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Biomedical subjects

W R McNabb

Publications and source records attributed to W R McNabb.

At least 19 recordsLinked to original sources
PubMed1997

Comparison between reagent strips used for detection of urinary tract infection in the elderly.

A comparison was made between the accuracy of Ames and Boehringer reagent strips for detecting urinary tract infections in 100 elderly patients (50 acutely ill patients admitted to hospital and 50 attending the day hospital). The results for urinary nitrite, blood and protein for both strips were documented. Nitrite provided the highest sensitivities and specificities. In the acute hospital patients, the sensitivities were 83% for the Ames and Boehringer strips respectively, while for the day hospital patients the sensitivities were 90% for both strips. Specificities were 100% for both strips in each group of patients. There was thus little difference between the accuracy of the Ames and Boehringer reagent strips in detecting urinary tract infection.

Aged↗
PubMed1994

Comparison of indirect and direct blood pressure measurements with Osler's manoeuvre in elderly hypertensive patients.

Indirect (cuff) and direct (intra-arterial) BPs were measured in 15 normotensive (mean age 79 years, range 72-88 years) and 21 hypertensive (mean age 76 years, range 65-89 years) elderly patients. Osler's test and arm arterial compliance, measured using Doppler-shifted ultrasound, were also assessed. In the normotensive, cuff systolic pressures were less than the direct by > 20 mmHg in 10 of the 15 (mean cuff systolic 139 +/- 13: direct 160 +/- 20 mmHg, P < 0.001); there was no statistical difference between the cuff and direct mean diastolic pressures (mean cuff diastolic 75 +/- 8; direct 70 +/- 10 mmHg). In the hypertensives, one had pseudohypertension (cuff systolic 186: direct 152 mmHg). However, cuff systolic pressures were less than the direct by > 20 mmHg in 11 (mean cuff systolic 205 +/- 26: direct 224 +/- 31 mmHg, P < 0.05); cuff diastolic pressures were greater than the direct by > 10 mmHg in 10 (mean cuff diastolic 102 +/- 14; direct 93 +/- 16 mmHg, P < 0.05). There was no significant difference between cuff and direct mean arterial pressures or the compliance in the normotensive and hypertensive groups. Osler's test was negative in the pseudohypertensive patient while in the four positive tests cuff systolic pressures were less than the direct measurements. In elderly patients there was no significant difference between the mean BP for cuff and direct measurements; systolic pseudohypotension and diastolic pseudohypertension are common and Osler's test is misleading.

Aged↗
PubMed1991

Patent foramina ovale in elderly stroke patients.

Fifty elderly patients who had suffered cerebrovascular incidents from no obvious cause and 33 age-matched controls were investigated for the presence of a patent foramen ovale by contrast 2-dimensional echocardiography at rest and after the Valsalva manoeuvre. Right-to-left shunting was found in only one patient and in none of the controls. This finding is in contradistinction to young adult stroke patients in whom the prevalence of a haemodynamically significant patent foramina ovale is high. Paradoxical embolism is an uncommon cause of stroke in the elderly.

Aged↗
PubMed1991

Accuracy of reagent strip testing for urinary tract infection in the elderly.

The accuracy of reagent strip testing for urinary tract infection (UTI) was assessed in 100 elderly patients (50 acute patients admitted to hospital and 50 attending the day hospital). Reagent strip sensitivities were: acute patients-urinary nitrite 83%, blood 67%, protein 72% and leucocytes 72%, and day hospital patients-urinary nitrite 90%, blood 65%, protein 30% and leucocytes 60%. Urinary nitrite specificities were 100% for both groups of patients. Only 28% of patients with a UTI had specific symptoms of the infection; pyrexia and a raised WBC also proved poor indicators. Urinary nitrite was thus the most accurate immediate indicator of UTI.

Aged↗
PubMed1990

Pharmacokinetic and pharmacodynamic actions of enalapril in humans: effect of probenecid pretreatment.

The pharmacokinetic and pharmacodynamic profiles of oral enalapril (20 mg), in absence and in presence of probenecid pretreatment (1 g twice daily for 5 days), were investigated in 12 healthy volunteers on normal salt intake (150 mmol/24 hr). Mean peak serum concentration of enalapril rose from 158 +/- 7 to 216 +/- 1 ng/ml (P less than .01), whereas that of its metabolite, enalaprilat, rose from 62 +/- 6 to 84 +/- 8 ng/ml (P less than .01) in the presence of probenecid pretreatment. Area under the curve of both enalapril and enalaprilat increased by 50% (P less than .001), which was accompanied by a reduction in renal excretion of both compounds. The renal clearance of enalapril decreased from 229 +/- 19 to 61 +/- 4 ml/min (P less than .001) and that of enalaprilat from 108 +/- 4 to 66 +/- 2 ml/min (P less than .001). The total drug recovery fell from 48 +/- 3 to 38 +/- 2% (P less than .01) of the administered dose with no accompanying changes in plasma elimination half-lives of the parent drug or metabolite. The pharmacodynamic response of enalapril such as fractional excretions of sodium, calcium, magnesium and urate were enhanced by probenecid pretreatment. Absolute urinary excretion of sodium increased from 51 +/- 5 to 91 +/- 8 mmol/6 hr (P less than .001) after enalapril and from 55 +/- 4 to 113 +/- 13 mmol/6 hr (P less than .01) after enalapril in presence of probenecid pretreatment, despite a significant decrease in the renal excretion of enalapril and enalaprilat over the same interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Renal responses and pharmacokinetics of piretanide in humans: effect of route of administration, state of hydration and probenecid pretreatment.

The influence of route of administration, state of hydration and transport inhibitor probenecid on the renal responses of a loop diuretic, piretanide, were investigated in 14 healthy volunteers. Maximally achieved plasma concentrations after i.v. and oral piretanide were higher in the nonhydrated state [+54% (i.v.); + 68% (oral)], accompanied by significant decreases in mean residence time, renal clearance and fraction of unchanged drug excreted with nonsignificant decreases in t1/2, steady-state volume of distribution and total clearance when compared with the hydrated state. Relative differences between the two hydrated states in maximal plasma concentrations of piretanide remained after probenecid [+26% (i.v.); +55% (oral)] but changes in kinetic parameters did not. Pretreatment with probenecid produced significant increases in absolute peak and plasma diuretic concentrations, t1/2 and mean residence time while decreasing steady-state volume of distribution, total clearance, renal clearance and fraction of unchanged drug excreted without affecting the bioavailability of piretanide. Urinary drug recovery was greater after i.v. than after oral piretanide, the recovery being consistently lower in nonhydrated state [iv: 2.78 (nonhydrated) versus 3.41 mg/24 h (hydrated); oral: 1.93 (nonhydrated) versus 2.76 mg/24 h (hydrated)]. Probenecid pretreatment reduced the overall urinary recovery of piretanide without altering the i.v./oral differences. Excretion of sodium paralleled piretanide excretion throughout the study except after i.v. dosing in the nonhydrated state where changes in drug excretion after probenecid (2.55 versus 1.63 mg/6 h) failed to influence sodium output (167 versus 152 mmol/6 h). These results demonstrate the importance of route of administration and state of hydration in determining the pharmacocological response of loop diuretics within the kidney.

Administration, Oral↗
PubMed1988

Acute and long-term renal and metabolic effects of piretanide in congestive cardiac failure.

1. The renal and metabolic effects of the sulphamoylbenzoic acid diuretic, piretanide, have been studied, under controlled dietary conditions, in 39 patients with congestive cardiac failure. 2. In acute studies, peak saluresis occurred within 4 h of oral piretanide administration; saluresis was complete within 6 h, after which a significant antidiuretic effect was observed. Addition of triamterene, 50 mg, blunted the 0-6 h kaliuretic effect of piretanide. Over 24 h, piretanide, alone, caused insignificant urinary losses of potassium when compared with control. 3. In comparative studies, the piretanide dose-response curve was found to be parallel to that of frusemide over the dose range studied. The 0-6 h saluretic responses of piretanide, 6, 12 and 18 mg, were found to be equivalent to frusemide, 40, 80 and 120 mg respectively. The collective mean ratios of all the saluretic responses to each dose of piretanide with the corresponding dose of frusemide was observed to be 0.99 +/- 0.12, over 0-6 h period, and 0.86 +/- 0.09 over the 24 h period. The relative potency of piretanide, when compared with frusemide was found to be 6.18 (95% confidence limits 4.87-8.33), over the 0-6 h period, and 4.73 (95% confidence limits 3.65-6.14), over 24 h period. 4. In 15 patients in severe cardiac failure, urinary recovery of piretanide, over first 6 h, at the start of treatment was 21.2 +/- 2.1% while efficiency of the diuretic (mmol Na/mg drug) was 47.3 +/- 4.1. Long-term piretanide therapy was continued in the same group for up to and in some cases over 3 years. No other diuretics or potassium supplements were given. Piretanide dosage ranged from 6 to 24 mg day-1 according to clinical need. Plasma potassium fell significantly at 12 and 24 months, though remaining within the normal range. At these same times, significant elevations in both plasma urate and total fasting cholesterol were observed. Two patients developed overt gout on high dose piretanide therapy (24 mg day-1). Piretanide was well tolerated, and effective in the management of congestive cardiac failure without any other recognized metabolic or electrolyte changes.

Adult↗
PubMed1986

The effects of enalapril on blood pressure and the kidney in normotensive subjects under altered sodium balance.

Eight healthy volunteers received both oral enalapril (EN; MK-421) 20 mg and placebo (PL) under stable conditions of sodium repletion, 300 mmol sodium/day (HS) and sodium depletion, 10 mmol sodium/day (LS). During PL therapy, fivefold increases in the plasma concentrations of renin and aldosterone were observed when measurements under LS were compared with those under HS conditions. Basal blood pressure (BP) readings were consistently higher and the hypotensive response to EN greater under LS compared with HS conditions. After EN, renal plasma flow increased significantly over the first 4 h, while the glomerular filtration rate, measured both by inulin and creatinine clearances, did not change. A significant natriuretic response was observed within 2 h; further natriuresis between 6 and 12 h after EN was accompanied by increased phosphate excretion.

Adult↗
PubMed1986

Chylothorax: a review of 18 cases.

Eighteen patients who had developed a chylothorax during a 25 year period, 1955-80, were reviewed. The chylothoraces occurred as a complication of cardiothoracic surgery in 11 patients, of whom eight were children in the first decade of life. Five cases followed operations for coarctation of the aorta and two occurred as a complication of a Blalock shunt for Fallot's tetralogy. The chylothorax was evident within 48 hours of the operation in all but two patients. In seven cases a second operation was performed to prevent further chylous leakage and in two infants the thoracic duct was ligated. The remainder of the postsurgical chylothoraces responded to either continuous drainage or repeated aspiration and a low fat diet. There were no late sequelae of chylothorax following surgery. Spontaneous chylothorax was identified in seven patients and in five of these it was bilateral. Patients with spontaneous chylothorax were all adults and, despite treatment, had a poor prognosis. Three with malignant disease and two with pulmonary lymphangioleiomyomatosis had died within two years of the appearance of the chylothorax. Two patients with chronic idiopathic chylothoraces survived for more than two years and one of these developed a secondary fibrothorax.

Adult↗
PubMed1985

Effects of repeated doses of enalapril on renal function in man.

Ten healthy subjects received 10 mg oral enalapril (MK 421) daily for a period of 8 days. Renal clearances of electrolytes, urate and phosphate were monitored and factored for glomerular filtration rate, as measured by creatinine clearance, with particular emphasis on the first and eighth day of treatment. Apart from a fall of around 10% in creatinine clearance between 1-2 h on both days 1 and 8, GFR remained unchanged throughout the study. Fractional sodium excretion increased in a biphasic manner by approximately 50% over control between 1-2 h and 4-8 h on day 1. Significant chloruresis (+39.0 +/- 12.9%) and kaluresis (+26.5 +/- 10.3%) occurred between 4-8 h. Urinary pH increased between 0-1 h (+0.29 +/- 0.12; P less than 0.05), and between 4-8 h (+0.50 +/- 0.08; P less than 0.01). The biphasic saluretic effect was also seen between 1-2 h and 4-8 h on day 8. Enalapril caused significant increases in urate and phosphate excretion on day 8 of therapy. There was a biphasic increase in fractional urate excretion at 1-2 h (+28.1 +/- 6.9%; P less than 0.05) and at 4-8 h (+21.0 +/- 6.0% P less than 0.01). Significant phosphaturia (+36.8 +/- 5.2%; P less than 0.05) was also observed at 4-8 h on day 8. Urinary drug excretion was also biphasic; over the first 2 h the predominant drug form was unchanged enalapril, whilst the peak excretion of the diacid metabolite, enalaprilat, occurred at 4-8 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Renal actions of piretanide and three other "loop" diuretics.

Thirty-nine clearance studies were performed in 17 healthy subjects under conditions of maximal hydration or hydropenia to compare the effects on renal solute and water handling of three sulfamoylbenzoic acid derivatives-piretanide, bumetanide, and furosemide-and the phenoxyacetic acid diuretic ethacrynic acid. Except for furosemide, which caused a 7% fall in effective renal plasma flow (ERPF), and ethacrynic acid, which reduced both the glomerular filtration rate (16%) and ERPF (23%) during maximal hydration, changes in hemodynamics were insignificant. At peak saluresis piretanide induced a mean reduction of -18.3% +/- 4.9% in fractional free-water clearance during hydration and -73.2% +/- 5.9% in fractional free-water reabsorption during hydropenia. The other sulfamoylbenzoates lowered fractional clearance and reabsorption of free water to similar extents, implying a major site of action within the medullary portion of the ascending limb. Ethacrynic acid reduced fractional free-water clearance to a greater degree than did the sulfamoylbenzoates. The mean reduction in fractional free-water reabsorption after ethacrynic acid (71.4% +/- 8.2%) was of the same order as that caused by the sulfamoylbenzoates. Similar excretory maxima for sodium, chloride, potassium, calcium, and magnesium were achieved for all four diuretics. Except for piretanide under hydropenia, sulfamoylbenzoate action did not change urinary pH. Ethacrynic acid consistently lowered urinary pH. During hydration piretanide induced phosphaturia (35.3% +/- 8.8%) and uricosuria (40.9% +/- 9.1%). Both bumetanide and piretanide increased fractional urate clearance during hydropenia (16.7% +/- 5.6% and 34.2% +/- 10.5%). There were no changes in phosphate or urate excretion after ethacrynic acid. Our data support the view that sulfamoylbenzoate diuretics exert additional effects on proximal tubular segments that are not shared by ethacrynic acid. Renal responses to piretanide most closely resemble those to bumetanide.

Absorption↗
PubMed1984

Erythromycin compared with a combination of ampicillin plus flucloxacillin for the treatment of community acquired pneumonia in adults.

Erythromycin was compared with a combination of ampicillin plus flucloxacillin for treating adults admitted to hospital with community acquired pneumonia. A satisfactory clinical response to a seven day course of antibiotics was observed in 29 of 36 patients (81%) in the erythromycin group and 35 of 39 patients (90%) treated with ampicillin plus flucloxacillin, as judged by a fall in temperature, improvement in the general condition, diminution of respiratory symptoms and radiographic improvement. Streptococcus pneumoniae was the causative organism most commonly detected and a satisfactory outcome of treatment of diagnosed pneumococcal pneumonia cases was observed in 16 of 18 patients (89%) treated with erythromycin compared with 20 of 22 patients (91%) treated with ampicillin plus flucloxacillin. These results indicate that erythromycin has similar clinical efficacy to ampicillin plus flucloxacillin, given as a seven day course, for the treatment of community acquired pneumonia in adults.

Adult↗
PubMed1984

The pharmacokinetics and tolerance of oral erythromycin stearate compared with erythromycin ethylsuccinate: implications for preventing endocarditis.

Serum concentrations of erythromycin were monitored in 11 healthy adult volunteers following single dose oral administration of erythromycin stearate, 1.5 g, and erythromycin ethylsuccinate 3.0 g. Peak serum concentrations occurred at 30 min to 2 h after the dose, usually at 1 h. Mean serum peak erythromycin concentrations (standard deviation) were 4.8 mg/l (+/- 2.0) following 1.5 g erythromycin stearate and 2.8 mg/l (+/- 1.4) after 3.0 g erythromycin ethylsuccinate. Both types of erythromycin frequently caused mild gastrointestinal side-effects but there were fewer side-effects associated with erythromycin ethylsuccinate. However, because of the increased serum erythromycin concentrations between 1 and 6 h after the dose of the stearate preparation compared to ethylsuccinate we recommend erythromycin stearate, 1.5 g, as the preferred loading dose, given 1 h before the dental procedure, for preventing endocarditis in susceptible patients allergic to penicillin.

Administration, Oral↗
PubMed1984

Renal actions of a uricosuric diuretic, racemic indacrinone, in man: comparison with ethacrynic acid and hydrochlorothiazide.

The effects of indacrinone (IND) have been investigated in a two part study. First, a total of 36 clearance studies have been performed in 14 healthy volunteers, under conditions of either maximal hydration or hydropenia, to compare the renal sites of action of single oral doses of IND, 20 mg, ethacrynic acid (EA), 100 mg, and hydrochorothiazide (HCTZ), 100 mg. Under conditions of maximal water hydration, IND increased fractional Na+ excretion from a mean of 1.19 +/- 0.05 to 4.93 +/- 0.67% of GFR. This was similar to the response seen with HCTZ, which increased fractional Na+ clearance up to 3.16 +/- 0.17% of GFR; EA increased fractional Na+ excretion up to 14.5 +/- 2.5% of GFR. The mean reduction in fractional free-water clearance (CH2O/GFR X 100%) invoked by IND, (delta = -34.8% of control) was similar to that produced by EA, (delta = -27.2% of control), and by HCTZ, (delta = -26.6% of control). During hydropenia with superimposed mannitol diuresis, both IND and EA caused a fall in fractional free-water reabsorption (TcH2O/GFR X 100%), delta IND = -20.3% of control, delta EA = -70.1% of control. HCTZ produced a significant increase in fractional free-water reabsorption, delta HCTZ = -20.7% of control. In all studies, single doses of IND were both uricosuric and hypouricaemic. Fractional urate excretion increased from a mean 6.7 +/- 0.1 to 15.2 +/- 2.1% of GFR whilst plasma urate concentration fell from a mean of 0.36 +/- 0.03 to 0.34 +/- 0.03 mM (P less than 0.05) within 2-3 h post drug. HCTZ and EA, in single doses, had little effect on urate excretion. In the second part of the study, a total of 16 healthy volunteers received either IND, 10 mg, or HCTZ 50 mg, orally for 8 days, whilst on a diet of controlled electrolyte content. Both drugs were well tolerated by both sets of subjects with no adverse clinical or pathological findings. Both IND and HCTZ caused a significant reduction in weight and standing systolic blood-pressure during the first 48 h of therapy. At the doses administered, IND and HCTZ displayed similar diuretic responses with respect to water, Na+, Cl-, Ca2+ and PO4(3-) excretion. IND produced less kaliuresis than HCTZ during the first treatment day but cumulative K+ loss was similar for both drugs over the eight days of therapy. Fractional urate excretion after IND remained elevated throughout the 8 days of therapy and the subjects remained isouricaemic for 7 days.(ABSTRACT TRUNCATED AT 400 WORDS)

Body Weight↗
PubMed1984

Stereo-specificity of diuretic receptors in the nephron: a study of the enantiomers of indacrinone (MK-196) in man.

Urinary clearance techniques have been employed to compare the renal sites of action of three phenoxyacetic acid diuretics in man: ethacrynic (etacrynic) acid and the two enantiomers of indacrinone (MK-196). The effects of these compounds on fractional free-water clearance and reabsorption during maximal hydration and hydropenia, respectively, indicate that whilst ethacrynic acid and (-)-indacrinone have their natriuretic site of action in the medullary portion of the thick ascending limb of Henle's Loop, the (+)-enantiomer of indacrinone acts in the 'cortical diluting segment' or early distal tubule. The natriuretic potencies of all three agents are different as is their effect on the renal handling of uric acid. Ethacrynic acid produces minor urate retention whilst both enantiomers of indacrinone produce uricosuria and hypouricaemia. The apparent difference in the renal sites of action of the enantiomers of indacrinone is discussed in relation to our current knowledge of stereo-selectivity in other pharmacological systems.

Absorption↗
PubMed1984

Adult community-acquired pneumonia in central London.

Strep. pneumoniae was diagnosed as the cause of pneumonia in 40 (50%) of 80 consecutive adults admitted to St Stephen's Hospital with community-acquired pneumonia. None of the patients had evidence of Mycoplasma pneumoniae infection, and Legionella pneumophila serology was positive on only one occasion. In 29 patients (36%) no causative organism was demonstrated. The diagnosis of pneumococcal infection was obtained in 15 cases by isolating Strep. pneumoniae from the sputum, in 13 further cases by demonstrating pneumococcal capsular antigen in sputum, and in 12 other cases by detecting pneumococcal antigen in serum only. Only 2 cases with pneumococcal pneumonia were bacteraemic and 3 patients (7%), all aged more than 75 years, died. The relatively low bacteraemic and mortality rates suggest that community-acquired pneumococcal pneumonia currently seen in patients admitted to hospital in central London may not be so severe as in some other areas.

Adult↗