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Biomedical subjects

L Peters

Publications and source records attributed to L Peters.

At least 19 recordsLinked to original sources
PubMed2004

Delayed therapy with curative intent in a contemporary prostate cancer watchful-waiting cohort.

OBJECTIVE: To identify predictors of delayed therapy with curative intent, an increasingly common option in contemporary patients with prostate cancer who initially choose watchful waiting. PATIENTS AND METHODS: The characteristics of all patients at one institution and diagnosed with T1-4NXM0 prostate cancer between 1993 and 2000 were prospectively recorded. Factors recorded included: age, tumour stage, histological type, Gleason score, serum prostate specific antigen (PSA) level, prostate volume, PSA density (PSAD), percentage of positive biopsy cores, and the initial treatment selection. Outcomes, including all cancer-directed interventions, all serum PSA values, and initial outcomes of all interventions with curative intent, were determined by review of all medical records and cancer registry data. RESULTS: Of 187 patients on watchful waiting, 175 had stage T1 or T2 cancer and were analysed primarily. Thirty-eight (22%) of these patients received delayed intervention with curative intent (15 radical prostatectomy, 17 external beam radiotherapy, six brachytherapy). Age (P < 0.001) and percentage of positive biopsy cores (P = 0.042) were significant independent predictors of intervention with curative intent. When the PSA doubling time was added to the model it became a significant predictor (P = 0.018), with percentage positive biopsy cores (P = 0.022) and age (P < 0.001). CONCLUSIONS: Therapy with curative intent is common in contemporary patients with prostate cancer who initially choose watchful waiting. Age and percentage positive biopsy cores are independent predictors of such intervention, with PSA doubling time also an independent predictor.

Adenocarcinoma↗
PubMed2003

Five-year survival predictive factors in patients with excessive alcohol intake and cirrhosis. Effect of alcoholic hepatitis, smoking and abstinence.

AIM: To evaluate 5-year survival predictive factors in hospitalised patients with excessive alcohol intake and cirrhosis, including in a multivariate analysis the severity of the liver disease, gastrointestinal bleeding, concomitant viral B or C infection, smoking status, presence of alcoholic hepatitis at inclusion and abstinence from alcohol during follow-up. METHODS: In a non-concurrent cohort study, 122 patients with excessive alcohol intake and cirrhosis were followed up at least five years or till death. Two patients were lost to follow-up. RESULTS: The 5-year survival rates were 43% in the 122 patients and 66%, 50% and 25% in Child-Pugh class A, B and C patients, respectively. In multivariate analysis, age (P = 0.01), Child-Pugh score (P = 0.0001), gastrointestinal bleeding (P = 0.01), presence of HBs Ag and/or anti-HCV (P = 0.03), smoking (P = 0.01), absence of histologically proven alcoholic hepatitis (P = 0.05) and persistent alcohol intake (P = 0.002) were associated with significantly increased risk ratios of death. CONCLUSIONS: In hospitalised patients with excessive alcohol intake and cirrhosis: (1) age, liver failure, gastrointestinal bleeding, concomitant viral B or C infection and persistent alcohol intake are independent poor prognostic markers, (2) smoking may contribute to the aggravation of cirrhosis, and (3) alcoholic hepatitis, being a potentially reversible cause of liver failure, has a favourable prognostic significance.

Alcohol Drinking↗
PubMed2001

Novel DNA sequence variants in the hHR21 DNA repair gene in radiosensitive cancer patients.

PURPOSE: Radiation therapy is an important treatment modality for oncology patients. DNA sequence variants have so far been identified in only a few genes in radiosensitive cancer patients. Patients known to be clinically radiosensitive were tested for mutation of a gene involved in DNA double-strand break repair and sister chromatid cohesion--hHR21. METHODS AND MATERIALS: Clinically radiation-sensitive patients were accrued to the study after giving informed consent. Blood samples were obtained and lymphoblastoid cell lines established. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to amplify the hHR21 gene, and the DNA product was sequenced to identify any genetic abnormalities. Northern blot analysis, cell survival, and growth assays were performed on control cells and cells with hHR21 variants, and a restriction digest assay was developed to screen for carriers of a detected gene variant. RESULTS: The DNA sequence of the hHR21 gene was determined in 19 radiation-sensitive cancer patients. In 6 of the 19 patients, a thymidine (T) to cytosine (C) transition was detected at position 1440 of the hHR21 open reading frame (T1440C). This variant did not alter the amino acid sequence and was likely to be a polymorphism. One patient with a particularly severe radiation reaction had a second sequence variant immediately adjacent to the first. This was a guanine (G) to adenine (A) transition (G1441A), resulting in a change of the amino acid sequence (glycine --> arginine) in a portion of the protein conserved in evolution. This suggests that this DNA alteration may be biologically significant. Restriction digest with the HpaII enzyme confirmed the presence of both sequence variants on the same allele. CONCLUSIONS: We describe the first two DNA sequence variants ever found in the hHR21 gene, in patients with clinical radiation hypersensitivity. Although no direct evidence for the involvement of hHR21 alterations in the radiosensitivity of the cancer patients examined has been demonstrated, the possibility exists that homozygous mutations or other mutations of this gene could contribute to radiosensitivity. A simple test is described that could be applied to screening for these variants in relevant populations.

Amino Acid Sequence↗
PubMed2001

Noncovalent interactions between tetrazole and an N,N'-diethyl-substituted benzamidine.

Amidines have long been known to form strong noncovalent complexes with carboxylates and phosphates. However, their interaction with tetrazoles, which are acidic heterocycles and important bioisosteric replacements for carboxylic acids in medicinal chemistry, has remained unexplored so far. The binding of a tetrazole to an N,N'-diethyl-substituted benzamidine has been studied for the first time by X-ray crystallography, solution NMR methods, and electrospray mass spectrometry. The amidinium group of model complex 3 was found to prefer an E,Z configuration in the crystal. Benzamidinium and tetrazolate groups alternate along an infinite chain of hydrogen bonds and salt bridges between the amidine-NH groups and the two tetrazole-N atoms next to the ring carbon. In solution, a 1:1 complex was evident from Job's method of continuous variation, and an association constant of 4.0 x 10(3) +/- 1.6 x 10(3) M(-)(1) (in CDCl(3)/CD(3)CN, 6:1) could be determined by (1)H NMR dilution experiments. Tetrazolate was not only found to be a weaker ligand than carboxylates but, surprisingly, the binding mode also changed with concentration in neat CDCl(3). At low concentrations, the amidine group in complex 3 adapted an E,E configuration as it does in a related carboxylic acid complex 4. With increasing concentration, the E,Z isomer starts to predominate. A free activation enthalpy DeltaG(298)() of 64 +/- 1 kJ mol(-)(1) for the E,E to E,Z isomerization was determined by line shape analysis at different magnetic fields. Binding strength was further probed in a competition experiment between a bisamidine, a carboxylate, and a tetrazolate by electrospray mass spectrometry.

Benzamidines↗
PubMed2001

Duration of untreated psychosis predicts treatment outcome in an early psychosis program.

For patients first presenting with a non-affective psychotic disorder, the duration of untreated psychosis (DUP; the time between the onset of positive psychotic symptoms and the initiation of appropriate treatment) varies widely, from a few weeks to several years. A number of studies report that a longer DUP is associated with poorer clinical outcomes. We studied DUP and its association with clinical outcomes in a group of patients with schizophrenia and related psychotic disorders treated in the naturalistic clinical setting of an early psychosis program. DUP was determined for 19 patients with a non-affective psychotic disorder (schizophrenia, schizoaffective disorder or schizophreniform disorder) and no previous treatment for psychosis, by use of the IRAOS, a retrospective structured interview carried out with patients and their families. Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Function (GAF) ratings were available at baseline and 6month follow-up. For analysis, patients were categorized into a short DUP (n=9) or long DUP (n=10) group. The median DUP (57weeks) was used as the dividing point. At baseline, the two groups did not differ significantly on positive symptoms or total PANSS ratings. However, negative symptoms were more severe in the long DUP group at baseline (P=0.029), and the long DUP group had a significantly higher mean rating for the passive/apathetic social withdrawal item of the PANSS (P=0.024). At 6month follow-up, the long DUP group had significantly higher ratings for positive symptoms (P=0.028) and had lower GAF scores (P=0.044). Significantly more (P=0.033) long DUP patients had enduring positive psychotic symptoms. The results confirm both the wide range of DUP among patients first presenting with schizophrenia and related psychotic disorders and the association of long DUP, defined as greater than approximately 1year, with a poorer clinical outcome. This study highlights the importance of collecting data regarding DUP and supports the view that patients with a long DUP are likely to be less responsive to treatment in general and will require greater resources and more intensive interventions.

Adolescent↗
PubMed2001

Phase I trial of concurrent tirapazamine, cisplatin, and radiotherapy in patients with advanced head and neck cancer.

PURPOSE: To determine the maximum-tolerated dose of tirapazamine when combined with cisplatin and radiation in patients with T3/4 and/or N2/3 squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: The starting schedule was conventionally fractionated radiotherapy (70 Gy in 7 weeks) with concomitant cisplatin 75 mg/m2 and tirapazamine 290 mg/m2 (before cisplatin) in weeks 1, 4, and 7 and tirapazamine alone 160 mg/m2 three times a week in weeks 2, 3, 5, and 6. Positron emission tomography scans for tumor hypoxia (18F misonidazole) were performed before and during radiotherapy. RESULTS: We treated 16 patients with predominantly oropharyngeal primary tumors, including 10 patients with T4 or N3 disease. Febrile neutropenia occurred toward the end of radiotherapy in three out of six patients treated on the initial dose level. Two of these patients also developed grade 4 acute radiation reactions. Another 10 patients were treated with the same doses, but the week 5 and week 6 tirapazamine doses were omitted. This resulted in less neutropenia and only one dose-limiting toxicity (DLT) (febrile neutropenia), and eight out of 10 patients completed treatment without any dose omissions. In these 10 patients, the acute radiation toxicities were not obviously enhanced compared with chemoradiotherapy regimens using concurrent platinum and fluorouracil. 18F misonidazole scans detected hypoxia in 14 of 15 patients at baseline, with only one patient having detectable hypoxia at the end of treatment. With a median follow-up of 2.7 years, the 3-year failure-free survival rate was 69% (SE, 12%), the 3-year local progression-free rate was 88% (SE, 8%), and the 3-year overall survival rate was 69% (SE, 12%). CONCLUSION: DLT was due unexpectedly to febrile neutropenia, which could be overcome by omitting tirapazamine in weeks 5 and 6. The combination of tirapazamine, cisplatin, and radiotherapy resulted in remarkably good and durable clinical responses in patients with very advanced head and neck cancers. It warrants further investigation.

Adult↗
PubMed2001

Predictors of sunburn among Canadian adults.

BACKGROUND: Data from the 1996 National Survey on Sun Exposure & Protective Behaviors (4,023 respondents) were analyzed to identify independent predictors of sunburn among adult Canadians. METHODS: Multivariate models predicting sunburn odds were developed using unconditional logistic regression. Backward elimination model selection was used to identify independent predictors of sunburn. RESULTS: Nonbehavioral characteristics found to predict sunburn were younger age, male sex, light skin color, nonblack hair color, and birthplace in North America or Europe. Behavioral predictors of sunburn included high awareness of the UV Index, working outdoors in the summer, longer leisure time in the sun, forgetfulness about protecting oneself from the sun, and seeking a tan. Sun avoidance between 11 AM and 4 PM was associated with lower odds of sunburn, while seeking shade when outside and use of protective clothing showed nonsignificant associations with lower sunburn odds. Sunscreen use was found to have a nonsignificant positive association with sunburn. CONCLUSIONS: These findings highlight risk factors to be considered in the targeting of sunburn reduction strategies to high-risk groups and suggest that sun avoidance, seeking shade, and use of protective clothing may be effective in preventing sunburn.

Adolescent↗
PubMed2000

Discriminant validity of the Social Phobia and Anxiety Inventory (SPAI), the Social Phobia Scale (SPS) and the Social Interaction Anxiety Scale (SIAS).

Three measures commonly used in assessment of social phobia, the Social Phobia and Anxiety Inventory (SPAI [Turner, S. M., Beidel, D. C. & Dancu, C. V. (1996). Social phobia and anxiety inventory: manual. Toronto, Ont.: Multi-Health Systems Inc.), the Social Phobia Scale (SPS [Mattick, R. P. & Clarke, J. C. (1998). Development and validation of measures of social phobia scrutiny fear and social interaction anxiety. Behaviour Research and Therapy, 36, 455-470] and the Social Interaction Anxiety Scale (SIAS [Mattick, R. P. & Clarke, J. C. (1998). Development and validation of measures of social phobia scrutiny fear and social interaction anxiety. Behaviour Research and Therapy, 36, 455-470], were compared for their ability to discriminate between social phobia and other anxiety disorders (panic disorder with or without agoraphobia). Participants were 117 patients attending a specialized anxiety disorders unit for treatment. While all three measures were able to detect differences between social phobic patients and patients with panic disorder with or without agoraphobia, a logistic regression analysis showed that the SPAI, but not the SPS and SIAS, was a significant predictor of membership of the social phobia group. Receiver operating characteristic (ROC) analysis also showed that the SPAI was the better measure for discriminating between social phobia and panic disorder with and without agoraphobia. Analysis of the sensitivity, specificity and positive and negative predictive power of the measures at the optimum cutoff scores produced by the ROC analysis are presented.

Adult↗
PubMed2000

Antigen-induced IL-17 response in the peripheral blood mononuclear cells (PBMC) of healthy controls.

IL-17 is a T cell cytokine with a complex and important role in the immune system. It has been detected in rheumatoid arthritis (RA) synovial membrane and found to stimulate the production of the proinflammatory cytokines IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. To date, there are few data available on the agents that stimulate IL-17 production. We therefore investigated the in vitro IL-17 response to a variety of mitogens and antigens, and compared the IL-17 response to interferon-gamma (IFN-gamma), IL-4, IL-10 and TNF-alpha. In this study we used a type-0 antigen, tetanus toxoid (TT), a type-1 antigen, PPD from Mycobacterium tuberculosis, a potential type-2 rye grass (RG) antigen (Lol I) and an autoantigen SS.B (La), to stimulate PBMC from healthy controls. Cytokine mRNA was measured using semiquantitative reverse transcriptase-polymerase chain reaction and cytokine protein measured using specific ELISA techniques, while the frequency of IL-17-producing T cells was determined by flow cytometry. The mitogens concanavalin A, phytohaemagglutinin and phorbol myristate acetate/ionomycin induced a significant increase in IL-17, with the highest levels being produced by anti-CD3/anti-CD28 stimulation. The antigens TT and PPD significantly increased IL-17 mRNA expression over time, but failed to have such an effect at the protein level. IL-17 protein was also detectable in both antigen-specific (TT, SS. B) and non-specific T cell clones, but at levels lower than IFN-gamma. IL-17 production did not correlate with either the type-1 cytokine IFN-gamma or TNF-alpha or the type-2 cytokine IL-4 or IL-10 at either the mRNA or protein level.

Adult↗
PubMed2000

Quality of care from the perspective of elderly people: the QUOTE-elderly instrument.

BACKGROUND: patient views on the quality of care are usually assessed by means of patient satisfaction questionnaires. AIM: to develop an instrument that would: (i) produce data related to the expectations and experiences of noninstitutionalized elderly people, (ii) contain items that had been formulated in collaboration with elderly people, (iii) measure quality from the perspective of the users of health care services and (iv) produce data on generic quality aspects and quality aspects specifically related to the needs of elderly people. METHODS: we developed the instrument for measuring quality of care from the perspective of non-institutionalized elderly people (QUOTE-Elderly) by using a combination of qualitative and quantitative methods. We obtained empirical data on the opinions and experiences of 338 elderly people. We evaluated the taxonomy of the instrument, internal consistency of (sub)scales and the feasibility of the instrument using explorative and confirmative factor analyses and reliability analysis. RESULTS: using scale optimization, we produced a self-administered questionnaire on quality of health care from the perspective of elderly people. This contains scientific characteristics and provides specific information for practical quality-assurance policies.

Aged↗
PubMed2000

The COPE program: treatment efficacy and medical utilization outcome of a chronic pain management program at a major military hospital.

This study presents a treatment efficacy and medical utilization evaluation of a cognitive-behavioral, outpatient, chronic pain management program in a military hospital setting. A total of 61 nonmalignant chronic pain patients with heterogeneous pain syndromes who participated in sequential group programs were included in the study. Comprehensive and multi-dimensional outcome criteria were used, including pain ratings, relaxation skills, quality of life, satisfaction ratings, and medical utilization. The findings demonstrated improvements on all general indices. Military status had no effect on any of the outcome measures. Most significant was an 87% reduction in outpatient clinic visits in the first 3 months after treatment. This reduction amounts to a projected net annual saving of $78,960 in the first year after behavioral medicine intervention. In light of the increasing cost of health care for chronic pain patients, psychological approaches as an adjunct to traditional medical care seem to present a sound solution for cost savings. This study also supports the notion that a strategic biopsychosocial pain program, which targets the multiple dimensions of persistent pain, provides effective treatment and increases patient satisfaction.

Adaptation, Psychological↗
PubMed1999

A comparison of ICD10 and DSM-IV criteria for posttraumatic stress disorder.

The assumption that participants receiving an ICD10 diagnosis of posttraumatic stress disorder (PTSD) will also receive a DSM-IV diagnosis of PTSD was tested. Data were gathered for 1,364 participants using the Composite International Diagnostic Interview (CIDI). The 12-month prevalence of PTSD was 3% for DSM-IV and 7% for ICD10 Diagnostic Criteria for Research (ICD10-DCR). The agreement between the two systems was fair (kappa = .50). Forty eight percent of the discrepancies between the systems were accounted for by the additional criterion requiring clinically significant distress or impairment included in DSM-IV. The inclusion of symptoms of general numbing of responsiveness accounted for 18% of the discrepancies. It is concluded that ICD10-DCR PTSD cannot be assumed to be identical to DSM-IV PTSD.

Adolescent↗
PubMed1999

Major carbohydrate epitopes in tissues of domestic and African wild animals of potential interest for xenotransplantation research.

We investigated the main glycotopes expressed on the tissues of 44 animal species, including primates, nonprimate mammals, marsupials, birds, and a reptile. Paraffin-embedded tissue sections of kidney, heart, liver, pancreas, lung, brain and intestine of 24 domestic animal species were stained with seven fluorescent-labeled lectins. Testis sections of 20 African wild animal species were tested with the same lectins. Overall, three main immunofluorescence patterns were found in the vascular compartment. First, humans and Old World monkeys express genetically polymorphic ABH antigens and do not express alphaGal. Second, New World monkeys, other mammals, and marsupials do not express ABH antigens, but have large amounts of a genetically monomorphic alphaGal. Third, birds and reptiles do not express either ABH or alphaGal, but have monomorphic betaGal, probably different from the lactosamine precursor of ABH and alphaGal. Epithelial cells producing exocrine secretions also expressed carbohydrate epitopes. The fluorescence patterns of the cells of the exocrine compartment are similar, but not identical, to those expressed in the vascular compartment. All the animals tested have some ABH and betaGal in exocrine tissues, but New World monkeys and lower mammals are the only ones expressing alphaGal in exocrine tissues.

Animals↗
PubMed1999

Quality assurance audit in an Australasian phase III trial of accelerated radiotherapy for head and neck cancer (TROG 91.01). Trans-Tasman Radiation Oncology Group.

The Trans-Tasman Radiation Oncology Group (TROG) initiated a randomized trial, testing accelerated (twice daily) radiotherapy against conventional radiotherapy for stage III and stage IV squamous cell carcinoma of the head and neck in 1991. In 1996, the Trial Management Committee arranged for a technical audit of 76 cases from 11 institutions, conducted by investigators from interstate institutions. A 10% unacceptable protocol violation rate was detected, which compares favourably with initial Radiation Therapy Oncology Group (RTOG) experience in the late 1970s. Infrastructural deficits with poor quality of documentation, incomplete retrieval of films and document return have been demonstrated in some cases. The Trans-Tasman Radiation Oncology Group is actively pursuing procedural and resourcing issues in order to redress this and is actively expanding its Quality Assurance (QA) Programme with an intercentre dosimetry study. Ultimately, comprehensive clinical and technical QA site visits are planned.

Australia↗