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Biomedical subjects

J Barton

Publications and source records attributed to J Barton.

At least 19 recordsLinked to original sources

Atomoxetine: a new pharmacotherapeutic approach in the management of attention deficit/hyperactivity disorder.

Atomoxetine is a novel, non-stimulant, highly selective noradrenaline reuptake inhibitor that has been studied for use in the treatment of attention deficit/hyperactivity disorder (ADHD). Data from clinical trials show it to be well tolerated and effective in the treatment of ADHD in children, adolescents, and adults. Improvements were seen not only in core symptoms of ADHD, but also in broader social and family functioning and self esteem. Once-daily dosing of atomoxetine has been shown to be effective in providing continuous symptom relief. Atomoxetine does not appear to have abuse potential and is associated with a benign side effect profile. The development of atomoxetine thus represents an important advance in the pharmacological management of ADHD.

Atomoxetine Hydrochloride↗

The impact of regional anaesthesia on outcome: a patient's perspective.

Peripheral nerve catheters are being used increasingly to manage acute pain. Whilst acknowledged as effective, their broader implications for patient outcome are less clear. In this case report, we describe the way in which not only was the pain management of an ischaemic leg successful via a sciatic nerve catheter, but decision-making around this strategy affected outcome.

Acute Disease↗

The importance of testing for adrenoleucodystrophy in males with idiopathic Addison's disease.

X linked adrenoleucodystrophy (X-ALD) is considered to be a rare cause of Addison's disease, although several small series suggest a high incidence in young Addisonian males. A survey in the south west of England identified 12 male patients diagnosed with Addison's disease in the period 1987-99. In 10 of these (83%) X-ALD was the underlying cause; the other two were of autoimmune aetiology. Five boys had developed Addison's disease subsequent to the diagnosis of X-ALD. Of the remaining five, in three boys the diagnosis of X-ALD was considerably delayed (by six months to two years from that of Addison's disease) and in two it was only made as a result of this survey. We also identified a patient who presented with Addison's disease at the age of 5 years but was only diagnosed as having X-ALD at the age of 34 years; in the interim his diagnosis of adrenomyeloneuropathy had been missed. Our experience highlights the absolute necessity of measuring very long chain fatty acids in all males with idiopathic Addison's disease.

Addison Disease↗

Growth factors and their receptors: new targets for prostate cancer therapy.

Stimulation of the signal transduction pathway of the epidermal growth-factor receptor (EGFR) tyrosine kinase family of receptors in tumor cells enhances cellular proliferation, prevents apoptosis, and promotes tumor-cell mobility, adhesion, and invasion. Therapeutic approaches used to target the EGFR and its signal transduction cascade include (1) monoclonal antibodies (eg, cetuximab [IMC-C225]) directed against the extracellular binding domain of the receptor; and (2) trastuzumab, a monoclonal antibody binding to the HER2 receptor; immunotoxin conjugates use an antibody directed against EGFR joined to a cell toxin. All are in clinical trials for a number of cancers, including prostate cancer. Antisense strategies are in preclinical development. Low-molecular-weight inhibitors of the EGFR tyrosine kinase also in clinical development include OSI-774, PD182905, PKI-166, CI-1033, and ZD1839. ZD1839 has shown encouraging results in patients with prostate cancer in phase 1 trials. mn

Antibodies, Bispecific↗

Physiologic modeling of the intravenous glucose tolerance test in type 2 diabetes: a new approach to the insulin compartment.

The minimal model of Bergman et al has been used to yield estimates of insulin sensitivity (Si) and glucose effectiveness (Sg) in type 2 diabetes by incorporating exogenous insulin protocols into the regular intravenous glucose tolerance test (IVGTT). These estimates, however, are influenced by the degree to which the dose of exogenous insulin is greater than the physiologic response to a glucose load. Moreover, most studies have related to type 2 diabetes subjects whose diabetes was relatively mild in terms of therapeutic requirements. To develop a "minimal disturbance" approach in estimating Si and Sg in type 2 diabetes, we have used a reduced glucose load (200 mg/kg) and a "physiologic" insulin infusion throughout the IVGTT in a series of 8 patients, 5 of whom were insulin-requiring. Data from this approach were analyzed using the modelling program CONSAM to apply the Bergman model, either unmodified (BMM), or incorporating an additional delay element between the plasma and "remote" insulin compartments (MMD). Application of the MMD and extension of the IVGTT from 3 to 5 hours improved successful resolution of Si and Sg from 37.5% (BMM, 3-hour IVGTT) to 100% (MMD, 5-hour IVGTT). Si was reduced in these type 2 diabetes patients compared with normal subjects (1.86 +/- 0.60 v. 8.65 +/- 2.27 min(-1) x microU(-1) x mL x 10(4) P <.01). The results were validated in the type 2 diabetes group using a 2-stage euglycemic clamp ((Si)CLAMP = 2.02 +/- 0.42 min(-1) x microU(-1) x mL x 10(4) P >.4). Sg was not significantly reduced (2.00 +/- 0.25 type 2 diabetes v. 1.55 +/- 0.26 normal min(-1) x 10(2)). Data from a group of normal nondiabetic subjects was then analyzed using the MMD, but this approach did not enhance the fit of the model compared with the BMM. This result indicates that the delay in insulin action in type 2 diabetes represents an abnormality whereby the onset of insulin action cannot be described as a single phase in the transfer of insulin from plasma to the remote compartment. It is postulated that the physiologic basis for this delayed action may relate to transcapillary endothelial transfer of insulin, this process limiting the rate of onset of insulin action.

Blood Glucose↗

Measurement properties of the Shiftwork Survey and Standard Shiftwork Index.

The Shiftwork Survey (SS) was introduced, along with the Standard Shiftwork Index (SSI), to provide a set of standardized self-report measures to be used in shiftwork research. However, beyond the initial assessment, no attempt has been made to examine the measurement properties of these scales in an independent sample of shiftworkers. Our goal, therefore, was to examine the measurement properties of these scales in an industrial sample of primarily male shiftworkers (N = 370). We found that all scales had acceptable reliabilities (alphas). The confirmatory factor analyses revealed that the chronic fatigue, coping, job satisfaction, and sleep scales are the weakest psychometrically, and the anxiety, personality (extraversion, neuroticism), general health, and physical health scales are the strongest psychometrically. Using item response theory analyses, we found that the scales overall are generally adequate measures of their underlying constructs, although many items should be altered or omitted. Our results, however, are limited by reliance on a single sample.

Adult↗

Genomics and agriculture. Collaborations in rice.

Advances in rice genomics will contribute to gene discovery and rice productivity, but many of the products with high potential for alleviating poverty and improving human nutrition may not be those that attract private investment. Although most genetic resources and biological expertise for functional genomics are in the public, many proprietary technologies are owned by the private sector. A public resource platform is needed for the application of genomic technology to accelerate gene discovery. We present a model and general principles in collaboration that can serve the poor and encourage innovation by both the public and private sectors.

Crops, Agricultural↗

Anti-EGF receptor therapy.

The epidermal growth factor receptor (EGFR) signalling pathway contributes to a number of processes important to tumour progression, including cell proliferation, apoptosis, angiogenesis and metastatic spread. EGFR signalling is thought to be an important cell survival mechanism in hormone-resistant prostate cancer. ZD1839 ('Iressa') is an orally active, selective EGFR-tyrosine kinase inhibitor (EGFR-TKI) which blocks signal transduction pathways implicated in promoting cancer growth. In preclinical studies, ZD1839 alone, and in combination with cytotoxic agents, produced reversible growth inhibition and growth delay in a wide range of tumour cell lines and human tumour xenografts. Preliminary results from phase I trials in patients with advanced disease suggest that ZD1839 has an acceptable tolerability profile and promising clinical efficacy in patients with a variety of tumour types, including hormone-resistant prostate cancer, where new treatment strategies are needed. Prostate Cancer and Prostatic Diseases (2000) 3, 296-302

Journal Article↗

Obstetric outcomes in 102 pregnancies after preimplantation genetic diagnosis.

OBJECTIVE: We sought to determine whether preimplantation genetic diagnosis is associated with particular pregnancy or delivery complications. STUDY DESIGN: A total of 102 consecutive pregnancies after preimplantation genetic diagnosis by polar body removal performed at Illinois Masonic Medical Center resulting in 114 live births were analyzed. All patients were given a delivery and newborn questionnaire, and attempts were made to contact and question them regarding any pregnancy complications and type of delivery. Permission was obtained to examine medical records and discuss the patient's pregnancy with her obstetrician when questions existed with respect to complications or indication for cesarean delivery. RESULTS: Delivery and newborn questionnaires were completed or telephone contact was achieved for 100 of the 102 pregnancies. There were 85 singleton, 9 twin, and 7 triplet pregnancies. Of the 7 triplet gestations, 3 couples elected multifetal pregnancy reduction to twins and healthy triplets were born to 4 couples between 32 and 36 weeks by cesarean delivery. Of the 80 singleton deliveries, 60 (75%) progressed to term. Of these 60 term singleton deliveries, 34 were vaginal, 23 were cesarean (40%), and 3 delivery types were unknown. The incidence of small-for-gestational-age infants was 3% for neonates in the 60 term singleton deliveries and 7% in the entire cohort of 80 singleton deliveries. Only 3 pregnancy complications (other than premature delivery) were reported more than once. There were 3 instances each of gestational diabetes, intrauterine growth restriction, and pregnancy-induced hypertension. There was 1 case each of HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, congestive heart failure, mild oligohydramnios, and abruptio placentae. The indications for cesarean delivery were (in descending order) failure of labor to progress (n = 7), fetal distress (n = 4), placenta previa (n = 4), elective repeat cesarean delivery (n = 4), triplets (n = 3), uterine scarring (n = 3), 1 twin in the breech position (n = 3), failed forceps delivery (n = 2), and a variety of other indications that occurred in only 1 patient each. All preimplantation genetic diagnoses were confirmed by prenatal or postnatal testing. No diagnostic errors were made in this cohort of patients or in any patients undergoing preimplantation genetic diagnosis having polar body removal in our center. CONCLUSIONS: Preimplantation genetic diagnosis is associated with a risk of multiple gestations, cesarean delivery, and placenta previa. Cesarean delivery rates and multiple gestation rates are comparable to those of patients undergoing in vitro fertilization in general. The preimplantation genetic diagnosis itself does not seem to cause an increased risk for any particular pregnancy complication, with the possible exception of placenta previa, which was seen in 4% of patients.

Cesarean Section↗

Aneurysmal bone cyst in a female collegiate field hockey player: a case report.

OBJECTIVE: To present the case of an intercollegiate field hockey player with an aneurysmal bone cyst of the femur and the clinical decision making necessary in the evaluation, management, surgical intervention, and positive outcome of this athlete. BACKGROUND: A 21-year-old field hockey player presented with signs and symptoms typical of a deep thigh contusion. She had no history of direct or indirect trauma, infection, or previous injury. DIFFERENTIAL DIAGNOSIS: Aneurysm, bone cyst, chondroma, giant cell tumor, osteochondroma, osteosarcoma, osteoid osteoma. TREATMENT: When her symptoms persisted beyond 6 months despite conservative care, she underwent radiographs, magnetic resonance imaging, and bone scan, which revealed a lesion in the right femur. At surgery, the lesion was diagnosed as an aneurysmal bone cyst, and it was excised by an incisional x-ray-guided biopsy followed by curettage and bone grafting. UNIQUENESS: The aneurysmal bone cyst presented as a typical thigh strain or deep contusion during the athlete's training and conditioning season. After all forms of conservative management proved ineffective, the athlete was referred to her physician. A detailed history and physical examination demonstrated no underlying musculoskeletal pathology coinciding with the athlete's symptoms. CONCLUSIONS: Increased clinical awareness is necessary when conservative management fails to resolve an athletic injury in an appropriate length of time. Proper diagnostic tools are essential in determining the pathology of the injury and whether surgical intervention is needed.

Journal Article↗

Aminoisoquinolines: design and synthesis of an orally active benzamidine isostere for the inhibition of factor XA.

The design, synthesis and SAR of sulfonamidopyrrolidinone fXa inhibitors incorporating a new benzamidine isostere, namely aminoisoquinolines, is described. These inhibitors have higher Caco-2 cell permeability than comparable benzamidines and attain higher levels of exposure upon oral dosing. The most potent member 14b (fXa Ki=6 nM) is selective against other serine proteases of interest (>600 fold).

Administration, Oral↗

Evaluation of the dizzy patient: experience from a multidisciplinary neurotology clinic.

In 1993 a multidisciplinary neurotology clinic was established at the Toronto Hospital, University of Toronto, where patients with symptoms of dizziness were assessed by both otolaryngologists and neurologists. The results from the first 400 patients seen in consultation are described. The disease pathologies identified in this patient population with dizziness showed some significant differences from other published series, which we believe reflects the specialized tertiary nature of referrals to this clinic. A model for the collaborative investigation of the dizzy patient is provided consistent with the current trend towards multidisciplinary approaches in medicine.

Adolescent↗

A process model of shiftwork and health.

The authors developed and tested a process model of adaptation to shiftwork, which hypothesizes that various individual and situational variables influence the development of sleep and social and domestic disturbances. Both types of disturbances trigger various types of coping behavior, leading to several proximal outcomes. The end result is the development of chronic health problems in the form of digestive and cardiovascular symptoms. The model was tested with survey data collected from 2 samples of nurses (N = 1,532) in the United Kingdom and was cross-validated against a 3rd sample of industrial workers (N = 370). Results indicate support for the model across the 3 samples, although some sample-specific and subgroup effects were found. Results have direct implications for the development of shiftwork theory and interventions.

Adaptation, Psychological↗

Phase II trial of docetaxel, cisplatin, fluorouracil, and leucovorin as induction for squamous cell carcinoma of the head and neck.

PURPOSE: To evaluate the toxicity and efficacy of a 4-day regimen of docetaxel, cisplatin, fluorouracil, and leucovorin (TPFL4) in patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Thirty previously untreated patients with stage III or IV SCCHN and Eastern Cooperative Oncology Group functional status of 2 or less were treated with TPFL4. Postchemotherapy support included prophylactic growth factors and antibiotics. Patients who achieved a complete response (CR) or partial response (PR) to three cycles of TPFL4 received definitive twice-daily radiation therapy. The primary end points were toxicity and response to TPFL4. RESULTS: Eighty-five cycles were administered to 30 patients. The major acute toxicities to TPFL4 were mucositis and nausea. One patient died of neutropenic sepsis during therapy. Additional major toxicities were neutropenia, anorexia, nephropathy, neuropathy, and diarrhea. Fourteen percent of all cycles were associated with hospitalization for toxicity. The overall clinical response rate to TPFL4 was 93%, with 63% CRs and 30% PRs. Primary tumor site clinical and pathologic response rates were 93% and 68%, respectively. CONCLUSION: TPFL4 has an acceptable toxicity profile in good-performance-status patients. Modification of the 5-day TPFL regimen (TPFL5: shorter chemotherapy infusion time, earlier intervention with growth factors and antibiotics) led to fewer episodes of febrile neutropenia and hospitalization. Response rates to TPFL justify further evaluation of combinations of these agents in the context of formal clinical trials.

Adult↗

Three births after preimplantation genetic diagnosis for cystic fibrosis with sequential first and second polar body analysis.

OBJECTIVE: The purpose of this study was to determine the accuracy and feasibility of sequential polar body removal and analysis for preimplantation genetic diagnosis of mendelian disorders. STUDY DESIGN: Three couples with risk factors for cystic fibrosis had preimplantation genetic diagnosis with the use of sequential polar body analysis. After stimulation, oocytes were harvested and the first polar bodies were removed and analyzed on the day of aspiration. The following day, after fertilization, the second polar bodies were aspirated. Only embryos known to have inherited the normal maternal allele were transferred. RESULTS: All three couples had successful pregnancies resulting in the births of unaffected infants. CONCLUSIONS: Preimplantation diagnosis with the use of sequential polar body removal is feasible and can prevent the establishment of genetically abnormal pregnancies for couples at risk.

Alleles↗