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Biomedical subjects

W A Briggs

Publications and source records attributed to W A Briggs.

At least 19 recordsLinked to original sources

Fine needle aspiration of palpable breast lumps: a 1-year audit using the Cytospin method.

A fine-needle aspiration (FNA) service for the diagnosis of palpable breast lumps was started at the Royal Preston Hospital, Preston, UK, in November 1989. Over the subsequent year, 407 FNAs were taken from 393 women. A simple technique was used which involved the surgeon flushing the aspirate into 10 ml of Cytospin collection fluid; cytocentrifuge preparations were then safely and conveniently prepared in the laboratory. Slides were stained with Papanicolaou and H&E. The method detected 112 out of a total of 121 cancers (92.6%); of the nine that were undetected, five aspirates were inadequate and four were falsely reported as negative. There were no false positives. The overall inadequate rate was 11.0%. Excluding inadequate samples, the absolute sensitivity was 89.7% and complete sensitivity 96.6% with 94.4% specificity. This 1-year audit has shown the Cytospin method of FNA in palpable breast disease to have a favourable sensitivity and specificity, and therefore to be an alternative to conventional FNA using direct smears.

Biopsy, Needle

Antiglomerular basement membrane antibody-mediated glomerulonephritis and Goodpasture's syndrome.

The originally dismal prognosis associated with anti-GBM Ab-mediated GN and Goodpasture's syndrome may be changing as we recognize a broader spectrum of disease, improve general supportive care, and improve specific treatment. Immunosuppressive therapy, if started early in the course of disease, may prevent or allow recovery from renal failure and may also result in cessation of recurrent pulmonary hemorrhage in most patients with this form of Goodpasture's syndrome. The administration of pharmacologic doses of corticosteroids intravenously can result in cessation of and dramatic recovery from severe pulmonary hemorrhage and obviate the need for emergency bilateral nephrectomy. Plasmaspheresis may represent a useful therapeutic procedure for the immediate and long term reduction in amounts of circulating anti-GBM Ab, but the definition of its true value and role awaits completion of controlled, prospective trials. Immunosuppressive therapy, with or without plasmapheresis, can reduce quantities of anti-GBM Ab in serum to undetectable levels without nephrectomy. Thus, it is likely, but not proven, that nephrectomy can be discontinued as a routine pretransplantation procedure in patients with anti-GBM Ab mediated GN. Finally, in patients who suffer irreversible renal failure, renal transplantation can be successfully undertaken with minimal risk of recurrent disease, when circulating anti-GBM Ab becomes undetectable.

Adolescent

Zinc metabolism in uremia.

Subnormal plasma zinc levels have been reported in uremic patients. However, detailed studies regarding zinc status in uremia are not available. Twenty-five patients with chronic renal failure (10 undergoing maintenance hemodialysis, five receiving chronic peritoneal dialysis, and 10 nondialyzed azotemic patients) had lower concentration of zinc in plasma, leukocytes, and hair as well as increased plasma ammonia and ribonuclease activity compared to age- and sex-matched controls (p less than 0.001). Similar biochemical changes have been reported in experimentally induced zinc deficiency in both animals and man, except that erythrocyte zinc concentration was elevated in these patients. High erythrocyte zinc concentration may be related to ineffective erythropoiesis in uremia. The results of this study suggest that abnormality in zinc metabolism occurs commonly in patients with chronic renal failure and that it develops prior to initiation of dialysis treatment.

Adult

Plasmapheresis and immunosuppressive agents in antibasement membrane antibody-induced Goodpasture's syndrome.

Four patients with rapidly progressive glomerulonephritis and pulmonary hemorrhage (Goodpasture's syndrome) induced by circulating anti-glomerular basement membrane (GBM) antibodies were treated with immunosuppressive agents and varying amounts of plasma exchange. All four patients showed progressive decreases in circulating anti-GBM antibody during therapy. Two patients with established renal failure before therapy showed no improvement in renal function but had a remission from pulmonary disease. In two other patients, renal failure developed early in the course of therapy and required maintenance hemodialysis. Later, their renal function improved coincident with a decrease in circulating anti-GBM antibody. Aggressive measures to reduce the levels of circulating anti-GBM antibody may have a salutory effect on the clinical course of the disease, particularly when undertaken early.

Adolescent

Effect of cyclic nucleotides on mitogen. Responsiveness of lymphocytes from patients undergoing dialysis.

Lymphocytes from 10 asymptomatic patients undergoing hemodialysis and from eight control subjects were repeatedly cultured with exposure to various concentrations of cyclic nucleotides and theophylline in addition to mitogen. The blastogenic response of the patients' lymphocytes was inhibited by molar concentrations of dibutyryl cyclic AMP which had much less or no inhibitory effected on the response of the control subjects' lymphocytes. This suppressive effect was not potentiated by theophylline. Cyclic GMP enhanced the proliferative response of the patients' lymphocytes as well as that of the controls. In contrast to absolute counts per minute per culture, the suppression by dibutyryl cyclic AMP of mitogen-induced blastogenesis noted in this study clearly separated the in vitro behavior of the patients' lymphocytes from that of the controls' lymphocytes and may serve as a useful marker of cellular dysfunction in such patients.

Bucladesine

Parenteral nutrition with essential amino acids in pretransplantation anephrics.

The effect of intravenous hyperalimentation with essential amino acids and hypertonic dextrose on nitrogen metabolism, total body urea and creatinine was studied in 16 patients with end-stage renal disease prior to and after bilateral nephrectomy, splenectomy and appendectomy. Parenteral essential amino acids and hypertonic dextrose are effective in lowering blood urea nitrogen in anephric patients who are incapable of improving renal function. The inclusion of essential amino acids in hypertonic dextrose increases nutritional value far beyond that which can be attributed to the caloric concentration of the amino acids themselves.

Adolescent

Kinetics of procainamide and N-acetylprocainamide in renal failure.

Four normal subjects and four functionally anephric patients were given 6.5 mg/kg of body wt of procainamide hydrochloride i.v., and plasma concentrations of procainamide (PA) and its major active metabolite N-acetylprocainamide (NAPA) were measured. Two individuals in each group were fast isonicotinic acid hydrazide (INH) and PA acetylators. The pharmacokinetics of PA and NAPA were analyzed with a computer program (SAAM 23). Volume of distribution (Vdss) and renal clearance of PA were similar in normal subjects regardless of acetylator phenotype. Nonrenal clearance was faster (383 vs. 244 ml/min), and PA elimination half-life (t 1/2) was shorter (2.6 vs. 3.5 hr) in fast acetylators. In the functionally anephric patients, Vdss was similar to that of normal subjects. Nonrenal clearence was faster (117.5 vs. 93.5 ml/min) and PA t 1/2 shorter (10.8 vs. 17.0 hr) in fast than in slow acetylators. In these patients, acetylation accounted for 56% of PA elimination, and NAPA concentrations reached 0.8 microgram/ml or more. The t 1/2 of NAPA in renal failure was 41.5 hr, in accord with predictions from studies in normal subjects, assuming no impairment in nonrenal NAPA elimination. PA metabolism, however, is severely impaired by renal failure, so PA t 1/2 was prolonged to an unpredictably greater extent than would be expected from studies in normal subjects.

Adult

N-Acetylprocainamide levels in patients with end-stage renal failure.

Serum concentrations of procainamide (PA) and N-acetylprocainamide (NAPA) were measured by fluorometry in subjects with normal renal function (n = 4) and in patients with end-stage renal failure (n = 3) after administration of 6.5 mg/kg of PA-HCl orally. Two subjects with normal renal function were rapid isonicotinic acid hydrazide (INH) acetylators and two were slow acetylators. The rapid acetylators had higher peak serum levels of NAPA (1.80 mug/ml) than the slow acetylators (0.40 mug/ml). Peak serum levels of PA were essentially identical in both. The half-life (T1/2) of PA was shorter, 2.5 hr, in the rapid acetylators than in the slow, 4.1 hr. The slope of the terminal portion of the blood time curve for NAPA was steeper (-0.087) for slow acetylators than for rapid (-0.078). These apparent differences between rapid and slow acetylators are not conclusive in themselves but tend to support the differences in acetylation previously reported. In the absence of renal function, the serum levels of PA were higher and the T1/2 prolonged. The serum levels of NAPA rose slowly and reached peak levels of 2 to 3 mug/ml and declined only with hemodialysis. In 3 patients measurable levels of NAPA were still present 78 hr (0.62 mug/ml), 94 hr (0.36 mug/ml), and 124 hr (0.70 mug/ml) after the single oral dose of PA. Clearance of NAPA during clinical hemodialysis was 48 +/- 10 cc/min compared to 75 +/- 12 ml/min for PA.

Acetylation

Artificial kidneys and clearance calculations.

Clearance of solutes by artificial kidneys can be calculated using plasma flow and solute concentration, whole blood flow and plasma solute concentration, and midpoint of dialysis blood or plasma solute concentration and total amount of solute removed. Using these methods, the clearance of procainamide (PA) and N-acetylprocainamide (NAPA) was determined in 4 patients. In all but one case clearances using total amount recovered were greater than clearances using whole blood flow and plasma concentration. Without exception, clearance determined using amount recovered was substantially greater than clearance using plasma flow and plasma levels, suggesting that both PA and NAPA are removed not only from plasma but also from red blood cells. In vitro clearance of PA, NAPA, quinidine, and phenobarbital by 11 clinically available artificial kidneys and an XAD-4 hemoperfusion column was determined and differences were found.

Blood Flow Velocity

Goodpasture's syndrome: two cases with contrasting early course and management.

In 2 patients with hemoptysis and hematuria, Goodpasture's syndrome was documented by clinical presentation, demonstration of circulating anti-glomerular basement membrane antibodies, and demonstration of linear immunofluorescence along glomerular and alveolar basement membranes. One patient was considered to have progressive disease and was treated with prednisone and cyclophosphamide. During the subsequent 18-month follow-up period, clinical remission occurred with eventual disappearance of hematuria and detectable circulating anti-glomerular basement membrane antibodies. The other patient did not have active hemoptysis at the time of referral and no therapy was instituted. After 12 months of follow-up, hemoptysis remains quiescent but hematuria and positive circulating anti-glomerular basement membrane antibodies persist. Although therapy appears to have been particularly effective in one patient, the benign course of the other patient precludes premature enthusiasm for early intervention.

Adult

Resin hemoperfusion: a method of removing circulating thyroid hormones.

The ability of an extracorporeal hemoperfusion system employing neutral Amberlite resin to bind thyroid hormone and to decrease circulating levels of triiodothyronine (T3), thyroxine (T4), and free thyroxine (FT4) was evaluated in dogs made thyrotoxic by the intramuscular administration of thyroid hormone. Since the resin column and tubing were charged with saline, the effects of hemodilution from this source on serum T3 and T4 was assessed by control perfusion through a column which did not contain any resin. After correction for hemodilution, the mean serum T3, T4 and FT4 decreased during 2 hours of resin hemoperfusion by 39%, 35%, and 46%, respectively. Hormonal clearance rates were calculated in two experiments and the estimated net hormone removed averaged 60.4 mug of T3 and 1990 mug of T4. Hematologic indices and routine chemistries did not change significantly in these dogs during the procedure except for a decrease in mean serum albumin concentration and an increase in mean serum glucose concentration. Hemoperfusion through this resin system seems to be a safe, effective means of decreasing serum T3, T4, and FT4 in thyrotoxic dogs and warrants evaluation for the treatment of thyroid storm in man.

Animals

Delivery of di-2-ethylhexyl phthalate to patients during hemodialysis.

It has been determined that the plasticizer di-2-ethylhexylphthalate (DEHP) can be leached from plastic bags used to store blood. During hemodialysis patient's blood is in contact with various plastic tubings; thus, studies were undertaken to determine how much, if any, DEHP was delivered into patients undergoing hemodialysis. Serial arterial and venous blood samples were drawn into glass syringes; serum was separated in acid-washed glass test tubes and stored at -80 degrees C. until analyzed for DEHP by gas-liquid chromatography. DEHP was delivered to each of nine patients studied. The amount delivered increased with the length of dialysis, up to 150 mg. during a 5-hour hemodialysis. The metabolic fate and toxicity, if any, of infused DEHP remains to be determined.

Acute Kidney Injury