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Biomedical subjects

G Constantine

Publications and source records attributed to G Constantine.

At least 19 recordsLinked to original sources
PubMed2005

Degree of inhibition of cortical acetylcholinesterase activity and cognitive effects by donepezil treatment in Alzheimer's disease.

OBJECTIVES: To determine in vivo cortical acetylcholinesterase (AChE) activity and cognitive effects in subjects with mild Alzheimer's disease (AD, n = 14) prior to and after 12 weeks of donepezil therapy. METHODS: Cognitive and N-[(11)C]methyl-piperidin-4-yl propionate ([(11)C]PMP) AChE positron emission tomography (PET) assessments before and after donepezil therapy. RESULTS: Analysis of the PET data revealed mean (temporal, parietal, and frontal) cortical donepezil induced AChE inhibition of 19.1% (SD 9.4%) (t = -7.9; p<0.0001). Enzyme inhibition was most robust in the anterior cingulate cortex (24.2% (6.9%), t = -14.1; p<0.0001). Donepezil induced cortical inhibition of AChE activity correlated with changes in the Stroop Color Word interference scores (R(2) = 0.59, p<0.01), but not with primary memory test scores. Analysis of the Stroop test data indicated that subjects with AChE inhibition greater than the median value (>22.2%) had improved scores on the Stroop Color Word Test compared with subjects with less inhibition who had stable to worsening scores (t = -2.7; p<0.05). CONCLUSIONS: Donepezil induced inhibition of cortical AChE enzyme activity is modest in patients with mild AD. The degree of cortical enzyme inhibition correlates with changes in executive and attentional functions.

Acetylcholinesterase↗
PubMed2002

A multicentre review of the tension-free vaginal tape procedure in clinical practice.

A multicentre study was conducted to determine the success of the TVT in a clinical practice and to try to identify factors which may be associated with operative failure or postoperative complications. Three hundred and twenty women were included; the overall subjective success rate was 92.2%; 245 patients had reliable documentation regarding postoperative voiding, 25 had voiding problems (10.2%). Operative success did not appear to be diminished by previous surgery. Increased patient weight had a positive effect on outcome. Irritative symptoms preoperatively had an odds ratio of 1.8 for postoperative voiding difficulties. This study shows that the TVT appears to be an effective operation for genuine stress incontinence with low intra and postoperative complication rates. These results also show that it is highly successful in patients who may not be ideal candidates for other continence procedures either because of previous pelvic surgery or body weight.

Adult↗
PubMed2001

Echocardiographic examination of women previously treated with fenfluramine: long-term follow-up of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Fenfluramine hydrochloride was withdrawn from the market in September 1997 after reports of heart valve abnormalities in patients who used it. The prevalence of echocardiographic abnormalities and the clinical cardiovascular status of patients who received fenfluramine monotherapy remains uncertain. METHODS: A long-term, follow-up evaluation was undertaken in subjects who were randomly assigned to receive either fenfluramine hydrochloride (60 mg daily) or placebo as part of a double-blind smoking cessation therapy study. Cardiovascular status was evaluated by echocardiography, medical history, and physical examination. RESULTS: From the group of 720 smokers who had originally participated in the smoking cessation therapy trial, 619 women were enrolled; data from 530 (276 in the fenfluramine group and 254 in the placebo group) were evaluable. No statistically significant differences were identified in the prevalence of aortic or mitral regurgitation by Food and Drug Administration criteria or by grade, aortic or mitral valve leaflet mobility restriction or thickening, elevated pulmonary artery systolic pressure, or abnormal left ventricular ejection fraction. No significant differences were demonstrated in cardiovascular status by physical examination, and no serious cardiac events were noted among fenfluramine-treated subjects. CONCLUSION: There was no evidence of drug-related heart disease up to 4.9 years after anorexigen therapy in subjects who were randomly assigned to receive fenfluramine at the recommended dose for up to 3 months.

Adolescent↗
PubMed2001

Urinary stress incontinence in obese women: tension-free vaginal tape is the answer.

OBJECTIVE: To determine the effectiveness of the tension-free vaginal tape (TVT) in obese women with genuine stress incontinence (GSI), in whom obesity is often considered a relative contraindication to surgical treatment by traditional approaches, e.g. Burch colposuspension and slings (which are difficult and carry increased morbidity) or injectable agents (which although simple, are unpredictable and expensive). PATIENTS AND METHODS: Data on 242 consecutive women with urodynamically proven GSI were collected prospectively. The women were subdivided into three groups with a body mass index (BMI) of < 25, 25-29 and >or=30; obesity was defined as a BMI of >or=30. All procedures were performed under spinal anaesthesia. The King's validated quality of life (QoL) questionnaires (version 7) were completed before and 6 months after surgery. The subjective results were defined as a cure, significant improvement or failure. RESULTS: Almost 90% of the obese women with GSI were cured, while the remaining 10% noted a considerable improvement in their symptoms. There was no significant difference in cure rates among the three groups. There was a highly significant (P < 0.001) improvement in QoL in all groups. CONCLUSION: The TVT is at least as effective in obese women as in those with a lower BMI. The TVT is a simple and minimally invasive procedure, with low morbidity even in the obese group. TVT can be offered confidently to all obese women with GSI.

Adult↗
PubMed2000

Valvular abnormalities and cardiovascular status following exposure to dexfenfluramine or phentermine/fenfluramine.

CONTEXT: Fenfluramine and dexfenfluramine were voluntarily withdrawn from the market in September 1997 because of reports of an association with heart valve abnormalities. Studies have been limited by lack of comparison with untreated controls. OBJECTIVE: To evaluate cardiovascular status and the prevalence of valvular abnormalities, as assessed by clinical cardiovascular parameters and echocardiography, in patients treated for obesity with dexfenfluramine or phentermine/fenfluramine. DESIGN: Reader-blinded controlled study completed in February 1998. SETTING AND PARTICIPANTS: Twenty-five clinical centers in the United States. Of 1640 enrolled subjects, 1473 were eligible (479 and 455 had taken dexfenfluramine and phentermine/fenfluramine, respectively, continuously for 30 days or more in the previous 14 months, and 539 were untreated matched controls) and provided clinical and echocardiographic data. Mean (SD) age was 47.4 (11.4) years, mean body mass index was 35.0 (7.4) kg/m2, and 74% were women. Mean (SD) duration of therapy was 6.0 (3.3) months (range, 1-18.4 months) in the dexfenfluramine group, and 11.9 (10.4) months (range, 1.4-63 months) in the phentermine/fenfluramine group, while the untreated group had no anorexigen use during the previous 5 years. MAIN OUTCOME MEASURES: Cardiovascular signs and symptoms; echocardiographic evidence of aortic (AR) or mitral (MR) regurgitation according to US Food and Drug Administration (FDA) criteria (AR > or = mild or MR > or = moderate) and by grade; tricuspid and pulmonic valve regurgitation; and aortic, mitral, and tricuspid valve leaflet mobility and thickness, for treated vs untreated subjects. RESULTS: Cardiovascular signs and symptoms were similar among anorexigen-treated and untreated subjects. Prevalence rates and relative risk (RR) of AR were significantly increased in anorexigen-treated patients and were 8.9% in the dexfenfluramine group (RR, 2.18; 95% confidence interval [CI], 1.32-3.59), 13.7% in the phentermine/fenfluramine group (RR, 3.34; 95% CI, 2.09-5.35), and 4.1% in the untreated group (P<.001). No statistically significant differences in prevalence were observed for MR, thickening or decreased mobility of any valve leaflet, calculated pulmonary artery systolic pressure, or left ventricular ejection fraction. Serious cardiac events (including myocardial infarction, congestive heart failure, or ventricular arrhythmia) occurring at any time were not statistically different in treated and untreated subjects (dexfenfluramine, 9.0%; phentermine/fenfluramine, 4.0%; and untreated, 8.4%); and following anorexigen treatment were uncommon (dexfenfluramine, 2.3%; phentermine/fenfluramine, 2.4%, and untreated, 3.3%, when adjusted for the median start date of anorexigen use). CONCLUSIONS: Our data indicate that use of dexfenfluramine and phentermine/fenfluramine is associated with an increase in the prevalence of AR using FDA echocardiographic criteria, but was not associated with an increase in the prevalence of MR using FDA criteria or with serious cardiac events.

Aortic Valve Insufficiency↗
PubMed2000

Complications of silicone sling insertion for stress urinary incontinence.

PURPOSE: A pilot study was performed to evaluate the suitability of silicone as a substance for suburethral sling placement. Using rectus sheath for sling placement can be time-consuming and can result in increased morbidity. Adjustable synthetic materials of consistent strength are available. Silicone has previously been used successfully and was chosen for this trial. MATERIALS AND METHODS: Slings were inserted in 7 women with stress urinary incontinence. Of the patients 3 had a history of continence surgery and presented with reduced vaginal mobility, and 2 who had not previously undergone continence surgery had intrinsic sphincter deficiency. RESULTS: In all women stress urinary incontinence was subjectively cured. However, after 7 slings were inserted the study was terminated due to a high complication rate related to erosion and sinus formation in 5 slings which were removed. Complications developed immediately or up to 11 months after sling insertion. Continence was maintained in 4 of the 5 women after the slings were removed. CONCLUSIONS: Silicone is an inappropriate material for suburethral sling placement when used as described in our cases, caution should be exercised when placing silicone slings at this site.

Aged↗
PubMed1998

In-phantom neutron fluence measurements in the orthogonal Birmingham boron neutron capture therapy beam.

This paper presents the results of an experimental investigation into the performance of the Birmingham accelerator-based epithermal BNCT beam. In-phantom gold foil activation and boron trifluoride tube measurements have been used. The results have been compared with calculated response rates using Monte Carlo modeling of the entire neutron system from source to phantom and detector. The excellent agreement obtained gives us confidence in the validity of the simulations and our ability to predict accurately the neutronic performance of our BNCT facility.

Biophysical Phenomena↗
PubMed1997

The requirements and development of neutron beams for neutron capture therapy of brain cancer.

One of the two overriding conditions for successful BNCT is that there must be a sufficient number of thermal neutrons delivered to each of the boronated cells in the tumour bed (target volume). Despite the poor experience with BNCT in the USA some 40 years ago, the continued apparent success of BNCT in Japan since 1968, lead indirectly to the re-start of clinical trials on BNCT in 1994 at both Brookhaven and MIT. Similar trials will start soon at Petten in Europe. At other centres worldwide, many neutron beam designs are being proposed with either thermal or epithermal neutrons, emanating predominantly from nuclear research reactors. It is apparent that whilst the success of BNCT depends on a suitable neutron beam, there is a diversity in available designs, as well as each proposed type of neutron source, with consequently different characteristics of the emergent neutron beam. The paper presents the historical development of neutron beams used for BNCT, addresses the requirements on the types of beams, describes some of the existing designs and other proposals elsewhere and lastly, considers the broader requirements in designing NCT facilities. The focus of the paper is on treatment of brain cancer, neutron beam requirements for other types of cancer may vary.

Boron Neutron Capture Therapy↗
PubMed1997

The Kleihauer technique: an accurate method of quantifying fetomaternal haemorrhage?

Blood was taken from 100 consecutive asymptomatic women at 17 to 18 weeks of pregnancy for Kleihauer testing. When a proportion of these slides were assessed at a different hospital there was agreement in only 46%. When the number of fetal cells were quantified there were differences of over 500%. These results show a large inter-observer and inter-hospital variation in interpreting Kleihauer slides. If these investigations are to be performed, it is essential that clinicians can rely on the results. There is a need for quality control measures and audit so that laboratories can rectify any deficiencies in their techniques.

Blood Cells↗
PubMed1997

Etodolac (Lodine) in the treatment of osteoarthritis: recent studies.

Etodolac (Lodine) has been marketed in the United States since 1991 for managing pain and for acute and longterm treatment of the signs and symptoms of osteoarthritis (OA). Etodolac was recently approved for the treatment of rheumatoid arthritis. We review the results of 3 recent 4 week, multicenter, placebo controlled, parallel group studies that compared the efficacy and safety of etodolac with naproxen and nabumetone. Because studies of etodolac in the treatment of OA concentrated on bid doses, the first study compared etodolac 800 mg/day given as 400 mg bid (106 patients) and 200 mg qid (105 patients) with naproxen 1000 mg/day (109 patients) and placebo (104 patients). Etodolac was as effective as naproxen, and the 2 dosage schedules of etodolac were comparable. The 2nd study compared etodolac 400 mg bid (86 patients) with naproxen 500 bid (82 patients) and placebo (86 patients). Etodolac was again found to be as effective as naproxen. The 3rd study compared etodolac 400 mg bid (91 patients) with nabumetone 1500 mg/day (89 patients) and placebo (90 patients). The results indicated that the efficacy of etodolac was comparable to that of nabumetone and resulted in significantly better scores at endpoint on the investigator's overall assessment and patient's global assessment. In all 3 studies there were no significant differences among the groups in the frequency of study events or premature discontinuations as a result of study events. The most common adverse event was digestive system disturbance, which was mild to moderate in severity. The results of these studies confirm the efficacy and safety of etodolac in managing the signs and symptoms of OA.

Administration, Oral↗
PubMed1993

Boron neutron capture therapy: long-term effects on the skin and spinal cord of the rat.

Our studies of the pharmacokinetics of boron focused on the variations in the concentration in blood of Sprague-Dawley rats with time after the administration of single intravenous doses of 50-200 mg/kg of 10B-enriched sodium mercaptoundecahydro-closo-dodecaborate (BSH). After the lowest dose of BSH there was a progressive decline in the boron content of the blood, with a biological half-life (t1/2) of approximately 4.5 h. Higher doses of BSH resulted in slower boron clearance rates. A dose of 100 mg/kg of BSH was the maximum safely tolerated by the rats. The boron content of the skin at this dose of BSH was a factor of 0.6 lower than that in the blood. To determine the dose-related changes in the response of the central nervous system to BNCT-type radiation exposures, a well-established and clinically relevant model, the rat spinal cord, was used. The spinal cords (20 mm field length) of rats, infused with 100 mg/kg of BSH, were irradiated for 3 to 5 h with cold thermal neutrons from the H6 beam on the DIDO reactor (AERE, Harwell). The skin surface neutron flux was 4.8 x 10(8) n/cm2/s. Exposure times of > or = 4 h resulted in vigorous, biphasic skin reactions, indicative of long-term vascular damage in the dermis. Rats were monitored closely for 84 weeks after irradiation. No abnormal neurological responses were observed and there was no histological evidence of lesions in the spinal cord at the end of the study. These findings indicate that the central nervous system has a high tolerance to BNCT-type radiation using BSH as the neutron capture agent.

Animals↗
PubMed1992

Placental biopsy in the third trimester of pregnancy.

Forty-two women with abnormal ultrasound findings after 27 weeks' gestation underwent a placental biopsy. In 39 cases, a karyotype was obtained from a direct preparation within 48 h, five abnormal karyotypes being detected (four trisomies and a triploidy). One confirmed placental mosaic was also detected. In one case, a small terminal deletion of chromosome 7 was not detected at the time due to the quality of the preparation. A karyotype can be obtained from a direct preparation in the third trimester in over 90 per cent of cases, the quality of the preparation allowing the reliable detection of abnormalities of chromosome number. We believe that this technique may be usefully, reliably, and safely employed in the third trimester of pregnancy by those with an interest in antenatal ultrasound diagnosis who do not have immediate access to a cytogenetics laboratory and who feel that cordocentesis is inappropriate for their situation.

Chorionic Villi Sampling↗
PubMed1991

Cystic adenomatoid malformation of the lung: an obstetric and ultrasound perspective.

Between 1986 and 1990, seven women were found to have fetuses with an abnormal antenatal ultrasound appearance of the chest and lungs suggestive of congenital cystic adenomatoid malformation of the lung (CCAM). All were confirmed by pathology. Cystic spaces were only visible in those women with macrocystic disease (Stocker types 1 and 11) whilst increased echogenicity of affected lung tissue and mediastinal deviation were seen in all types. Cystic adenomatoid malformation of the lung was also found in one woman with a raised maternal serum alpha-fetoprotein. The appearances are distinctive, and should be sought in all cases of polyhydramnios, fetal ascites and raised maternal serum alpha-fetoprotein.

Cystic Adenomatoid Malformation of Lung, Congenita↗
PubMed1991

Prenatal diagnosis of severe osteogenesis imperfecta.

The ultrasound findings in a series of 15 prenatally diagnosed cases of severe osteogenesis imperfecta types IIA, IIB, IIC, and III are described, eleven being detected on routine scans of women with no relevant history. As most cases of osteogenesis imperfecta type IIA are dominant sporadic mutations, the importance of prenatal diagnosis during routine scanning at a local level is emphasized. In addition to characteristic broad, shortened and fractured long bones, striking features of the chest and head are highlighted which may be encountered during a routine scan, prompting further assessment.

Female↗
PubMed1991

Comparative audit of booking and mid-trimester ultrasound scans in the prenatal diagnosis of congenital anomalies.

During 1988 and 1989, 3565 women booked under consultants who performed an ultrasound scan at booking, whilst 4984 booked under consultants who performed a formal mid-trimester scan between 16 and 18 weeks. All significant anomalies diagnosed prenatally and in the neonatal period were recorded, the incidence in each group being 12.9/1000 and 9.83/1000, respectively (NS). The sensitivity of diagnosis before 20 weeks was 45 percent in the 'mid-trimester' group (kappa 0.62) compared with 30 percent in the 'booking' group (kappa 0.46), overall sensitivity of prenatal diagnosis, however, being similar in both groups (63 vs. 65 percent, kappa 0.77 vs. 0.79). Cardiac anomalies were the single largest group which were not detected equally prenatally in both groups. This study shows that formal mid-trimester scanning leads to anomalies being detected significantly earlier in the antenatal period. Although not statistically significant, three lethal anomalies were missed prenatally in the 'booking' group which we would have expected to diagnose on a mid-trimester scan. These figures are discussed in the light of previous reports.

Congenital Abnormalities↗