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Biomedical subjects

D Nicol

Publications and source records attributed to D Nicol.

At least 19 recordsLinked to original sources
PubMed2004

Are patents for methods of medical treatment contrary to the ordre public and morality or "generally inconvenient"?

"No one has advanced a just and logical reason why reward for service to the public should be extended to the inventor of a mechanical toy and denied to the genius whose patience, foresight, and effort have given a valuable new [discovery] to mankind" (Katopis CJ. Patents v patents: policy implications of recent patent legislation. St John's Law Review 1997;71:329). The law around the world permits the granting of patents for drugs, medical devices, and cosmetic treatment of the human body. At the same time, patentability for a method of treatment of the same body is denied in some countries on various public policy grounds. Is there any logical justification for this distinction? Are methods of medical treatment not as vital to the health or even to the life of a patient as drugs or medical devices? Why is a cosmetic result patentable and a curative result not?

Australia↗
PubMed2003

Prostatic and peripheral blood selenium levels after oral supplementation.

PURPOSE: The dietary trace element selenium has been proposed to be a potential chemopreventive agent for prostate cancer. Epidemiological studies have suggested an inverse association between blood selenium and prostate cancer incidence. However, to our knowledge no study to date has examined selenium absorption by the prostate. Therefore, we determine whether oral selenium supplementation alters selenium levels within the prostate and/or peripheral blood. MATERIALS AND METHODS: In this prospective trial 51 men undergoing transurethral resection of the prostate for benign prostatic hyperplasia were randomly assigned to serve as controls or receive 200 microg selenium daily orally for 1 month. Sample size was calculated to detect a difference of 30 ng/gm in prostate tissue with a power of 80%. Peripheral blood was obtained at enrollment and subsequently at surgery, when prostate tissue was also sampled. Selenium levels were determined using inductively coupled plasma mass spectrometry. RESULTS: Baseline erythrocyte selenium was within the standard reference range. Supplementation increased erythrocyte (initial median 173 and final median 209 ng/ml, p = 0.008) and prostate (supplement median 241 and control median 196 ng/gm, p = 0.016) levels. Erythrocyte levels at surgery correlated poorly with prostate levels in the control (r = 0.18) and supplement (r = 0.07) groups. CONCLUSIONS: Oral selenium supplementation increases prostatic and peripheral blood levels in men in a nonselenium deficient population. Blood and prostate levels correlated poorly, suggesting that peripheral blood measurements are a poor indicator of prostatic selenium content.

Aged↗
PubMed2002

Familial adult renal neoplasia.

Our understanding of the molecular mechanisms underlying the tumorigenesis of renal cell carcinoma (RCC) has partially come from studies of RCC related familial cancer syndromes such as von Hippel-Lindau (VHL) disease and hereditary papillary RCC (HPRC). These studies have led to the identification of RCC related genes, which, besides allowing accurate diagnosis of these diseases, have been found mutated or abnormally expressed in the sporadic counterparts of these familial renal tumours. To date, a number of renal tumour related syndromes have been described. We review recent advances in this field and discuss a genetic approach to managing familial cases of renal tumours occasionally encountered by cancer geneticists and urologists.

Adult↗
PubMed2001

Consent, commercialisation and benefit-sharing.

This article considers two issues in relation to the increasing commercial exploitation of biological materials: first, whether the consent of the individual who is the source of biological material is needed for the material to be used commercially; and secondly, whether the source has any right to share in the profits. Whilst the legal requirement for consent to commercial use is uncertain, the overwhelming view from ethical statements suggests that such consent is appropriate. With regard to profit-sharing, source individuals have no legal right to share in the profits of commercial exploitation of their sample. However, there is support in some ethical statements for benefit-sharing with source individuals and their communities.

Australia↗
PubMed2000

Corpus cavernosum as an alternative means of intravenous access in the emergency setting.

BACKGROUND: The present study was designed to investigate the feasibility of using the corpus cavernosum as an alternative means of intravenous access in the emergency setting. METHODS: The feasibility of achieving the infusion flow rates was first ascertained using direct intracavernous infusion of normal saline. The effect of atropine and adrenaline when given via this route was then studied. Hypovolaemic shock was then induced in dogs who were then actively resuscitated via this route using normal saline, Haemaccel and whole blood. RESULTS: Infusion flow rates were achieved for normal saline of 32.3, 50.3 and 67.3 mL per min at 100, 200 and 300 mmHg pressure, respectively. The peak effects of atropine and adrenaline via this route were seen at approximately 1 min after injection. Resuscitation using this method was uniformly successful in all dogs via the corpus cavernosum, with all reaching or exceeding their premorbid central venous pressure (CVP), and approaching or reaching their premorbid mean arterial pressure (MAP). In comparison the control dog's CVP and MAP did not rise during the period of observation after it was bled. CONCLUSIONS: The corpus cavernosum is a practical alternative means of intravenous access in the emergency setting in the dog model.

Adrenergic Agonists↗
PubMed2000

The effects of heparin and extracorporeal circulation on platelet counts and platelet microaggregation during cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass is associated with platelet activation and reduced platelet counts. Platelet activation may artifactually lower platelet counts by causing aggregation. In vivo platelet activation may increase existent platelet microaggregation ex vivo. We studied platelet counts and existent platelet microaggregation at different stages of cardiopulmonary bypass. METHODS: Twenty-one patients were studied before and after heparinization (300 U. kg(-1)) and at the end of cardiopulmonary bypass. Unaggregated (or single) platelets were counted in hirudin-anticoagulated blood, and total platelets were counted in ethylenediaminetetraacetic acid-anticoagulated blood. RESULTS: The total platelet count, 198 +/- 61 x 10(9). L(-1), was unaffected by heparin and stayed at 197 +/- 60 x 10(9). L(-1) (P =.7) but fell during extracorporeal circulation; the hemodilution-corrected count was 163 +/- 52 x 10(9). L(-1) (P =.0004). Heparinization reduced the unaggregated platelet count from (mean +/- 1 SD) 178 +/- 62 x 10(9). L(-1) to 155 +/- 60 x 10(9). L(-1) (P =.0001). Extracorporeal circulation had little additional effect. The hemodilution-corrected count was 142 +/- 48 x 10(9). L(-1) (P =.6). CONCLUSIONS: Heparinization caused platelet activation and increased existent platelet microaggregation ex vivo. During extracorporeal circulation, there was a reduction in total platelets that was greater than could be explained by hemodilution alone, but the unaggregated platelet count did not change significantly when corrected for hemodilution. Furthermore, the increased platelet microaggregation observed after heparinization was no longer evident after this loss. These findings suggest that during extracorporeal circulation, the platelets that formed into microaggregates after heparinization were lost from the circulation in preference to single platelets.

Adult↗
PubMed1999

The kinetics of mycophenolic acid and its glucuronide metabolite in adult kidney transplant recipients.

BACKGROUND: Mycophenolic acid kinetics have been reported to vary after renal transplantation, and mycophenolic acid area under the concentration-time curve (AUC) is the best predictor of suppression of graft rejection. METHODS: To determine whether mycophenolic acid kinetics vary after renal transplantation and to examine the potential role of enterohepatic recirculation, we investigated the kinetics of mycophenolic acid and mycophenolic acid glucuronide on days 2, 5, and 28 after transplantation in 10 kidney transplant recipients (male/female ratio, 1.5; mean age, 41.7 +/- 5.0 years) given 1 g mycophenolate mofetil twice a day. To facilitate therapeutic drug monitoring, we examined a limited sampling strategy for estimating 12-hour mycophenolic acid [AUC(0-12)]. RESULTS: The mean +/- SE AUC(0-12) for mycophenolic acid on day 28 was 38.5 +/- 1.6 mg x h/L, with a secondary peak 4 to 8 hours after dosing that was attributable to enterohepatic recirculation. Marked variability was shown in the kinetic profile of mycophenolic acid among patients across the three sampling days. Mycophenolic acid AUC(0-12) was positively predicted by both serum creatinine (P = .01) and serum albumin (P = .03) but not by time after transplantation, body weight, or trough concentration. Limited sampling (at 0, 1, 3, and 6 hours) accounted for 84.1% of the variability in the mycophenolic acid AUC(0-12) data and predicted the AUC(0-12) closely (r2 = 0.954) when evaluated in 10 different kidney transplant recipients. CONCLUSIONS: Mycophenolic acid AUC(0-12) is predicted by serum albumin and creatinine after kidney transplantation, and the AUC(0-12) may be determined during the early posttransplant period while the patient remains hospitalized with use of a limited sampling strategy to facilitate therapeutic drug monitoring.

Adult↗
PubMed1999

The human tissue kallikreins (KLKs 1-3) and a novel KLK1 mRNA transcript are expressed in a renal cell carcinoma cDNA library.

Renal cell carcinoma (RCC) is the most common form of kidney cancer, for which there is no biochemical marker. We and others have previously shown that a prostate specific antigen (PSA)-like protein is elevated in the serum of women with RCC. PSA is a member of the tissue kallikrein (KLK) gene family of enzymes. We have constructed a RCC cDNA expression library and screened it for PSA and KLK expression to determine whether they may be responsible for this PSA-like activity. Since immunoscreening of the RCC library for expressed PSA-like proteins was unsuccessful, polymerase chain reaction (PCR) analysis of the RCC cDNA library was performed using universal KLK primers, directed to the common regions in exon 3 and exon 5 of KLK1, KLK2 and KLK3. Sequences identical to all three KLKs were present in the RCC cDNA library. In addition, a novel KLK1 transcript with a 104 base pair deletion in exon 4 that predicted a C terminal sequence minus the crucial Ser190, was detected. The role of these tissue kallikreins in RCC and the significance of the variant KLK1 transcript is yet to be established. It is still unclear which of these gene products, if any, was detected in the sera of the women with RCC.

Alleles↗
PubMed1999

Expression of apoptotic regulatory molecules in renal cell carcinoma: elevated expression of Fas ligand.

Renal cell carcinoma (RCC) is the most common renal neoplasm. Despite being infiltrated by tumour infiltrating lymphocytes (TIL), these TIL are unable to control tumour growth in vivo, suggesting that the cytotoxic capacity of TIL against RCC is impaired, or that the tumour cells are resistant to killing and therefore escape detection by the immune system. It is postulated that the expression of apoptotic regulatory molecules in RCC favours tumour cell survival. The present study has therefore determined the expression of Fas (APO-1/CD95), Fas ligand (Fas L) and bcl-2 in these tumours. The expression of Fas, Fas L and bcl-2 mRNA transcripts was determined in RCC, normal kidney and peripheral blood by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), following RNA extraction and cDNA synthesis from tissues and cell samples. Transcript levels were measured by densitometry after Southern blot hybridization of PCR products with internal radio-labelled oligonucleotide probes; a densitometry score was assigned to each hybridizing DNA band and expressed as a ratio of the glyceraldehyde-3-phosphate dehydrogenase content. In peripheral blood, the expression of Fas L and bcl-2 transcripts was similar between patients and normal healthy individuals; however, Fas transcript expression was significantly down-regulated in the patients' versus normal peripheral blood (P = 0.026). Most interestingly, significantly up-regulated Fas L expression was observed in RCC compared to normal kidney (P = 0.041). In contrast, bcl-2 transcripts were well represented in normal kidney but markedly decreased in RCC (P = 0.021). The expression of Fas transcripts in normal kidney and RCC was variable. These data demonstrate elevated expression of Fas L transcripts in RCC, but the functional relevance of this remains to be investigated.

Adult↗
PubMed1998

Bilateral multiple renal oncocytomas and cysts associated with a constitutional translocation (8;9)(q24.1;q34.3) and a rare constitutional VHL missense substitution.

We report here on a patient with bilateral multifocal renal oncocytomas and cysts. Cytogenetic analysis of the patient's lymphocytes revealed a constitutional 46,XY,add (9)(q34.3) karyotype. The rearrangement was further resolved as a constitutional reciprocal t(8;9)(q24.1;q34.3) by microdissection and FISH. Because the 9q breakpoint was located in the same region as the tuberous sclerosis type I locus (TSC1), which is associated with renal tumors, we performed FISH with two TSC1 flanking cosmids that were mapped proximal to the 9q breakpoint, thus excluding its involvement. Loss of heterozygosity (LOH) studies of the tumors revealed LOH in chromosome I, further strengthening the molecular diagnosis of oncocytoma. A previously unreported germline missense substitution, Pro40Arg, in exon I of the VHL gene was also found in the patient's constitutional DNA, adding to the complexity of the genetic profile.

Adenoma, Oxyphilic↗
PubMed1998

Expression of cytokine mRNA transcripts in renal cell carcinoma.

Renal cell carcinoma (RCC) is a solid tumour of the kidney and is the most common renal neoplasm. Despite the presence of tumour infiltrating lymphocytes (TIL) in RCC, these tumours continue to progress in vivo suggesting a poor host immune response to the tumour, and the suppression of TIL effector function. Cytokines are key molecules that modulate the function of T cells. The possibility is investigated that the local production of cytokines in RCC contributes to immunosuppression of TIL. The expression of pro-inflammatory (IFN-gamma/IL-2) and immunosuppressive (IL-10/TGF-beta) cytokine mRNA transcripts was determined in RCC, normal kidney and peripheral blood of RCC patients using a semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) with cytokine-specific primers. Following Southern blot hybridization of the PCR products with internal radiolabelled oligonucleotide probes, cytokine transcript levels were measured by densitometry and expressed relative to the glyceraldehyde-3-phosphate dehydrogenase densitometry score. With the exception of IL-10, there were no differences in expression of cytokine mRNA transcripts between the peripheral blood of patients and normal healthy individuals. It was found that TGF-beta transcripts were well represented in normal kidney and RCC. In contrast, the expression of IFN-gamma transcripts, while low in the majority of samples, was significantly increased in RCC when compared to normal kidney (P=0.05). The IL-2 and IL-10 transcripts showed a more variable expression in normal kidney and RCC, with no significant differences in expression between the sample groups. The data demonstrating pro-inflammatory and immunosuppressive cytokine expression in RCC do not support a prominent immunosuppressive cytokine profile in these tumours.

Adult↗
PubMed1998

Transitional cell carcinoma in renal transplant recipients: the influence of compound analgesics.

OBJECTIVES: To determine the incidence of transitional cell carcinoma (TCC) in a renal transplant population and to compare the pattern of neoplasia in patients with analgesic nephropathy (AN) with that in other patients. PATIENTS AND METHODS: Using the Australia and New Zealand Dialysis and Transplant Registry, renal transplant recipients of the Princess Alexandra Hospital with TCC were identified. They were separated into two groups based on their primary disease, i.e. AN (group 1) and other causes of renal failure (group 2). The age at diagnosis of TCC, site, grade, stage of TCC and outcome were then compared between the groups. RESULTS: There were 250 (15%) patients in group 1 and 1424 (85%) in group 2; seven patients in each group were found to have TCC, which thus occurred more frequently in the AN group (2.8%) than in group 2 (0.49%). In group 1, five patients died, four from metastatic disease; of these, the mean time from transplantation to diagnosis of the initial tumour was 4.4 years, with a mean time from diagnosis to death of 9 months. In contrast, there were no deaths from metastatic disease in group 2. In group 1, all patients had upper tract tumours, with five patients also having bladder involvement. The upper tract tumours tended to be of a high stage and grade (grade II-III) and were aggressive. In group 2, all the tumours were confined to the bladder and tended to be of low stage and grade (grade I-II Ta). CONCLUSIONS: Patients undergoing renal transplantation as a result of AN are at high risk of developing TCCs of the upper urinary tracts. These tumours tend to be of a high grade and stage and the patients have a poor outcome. Screening with urine analysis and voided urine cytology do not appear to be reliable for the early diagnosis of upper renal tract TCCs in the renal transplant patient. We advocate annual cystoscopy and retrograde ureteric catheterization with washings, brushings and radiological imaging to diagnose upper tract TCCs at an early stage. These patients should also be screened before transplantation using the same technique.

Adult↗
PubMed1997

Characterisation of gamma delta T cells in renal cell carcinoma patients by polymerase chain reaction analysis of T cell receptor transcripts.

Renal cell carcinomas (RCC) contain tumour infiltrating lymphocytes (TIL) but these are essentially immunosuppressed in that they do not generate effective antitumour immune responses in vivo. These TIL comprise predominantly alpha beta T cells, although gamma delta T cells are also present. The repertoire of gamma delta T cells in RCC, however, has not been fully investigated. To identify the gamma delta T cell populations infiltrating RCC, this study has characterised the gamma delta T cell receptor (TCR) repertoire expression in these tumours and compared this to autologous normal kidney and autologous peripheral blood. A semi-quantitative reverse transcriptase/polymerase chain reaction technique was used for amplification of rearranged TCR V-C mRNA transcripts. Primers specific for the four human TCR V gamma and six V delta subfamilies were used, each in conjunction with a primer specific for either the C gamma or C delta region. The specificity of the PCR products was confirmed by Southern blotting and hybridisation with an internal C region probe. A densitometry score was assigned to each DNA band and the level of V gene expression was determined as ratio of C delta gene expression. The gamma delta TCR expression in each sample was determined as a ratio of C delta: glyceraldehyde phosphate dehydrogenase densitometry score. This demonstrated that TCR C delta gene expression was significantly higher in RCC compared to normal kidney (P < 0.019), suggesting a selective infiltration of gamma delta T cells into the tumour. Furthermore, we observed differences in the TCR V gamma and V delta repertoires between RCC and peripheral blood. V gamma l expression was significantly decreased (P < 0.043) whereas there was an over-representation of V gamma 4 transcripts (P < 0.028) in RCC compared to blood. A significant reduction in expression of both V delta 1 (P < 0.028) and V delta 3 (P < 0.051) was also observed within kidney tumour compared to peripheral blood. These findings show that expression of the gamma delta TCR repertoire in RCC differs from that in peripheral blood and normal kidney.

Carcinoma, Renal Cell↗
PubMed1997

Changes in folate supplementation, and in serum and red cell folate levels in antenatal patients over the course of a health promotion project for the prevention of neural tube defects.

We assessed the use of folic acid supplements and changes in serum and red cell folate levels in pregnancy over the course of a health promotion project in Western Australia by 4 cross-sectional studies of women attending a public antenatal outpatient clinic in 1992 (before the launch of the health promotion project), 1993, 1994, and 1995. A short questionnaire was completed and blood taken for estimation of serum and red cell folate. There was an increase in the proportion of women taking folic acid supplements in the first trimester (51.9% in the final phase) and before pregnancy (15% in the final phase of the study), and no change in the proportion taking other vitamin supplements. Serum and red cell folate levels increased significantly over the study period in both women taking and not taking folic acid supplements. The proportion of women who had seen the pamphlet used in the health promotion project rose to 35.4% in the third phase, and fell to 27.8% in the final phase. Coincident with the health promotion project, there was an increase in folate status in early pregnancy. However, most women were not taking folic acid supplements before they became pregnant and, hence may not have had sufficient folate at the time of normal neural tube closure.

Erythrocytes↗
PubMed1997

Vascular endothelial growth factor expression is increased in renal cell carcinoma.

PURPOSE: To compare the expression of VEGF in renal cell carcinoma (RCC) and normal kidney. MATERIALS AND METHODS: RT-PCR and Western blot analysis were performed on tumour and normal adjacent kidney collected from 31 patients (29 RCC and 2 oncocytomas) as well as proliferating vascular endothelial cells (VEC) in culture. RESULTS: Expression of 3 VEGF isoforms was detected in normal renal parenchyma and all ROC by RT-PCR, but was not apparent in proliferating VEC. In 27 RCC, Western blot analysis demonstrated 3-37 fold increases in VEGF expression when compared to normal parenchyma. Immunohistochemistry demonstrated VEGF staining of both tumour cells and adjacent vascular endothelium. Normal kidney showed no staining for VEGF. In the 2 remaining RCC and both oncocytomas VEGF was not increased. CONCLUSIONS: VEGF expression is increased in RCC and may have a paracrine effect in these tumours in stimulating angiogenesis.

Carcinoma, Renal Cell↗