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Biomedical subjects

S L Carney

Publications and source records attributed to S L Carney.

At least 37 records · Page 2Linked to original sources

Hospital sphygmomanometer use: an audit.

Periodic evaluation over the past 20 years of the ability of clinical staff to accurately measure blood pressure, as well as the functional state of sphygmomanometers, has frequently demonstrated significant deficiencies. The data presented here are the results of a recent audit in the Newcastle area. Medical (48) and nursing (217) staff in five general hospitals (3 public, 2 private), were questioned on sphygmomanometer use, observed taking a blood pressure reading and asked to record blood pressures from a videotape. In addition, all hospital sphygmomanometers were checked to see if they were in working order. Of 463 sphygmomanometers evaluated, 58% were in perfect working order. There was a marked variation in the state of equipment between institutions (40 to 94%). Staff knowledge and technical ability in sphygmomanometer use was similar in doctors and nurses, with 69% of doctors and 71% of nurses knowing that phase V Korotkoff sounds best approximated adult diastolic blood pressure. Knowledge of appropriate cuff size and ability to use a sphygmomanometer was also similar between the two groups. However, doctors performed better in measuring systolic and diastolic blood pressures from a videotape (9.3 +/- 1.7 correct compared with 7.8 +/- 1.9 for nurses; P < 0.01). It was concluded that, with the exception of one hospital, the state of repair of sphygmomanometers was poor. Staff knowledge of sphygmomanometer usage and their ability to record blood pressure was satisfactory. However, not all practising health professionals are competent in using a sphygmomanometer.

Blood Pressure Determination↗

The renal medulla in acute renal allograft rejection: comparison with renal cortex.

A retrospective cohort study was undertaken to evaluate the diagnostic value of the renal medulla in acute renal allograft rejection (ARAR). One hundred and ninety-five biopsies from 98 patients were randomly selected out of 565 transplant biopsies. Biopsies were graded blindly from Grade 0 (no rejection) to Grade 3 (severe rejection) using standard criteria; ARAR was confirmed by a fall in all cases of mean serum creatinine concentration from 0.331 +/- 0.182 to 0.184 +/- 0.079 mmol/l, with anti-rejection therapy. In the 43 biopsies which contained both cortex and medulla, the ARAR grades and the intensities of mononuclear cell, plasma cell, polymorphonuclear cell and eosinophil infiltrates, and of interstitial oedema and haemorrhage, were similar in cortex and medulla (Spearman's Rank Correlation r = 0.55-0.81, P < 0.001). The sensitivity, specificity and overall accuracy of medullary changes in predicting ARAR changes in the cortex were 77%, 100% and 38%, respectively. Acute vascular rejection changes could not be compared between renal cortex and renal medulla because of the anatomical differences between cortex and medulla. Further evaluation of ARAR in the all 195 biopsies, of which 188 had cortical tissue and 50 had medullary tissue, showed no significant differences in histological features (P > 0.05), except for more cortical biopsies with plasma cells (29%) than medullary biopsies with plasma cells (10%; P < 0.02). It is concluded that: (1) ARAR histological changes are similar in cortex and medulla; (2) the predictive value of ARAR medullary changes for cortical rejection changes has low sensitivity (77%) and high specificity (100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Acute effect of endogenous calcitonin on rat renal function.

To evaluate the physiological role of calcitonin (CT) in the renal Ca transport, increasing Ca concentrations (0-7.5 mM) were administered to thyroparathyroid-intact rats to provoke parathyroid hormone suppression and CT secretion. These groups of rats were compared to acutely thyroparathyroidectomized (TPTX) rats also infused with increasing Ca concentrations to produce comparable plasma Ca levels. A parathyroidectomized group was also studied. The presence of a high CT level was associated with a reduced fractional Ca excretion when compared to a TPTX group with a similar ultrafiltered Ca level (5.3 +/- 0.4 as compared with 10.6 +/- 0.4%; p < 0.01). The fractional Mg excretion was similarly reduced by endogenous CT (26.8 +/- 0.9 as compared with 37.3 +/- 2.1%; p < 0.01). The glomerular filtration rate was increased by CT, although the filtration fraction was unchanged. Because of changes in filtered Ca load due to an elevated glomerular filtration rate, comparison of TPTX and intact groups with comparable filtered Ca loads again demonstrated greater absolute Ca and Mg reabsorption in the presence of CT. Therefore, these studies that evaluated the effect of endogenous secretion of CT on nephron function confirm more recent studies using exogenous CT (human and salmon) that had suggested that CT is a renal Ca-conserving hormone like parathyroid hormone.

Absorption↗

Preliminary investigation into the purification, NMR analysis, and molecular modelling of chondroitin sulphate epitopes.

Electrophoretic methods are outlined for the rapid purification and analysis of chondroitin sulphate oligosaccharides on a milligram scale. Isomeric impurities however, exist within specific sized oligosaccharides. Detailed 1H and 13C NMR data for the chondroitin sulphate disaccharides delta 4HexA(1-3)GalNAc6SO3- and delta 4HexA(1-3)GalNAc4SO3- (prepared from shark chondroitin sulphate) are reported. Two-dimensional NMR methods have been employed in the assignment of spectra. Preliminary models of these disaccharides are proposed from molecular mechanics conformational searching and molecular dynamics procedures. This study provides 1H and 13C NMR reference data which will be useful in the investigation of larger chondroitin sulphate oligosaccharides, such as those prepared by the electrophoretic methods mentioned above.

Animals↗

In vitro and in vivo effects of proteoglycan fractions in adjuvant treated rats.

Differential stimulatory effects by proteoglycan fractions: chondroitin (CS)- and keratan-sulphate regions; link protein and binding region were observed in cultures of spleen and lymph node lymphocytes taken from normal and adjuvant treated Lewis rats. In vivo, none of the fractions induced symptoms of arthritis but that pretreatment with the CS rich region produced an inhibition of Mycobacterium tuberculosis induced arthritis.

Adjuvants, Immunologic↗

Acute effect of physiological concentrations of vasopressin on rat renal function.

1. The antidiuretic, pressor and electrolyte transport effects of arginine vasopressin (AVP) were simultaneously evaluated in the anaesthetized water diuretic rat. Increasing concentrations of AVP (7.5, 75 and 750 ng/kg bolus and per h), were used to produce plasma levels which approximate the physiological range (408 +/- 2.4, 35.7 +/- 12.5, 85.2 +/- 16.1 pg/mL respectively). 2. Administration of a minimally effective antidiuretic dose (7.5 ng) increased mean urine osmolality (from 101 +/- 7 to 312 +/- 89 mosmol/kg) without altering mean arterial pressure (MAP), renal plasma flow (RPF) or glomerular filtration rate (GFR). A maximal antidiuretic dose of AVP (75 ng) increased mean urine osmolality to 2002 +/- 109 mosmol/kg and was associated with significant mean increases in MAP (9 mmHg), RPF and GFR (25%) by 30-60 min. A further ten-fold increase in AVP (750 ng) produced a greater increase in MAP (116 +/- 6 to 134 +/- 7 mmHg; P < 0.01) as well as increasing RPF and GFR by 35.5 and 38.9% respectively. 3. Increasing concentrations of AVP also progressively increased the fractional excretion of sodium, potassium and phosphate. However, fractional calcium and magnesium excretion was significantly decreased with maximal and supramaximal concentrations. 4. These studies support evidence that AVP is a pressor hormone in physiological concentrations in baroreceptor intact animals. Its role in renal electrolyte transport is unclear. Measured increases in RPF and GFR with the maximal and supramaximal AVP concentrations appear to be correlated with the increase in MAP.

Animals↗

Changes in proteoglycan turnover in experimental canine osteoarthritic cartilage.

The metabolism of newly-synthesised and total ("resident") proteoglycans was examined in control and osteoarthritic cartilage explants obtained from an experimental model (Pond and Nuki, 1973) of canine osteoarthritis. The following findings were obtained: (i) Non-labelled proteoglycans extracted from normal cartilage with 4 M guanidine HCl showed two bands visualised by staining with toluidine blue. The electrophoretic mobilities of proteoglycans from osteoarthritic cartilage were unchanged but the relative abundance of the slower migrating band increased with time after surgery. (ii) There were qualitative differences in the proteoglycan breakdown products released into the medium of explant cultures of osteoarthritic compared with control cartilage. This was apparent for both labelled and total unlabelled proteoglycans. (iii) There were similarities in the electrophoretic mobilities of the major labelled and non-labelled proteoglycan breakdown products suggesting that total ("resident") proteoglycans and newly-formed proteoglycans were degraded by similar mechanisms. There were however some differences in the labelled and non-labelled proteoglycans, suggesting that the mechanisms of breakdown were not identical. (iv) Immunoblotting techniques showed differences in the distribution of various glycosaminoglycans in proteoglycan breakdown products from control compared with osteoarthritic cartilage explant cultures. (v) Monoclonal antibodies 7-D-4 and 3-B-3 (which recognise unusual native chondroitin sulphate epitopes) showed greatly increased expression on proteoglycans from osteoarthritic cartilage compared with controls.

Animals↗

Comparison of parathyroid hormone and calcitonin on rat renal calcium and magnesium transport.

1. Because in vitro adenylate cyclase activity studies suggest that parathyroid hormone (PTH) and calcitonin (CT) increase renal tubular calcium and magnesium reabsorption by stimulating the same transport mechanism, the separate and combined effects of these hormones on calcium and magnesium transport was assessed in the rat. 2. Fractional excretion of calcium was 9.5 +/- 0.5% in calcium-infused thyroparathyroidectomized (TPTX) rats and was reduced to 5.1 +/- 0.6 and 4.1 +/- 0.6% by maximal hypocalciuric concentrations of PTH and CT, respectively. 3. Combined administration of maximal PTH and CT produced an effect on fractional and absolute calcium excretion similar to that recorded with maximal CT alone. The combined administration of half-maximal concentrations of PTH and CT also produced a comparable fall in the fractional excretion of calcium to 3.0 +/- 0.7%, which was similar to that observed in the 'maximal CT' and 'maximal PTH plus CT' groups. The magnesium reabsorption data were comparable. 4. These results support biochemical data suggesting that PTH and CT act upon the same transport site, presumably within the thick ascending limb of Henle's loop, to facilitate calcium and magnesium reabsorption.

Animals↗

Effect of ethanol on water and chloride transport in the rat papillary collecting duct.

While it is believed that the effect of ethanol on human renal water homeostasis is indirect, amphibian membrane experiments have demonstrated direct effects albeit at high concentrations. To evaluate the direct effect of ethanol, diffusional water and chloride permeability was simultaneously measured in isolated rat papillary collecting ducts with increasing concentrations of ethanol (0, 0.12, 0.24, 0.48, 0.96 and 1.92 g%) both in the presence and absence of arginine vasopressin (AVP). Low concentration of ethanol (0.12 g%) increased basal water permeability by 9%. With increasing concentrations it then fell to control levels (0.48 g%) only to increase again with concentrations of 0.96 and 1.92 g% to a maximum increase of 26%. Similar changes in chloride permeability occurred. Water permeability in the presence of submaximal concentrations of AVP (20 microU/ml) was also significantly increased with lower concentrations of ethanol (0.12, 0.24 and 0.48 g%) but fell to control levels with higher concentrations. With the highest ethanol concentration (1.92 g%), submaximal AVP did not significantly increase water permeability. However water permeability was unaltered by increasing concentrations of ethanol in the presence of supramaximal AVP (2,000 microU/ml). These results demonstrate a direct effect of ethanol upon distal nephron water and chloride transport.

Animals↗

Ionized calcium concentration in maintenance hemodialysis patients.

Since numerous formulae for "adjusted" total calcium and "calculated" ionized calcium are used in clinical practice, serum total and ionised calcium concentrations were measured in 20 hemodialysis patients with a wide range of serum total calcium and albumin concentrations. Patients were evaluated pre- and post-dialysis to document the effect of pH. Pre-dialysis total calcium varied from 1.70 to 3.17 mmol/L (mean 2.52 +/- 0.08) and a very close correlation between total and ionized calcium was found (r = 0.842; p less than 0.001) with 50.2% being in the ionized form. Dialysis did not alter this relationship despite a significant increase in pH (0.09; p less than 0.01). A normal volunteer group also demonstrated a similar correlation between total and ionized calcium and while the non-ionized calcium concentration was positively and significantly correlated to the serum albumin concentration (r = 0.629; p less than 0.01) this was not the case in the dialysis patients, although the serum albumin range was much greater (18 to 46 g/L). These results suggest that the percentage of total calcium in the ionized form in dialysis patients is not different from the normal population and that minor changes in pH and albumin may not be as important as has previously been believed. While direct measurement is preferable, halving of the total calcium is a simple prediction of the ionized fraction.

Calcium↗

The separation of chondroitin sulfate disaccharides and hyaluronan oligosaccharides by capillary zone electrophoresis.

We have developed techniques for the separation of unsulfated (2-acetamido-2-deoxy-3-O-(4-deoxy-alpha-L-threo- hex-4-enopyranosyluronicacid)-D-galactose and -D-glucose), monosulfated (2-acetamido-2-deoxy-3- O-(4-deoxy-2-O-sulfo-alpha-L-threo-hex-4-enopyranosyluronic acid)-D-galactose and 2-acetamido-2-deoxy-3-O-(4-deoxy-alpha-L-threo-hex- 4-enopyranosyluronic acid)-4-sulfo-D-galactose and -6-sulfo-D-galactose),disulfated (2-acetamido-2-deoxy-3-O-(4-deoxy-2-O-sulfo-alpha-L-threo-hex-4- enopyranosyluronic acid)-4-sulfo-D-galactose and -6-sulfo-D-galactose and 2-acet-amido-2-deoxy-3-O-(4-deoxy-alpha-L-threo-hex-4-enopy- ranosyluronic acid)-4,6-di-O-sulfo-D-galactose), and trisulfated (2-acetamido-2-deoxy-3-O-(4-deoxy-2-O- sulfo-alpha-L-threo-hex-4-enopyranosyluronic acid)-4,6-di-O-sulfo-D-galactose) isomers of chondroitin using capillary zone electrophoresis. In addition, it is possible to separate oligomers of hyaluronan by similar protocols. These techniques represent a rapid, sensitive, and reproducible technique for the assay of these molecules from digests of connective tissues.

Boric Acids↗

Cartilage research, biochemical, histologic, and immunohistochemical markers in cartilage, and animal models of osteoarthritis.

Over the past 20 years, there has been growing interest in the biochemistry, molecular biology, and physiology of cartilage. In the last year, there have been considerable advances in the understanding of the processes involved in the anabolism and breakdown of cartilage and the influence of cytokines and growth factors. This review addresses the area of cartilage research, the investigation of markers of cartilage, and the biochemical mechanisms involved in the development of osteoarthritis in animal models. The volume of cartilage research is extensive, and due to the nature of this review, I concentrate on work that is directly related to the anabolic and catabolic response of cartilage to various agents and to those investigations of cartilage with particular relevance to the development of osteoarthritis both in experimental models and in humans.

Animals↗

Increased dietary sodium chloride in patients treated with antihypertensive drugs.

Eleven patients on a normal diet with mild to moderate essential hypertension satisfactorily treated with diverse hypotensive agents entered a randomized double-blind cross-over study to evaluate the effect of additional sodium chloride (100 mmol slow sodium) compared with placebo on blood pressure control over a 6 week period. Despite excellent tablet compliance, sodium chloride failed to significantly alter mean supine or erect blood pressure. These findings as well as a review of the relevant literature suggest that excess dietary sodium does not jeopardize blood pressure control in such patients.

Adult↗

Synthetic human parathyroid hormone-related protein and rat renal electrolyte transport.

The effect of parathyroid hormone (PTH)-like peptide PTH-related protein (PTHrP)(1-34) from a human cancer cell line on renal electrolyte transport was compared with human PTH(1-34) in a thyroparathyroidectomized anesthetized rat model. Comparing submaximal, maximal and supramaximal phosphaturic concentrations of hPTH with the same PTHrP concentrations, no significant difference could be demonstrated in the urinary excretion of calcium, magnesium, inorganic phosphate or cAMP. Even the small (30.3%) and brief (45 min) reduction in fractional water excretion with the maximal (1 nM/kg/h) hPTH concentration was approximated by PTHrP. It is concluded that the structural homology between hPTH and PTHrP allows a similar action on renal electrolyte transport, including the partial agonist effect of higher concentrations of PTH on vasopressin-induced water transport.

Animals↗

An ELISA plate-based assay for hyaluronan using biotinylated proteoglycan G1 domain (HA-binding region).

An enzyme-linked absorbent assay for the determination of hyaluronan (HA) has been developed. The procedure is sensitive, simple and is based on a microtitre plate format. The assay involves competition between HA absorbed to the plate and HA free in solution for binding to biotinylated cartilage proteoglycan binding region (G1 domain). The range of the assay is 10-2500 ng/ml with 50% inhibition at about 200 ng/ml. The assay can be used in guanidine HCl up to 0.6 M and in 0.5% deoxycholate or 0.5% nonidet. This new technique involves fewer experimental steps and is simpler to perform than other methods.

Animals↗

Modulation of native chondroitin sulphate structure in tissue development and in disease.

Chondroitin sulphate proteoglycans are synthesised by different tissues and cell types, and the chondroitin sulphate chains are variably sulphated. Three monoclonal antibodies 3B3, 7D4 and 6C3 that recognise different native chondroitin sulphate epitopes have been used to investigate changes in structure during embryonic tissue development in the chick and in the response of mature canine articular cartilage during experimental osteoarthritis. Strong focal expression of the epitopes was seen during development of chick bursa, which was different for the three epitopes and which changed during 5 days of development. In embryonic chick limb, although chondroitin sulphate is present throughout the cartilage, the 3B3 epitope, which is at the non-reducing terminus of chains, was only expressed on chondroitin sulphate within one region of the sub-articular cartilage. In mature canine articular cartilage the expression of this epitope on proteoglycans was very low, but when determined 3 or 6 months after induction of experimental osteoarthritis the level was greatly increased in all joints tested (23/23). The abundance of the other two native chondroitin sulphate epitopes was also increased in this experimental disease. The results show that expression of the chondroitin sulphate epitopes detected by the monoclonal antibodies changes during cellular differentiation and development and suggests that it is closely controlled by the cells synthesising chondroitin sulphate chains.

Animals↗

Acute dialysis hypercalcemia and dialysis phosphate loss.

During maintenance hemodialysis in patients with chronic renal failure, acute elevations of the plasma calcium are common, although of doubtful significance. Because the mechanisms for this hypercalcemia are unclear, calcium, magnesium, and inorganic phosphate mass transfer data was collected during routine hemodialysis. While the increase in the plasma calcium did not significantly correlate with the gain of calcium from the dialysate nor with the dialysate calcium concentration, there was a significant positive correlation between the degree of hypercalcemia and the loss of body phosphate (r = 0.66, P less than 0.05, n = 15). Hemodialysis without ultrafiltration and concomitant hemoconcentration depressed the dialysis hypercalcemia by 46% (P less than 0.001). However, continuous infusion of 33.5 mmol of phosphate during a 5-hour dialysis period, which reduced the plasma phosphate fall (1.53 +/- 0.16 to 0.87 +/- 0.08 mmol/L, P less than 0.01, in the control group; compared with 1.59 +/- 0.19 to 1.35 +/- 0.11 mmol/L, not significant [NS], in the phosphate infusion group) abolished the hypercalcemia (2.38 +/- 0.07 to 2.54 +/- 0.04 mmol/L, P less than 0.01, in the control group and 2.39 +/- 0.06 to 2.41 +/- 0.04 mmol/L, NS, in the phosphate infusion group). It is suggested that during routine hemodialysis, the loss of inorganic phosphate from the body is excessive, and that phosphate as well as calcium is released from the intracellular pool in response to the rapid fall in the plasma phosphate concentration. Such rapid, repetitive, and excessive losses of phosphate, particularly from bone, may be an important cause of renal osteodystrophy.

Acute Disease↗