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Biomedical subjects

S Brown

Publications and source records attributed to S Brown.

At least 55 records · Page 3Linked to original sources
PubMed2004

Endoscopic morphological anticipation of submucosal invasion in flat and depressed colorectal lesions: clinical implications and subtype analysis of the kudo type V pit pattern using high-magnification-chromoscopic colonoscopy.

OBJECTIVE: Focal submucosal invasive colorectal cancers (submucosa-sm1) can be managed by endoscopic mucosal resection (EMR) as local lymph node metastasis (LNM) are rare. Lesions are usually flat, depressed or mixed. In deeper vertical submucosal invasion (sm2-3) LNM rates exceed 10-15%. EMR within this group can be complicated by perforation, noncurative resection and may leave LNM untreated. It is therefore essential to differentiate accurately focal sm1 disease from submucosal sm2/3 disease. The aim of this study was to evaluate the relationship between the invasive type V pit pattern using high-magnification-chromoscopic-colonoscopy (HMCC) and submucosal invasive depth for flat and depressed colorectal lesions. METHODS: Total colonoscopy was performed by a highly selected single endoscopist using the Olympus C240Z on 850 patients between January 2001 and July 2003. Kudo type V pits were identified using 0.05% crystal violet (CV) applied directly to the lesion using a steel tipped catheter. Type V pits were graded into class V(n)A-C as described by Nagata. Morphology was documented using the Japanese Research Society classification (JRSC). Histological sections, with reference to mucosal invasive characteristics, acquired using EMR or surgical excision were then compared with the pit pattern. RESULTS: Fifty-one lesions showed a type V pit pattern. The kappa coefficient of agreement between pit the type V pit pattern and histologically confirmed submucosal invasion was 0.51 (95% CI). Following resection, 97% of lesions were correctly anticipated to have sm2 + invasion using pit type Vn(B) and Vn(C) as clinical indicators of invasive disease. Specificity was low at 50% with an accuracy of 78%. CONCLUSIONS: The type V pit pattern is useful for the in vivo staging of submucosal invasive depth in flat and depressed colorectal lesions and is as sensitive as conventional 7.5 MHz EUS. There was a tendency to over-stage lesions and hence the technique is limited by its low overall specificity.

Biopsy, Needle↗
PubMed2004

A randomized open-label study of immediate versus delayed polylactic acid injections for the cosmetic management of facial lipoatrophy in persons with HIV infection.

BACKGROUND: Polylactic acid (PLA, New-Fill; Medifill, London, UK and Dermic Labs, a division of Eventis, Strasbourg, France) injections into the deep dermis increase fibroblast numbers and collagen production. The substance is widely used in medical applications including cosmetic procedures. METHODS: HIV-positive individuals with facial lipoatrophy (based on physician assessment) were randomized to immediate (weeks 0, 2 and 4) or delayed (weeks 12, 14 and 16) PLA given as three bilateral injections 2 weeks apart into the deep dermis overlying the buccal fat pad. Assessments included facial ultrasound, visual analogue scales, the Hospital Anxiety and Depression Scale (HADS) and assessment using photographs at weeks 0, 12 and 24. RESULTS: All 30 patients completed 24 weeks of treatment. The median age of the patients was 41 years, with a mean of 80 months of nucleoside reverse transcriptase inhibitor (NRTI) therapy and a mean of 44 months of prior protease inhibitor (PI) therapy. The median CD4 count was 428-460 cells/microL, with 47% of patients in the immediate-treatment group and 93% of patients in the delayed-treatment groups with <50 HIV-1 RNA copies/mL at baseline. No differences in immunological, virological, biochemical, haematological or metabolic parameters emerged during the study. Injections were well tolerated with only two adverse events (cellulitis and bruising) recorded, one of which delayed treatment by 1 week. There were no discontinuations. Patient visual analogue assessments, photographic assessments, and anxiety and depression scores improved with treatment. At week 12, immediate-treatment patients had significantly better visual analogue scores (7 vs. 1, P<0.001) and lower anxiety scores (6 vs. 9, P=0.056) than delayed-treatment patients. Benefits on visual analogue and HADS scores persisted until week 24. CONCLUSIONS: PLA injections led to improvements in patient self-perception, anxiety and depression scores in individuals with facial lipoatrophy. Adverse events were uncommon. The benefits of PLA persisted for at least 18 weeks beyond the last injection.

Administration, Cutaneous↗
PubMed2004

Clinical and bacteriological efficacy of the ketolide telithromycin against isolates of key respiratory pathogens: a pooled analysis of phase III studies.

A pooled analysis of data from 13 phase III studies of telithromycin in the treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute sinusitis or group A beta-haemolytic streptococcal pharyngitis and tonsillitis was undertaken. Causative key respiratory tract pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Streptococcus pyogenes) were isolated at entry to the studies from cultures of relevant respiratory samples and tested for their susceptibility to telithromycin, penicillin and macrolides (erythromycin A). The combined clinical and bacteriological efficacy of telithromycin at the post-therapy, test-of-cure visit (days 17-24) was assessed in patients from whom a microbiologically evaluable pathogen was isolated at entry. More than 98% of key respiratory pathogens isolated, including penicillin G- and macrolide (erythromycin A)-resistant strains of S. pneumoniae, demonstrated full or intermediate susceptibility to telithromycin in vitro at the breakpoints of < or = 1.0 mg/L (susceptible) and 2.0 mg/L (intermediate) used for the purpose of evaluating the susceptibility of isolates recovered during the clinical trials. Treatment with telithromycin 800 mg once-daily for 5, 7 or 7-10 days resulted in high rates of clinical cure (88.5%) and a satisfactory bacteriological outcome (88.9%), similar to the figures seen with comparator antibacterial agents. Clinical cure and eradication rates were good for all key respiratory pathogens, including penicillin G- and macrolide (erythromycin A)-resistant S. pneumoniae. The results suggest that telithromycin will provide effective empirical therapy for community-acquired upper and lower respiratory tract infections.

Adolescent↗
PubMed2004

Preparation of stock solutions of macrolide and ketolide compounds for antimicrobial susceptibility tests.

Stock solutions of telithromycin, ABT-773, azithromycin, clarithromycin, erythromycin, roxithromycin and dirithromycin were each prepared with eight different combinations of solvents and diluents. Broth microdilution trays were then prepared and frozen at -60 degrees C. Standard quality control strains were evaluated periodically during a 12-week storage time. There were no significant changes in MICs with different solvents and diluents. It was concluded that the easiest approach was to dissolve each compound in water with a small volume (< 2.5 microL/mL) of glacial acetic acid added in a dropwise fashion, followed by further dilutions in deionised water.

Acetic Acid↗
PubMed2004

Quality control limits for voriconazole disk susceptibility tests on Mueller-Hinton agar with glucose and methylene blue.

An international collaborative study was performed in order to propose quality control limits for voriconazole disk diffusion tests on Mueller-Hinton agar with 2% glucose and 0.5 micro g of methylene blue per ml. The supplement may be added to the agar before autoclaving, or Mueller-Hinton agar plates may be flooded with a glucose-methylene blue solution. Replicate tests on both types of agar plates with 1- micro g voriconazole disks generated data to propose zone size limits for tests of Candida parapsilosis ATCC 22019 (28 to 37 mm), Candida albicans ATCC 90028 (31 to 42 mm), and Candida krusei ATCC 6258 (16 to 25 mm). Candida tropicalis ATCC 750 was not useful for this purpose.

Agar↗
PubMed2004

Efficacy of high magnification chromoscopic colonoscopy for the diagnosis of neoplasia in flat and depressed lesions of the colorectum: a prospective analysis.

BACKGROUND: High magnification chromoscopic colonoscopy (HMCC) permits the in vivo examination of the colorectal pit pattern, which has a high correlation with stereomicroscopic appearances of resected specimens. This new technology may provide an "optical biopsy" which can be used to aid diagnostic precision and guide therapeutic strategies. Conflicting data exist concerning the accuracy of this technique when discriminating neoplastic from non-neoplastic lesions, particularly when flat and depressed. AIM: To prospectively examine the efficacy of HMCC for the diagnosis of neoplasia in flat and depressed colorectal lesions using standardised morphological, pit pattern, and histopathological criteria. Clinical recommendations for the use of HMCC are made. METHODS: Total colonoscopy was performed on 1850 patients by a single endoscopist from January 2001 to July 2003 using the C240Z magnifying colonoscope. Identified lesions were classed according to the Japanese Research Society guidelines, and pit pattern according to Kudos modified criteria. Pit pattern appearances were then compared with histopathology. RESULTS: A total of 1008 flat lesions were identified. The sensitivity and specificity of HMCC in distinguishing non-neoplastic from neoplastic lesions were 98% and 92%, respectively. However, when using HMCC to differentiate neoplastic/non-invasive from neoplastic/invasive lesions, sensitivity was poor (50%) with a specificity of 98%. Diagnostic accuracy was not influenced by size or morphological classification of lesions. CONCLUSION: HMCC has a high overall accuracy at discriminating neoplastic from non-neoplastic lesions but is not 100% accurate. HMCC is a useful diagnostic tool in vivo but presently is not a replacement for histology. Requirements for further education and training in these techniques need to be addressed.

Adolescent↗
PubMed2004

Detecting diminutive colorectal lesions at colonoscopy: a randomised controlled trial of pan-colonic versus targeted chromoscopy.

BACKGROUND: Diminutive and flat colorectal lesions can be difficult to detect using conventional colonoscopic techniques. Previous data have suggested that pan-chromoscopy may improve detection rates. No randomised control trial has been performed examining detection rates of such lesions while controlling for extubation time and lavage effect. AIM: We conducted a randomised controlled trial of pan-colonic chromoscopic colonoscopy for the detection of diminutive and flat colorectal lesions while controlling for extubation time and lavage effect. METHODS: Consecutive patients attending for routine colonoscopy were randomised to either pan-chromoscopy using 0.5% indigo carmine (IC) or targeted chromoscopy (control group). A minimum diagnostic extubation time was set at eight minutes with controls undergoing a matched volume of saline wash. RESULTS: A total of 260 patients were randomised; 132 controls and 128 to pan-colonic chromoscopy. Extubation times did not differ significantly between the control (median 15 minutes (range 8-41)) and chromoscopy (median 17 minutes (range 8-39)) groups. The volume of IC used in the pan-chromoscopy group (median 68 ml (range 65-90)) and normal saline used in the control group (69 ml (range 60-93)) did not differ significantly. There was a statistically significant difference between the groups regarding the total number of adenomas detected (p<0.05) with significantly more diminutive (<4 mm) adenomas detected in the pan-chromoscopy group (p = 0.03). Pan-chromoscopy diagnosed more diminutive and flat lesions in the right colon compared with controls (p<0.05), with more patients with multiple adenomas (>3) detected using pan-chromoscopy (p<0.01). Hyperplastic lesions were more commonly detected in the pan-chromoscopy group compared with controls (p<0.001). More hyperplastic polyps were detected in the left colon (86% rectosigmoid) using chromoscopy compared with controls. CONCLUSION: Chromoscopy improves the total number of adenomas detected and enhances the detection of diminutive and flat lesions. Importantly, eight diminutive lesions had foci of high grade dysplasia. Chromoscopy may benefit patients, assuming a high risk of colorectal cancer, and help in risk stratification and planning follow up colonoscopy intervals.

Adenoma↗
PubMed2004

Colonoscopic resection of lateral spreading tumours: a prospective analysis of endoscopic mucosal resection.

BACKGROUND: Lateral spreading tumours are superficial spreading neoplasms now increasingly diagnosed using chromoscopic colonoscopy. The clinicopathological features and safety of endoscopic mucosal resection for lateral spreading tumours (G-type "aggregate" and F-type "flat") has yet to be clarified in Western cohorts. METHODS: Eighty two patients underwent magnification chromoscopic colonoscopy using the Olympus CF240Z by a single endoscopist. All patients had received a previous colonoscopy where an endoscopic diagnosis of lateral spreading tumour was made. All lesions were examined initially using indigo carmine chromoscopy to delineate contour followed by crystal violet for magnification crypt pattern analysis. A 20 MHz "mini probe" ultrasound was used if T2 disease was suspected. Following endoscopic mucosal resection, patients were followed up at 3, 6, 12, and 24 months using total colonoscopy. RESULTS: Eighty two lateral spreading tumours were diagnosed in 80 patients (32% (26/82) F-type and 68% (56/82) G-type). G-type lesions were larger than F-type (G-type mean 42 (SD 14) mm v F-type 24 (6.4) mm; p<0.01). F-type lesions were more common in the right colon (F-type 77% (20/26) compared with G-type 39% (22/56); p<0.01) and more often associated with invasive disease (stage T2) (66% (10/15) v 33% (5/15); p<0.001). Fifty eight lesions underwent endoscopic mucosal resection (G-type 64% (37/58)/F-type 36% (21/58)). Local recurrent disease was detected in 17% of patients (10/58), all within six months of the index resection. Piecemeal resection and G-type morphology were significantly associated with recurrent disease (p<0.1). Overall "cure" rates for lateral spreading tumours using endoscopic mucosal resection at two years of follow-up was 96% (56/58). CONCLUSIONS: Endoscopic mucosal resection for lateral spreading tumours, staged as T1, is a safe and effective treatment despite their large size. Endoscopic mucosal resection may be an alternative to surgery in selected patients.

Adult↗
PubMed2004

Rehabilitation of schizophrenic patients.

Schizophrenia is a maldevelopmental disorder of the brain that manifests in positive, negative, cognitive and affective symptoms. Currently, the mainstay of treatment involves pharmacotherapy. The limitations of antipsychotic treatment are that they can only control symptoms and cannot cure the illness, and 20% of patients do not respond, thus leading to the requirement of maintenance treatment. Patients that do respond continue to have disabling residual symptoms such as amotivation and isolation, maladaptive behavior, and impaired social functioning. These symptoms prevent patients from attaining educational, occupational, and social roles. Psychosocial interventions and models of quality of life in schizophrenia are based on the notion that increases in psychosocial functioning will be related to improvement in subjective experiences, such as self-esteem and satisfaction with life. The comparative effect of specific treatment methods and the additional benefits of multiple treatments need to be explored. Diversified techniques have also been employed, such as shaping, cognitive process therapy, mastery-oriented skill training, motivation and enhancement. Issues in designing psychosocial interventions and the role of various professionals in providing such interventions need to be carefully considered. Predictor variables and the indications for particular therapies in an individual need to be explored. Generalizability of the gains made by rehabilitation/recovery is also an important consideration. Patients in jail, chronic mental hospitals, private facilities, and the Veterans Administration system are all different in their ability to benefit, their motivations, and the severity of their psychopathology. Therefore, it is very difficult to generalize findings from one setting to another.

Humans↗
PubMed2004

Beyond curve fitting? Comment on Liu, Mayer-Kress, and Newell (2003).

Y.-T. Liu, G. Mayer-Kress, and K. M. Newell (2003) fit learning curves to movement time data and suggested 2 new methods for analyzing learning. They claimed that the methods go "beyond curve fitting." However, in neither their curve fitting nor their new methods is measurement noise accounted for, and therefore they produce inefficient and biased results. Using the data of Liu et al., in which variance caused by learning is small relative to the level of noise for most participants, the present authors demonstrate those problems and provide better alternatives that are more noise tolerant, more powerful, and go beyond curve fitting without displaying the extreme bias produced by the methods of Liu et al.

Humans↗
PubMed2003

The Arabidopsis KAKTUS gene encodes a HECT protein and controls the number of endoreduplication cycles.

In animals and plants, many cell types switch from mitotic cycles to endoreduplication cycles during differentiation. Little is known about the way in which the number of endoreduplication cycles is controlled in such endopolyploid cells. In this study we have characterized at the molecular level three mutations in the Arabidopsis gene KAKTUS ( KAK), which were previously shown specifically to repress endoreduplication in trichomes. We show that KAK is also involved in the regulation of the number of endoreduplication cycles in various organs that are devoid of trichomes. KAK encodes a protein with sequence similarity to HECT domain proteins. As this class of proteins is known to be involved in ubiquitin-mediated protein degradation, our finding suggests that the number of endoreduplication cycles that occur in several cell types is controlled by this pathway. The KAK gene defines a monophylogenetic subgroup of HECT proteins that also contain Armadillo-like repeats.

Amino Acid Sequence↗
PubMed2003

A new multitool for hand-assisted advanced laparoscopic surgery (HALS).

BACKGROUND: Hand-assisted laparoscopic surgery (HALS), which has become possible due to the introduction of effective hand-access devices, facilitates the execution of major operations. Over the past 2 years, we have been evaluating various designs for small instruments that can be used by the internal assisting hand. Here we report on the development, testing, and evaluation of a small reusable multitool that hangs from the little finger of the internal assisting hand of the surgeon when not in use. METHODS: The Dundee Multitool (DMT) was designed to enable the internal deployment (by thumb extrusion) of a small dissecting forceps (pickup), needle driver, and scissors. The multitool hangs from the little finger of the internal assisting hand when not in use. The instrument was subjected to beta testing in the laboratory using HALS trainers. When testing was completed, it was used in major HALS operations after approval by the hospital and consent of the individual patients. RESULTS: The DMT was found to work well. The various active instruments could be extruded from the casing with ease and functioned well in picking up tissues, intracorporeal suturing/tying, and the cutting of sutures and ligatures. Both in laboratory experiments and during clinical evaluation, suturing was easy when the active driving of the needle though the tissues was carried out by the external hand. The multitool needle driver, held by the internal hand as an assisting instrument in conjunction with active needle driving through the tissue edges by the dominant (external) hand, improved suturing efficiency (i.e., reduced execution time) by 30% when compared to total laparoscopic suturing. CONCLUSIONS: We have described a novel little-finger-hung multitool for HALS surgery that deploys with ease at any one time. It incorporates a needle driver, a dissecting forceps, and a suture scissors. The good functionality of the multitool has been confirmed by both laboratory experiments and clinical evaluation.

Animals↗
PubMed2003

A primigravida allegedly allergic to local anaesthetics.

Pregnant patients may give a history of allergy to local anaesthetics, but many of these supposed allergies have not been investigated. There is cross-reactivity between the amide local anaesthetics, which are the only group available in the UK for regional analgesia. We report the management of a primigravida who gave a history of allergy to two local anaesthetics, lidocaine and prilocaine. She was admitted to the labour ward at 38 weeks' gestation for challenge testing to the amide local anaesthetic bupivacaine, with full resuscitation and delivery facilities available. The tests proved negative and she was allowed home. She was re-admitted at term in labour and requested epidural analgesia. Epidural bupivacaine with fentanyl was used without incident for labour and forceps delivery. Subsequent allergy testing to lidocaine also proved negative.

Journal Article↗
PubMed2003

The role of flat and depressed colorectal lesions in colorectal carcinogenesis: new insights from clinicopathological findings in high-magnification chromoscopic colonoscopy.

High-magnification chromoscopic endoscopy is a new technique which has been recently introduced to the UK. This technology, initially pioneered by the Japanese in the 1980s, has changed our understanding of the pathogenesis of colorectal cancer and our subsequent therapeutic strategies aimed at the secondary prevention of cancer. Magnification colonoscopic techniques when combined with colonic chromoscopy (dye spraying of the colon) permit in vivo assessments of lesions at a magnification and resolution similar to a stereomicroscope. Furthermore, flat/depressed adenomas and cancers can be diagnosed with increasing frequency and new resection practices performed. This technique is known as endoscopic mucosal resection. As gastrointestinal endoscopists adopt these new techniques, close liaison with histopathologists is essential to provide the highest standards of diagnostic accuracy. The histopathologist also needs to be aware of the endoscopic findings when interpreting specimens and hence must understand new endoscopic terminologies and classification systems that accompany the introduction of new technologies and therapeutic techniques. This article describes the controversies relating to the flat and depressed colorectal lesion, where these new endoscopic technologies are ideally suited. It then provides a working description of high-magnification chromoscopic colonoscopy including the Japanese 'pit pattern' and morphological classification system-information which will be provided to histopathologists with specimens obtained by these new techniques. Finally, we describe the procedure of endoscopic mucosal resection, as the type and quality of specimens received for histopathological analysis will be highly influenced by these techniques.

Colonoscopy↗
PubMed2003

Occipito-temporal polymicrogyria and subclinical muscular dystrophy.

We report a two-year-old Caucasian boy who had neonatal seizures and was found to have bilateral occipito-temporal polymicrogyria on neonatal brain MRI. The child had no additional neurological abnormality other than the neonatal seizures, but serum CK was found to be elevated (5 - 7 times normal values) and the muscle biopsy showed evidence of early muscular dystrophy. Detailed protein and genetic studies did not allow the identification of a known form of muscular dystrophy. The boy has been followed regularly and he currently has mild global developmental delay but no clinical signs of muscle involvement. The association of polymicrogyria and muscular dystrophy is known to occur in Fukuyama and Walker Warburg muscular dystrophies, in muscle-eye-brain disease and in some patients with merosin deficient CMD. However the absence of weakness and of eye involvement, the normal expression of merosin and alpha dystroglycan and the pattern of brain involvement make it very unlikely that the child is affected by one of these forms. As the pattern of brain involvement and the muscle pathology is not typical of one of the forms of neuronal migration disorders secondary to a known gene defect, we suspect that the combination of muscle and brain involvement found in this child is not coincidental. Our findings suggest that serum CK should be determined in children with undiagnosed polymicrogyria, even in the absence of weakness. This may lead to an expansion of our understanding of muscle dystrophies and cortical dysplasias.

Child, Preschool↗