Value of the unipolar electrogram in the diagnosis of right ventricular perforation following pacemaker implantation.
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Aged↗
Biomedical subjects
J Macdonald
Publications and source records attributed to J Macdonald.
Therapeutic strategies in gastric cancer.
Gastric cancer continues to be a major public health problem and is the second most common cause of cancer-related deaths in the world. These statistics led the American Society of Clinical Oncology (ASCO) International Affairs Committee to choose gastric cancer as the topic for the International Symposium held at the 2003 ASCO Annual Meeting. Dr Yoshiaki Ito will discuss the role of RUNX3 in the genesis and progression of human gastric cancer. Dr Pelayo Correa will present a compelling argument on the use of Helicobacter pylori therapy and antioxidants in selected high-risk population as chemoprevention strategies for gastric cancer. The controversy regarding the role of extended lymph node dissection for gastric cancer will be discussed by Dr Cornelis J.H. Van De Velde and Dr Mitsuru Sasako. Dr Van De Velde will present the European surgical approach to gastric cancer, and Dr Sasako will review the Japanese experience. The issues of whether certain patients benefit from more aggressive surgical dissection and the potential risks compared with benefits will also be discussed. Dr John Macdonald will discuss the role of adjuvant chemotherapy and adjuvant chemoradiotherapy in resected gastric cancer, as well as the role of chemotherapy in metastatic gastric cancer.
Animals↗
Oxidative stress and gene expression in sepsis.
Dysregulation of the immuno-inflammatory response, as seen in sepsis, may culminate in host cell and organ damage. Lipopolysaccharide from Gram-negative bacterial cell walls induces gene activation and subsequent inflammatory mediator expression. Gene activation is regulated by a number of transcription factors at the nuclear level, of which nuclear factor kappaB appears to have a central role. The redox (reduction-oxidation) cellular balance is important for normal cellular function, including transcription factor regulation. In sepsis, a state of severe oxidative stress is encountered, with host endogenous antioxidant defences overcome. This has implications for cellular function and the regulation of gene expression. This review gives an overview of the mechanisms by which transcription factor activation and inflammatory mediator overexpression occur in sepsis, together with the events surrounding the state of oxidative stress encountered and the effects on the host's antioxidant defences. The effect of oxidative stress on transcription factor regulation is considered, together with the role of antioxidant repletion in transcription factor activation and in sepsis in general. Other interventions that may modulate transcription factor activation are also highlighted.
Animals↗
A new injectable bulking agent for treatment of stress urinary incontinence: results of a multicenter, randomized, controlled, double-blind study of Durasphere.
OBJECTIVES: To assess the safety and effectiveness of Durasphere compared with bovine collagen in the treatment of stress urinary incontinence (SUI) due to intrinsic sphincter deficiency (ISD). METHODS: This multicenter, randomized, controlled, double-blind trial was composed of 355 women diagnosed with SUI due to ISD and used a standardized pad test and the Stamey continence grade as the primary endpoints. The participants' ages ranged from 26 to 84 years. All patients had an abdominal leak point pressure of less than 90 cm H(2)O (average 51). RESULTS: At 12 months after the first injection, the two materials were equivalent with respect to the improvement in continence grade and pad weight testing. Less Durasphere was injected to obtain comparable clinical results (Durasphere 4.83 mL versus bovine collagen 6.23 mL, P <0.001). When examined 1 year after the date of the last treatment, 49 (80.3%) of the 61 women treated with Durasphere showed improvement of 1 continence grade or more compared with 47 (69.1%) of 68 women treated with bovine collagen (P value for difference = 0.162). Although the adverse events reported for both groups were similar, the Durasphere group had an increased short-term risk of urgency and urinary retention. CONCLUSIONS: The use of Durasphere for the treatment of SUI due to ISD was equally effective as bovine collagen and used less material. The U.S. Food and Drug Administration granted market approval for Durasphere on September 13, 1999. The product design and initial clinical data suggest the potential for greater durability of the clinical benefit, with the possibility of a permanent solution for SUI due to ISD in some patients.
Adult↗
The appearance of a second genotype of Japanese encephalitis virus in the Australasian region.
In mid-January 2000, the reappearance of Japanese encephalitis (JE) virus activity in the Australasian region was first demonstrated by the isolation of JE virus from 3 sentinel pigs on Badu Island in the Torres Strait. Further evidence of JE virus activity was revealed through the isolation of JE virus from Culex gelidus mosquitoes collected on Badu Island and the detection of specific JE virus neutralizing antibodies in 3 pigs from Saint Pauls community on Moa Island. Nucleotide sequencing and phylogenetic analyses of the premembrane and envelope genes were performed which showed that both the pig and mosquito JE virus isolates (TS00 and TS4152, respectively) clustered in genotype I, along with northern Thai, Cambodian, and Korean isolates. All previous Australasian JE virus isolates belong to genotype II, along with Malaysian and Indonesian isolates. Therefore, for the first time, the appearance and transmission of a second genotype of JE virus in the Australasian region has been demonstrated.
Animals↗
Shame and non-disclosure: a study of the emotional isolation of people referred for psychotherapy.
Thirty-four people referred to an NHS psychotherapy department were given a modified form of Oatley and Duncan's (1992) emotion diary which included questions about whether each recorded emotion had been subsequently disclosed to anyone (for example a partner, friend or professional). One week later the diaries were collected and participants interviewed. Interviews focused, among other things, on reasons for nondisclosure of recorded emotional experiences and the relationship between shame and non-disclosure. The results indicated that a majority of the emotional incidents recorded in the diaries were not disclosed (68%). This result contrasts with studies on non-clinical samples in which only approximately 10% of everyday emotions are kept secret. Qualitative analysis of the interview data revealed that participants appeared to be habitual non-disclosers of emotional and personal experiences and that non-disclosure was related to the anticipation of negative interpersonal responses to disclosure (in particular labelling and judging responses) in addition to more self-critical factors including shame. It is suggested that these results add to the existing literature on shame by illustrating the interpersonal effects of shame in a clinical sample.
Adult↗
Acute adrenocortical crisis: three different presentations.
The adrenal cortex normally produces three principal steroid hormones: the glucocorticoid cortisol, the mineralocorticoid aldosterone, and a small quantity of sex steroids. In primary adrenocortical insufficiency, there is a deficiency of both cortisol and aldosterone with characteristic clinical and laboratory findings. In contrast, with a pituitary disorder there is isolated hypocortisolism, because its production is dependent on pituitary adrenocorticotropic hormone (ACTH), whereas aldosterone production is controlled by extracellular fluid volume, renin and serum potassium. Acute adrenocortical crisis is an absolute medical emergency and its presentation is not always typical. We describe three recent cases of acute adrenocortical crisis in our hospital who presented in three different ways in three different wards.
Acute Disease↗
Alterations in exon 4 of the p53 gene in gastric carcinoma.
BACKGROUND & AIMS: Our long-term goal was to evaluate the role of p53 in the prognosis of gastric cancer. We previously showed a discrepancy between p53 expression and the presence of mutations when only exons 5-9 were examined. We then evaluated exon 4. METHODS: DNA was sequenced from 217 gastric cancers to detect exon 4 alterations. Codon 72 was examined by restriction enzyme digestion. RESULTS: Mutations were present in 3.2% of tumors. In addition, 2 polymorphic sites were found at codons 36 and 72. Polymorphisms at codon 36 were only found in 2 patients. In contrast, the codon 72 polymorphism was very frequent. The genotype frequency was arg/arg (54%), arg/pro (33%), and pro/pro (14%). The genotype of the polymorphic site varied with race (P = 0.001): 64% of whites had the arg/arg genotype, compared with 24% of blacks. The difference in genotype by site, sex, or histological tumor type was not statistically significant (P = 0.067). CONCLUSIONS: There are several exon 4 alterations in gastric cancers. These include the rare mutations and the very rare codon 36 polymorphism. The most common change is the codon 72 polymorphism, the genotype of which differs significantly with race. The more common arg/arg genotype in whites may explain why whites are more prone to develop cardiac cancer, whereas the more common proline allele in blacks may explain why they are more prone to develop antral cancers. Further studies are required to determine whether the codon 72 polymorphism affects patient predisposition to gastric cancer.
Adenocarcinoma, Mucinous↗
Inspiratory vocal cord dysfunction, a new approach in treatment.
Vocal cord dysfunction is a well recognized respiratory condition in which adduction of the vocal cords during either inspiration or expiration, or both, causes functional airways obstruction. Diagnosis is usually made by laryngofibreoscopy, however treatment of this condition has generally been unsatisfactory, requiring a multi-disciplinary approach consisting of speech therapy, psychological counselling, sedatives and anaesthetic agents. Here we use an innovative approach which requires relatively inexpensive and simple anaesthetic equipment in order to manipulate airways resistance and thus reduce any vocal cord dysfunction as it occurs. The patient involved found instant relief when using this simple device which is easy to use and is portable.
Adult↗
Thioredoxin, a putative oncogene product, is overexpressed in gastric carcinoma and associated with increased proliferation and increased cell survival.
Human thioredoxin is a putative oncogene that may confer both a growth and survival advantage to tumor cells. Overexpressed thioredoxin mRNA has been found in both primary human lung and colorectal cancers. To determine the intratumor distribution and amount of thioredoxin protein in human primary carcinomas, we developed an immunohistochemical assay for thioredoxin in paraffin-embedded tissue. We then studied 10 patients with primary high-risk gastric carcinoma. To further relate thioredoxin protein overexpression to cell death and survival, we used a paraffin-based in situ end-labeling (ISEL) assay. To delineate proliferation, we used the nuclear proliferation antigen detected by Ki-67. In this survey, we found that thioredoxin was localized to tumor cells and overexpressed compared with normal gastric mucosa in 8 of 10 gastric carcinomas. The thioredoxin was found at high levels in 5 of the 8 overexpressing carcinomas. The overexpression of thioredoxin was typically found in both a nuclear and cytoplasmic location in the neoplastic cells. There was a significant positive correlation (P = .0061) with cancer cell proliferation measured by Ki-67. There was a significant negative correlation (P = .0001) with DNA damage measured by the ISEL assay, suggesting decreased apoptosis and increased carcinoma cell survival. Thus, human primary gastric tumors that are highly expressive of thioredoxin have both a higher proliferative rate and a higher survival rate than tumors that do not express thioredoxin. With these newly developed assays in hand, it is now feasible to question whether this thioredoxin-related combined growth and survival advantage translates into poor clinical outcome.
Adenocarcinoma↗
The performance of a CCD digital autoradiography imaging system.
Autoradiography is a widely used technique for imaging trace quantities of radioactivity within biological samples, conventionally using photographic film. This method produces images with high spatial resolution, but it suffers from very low sensitivity and poor dynamic range. Digital autoradiography systems with greatly improved sensitivity and linearity are commercially available, but the spatial resolution is usually much less than that achieved using film. We report here the design, construction and characterization of a novel digital autoradiography system based on scientific-grade charged coupled devices (CCDs). Images of x-ray and beta emissions from radionuclides commonly used in autoradiography show that the system can perform high-speed quantitative imaging with a spatial resolution of approximately 30, microm. Using a frame by frame acquisition method the dynamic range is shown to be at least three orders of magnitude. The absolute detection efficiency is comparable to the best of the currently available digital systems. CCD images of 125I and 14C radioisotope distributions in tissue samples are superior to the equivalent film images and have been acquired in 1-10% of the time.
Animals↗
Vaccination with inactivated virus but not viral DNA reduces virus load following challenge with a heterologous and virulent isolate of feline immunodeficiency virus.
It has been shown that cats can be protected against infection with the prototypic Petaluma strain of feline immunodeficiency virus (FIV(PET)) using vaccines based on either inactivated virus particles or replication-defective proviral DNA. However, the utility of such vaccines in the field is uncertain, given the absence of consistent protection against antigenically distinct strains and the concern that the Petaluma strain may be an unrepresentative, attenuated isolate. Since reduction of viral pathogenicity and dissemination may be useful outcomes of vaccination, even in the absence of complete protection, we tested whether either of these vaccine strategies ameliorates the early course of infection following challenge with heterologous and more virulent isolates. We now report that an inactivated virus vaccine, which generates high levels of virus neutralizing antibodies, confers reduced virus loads following challenge with two heterologous isolates, FIV(AM6) and FIV(GL8). This vaccine also prevented the marked early decline in CD4/CD8 ratio seen in FIV(GL8)-infected cats. In contrast, DNA vaccines based on either FIV(PET) or FIV(GL8), which induce cell-mediated responses but no detectable antiviral antibodies, protected a fraction of cats against infection with FIV(PET) but had no measurable effect on virus load when the infecting virus was FIV(GL8). These results indicate that the more virulent FIV(GL8) is intrinsically more resistant to vaccinal immunity than the FIV(PET) strain and that a broad spectrum of responses which includes virus neutralizing antibodies is a desirable goal for lentivirus vaccine development.
Animals↗
Isolation of Japanese encephalitis virus from mosquitoes (Diptera: Culicidae) collected in the Western Province of Papua New Guinea, 1997-1998.
After Japanese encephalitis (JE) virus emerged in the Torres Strait in Australia in 1995, investigations were initiated into the origin of the incursion. New Guinea was considered the most likely source, given its proximity to islands of the Torres Strait. Almost 400,000 adult mosquitoes were processed for virus isolation from 26 locations in the Western Province of Papua New Guinea (PNG) between February 1996 and February 1998, yielding three isolates of JE virus. Two isolates of Murray Valley encephalitis, 17 isolates of Sindbis, and 1 each of Sepik and Ross River viruses were also obtained. Nucleic acid sequences of the PNG JE isolates were determined in the prM region, and in a region overlapping a part of the fifth nonstructural protein and the 3' untranslated region. The PNG isolates belonged to genotype II, and shared > 99.2% identity with isolates from humans and mosquitoes from the Torres Strait, suggesting that PNG is the source of incursions of JE virus into Australia.
3' Untranslated Regions↗
Blood perfusion hyperaemia in response to graded loading of human heels assessed by laser-Doppler imaging.
Heel pressure ulcers are important clinical, humanitarian and economic problems arising in part from localized blood flow deficits during loading and inadequate flow recovery. Because there are few data available with regard to the intrinsic physiological responses of heel skin to pressure-induced ischaemia, the present study was undertaken to characterize the main features of the post-loading hyperaemic response. Laser-Doppler perfusion imaging was used to measure hyperaemia in 14 vascularly normal women who were subjected to sequential local heel loading with graded magnitudes (30-140 mmHg) and durations (2.5-20 min). Peak heel perfusion produced by local heating to 44 degrees C for 5 min was used as a comparison standard. All heel loads and durations resulted in hyperaemic responses, with the largest increase in peak response occurring between heel loads of 60 and 120 mmHg. During this transition, peak hyperaemia increased from about 32% to 79% of the local maximal microvascular vasodilatory capacity. Recovery times also increased with both load duration and magnitude, with the longest recovery time being about 7.5 min. Hyperaemic responses and recovery times were analytically dependent on the heel load pressure duration product, with evidence of suppression of the peak response at 1500 mmHg min and a levelling off of recovery time at higher pressure durations. These findings serve to characterize normal physiological perfusion responses to pressure-induced ischaemia at an anatomical site prone to pressure ulceration. The results suggest the possibility of a 'critical' heel loading, above which a near-maximum response is elicited and beyond which vasodilatory recovery potential is blunted.
Adult↗
Endovascular beta-radiation to reduce restenosis after coronary balloon angioplasty: results of the beta energy restenosis trial (BERT).
BACKGROUND: In the porcine overstretch injury model of restenosis, endovascular beta-radiation reduces neointima formation. To determine whether this therapy could be applied to patients with coronary artery disease, a special device was developed to allow delivery of 12 encapsulated 90Sr/Y sources, measuring a total of 30 mm, to various sites within the coronary arterial tree. This study was designed to evaluate the feasibility of the delivery of 12, 14, or 16 Gy at 2 mm after balloon angioplasty of stenoses of native coronary vessels. METHODS AND RESULTS: Delivery of beta-radiation was attempted in 23 patients after successful balloon angioplasty. Source delivery was successful in 21 of the 23 patients (91%). There was no in-hospital or 30-day morbidity or mortality. Follow-up quantitative coronary arteriography in 20 patients demonstrated a late loss of 0.05 mm, a late loss index of 4%, and a restenosis rate of 15%. The use of the beta-emitter 90Sr/Y significantly reduced treatment time and operator exposure compared with previous trials with the gamma-emitter 192Ir. CONCLUSIONS: In this study, the administration of endovascular beta-radiation after angioplasty was safe and feasible and substantially altered the postangioplasty late lumen loss, resulting in a lower-than-expected rate of restenosis. On the basis of these encouraging results, a multicenter, randomized trial with operators and patients blinded to treatment assignment is planned.
Adolescent↗
Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer.
PURPOSE: The administration of fluorouracil (5-FU) by continuous intravenous infusion (CI) is an alternative to the bolus administration of 5-FU in patients with advanced colorectal cancer. Although more than 1,200 patients have been enrolled onto randomized trials that compared these two treatment modalities, there is still no definitive evidence of an advantage of 5-FU CI, and the magnitude of this advantage, if any, is also controversial. A meta-analysis was performed to assess this benefit in terms of tumor response and survival, and to compare the toxicity profiles of these two modalities of administration of 5-FU. DESIGN: Individual data of 1,219 patients included in six randomized trials served as the basis for this meta-analysis, which was conducted by an independent secretariat in close collaboration with the investigators. RESULTS: Tumor response rate was significantly higher in patients assigned to 5-FU CI than in patients assigned to 5-FU bolus (22% v 14%; overall response odds ratio, 0.55; 95% confidence interval [95% CI], 0.41 to 0.75; P = .0002). Overall survival was also significantly higher in patients assigned to 5-FU CI (overall hazards ratio [HR], 0.88; 95% CI, 0.78 to 0.99; P = .04), although the median survival times were close. Multivariate analyses showed that randomized treatment and performance status were the only two significant predictors of tumor response, whereas the same plus primary tumor site were independent significant predictors of survival (patients with rectal cancer did somewhat better). Grade 3 or 4 hematologic toxicity was more frequent in patients assigned to 5-FU bolus (31% v 4%; P < 10(-16)), whereas hand-foot syndrome was more frequent in the 5-FU CI group (34% v 13%; P < 10(-7)). CONCLUSION: 5-FU CI is superior to 5-FU bolus in terms of tumor response and achieves a slight increase of overall survival. The hematologic toxicity is much less important in patients who receive 5-FU CI, but hand-foot syndrome is frequent in this group of patients.
Antimetabolites, Antineoplastic↗
Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors.
PURPOSE: Fluorouracil (5-FU) continuous infusion is superior to 5-FU bolus in patients with advanced colorectal cancer, but the survival difference between the two treatments is small and, therefore, the difference in toxicity profile is crucial in choosing a treatment for individual patients. MATERIALS AND METHODS: We conducted a meta-analysis of all randomized trials that compared 5-FU bolus with 5-FU CI, based on individual data from 1,219 patients, to compare the toxicity of the two schedules of 5-FU administration and to identify predictive factors for toxicity. The toxicities considered were World Health Organization (WHO) grade 3 to 4 anemia, thrombopenia, leukopenia, neutropenia, nausea/vomiting, diarrhea, mucositis, and hand-foot syndrome. RESULTS: Hematologic toxicity, mainly neutropenia, was more frequent with 5-FU bolus than with 5-FU CI (31% and 4%, respectively; P < .0001). Hand-foot syndrome was less frequent with 5-FU bolus than with 5-FU CI (13% and 34%, respectively; P < .0001). There was no difference between the two treatment groups in terms of other nonhematologic toxicities. Independent prognostic factors were age, sex, and performance status for nonhematologic toxicities, performance status, and treatment for hematologic toxicities, and age, sex, and treatment for hand-foot syndrome. CONCLUSION: Based on a large data set, this study confirmed and quantified the toxicity profile of the two schedules of administration of 5-FU and allowed the identification of clinical predictors of toxicity.
Colorectal Neoplasms↗