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Biomedical subjects

S Ash

Publications and source records attributed to S Ash.

At least 19 recordsLinked to original sources

Trying to tell a tale: discourse impairments in progressive aphasia and frontotemporal dementia.

OBJECTIVE: To assess discourse in patients with frontotemporal dementia (FTD). METHODS: The authors asked patients with progressive nonfluent aphasia (PNFA), patients with semantic dementia (SemD), and nonaphasic patients with a disorder of social comportment and executive functioning (SOC/EXEC) to narrate the story of a wordless children's picture book. RESULTS: The authors found significant discourse impairments in all three groups of patients. Moreover, there were qualitatively important differences between the groups. Patients with PNFA had the sparsest output, producing narratives with the fewest words per minute. Patients with SemD had difficulty retrieving words needed to tell their narratives. Though not aphasic, patients with SOC/EXEC had profound difficulty organizing their narratives, and they could not effectively express the point of the story. This deficit correlated with poor performance on a measure of executive resources requiring an organized mental search. In addition, a correlation of narrative organization with cortical atrophy in patients with SOC/EXEC was significant in right frontal and anterior temporal brain regions. CONCLUSIONS: Impaired day-to-day communication in nonaphasic frontotemporal dementia patients with a disorder of social comportment and executive functioning is due in part to a striking deficit in discourse organization associated with right frontotemporal disease. Difficulty with discourse in progressive aphasia is due largely to the language impairments of these patients.

Aged↗

A randomised control trial comparing lifestyle groups, individual counselling and written information in the management of weight and health outcomes over 12 months.

OBJECTIVE: To investigate the effect of an 8-week group-based cognitive behaviour therapy lifestyle intervention with monthly follow-up to 6 months and further follow up at 12 months on change in weight and other weight-related variables, change in physical activity and change in health and well being compared to individualised dietetic treatment or giving an information booklet only (BO). DESIGN: A randomised controlled trial of two intervention groups, a group-based cognitive behaviour therapy lifestyle intervention, Fat Booters Incorporated--(FBI) and individualised dietetic treatment (IDT) and control group receiving an information booklet only (BO). The intervention groups involved weekly contact for 8 weeks with monthly follow-up to 6 months and further follow-up at 12 months, conducted in real practice setting. SUBJECTS: A total of 176 adults with body mass index (BMI)>27 kg/m2, mean (+/-s.d.) age 48+/-13 years, mean BMI 34+/-5.5 kg/m2. MAIN OUTCOME MEASURES: Weight, percent body fat, waist circumference, physical activity, health status, self-efficacy and satisfaction with life were measured at baseline, 3, 6 and 12 months. RESULTS: A statistically significant difference between groups was observed for weight change over time (P=0.05). The change in weight (mean+/-s.e.) for the FBI group was significantly greater than the BO group at 3 and 12 months (-2.8+/-0.7 compared to -1.0+/-0.6 kg, P<0.05 and -2.9+/-0.9 compared to +0.5+/-0.9 kg, P<0.005, respectively). Change in weight in the IDT group did not differ from the FBI group at any time point. For all groups, waist circumference was significantly less than baseline at all time points (P<0.001). Significant differences in self-efficacy were observed over time (P=0.02), with both intervention groups having greater self-efficacy than the BO group. Significant drop-outs occurred over time for all three groups. CONCLUSIONS: A cognitive behaviour-based lifestyle intervention was more effective than providing an information booklet alone and as effective as intensive individualised dietetic intervention in weight loss and improvements in self-efficacy.

Adult↗

The role of orthodontics and oral and maxillofacial surgery in the management of obstructive sleep apnoea - a single case report.

Obstructive sleep apnoea (OSA) is a potentially fatal breathing disorder, yet is widely under-diagnosed. It is a multi-factorial condition associated with high morbidity, a degree of mortality and is associated with an increase risk of car crashes. A case is presented which demonstrates the inter-disciplinary approach to this condition and the successful treatment through mandibular advancement by orthodontic means followed by orthognathic surgery. The experience of this patient illustrates the importance of the disciplines of orthodontics and oral and maxillofacial surgery in the multi-disciplinary management of these patients.

Continuous Positive Airway Pressure↗

Tumor cells are present in stem cell harvests of Ewings sarcoma patients and their persistence following transplantation is associated with relapse.

BACKGROUND: Tumor cells frequently contaminate autologous stem cell products in a variety of malignancies, but their clinical significance remains controversial. We retrospectively monitored tumor contamination in stem cell harvests from patients with Ewing family of tumors (EFT) all harboring the specific translocation EWS-FLI-1 that characterize these tumors. PROCEDURE: Twenty- seven harvests from 11 patients were included in the study. In addition, 6 and 19 bone marrow (BM) or peripheral blood (PBL) samples were available before and after transplantation, respectively, for RT-PCR and nested PCR analyzes. RESULTS: All 11 patients had contaminating tumor cells in their harvests. All samples prior to transplantation were RT-PCR positive. Two out of the 11 patients who underwent transplantation died of complications. Out of the remaining nine patients, two are alive and well 68 and 84 months from diagnosis, and are the only patients with no detectable tumor cells in their samples after transplantation. One of these patients harbored contaminating tumor cells in only one of the two harvests collected. Seven patients relapsed after transplant, and in four patients BM/PBL samples were available prior to the clinical relapse. All these samples harbored contaminating tumor cells. CONCLUSIONS: We suggest a possible correlation between the amount of contaminating cells in the harvest and relapse after transplantation. Quantitative RT-PCR studies of the chimeric transcripts are underway to explore this issue.

Adolescent↗

Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life.

BACKGROUND AND AIM: Obesity is a risk factor for progression of fibrosis in chronic liver diseases such as non-alcoholic fatty liver disease and hepatitis C. The aim of this study was to investigate the longer term effect of weight loss on liver biochemistry, serum insulin levels, and quality of life in overweight patients with liver disease and the effect of subsequent weight maintenance or regain. PATIENTS: Thirty one patients completed a 15 month diet and exercise intervention. RESULTS: On completion of the intervention, 21 patients (68%) had achieved and maintained weight loss with a mean reduction of 9.4 (4.0)% body weight. Improvements in serum alanine aminotransferase (ALT) levels were correlated with the amount of weight loss (r = 0.35, p = 0.04). In patients who maintained weight loss, mean ALT levels at 15 months remained significantly lower than values at enrollment (p = 0.004), while in regainers (n = 10), mean ALT levels at 15 months were no different to values at enrollment (p = 0.79). Improvements in fasting serum insulin levels were also correlated with weight loss (r = 0.46, p = 0.04), and subsequent weight maintenance sustained this improvement. Quality of life was significantly improved after weight loss. Weight maintainers sustained recommended levels of physical activity and had higher fasting insulin levels (p = 0.03) at enrollment than weight regainers. CONCLUSION: In summary, these findings demonstrate that maintenance of weight loss and exercise in overweight patients with liver disease results in a sustained improvement in liver enzymes, serum insulin levels, and quality of life. Treatment of overweight patients should form an important component of the management of those with chronic liver disease.

Adult↗

Effect of intensive dietetic interventions on weight and glycaemic control in overweight men with Type II diabetes: a randomised trial.

OBJECTIVE: To investigate the effectiveness of intensive innovative methods for implementing dietary prescriptions on weight management and glycaemic control in overweight men with Type II diabetes. DESIGN: A randomised clinical trial with a 12-week intervention period - three isocaloric dietary intervention groups (intermittent energy restriction, pre-portioned meals and self-selected meals) each with weekly dietitian contact - and a follow-up visit after 18 months. SUBJECTS: A total of 51 men with Type II diabetes (mean age 54 y, mean body mass index (BMI) 31.7 kg/m(2)). MEASUREMENTS: Weight, body composition, waist circumference, glycaemic control (HbA(1c)) and blood lipids. RESULTS: For all subjects, intensive diet therapy over the 12-week intervention period resulted in a mean reduction in energy intake of 2360+/-2780 kJ/day (564+/-665 kcal/day) and significant reductions in weight (6.4+/-4.6 kg), waist circumference (8.1+/-4.6 cm), percent body fat (1.9+/-1.5%), HbA(1c) (1.0+/-1.4%) and triglyceride levels (0.3+/-0.6 mmol/l) compared to baseline levels. Intervention group did not affect clinical outcomes, with the exception of percent body fat. A total of 27 (52.9%) subjects attended the 18-month follow-up visit. At this visit, none of the improvements in clinical parameters was maintained, with all parameters returning to preintervention levels. CONCLUSIONS: : A dietary prescription of 6000-7000 kJ/day (1400-1700 kcal/day) was effective in achieving a 6% weight loss and improving glycaemic control. The method of implementation made no difference to the outcomes between groups at 12 weeks or 18 months. Thus, we propose that it was the intensive weekly contact with a health professional in combination with moderate energy restriction that facilitated the successful short-term results seen.

Adult↗

Central nervous system involvement in children with sarcoma.

OBJECTIVES: To summarize and analyze the experience in CNS involvement (CNSI) in children with sarcomas treated in the above-mentioned institutions. PATIENTS AND METHODS: From 1990 to 2001, all medical charts were retrospectively reviewed: 19 sarcoma patients (12 boys and 7 girls) were diagnosed with CNSI (4 osteogenic sarcomas, 11 Ewing sarcomas, 2 rhabdomyosarcomas, 1 alveolar soft part sarcoma and 1 mesenchymal chondrosarcoma). Mean age of all patients at the time of initial diagnosis was 14.9 years (range: 4-24 years), mean age at the time when CNSI was diagnosed was 16.9 years (range: 5.5-27 years). RESULTS: The frequency of CNSI among our patients was 6.17%. The following symptoms and signs (sometimes combined) presented: headache (10 patients), nausea and vomiting (6 patients), seizures (11 patients) and focal neurological signs (9 patients). The mean duration of time elapsed since diagnosis of CNSI till death or last follow-up was 5.2 months (SD: +/-5.7 months). Four patients received chemotherapy (CT) alone, 8 CT and radiotherapy (RT), 2 RT alone, 3 supportive treatment only, 1 CT and surgery and 1 surgery alone. Sixteen patients died; there was no significant difference in the duration of survival between those who were treated with RT or surgery (mean +/- SD: 6.77 +/- 6.56 months) and those who received only CT or supportive treatment (mean +/- SD: 2.60 +/- 2.94 months) (p = 0.07). Brain disease was the main cause of death in all but 1 patient who died 4 days after autologous bone marrow transplantation from uncontrolled sepsis. In 16 patients, CNSI was part of a metastatic disease. CONCLUSIONS: Among children with sarcoma, CNSI is encountered in 6.17% of cases. More effective therapy has to be developed in order to improve their outcome.

Adolescent↗

Estimation of total body water from bioelectrical impedance analysis in patients with pancreatic cancer -- agreement between three methods of prediction.

INTRODUCTION: Bioelectrical impedance analysis (BIA) is a useful field measure to estimate total body water (TBW). No prediction formulae have been developed or validated against a reference method in patients with pancreatic cancer. The aim of this study was to assess the agreement between three prediction equations for the estimation of TBW in cachectic patients with pancreatic cancer. METHODS: Resistance was measured at frequencies of 50 and 200 kHz in 18 outpatients (10 males and eight females, age 70.2 +/- 11.8 years) with pancreatic cancer from two tertiary Australian hospitals. Three published prediction formulae were used to calculate TBW - TBWs developed in surgical patients, TBWca-uw and TBWca-nw developed in underweight and normal weight patients with end-stage cancer. RESULTS: There was no significant difference in the TBW estimated by the three prediction equations - TBWs 32.9 +/- 8.3 L, TBWca-nw 36.3 +/- 7.4 L, TBWca-uw 34.6 +/- 7.6 L. At a population level, there is agreement between prediction of TBW in patients with pancreatic cancer estimated from the three equations. The best combination of low bias and narrow limits of agreement was observed when TBW was estimated from the equation developed in the underweight cancer patients relative to the normal weight cancer patients. When no established BIA prediction equation exists, practitioners should utilize an equation developed in a population with similar critical characteristics such as diagnosis, weight loss, body mass index and/or age. CONCLUSIONS: Further research is required to determine the accuracy of the BIA prediction technique against a reference method in patients with pancreatic cancer.

Aged↗

Effect of weight reduction on liver histology and biochemistry in patients with chronic hepatitis C.

BACKGROUND: Steatosis occurs in more than 50% of patients with chronic hepatitis C and is associated with increased hepatic fibrosis. In many of these patients the pathogenesis of steatosis appears to be the same as for patients with non-alcoholic fatty liver disease-that is, related to visceral adiposity and obesity. METHODS: The effect of a three month weight reduction programme on liver biochemistry and metabolic parameters was examined in 19 subjects with steatosis and chronic hepatitis C. Paired liver biopsies were performed in 10 subjects, prior to and 3-6 months following the intervention, to determine the effect of weight loss on liver histology. RESULTS: There was a mean weight loss of 5.9 (3.2) kg and a mean reduction in waist circumference of 9.0 (5.0) cm. In 16 of the 19 patients, serum alanine aminotransferase levels fell progressively with weight loss. Mean fasting insulin fell from 16 (7) to 11 (4) mmol/l (p<0.002). Nine of 10 patients with paired liver biopsies had a reduction in steatosis irrespective of viral genotype. In these subjects the median modified Knodell fibrosis score decreased from 3 to 1 (p=0.04) and activated stellate cells significantly decreased (p<0.004). CONCLUSIONS: Weight loss in patients with chronic hepatitis C may be associated with a reduction in steatosis and abnormal liver enzymes and an improvement in fibrosis, despite the persistence of the virus. Weight reduction may provide an important adjunct treatment strategy for patients with chronic hepatitis C.

Adult↗

A phase III study of recombinant human interferon gamma to prevent opportunistic infections in advanced HIV disease.

The efficacy and safety of recombinant human interferon gamma (rIFN-gamma) in the reduction of opportunistic disease in patients with advanced HIV-1 infection are assessed. A 12-month double-blind, placebo-controlled, multicenter, Phase III trial of rIFN-gamma in HIV-positive patients with CD4 < 100 x 10(9)/liter on stable antiretroviral therapy. Eighty-four patients were allocated treatment on a 1:1 basis to rIFN-gamma or placebo. Patients received rIFN-gamma 0.05 mg/m(2) or 0.9% saline subcutaneously three times weekly for 48 weeks (optional extension to 18 months). The primary end point was the incidence of opportunist infections (CDC categories B/C). Secondary end points included mortality, immunological, and virological parameters. Patients on placebo had a mean of 3.45 opportunist infections (OIs) in the first 48 weeks. Patients treated with rIFN-gamma had a mean of 1.71 OIs (p = 0.04). However, the model showed overdispersion and the inclusion of a dispersion factor raised the p value to 0.13. rIFN-gamma appeared to have a particular effect on the incidence of Candida, herpes simplex, and cytomegalovirus infections. Three-year survival in the rIFN-gamma arm was 28% compared to 18% in the placebo group (not significant). rIFN-gamma-associated side-effects of headache, fatigue, rigors, influenza-like symptoms, depression, myalgia, and granulocytopenia were reversible. There was no evidence for HIV activation. Although not significant, the trend towards decreased opportunistic infections and increased survival warrants consideration of further trials of rIFN-gamma. The study gives additional information on the safety profile of this cytokine.

AIDS-Related Opportunistic Infections↗

Longitudinal study of serum neutralization of HIV-1 in infected plasma donors.

Earlier studies provided suggestive evidence about the effectiveness of passive immunotherapy for AIDS patients using plasma donated by healthy HIV-1 infected individuals and revealed beneficial effects of plasmapheresis for the immune system of the donors. In this study, anti-HIV-1 neutralizing activity in 31 healthy HIV-1 infected donors of plasma participating in a passive immunotherapy study was investigated as a function of time. Average studied period was 33 months. Using the highly cytopathic HIV-1 NDK strain and MOLT4 cells, it was shown by means of syncytia formation inhibition assay and polyclonal HIV-1 antigen-capture assay that viral neutralizing titers tend either to remain unchanged or increase over time. These findings support the notion that the immune system is not affected adversely in HIV-1 infected plasma donors and lend further support to the feasibility of passive immunotherapy for AIDS patients.

Blood Donors↗

Significance of residual abdominal masses in children with abdominal Burkitt's lymphoma.

PURPOSE: To evaluate the natural history of children with abdominal Burkitt's lymphoma who had complete clinical remission and residual abdominal mass after treatment. MATERIAL AND METHODS: The charts and imaging findings of all children with abdominal Burkitt's lymphoma treated and followed at our medical center between 1988 and 1999 were reviewed for the presence, management, clinical course, and prognosis of residual mass. RESULTS: Only children who achieved complete clinical remission were included. The study group consisted of 33 children (20 boys and 13 girls) aged 2.6-17.6 years (mean 7.2 years). Of these, seven (20.6 %) were found to have a residual abdominal mass. Two underwent second-look operation with no evidence of viable tumor on histology. The remaining five were followed by imaging studies for 2.2-9.1 years (mean 6.1 years); none relapsed. CONCLUSION: Residual mass is not uncommon in children with abdominal Burkitt's lymphoma. The presence of residual mass in a child with complete clinical remission does not alter the long-term prognosis. Therefore, in children with Burkitt's lymphoma and residual mass with no other signs of disease activity, expectant watching may be appropriate.

Abdominal Neoplasms↗

Apparently unrelated clones shown by spectral karyotyping to represent clonal evolution of cryptic t(10;11)(p13;q23) in a patient with acute monoblastic leukemia.

The accurate genetic classification of acute leukemia is of the utmost clinical importance for treatment stratification. In the present study, we report on a young girl with aggressive acute monoblastic leukemia (AML) (M5b) with skin, lymph node, and bone marrow involvement, in whom cytogenetic analysis revealed three clones with different secondary chromosomal changes. Two clones had the secondary +8 and del(9q) aberrations, with the der(11)t(1;11) in the second one; the third clone was apparently unrelated to the others, and had add(7)(p?21),-13,+22. Using the spectral karyotyping (SKY) technique, we found that all three clones originated from a common clone that harbored the hidden primary t(10;11)(p13;q23) or its derivatives, suggesting clonal evolution. The first clone had the balanced t(10;11), the second had its derivative, der(10)t(10;11), and the third had the other derivative, der(11)t(10;11). On fluorescence in situ hybridization (FISH), MLL gene splitting, with translocation of its centromeric portion to 10p, and deletion of its telomeric portion, was demonstrated. In conclusion, the detection of the very poor prognostic t(10;11) aberration in AML, was possible by complementing the traditional cytogenetic analysis with SKY and FISH.

Bone Marrow Cells↗

High frequency of loss of heterozygosity for 1p35-p36 (D1S247) in Wilms tumor.

We analyzed the loss of heterozygosity (LOH) for 1p in 18 Wilms tumors using a panel of 11 polymorphic markers. Loss of heterozygosity was identified in 56% of the tumors. The smallest region of overlap was defined for marker D1S247, underlying the 1p35-1p36.1 locus. This is the highest LOH frequency for 1p, or for the well-defined 11p13 and 11p15.5 loci. Based on the fact that tumors of all stages, with both favorable and unfavorable histology, exhibited LOH, we suggest that the 1p35-1p36.1 locus is involved in the etiology of Wilms tumor.

Child↗