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Biomedical subjects

D J Goldsmith

Publications and source records attributed to D J Goldsmith.

72 records · Page 4Linked to original sources

Limitations of the peritoneal equilibration test in prescribing and monitoring dialysis therapy.

Based on correlation analysis with 24-h dialysis collections the peritoneal equilibration test (PET) has been promoted as an aid to prescribe and monitor dialysis dose. However correlation is an incorrect statistical technique to demonstrate the similarity of one measure to another. The closeness (or limits) of agreement should be measured using the technique of Bland and Altman. One hundred and nineteen patients underwent a 24-h dialysate collection and a PET. D/P ratios for urea and creatinine, dialysate volume, urea and creatinine clearance and KT/V (urea) were calculated using both methods and compared using correlation analysis. In addition the limits of agreement, reflecting the potential margins of difference between the two methods, were determined. When used to calculate a daily dialysate volume required to achieve adequacy targets, the PET was found to result in a prescription error range of -0.6 to +1.51/day for creatinine clearance and -0.9 to +0.61/day for urea clearance. The tendency of the PET to exaggerate clearance resulted in 14% of patients incorrectly achieving a target creatinine clearance of 50 1/week and 17% incorrectly reaching a target KT/V of 1.7. The PET cannot be used in place of 24-h dialysis collections to prescribe or monitor dialysis therapy.

Adult↗

Elective rather than emergency intervention for acute renal artery occlusion with anuria.

We describe a case in which surgical revascularisation was electively delayed until 27 days after acute renal artery occlusion, allowing surgery to be performed after a period of haemodialysis and pre-operative cardiac assessment. Owing to the collateral blood supply to the kidney, emergency surgery in cases of acute renal artery occlusion may not be necessary, and may be hazardous.

Acute Disease↗

Relationship between intracellular proton buffering capacity and intracellular pH.

In a recent publication the widely held view that the intracellular proton buffering power [defined as the amount of acid or base that has to be added to the cytosol to change the intracellular pH (pHi) by one pH unit] increases as the intracellular pH decreases, has been challenged, with the opposite relationship being proposed. In that publication, buffering was defined not in terms of pH change, but in terms of the change in proton concentration. The reason for this re-definition was the fear that the conventional analysis, using as it does a logarithmic function (pHi), could bias the outcome in favor of an increasing buffering power with decreasing pHi. The new system uses a "buffering co-efficient," defined as the number of protons necessary to be added to the cytosol to change the intracellular proton concentration by 1 mM. We report the use of both of these methods to analyze the relationship of pHi and buffering power, using human peripheral leucocytes loaded with the pH-sensitive fluorophore BCECF examined over a very wide range of pHi values (pHi 6.0 to 7.5). The most common method for pHi perturbation for the measurement of buffering is used, the rapid diffusion of ammonia across the cell membrane. In this study, analysis for both a bicarbonate-containing "open" system and for a Hepes-buffered "closed" system was performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Buffers↗

Leucocyte intracellular pH and Na(+)-H+ exchange activity in essential hypertension: an in vitro study under physiological conditions.

The cellular basis for essential hypertension remains obscure. Abnormal ion transport has been demonstrated in both experimental and essential hypertension, raised levels of sodium-lithium (Na(+)-Li+) and sodium-proton (Na(+)-H+) exchange in blood cells being a consistent feature. However, Na(+)-H+ exchange is not the main regulator of intracellular pH at resting pH, while the importance of the contribution of bicarbonate to cellular pH regulation is now increasingly appreciated. Serum and serum-derived growth factors are known to affect intracellular pH and the activity of the Na(+)-H+ antiporter. This study was designed to investigate the activity of Na(+)-H+ exchange in the leucocytes of patients with essential hypertension in the presence of bicarbonate in vitro and to measure the effect of autologous serum on intracellular pH and Na(+)-H+ exchange. Paired serum samples from essential hypertensives and their controls were used on leucocytes from other (unrelated, normotensive) donors to investigate the same parameters. In a study of 30 patients with untreated essential hypertension and 30 controls matched for age, sex, race and body habitus we found no difference in resting pH or buffering capacity (pH 7.28 +/- 0.01 and 32.0 +/- 1.6 mmol/l per pH, hypertensives, versus 7.27 +/- 0.02 and 34.5 +/- 1.8 mmol/l per pH, controls) but a marked difference in the maximal rate of Na(+)-H+ exchange in response to intracellular acidification (57.8 +/- 3.2 mmol/l per min versus 47.2 +/- 1.4 mmol/l per min, P = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of autologous serum on human leucocyte Na+/H+ exchange and intracellular pH.

1. Leucocyte Na+/H+ exchange and intracellular pH were investigated in physiological buffer containing bicarbonate. 2. The amiloride analogue 5-(N,N-hexamethylene) amiloride (1 x 10(-5) mol/l), an inhibitor of Na+/H+ exchange, had no significant effect on resting leucocyte pH, Na+ influx or Na+ content. 3. Ammonium chloride washout induced a profound intracellular acidosis, stimulating Na+/H+ exchange. This led to a 236% increase in Na+ influx. Eighty-eight per cent of this increase was inhibited by 5-(N,N-hexamethylene) amiloride. This demonstrates that 5-(N,N-hexamethylene) amiloride is an effective inhibitor of Na+/H+ exchange in human leucocytes. 4. The recovery from intracellular acidosis was shown to be dependent entirely on the presence of extracellular Na+. The Ki for inhibition by 5-(N,N-hexamethylene) amiloride of the recovery was 0.5 mumol/l. 5. Incubation with serum increased Na+ influx and Na+ content: the maximal effect was reached at 20% dilution. Serum (10%, v/v) increased influx by 40%, and 20% (v/v) serum by 102%, over resting levels. Only 43% of the serum-induced increase in Na+ influx was inhibited by 5-(N,N-hexamethylene) amiloride. This represented one-fifth of total Na+ influx. 6. Leucocyte intracellular pH increased on incubation with serum. This alkalinization was inhibited using 5-(N,N-hexamethylene) amiloride. 7. Studies of Na+/H+ exchange in leucocytes in physiological and pathological states are more likely to reflect the state in vivo if carried out in the presence of autologous serum.

Amiloride↗

Endothelin-induced contraction of human peripheral resistance vessels is partly dependent on stimulation of sodium-hydrogen exchange.

The role of Na-H exchange in endothelin-induced contraction of human peripheral resistance vessels was investigated. Endothelin produced a dose-dependent contraction which was greatly attenuated in the presence of a low extracellular sodium concentration. Inhibition of Na-H exchange by the amiloride analogue 5-(N,N-hexamethylene) amiloride (5-NNHA) resulted in a greater than 65% relaxation of a maximal endothelin-induced contraction in the presence of normal extracellular sodium. However, in the presence of a low extracellular sodium concentration, inhibition of Na-H exchange only resulted in a 25% relaxation. These data suggest that endothelin-induced vasoconstriction of human peripheral resistance vessels is mediated in part by stimulation of Na-H exchange.

Amiloride↗

Olfactory cuing of autobiographical memory.

In Experiment 1, subjects were presented with either the odors or the names of 15 common objects. In Experiment 2, subjects were presented with either the odors, photographs, or names of 16 common objects. All subjects were asked to describe an autobiographical memory evoked by each cue, to date each memory, and to rate each memory on vividness, pleasantness, and the number of times that the memory had been thought of and talked about prior to the experiment. Compared with memories evoked by photographs or names, memories evoked by odors were reported to be thought of and talked about less often prior to the experiment and were more likely to be reported as never having been thought of or talked about prior to the experiment. No other effects were consistently found, though there was a suggestion that odors might evoke more pleasant and emotional memories than other types of cues. The relation of these results to the folklore concerning olfactory cuing is discussed.

Cues↗

Production of hydrocinnamic acid by clostridia.

Hydrocinnamic acid was found in acid extracts of spent growth medium from cultures of Clostridium sporogenes. The acid was identified by mass spectrometry and its identity was confirmed by gas chromatography. The acid was produced in relatively large amounts (2 to 3 mumoles/ml of medium) by C. sporogenes, toxigenic types A, B, D, and F of C. botulinum, and some strains of C. bifermentans. Other strains of C. bifermentans and strains of C. sordellii and C. caproicum produced only small amounts (0.1 to 0.4 mumoles/ml) of the acid. The acid was not detected in spent medium from toxigenic types C and E of C. botulinum or from 25 other strains representing eight Clostridium species. Resting cell suspensions exposed to l-phenylalanine produced hydrocinnamic and cinnamic acid; the latter compound probably functions as an intermediate in the metabolism of l-phenylalanine.

Chromatography, Gas↗

Ambulatory blood pressure monitoring in nephrology: focus on BP variability.

As accurate assessment of hypertension in renal patients must be the cornerstone of better prevention of its deleterious effects, ambulatory blood pressure monitoring (ABPM) has become an essential clinical and research procedure in day to day nephrological practice. However, despite numerous studies in the renal literature, a consensus is needed for normal (desirable?!) ambulatory daytime and nighttime BP levels and for defining normal sleep BP dipping. Nevertheless, blunted sleep BP fall appears to be a ubiquitous finding in renal disease (primary renal conditions, chronic renal failure pre-dialysis, peritoneal and hemodialysis, and renal transplantation). Abnormal diurnal variability should be considered as an important contributor to cardiac and general morbidity as it is clearly associated with a faster decline in renal function and also with more cardiac structural and functional abnormalities - especially left ventricular dilatation. Several mechanisms have been proposed to explain the reduced BP circadian rhythm, but the majority of the supporting evidence is still contradictory. A novel, unifying hypothesis to be tested in future studies, is linking the common diurnal rhythm abnormalities with functional disturbances in aortic and carotid baroreflexes caused by uraemia-related large arterial structural changes (arterial intima and media thickening, arterial calcifications and increased arterial stiffness).

Blood Pressure↗

How reproducible is diurnal blood pressure rhythm in patients with secondary (renal) hypertension?

Abnormalities (reduction in/absence of) in diurnal bp rhythm are much more commonly seen in patients with chronic uremia than in patients with primary hypertension or in normal subjects. Target-organ damage is greater in these patients. However, the extent to which these diurnal bp rhythm changes are consistent or variable is untested. We retrospectively examined 223 ambulatory blood pressure monitoring (ABPM) traces in 92 patients with chronic uremia who had undergone ABPM at least twice (mean 2.3 ABPM traces/patient) over the period 1991-1997. ABPM technique and analysis were constant over this period. We found that for patients with chronic declining renal function but not yet on dialysis therapy, 67% retained the same diurnal rhythm from one ABPM recording to the next; if the known tendency for declining renal function to accompanied by a greater prevalence of "non-dipping" is taken into account, 82% of all patients had a "predictable" diurnal pattern. 79% of transplant patients, 87% of haemodialysis patients and 100% of CAPD patients retained the diurnal rhythmicity from one ABPM session to the next. Non-dipping was much more frequent than dipping (67% vs 33%). We conclude that abnormalities of diurnal BP rhythm are reasonably consistent in patients with renal hypertension, especially as renal function declines and patients enter the renal replacement therapy programme.

Adult↗

What added value does ambulatory blood pressure monitoring brings to the management of post renal transplantation hypertension?

OBJECTIVE: To evaluate BP control, white coat hypertension (WCH) and abnormal circadian variability in a significant outpatient sample of renal transplant (RTx) subjects, normotensive at the last regular visit. METHODS: ABPM (Spacelab 90217) was performed every 15 min between 07:00-23:00 h and every 30 min between 23:01-06.59 h. in all patients (N = 68, 39M, S-Cr. = 153 +/- 49 mumol/l) normotensive at their last regular office BP (O-BP) measurement and with available BP records for the 12 months preceding RTx and 6 months preceding ABPM. RESULTS: BP values were frequently abnormal in this RTx cohort considered to have a satisfactory BP control. O-BP (measured with a Hawksley random-0 sphygmomanometer on the day of ABPM) was 135.5/80.6 mmHg, 47.1% of the patients with abnormal BP values. By comparison, ABPM showed a lower prevalence of uncontrolled BP: 44.1% for 24 h.-BP and only 35.3% for the daytime awake period, with values of 134.5/80.4 and 135.3/81 mmHg respectively (P = NS from O-BP). The prevalence of WCH was 12%. 24-h SBP is related to O-SBP (r = 0.71, P < 0.01) and Bland-Altman analysis demonstrates that > 95.6% of all differences between systolic ABPM and O-BP values are within +/- 2SD of the identity line. However, although 24-h DBP is equally related to O-DBP (r = 0.64, P < 0.01), on Bland-Altman analysis, 8.8% of the differences between diastolic ABPM and O-BP values are outside +/- 2SD of the identity line. Thus, systolic but not diastolic O-BP correlates with, and can be substituted to ABPM derived values. Non-dipping was frequent, regardless of the definition of normal nocturnal BP fall (10 mmHg or 10% of the daytime SBP): 82.4%, 89.7%. Even if normality was strictly defined as a night/day ratio < 0.90 for SBP and < 0.92 for DBP, non-dipping prevalence was high 73.5%, with more than one-third of the RTx patients having nocturnal hypertension (ratio > 1). CONCLUSIONS: BP control is not optimal in one-third of a typical RTx population. Furthermore, nocturnal hypertension is a frequent and underestimated phenomenon in this population. There is a good agreement between ABPM derived and casual systolic values. Office measurements, due to WCH, are under-evaluating the quality and efficacy of the antihypertensive regimens.

Adult↗

Atypical post-renal transplantation hyperparathyroidism--further support for "removing all enlarged glands".

Hyperparathyroidism is an important sequela of chronic renal failure, remains a considerable challenge to nephrologists, and can be seen as inevitable in patients undergoing long-term renal replacement therapy. As time with renal disease increases then so does the cumulative risk of hyperparathyroidism, and the eventual need for surgical parathyroidectomy when hyperparathyroidism becomes refractory to medical intervention. Parathyroidectomy before dialysis treatment has started, or after successful renal transplantation, is much less commonly performed than when the patient is receiving dialysis. Increasingly the propensity for residual parathyroid tissue left behind (by design or accident) at an initial parathyroidectomy to undergo progressive hyperplasia under the constant stimulus of uremia, and by so doing result in the need for a second, more complex, neck exploration, has increased support for initial total parathyroidectomy for patients on dialysis. The optimal operative procedure for autonomous hyperparathyroidism after successful renal engraftment is however less clearly established. We discuss two very unusual but instructive cases of post renal transplantation autonomous hyperparathyroidism requiring surgical parathyroidectomy. Using these cases as examples we discuss the various surgical options, and discuss the contentious issue of the place for autografting parathyroid tissue.

Adult↗

Aortic pulse wave velocity and arterial wave reflections predict the extent and severity of coronary artery disease in chronic kidney disease patients.

BACKGROUND: Increased aortic stiffness markers - aortic pulse wave velocity (PWV) and augmentation index (AIx) - are powerful predictors of survival in ESRD patients - well-recognized for the high prevalence of coronary artery disease (CAD) and unusually high PWV and AIx. Recently, decreased aortic compliance has been shown to be predictive of primary coronary events in hypertensive patients with normal renal function. We aimed to explore relationships between arterial stiffness and CAD in cohorts of patients with chronic kidney disease (CKD). METHODS AND RESULTS: 46 patients with chronic kidney disease (33 males, aged 55.7+/- 13.2 years, 20 on dialysis, 18 post renal transplantation, and 8 with glomerular filtration rate (GFR) between 10 and 25 ml/min) underwent coronary angiography for the assessment of CAD. PWV and aortic AIx were determined from pulse waveform analysis of arterial waveforms recorded by applanation tonometry using a SphygmoCortm device. The atherosclerosis burden score was calculated by adding the percentage luminal reduction of the most severe lesion in each artery. Patients with normal angiograms had significantly less arterial stiffness (as reflected by both a lower PWV=8.42+/-1.53 m/s and a lower AIx=17.9+/-5.55 %) compared with the 35 subjects with evidence of obstructive coronary disease at angiography (PWV=9.21+/-1.15 m/s and AIx=23.4+/-5.4 %, P<0.05 for both). Moreover, as more coronary vessels were affected, PWV and AIx increased proportionally. Based on receiver operating characteristics (ROC) curve analysis mean PWV levels showed an optimal cut-off point at 8.35 m/s (sensitivity=0.77; specificity=0.60), while mean AIx levels showed an optimal cut-off point at 17% (sensitivity=0.87; specificity=0.70). There was a statistically significant linear relationship between the atherosclerosis burden and both measures of arterial stiffness: PWV (r=0.31, p=0.007) and AIx (r=0.46, p=0.003). Independent predictors for the arterial stiffness parameters in this CKD population (multiple stepwise regression analysis) were age (r=0.69 for PWV and r=0.62 for AIx), and mean arterial pressure (MAP) (for AIx, p<0.0001). CONCLUSION: This study provides the first direct evidence in a cross-sectional investigation that PWV and AIx are related to the extent of coronary obstruction in CKD patients.

Adult↗

[The progression factors in autosomal dominant polycystic disease].

This study was performed to evaluate prognostic factors in ADPKD progression to ERSF. Previously reported negative factors (male gender, age, hypertension, palpable kidneys and UTI) as well as the extra-renal presence of cysts and proteinuria, were analysed in a group of 45 ADPKD patients (Male/Female, 25/20; Age = 40.1 +/- 19.7 yrs, range 21-69). Palpable kidneys were associated with higher serum creatinine values (955 +/- 689 vs 743 +/- 504 umol/l, p < 0.001) but not with a greater prevalence of renal failure. Renal failure (100% vs 60%), higher creatinine values (981 +/- 495 vs 778 +/- 654 umol/l) and hypertension (50% vs 18%) were related to a higher prevalence of extra-renal cysts (p < 0.05). Older patients (> 40 years) had a greater prevalence of renal failure (96% vs 32%, p < 0.001). Also, subjects with palpable kidneys, and those with extra-renal cysts, were significantly older (52.8 +/- 10.3 vs 30.5 +/- 20.6 yrs, p < 0.025; and 42.1 +/- 21.9 vs 38.1 +/- 18.2 yrs, p < 0.025). Patients with renal failure and those with extra-renal cysts had a greater prevalence of proteinuria (65% vs 0%, p < 0.001; and 100% vs 24%, p < 0.001). No correlation was seen for male gender, hypertension or UTI with any known complications of ADPKD. The extrarenal presence of cysts, older age, proteinuria and palpable kidneys were associated with a worse renal outcome, but for this Romanian population we can't confirm previous reports suggesting a role for male gender and early onset of disease.

Adult↗