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Biomedical subjects

A R Watson

Publications and source records attributed to A R Watson.

At least 73 records · Page 4Linked to original sources

Monoclonal antibody-based enzyme immunoassay for trypsinogen in neonatal screening for cystic fibrosis.

An enzyme immunoassay (EIA) with monoclonal antibodies against human trypsinogen in neonatal blood-spots has been evaluated for screening for neonatal cystic fibrosis (CF). In a retrospective study, 36 of 39 CF samples were distinguished from controls matched for age and storage time. 7 infants with CF were detected in 16,500 infants screened in a prospective study. The EIA is quicker and less labour intensive than conventional assays for the detection of immunoreactive trypsin and may have further advantages of specificity and sensitivity for monitoring the release of pancreatic zymogens in CF.

Antibodies, Monoclonal↗

Use of an antigen detection assay to determine mortality of Dirofilaria immitis after thiacetarsamide therapy.

The use of an antigen detection enzyme immunoassay (EIA) to determine the post-treatment infection status of 16 dogs naturally infected with Dirofilaria immitis was investigated. Dogs were treated with thiacetarsamide at a dose rate of 12mg/4.5kg twice daily for 2 days, bled at regular intervals and necropsied 9 weeks later. The infection status of all dogs at necropsy was compared to the ratios of optical density (OD) values from the EIA using fresh plasma samples (day 60/day 0 = R60) and dogs were divided into 2 groups. Using the R60 ratios, those dogs with fewer than 2 live adult worms or immature worms at necropsy ("cleared" dogs) could be differentiated with 95% confidence from those dogs with more than 1 live adult worm ("non-cleared" dogs). Changes in the average OD values from the plasma of "cleared" dogs and "non-cleared" dogs were similar up to 46 days after treatment but diverged significantly thereafter. The efficacy of thiacetarsamide was 50% if all worms were considered and 75% if the presence of immature worms was ignored. The benefits of antigen detection assays for diagnosis and improved patient assessment and the use of an R60 ratio to assess the efficacy of adulticides such as thiacetarsamide are discussed in relation to their practical significance for clinicians.

Animals↗

Central nervous system dysfunction and erythrocyte guanosine triphosphate depletion in purine nucleoside phosphorylase deficiency.

Developmental retardation was a prominent clinical feature in six infants from three kindreds deficient in the enzyme purine nucleoside phosphorylase (PNP) and was present before development of T cell immunodeficiency. Guanosine triphosphate (GTP) depletion was noted in the erythrocytes of all surviving homozygotes and was of equivalent magnitude to that found in the Lesch-Nyhan syndrome (complete hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency). The similarity between the neurological complications in both disorders indicates that the two major clinical consequences of complete PNP deficiency have differing aetiologies: neurological effects resulting from deficiency of the PNP enzyme products, which are the substrates for HGPRT, leading to functional deficiency of this enzyme. immunodeficiency caused by accumulation of the PNP enzyme substrates, one of which, deoxyguanosine, is toxic to T cells. These studies show the need to consider PNP deficiency (suggested by the finding of hypouricaemia) in patients with neurological dysfunction, as well as in T cell immunodeficiency. They suggest an important role for GTP in normal central nervous system function.

Central Nervous System↗

Peritonitis during continuous ambulatory peritoneal dialysis in children.

The use of continuous ambulatory peritoneal dialysis (CAPD) in children has proved beneficial. However, peritonitis remains the major complication. A review of the incidence of peritonitis in 55 children (mean age 9.6 years) who underwent CAPD between 1978 and 1984 showed that there were 67 episodes of peritonitis (1 per 9.4 patient-months) in 33 of the 55. Three patients accounted for 22 of the episodes. In all cases, treatment with antibiotics, given intraperitoneally, was successful. Cephalothin was routinely given for infections due to gram-positive organisms, tobramycin for infections due to gram-negative organisms. Peritonitis recurred in seven patients, of whom five had to have their catheters replaced because of associated chronic infections of the deep peritoneal cuff, the exit site or the catheter tunnel. Although peritonitis was a common complication of CAPD in this population, it did not affect the success of the technique.

Adolescent↗

Gonadal function in women treated with cyclophosphamide for childhood nephrotic syndrome: a long-term follow-up study.

The gonadal function of 18 women who were treated for childhood nephrotic syndrome at a mean age of 10.7 years with cyclophosphamide (mean dosage, 28 gm; mean duration of therapy, 354 days) was evaluated at a mean of 14.5 years after treatment by means of detailed questionnaires. Menstrual patterns were normal in all except two, who were still receiving intermittent prednisone therapy. Eight healthy children had been born to five mothers. Compared with males, there is little current evidence of gonadal toxicity in this patient group. Further follow-up is required to determine whether these women will undergo premature menopause.

Adolescent↗

A central venous (W-B-W) catheter for multipurpose vascular access in children.

A central venous (W-B-W) catheter has been developed for vascular access in children of all ages and sizes. The catheter design and implantation technique permit nonsurgical bedside adjustment of catheter position and ease of removal. Multiple possible uses include intravenous fluid administration, blood sampling, central venous pressure monitoring, and plasma exchange therapy in addition to hemodialysis. Twenty-seven W-B-W catheters were placed in 24 patients in a 12-month period. The catheter provided adequate blood flow for hemodialysis. Seven catheters were removed nonelectively in five patients. One episode of catheter-associated sepsis occurred after renal transplantation in a patient on immunosuppressive therapy. It is concluded that the W-B-W catheter is a relatively safe, multipurpose, pain-free acute vascular access for children, which may also suffice for chronic hemodialysis.

Adolescent↗

Renovascular hypertension: treatment choices.

Over a 10 year period, 17 children received treatment for renovascular hypertension. A stenosis of the main renal artery was demonstrated in 10 patients (bilateral involvement in two) and a branch artery in 7. Fifteen of the 16 patients available for follow up are normotensive after a mean of 3.7 years. The initial treatment choice consisted of nephrectomy (1 patient), partial nephrectomy (1 patient), ligation of a branch artery (1 patient), surgical angioplasty (3 patients), autotransplantation (6 patients), and percutaneous transluminal balloon angioplasty (7 patients). Six patients required secondary surgical procedures (4 nephrectomy, 1 surgical angioplasty and 1 autotransplantation) before the blood pressure was normalised. Transluminal balloon angioplasty was attempted in seven patients but was successful in only two with main renal artery stenoses. Treatment choices have increased for patients with renal artery stenosis lesions and increasing experience and assessment of techniques such as PTA are required.

Adolescent↗

Long term effects of cyclophosphamide on testicular function.

Thirty men treated in childhood with cyclophosphamide for a mean of 280 days were assessed at a mean of 12.8 years after treatment for hormone concentrations and spermatogenesis. Four were azoospermic, nine oligospermic, and 17 normospermic. There was a significant inverse correlation of sperm density with cyclophosphamide dosage and duration of treatment. After a further mean follow up of 7.2 years three patients who were previously oligospermic and one who was azoospermic had normal sperm counts. All patients had normal sexual characteristics and libido. Serum androgen and prolactin concentrations did not differ significantly between patients and controls. Raised basal and stimulated follicle stimulating hormone concentrations were in keeping with impaired spermatogenesis. All patients had significantly raised luteinising hormone responses on stimulation with luteinising hormone releasing hormone. The results suggest compensated Leydig cell failure, and patients with this condition require long term evaluation of testicular function. Potential recovery of spermatogenesis with time requires appropriate counselling and contraceptive advice.

Adult↗

Renovascular hypertension in childhood: a changing perspective in management.

Seventeen children with renovascular hypertension caused by intrinsic renal artery lesions received treatment during the past 10 years. At presentation nine were asymptomatic, four had headaches, and one had epistaxis; three infants had anorexia and failure to thrive. Routine intravenous pyelogram and radionuclide renal scan findings were abnormal in 29% and 31% of patients, respectively. Arteriography showed a branch artery stenosis in seven patients and a main artery lesion in 10. A renal vein renin ratio of greater than or equal to 1.5 between the affected and the contralateral kidney was obtained in 10 of 17 patients. Of 16 patients available for follow-up, 15 are normotensive after a mean follow-up of 3.7 years. Cure was achieved by partial nephrectomy and ligation of a stenosed vessel in two and nephrectomy in five (three having undergone an unsuccessful angioplasty procedure). Autotransplantation or angioplasty was curative in a further six. Transluminal balloon angioplasty was attempted in seven patients but was successful in only two with main renal artery stenoses. With preservation of renal parenchyma as the main goal, medical and surgical therapy can be individualized for each patient.

Adolescent↗

Membranoproliferative glomerulonephritis type I in children: correlation of clinical features with pathologic subtypes.

Renal biopsies from 33 patients with membranoproliferative glomerulonephritis (MPGN) type I were reviewed to identify pathologic subtypes of this disease and assess their correlation to clinical features. The patients were divided into two groups: group A included 16 patients in chronic or end-stage renal failure and group B 17 patients with no evidence of renal insufficiency. At presentation, a nephrotic or nephritic syndrome and azotemia were equally common in both groups. The incidence of hypertension was significantly increased in group A (P less than 0.05), while recurrent gross hematuria was more common in group B. Nephrotic syndrome was more common during the course of illness in group A. Three subtypes of MPGN type I were recognized, based on whether duplication of glomerular capillary basement membranes was focal segmental (FS; 9 cases), diffuse global (DG; 18 cases), or mixed segmental and global (6 cases). Eight of nine patients showing FS MPGN type I were in group B (p less than 0.05). In contrast, 11 of 18 patients with DG MPGN type I and 4 of 6 with a segmental and global pattern were in group A (P = not significant). Therefore, FS MPGN is a good predictor of a favorable clinical outcome, whereas the other two subtypes are not. This was confirmed by a 100% actuarial kidney survival for the nine patients with FS MPGN and a 50% kidney survival of 7.5 years for patients with the other two subtypes.

Adolescent↗

On the metabolism of allopurinol. Formation of allopurinol-1-riboside in purine nucleoside phosphorylase deficiency.

Allopurinol-1-riboside, a major metabolite of allopurinol, is commonly thought to be directly synthesized by purine nucleoside phosphorylase (PNP) in vivo. As this enzyme is otherwise believed to function in vivo primarily in the direction of nucleoside breakdown, we have determined by high performance liquid chromatography and a conventional chromatographic method the urinary metabolites of allopurinol in a child deficient of PNP. In this patient approximately 40% of urinary allopurinol metabolites consisted of allopurinol-1-riboside, thus proving the possibility of indirect formation of allopurinol-1-riboside via allopurinol-1-ribotide in vivo, catalysed by hypoxanthine guanine phosphoribosyltransferase (HGPRT) and a phosphatase.

Allopurinol↗

Importance of platelet-free preparations for evaluating lymphocyte nucleotide levels in inherited or acquired immunodeficiency syndromes.

Low ATP/ADP ratios have been reported consistently for nucleotide levels of mononuclear cells separated from peripheral blood by conventional techniques. We have established that these low values (mean 2.3:1) were not due to cell damage or poor viability, but resulted from heavy platelet contamination, which is unavoidable when heparinized blood is used. The results reflect the low ATP/ADP ratios (mean 1.6:1) characteristic of platelets. Platelet-free extracts from defibrinated blood had very high ATP/ADP ratios (mean 17.4:1). The initial finding of detectable amounts of deoxy-ATP and deoxy-GTP in mononuclear cells from children with two distinct inherited immunodeficiency disorders [adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiency respectively] many have been due to contamination by nucleated erythrocytes as well as platelets in non-defibrinated preparations. Defibrination before nucleotide extraction of mononuclear cells from a patient with T-cell leukaemic/lymphoma treated with the ADA inhibitor deoxycoformycin enabled the demonstration of grossly raised deoxy-ATP levels relative to deoxy-ADP levels (ratio 16.1:1), associated with severe ATP depletion. This reciprocal relationship between ATP and dATP was found by us previously in the erythrocytes in inherited ADA deficiency. These findings underline the importance of extracts uncontaminated by platelets, or nucleated erythrocytes, in the evaluation of lymphocyte nucleotide levels in inherited or acquired immunodeficiency syndromes.

Adenosine Deaminase↗

Zinc supplementation and its effect on taste acuity in children with chronic renal failure.

Diminished taste acuity (hypogeusia) and zinc deficiency have been reported in children on maintenance haemodialysis and with varying degrees of chronic renal failure. We have studied the effect of 6 weeks' zinc supplementation in 20 children with chronic renal impairment using a double-blind crossover trial. Although we achieved significant increases in serum zinc levels no significant improvement in taste acuity could be demonstrated. These studies provide no support for the belief that routine zine supplements are necessary in children with chronic renal failure.

Adolescent↗