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Biomedical subjects

R E Pugh

Publications and source records attributed to R E Pugh.

12 recordsLinked to original sources

Onshore catering increases the risk of diarrhoeal illness amongst cruise ship passengers.

Of 134 Queensland passengers on a cruise, 91 (67.9%) people reported various illnesses including 41 (30.6%) who reported diarrhoeal symptoms. Queensland passengers who ate while onshore at non-Australian ports were significantly more at risk of developing diarrhoeal symptoms than those who did not. Passengers were particularly at risk when they ate onshore while undertaking a tour compared with those who did not undertake this tour. Travellers should be warned of the possibility of contracting diarrhoeal illness from onshore catering.

Adolescent↗

CD19 selection improves the sensitivity of B cell lymphoma detection.

Reinfusion of residual tumor cells into B cell non-Hodgkin's lymphoma (B-NHL) patients during autologous transplantation may be an important cause of disease relapse. Determining the extent to which B-NHL cells are present in autologous progenitor cell products and if the presence of residual B-NHL cells is predictive of relapse will require extremely sensitive methods of detecting rare B-NHL cells. We attempted to improve the sensitivity of polymerase chain reaction (PCR)-based detection of rare B-NHL cells by preselecting CD19+ cells using an immunomagnetic column. To measure detection sensitivity, we prepared samples containing different levels of B-NHL cell contamination by mixing B-NHL cell lines containing the chromosomal translocation t(14;18) bcl-2/JH) with control leukapheresis samples. DNA extracted from each CD19-selected sample and from each matched nonselected sample was added to a PCR to amplify the bcl-2/JH breakdown junction. CD19 preselection improved the sensitivity of detection of t(14;18)-positive B-NHL cells 115-fold, so that B-NHL cells at a concentration of 1 tumor cell per 1 x 10(6) hematopoietic cells were detected in every specimen evaluated. t(14;18)-positive cells were not detected in any of 13 control leukapheresis specimens. We conclude that a combination of CD19 preselection and PCR amplification may improve the sensitivity of detection of rare lymphoma cells by two orders of magnitude without a significant decrease in specificity.

Antigens, CD19↗

Six point mutations that cause factor XI deficiency.

We have identified six novel types of mutation that cause factor XI deficiency, an inherited bleeding disorder. Two are point mutations that interfere with the normal splicing of exons in the mRNA and four are point mutations that result in amino acid substitutions. One of these amino acid substitutions (Asp 16-->His) is near the amino terminal end of the protein. The other three amino acid substitutions (Leu 302-->Pro, Thr 304-->Ile, and Glu 323-->Lys) are in the fourth apple domain, a region that mediates dimerization of identical subunits of factor XI. All four amino acid substitutions cause a reduction in the amount of factor XI secreted from cells grown in vitro.

Amino Acid Sequence↗

A molecular genetic study of factor XI deficiency.

Factor XI deficiency is a rare bleeding diathesis found predominantly in Ashkenazi Jewish kindreds. A recent study of six Jewish patients identified three distinct mutations (Types I, II, and III) in the factor XI gene that were sufficient to fully define the genotypes of the patients. We have investigated 63 patients with factor XI deficiency and find overall allele frequencies of 44% for the type II mutation, 31% for the type III mutation, and 0% for the type I mutation. Therefore, 25% of the mutant factor XI alleles in our sample remain undefined. However, the distribution of mutant alleles is significantly different between Jewish and non-Jewish populations with hitherto undefined mutations accounting for 84% of the disease alleles in non-Jewish patients. Plasma factor XI:C levels were found to differ significantly between different homozygous and compound heterozygous genotypes and the inheritance of the II/III genotype was found to carry an increased risk of the most severe bleeding tendency.

Alleles↗

A Southwest Oncology Group study on the use of a human tumor cloning assay for predicting response in patients with ovarian cancer.

A total of 211 patients with epithelial ovarian cancer (168 with tumors refractory to prior chemotherapy and 43 with no prior chemotherapy) from 33 different Southwest Oncology Group institutions had their tumors sampled and specimens shipped to two central laboratories for drug-sensitivity testing in a human tumor cloning assay. The 168 patients with a prior history of chemotherapy failure (median of four prior chemotherapeutic agents) were treated with the most effective agent(s) found in the cloning assay (23 patients), and those patients whose tumors did not form colonies in vitro or did not manifest any sensitivity to agent(s) were treated with a clinician's choice of agent(s) (101 patients). The remaining 44 of the 168 patients were not treated with chemotherapy because of deteriorating performance status or early death. The complete and partial response rate in patients treated according to assay results was 28% versus 11% for the patients treated according to clinician's choice (P = 0.03). There was no statistically significant difference in survival between the two options (6.25 versus 7 months, respectively). The 43 patients with no history of prior chemotherapy were all treated with standard combination chemotherapy, and their clinical response was compared with their in vitro sensitivity to the same agents. Overall there was a 100% true-positive rate and 100% true-negative rate for the seven evaluable patients. From these data the authors conclude that use of the human tumor cloning assay may increase the response rate but not the survival for selected patients with advanced chemotherapy-refractory ovarian cancer. The study is weakened, however, by the many steps of patient selection necessitated by inadequate tumor colony formation in vitro and the inability to treat all patients (because of early death or a rapid decline in performance status). The assay does appear to be worthy of additional study for predicting response to combination chemotherapy in patients without a prior history of chemotherapy. Finally the use of central chemosensitivity testing laboratories is feasible for testing in vitro predictive assays in a cooperative group setting.

Antineoplastic Combined Chemotherapy Protocols↗

Ablepharon macrostomia syndrome.

The association of congenital ablepharon with the absence of eyelashes and eyebrows, a wide mouth (macrostomia), and auricular, nasal, genital, and other systemic anomalies has been termed the ablepharon macrostomia syndrome. One such case is reported which illustrates the importance of immediate postnatal ocular management to minimise severe visual loss.

Abnormalities, Multiple↗

Effects on the development of Dipylidium caninum and on the host reaction to this parasite in the adult flea (Ctenocephalides felis felis).

Temperature was found to be a major factor affecting the development of Dipylidium caninum and the presence of a host reaction of adult Ctenocephalides felis felis to D. caninum. Adult fleas reared at 30-32 degrees C contained fully developed metacestodes when they emerged from their cocoons. However at lower temperatures, D. caninum could not complete development until the flea hosts had spent some time on their mammalian hosts. It was the surface temperature of the mammals (31-36 degrees C) and not the fleas' blood meals which resulted in the metacestodes completing their development. This development of D. caninum was therefore independent of the flea development. At 20 degrees C, a larger and more prolonged host reaction was mounted than at higher temperatures. The larval flea diet had a small effect on the subsequent cestode development and the adult fleas' reaction to it.

Animals↗

Factors affecting the development of Dipylidium caninum in Ctenocephalides felis felis (Bouché, 1835).

Ctenocephalides felis felis larvae were infected with Dipylidium caninum at a range of temperatures from 20 degrees - 35 degrees C at 3 mm Hg saturation deficit (SD) and 30 degrees C at 8 mm Hg SD. Hosts were subsequently dissected at 6, 9 and 12 days after infection. Four replicate experiments were performed and results of development, and host reactions analysed by the Genstat computer programme. These were found to depend on the temperature and saturation deficit of the environment. Unlike previous findings, parasite development and host reaction were found to be independent of host development. Host reaction was more marked and prolonged at 20 degrees - 25 degrees C than at higher temperatures. No perceptible growth of the parasite occurred at 20 degrees C. The development patterns of growth at the higher temperatures were similar but shifted in time so that faster growth occurred at higher temperatures. Rate of growth was fastest at 35 degrees C, despite the fact that this temperature was unfavourable to the hosts, all of which died at the time of pupation.

Animals↗

The Liverpool Visual Assessment Team: 10 years' experience.

The Liverpool Visual Assessment Team (VAT) was established in 1975 as a multidisciplinary service for the evaluation of the disabilities of visually handicapped children. Team membership and patterns of practice are described. Two hundred and fifty-four children have now been seen by the VAT over a 10-year period. The mean age of referral was 4.2 years; only 46% of the children had an isolated visual handicap. The aetiology of disabilities was known in 58% of the children. Genetically determined visual handicap was likely to be associated with normal intelligence. Ophthalmological diagnoses are described. In comparison to what would be predicted, there were fewer children with retinopathy of prematurity and more with cerebral (cortical) blindness. The educational needs and placements of the children are described and the implications of the implementation of the 1981 Education Act for visually handicapped children are discussed.

Adolescent↗