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Biomedical subjects

A D Pearson

Publications and source records attributed to A D Pearson.

At least 19 recordsLinked to original sources
PubMed1992

The surveillance and control of campylobacter infection.

Campylobacter jejuni and C. coli are the most commonly reported bacterial causes of enteritis in man in the United Kingdom. The reported incidence of campylobacter infection varies with place and time. Its epidemiology differs from that of salmonella: campylobacters do not multiply on food, secondary spread is rare, and infections peak at the end of May (salmonellas peak in July). Known sources of infection include poultry, milk, water, pets and other domestic animals. Campylobacters are widespread in the environment, and in domestic and wild birds and mammals. About 10% of infections reported in the UK are acquired abroad. The application of preventive measures can be effective in reducing the incidence of infection and its not inconsiderable financial burden.

Adolescent↗
PubMed1992

Pharmacokinetics and metabolism of cyclophosphamide in paediatric patients.

The pharmacokinetics and metabolism of cyclophosphamide were studied in nine paediatric patients. Plasma samples were obtained from eight subjects and urine was collected from six children during a 24-h period after drug administration. Cyclophosphamide and its major metabolites phosphoramide mustard (PM), carboxyphosphamide (CX), dechloroethylcyclophosphamide (DCCP) and 4-ketocyclophosphamide (KETO) were determined in plasma and urine using high-performance thin-layer chromatography-photographic densitometry (HPTLC-PD). Cyclophosphamide (CP) was nearly, if not completely, cleared from plasma by 24 h after its administration. The plasma half-life of CP ranged from 2.15 to 8.15 h; it decreased following higher doses and was shorter than that previously reported for adult patients. Both the apparent volume of distribution (0.49 +/- 1.4 l/kg) and the total body clearance (2.14 +/- 1.4 l m-2 h-1) increased with increasing dose. Renal clearance ranged between 0.12 and 0.58 l/h (mean, 0.43 +/- 0.19 l/h). Between 5.4% and 86.1% of the total delivered dose was recovered as unchanged drug in the urine. The major metabolites identified in plasma and urine were PM and CX. One patient appeared to be deficient in CX formation. This study suggests that there is interpatient variability in the pharmacokinetics and metabolism of CP in paediatric patients. The shorter half-life and higher clearance as compared with adult values indicate faster CP metabolism in children.

Absorptiometry, Photon↗
PubMed1992

Gut hormones and gastrointestinal motility in children with cystic fibrosis.

Intestinal dysmotility may be an important factor contributing to various gastrointestinal complications associated with cystic fibrosis. Motilin, enteroglucagon, neurotensin, and peptide YY may each play a role as endocrine hormones influencing gastrointestinal motor activity. Fasting children with cystic fibrosis (N = 8) and controls (N = 18) received a liquid nutrient test meal (fat 4 g/100 ml, protein 4 g/100 ml, carbohydrate 20 g/100 ml, 125 kcal/100 ml; 200 ml/m2) containing lactulose (5 g/100 ml), and the plasma concentrations of these peptides were studied. Mouth-to-cecum transit time was simultaneously studied using the breath H2 technique. Fasting levels of peptide YY and the postprandial response of all four peptides were significantly increased in those with cystic fibrosis. In repeat studies on those with cystic fibrosis after a period of altered pancreatic enzyme supplementation, no significant changes in peptide concentrations were observed. A rise in breath H2 permitting estimation of mouth-to-cecum transit time was noted in 17 control subjects (70-220 min, median 140). In contrast, a rise occurred in only two with cystic fibrosis after low-dose enzyme (70 and 180 min), and four after high-dose enzyme replacement (120-230 min, median 155). Altered gut hormone secretion may play a role in the pathophysiology of intestinal dysmotility in patients with cystic fibrosis.

Adolescent↗
PubMed1992

Comparison of saphenous versus jugular veins for central venous access in children with malignancy.

A retrospective analysis was carried out to compare the performance and complications of central catheters inserted into either the saphenous (27) or jugular (52) veins. The saphenous route may be preferred in certain circumstances including extensive mediastinal pathology, prior neck surgery, previous catheter(s), and cosmetic reasons. There was no difference in complications (local or systemic catheter-related infections, catheter occlusions, or venous thrombosis). The incidence of catheter removal due to complications was also not different between sites. Hence, the saphenous route can provide an additional portal of vascular access in selected patients.

Adolescent↗
PubMed1992

High-dose rapid schedule chemotherapy for disseminated neuroblastoma.

In a high-dose schedule for disseminated neuroblastoma, eight courses of chemotherapy were administered every 10 days, regardless of myelosuppression, to eradicate tumour cells rapidly and reduce emergence of drug-resistant clones. Relatively non-myelotoxic vincristine and cisplatin were alternated with high-dose cisplatin-etoposide and cyclophosphamide-etoposide. Of 12 evaluable patients, there were 1 complete (CR), 3 very good partial (VGPR), 5 partial (PR) and 3 mixed responses (MR) 100 days after starting treatment. 6 out of 9 achieved a bone marrow CR at 40 days. 9 of 11 primary tumours were completely resected, after which 4 patients had CR, 3 VGPR (bone scan alone being abnormal), 4 PR and 1 mixed response (MR). Myelotoxicity was the major adverse effect. The only death was due to fungal infection. Clinically important renal dysfunction occurred in 3 patients. 4 had convulsions and 4 temporary hypertension. This schedule produced a rapid response and its toxicity, though serious, was manageable. Further evaluation is warranted.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Toxicity of single-day high-dose vincristine, melphalan, etoposide and carboplatin consolidation with autologous bone marrow rescue in advanced neuroblastoma.

16 unselected patients with advanced neuroblastoma were given high-dose consolidation chemotherapy with vincristine, melphalan, etoposide and carboplatin over 5 h followed by autologous bone marrow rescue. 3 patients died from treatment-related toxicity, 2 from disease, 1 is alive with disease and 10 are alive and disease-free a median of 12.5 months (range 2-38 months) after bone marrow rescue. All had bone marrow toxicity, most mucositis and 6 had seizures. Renal failure was unexpectedly severe. In the last 3 patients, administration of carboplatin was delayed by 18 h in an attempt to reduce renal damage. The results show that this regimen produces significant morbidity and has a high mortality. Although the overall outcome is encouraging, too few patients have been studied to gauge its efficacy. Whether such aggressive consolidation is necessary in heavily pretreated children with neuroblastoma remains unknown.

Adolescent↗
PubMed1992

Prognostic implications of p53 protein, epidermal growth factor receptor, and Ki-67 labelling in brain tumours.

The expression of p53 protein, epidermal growth factor receptor (EGFR), and Ki-67 nuclear antigen was examined by immunohistochemistry in biopsies of 16 types of human brain tumours, including 43 astrocytomas. P53 protein, almost certainly its mutant form, was expressed in seven of the 16, and EGFR in 11 of the 16 types of tumours. In astrocytomas both the proportion of tumours which expressed p53 or EGFR increased with grade of malignancy as did the mean Ki-67 labelling index (LI): p53-0% in grade 1, 17% in grade 2, 38% in grade 3, 65% in grade 4; EGFR-0% in grade 1, 33% in grade 2, 85% in grade 3, 95% in grade 4; mean Ki-67 L1-1.1% in grades 1 and 2, 8.3% in grade 3, and 13.4% in grade 4. Astrocytomas which expressed p53 or EGFR had a significantly higher Ki-67 LI at P less than 0.05 (11.8% and 10.7%, resp.) than those that did not (6.2% or 4.1%, resp.). Patients with astrocytomas expressing p53 or EGFR had a significantly reduced survival (P = 0.035 and P = 0.007, resp.): only 11% of the p53 + ve and 13% of the EGFR + ve patients were alive at 100 weeks following diagnosis compared to 36% of p53-ve or 60% of EGFR-ve patients. Patients with Ki-67 LI greater than 5% had a reduced survival (P less than 0.0001)--none survived beyond 86 weeks following diagnosis, whilst 63% of patients with less than 5% positive cells were still alive at 100 weeks. The univariate analysis showed that in astrocytomas expression of p53 mutants, EGFR protein, and Ki-67 greater than 5% are associated with malignant progression and poor prognosis. The multivariate analysis revealed that only tumour grade and Ki-67LI were independent prognostic factors for survival.

Adolescent↗
PubMed1992

Necrobacillosis with pancytopenia.

Two young children whose presentation with necrobacillosis caused considerable diagnostic difficulty resulting in referral to an oncology unit are described. In both cases their severe suppurative multisystem illness was complicated by pancytopenia. One had bone marrow infarcts and severe endocarditis in addition to pulmonary involvement and the other had osteitis which resulted in a deformed humerus.

Anti-Bacterial Agents↗
PubMed1992

Increase in severity of graft versus host disease by cytomegalovirus.

An allogeneic transplant recipient developed severe graft versus host disease (GvHD) 48 days after transplantation that was concomitant with a cytomegalovirus (CMV) viraemia, from which she subsequently died. CMV infection was detected in blood by the polymerase chain reaction and later in tissue by immunohistochemical techniques. CMV should be considered in patients in whom GvHD does not respond to appropriate treatment, and this case suggests that herpes viruses may increase the severity of GvHD by synergistically enhancing the graft versus host reaction.

Adult↗
PubMed1992

Human herpes virus 6 and endogenous biotin in salivary glands.

AIMS: To detect the presence of human herpes virus 6 (HHV6) and endogenous biotin in paraffin wax embedded and frozen salivary glands. METHODS: Two stage indirect and streptavidin-biotin immunoperoxidase techniques were used to visualise the antigens. RESULTS: HHV6 could not be shown in any of the tissues. However, considerable endogenous biotin antigenicity was detected in the glandular elements of the paraffin wax embedded material. CONCLUSIONS: Results obtained with avidin-biotin detection systems should be interpreted with caution, especially when glandular epithelium is being stained. This may apply to both immunoperoxidase and in situ hybridisation techniques. The use of an anti-biotin antibody as a standard control should be considered.

Biotin↗
PubMed1992

The influence of age on nephrotoxicity following chemotherapy in children.

Nephrotoxicity is an important adverse effect of chemotherapy in children. Renal function after treatment with either ifosfamide or cisplatinum in children aged 5 years or less ('younger children') was compared with that in those over 5 years ('older children'). Eighteen children (six younger, 12 older) given ifosfamide were studied after completion of chemotherapy, and 28 patients (16 younger, 12 older) were evaluated after cisplatinum. Glomerular filtration rate was measured from the plasma clearance of 51chromium-labelled edetic acid. Proximal tubular function was assessed by determination of plasma and urine calcium, phosphate, magnesium and glucose concentration; calculations of their fractional excretions, and of the renal threshold for phosphate; and measurement of urinary excretion of beta 2-microglobulin. Distal tubular function was evaluated by measurement of the early morning urine osmolality. Younger children had more severe proximal tubular toxicity than older children treated with ifosfamide, with significantly lower plasma phosphate concentrations and higher fractional excretions of glucose. However, there was no evidence of any such difference in glomerular or distal tubular damage after ifosfamide, and no difference in any aspect of renal function between younger and older children treated with cisplatinum. Increased proximal tubular toxicity after ifosfamide in younger children may have serious implications for future growth and development.

Age Factors↗
PubMed1991

Assessment of chemotherapy-associated nephrotoxicity in children with cancer.

Assessment of the toxicity caused by chemotherapy in children with cancer has become more important as the number of long-term survivors has continued to increase. It is vital to monitor both acute life-threatening adverse effects and long-term toxicity that may impair the child's development and cause permanent morbidity. Renal damage may follow treatment with cytotoxic drugs, especially cisplatin or ifosfamide, and lead to glomerular, proximal tubular or distal tubular impairment or to any combination of these. Greater understanding of nephrotoxicity and of its prevention may enable the use of more intensive schedules or of higher doses of potentially nephrotoxic chemotherapy. However, the evaluation of cytotoxic drug-induced nephrotoxicity has frequently depended mainly on measurement of the plasma creatinine concentration, which may remain normal despite substantial glomerular impairment or severe tubular dysfunction. Detailed assessment of nephrotoxicity depends on an understanding of normal renal physiology and requires evaluation of all aspects of function. A comprehensive but simple investigatory protocol that enables assessment of the nature and severity of nephrotoxicity in children is described, which can be performed without admission to hospital. Glomerular function is assessed by measurement of the glomerular filtration rate from the plasma clearance of [51Cr]-ethylenediaminetetraacetic acid ([51Cr]-EDTA). Proximal nephron function is evaluated in three ways: by measurement of the concentration of calcium, magnesium, phosphate, glucose and urate in blood and urine along with calculations of their fractional excretion and of the renal threshold for phosphate; by determination of the excretion in urine of low-molecular-weight proteins (e.g. retinol-binding protein); and by investigation of urinary bicarbonate excretion in patients who are acidotic. Distal nephron function is initially investigated by examination of the concentration (osmolality) and acidification (pH) of an early morning sample of urine. Finally, a group of general investigations is performed, including quantitation of urinary excretion of renal tubular enzymes (e.g. N-acetylglucosaminidase) and measurement of blood pressure.

Acid-Base Equilibrium↗
PubMed1991

Cytogenetic analysis of a congenital fibrosarcoma.

Congenital (infantile) fibrosarcoma is a rare soft tissue sarcoma occurring in children aged less than 5 years. We performed cytogenetic analysis on such a tumor, which had an abnormal karyotype: 48,XY, +11, +20. Three other reports of karyotypes in congenital fibrosarcoma describe similar cytogenetic changes, and a specific pattern of trisomies that may prove diagnostic for this tumor is beginning to emerge.

Fibrosarcoma↗
PubMed1991

The influence of serum methotrexate concentrations and drug dosage on outcome in childhood acute lymphoblastic leukaemia.

Sequential methotrexate (Mtx) absorption studies were undertaken in 127 children undergoing treatment for childhood non-T acute lymphoblastic leukaemia (ALL) to determine whether serum drug concentration, clearance and dosage affect event free survival (EFS). Higher serum concentration and area under the plasma concentration curve (AUC) were not associated with an improved EFS. Methotrexate clearance was not found to be of prognostic significance. Patients who tolerated only low 6-mercaptopurine (6-MP) doses because of neutropaenia and those who randomly were prescribed higher doses of Mtx had a lower rate of leukaemia relapse after the completion of therapy. This suggests that the use of maintenance therapy in maximally tolerated doses may be associated with an increased survival in childhood ALL.

Administration, Oral↗