A free-ranging roundtable discussion on hypertension.
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Biomedical Research↗
Biomedical subjects
M Brown
Publications and source records attributed to M Brown.
A genome scan in multigenerational families with dyslexia: Identification of a novel locus on chromosome 2q that contributes to phonological decoding efficiency.
Dyslexia is a common and complex developmental disorder manifested by unexpected difficulty in learning to read. Multiple different measures are used for diagnosis, and may reflect different biological pathways related to the disorder. Impaired phonological decoding (translation of written words without meaning cues into spoken words) is thought to be a core deficit. We present a genome scan of two continuous measures of phonological decoding ability: phonemic decoding efficiency (PDE) and word attack (WA). PDE measures both accuracy and speed of phonological decoding, whereas WA measures accuracy alone. Multipoint variance component linkage analyses (VC) and Markov chain Monte-Carlo (MCMC) multipoint joint linkage and segregation analyses were performed on 108 families. A strong signal was observed on chromosome 2 for PDE using both VC (LOD=2.65) and MCMC methods (intensity ratio (IR)=32.1). The IR is an estimate of the ratio of the posterior to prior probability of linkage in MCMC analysis. The chromosome 2 signal was not seen for WA. More detailed mapping with additional markers provided statistically significant evidence for linkage of PDE to chromosome 2, with VC-LOD=3.0 and IR=59.6 at D2S1399. Parametric analyses of PDE, using a model obtained by complex segregation analysis, provided a multipoint maximum LOD=2.89. The consistency of results from three analytic approaches provides strong evidence for a locus on chromosome 2 that influences speed but not accuracy of phonological decoding.
Adolescent↗
Successful liposomal amphotericin B treatment of Leishmania braziliensis cutaneous leishmaniasis.
Existing systemic treatments for New World cutaneous leishmaniasis (CL) caused by Leishmania (vianna) braziliensis are unsatisfactory. Liposomal amphotericin B has been used extensively for the treatment of visceral leishmaniasis, but in few cases of CL, and an appropriate regimen for CL has not been described. We successfully treated a patient with multiple L. braziliensis CL lesions acquired in Belize. Liposomal amphotericin B (AmBisome) was given to our patient as an inpatient for seven daily doses of 3 mg kg(-1) day(-1) and then as an outpatient at 3 mg kg(-1) twice weekly for a further three weeks, a total of 40 mg kg(-1). Liposomal amphotericin offers a well-tolerated alternative to pentavalent antimony or amphotericin B deoxycholate for the systemic treatment of New World CL.
Adult↗
Randomized placebo-controlled trial of a flavonoid-rich plant extract-based cream in the treatment of rosacea.
BACKGROUND: Biological research suggests that vascular changes may play a major role in rosacea pathogenesis. Chrysanthellum indicum is a plant-based extract containing a unique combination of phenylpropenoic acids, flavonoids and saponosids, and has a well-documented effect on vascular wall permeability and increase of the mechanical resistance of capillaries. OBJECTIVE: To determine the efficacy and safety of a cream containing 1%C. indicum extract with vitamin P properties in the treatment of rosacea. METHODS: This study included 246 patients diagnosed clinically as having moderate rosacea. Patients were randomly allocated to C. indicum extract-based cream (n = 125) and placebo (n = 121) groups. Patients were advised to apply the products on their face twice a day for a 12-week period. The patients were examined at the end of each 4-week period. Severity of erythema (graded by reference to six photographs), surface of erythema and rosacea overall severity scores were recorded at each visit on days 0, 28, 56 and 84. Investigators carried out a final efficacy assessment at the end of week 12. Volunteers' final overall efficacy assessment was recorded in a self-administered questionnaire. Adverse events were identified through examination, interview and collection of comments in patients' questionnaires. RESULTS: Treatment with the C. indicum extract-based cream resulted in significant improvement (P < 0.05) in severity of erythema, overall rosacea severity compared to baseline and placebo, and investigator and patient overall efficacy assessment scores (P = 0.046 and P = 0.001, respectively) compared with placebo scores. Adverse reactions were mild, and did not differ between the C. indicum extract-based cream and the placebo groups. CONCLUSION: Chrysanthellum indicum extract-based cream is an effective and well-tolerated topical agent for the treatment of moderate rosacea. The mode of action of the active ingredient suggests that additional efficacy might be expected from combination with other topical treatments.
Administration, Topical↗
Utility analysis tells all.
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Health Status Indicators↗
Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations.
The genetic aetiology of autism remains elusive. Occasionally, individuals with Cowden syndrome (a cancer syndrome) and other related hamartoma disorders such as Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-like conditions, are characterised by germline PTEN mutations, and may have neurobehavioural features resembling autism as well as overgrowth and macrocephaly. Therefore, we undertook PTEN gene mutation analysis in 18 subjects mainly prospectively ascertained with autism spectrum disorder and macrocephaly. Of these 18 autistic subjects (13 males and five females; ages 3.1-18.4 years) with a head circumference range from 2.5 to 8.0 standard deviations above the mean, three males (17%) carried germline PTEN mutations. These three probands had previously undescribed PTEN mutations: H93R (exon 4), D252G (exon 7), and F241S (exon 7). They had the larger head circumference measurements amongst all our study subjects. The three residues altered in our patients were highly evolutionarily conserved. We suggest that PTEN gene testing be considered for patients with autistic behaviour and extreme macrocephaly. The gene findings may impact on recurrence risks as well as medical management for the patient.
Adolescent↗
Pyrexia of unknown origin: a review of studies from the developing world.
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Developing Countries↗
Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group.
Previous studies have shown that activating mutations of c-KIT/PDGFRA, potential therapeutic targets for imatinib mesylate, are implicated in the pathophysiology of gastrointestinal stromal tumours (GISTs). In this study, GISTs from 37 patients enrolled in an European Organisation for Research and Treatment of Cancer (EORTC) phase I/II clinical study of imatinib were examined for mutations of c-KIT/PDGFRA in order to explore whether the mutational status of the tumour predicts the clinical response to therapy. Mutations were screened by denaturing high-pressure liquid chromatography (DHPLC) and characterised by bi-directional DNA sequencing. Activating mutations of c-KIT or PDGFRA were found in 29 (78%) and 2 (6%) GISTs, respectively. Most c-KIT mutations involved exon 11 (n=24; 83%), all but one being an in-frame deletion; no isolated point mutations were found. The other c-KIT mutations included exon 9 AY 502-503 duplication (n=4; 14%) and exon 13 Lys-->Glu(642) missense mutation (n=1; 3%). Two tumours with no detectable c-KIT mutations demonstrated PDGFRA Asp-->Glu(842) amino acid substitutions. Patients with GISTs harbouring exon 11 mutations were more likely to achieve a partial response (PR) on imatinib therapy (83%) than all of the others (23%). The overall survival and progression-free survival rates for the entire group at 106 weeks were 78.3% and 46.9%, respectively. Based on a Kaplan-Meier analysis, patients with GISTs harbouring c-KIT mutations had longer median survival times and were less likely to progress than the other patients. These findings indicate that the mutational status of the c-KIT/PDGFRA oncoproteins could be useful to predict the clinical response of patients imatinib therapy.
Adult↗
Congenital ocular motor apraxia associated with idiopathic generalized epilepsy in monozygotic twins.
Identical female twins (age 11 years) with congenital ocular motor apraxia and generalized idiopathic epilepsy are reported. Their presenting symptoms were a long history of abnormal head and eye movements. One twin developed partial sensory seizures. The patients underwent 16-channel EEG, electro-oculographic recordings, MRI of the brain, and genetic and metabolic investigations. EEG findings were consistent with idiopathic generalized epilepsy. Electrooculographic recordings of the saccades confirmed an inability to elicit horizontal saccades without preceding head movement; saccades to the left were better than saccades to the right. MR scans for one twin showed normal findings, however, for the twin who had meningitis they revealed asymmetry between the right and left temporal lobes but no specific abnormality. DNA analysis using a series of autosomal polymorphic markers confirmed the monozygocity of the twins. White blood cell enzyme analysis excluded Sandhoff disease, Tay-Sachs disease, GM1 gangliosidosis, metacromatic leucodystrophy, Gaucher disease, Niemann-Pick disease (A and B), and Krabbe leucodystrophy. Albumin and immunoglobulin (IgA, IgG, and IgM) levels were normal. It is concluded that autosomal recessive inheritance seems the most likely explanation here, as recent studies have found insertion and missense mutations of the aprataxin gene which have been related to an early onset form of ataxia with ocular motor apraxia and hypoalbuminaemia.
Apraxias↗
A pilot study of targeted itraconazole prophylaxis in patients with graft-versus-host disease at high risk of invasive mould infections following allogeneic stem cell transplantation.
Patients with severe graft-versus-host disease (GVHD) requiring intensive immunosuppression are at high risk of invasive mould infections (IMI). Prophylaxis with an active, oral antifungal agents with reliable absorption in this context is desirable. A total of 44 patients at high risk of post-engraftment IMI received itraconazole solution 2.5 mg/kg b.d. as prophylaxis. Two of the first nine patients, in whom bioavailability was compromised due to significant vomiting and/or diarrhoea, died of probable or proven invasive aspergillus. None of the subsequent 35 patients, some of whom had severe gut GVHD and who received liposomal amphotericin B prophylaxis until itraconazole was reliably tolerated and absorbed, developed IMI. The overall incidence of IMI was substantially lower than in historical controls. Itraconazole was generally well tolerated, with five patients (11%) ceasing the drug due to intolerance or disturbed liver function. Targeted prophylaxis with oral or parenteral antifungal agents in high-risk allograft recipients appears to be effective in reducing the incidence of IMI.
Adolescent↗
Five to 15 year follow-up of resolved idiopathic central serous chorioretinopathy.
PURPOSE: To recognize the long-term sequelae of resolved idiopathic central serous chorioretinopathy (ICSC) in relation to visual acuity, contrast sensitivity, and lesion size between time elapsed since disease onset. METHODS: Patients were recruited from fluorescein angiogram records between January 1985 and December 1995 with confirmed ICSC. Visual acuity, contrast sensitivity, and digital fundus photographs were recorded on follow-up. Comparison with the initial red-free photographs were made. RESULTS: There was no statistically significant deterioration of visual acuity over time compared to eyes with ICSC after initial resolution and the normal eyes. The change of lesion size over time was also statistically insignificant. Contrast sensitivity compared to visual acuity showed positive correlation in both ICSC and normal eyes, but the results were statistically insignificant. Lesion size correlates negatively with visual acuity and contrast sensitivity although this was statistically insignificant. CONCLUSION: This study shows little, if any, correlation between time and progression of retinal pigment epitheliopathy following resolution of ICSC. Visual acuity did not seem to worsen over time. Our data were not statistically significant, but it does give insight into the natural history of what is still a relatively poorly understood disease.
Adult↗
Effects of exercise training on bone mineral density in frail older women and men: a randomised controlled trial.
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Aged↗
UK guidelines on management of Paget's disease of bone.
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Bone and Bones↗
Open surgical wounds: how does Aquacel compare with wet-to-dry gauze?
OBJECTIVE: To compare the healing rates of a hydrofibre dressing (Aquacel) and normal wet-to-dry gauze in the treatment of open surgical wounds. METHOD: Fifty patients with open surgical wounds were randomized to receive either saline-moistened gauze or Aquacel. The rate of wound healing was measured as ml/day (deep wounds) or cm2/day (superficial wounds) at each dressing change until an investigator blinded to the patient group diagnosed the wounds as having healed or the patient was withdrawn from the study. RESULTS: Of the 50 patients, seven were withdrawn from the study after the first evaluation. Of the remaining 43 patients, 21 had been randomly allocated to the gauze group and 22 to the Aquacel group. For deep wounds, a mean change in the wound healing rate of 1.9 +/- 1.3 cm3/day was reported for the gauze group and 2.9 +/- 2.3 cm3/day for the Aquacel group. These results approach statistical significance (p = 0.082). For superficial wounds, the mean change in the healing rate was 1.6 +/- 1.5 cm2/day for the gauze group and 1.9 +/- 2.2 cm2/day for the Aquacel group, but this was not statistically significant. CONCLUSION: Aquacel appears to be at least as effective as wet-to-dry gauze in the healing of open surgical wounds.
Bandages↗
The relationship between T-lymphocyte infiltration, stage, tumour grade and survival in patients undergoing curative surgery for renal cell cancer.
The present study examined the relationship between tumour stage, grade, T-lymphocyte subset infiltration and survival in patients who had undergone potentially curative surgery for renal clear-cell cancer (n=73). Intratumoural CD4+ T-lymphocyte infiltrate was associated with poor cancer-specific survival, independent of grade, in this cohort.
Aged↗
Albuminuria in a remote South Australian Aboriginal community: results of a community-based screening program for renal disease.
INTRODUCTION: The poverty, poor environmental living conditions and poor health standards experienced by Aboriginal Australians in some communities in rural and remote Australia have been described recently as 'fourth world'. For more than a century Aboriginal people have suffered the effects of dispossession of their land; destruction of their traditional culture and values; and exposure to infectious diseases, alcohol and the Western diet that is high in fat and sugar. Collectively these factors have contributed to the prevalence of chronic disease that afflicts Aboriginal people. In particular, renal disease has emerged during the last decade as a major contemporary health problem for Aboriginal Australians. According to the latest age- and sex-adjusted figures, Aboriginal people now have approximately nine-fold the risk of non-Aboriginal Australians of developing end-stage renal disease. In parts of Australia's Northern Territory, where Aboriginal people represent over 20% of the Territory's population, the rates of end-stage renal disease have been described as 'epidemic', reaching 2700 per million in the Tiwi Islands. In response to a request from the Umoona Tjutagku Health Service in mid 1997, the Renal Unit at Flinders Medical Centre, Adelaide, South Australia, formed a partnership with the health service to conduct a renal-disease screening program for adult members of the Umoona Community at Coober Pedy, a town 850 kilometres north of Adelaide. The partnership was later expanded to include screening for children (conducted by the Renal Unit at the Women's and Children's Hospital, Adelaide, South Australia). The community named the program 'The Umoona Kidney Project'. The Umoona community had recently experienced the dislocation of a number of its older people who suffered from advanced renal disease and were undergoing dialysis in a variety of centres in South Australia and the Northern Territory. As a result, the community had suffered social trauma. Consistent with the community's overall holistic approach to healthcare, the community wanted the renal program to provide a focus for community awareness of and knowledge about chronic disease, as well as to complement existing health programs. OBJECTIVES: The study objectives were to identify the prevalence of risk factors for renal disease, notably albuminuria, in adults from a remote Aboriginal community, and to examine the association of albuminuria with other risk factors; to empower Aboriginal health workers to self-manage a sustainable, community-controlled renal health program; and to assess the reliability and cultural acceptability of point-of-care technology for detecting renal disease. METHOD: The study was a three-year cross-sectional voluntary adult screening program (The Umoona Kidney Project). The study was performed as a partnership between the Flinders Medical Centre Renal Unit and the Umoona Tjutagku Health Service, and it involved nephrologists, medical scientists, Aboriginal health workers and clinical nurses. SETTING: Umoona Tjutagku Health Service, 850 km north of Adelaide. PARTICIPANTS: 158 adult members of the Umoona community: 58 males (37%; mean age = 43.8 years, range 23-78) and 100 females (63%; mean age = 39.6 years, range 18-72). MAIN OUTCOME MEASURES: First morning urine albumin : creatinine ratio measured by the Bayer DCA 2000 point-of-care analyser machine (Bayer Australia, Melbourne, Australia); lying and standing blood pressure; random blood glucose; body mass index; urinalysis. RESULTS: The study found that of screened adults, 29/149 (19%, 95% C.I. 13%-27%) had persistent microalbuminuria and 13/149 (9%, 95% C.I. 4%-14%) had persistent macroalbuminuria; 62/148 participants (42%, 95% C.I. 34%-50%) had overt hypertension; 35/145 participants (24%, 95% C.I. 17%-32%) had diabetes; 3 participants were newly diagnosed as having non-insulin dependent diabetes; 96/148 participants (65%, 95% C.I. 57%-73%) were either overweight or obese. Strong correlation was observed between the progression of albuminuria and age, all blood pressure categories, blood glucose, body mass index and an increasing number of risk factors. CONCLUSIONS: The Umoona Kidney Project identified a significant community burden of previously unknown incipient and established renal disease that required addressing via clinical- and community-based interventions. The DCA 2000 was a reliable instrument for detecting albuminuria on-site in the remote clinical location and was well accepted by Aboriginal health workers and community participants.
Journal Article↗
Randomized clinical trial of intermittent pneumatic compression and low molecular weight heparin in trauma.
BACKGROUND: After trauma, up to 60 per cent of immobilized patients have been reported to develop a silent deep vein thrombosis (DVT). No large, prospective randomized trials have tested the efficacy of intermittent pneumatic compression (IPC) devices in these patients. METHODS: A prospective randomized trial was performed of 442 patients who received thromboprophylaxis using either an IPC device or low molecular weight heparin (LMWH). Duplex imaging was performed on both legs on admission, and was repeated weekly thereafter until discharge, at 30 days or when there was a thrombotic event, whichever occurred first. RESULTS: There were no significant differences in time spent in intensive care, or the proportion of patients with pelvic fractures, spinal cord or head injuries between the two groups. Six patients (2.7 per cent) developed a DVT in the IPC group and one (0.5 per cent) in the LMWH group (P = 0.122). Pulmonary embolism occurred in one patient in each group. There were 13 minor bleeding episodes (four in the IPC group and nine in the LMWH group) and eight major bleeding episodes (four in each group), none of which required operative intervention. CONCLUSION: The low rate of thromboembolic complications and the cost savings suggest that IPC might be used safely and effectively for thromboprophylaxis in trauma patients.
Adult↗
Applications of Fourier transform infrared microspectroscopy in studies of benign prostate and prostate cancer. A pilot study.
Fourier transform infrared (FTIR) microspectroscopy has been applied to a study of prostate cancer cell lines derived from different metastatic sites and to tissue from benign prostate and Gleason-graded malignant prostate tissue. Paraffin-embedded tissue samples were analysed by FTIR, after mounting onto a BaF(2) plate and subsequent removal of wax using Citroclear followed by acetone. Cell lines were analysed as aliquots of cell suspension held between two BaF(2) plates. It was found that the ratio of peak areas at 1030 and 1080 cm(-1), corresponding to the glycogen and phosphate vibrations respectively, suggests a potential method for the differentiation of benign from malignant cells. The use of this ratio in association with FTIR spectral imaging provides a basis for estimating areas of malignant tissue within defined regions of a specimen. Initial chemometric treatment of FTIR spectra, using the linear discriminant algorithm, demonstrates a promising method for the classification of benign and malignant tissue and the separation of Gleason-graded CaP spectra. Using the principle component analysis, this study has achieved for the first time the separation of FTIR spectra of prostate cancer cell lines derived from different metastatic sites.
Adenocarcinoma↗