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P S Williams

Publications and source records attributed to P S Williams.

At least 19 recordsLinked to original sources
PubMed1994

Theory of field-programmed field-flow fractionation with corrections for steric effects.

This paper deals with the principal perturbation to ideal normal-mode elution of particles in field-flow fractionation (FFF). This perturbation is due to the finite size of particles undergoing migration in the FFF channel. The effects of a first-order correction for particle size are examined. Equations are derived for retention time, fractionating power, and steric inversion diameter for operation at constant field strength, as well as under conditions of both exponential and power programmed field decay. Useful limiting equations for fractionating power are derived and their validity is confirmed for typical experimental conditions. The derived equations are necessary for the future development of a systematic optimization strategy for the selection of operating conditions for particle size analysis by FFF. Calculations confirm our previous conclusion that the fractionating power for exponential field programming varies strongly with particle size; this variation is only slightly reduced by steric perturbations. The uniform fractionating power of power programming is slightly disturbed by steric effects although fractionating power remains much more uniform than for exponential programming. It is shown that a higher uniformity in fractionating power can be gained by manipulating the parameters of power programming but that no improvement is possible with exponential programming. Phenomena giving rise to higher order perturbations and to secondary relaxation are discussed and the conditions identified under which these effects are minimized.

Chemical Fractionation↗
PubMed1992

Rapid breakthrough measurement of void volume for field-flow fractionation channels.

A peak breakthrough technique is described and evaluated for measuring the void volume of field-flow fractionation (FFF) channels, particularly those used for flow FFF. This technique uses a high-molecular-mass macromolecular or particulate probe that can be displaced rapidly by flow through the FFF channel with minimal transverse diffusion. The particles that emerge first are those carried through the entire length near the channel centerline at the apex of the parabolic flow profile. These particles generate a sharp breakthrough profile. The measured breakthrough time is two thirds of the void time, thus making it possible to calculate both the void time and the associated void volume. This method, although applicable to all FFF channels (and capable of extension to open tubes), is particularly useful for flow FFF because conventional low-molecular-mass void probes can diffuse into the permeable walls and thus distort void measurements. The theoretical basis of the breakthrough technique and an explanation for the sharpness of the breakthrough front are given. A method for compensating for deviations from perfect sharpness is developed in which the breakthrough time is identified with the time needed to reach 85-88% of the breakthrough peak maximum. Preliminary experimental results are shown using various protein probes in four different FFF channel systems.

Chemical Fractionation↗
PubMed1991

Hydrodynamic relaxation in flow field-flow fractionation using both split and frit inlets.

Two means are described for achieving hydrodynamic relaxation and thus avoiding the stopflow injection procedure in field-flow fractionation (FFF): split flow injection and frit inlet injection. The advantages, disadvantages, and the theoretical basis of these procedures are discussed. Incremental band broadening due to the final relaxation step is examined theoretically and shown to be negligible when the flow rate of the sample inlet substream is small compared to the total channel flow rate. The optimization of the sample inlet flow rate is discussed. Experimental results for both injection procedures are reported for flow/steric (or hyperlayer) FFF applied to latex standards, confirming the expected trends. However, closer examination shows that the observed incremental band broadening associated with hydrodynamic relaxation is somewhat larger than the value predicted.

Chemical Phenomena↗
PubMed1991

Comparison of power and exponential field programming in field-flow fractionation.

Field programming in field-flow fractionation has the purpose of expanding the molecular weight or particle diameter range subject to a single analytical run. The two most widely used field programs are those in which the field strength decays with time according to an exponential function and a power function, respectively. The performances of these two programming functions are compared by obtaining limiting equations showing how retention time tr, standard deviation in retention sigma t, and fractionating power Fd vary with particle diameter d. It is shown that uniform fractionating power (Fd independent of d) can be obtained with power programming but that in exponential programming Fd is always non-uniform, varying as d-1/2. In exponential programming a linear relationship arises between tr and log d. This particular relationship is impossible to realize in power programming but an alternative linear relationship can be obtained by plotting tr versus dt/3. These results are made more concrete by plotting and comparing field strength, relative field strength, Fd and tr for specific programming cases.

Chemical Fractionation↗
PubMed1991

Particle size distribution by sedimentation/steric field-flow fractionation: development of a calibration procedure based on density compensation.

Because of the important but mathematically complex role played by hydrodynamic lift forces in sedimentation/steric FFF, applied generally to particles greater than 1 micron in diameter, retention cannot readily be related to particle diameter on the basis of simple theory. Consequently, empirical calibration is needed. Unfortunately, retention is based on particle density as well as size so that a purely size-based calibration (e.g., with polystyrene latex standards) is not generally valid. By examining the balance between driving and lift forces, it is concluded that equal retention will be observed for equal size particles subject to equal driving forces irrespective of particle density. Therefore by adjusting the rotation rate to exactly compensate for density, retention can be brought in line with that of standards, a conclusion verified by microscopy. Linear calibration plots of log (retention time) versus log (diameter) can then be used. This approach is applied to two glass bead samples (5-30 and 5-50 microns) using both a conventional and a pinched inlet channel. The resulting size distribution curves are self consistent and in good agreement with results obtained independently.

Calibration↗
PubMed1991

Failure of dietary protein and phosphate restriction to retard the rate of progression of chronic renal failure: a prospective, randomized, controlled trial.

Ninety-five patients (63 male, 32 female), age 45 +/- 2 years (mean +/- SEM) with chronic renal failure of varied aetiology were randomized to receive either a conventional low protein diet (0.6 g/kg/day protein, 800 mg phosphate; n = 33), a low phosphate diet (providing approximately 1000 mg phosphate plus an orally administered phosphate binder, minimum protein intake 0.8 g/kg/day; n = 30) or to control (minimum protein intake 0.8 g/kg/day, no phosphate restriction; n = 32). Patients were reviewed for a minimum of 6 months before randomization and were withdrawn from the study if plasma creatinine exceeded 900 mumol/l, plasma phosphate was greater than 2.0 mmol/l or at the onset of uraemic symptoms. Following randomization patients were studied for an average of 19 +/- 3 months. Mean plasma creatinine rose from 398 +/- 33 to 600 +/- 50 mumol/l. Dietary protein intake was estimated at 0.69 +/- 0.02 g/kg/day in the low protein group, 1.02 +/- 0.05 in the low phosphate and 1.14 +/- 0.05 in the controls, phosphate intake was 815 +/- 43, 1000 +/- 47, and 1315 +/- 57 mg/day, respectively. Urinary urea excretion and protein catabolic rates were significantly reduced (p less than 0.01) only in those on protein restriction, at 213 +/- 9 mmol/24 hours and 0.71 g/kg/day, respectively. Phosphate excretion was significantly lower (p less than 0.05) in both the low protein group (17.9 +/- 0.8 mmol/24 hours) and the low phosphate group (18.6 +/- 1.0 mmol/24 hours) compared to controls. Changes in body weight, muscle mass and serum transferrin, albumin and immunoglobulins were comparable between the groups. Mean blood pressure following randomization was 150/89 +/- 3/1 (low protein), 148/87 +/- 3/1 (low phosphate) and 146/87 +/- 3/1 (controls). Progression of renal failure was analysed by rate of all of creatinine clearance (ml/min/1.73 m2/month), by rate of deterioration derived from reciprocal plasma creatinine against time plots (1/mmol/year) and to assess individual patient's response to treatment by two phase linear regression ('breakpoint') analysis of reciprocal plasma creatinine/time plots. Progression was analysed only in patients seen for at least 3 months following randomization. The rate of fall of creatinine clearance was not significantly different between the groups (ANOVA): 0.56 +/- 0.08 ml/min/1.73 m2/month (low protein, n = 28), 0.44 +/- 0.07 (low phosphate, n = 23) and 0.69 +/- 0.11 (control, n = 27).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Multiple organ failure--a role for plasma exchange?

Two patients with multiple organ failure, septicaemia and a deteriorating clinical course were treated by plasma exchange in addition to standard supportive measures. Dramatic improvements were seen in cardio-respiratory (patient 1), neurological and renal parameters (patient 2) which were attributable to the exchanges. Plasma exchange might be of value as adjunctive therapy where overwhelming septicaemia occurs with multiple organ failure.

Adult↗
PubMed1990

Reducing sepsis in severe combined acute renal and respiratory failure by selective decontamination of the digestive tract.

Fifteen patients with severe combined acute renal and respiratory failure (SCARRF), who required mechanical ventilation and renal replacement therapy for at least 5 days, were treated with a regimen to selectively decontaminate the digestive tract (SDD). In these patients the incidence of significant infection was compared with the infection rate in 12 similar patients with SCARRF who had not received SDD, treated over the preceding 12 months. Both groups were comparable for age, study period, sepsis score, and therapeutic intervention scoring system on admission, although the Acute Physiology and Chronic Health Evaluation score was higher (p less than .05) in the SDD-treated group. Ten (83%) of 12 control patients developed definable infections compared with five (33%) of 15 in the SDD group (p less than .05). Gram-negative bacteria and fungi were responsible for 14 of the 17 infections affecting ten control patients, compared with six of the seven infections in only four SDD patients (p less than .05). The most notable site to benefit was the respiratory tract, with only one patient in the SDD group developing a pulmonary infection compared with five in the control patients (p less than .05). Urine infections may have been reduced from six (50%) of the 12 control patients to two (13%) of the 15 SDD patients, but this difference was not significant. Although survival in the control and SDD group was comparable (42% vs. 40%), mortality overall seemed related to infection. Eleven (73%) of 15 patients with definite infection died, in contrast with five (42%) of 12 who had no infections, although this was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1989

Immunosuppression can arrest progressive renal failure due to idiopathic membranous glomerulonephritis.

The effect of pulse intravenous methylprednisolone therapy followed by oral immunosuppression was evaluated in ten patients with idiopathic membranous glomerulonephritis who had developed progressive renal failure--a group generally considered to have a poor prognosis. The patients (six male, four female, mean age 50 years) were monitored over 9-30 months during which time creatinine clearance reduced from (mean +/- SEM) 83 +/- 10 to 29 +/- 6 ml/min, and plasma creatinine increased from 135 +/- 22 to 297 +/- 35 mumol/l. All patient were nephrotic with mean 24-h urinary protein excretion ranging from 5.8 to 19.6 g. Treatment administered was pulse intravenous methyl-prednisolone 1 g X 3 then oral prednisolone 30 mg and azathioprine 50 mg (nine patients) or cyclophosphamide 50 mg (one patient). Mean prednisolone dosage was 25 mg at 3 months, 16 mg at 6, and 10 mg at 12 months. Patients have been followed up for between 12 and 57 months on therapy. Creatinine clearance increased to 39 +/- 6, 47 +/- 5 and 48 +/- 18 ml/min after 3, 6 and 12 months treatment with a fall in proteinuria to 6.2 +/- 1.7, 5.7 +/- 1.4, and 3.1 +/- 1.1 g/24h. The deterioration of renal function was reversed in six patients (associated with a reduction in proteinuria to less than 1 g/24 hours in five), slowed in three (with a significant reduction in proteinuria in two), and only one patient with more advanced renal failure before treatment progressed to end-stage failure without any retardation of the rate of deterioration or change in proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Novel inhibitors of enkephalin-degrading enzymes. I: Inhibitors of enkephalinase by penicillins.

Several penicillins have been found to have pro-antinociceptive properties and also to be enkephalinase (neutral endopeptidase-24.11) inhibitors, carfecillin being the most potent. Carfecillin i.c.v. (but not i.p.) had significant antinociceptive activity in the mouse tail immersion test and completely suppressed abdominal constrictions (acetic acid) in mice (IC50 = 23 micrograms/animal). In combination with (D-Ala2-D-leu5)-enkephalin (DADL) i.c.v. in the abdominal constriction test the complete protection observed was reversed by the opioid receptor antagonist naltrexone. Carfecillin was a competitive inhibitor of enkephalinase from mouse brain striata (IC50 = 207 + 57 nM, cf thiorphan 10.6 +/- 1.9 nM) but did not inhibit other known enkephalin- degrading enzymes. Carfecillin provides a new lead structure for the development of more potent enkephalinase inhibitors.

Analgesics↗
PubMed1989

Novel inhibitors of enkephalin-degrading enzymes. II: N5'-substituted-4-thioxohydantoic acids as aminopeptidase inhibitors.

Some 2-substituted-(2'-aminophenyl)-4-thioxohydantoic acids (o-amino PTC-amino acids) have antinociceptive activity when administered (icv) alone (IC50 = 0.04-0.87 microM/animal) and show a striking prolongation of the antinociceptive action of (D-Ala-2 D-Leu5)-enkephalin (DADL) in combination. The effects are thought to be mediated via opioid receptors since they are naloxone-reversible. Although inhibitors of the enkephalin degrading puromycin-insensitive, bestatin-sensitive aminopeptidase (possibly aminopeptidase M) their action is weak (IC50 = 32 microM leucine, 536 microM, glycine) and they might be considered to have a direct antinociceptive effect on opioid receptors. The titled compounds constitute novel 'lead' compounds for the development of potent aminopeptidase M inhibitors.

Aminopeptidases↗