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Biomedical subjects

P Parsons

Publications and source records attributed to P Parsons.

At least 37 records · Page 2Linked to original sources
PubMed1994

The Nambour Skin Cancer and Actinic Eye Disease Prevention Trial: design and baseline characteristics of participants.

The Nambour Skin Cancer and Actinic Eye Disease Prevention Trial (the Nambour Trial) is a field trial conducted in an unselected adult population in Australia. Using a randomized 2 x 2 factorial design, the principal aim is to evaluate whether regular use of high-protection sunscreen and/or dietary supplementation with beta-carotene (30 mg daily) can alter the incidence rates of basal cell carcinomas and squamous cell carcinomas of the skin over a minimum follow-up time of 4.5 years. Changes in the incidence of solar keratoses and actinic eye disease and the rate of photoaging after intervention will also be investigated. In 1992, 1626 participants between the ages of 25 and 75 years were enrolled, all of whom had been randomly selected from residents of the southeastern Queensland township of Nambour for an earlier skin cancer prevalence survey. This paper describes the background to the trial and its design, with respect to evaluation of effects on actinic skin disease, and documents the baseline characteristics of participants recruited into the Nambour Trial.

Adult↗
PubMed1992

Gut and liver coordinated metabolic response following major torso injury.

Major trauma provokes a stress response which is mediated, in part, via glucagon, catecholamines, and cortisol. These stress hormones modulate the choice of energy substrate for various tissues. While glucose and fatty acids are considered the preferred fuels, ketone bodies (26/ATP/mole) may be a viable alternative. In this study, we measured the concentrations of acetoacetate and beta-hydroxybutyrate (3-OHB) in the portal as well as systemic circulations of 10 critically injured patients (revised trauma score = 6.8 +/- 0.5, injury severity score = 27 +/- 3) during the first 5 postoperative days. At 6 hr postinjury, 3-OHB was elevated in the portal system (0.34 +/- 0.01 mM) while depressed systemically (0.09 +/- 0.02 mM), indicating that the gut was capable of ketogenesis. In contrast, at 24 hr, 3-OHB rose systemically (0.39 +/- 0.02 mM) while decreasing in portal blood (0.09 +/- 0.01 mM) implying gut ketone consumption. Moreover, the systemic ketone body ratio became elevated at 24 hr, suggesting an enhanced liver energy status. In summary, we believe ketogenesis is stimulated by major trauma. Initially, the gut supports ketone concentration in the systemic circulation, whereas, by 24 hr, the gut becomes a ketone consumer and the liver maintains circulating levels.

Abdominal Injuries↗
PubMed1991

Selective uptake of glutamine in the gastrointestinal tract: confirmation in a human study.

Recent animal data suggest that the gut plays a far more important metabolic role than previously thought. During critical illness, disruption in bowel barrier function may result in a chronic hypermetabolic state and contribute to multiorgan failure. Animal studies have demonstrated that enterocytes of the gastrointestinal tract use glutamine as a respiratory fuel and during critical illness the consumption of glutamine by the gut significantly increases. The selective uptake of glutamine by the gut, to date, has not been confirmed in humans. Seven patients who sustained multisystem trauma necessitating laparotomy underwent portal venous catheterization. This was done by carefully reopening the obliterated umbilical vein and facilitating access to the left branch of the portal vein using a standard central venous catheter. Portal venous and systemic blood samples were recorded for 5 days after operation. Amino acid levels in both circulations were recorded at 48 h and 5 days. Using Student's t test for related samples, the differences between individual amino acids in portal and systemic circulations were compared. At 48 h, mean(s.d.) portal venous glutamine was 85(5) per cent of the systemic levels (253(80) compared with 296(90) mumol/ml, P less than 0.002). At 5 days, portal glutamine was 87(3) per cent of the systemic levels (255(69) compared with 292(83) mumol/ml, P less than 0.003). Levels of citrulline, a breakdown product of glutamine metabolism, were elevated in the portal venous circulation at 48 h (20(4) compared with 16(3) mumol/ml, P less than 0.005) and at 5 days (21(5) compared with 14(3) mumol/ml, P less than 0.002). No significant differences between any of the other amino acids analysed were identified. This study confirms, for the first time in humans, that selective uptake of glutamine occurs in the gut. In stressed states, glutamine deficiency is associated with gut mucosal atrophy. This has significant implications as glutamine is not provided in most commercially available parenteral and enteral nutrition formulations.

Adolescent↗
PubMed1989

Sputum induction for diagnosis of Pneumocystis carinii pneumonia.

51 patients infected with the human immunodeficiency virus (HIV) and with suspected Pneumocystis carinii pneumonia underwent sputum induction. Sputum specimens from 18 patients were positive for P carinii and patients were treated appropriately 25 of the 33 patients with negative specimens underwent bronchoscopy and bronchoalveolar lavage within 4 days of sputum induction, only 1 of whom had evidence of Pneumocystis infection. For diagnosis of Pneumocystis carinii pneumonia, sputum induction according to a strict protocol had a sensitivity of 94.7% and a negative predictive value of 96%, compared with bronchoalveolar lavage.

Acquired Immunodeficiency Syndrome↗
PubMed1989

In vitro sensitivity of ovarian cancer as determined by a short-term biochemical assay: comparison between primary and metastatic sites in the same patient.

Tumor sensitivity of ovarian cancer to cytotoxic drugs in vitro was examined between paired samples taken from the primary tumor and its metastases in the same patient. A 3-hour assay of primary cultures of the tumor was used to determine cellular response to the drugs by measurement of the incorporation of [3H]thymidine. Although there was variability, a reasonable correlation was found between the primary tumor and its different metastases, between the different metastases, and between the different tumor sites and cells from the peritoneal fluid. However, there was discordance between some of the pairings; the rate varied between 12 and 42% when the criterion was greater than 20% inhibition. Consistent drug sensitivity for all sites tested was present in only 8 of the 18 patients. Because of the discordance in some pairings, attempts should be made to sample all metastatic tumors, particularly those which cannot be removed completely by surgery. The discordant subgroup may be a source of false-negative and false-positive results of the assay.

Cisplatin↗
PubMed1989

Histologic features predictive of an increased risk of early local recurrence after treatment of breast cancer by local tumor excision and radical radiotherapy.

A histopathologic review was undertaken of 293 patients with breast cancer treated by local tumor excision and radical radiotherapy. In a 6-year period, there were 37 local treatment failures with 16 deaths, and an additional 20 patients died without local recurrence. Pathologic data were available for 272 patients. Multivariate analysis indicated that the pathologic features in an invasive tumor most predictive for local recurrence were the combination of a high proportion of intraduct carcinoma with extensive necrosis (comedocarcinoma). Of 18 patients with these features, nine have had early local recurrence (a risk of 50% with these features vs 10% in those without), and four have died (a risk of 22% against 12%). Despite the short follow-up, the results already appear significant, and the study is ongoing. The importance of comedonecrosis in the intraduct component as a prognostic indicator in invasive carcinoma of the breast is not widely recognized and might constitute a relative contraindication to conservative treatment of the breast.

Actuarial Analysis↗
PubMed1988

A Taqi RFLP of the human TGF alpha gene is significantly associated with cutaneous malignant melanoma.

A TaqI restriction fragment length polymorphism (RFLP) of the human transforming growth factor alpha (hTGF alpha) locus was analyzed in DNA from 63 normal individuals, 34 malignant melanoma (MM) cell lines, and 18 melanoma biopsy specimens. The frequency of a 2.7-kb allele (0.18) in MM cell lines was significantly higher (p less than 0.01) than in lymphoblastoid cell lines (LCLs) derived from unaffected controls (0.05). The frequency (0.14) in MM biopsies was similar to that in MM cell lines although, owing to the small numbers investigated, it was not significantly higher than in controls. In the case of 5 MM patients who were constitutionally heterozygous for alleles at the TGF alpha locus, no apparent losses of heterozygosity were observed in the corresponding tumour DNA. Thus, the constitutional presence of the 2.7-kb allele may be a risk factor for melanoma.

Alleles↗
PubMed1988

Serial D-dimer levels in the assessment of tumor mass and clinical outcome in ovarian cancer.

D-dimer (DD)--an end product of fibrinolysis--was measured in serum by enzyme immunoassay using a monoclonal antibody to the gamma gamma crosslink in patients with ovarian cancer, before primary surgery and during chemotherapy for 12 months or more. Serial DD levels were found to have a high sensitivity for the detection of tumor in patients with subclinical disease (91%) as well as for predicting progression of disease (100%). As determined by a careful second-look laparotomy in patients with complete clinical remission the DD marker was highly predictive of tumors less than 1 cm. The negative predictive value (82%) was higher than the positive predictive value (69%). However, there were 31% of the patients who showed a false-positive result; a close examination of the clinical data of these 9 patients failed to reveal an explanation for the positive DD levels. Despite the lack of specificity (50% in the present series), the findings support the use of DD in the assessment of patients with ovarian cancer, especially those with subclinical disease.

Antibodies, Monoclonal↗
PubMed1988

Pathological features of invasive breast cancer associated with a high risk of local recurrence after tumour excision and radical radiotherapy.

The histological slides of 273 breast cancer patients, treated by local excision and radiotherapy and followed up for 2-6 years, were reviewed in search of factors predictive of local recurrence. Local recurrence was found to be most closely related to the combination of a high proportion of intraduct carcinoma and extensive necrosis (comedocarcinoma). This latter group of 18 patients had a local recurrence rate of 50%. These patients are of particular interest since they form a small group with readily identifiable histological features.

Breast Diseases↗
PubMed1986

Processing of pro-vitellogenin in insect fat body: a role for high-mannose oligosaccharide.

Several discrete events were resolved in the processing of vitellogenin in Blattella germanica. Using tunicamycin to inhibit the synthesis of high-mannose oligosaccharide, a high molecular weight pro-vitellogenin peptide (apo-proVG, Mr 215,000) was identified in fat body. Dosages of tunicamycin which inhibited glycosylation of vitellogenin by 98% inhibited its synthesis by as much as 59%, yet led to an intracellular accumulation of apo-proVG. Reversibility and dose dependency of these effects on vitellogenin synthesis, glycosylation, proteolytic processing, and secretion were demonstrated. In control insects, glycosylation of apo-proVG yielded a Mr 240,000 pro-vitellogenin peptide (proVG). FITC-Concanavalin A bound to purified proVG but not to apo-proVG, thus confirming an absence of high-mannose oligosaccharide in the apo-protein. Following its glycosylation, proVG was processed rapidly in fat body to Mr 160,000 (VG160) and Mr 102,000 (VG102) peptides which subsequently were secreted into hemolymph. After uptake into developing oocytes, the VG160 peptide was processed further prior to chorionation, yielding subunits of Mr 95,000 and 50,000. Uniqueness of the peptides of mature vitellin (Mr 102,000, 95,000, and 50,000) was indicated by comparison of the CNBr fragments of each purified subunit. Staining of CNBr fragments with FITC-Concanavalin A also indicated that high-mannose oligosaccharides are attached at one or more sites within each vitellin subunit. Resolution of the substructure of this insect vitellin and identification of events involved in the processing and secretion of its fat body apo-protein provide a basis for further study of the assembly and transport of vitellogenin, its packaging in eggs, and utilization during embryogenesis.

Adipose Tissue↗
PubMed1984

Multiple sequential biomarkers in monitoring patients with carcinoma of the lung.

To correlate serial biomarkers and disease activity in carcinoma of the lung, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), adrenocorticotropic hormone (ACTH), C3-derived protein (C3DP-C), and LDH were assayed in 43 patients with small cell lung carcinoma (SCLC) and in 20 patients with non-small cell lung cancer (NSCLC) (15 with adenocarcinoma, three with squamous cell carcinoma, and two with mixed histology). Disease status after treatment was rated as one of the following: complete response, partial response, minor regression, stable disease, and progressive disease. Significant correlations between disease status and markers in SCLC were found for CEA, NSE, LDH, and ACTH. In NSCLC, only CEA and LDH showed significant correlation. Marker-marker correlations were significant in SCLC for CEA and NSE (P less than 0.05), CEA and LDH (P = 0.01), and NSE and LDH (P less than 0.01); in NSCLC none were significant. None of the markers exhibited significant correlations with specific metastatic sites. Certain biomarkers (CEA, NSE, and LDH in SCLC; CEA and LDH in NSCLC) can be used alone or in combination to monitor disease activity but appear to be no more sensitive than standard clinical investigational methods.

Adenocarcinoma↗
PubMed1979

Kinetic characterization of long chain fatty acyl coenzyme A ligase from rat liver mitochondria.

Long chain fatty acyl coenzyme A ligase (EC 6.2.1.3) purified from rat liver mitochondria has been characterized with respect to several kinetic parameters. Many of the kinetic properties of the mitochondrial enzyme are similar to those of the purified microsomal enzyme with respect to palmitoyl-CoA formation, but there are distinct differences. The fatty acid and nucleotide specificities of the mitochondrial enzyme are similar to those of the microsomal enzyme, as are the apparent Km values for ATP and coenzyme A. On the other hand, the mitochondrial enzyme differs from the microsomal enzyme in that it has a lower pH optimum, is different in molecular weight, and does not show simple saturation kinetics with palmitate as substrate. Of particular interest is the evidence presented which indicates that the mitochondrial long chain fatty acyl-CoA ligase, unlike short and medium chain ligases, does not utilize an acyladenylate as an intermediate in the formation of fatty acyl-CoA.

Animals↗
PubMed1979

Purification and characterization of cytochrome c oxidase from rat liver mitochondria.

Cytochrome c oxidase has been purified from rat liver mitochondria using affinity chromatography. The preparation contains 10.5 to 13.4 nmol of heme a + a3 per mg of protein and migrates as a single band during polyacrylamide gel electrophoresis under nondissociating conditions. It has a heme a/a3 ratio of 1.12 and is free of cytochromes b, c, and c1 as well as the enzymes, NADH dehydrogenase, succinic dehydrogenase, coenzyme Q-cytochrome c reductase, and ATPase. The enzyme preparation consists of six polypeptides having apparent Mr of 66,000, 39,000, 23,000, 14,000, 12,500 and 10,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The peptide composition is similar to those found for cytochrome c oxidases from other systems. The enzymatic activity of the purified enzyme is completely inhibited by carbon monoxide or cyanide, partially inhibited by Triton X-100 and dramatically enhanced by Tween 80 or phospholipids.

Animals↗