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Biomedical subjects

W R Adam

Publications and source records attributed to W R Adam.

At least 19 recordsLinked to original sources
PubMed1998

Comorbidities and prediction of length of hospital stay.

BACKGROUND: Variability in length of stay (LOS) within Australian National Diagnosis Related Groups (AN-DRGs) reflects clinical heterogeneity in age, severity of illness, complications and comorbidities. AIM: To develop a clinically based score which measures patient morbidity and which will better predict LOS compared to existing methods. METHODS: ICD-9-CM codes of diseases and procedures were allocated to one of 23 body system categories to calculate the body burden of disease (BBD) score. Evaluation of BBD in predicting LOS was performed using multiple regression and analysis of variance with a data set of 34,079 cases from 75 AN-DRGs from three Victorian hospitals. RESULTS: Adding BBD and age improved prediction of LOS by 27.2% in AN-DRG version 1.0 and by 17.5% in AN-DRG version 3.1. When using average inlier LOS for AN-DRG, BBD and age improved prediction of LOS by 44.6% and by 14.8% in AN-DRG version 1.0 and version 3.1 respectively. Deaths were positively related to BBD. CONCLUSIONS: BBD is a simple quantitative measure of extent of disease that improves current methods in accounting for variability in LOS.

Age Factors↗
PubMed1997

Involvement of both the classical and alternate pathways of complement in an ex vivo model of xenograft rejection.

BACKGROUND: It is now generally accepted that complement activation is critical for the hyperacute rejection of xenografts. Activation of the classical pathway as the result of the interaction of xenoreactive IgM xenoantibodies with the vascular endothelium has been observed in all species combinations examined to date. A number of studies using a variety of species combinations have also implicated alternate pathway involvement; however, these studies do not enable a conclusion to be drawn as to whether the alternate pathway can be activated in the complete absence of classical pathway activation. METHODS: In this study, human plasma was depleted of both Clq and factor D and then reconstituted with purified Clq or factor D to restore the classical and alternate complement pathways, respectively. The ability of these modified plasmas to prosecute hyperacute rejection was then examined using an ex vivo isolated mouse heart perfusion model based on the Langendorff system. RESULTS AND CONCLUSIONS: In the mouse to human species combination, both the classical and alternate pathways of complement are independently capable of initiating complement activation and mediating xenograft rejection.

Animals↗
PubMed1996

Expression of functional decay-accelerating factor (CD55) in transgenic mice protects against human complement-mediated attack.

Transgenic mice expressing human CD55 were generated by microinjection of a CD55-minigene under the control of the mouse H2K(b) (MHC class I) promoter. Offspring were tested for transgene integration by PCR analysis, and for CD55 expression on peripheral blood leukocytes (PBLs) by flow cytometry. Expression levels of 15 founders ranged from 30 to 80% of that on human neutrophils. Immunohistochemical analysis of kidney, heart, liver, and lung tissue demonstrated staining for CD55 on endothelial surfaces as well as general diffuse staining throughout the tissues. The capacity of the transgenically expressed CD55 to prevent human C3 deposition on the surface of mouse splenocytes was assessed by flow cytometry. Cells from hemizygous mice incubated with 10% fresh human serum as a source of natural antibody and complement bound approximately 65% less C3 than control littermates. No further protection was seen using cells from homozygous littermates, and the protective effect was abrogated by prior incubation with an OFFi-CD55 monoclonal antibody. Similarly, transgenic mice were afforded significant protection from human serum-mediated lysis, determined using an LDH release assay. Hearts perfused with human plasma showed no increase in survival time in a modified Langendorff perfusion system, however deposition of human C3c was greatly reduced in transgenic hearts.

Animals↗
PubMed1995

133Cs relaxation times in rat tissues.

133Cs relaxation-time studies of tissues from rats into which cesium has been incorporated by dietary loading have been carried out in vivo and in vitro. Whereas tissue T1 values are on the order of seconds, T2 values are as low as a few tens of milliseconds. 133Cs tissue relaxation times are analogous to those of 39K in the same tissues, but are more readily measured because of the greater sensitivity of 133Cs compared with 39K. T1 and T2 data of excised tissue at two resonance frequencies (65.60 and 39.37 MHz) and temperatures (302 and 278K) have been analyzed in terms of a general description of spin-7/2 relaxation. The results are consistent with most of the cesium ions being in a free state, undergoing fast exchange with bound ions having long correlation times located in one or more intracellular compartments.

Animals↗
PubMed1994

Clusterin depletion enhances immune glomerular injury in the isolated perfused kidney.

Clusterin is a normal plasma protein, shown to be an inhibitor of reactive complement hemolysis and a component of the fluid phase SC5b-9 terminal complement complexes. It is a component of glomerular immune deposits in human and experimental glomerulonephritis. Using the complement-dependent isolated perfused rat kidney model of autologous phase passive Heymann nephritis, we have studied the effect of clusterin depletion of perfused plasma on the development of glomerular injury. Kidneys with planted glomerular sheep anti-rat Fx1A antibody were perfused with human plasma either depleted of clusterin to < or = 30%, or control plasma depleted of plasma fibronectin. Glomerular injury was then initiated by the addition of guinea pig anti-sheep immunoglobulins to the perfusate. Kidneys perfused with clusterin depleted plasma developed significantly greater proteinuria at all time points when compared to control kidneys. Glomerular antibody binding and C3 deposition were similar in the two groups, but terminal complement components were deposited in larger amounts in the clusterin depleted group. These data support a possible role for clusterin in vivo in the protection of complement-induced glomerular injury.

Animals↗
PubMed1993

NMR measurement of 39K detectability and relaxation constants in rat tissue.

Differences in the NMR detectability of 39K in various excised rat tissues (liver, brain, kidney, muscle, and testes) have been observed. The lowest NMR detectability occurs for liver (61 +/- 3% of potassium as measured by flame photometry) and highest for erythrocytes (100 +/- 7%). These differences in detectability correlate with differences in the measured 39K NMR relaxation constants in the same tissues. 39K detectabilities were also found to correlate inversely with the mitochondrial content of the tissues. Mitochondria prepared from liver showed greatly reduced 39K NMR detectability when compared with the tissue from which it was derived, 31.6 +/- 9% of potassium measured by flame photometry compared to 61 +/- 3%. The detectability of potassium in mitochondria was too low to enable the measurement of relaxation constants. This study indicates that differences in tissue structure, particularly mitochondrial content are important in determining 39K detectability and measured relaxation rates.

Animals↗
PubMed1993

The use of dietary loading of 133Cs as a potassium substitute in NMR studies of tissues.

133Cs NMR chemical shifts and relaxation times have been measured for tissue samples in vitro and in vivo from rats which have been fed on a high cesium, low potassium diet, which leads to a predominantly intracellular distribution of this ion, similar to that of K+. The high sensitivity, large chemical shift range, and narrow linewidths of 133Cs, compared with 39K, allow chemical shift differences to be observed between tissues, and in subcellular organelles such as mitochondria. For example, in vitro tissue chemical shifts, relative to 150 mM CsCl, are 1.06 +/- 0.11 ppm for liver, 0.02 +/- 0.05 ppm for brain, 1.76 +/- 0.20 ppm for erythrocytes, and -0.13 +/- 0.02 ppm for plasma. T1 and spin-echo T2 values range from 1.26 +/- 0.05 s (T1), and 0.028 +/- 0.006 s (T2) for liver, to 6.49 +/- 0.19 s and 1.12 +/- 0.03 s for plasma. 133Cs relaxation times show the same relative trends between tissues as are observed in 39K tissue studies.

Animals↗
PubMed1993

Altered blood pressure, renal tubular function and levels of circulating inhibitors of Na-K-ATPase in mature SHR exposed to low salt diet in the perinatal period.

1. It has been shown previously that low salt diet, confined to the perinatal period only, reduces blood pressure (BP) and sodium retention in spontaneously hypertensive rat (SHR) offspring at maturity when compared with those given high salt diet. 2. In this study it is shown that such high salt diets are associated with an increased level of circulating Na-K-ATPase inhibitor (CINK) activity. 3. Animals given perinatal high salt diet have a significantly greater tubular reabsorptive capacity when compared with those given low salt diet. 4. The finding of a high level of circulating Na-K-ATPase inhibitory material in the face of increased renal tubular capacity and blood pressure suggests that while this inhibitory material may play a role in the elevated blood pressure of animals given high salt diet, it cannot cause the elevated rate of fluid reabsorption.

Animals↗
PubMed1991

Factors affecting 39K NMR detectability in rat tissue.

In this study we have found that NMR detectability of 39K in rat thigh muscle may be substantially higher (up to 100% of total tissue potassium) than values previously reported of around 40%. The signal was found to consist of two superimposed components, one broad and one narrow, of approximately equal area. Investigations involving improvements in spectral parameters such as signal-to-noise ratio and baseline roll, together with computer simulations of spectra, show that the quality of the spectra has a major effect on the amount of signal detected, which is largely due to the loss of detectability of the broad signal component. In particular, lower-field spectrometers using conventional probes and detection methods generally have poorer signal-to-noise and worse baseline roll artifacts, which make detection of a broad component of the muscle signal difficult.

Animals↗
PubMed1991

Effects of opiates on sodium excretion in the isolated perfused rat kidney.

1. A rat isolated perfused kidney preparation was utilized to define clearly a renal site of action. The variables measured were perfusate pressure and flow, glomerular filtration rate, urine volume, sodium excretion and potassium excretion. 2. Dextromethorphan (3 nmol/L) and dextrorphan (10 nmol/L) reduced sodium excretion in kidneys from rats on either control or high K+ diet, in the absence of any other measured renal effects. Dextromethorphan (10 nmol/L) produced a decrease in glomerular filtration rate as well as a decrease in sodium excretion. Naloxone (1 mumol/L) inhibited the effect of dextromethorphan on sodium excretion but had no effect when administered alone. 3. The levorotatory opiates levorphanol and levomethorphan, the kappa agonist ketocyclazocine and a range of other opiates had no effect on sodium excretion. 4. The results suggest a renal action specific for dextrorotatory opiates. This renal action is consistent with earlier binding studies suggesting preferential recognition of dextrorotatory opiates.

Animals↗
PubMed1990

Angiotensin II receptors in the kidney. Localization and physiological significance.

Angiotensin II (Ang II) exerts a variety of actions through specific receptor binding in the kidney. These include modulation of renal hemodynamics, glomerular filtration rate (GFR), and tubular reabsorption. Quantitative in vitro autoradiography was used to localize the Ang II receptors and angiotensin converting enzyme (ACE) in rat, rabbit, and human kidney. We incubated 20 microns cryostat sections of kidney with either 125I-[Sar1]Ang II or 125I-[Sar1,Ile8]Ang II for Ang II binding or with 125I-351A for ACE localization. The resulting autoradiographs were analyzed by computerized densitometry. A high density of Ang II binding was found over glomeruli and vasa recta bundles in all species examined. The interbundle area of the outer medulla was associated with low to moderate binding of Ang II. Moderate binding of Ang II was observed over proximal convoluted tubules in the outer cortex of rat kidney. ACE was predominantly distributed in proximal convoluted tubules in all species. These studies reveal multiple sites where Ang II could modulate renal function by acting on the renal vasculature, glomeruli, vasa recta bundles, and proximal tubular sites.

Angiotensin II↗
PubMed1990

Comparison of the effects of parathyroid hormone (PTH) and recombinant PTH-related protein on bicarbonate excretion by the isolated perfused rat kidney.

The isolated perfused rat kidney was used to study the effects of amino-terminal fragments of human parathyroid hormone, hPTH(1-34), bovine parathyroid hormone, bPTH(1-84) and of PTH-related proteins, PTHrP(1-34), PTHrP(1-84), PTHrP(1-108) and PTHrP(1-141) on urinary bicarbonate excretion. PTHrP(1-34) (7 nmol/l), bPTH(1-84) (5.5 nmol/l) and hPTH(1-34) (7 nmol/l) had similar effects in increasing bicarbonate excretion with respect to the control. At lower concentrations (0.7 nmol/l) all PTHrP components, but not hPTH(1-34) or bPTH(1-84) increased bicarbonate excretion significantly. Infusions of PTHrP(1-108) and PTHrP(1-141) at 0.7 nmol/l, while associated with a rise in urinary bicarbonate concentration and excretion during the early stages of perfusion, produced a sharp decline in bicarbonate concentration and excretion in the latter part of perfusion. The different peptides produced no significant differences in glomerular filtration rate, fractional excretion of sodium or urine volume. The absence of substantial differences between the effects of hPTH(1-34) and PTHrP(1-34) are as noted in previous studies. The differences between PTHrP(1-108)/PTHrP(1-141) and PTHrP(1-34) demonstrated here are consistent with (1) the clinical manifestations of acidosis in hyperparathyroidism and alkalosis in humoral hypercalcaemia of malignancy, and (2) an independent action of a component of PTHrP beyond amino acids 1-34.

Animals↗
PubMed1989

Intracellular compartmentalization of potassium.

The evidence that there is intracellular compartmentalization of potassium is indirect but diverse. Intracellular electrode measurement of potassium activity, 42K radioisotope studies, and more recently 39K nuclear magnetic resonance (NMR) all support such compartmentalization. The use of rubidium to apparently shift potassium between sites with different NMR characteristics (visibility) is strong evidence for such compartmentalization. The evidence that intracellular compartmentalization of potassium is of (patho) physiological significance is also indirect. Postulated roles for regulation of intracellular K+ activity, perhaps by control of compartmentalization, include enzyme activity, protein synthesis, and cell growth. There is also evidence that compartmentalization of potassium may contribute to the maintenance of a stable intracellular environment following potassium loading. The apparent magnetic field dependence of the visibility of K+ by 39K NMR offers the opportunity to explore further the phenomenon of compartmentalization.

Animals↗
PubMed1989

Potassium tolerance.

The maintenance of potassium homeostasis with an increased potassium intake or decreased renal function is dependent in part on the renal adaptation observed in 'potassium tolerance'. However other factors, including control of ingestion, and increased distal delivery of fluid, also play a role.

Animals↗
PubMed1989

Effect of magnesium depletion and potassium depletion and chlorothiazide on intracellular pH in the rat, studied by 31P NMR.

1. Both dietary magnesium depletion and potassium depletion (confirmed by tissue analysis) were induced in rats which were then compared with rats treated with chlorothiazide (250 mg/kg diet) and rats on a control synthetic diet. 2. Brain and muscle intracellular pH was measured by using a surface coil and [31P]-NMR to measure the chemical shift of inorganic phosphate. pH was also measured in isolated perfused hearts from control and magnesium-deficient rats. Intracellular magnesium status was assessed by measuring the chemical shift of beta-ATP in brain. 3. There was no evidence for magnesium deficiency in the chlorothiazide-treated rats on tissue analysis or on chemical shift of beta-ATP in brain. Both magnesium and potassium deficiency, but not chlorothiazide treatment, were associated with an extracellular alkalosis. 4. Magnesium deficiency led to an intracellular alkalosis in brain, muscle and heart. Chlorothiazide treatment led to an alkalosis in brain. Potassium deficiency was associated with a normal intracellular pH in brain and muscle. 5. Magnesium depletion and chlorothiazide treatment produce intracellular alkalosis by unknown mechanism(s).

Acid-Base Equilibrium↗
PubMed1989

Actions of synthetic parathyroid hormone-related protein(1-34) on the isolated rat kidney.

The isolated perfused rat kidney was used to study the effects of parathyroid hormone-related protein (PTHrP) on renal cyclic AMP (cAMP) and electrolyte excretion. A perfusate of PTHrP(1-34) increased cAMP excretion from 0.14 +/- 0.09 (S.E.M.) nmol/l glomerular filtrate (GF) in controls to 24.67 +/- 5.14 (P less than 0.01) and decreased calcium excretion from 0.278 +/- 0.033 to 0.162 +/- 0.011 mumol/l GF (P less than 0.01). Human PTH(1-34) (0.7 nmol/l) caused no significant change in calcium excretion, whilst the rise in cAMP excretion was similar to that with PTHrP. PTHrP(1-34) (7 nmol/l) further increased cAMP production to 366.7 +/- 100.8 nmol/l GF (P less than 0.01), higher than the rise with hPTH(1-34) (7 nmol/l) which was 76.7 +/- 46.8 (P less than 0.05). With the higher concentrations of both peptides (7 nmol/l), calcium excretion was further reduced to 0.090 +/- 0.009 mumol/l GF (P less than 0.01), whilst phosphate excretion increased with both PTHrP and PTH. PTHrP (7 nmol/l) caused a fall in urinary pH compared with controls (P less than 0.05). At low and high concentrations of both hormones, urinary pH was lower with PTHrP than hPTH (P less than 0.01). Thus PTHrP, like PTH, acts on the kidney to increase cAMP and phosphate excretion and reduce calcium excretion, but PTHrP may be more effective. Disparate effects on urinary pH could be reflected in the clinical features of humoral hypercalcaemia of malignancy.

Animals↗
PubMed1988

Problems in the assessment of magnesium depletion in the rat by in vivo 31P NMR.

Prior in vitro studies, utilizing 31P nuclear magnetic resonance (31P NMR) to measure the chemical shift (sigma) of beta-ATP and lengthening of the phosphocreatine spin-spin (T2) relaxation time, suggested an assessment of their efficacy in measuring magnesium depletion in vivo. Dietary magnesium depletion (Mg2+ decreases) produced markedly lower magnesium in plasma (0.44 vs 1.13 mmol/liter) and bone (130 vs 190 mumol/g) but much smaller changes in muscle (41 vs 45 mumol/g, P less than 0.01), heart (42.5 vs 44.6 mumol/g), and brain (30 vs 32 mumol/g). NMR experiments in anesthetized rats in a Bruker 7-T vertical bore magnet showed that in Mg2+ decreases rats there was a significant change in brain beta-ATP shift (16.15 vs 16.03 ppm, P less than 0.05). These chemical shifts gave a calculated free [Mg2+] of 0.71 mM (control) and 0.48 mM (Mg2+ decreases). In muscle the change in beta-ATP shift was not significant (Mg2+ decreases 15.99 ppm, controls 15.96 ppm), corresponding to a calculated free Mg2+ of 0.83 and 0.95 mM, respectively. Phosphocreatine T2 (Carr-Purcell, spin-echo pulse sequence) was no different with Mg2+ decreases in muscle in vivo (surface coil) (Mg2+ decreases 136, control 142 ms) or in isolated perfused hearts (Helmholtz coil) (control 83, Mg2+ decreases 92 ms). 31P NMR is severely limited in its ability to detect dietary magnesium depletion in vivo. Measurement of beta-ATP shift in brain may allow studies of the effects of interaction in group studies but does not allow prediction of an individual magnesium status.

Animals↗