3. Univariate linear regression showed seven significant independent predictors of erythropoietin requirements. Low serum albumin (p < 0.001), low serum calcium (p = 0.002), high serum phosphate (p = 0.004), and high serum iPTH (p = 0.007) were all associated with lower levels of ERSP. Lower ERSP was also correlated with lower hemoglobin and lower serum iron and transferrin saturation. Delivered dialysis (Kt/ V(urea)) was not a significant predictor of ERSP (p = 0.61). Multivariate regression confirmed low serum albumin (p < 0.01), high serum phosphate (p = 0.001), high immunoreactive parathyroid hormone (p = 0.025), and low transferrin saturation (p < 0.0005) as predictors of low ERSP, and also found high serum ferritin to be correlated with low ERSP (p = 0.016). We found no relationship between erythropoietin responsiveness and intensity of hemodialysis in this population of patients with a mean delivered Kt/V(urea) of 1.6. This may indicate a threshold effect beyond which more dialysis will not improve ERSP. However, markers of an underlying inflammatory state and of secondary hyperparathyroidism were associated with decreased response to erythropoietin.

Adolescent↗