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Biomedical subjects

G Brown

Publications and source records attributed to G Brown.

At least 55 records · Page 3Linked to original sources

Rupture of the biceps brachii tendon sheath in two dogs.

Rupture of the biceps brachii tendon sheath was diagnosed in two dogs which were presented with chronic thoracic limb lameness. In each case, diagnosis was achieved by positive contrast arthrography, which revealed obvious leakage of contrast agent from the distal portion of the tendon sheath. Arthroscopy was performed in each affected shoulder joint and no other significant lesions were found. In one dog, concomitant bicipital tendinopathy was confirmed by histopathology. Both dogs were treated by bicipital tendon transposition, and tenodesis and both showed improvement in the degree of lameness following surgery. Tearing of the biceps brachii tendon sheath has not been reported previously but should be included in the differential diagnosis for shoulder lameness in the adult dog.

Animals↗

Best evidence topic reports. Does nimodipine reduce mortality and secondary ischaemic events after subarachnoid haemorrhage?

A short cut review was carried out to establish whether nimodipine is better than placebo at reducing mortality and neurological sequelae in patients with subarachnoid haemorrhage. Altogether 465 papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this best paper are tabulated. A clinical bottom line is stated.

Adult↗

Colonic anastomotic disruption in the immediate postoperative period.

BACKGROUND: Muscle relaxation is administered to patients undergoing laparotomy for colonic surgery. At the end of the procedure, relaxation needs to be reversed to facilitate extubation. This may be achieved by administering anticholinesterases such as neostigmine. PATIENT PRESENTATION: We present a case of colonic anastomotic dehiscence in the immediate postoperative period following the use of neostigmine to reverse intra-operative muscle relaxation. CONCLUSION: Neostigmine is frequently used to reverse muscle relaxation at the end of colonic surgery. However, the drug should be used with caution as it has been implicated as a cause of early anastomotic disruption.

Aged↗

Neoadjuvant systemic fluorouracil and mitomycin C prior to synchronous chemoradiation is an effective strategy in locally advanced rectal cancer.

This study was designed to evaluate the benefits of neoadjuvant chemotherapy prior to chemoradiation and surgery in patients with locally advanced rectal cancer. Patients with previously untreated primary rectal cancer, reviewed in a multidisciplinary meeting and considered to have locally advanced disease on the basis of physical examination and imaging (MRI+CT n=30, CT alone n=6), were recruited. Patients received protracted venous infusion 5-FU (300 mg m(-2) day(-1) for 12 weeks) with mitomycin C (MMC) (7 mg m(-2) i.v. bolus every 6 weeks). Starting on week 13, 5-FU was reduced to 200 mg m(-2) day(-1) and concomitant pelvic radiotherapy 45 Gy in 25 fractions was commenced followed by 5.4-9 Gy boost to tumour bed. Surgery was planned 6 weeks after chemoradiation. Postoperatively, patients received 12 weeks of MMC and 5-FU at the same preoperative doses. Between January 99 and August 01, 36 eligible patients were recruited. Median age was 63 years (range=40-85). Following neoadjuvant chemotherapy, radiological tumour response was 27.8% (one CR and nine PRs) and no patient had progressive disease. In addition, 65% of patients had a symptomatic response including improvement in diarrhoea/constipation (59%), reduced rectal bleeding (60%) and diminished pelvic pain/tenesmus (78%). Following chemoradiation, tumour regression occurred in 80.6% (six CRs and 23 PRs; 95% CI=64-91.8%) and only one patient still had an inoperable tumour. R0 resection was achieved in 28 patients (82%). When compared with initial clinical staging, the pathological downstaging rate in T and/or N stage was 73.5% and pathological CR was found in one patient. Neoadjuvant systemic chemotherapy as a prelude to synchronous chemoradiation can be administered with negligible risk of disease progression and produces considerable symptomatic response with associated tumour regression.

Adult↗

Rapid access multidisciplinary lymph node diagnostic clinic: analysis of 550 patients.

Lymphadenopathy is common, affecting patients of all ages. The current referral pattern for investigating patients with lymphadenopathy varies widely with no universally practised pathway. Our institution set up a lymph node diagnostic clinic (LNDC) accepting direct referrals from primary care physicians. Details of clinical presentation and investigations were recorded prospectively. Between December 1996 and July 2001, 550 patients were referred (M: 203; F:347). The median age was 40 years (range 14-90). The median time between initial referral and the first clinic visit was 6 days. Of 95 patients diagnosed to have malignant diseases, the median time from the first clinic visit to reaching malignant diagnosis was 15 days. Multivariate logistic regression analysis identified five significant predictors for malignant nodes: male gender (risk ratio (RR)=2.72; 95% confidence interval (CI): 1.63-4.56), increasing age (RR=1.05; 95% CI: 1.04-1.07), white ethnicity (RR=3.01; 95% CI: 1.19-7.6) and sites of lymph nodes: supraclavicular region (RR=3.72; 95% CI: 1.52-9.12) and > or = 2 regions of lymph nodes (RR=6.41; 95% CI: 2.82-14.58). Ultrasound and fine-needle aspiration cytology of palpable lymph nodes were performed in 154 and 289 patients, respectively. An accuracy of 97 and 84% was found, respectively. In conclusion, a multidisciplinary lymph node diagnostic clinic enables a rapid, concerted approach to a common medical problem and patients with malignant diseases were diagnosed in a timely fashion.

Adult↗

Preoperative assessment of prognostic factors in rectal cancer using high-resolution magnetic resonance imaging.

BACKGROUND: The aim was to determine the accuracy of preoperative magnetic resonance imaging (MRI) in the evaluation of pathological prognostic factors that influence local recurrence and survival in rectal cancer. METHODS: Ninety-eight patients undergoing total mesorectal excision for biopsy-proven rectal cancer were assessed prospectively using high-resolution MRI for tumour (T) and nodal (N) staging using the tumour node metastasis classification, depth of extramural tumour spread, the presence or absence of extramural venous invasion, a threatened circumferential resection margin and serosal involvement at or above the peritoneal reflection. Preoperative magnetic resonance assessment of these prognostic factors was compared with histopathological findings in carefully matched whole-mount sections of the resection specimen. RESULTS: There was 94 per cent weighted agreement (weighted kappa = 0.67) between MRI and pathology assessment of T stage. Agreement between MRI and histological assessment of nodal status was 85 per cent (kappa = 0.68). Although involvement of small veins by tumour was not discernible using MRI, large (calibre greater than 3 mm) extramural venous invasion was identified correctly in 15 of 18 patients (kappa = 0.64). MRI predicted circumferential resection margin involvement with 92 per cent agreement (kappa = 0.81). Seven of nine patients with peritoneal perforation by tumour (stage T4) were identified correctly using MRI. CONCLUSION: High-resolution MRI of the rectum allows preoperative identification of important surgical and pathological prognostic risk factors. This may allow both better selection and assessment of patients undergoing preoperative therapy.

Adult↗

LPA1 receptor-deficient mice have phenotypic changes observed in psychiatric disease.

Several psychiatric diseases, including schizophrenia, are thought to have a developmental aetiology, but to date no clear link has been made between psychiatric disease and a specific developmental process. LPA(1) is a G(i)-coupled seven transmembrane receptor with high affinity for lysophosphatidic acid. Although LPA(1) is expressed in several peripheral tissues, in the nervous system it shows relatively restricted temporal expression to neuroepithelia during CNS development and to myelinating glia in the adult. We report the detailed neurological and behavioural analysis of mice homozygous for a targeted deletion at the lpa(1) locus. Our observations reveal a marked deficit in prepulse inhibition, widespread changes in the levels and turnover of the neurotransmitter 5-HT, a brain region-specific alteration in levels of amino acids, and a craniofacial dysmorphism in these mice. We suggest that the loss of LPA(1) receptor generates defects resembling those found in psychiatric disease.

Animals↗

Rapid vegetation regeneration in a seriously degraded Rhanterium epapposum community in northern Kuwait after 4 years of protection.

A study was carried out in northern Kuwait to investigate vegetation recovery in sandy depressions in the Sabriya oilfield ('Sabriya-IN'), 4 years after it was completely protected from livestock grazing and other anthropogenic activities which have largely depleted the dwarf shrub vegetation. This vegetation was compared with that in seriously overgrazed depressions outside the oilfield ('Sabriya-OUT'), where negative influences persist, and with a sandy site in central Kuwait which has been protected for over 20 years ('Sulaibiya'). There has been a striking recovery of the dwarf shrub vegetation in Sabriya-IN during the 4 years, with cover values of shrubs as high as at Sulaibiya. Rhanterium epapposum has been the main species to benefit from protection. However, the shrubs have not regenerated from seed, but rather from underground stumps that have probably remained in the soil for decades. Cover values of the annual flora at Sabriya-IN were very similar to those at Sulaibiya, and they were significantly higher than at Sabriya-OUT. However, it appears that some species may have disappeared or become extremely rare at Sabriya-IN when compared with Sulaibiya, as Sabriya-IN and Sabriya-OUT are remarkably similar floristically. Despite the impressive regeneration of the dwarf shrub vegetation at Sabriya-IN, which contradicts the view that vegetation recovery is a slow process in desert ecosystems, it is important to consider what the natural vegetation was in this part of the world. It is suggested that the region was once dominated by an open Acacia woodland, in which perennial grasses comprised most of the ground layer, and that the current dwarf shrub vegetation is a response to decades, if not centuries, of moderate to heavy grazing.

Animals↗

CT detection of hydronephrosis in resected colorectal cancer: a predictor of recurrent disease.

AIM: To investigate the causes and significance of hydronephrosis in follow-up of colorectal cancer. METHODS AND MATERIALS: Case notes and serial computed tomography (CT) examinations were reviewed of 75 patients (250 CT examinations) after resection for colorectal cancer in whom hydronephrosis developed on follow-up. RESULTS: The most common cause of hydronephrosis was a focal plaque-like mass centred on the peritoneum, demonstrated in 37 cases (49%). Patients with R1 (microscopic residual tumour) or R2 (macroscopic residual tumour) disease developed hydronephrosis at a median time of 13 months (90% CI: 9-18 months) compared with 22 months (90% CI: 17-26 months) for those having (R0) curative resection. Patients with pT4 invasion of peritoneum or adjacent organs developed hydronephrosis at a median of 14 months (90% CI: 6-16 months) compared with a median of 22 months in patients with pT3 tumours (90% CI: 11-27 months). Of 26 patients without an obvious cause of hydronephrosis on initial CT examination, follow-up CT demonstrated a definite mass lesion in 50%. Median survival after the onset of hydronephrosis was 6 months (range 1-34 months) with a 1-year mortality of 62%. CONCLUSIONS: Hydronephrosis is an important early indicator of colorectal cancer recurrence, even in the absence of a mass.

Adult↗

Sequence analysis of a rainbow trout cDNA library and creation of a gene index.

Expressed sequence tag (EST) projects have produced extremely valuable resources for identifying genes affecting phenotypes of interest. A large-scale EST sequencing project for rainbow trout was initiated to identify and functionally annotate as many unique transcripts as possible. Over 45,000 5' ESTs were obtained by sequencing clones from a single normalized library constructed using mRNA from six tissues. The production of this sequence data and creation of a rainbow trout Gene Index eliminating redundancy and providing annotation for these sequences will facilitate research in this species.

Animals↗

Primary care physicians attitude toward diagnosis and treatment of late-life depression.

Underdiagnosis and undertreatment of late-life depression is common, especially in primary care settings. To help assess whether physicians attitude and confidence in diagnosing and managing depression serve as barriers to care, a total of 176 physicians employed in 18 primary care groups were administered surveys to assess attitudes towards diagnosis, treatment, and management of depression in elderly patients, (individuals over 65 years of age). Logistic regression was performed to assess the association of physician characteristics on attitudes. Nearly all of the physicians surveyed felt that depression in the elderly was a primary care problem, and 41% reported late-life depression as the most common problem seen in older patients. Physicians were confident in their ability to diagnose and manage depression, yet 45% had no medical education on depression in the previous three years. Physicians confidence in their ability to diagnose, treat, and manage depression, and their reported adequacy of training, do not appear to correspond to the amount of continuing medical education in depression, suggesting that physician overconfidence may potentially be serving as a barrier to care.

Journal Article↗

A retrospective study comparing the individual modalities of triple assessment in the pre-operative diagnosis of invasive lobular breast carcinoma.

AIMS: Early invasive lobular breast carcinoma (ILC) is associated with few symptoms and signs. The individual sensitivity of clinical examination, mammography, ultrasonography, cytology and core biopsy have each been reported to be of limited value. The aim of this study was to evaluate the accuracy of triple assessment in the pre-operative detection of patients identified to have ILC from their surgical pathology. METHODS: Pure ILC was defined as tumours containing at least 90% lobular features. The triple assessment of 273 patients diagnosed primarily at our institution were reviewed. RESULTS: 87.5% of women were symptomatic and 12.5% were screen detected. The mean patient age was 59 (range 30-81) years and the median tumour size was 26 (range 5-110) mm. The main mammographic abnormalities were a spiculated lesion (33.3%), an ill-defined mass (33.3%) or architectural distortion (23.5%). The sensitivities for detecting ILC of each modality were: clinical examination (76.6%), mammography (79.8%), ultrasound examination (93.9%), fine-needle aspiration cytology (FNAC) (60.5%) and core biopsy (90.8%). Combining the three modalities of clinical examination, imaging and cyto/pathology increased the pre-operative detection rate of ILC. CONCLUSION: Triple assessment is useful in the diagnosis of ILC. As the features of ILC may be subtle, a high index of suspicion is required to facilitate early diagnosis.

Adult↗

Effects of cocaine on responding for ethanol or sucrose under a progressive ratio schedule.

Progressive ratio (PR) schedules have been increasingly used to study motivation for self-administered drugs of abuse, such as psychostimulants and ethanol. In these and other studies, the breaking point (BP) is thought to be a measure of the motivation of the animal to work for a particular reward. Ethanol, a highly abused drug, maintains only low BPs. The present experiment was designed to examine if the low BP achieved by animals working for ethanol could be increased by the administration of a psychostimulant. A group working for a sucrose reinforcer was included for comparison. Rats previously trained to lever press under a PR schedule for 0.1 ml aliquots of 10% ethanol or 5% sucrose reinforcers were dosed once a week with cocaine (0, 5 and 15 mg/kg intraperitoneally) 30 min prior to their daily operant session using a Latin square design. Vehicle and 5 mg/kg cocaine had no effect on BP for any reinforcer, but 15 mg/kg cocaine produced a significantly higher BP (P<0.05) for animals working for either ethanol or sucrose. The same doses of cocaine decreased consumption of, and preference for, a 5% sucrose solution. These results indicate that, although cocaine administration does not increase sucrose preference, it may increase BP values in PR schedules. It is therefore unlikely that the increases in BP reflect cocaine-induced increased motivation, and they may be due to cocaine's stimulant or other properties. These data reinforce opinions that PR schedules may be unsuitable for assessing the effects of experimental manipulations on motivation for drugs with stimulant actions.

Animals↗

What's the point of ST elevation?

OBJECTIVE: The magnitude of ST elevation is a key piece of information in the decision to thrombolyse in acute myocardial infarction. The ability of clinicians to reliably identify ST elevation has not been previously assessed. This study sought to determine the variability in assessment of ST elevation in a group of doctors who commonly prescribe thrombolysis. METHODS: The study was conducted in three large teaching hospitals in Manchester, England. A convenience sample of 63 SHOs and SpRs from emergency and general medicine were recruited. Each was shown three sample ECG complexes. They were asked to identify and quantify the degree of ST elevation. They then indicated the points on the ECG from which they measured ST elevation. RESULTS: ST elevation was not identified in 12% of cases. Doctors used a wide variety of points on the ST segment to assess elevation, this resulted in a wide variation in the observed magnitude of ST elevation. CONCLUSION: No guidance exists on where exactly ST elevation should be measured. This study shows a wide variation in practice. Protocol led thrombolysis decision pathways may be compromised by these findings.

Electrocardiography↗

Antagonists of retinoic acid receptors (RARs) are potent growth inhibitors of prostate carcinoma cells.

Novel synthetic antagonists of retinoic acid receptors (RARs) have been developed. To avoid interference by serum retinoids when testing these compounds, we established serum-free grown sub-lines (>3 years) of the prostate carcinoma lines LNCaP, PC3 and DU145. A high affinity pan-RAR antagonist (AGN194310, K(d) for binding to RARs = 2-5 nM) inhibited colony formation (by 50%) by all three lines at 16-34 nM, and led to a transient accumulation of flask-cultured cells in G1 followed by apoptosis. AGN194310 is 12-22 fold more potent than all-trans retinoic acid (ATRA) against cell lines and also more potent in inhibiting the growth of primary prostate carcinoma cells. PC3 and DU145 cells do not express RARbeta, and an antagonist with predominant activity at RARbeta and RARgamma (AGN194431) inhibited colony formation at concentrations (approximately 100 nM) commensurate with a K(d)value of 70 nM at RARgamma. An RARalpha antagonist (AGN194301) was less potent (IC(50) approximately 200 nM), but was more active than specific agonists of RARalpha and of betagamma. A component(s) of serum and of LNCaP-conditioned medium diminishes the activity of antagonists: this factor is not the most likely candidates IGF-1 and EGF. In vitro studies of RAR antagonists together with data from RAR-null mice lead to the hypothesis that RARgamma-regulated gene transcription is necessary for the survival and maintenance of prostate epithelium. The increased potencies of RAR antagonists, as compared with agonists, suggest that antagonists may be useful in the treatment of prostate carcinoma.

Antineoplastic Agents↗

Glucose-induced metabolic oscillations parallel those of Ca(2+) and insulin release in clonal insulin-secreting cells. A multiwell approach to oscillatory cell behavior.

Insulin secretion from glucose-stimulated pancreatic beta-cells is oscillatory, and this is thought to result from oscillations in glucose metabolism. One of the primary metabolic stimulus-secretion coupling factors is the ATP/ADP ratio, which can oscillate as a result of oscillations in glycolysis. Using a novel multiwell culture plate system, we examined oscillations in insulin release and the ATP/ADP ratio in the clonal insulin-secreting cell lines HIT T-15 and INS-1. Insulin secretion from HIT cells grown in multiwell plates oscillated with a period of 4 min, similar to that seen previously in perifusion experiments. Oscillations in the ATP/ADP ratio in cells grown under the same conditions also occurred with a period of 4 min, as did oscillations in [Ca(2+)](i) monitored by fluorescence microscopy. In INS-1 cells oscillations in insulin secretion, the ATP/ADP ratio, and [Ca(2+)](i) were also seen, but with a shorter period of about 1.5 min. These observations of oscillations in the ATP/ADP ratio are consistent with their proposed role in driving the oscillations in [Ca(2+)](i) and insulin secretion. Furthermore, these data show that, at least in the clonal beta-cell lines, cell contact or even circulatory connection is not necessary for synchronous oscillations induced by a rise in glucose.

Adenosine Diphosphate↗