PubMed Health⌕ Search

Biomedical subjects

D Shaw

Publications and source records attributed to D Shaw.

At least 19 recordsLinked to original sources
PubMed2006

Women's right to health and the Millennium Development Goals: promoting partnerships to improve access.

The Millennium Development Goals (MGD) represent a commitment of 189 member states that adopted them during the Millennium Summit in September 2000. This UN General Assembly recognized that gender equality and women's empowerment are both central to achieving sustainable development by means of combating poverty, hunger and disease. Neither reproductive nor sexual health was explicitly articulated in the original MDGs and indicators-a critical omission, as globally women are more disadvantaged than men. However, a clear link exists between all of the MDGs and the reproductive and sexual health of women, who cannot contribute to sustainable development, unless their right to health is met through improved access. The FIGO 2006 World Report on Women's Health addresses many issues critical to the success of the MDGs, with a focus on how partnerships have become a crucial vehicle to improve access to health for women.

Child Mortality↗
PubMed2006

Early experience with linezolid for infections in orthopaedics.

In infections following orthopaedic surgery, isolated staphylococci are reported to be methicillin resistant (MRSA) in up to 50% of cases. Linezolid, the first in a new class of antibiotics, has excellent efficacy against gram positive organisms that are resistant to other therapies and is 100% orally bioavailable. We report early results of its use for the treatment of resistant infections in orthopaedic practice. Infections were characterised according to the UK Nosocomial Infections National Surveillance Service classification of surgical infections as superficial, deep or organ/space. Osteomyelitis, joint sepsis and deep infection involving orthopaedic implants were included into the final category. Outcome was recorded as clinical, microbiological and blood parameter cure or fail. Over the 12-month study period, 54 patients received linezolid therapy, 41% of these had significant co-morbidity that might affect their ability to fight infection. Sixty-seven percent of infections were in association with implanted metal work. The majority of patients were treated with vancomycin for a short period before linezolid was used as oral 'switch' therapy for longer-term administration, allowing early discharge in all cases. MRSA was isolated in 87% of the patients treated. The mean length of linezolid therapy was 39 days (2-151). Clinical success was achieved in 90% of patients overall. Though there were no life-threatening complications, adverse event rates were significantly higher than those recorded in the literature, with 19% of patients needing to cease therapy. Linezolid offers an alternative to traditional treatments for resistant infections and can facilitate early discharge. Patients need to be monitored closely, particularly where long-term therapy is planned.

Acetamides↗
PubMed2006

Phase II trial of intravenous lobradimil and carboplatin in childhood brain tumors: a report from the Children's Oncology Group.

BACKGROUND: [corrected] Lobradimil is a synthetic bradykinin analog that rapidly and transiently increases the permeability of the blood-brain barrier (BBB). The combination of lobradimil and carboplatin was studied in pediatric patients with primary brain tumors in a phase II trial, the primary endpoints of which were to estimate the response rate and time to disease progression. PATIENTS AND METHODS: Patients were stratified by histology into five cohorts: brainstem glioma, high-grade glioma, low-grade glioma, medullobastoma/primitive neuroectodermal tumor (PNET), and ependymoma. Patients received carboplatin adaptively dosed to achieve a target AUC of 3.5 mg min/ml per day (7 mg.min/ml/cycle) intravenously over 15 min on 2 consecutive days and lobradimil 600 ng/kg ideal body weight/day on 2 consecutive days each 28 day cycle. RESULTS: Forty-one patients, age 2-19 years, were enrolled; 38 patients, including 1 patient ultimately determined to have atypical neurocytoma, were evaluable for response. No objective responses were observed in the brainstem glioma (n=12) and high-grade glioma (n = 9) cohorts, although two patients with high-grade glioma had prolonged disease stabilization (>6 months). The study was closed for commercial reasons prior to achieving the accrual goals for the ependymoma (n = 8), medulloblastoma/PNET (n = 6) and low-grade glioma (n = 2) cohorts, although responses were observed in 1 patient with PNET and 2 patients with ependymoma. CONCLUSION: The combination of lobradimil and carboplatin was inactive in childhood high-grade gliomas and brainstem gliomas.

Adolescent↗
PubMed2005

Safety of arch aortography for assessment of carotid arteries.

PURPOSE: To retrospectively review the safety of arch aortography and compare complication rates with published figures for selective catheter angiography. METHODS: The medical records of patients undergoing arch aortography over the last 3 years (n=311; 180 male, 131 female; mean+/-SD age 71.0+/-9.2 years, range 42-90 years) were retrospectively reviewed. Any peri-procedural (0-48 h) complications were recorded. A certified neurologist (MSR/GSV) classified all questionable neurological events. RESULTS: There were no focal neurological events or deaths (n=0; 0%; CI: 0-0.96%). Non-focal neurological events included mild disorientation (n=2; 0.6%; CI: 0.176-2.31) and unequal pupils (n=1; 0.3%; CI: 0.056-1.79%). Cardiovascular events included symptomatic hypotension (n=4; 1.3%; CI: 0.50-3.25%), angina (n=1; 0.3%; CI: 0.056-1.79%) and arrhythmia (n=4; 1.3%; CI: 0.50-3.25). There were 27 minor access site complications (8.7%; CI: 6.0-12.3). None of these complications extended hospital stay. None of the arch angiograms had to be followed by selective carotid angiography. CONCLUSION: Arch aortography appears to have a lower neurological complication rate than selective carotid angiography.

Adult↗
PubMed2005

Evaluation of an in vitro method for the measurement of specific IgE antibody responses: the rat basophilic leukemia (RBL) cell assay.

The evaluation of allergenic potential is a key parameter in the safety assessment of novel proteins, including those expressed in genetically modified crops and foodstuffs. The majority of allergic reactions to food proteins are immediate type hypersensitivity reactions in which the principal biological effector is IgE antibody; the accurate measurement of specific IgE antibody is therefore a critical factor in experimental systems designed to characterize protein allergenic potential. Due to the presence of much higher concentrations of other immunoglobulin isotypes, the assessment of specific serum IgE antibody poses substantial technical challenges. We have examined the utility of the rat basophilic leukemia (RBL) cell line for the measurement of murine IgE responses. RBL cells were sensitized with mouse monoclonal anti-dinitrophenyl (DNP) IgE antibody and challenged with DNP-albumin conjugates with various hapten substitution ratios (SR). Polyclonal anti-OVA IgE antisera were also assessed for activity in the RBL assay. Results were compared with titers measured in homologous passive cutaneous anaphylaxis (PCA) assay. Marked degranulation of RBL cells was induced by conjugates with SRs of between 16 and 32, whereas conjugates with lower SRs (of 10 or 3) failed to elicit significant serotonin release. All conjugates were able to induce mast cell degranulation in vivo in a PCA assay. Anti-OVA antisera with PCA titers of 1/32 to 1/64 failed to stimulate RBL cell degranulation, whereas high titer antibody (1/2048 to 1/4096 by PCA) induced a positive RBL cell response. Successful stimulation of RBL cell degranulation requires not only appropriate epitope densities but also high affinity antibody. These data indicate that this assay is inappropriate for the routine analysis of specific polyclonal IgE antibody responses such as those that are induced by exposure to complex protein allergens.

Allergens↗
PubMed2005

Observational study of the natural history of eosinophilic bronchitis.

BACKGROUND: Eosinophilic bronchitis is an important cause of chronic cough. Treatment with inhaled corticosteroids is associated with a short-term improvement in cough and reduced sputum eosinophil count but the long-term outcome is uncertain. OBJECTIVE: To determine the long-term outcome in patients diagnosed with and treated for eosinophilic bronchitis. METHODS: We have performed a longitudinal study of symptoms, eosinophilic airway inflammation, spirometry and airway hyper-responsiveness in all patients diagnosed with eosinophilic bronchitis over 7 years. RESULTS: We identified 52 patients with eosinophilic bronchitis and longitudinal data of greater than 1 year (mean 3.1 years) was available in 32 patients, all of whom were treated with inhaled steroids. Three (9%) patients developed symptoms consistent with asthma and a methacholine PC20<8 mg/mL on one or more occasion. Five (16%) patients developed fixed airflow obstruction defined by a persistent post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity<70%. One (3%) patient had complete resolution of symptoms and eosinophilic airway inflammation off treatment. The remaining patients had ongoing eosinophilic airway inflammation and/or continuing symptoms. Multiple linear regression identified smoking, female gender and area under the curve of sputum eosinophil count over time as the most important predictors of decline in FEV1. CONCLUSIONS: The most common outcome in eosinophilic bronchitis is continuing disease and complete resolution is rare. Asthma and fixed airflow obstruction developed in relatively few patients. The most important factors associated with a more rapid decline in FEV1 were female gender, smoking and prolonged eosinophilic airway inflammation.

Administration, Inhalation↗
PubMed2005

Chromoendoscopic surveillance in hereditary diffuse gastric cancer: an alternative to prophylactic gastrectomy?

BACKGROUND: Hereditary diffuse gastric cancer (HDGC) is defined by germline mutations in the E-cadherin gene, CDH-1. The first family in which CDH-1 mutations were identified was a large Maori kindred, where lifetime penetrance is 70%. Prophylactic gastrectomy is an unacceptable option for many mutation carriers. The results of annual chromoendoscopic surveillance using the methylene blue/congo red technique in 33 mutation carriers over a five year period are described. PATIENTS AND METHODS: Thirty three confirmed CDH-1 mutation carriers (18 males, 15 females), median age 32 years (range 14-69), were enrolled in 1999-2003. Medical records, endoscopy, and pathology were reviewed retrospectively. RESULTS: Over five years, 99 surveillance endoscopies were performed, of which 93 were chromo-dye enhanced. Sixty nine chromoendoscopies were normal. In 24 procedures, 1-6 pale areas/stomach (size 2-10 mm) were detected post chromo-dye application (totalling 56 pale lesions). One biopsy was taken from each pale lesion: 23 lesions (41%) showed signet ring cell carcinoma (10 patients), 10 lesions (18%) gastritis (four patients), and 23 (41%) normal mucosa (10 patients). No chromo-dyes were used in six procedures with macroscopic lesions (two HDGC, four ulceration). Total gastrectomies from patients with carcinoma were macroscopically normal but pathological mapping showed multiple microscopic foci of early signet ring cell carcinoma. Correlation of chromoendoscopic and gastrectomy findings showed that congo red/methylene blue detected carcinoma foci 4-10 mm in size but not foci <4 mm. CONCLUSIONS: The use of chromoendoscopy following normal white light gastroscopy facilitated detection of early gastric carcinoma foci not visible with white light gastroscopy. If these findings are validated in other HDGC kindred, chromogastroscopy represents an improved surveillance technique that can be safely considered alongside prophylactic gastrectomy.

Adolescent↗
PubMed2005

Alveolar nitric oxide in adults with asthma: evidence of distal lung inflammation in refractory asthma.

Recent studies have suggested that alveolar nitric oxide (NO) concentration is a noninvasive test of distal lung inflammation. The current study determined whether alveolar NO concentration can be measured in patients with asthma of varying severity, tested the hypothesis that there is an association between alveolar NO and bronchoalveolar lavage (BAL) eosinophil count and determined whether refractory asthma is characterised by a raised alveolar NO concentration. Finally, the present authors assessed the effect of 2 weeks of prednisolone (30 mg q.d.) on alveolar NO concentration. Alveolar NO concentration was both measurable and repeatable in patients with refractory asthma. A positive correlation was found between alveolar NO concentration and BAL eosinophil count but not with bronchial wash or sputum eosinophil count. Alveolar NO concentration was increased in patients with refractory asthma (7.1 ppb) compared with mild-to-moderate asthma (3.4 ppb) and normal controls (3.4 ppb) and reduced by treatment with prednisolone. In conclusion, these findings support the hypothesis that alveolar nitric oxide is a measure of distal airway inflammation and suggest that distal lung inflammation is present in refractory asthma.

Administration, Inhalation↗
PubMed2004

Late first-trimester invasive prenatal diagnosis: results of an international randomized trial.

OBJECTIVE: To assess, in a randomized trial, the safety and accuracy of amniocentesis and transabdominal chorionic villus sampling (CVS) performed at 11-14 weeks of gestation, given that this time frame is increasingly relevant to early trisomy screening. METHODS: We compared amniocentesis with CVS from 77 to 104 days of gestation in a randomized trial in a predominantly advanced maternal age population. Before randomization, the feasibility of both procedures was confirmed by ultrasonography, and experienced operators performed sampling under ultrasound guidance; conventional cytogenetic analysis was employed. The primary outcome measure was a composite of fetal loss plus preterm delivery before 28 weeks of gestation in cytogenetically normal pregnancies. RESULTS: We randomized 3,775 women into 2 groups (1,914 to CVS; 1,861 to amniocentesis), which were comparable at baseline. More than 99.6% had the assigned procedure, and 99.9% were followed through delivery. In contrast to previous thinking, in the cytogenetically normal cohort (n = 3,698), no difference in primary study outcome was observed: 2.1% (95% confidence interval 1.5, 2.8) for CVS and 2.3% (95% confidence interval, 1.7, 3.1) for amniocentesis. However, spontaneous losses before 20 weeks and procedure-related, indicated terminations combined were increased in the amniocentesis group (P =.07, relative risk 1.74). We found a 4-fold increase in the rate of talipes equinovarus after amniocentesis (P =.02) overall and in week 13 (P =.03, relative risk = 4.65), but data were insufficient to determine this risk in week 14. CONCLUSION: Amniocentesis at 13 weeks carries a significantly increased risk of talipes equinovarus compared with CVS and also suggests an increase in early, unintended pregnancy loss. LEVEL OF EVIDENCE: I

Abortion, Induced↗
PubMed2004

Long-term outcome of pediatric obsessive-compulsive disorder: a meta-analysis and qualitative review of the literature.

OBJECTIVE: To review the extant literature on the long-term outcome of child/adolescent-onset obsessive-compulsive disorder (OCD). METHOD: Medline and Psychlit databases were systematically searched for articles regarding long-term outcomes of child/adolescent-onset OCD. Meta-analysis regression was applied to evaluate predictors and persistence of OCD. RESULTS: Sixteen study samples (n = 6-132; total = 521 participants) in 22 studies had follow-up periods ranging between 1 and 15.6 years. Pooled mean persistence rates were 41% for full OCD and 60% for full or subthreshold OCD. Earlier age of OCD onset (z = -3.26, P = 0.001), increased OCD duration (z = 2.22, P = 0.027) and in-patient vs. out-patient status (z = 2.94, P = 0.003) predicted greater persistence. Comorbid psychiatric illness and poor initial treatment response were poor prognostic factors. Although psychosocial function was frequently compromised, most studies lacked comprehensive outcome measures. CONCLUSION: Long-term persistence of pediatric OCD may be lower than believed. Future studies should include broader measures of outcome including symptomatic persistence and functional impairment in multiple domains.

Adolescent↗
PubMed2004

Hereditary diffuse gastric cancer: predominance of multiple foci of signet ring cell carcinoma in distal stomach and transitional zone.

BACKGROUND AND AIMS: Germline mutations in the CDH-1/E-cadherin gene are, to date, the only known cause of hereditary diffuse gastric cancer (HDGC). While two recent series of prophylactic gastrectomy described microscopic foci of signet ring cell carcinoma in sample sections from 10 macroscopically normal stomachs, whole stomach phenotype has not been mapped. We aimed to describe the size and distribution of foci in relation to mucosal zones and anatomical location. METHODS: Six patients (from three HDGC kindred) were referred for total gastrectomy via three different referral pathways. Following fixation, five stomachs were completely blocked and one extensively sampled. Histopathology was mapped to a mucosal photograph of each stomach, enabling precise localisation of carcinoma foci, benign pathology, and mucosal zones. RESULTS: There were 4-318 microscopic foci of intramucosal signet ring cell adenocarcinoma in the six macroscopically normal stomachs (foci size 0.1-10 mm in diameter). The distal third of the stomach contained 48% of total foci (range 29-75%). The body-antral transitional zone occupied 7.7% of mucosal area (range 3.6-11.8) but had 37% of foci (range 10%-75%). The largest foci were found in the transitional zone and foci density was five times greater in the transitional zone than in body or antral type mucosa. CONCLUSIONS: In germline CDH-1 mutation carriers, multiple microscopic foci of intramucosal signet ring cell carcinoma show a predilection for the distal stomach and the body-antral transitional zone. Targeting the transitional zone would maximise the likelihood of finding foci in macroscopically normal gastrectomies, and particular attention should be paid to this area during endoscopy.

Adolescent↗
PubMed2004

Effects of chlordiazepoxide on extinction and re-acquisition of operant behaviour in mice.

Relatively little is known about the role of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in extinction of appetitively motivated tasks. The benzodiazepine (BZ) chlordiazepoxide (CDP) was administered during extinction and re-acquisition of lever pressing by mice following food reinforced discrete-trial fixed-ratio 5 (FR-5) training. Typical FR behaviour was established during baseline training and persisted for several extinction sessions. There were 15 extinction sessions in all, followed by six re-acquisition sessions where food reinforcement was re-introduced. In a 2x2x2 between-group design, CDP (15 mg/kg) or vehicle injections were given prior to either the last two food reinforcement sessions and the first 10 extinction sessions, or the final five extinction sessions, or the six re-acquisition sessions. Initially CDP had no effect on the rate of extinction, but after several extinction sessions it significantly facilitated it. Surprisingly, if CDP was administered only after several sessions of extinction, it immediately produced facilitation. Thus the delayed effects of CDP are not due to drug accumulation. These data suggest that some neural change must occur before CDP can affect extinction processes. In re-acquisition sessions, CDP facilitated the reinstatement of food-reinforced lever pressing. Implications for neural and behavioural accounts of operant extinction are discussed.

Animals↗
PubMed2002

Prenatal diagnosis of apparently isolated unilateral multicystic kidney: implications for counselling and management.

Cases where initial prenatal diagnosis was made of isolated unilateral multicystic kidney (UMCK) were reviewed to determine appropriate counselling and management strategies. For the 73 cases, chromosome abnormalities, pregnancy complications and family histories were reviewed. In addition, subsequently diagnosed birth defects, and pediatric medical and surgical outcomes were available for 54 cases. Of those with outcome information available renal/genital-urinary tract abnormalities were diagnosed subsequently in 33% and non-renal abnormalities in 16% of cases. Of the non-renal abnormalities, congenital heart defects were most frequent (7%). One chromosome abnormality, a trisomy 21, was present among 32 cases where karyotypes were known (3%). Amniotic fluid volume abnormalities were present in 11 cases but not predictive of associated anomalies, with the exception of one case where polyhydramnios accompanied multiple malformations consistent with VATER association. A family history of structural renal anomalies was reported in 11 cases (20%). There were 14 cases of partial or complete involution (25%), including two cases of complete prenatal involution of the cystic kidneys. No long-term associated morbidity such as hypertension or malignancy was present in our cohort. Based on our study and corroborating literature, amniocentesis should be offered to women when a seemingly isolated UMCK is detected on routine prenatal ultrasound. Furthermore, a detailed ultrasound with careful assessment of the fetal heart and contralateral kidney is indicated at diagnosis and during the third trimester to assess for further evidence of structural abnormalities, as well as amniotic fluid volume abnormalities. Careful assessment of the newborn is indicated with appropriate speciality referral as required.

Abnormalities, Multiple↗