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Biomedical subjects

M Sawyer

Publications and source records attributed to M Sawyer.

At least 19 recordsLinked to original sources
PubMed2006

Overweight, obesity and girth of Australian preschoolers: prevalence and socio-economic correlates.

OBJECTIVE: (1) To determine the prevalence of overweight and obesity in Australian 4-5-year-old children. (2) To investigate associations between socio-economic characteristics and (a) overweight/obesity and (b) waist circumference. DESIGN: Cross-sectional population survey. SETTING: Wave 1 (2004) of the Longitudinal Study of Australian Children. PARTICIPANTS: Nationally representative sample of 4983 4-5-year-old children (2537 boys and 2446 girls; mean age 56.9 months (s.d. 2.64 months; range 51-67 months)). MAIN OUTCOME MEASURES: Prevalence of overweight and obesity (International Obesity TaskForce definitions) and waist circumference (cm). ANALYSIS: Prevalence estimates were obtained as weighted percentages. Uni- and multivariable ordinal logistic regression (using the proportional odds model) were used to assess associations between potential predictors and the risk of higher child body mass index status and a multivariable linear regression model to assess relationships between the same potential predictors and waist circumference. RESULTS: 15.2% of Australian preschoolers are estimated to be overweight and 5.5% obese. In univariate analyses, seven of the 12 variables were associated with higher odds of being in a heavier body mass index category. In a multivariable regression model, speaking a language other than English (particularly for boys), indigenous status and lower disadvantage quintile were the clearest independent predictors of higher body mass index status, with children in the lowest quintile of social disadvantage having 47% higher odds (95% CI 14, 92%) of being in a heavier body mass index category compared to those in the highest quintile. Waist circumference was not related to any socio-economic variable. CONCLUSIONS: This nationally representative survey confirms high rates of overweight and obesity in preschoolers throughout Australia. The recent emergence of a substantial socio-economic gradient should bring new urgency to public health measures to combat the obesity epidemic.

Abdomen↗
PubMed2005

The Na(+)/H(+) exchanger: a target for cardiac therapeutic intervention.

The Na(+)/H(+) exchanger (NHE) is a ubiquitous protein present in mammalian cells. In higher eukaryotes this integral membrane protein removes one intracellular H(+) for one extracellular Na(+) protecting cells from intracellular acidification. NHE is of essential importance in the myocardium. It prevents intracellular acidosis that inhibits contractility. NHE also plays a key role in damage to the mammalian myocardium that occurs during ischemia and reperfusion and is involved in hypertrophy of the myocardium. NHE is composed of a membrane bound domain of approximately 500 amino acids plus a hydrophilic regulatory cytoplasmic domain of approximately 315 amino acids. The NHE1 isoform is the only significant plasma membrane isoform present in the myocardium. The activity of NHE1 is elevated in animal models of myocardial infarcts and in left ventricular hypertrophy. During ischemia and reperfusion of the myocardium, NHE activity catalyzes increased uptake of intracellular sodium. This in turn is exchanged for extracellular calcium by the Na(+)/Ca(2+) exchanger resulting in calcium overload and damage to the myocardium. Numerous inhibitors of NHE have been developed to attempt to break this cycle of calcium overload. In animal models excellent success has been obtained in this regard. However in humans, clinical trials have resulted in only modest success and recently, significant detrimental side effects were note of one NHE inhibitor. The mechanisms by which these inhibitors affect NHE activity are presently being investigated and regions of the protein important in NHE activity and inhibitor efficacy are related but not identical. Future studies may develop superior inhibitors that may circumvent recently reported side effects. Recently, NHE inhibition has been shown to be remarkably effective in preventing hypertrophy in some animal models. Whether this proves to be a practical treatment for hypertrophy in humans has yet to be determined.

Animals↗
PubMed2001

Mutability of p53 hotspot codons to benzo(a)pyrene diol epoxide (BPDE) and the frequency of p53 mutations in nontumorous human lung.

p53 mutations are common in lung cancer. In smoking-associated lung cancer,the occurrence of G:C to T:A transversions at hotspot codons, e.g., 157, 248, 249,and 273, has been linked to the presence of carcinogenic chemicalsin tobacco smoke including polycyclic aromatic hydrocarbons suchas benzo(a)pyrene (BP). In the present study, we have used a highly sensitive mutation assay to determine the p53 mutation load in nontumorous human lung and to study the mutability of p53 codons 157, 248, 249, and 250 to benzo(a)pyrene-diol-epoxide (BPDE), an active metabolite of BP in human bronchial epithelial BEAS-2B cells. We determined the p53 mutational load at codons 157, 248, 249, and 250 in nontumorous peripheral lung tissue either from lung cancer cases among smokers or noncancer controls among smokers and nonsmokers. A 5-25-fold higher frequency of GTC(val) to TTC(phe) transversions at codon 157 was found in nontumorous samples (57%) from cancer cases (n = 14) when compared with noncancer controls (n = 8; P < 0.01). Fifty percent (7/14) of the nontumorous samples from lung cancer cases showed a high frequency of codon 249 AGG(arg) to AGT(ser) mutations (P < 0.02). Four of these seven samples with AGT(ser) mutations also showed a high frequency of codon 249 AGG(arg) to ATG(met) mutations, whereas only one sample showed a codon 250 CCC to ACC transversion. Tumor tissue from these lung cancer cases (38%) contained p53 mutations but were different from the above mutations found in the nontumorous pair. Noncancer control samples from smokers or nonsmokers did not contain any detectable mutations at codons 248, 249, or 250. BEAS-2B bronchial epithelial cells exposed to doses of 0.125, 0.5, and 1.0 microM BPDE, showed G:C to T:A transversions at codon 157 at a frequency of 3.5 x 10(-7), 4.4 x 10(-7), and 8.9 x 10(-7), respectively. No mutations at codon 157 were found in the DMSO-treated controls. These doses of BPDE induced higher frequencies, ranging from 4-12-fold, of G:C to T:A transversions at codon 248, G:C to T:A transversions and G:C to A:T transitions at codon 249, and C:G to T:A transitions at codon 250 when compared with the DMSO-treated controls. These data are consistent with the hypothesis that chemical carcinogens such as BP in cigarette smoke cause G:C to T:A transversions at p53 codons 157, 248, and 249 and that nontumorous lung tissues from smokers with lung cancer carry a high p53 mutational load at these codons.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2001

Body surface area as a determinant of pharmacokinetics and drug dosing.

Body surface area (BSA) was introduced into medical oncology in order to derive a safe starting dose for phase I studies of anticancer drugs from preclinical animal toxicology data. It is not clear however, as to why dosing by BSA was extended to the routine dosing of antineoplastic agents. Several formulas exist to estimate BSA, but the formula derived by DuBois and DuBois is the one used in adult medical oncology. This formula was derived based on data from only nine patients; subsequent attempts to validate the formula have found the DuBois formula to either over or underestimate the actual determined BSA. While cardiac output does correlate with BSA, the relationship between BSA and other physiologic measures relevant for drug metabolism and disposition, such as, renal and hepatic function, is weak or nonexistent. Further only epirubicin, etoposide, and carboplatin have been studied to determine if dosing by BSA would reduce interpatient variability, and none of these drugs were found to have significant relationships between their pharmacokinetics and BSA. Future clinical trials of new agents should not presume that dosing based on BSA reduces interpatient variability. Studies should examine the role, if any, BSA has in dosing new chemotherapeutic agents in initial phase I studies.

Adult↗
PubMed2001

Medical student interviewing skills and mother-reported satisfaction and recall.

BACKGROUND: Providing feedback to medical students about their interviewing skills is an important component of teaching programmes. There is very little information about mothers' views of medical student consultations in paediatrics, and in particular about what mothers consider to be the key elements of a successful consultation. Patient-centred interviewing is a model which emphasizes the active seeking of patient views. In association with appropriate clinical skills, it is reported to promote improved health outcomes. OBJECTIVES: To examine whether greater medical student clinical competence and more frequent use of patient-centred techniques is associated with higher maternal satisfaction, higher maternal rating of the medical student's interpersonal skills, and greater maternal recall of relevant diagnosis and treatment recommendations. METHOD: Two standardized 'medical student' videotaped interviews were created based on actual senior medical student consultations. Interview A demonstrated both higher student clinical competence and higher patient-centredness compared with interview B. Both videotaped interviews were viewed and then rated, using a questionnaire, by 11 mothers attending a teaching general practice. RESULTS: Significantly higher mean scores, indicating greater maternal satisfaction, were associated with interview A (P < 0.01 for all measures). Accurate recall for diagnosis and management was also significantly greater after interview A (mean diagnosis recall, interview A 35%, interview B 14%, P < 0.01; mean management recall, interview A 95%, interview B 57%, P < 0.01). CONCLUSIONS: Maternal satisfaction and recall were higher following a more clinically competent and patient-centred medical student interview. Maternal ratings of student interviews could be used as an additional method of assessment as well as providing feedback to medical students on their interview skills development.

Clinical Competence↗
PubMed2000

Increased p53 mutation load in nontumorous human liver of wilson disease and hemochromatosis: oxyradical overload diseases.

Hemochromatosis and Wilson disease (WD), characterized by the excess hepatic deposition of iron and copper, respectively, produce oxidative stress and increase the risk of liver cancer. Because the frequency of p53 mutated alleles in nontumorous human tissue may be a biomarker of oxyradical damage and identify individuals at increased cancer risk, we have determined the frequency of p53 mutated alleles in nontumorous liver tissue from WD and hemochromatosis patients. When compared with the liver samples from normal controls, higher frequencies of G:C to T:A transversions at codon 249 (P < 0.001) and C:G to A:T transversions and C:G to T:A transitions at codon 250 (P < 0.001 and P < 0.005) were found in liver tissue from WD cases, and a higher frequency of G:C to T:A transversions at codon 249 (P < 0.05) also was found in liver tissue from hemochromatosis cases. Sixty percent of the WD and 28% of hemochromatosis cases also showed a higher expression of inducible nitric oxide synthase in the liver, which suggests nitric oxide as a source of increased oxidative stress. A high level of etheno-DNA adducts, formed from oxyradical-induced lipid peroxidation, in liver from WD and hemochromatosis patients has been reported previously. Therefore, we exposed a wild-type p53 TK-6 lymphoblastoid cell line to 4-hydroxynonenal, an unsaturated aldehyde involved in lipid peroxidation, and observed an increase in G to T transversions at p53 codon 249 (AGG to AGT). These results are consistent with the hypothesis that the generation of oxygen/nitrogen species and unsaturated aldehydes from iron and copper overload in hemochromatosis and WD causes mutations in the p53 tumor suppressor gene.

Aldehydes↗
PubMed2000

Lipid-lowering therapy after coronary revascularization.

Atherosclerosis is often asymptomatic, unrecognized, and undertreated. Lumen irregularities are important angiographic findings that should be addressed aggressively through risk factor modification, medical therapy, and coronary revascularization. Both angiographic and clinical benefits have been demonstrated with lipid reduction therapy in randomized clinical trials. Coronary revascularization is indicated for symptom relief and improvement in quality of life in patients with acute coronary syndromes at "intermediate" and "high" risk of subsequent death or myocardial infarction. In patients following percutaneous coronary intervention (PCI), future cardiac events may be related to lumen renarrowing or to progression of atherosclerotic disease at sites remote from the site of coronary revascularization. The time course of restenosis is relatively self-limiting, generally occurring within 6-12 months after the procedure. Clinical events occurring > 1 year after PCI generally relate to new lesions or progression of existing atherosclerotic disease. Patients with diabetes mellitus may be at higher risk for late coronary events than nondiabetic patients. In post-coronary artery bypass surgery (CABG) patients, the majority of late events relate to degeneration of saphenous vein grafts. Lipid lowering therapy after coronary revascularization has been shown to prevent clinical events related to plaque instability and inhibit progression of saphenous vein graft disease. Thus, there are 2 goals in management of patients with symptomatic coronary artery disease: (1) to relieve the flow-limiting stenosis, and (2) to prevent future clinical events with aggressive lipid lowering and modification of other risk factors. Patients, specialists, and primary care physicians each need to take accountability for this risk-factor modification.

Coronary Angiography↗
PubMed2000

Applying workflow analysis tools to assess immunization delivery in outpatient primary care settings.

BACKGROUND: As health care organizations face increasing pressure to institute quality assurance activities, the already-underfunded community clinics that treat the poor and underserved are challenged to perform these activities within tight constraints of human and financial resources. With pediatric immunizations as a marker, a workflow observation tool was used to identify causal processes affecting immunization delivery. METHODS: Ten clinics and five private practices, located in areas designated as health professional shortage areas, participated in the study, gaining access to a tool that would have been unaffordable to them from the private sector. Trained observers followed families through the clinic, using a 127-item workflow observation form--the Observational Checklist of Patient Encounters (OCPE)--assessing discrete activities that families encountered during the checkin/pre-exam, exam, discharge, and billing processes. A convenience sampling of the targeted population--children younger than three years of age--included observations of scheduled acute, scheduled well-child, follow-up, and walk-in visits. In the feedback session, a summary of each clinic's immunization delivery patterns was presented, with an emphasis on the individual health center's operational issues. RESULTS: The workflow observation tool was used to identify operational errors affecting both clinical and fiscal processes in each of the clinics that had not been previously apparent to either clinic management or the quality improvement (QI) teams. DISCUSSION: Feedback addressed and encouraged process-oriented improvements in response to the workflow observations, which were incorporated into the clinics' QI procedures. Twelve of the 15 clinics have formed process action teams to address QI issues on an ongoing basis.

Age Factors↗
PubMed2000

Standard dose (Mayo regimen) 5-fluorouracil and low dose folinic acid: prohibitive toxicity?

Despite the perception that standard 5-fluorouracil/folinic acid (5-FU/FA) (425 mg/m2 per day and 20 mg/m2 per day intravenously once daily x 5 every 4 or 5 weeks) is well tolerated, we have been impressed by toxicity seen and frequent need for dose modification. We performed a retrospective analysis to quantitate the proportion of patients experiencing toxicity and attempted to identify associated clinical characteristics. One hundred thirty-four patients received 5-FU/FA at standard doses described by the Mayo regimen. Patient characteristics were as follows: female 35%, median age 66 years, Eastern Cooperative Oncology Group performance status less than or equal to 2, 96%. Sixty-eight percent received chemotherapy for metastatic disease. Forty-seven patients (35%+/-8%) experienced significant toxicity and were unable to receive the second cycle as scheduled: 76% required dose reduction, 11% discontinued therapy (including two toxic deaths), 11% discontinued therapy during the first cycle, and 2% required dose delay. Logistic regression was used to explore the following as predictors of toxicity: age, sex, performance status, adjuvant versus metastatic setting, prior chemotherapy, prior radiation, mean corpuscular volume, red blood cell distribution width, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, and calculated creatinine clearance. No clinical characteristic was found to predict toxicity. Only high bilirubin approached statistical significance. We conclude that standard 5-FU/FA, when used in the general population, is associated with significant toxicity. Known clinical characteristics are not helpful in predicting toxicity. The lack of previous formal phase I evaluation of this regimen of 5-FU/FA raises concerns regarding its safety and generalizability in clinical practice.

Adult↗
PubMed1999

A comparison of parent and adolescent reports describing the health-related quality of life of adolescents treated for cancer.

Our objectives were to compare adolescent and parent ratings of the health-related quality of life (HRQL) of adolescents treated for cancer, to compare the HRQL of adolescents who were on treatment vs. the HRQL of those who were off treatment following their diagnosis with cancer and to assess the HRQL of adolescents who were at different points of time following their diagnosis with cancer. The HRQL of 70 adolescents (aged 10 to 18 years) consecutively attending the Women's and Children's Hospital Oncology Clinic in South Australia was assessed by means of standard questionnaires. Parents completed the Child Health Questionnaire, the Functional Status II(R) Questionnaire and the Impact-on-Family Scale. Adolescents completed the self-report version of the Child Health Questionnaire. In general, there was good agreement between parent and adolescent reports. However, parents of adolescents receiving active treatment for cancer reported that their illness was having a greater impact on the adolescents' physical functioning than was reported by the adolescents. The psycho-social functioning of adolescents in single-parent families was reported also by parents to be worse than that of adolescents in 2-parent families. The physical functioning of adolescents had only a weak relationship with parental status but a significant relationship with treatment status. Despite generally good agreement between parent and adolescent reports describing the HRQL of adolescents treated for cancer, it cannot be assumed that reports from parents are always an accurate reflection of the views of the adolescents. Studies examining the influence of independent factors on adolescents' HRQL must take into account differences in reports from these 2 informants and the possibility that key independent variables have differing relationships with the various domains which comprise adolescents' HRQL.

Adolescent↗
PubMed1999

The treatment of distant metastases in soft tissue sarcoma.

This article reviews the current standard approaches to the treatment of metastatic soft tissue sarcoma (STS) and evaluates new chemotherapy agents and novel approaches. A computerized search strategy was used to identify articles examining the role of chemotherapy and surgery in metastatic STS, which were published between January 1992 and December 1998. This search was supplemented by key articles from our files published before 1992. In selecting articles for inclusion in this review, emphasis was placed on randomized data and novel approaches. Only three agents-doxorubicin, ifosfamide, and dacarbazine-have shown significant activity in metastatic STS. Numerous studies have examined the efficacy and toxicity of combining the known active agents in standard doses or in high doses with cytokine support. Promising results, in terms of increased response rates, often have not been reproduced in randomized trials, and there is no convincing evidence of enhanced overall survival. New regimens should be evaluated in randomized trials incorporating quality-of-life endpoints. High-dose chemotherapy with bone marrow/stem cell rescue remains an investigational procedure of uncertain efficacy. Pilot studies have established the feasibility of intraperitoneal chemotherapy, after cytoreductive surgery, in patients with peritoneal sarcomatosis. To date, the efficacy of this approach has not been validated in phase II or III trials. The role of surgery in the treatment of isolated pulmonary metastases is well established. Results of small series raise the possibility that resection of hepatic metastases is beneficial in selected patients. Current chemotherapy options for patients with STS are limited. There is reason to hope that the situation will change with the further development of new agents that have novel and specific mechanisms of action.

Antineoplastic Agents, Alkylating↗
PubMed1999

The role of the family for behavioral outcome in children and adolescents following traumatic brain injury.

This study assessed the behavioral outcome of 51 children with traumatic brain injury (TBI) up to 2 years following injury. Children with severe injuries, but not those with mild or moderate injuries, were reported by parents to have a greater incidence of behavior problems following TBI. Regression analyses indicated that the presence of a partner for the primary caregiver of the child and the acute emotional reaction of the parent to the injury were both predictive of child behavioral outcome, although not by 2-year follow-up. These findings suggest that parental coping resources may impact on the development of child behavioral sequelae following TBI, emphasizing the role of the family in the child's response and the importance of supportive intervention.

Adolescent↗
PubMed1999

Failure to maintain the benefits of home-based intervention in adolescents with poorly controlled type 1 diabetes.

OBJECTIVE: To determine whether a 6-month home-based intervention program in adolescents with poorly controlled diabetes improves metabolic control and whether benefits are maintained after the intervention. RESEARCH DESIGN AND METHODS: Adolescents with a mean HbA1c of > 9.0% over the preceding 12 months received either routine care in a diabetes clinic and an ambulatory intervention for 6 months (n = 37) or routine care only (n = 32). A diabetes educator provided monthly home visits and weekly phone contact to educate and support the adolescents in setting goals for insulin adjustment, blood glucose monitoring, and target blood glucose range. There was no systematic change in the frequency of insulin injections. After the intervention, there was a 12-month follow-up when the intervention and control groups both received only routine care. Outcome measures were HbA1c and Diabetes Knowledge Assessment (DKN). RESULTS: During the intervention, mean HbA1c fell (baseline: 11.1 +/- 1.3%, 6 months: 9.7 +/- 1.6%; P = 0.0001) and mean knowledge scores increased (P = 0.0001) in the intervention group but not in control subjects. However, this improvement in HbA1c and increase in knowledge was not maintained in the intervention group at 12- and 18-month follow-up assessments. Parents' knowledge scores also improved significantly from baseline levels in the intervention group at 6 and 12 months (P = 0.001, P = 0.005, respectively). CONCLUSIONS: An ambulatory program improves metabolic control and knowledge in adolescents with poorly controlled type 1 diabetes; however, it is effective only while the intervention is maintained.

Adolescent↗
PubMed1998

Individual change after genocide in Bosnian survivors of "ethnic cleansing": assessing personality dysfunction.

The authors used the SCID-DES (disorders of extreme stress) instrument to assess for personality change in Bosnian survivors of "ethnic cleansing." Twenty four refugees underwent systematic, trauma-focused, research assessments, including the SCID-DES interview. Overall, this group of Bosnian survivors had been severely traumatized as a result of the Serbian nationalists' genocide. However, no subject met diagnostic criteria for DES. The SCID-DES yields far lower rates of trauma-related personality change in Bosnian survivors of genocide than in adult survivors of prolonged early life traumas. Therefore, the DES construct may have better application to prolonged, interpersonal, early life traumas than to the prolonged, communal traumas of genocide.

Adolescent↗
PubMed1998

The use of alternative therapies by children with asthma: a brief report.

OBJECTIVE: To identify the nature and prevalence of alternative therapies used by children with asthma attending a children's hospital. METHODOLOGY: Subjects consisted of a consecutive series of 51 children with asthma aged 1-6 years who were attending the Women's and Children's Hospital, South Australia. Parents of the children completed a questionnaire describing the use of alternative therapies by the children. RESULTS: Approximately 55% of children used alternative therapies for asthma management. Therapies used most commonly were massage, relaxation exercises, diet therapy and vitamins. There was no significant difference in the age, asthma severity, length of time since diagnosis or presence of another illness amongst children who did or did not use alternative therapies. CONCLUSIONS: A substantial proportion of children with asthma who attend paediatric clinics use alternative therapies. Paediatricians should be aware of this and be prepared to discuss alternative therapies with parents. This may facilitate more open doctor-patient relationships and better management of children's asthma.

Asthma↗
PubMed1998

PTSD symptoms in Bosnian refugees 1 year after resettlement in the United States.

OBJECTIVE: The authors' goal was to describe the characteristics of posttraumatic stress disorder (PTSD) symptoms on resettlement in the United States and at 1-year follow-up among Bosnian refugees as well as possible factors affecting the PTSD symptom profile among these refugees. METHOD: They used standardized instruments to assess 34 Bosnian refugees for PTSD at resettlement in the United States and 1 year later. RESULTS: Fifteen of the refugees were diagnosed with PTSD at 1-year follow-up, compared with 25 at initial assessment. The average PTSD severity score at follow-up was 12.5, compared with 20.6 at initial assessment. At 1-year follow-up, 25 of the refugees experienced a decrease in severity of PTSD symptoms, one remained the same, and eight experienced an increase in severity. Older refugees were significantly more likely to have PTSD than younger refugees, and older refugees had more severe symptoms. CONCLUSIONS: The level of PTSD diagnosis and symptoms in Bosnian refugees remained substantial 1 year after their resettlement in the United States, although there were notable overall decreases. Older refugees appeared to be at greater risk.

Adolescent↗