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Biomedical subjects

A D Pearson

Publications and source records attributed to A D Pearson.

At least 163 records · Page 9Linked to original sources
PubMed1991

Routine histological compared with immunohistological examination of bone marrow trephine biopsy specimens in disseminated neuroblastoma.

The ability to detect infiltration in bone marrow biopsy specimens from patients with disseminated neuroblastoma was assessed by immunohistological and routine histological methods. Frozen cores from 33 staging procedures were tested with UJ13A and UJ127.11. Immunopositive tumour cells were found in 10 of 17 staging procedures in which tumour was detectable by routine histological methods. Positive cells or stromal material were also found in eight of 12 staging procedures in which distorted architecture and fibrosis, but no obvious tumour, had been noted. Paraffin wax embedded cores from 29 of the same staging procedures were tested with antibodies against neurone specific enolase and neurofilament. Only a single core reacted with anti-neurofilament antibody. Neurone specific enolase positive cells or stromal material were found in nine of 15 staging procedures in which obvious tumour was detectable. Although these immunohistochemical techniques proved inferior to routine histology in their ability to detect obvious tumour, the demonstration of immunopositive stromal tissue which was not frankly malignant supports the view that distorted, fibrotic marrow may reflect persistence of neuroectodermal tissue and justifies its distinction from normal marrow when reporting the response to treatment.

Adolescent↗
PubMed1991

Urinary retention--an unusual dystonic reaction to continuous metoclopramide infusion.

Vomiting is one of the most distressing adverse effects of cancer chemotherapy. Metoclopramide by continuous infusion (400 micrograms/kg/h after a loading dose of 2.5 mg/kg) is a novel administration method for optimizing efficacy. A two-year-old boy developed urinary retention on three occasions, once accompanied by priapism and slurred speech, while receiving a continuous infusion. This was reversed by procyclidine, suggesting that it may have been a dystonic reaction.

Child, Preschool↗
PubMed1990

Ototoxicity of cisplatinum in children and adolescents.

Twenty-two children and adolescents who had received cisplatinum for the treatment of solid tumours underwent audiometry to ascertain the extent of hearing damage. Five patients complained of hearing difficulties, causing difficulty at school in one child. Hearing loss greater than 20 decibels occurred in four patients at 1,000 Hz, seven at 2,000 Hz, 13 at 4,000 Hz and 21 at 8,000 Hz. Median hearing loss was greater at higher frequencies (P less than 0.0001), and with increasing cumulative dose of cisplatinum. However, a 'plateau' phenomenon was observed, with no apparent further deterioration in hearing loss at doses greater than 600 mg m-2. Two children who had received prior aural radiotherapy had severe hearing loss. Severe, mostly asymptomatic, ototoxicity is common in children given cisplatinum. However, there is considerable interpatient variability in the hearing loss suffered.

Adolescent↗
PubMed1990

Short duration, high dose, alternating chemotherapy in metastatic neuroblastoma. (ENSG 3C induction regimen). The European Neuroblastoma Study Group.

Fifty-one children, aged from 15 months to 13 years 5 months with metastatic neuroblastoma presenting sequentially at the participating institutions received four 3 to 4 weekly courses of high dose multiagent chemotherapy. High dose cisplatin (200 mg m-2) combined with etoposide (500 mg m-2), HIPE, was alternated with ifosfamide (9 g m-2), vincristine (1.5 mg m-2), and adriamycin (60 mg m-1), IVAd. Disease status was re-evaluated 3 to 4 weeks after the fourth course and the response classified according to the International Neuroblastoma Response Criteria (INRC). The overall response rate in evaluable patients was 55% and response rates by site were: bone marrow 67% (complete response 47%); bone scan 68%; primary tumour 61%, and urinary catecholamine metabolites (VMA/HVA) 95%. Serial 51Cr EDTA renal clearance studies showed a glomerular filtration rate (GFR) decline in 40% of patients but in only seven cases to below 50% of the pretreatment value. There was no instance of renal failure during induction, though two patients developed severe renal failure following 'megatherapy' given to consolidate remission. Serial audiometry showed a significant decline in hearing at frequencies above 2,000 Hz in 37% of children but at or below 2,000 Hz in only 17%. Neutropenia and thrombocytopenia were severe and intravenous antibiotics were required after 30% of courses. Each of two treatment-related deaths occurred during pancytopenia following courses of IVAd. Complete, or greater than 90%, removal of primary site tumour was possible in 70% of cases following this induction regimen and 75% of patients proceeded to elective megatherapy within a median time of 24 weeks after diagnosis. This short intensive induction programme is highly effective at achieving cytoreduction, enabling early surgery and early megatherapy procedures. It is, however, too early to draw firm conclusions about the impact of this approach to treatment on the cure rate.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

The effect of pharmacological modification of gastric emptying and mouth-to-caecum transit time on the absorption of sugar probe marker molecules of intestinal permeability in normal man.

The present study examined the hypothesis that altered motility of the gastrointestinal tract affects absorption of probe markers of intestinal permeability. Seven healthy subjects, aged 32-44 years, received saline, 600 micrograms atropine or 10 mg metoclopramide in randomized order at weekly intervals. After 10 min they ingested a test solution containing 5 g lactulose, 5 g mannitol and 2 g 3-O-methyl glucose in 100 ml tap water. The molarity of the solution was 542 mmol l-1 and the dose administered was 80 ml m-2 body surface area. Gastric emptying was measured by ultrasound, mouth-to-caecum transit time by breath hydrogen analysis and sugar concentrations by gas-liquid chromatography. Gastric emptying half-times (min) were [mean (95% confidence intervals)] 14.9 (11:4-18.5) after saline, 22 (18.7-25.2) after atropine and 10.3 (7.0-12.6) after metoclopramide (P less than 0.002). Transit times (min) were 68.9 (52-85.2) after saline, 143 (126-159) after atropine and 38 (21.2-54.5) after metoclopramide; P less than 0.0001. Analysis of plasma levels of mannitol and 3-O-methyl glucose showed a significant within-subject effect of drug with time (P less than 0.03). Urinary excretion of mannitol in the first 5 h after ingestion of the test solution was 1256 (974-1620) mg after saline, 1560 (1210-2013) mg after atropine and 955 (740-1232) mg after metoclopramide (P less than 0.03). There were no significant differences in lactulose and 3-O-methyl glucose urinary excretion between drug treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Nephrotoxicity after ifosfamide.

Eleven children and adolescents with previously normal renal function who received ifosfamide for the treatment of extrarenal solid tumours underwent detailed investigation of glomerular and renal tubular function to assess the incidence and extent of renal damage. None had received cisplatin. Glomerular filtration rate (measured by plasma clearance of 51Cr labelled edetic acid) was reduced in six children. All 11 patients had evidence of proximal, and six of distal, tubular damage. Proximal tubular toxicity was indicated by phosphaturia and hypophosphataemia (n = 4), glycosuria (n = 5), increased urine beta 2 microglobulin excretion (n = 11), and generalised aminoaciduria (n = 10); distal tubular damage caused a reduction of the osmolality of the urine in an early morning sample. Two children developed clinical hypophosphataemic rickets, and one of these also had severe nephrogenic diabetes insipidus. Glomerular and tubular nephrotoxicity are common and potentially serious complications of ifosfamide treatment in children.

Adolescent↗
PubMed1990

Virus infections in bone marrow transplant recipients: a three year prospective study.

Over three years 81 consecutive bone marrow transplant recipients (32 allogeneic and 49 autologous) who received prophylaxis with acyclovir, were studied for symptomatic virus infection. Thirty nine infections were documented in a total of 28 patients. Thirty two infections were mild, five were moderately severe, and two were severe. Cytomegalovirus infection occurred in only six allogeneic recipients. Herpes simplex virus and varicella zoster virus infections occurred infrequently. Seven patients who were considered at the time of death to have died due to an infectious cause were studied virologically at necropsy. In only one patient was a virus infection thought to have been the cause of death. Prophylaxis with acyclovir may have influenced the rate and clinical prominence of herpes virus infections. In this study viruses were considered to have had a relatively minor role in causing morbidity and mortality.

Acyclovir↗
PubMed1990

An in vitro predictive test for clinical graft-versus-host disease in allogeneic bone marrow transplant recipients.

An in vitro skin explant model has been used in an attempt to predict the severity of graft-versus-host disease (GVHD) in HLA-identical donor-recipient pairs. The skin explant model involves the use of donor lymphocytes which have been sensitized against recipient lymphocytes in vitro and then co-cultured with the recipient's skin. Thirteen patients were studied in a prospective manner and results from the skin explant model compared with the clinical status of the patient post-transplant showed good correlation (p less than 0.001). Results from T cell-depletion studies indicated a role for both CD4 and CD8 positive cells in GVHD. In conclusion the results confirmed that the skin explant assay is a useful and predictive test of GVHD in humans.

Adult↗
PubMed1989

A preliminary study of serum class II levels in healthy individuals and bone-marrow transplant patients.

A double-determinant ELISA has been developed to measure class II major histocompatibility complex molecules in blood from healthy individuals and patients who received either an allogeneic or an autologous bone-marrow transplant. Levels were higher in pre-transplant patients than in healthy individuals, and in the majority of patients, these levels rose even higher at 4 weeks post-transplantation. At later times after transplantation, it was difficult to draw firm conclusions, because the number of values available were too limited. Nevertheless, in the autologous group with no graft-versus-host disease (GVHD), levels were consistently lower at 6 months and one year; in the allogeneic group these long-term levels varied. As class II antigens are expressed on skin and rectal epithelia in GVHD, this study suggests that serial measurement of serum class II levels may be useful for monitoring GVHD in bone-marrow transplantation.

Adult↗
PubMed1989

Toxicity of high-dose ifosfamide in children.

Ifosfamide has been shown to be an active agent in the treatment of several childhood cancers. However, the optimal dose and method of administration remains to be established. The dose/response relationship of ifosfamide suggests that a maximum tolerable, fractionated dose be given, and to reduce hospitalisation this dose should be given in the shortest possible time. A total of 20 patients aged 1-23 years received 124 courses (mean, 6 courses/patient; range, 1-16); 9 subjects had either relapsed or resistant disease, and all of these had previously received cyclophosphamide. A dose of 3 g/m2 ifosfamide was given for 2 (five patients) or 3 (15 patients) successive days. In all, 9 patients received the drug twice daily as a bolus and 11 were given a continuous infusion. All patients received 3 g/m2 mesna per day with ifosfamide and for 12 h there after, and hydration was maintained with 3 l/m2 fluid daily. Myelosuppression occurred in all patients but was mild and reversible, with no toxic deaths. On four occasions in three patients treatment had to be delayed due to myelosuppression. Seven episodes of fever and neutropaenia were successfully treated with antibiotics. The mean glomerular filtration rate in 13 patients at the start of treatment was 104 ml/min per 1.73 m2 and at the end was 92 ml/min per 1.73 m2. In all, 19 patients had microscopic and 1 macroscopic haematuria, with no clinical sequelae. Two patients with grossly impaired renal function following previous cisplatin therapy may have been precipitated into terminal renal failure by the ifosfamide therapy. Only one person developed neurotoxicity, which recurred on further treatment with ifosfamide but was fully reversible. All patients had moderate to severe vomiting, which was controlled with anti-emetics. No abnormalities of liver or cardiac function were detected. We conclude that ifosfamide given by this schedule is safe in patients with normal renal function.

Adolescent↗
PubMed1989

Strain variation in Campylobacter pylori detected by numerical analysis of one-dimensional electrophoretic protein patterns.

A total of 21 clinical isolates of Campylobacter pylori from Peru and the United Kingdom and two reference strains (from Australia), including the type strain (NCTC 11637T), were characterized by high resolution one-dimensional SDS-polyacrylamide gel electrophoresis of cellular proteins. The protein patterns contained more than 40 discrete bands and the approximate molecular weights of the major bands were 22, 27, 46, 57, 60, 65 and 93 kD. The total patterns were used as the basis of numerical analysis. Most strains were clustered in four phenons at 91% similarity with the exception of six ungrouped strains. Overall similarity was high with all strains linked in the phenogram at greater than or equal to 81%. Variation among strains was attributable principally to qualitative and quantitative band differences in the 47 to 56 kD (hypervariable) region of the C. pylori protein profile. From the analysis, ten different electropherotypes (EP-types) were identified. We demonstrated that differences were detectable among isolates from widely separated geographical locations as well as from the same location, although multiple isolates from two Peruvian patients had the same electropherotype. Our results indicate that determination of protein profiles provides the basis of a reproducible method for characterization of C. pylori isolates.

Bacterial Proteins↗
PubMed1989

Active and passive sugar absorption in pancreatic insufficiency.

Urinary excretion of lactulose, mannitol, and 3-0-methylglucose, following oral administration (5 g, 5 g, and 2 g, respectively, in 100 ml H2O; 80 ml/m2), has been measured in subjects with cystic fibrosis (CF) (22), Shwachman syndrome (3), chronic pancreatitis (3), and normal controls (46). Mean lactulose excretion was increased 10-fold in CF (p less than 0.001), and two-fold in other disorders associated with pancreatic insufficiency (PI) (p less than 0.05). Mean mannitol excretion was 1.6 times greater in CF (p less than 0.001), compared with controls, but was reduced in other forms of PI (p less than 0.03). The mean lactulose/mannitol excretion ratio was increased in all types of PI (p less than 0.001). There were no significant differences in 3-0-methylglucose excretion. This study confirms the large increase in lactulose absorption recently reported in CF and also demonstrates increased absorption of mannitol; these changes are different than those in other forms of PI. This study provides further evidence for a specific abnormality of the mucosal barrier to the absorption of passively absorbed, water soluble molecules in CF.

3-O-Methylglucose↗