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Biomedical subjects

G S Gordon

Publications and source records attributed to G S Gordon.

At least 19 recordsLinked to original sources
PubMed2006

A systematic review of the evidence for hip surveillance in children with cerebral palsy.

We reviewed the evidence for hip surveillance in children with cerebral palsy from the published literature. Publications were identified using the Cochrane controlled trials register, the MEDLINE, EMBASE and CINAHL databases and by hand searching key journals and their references. Studies were included if they reported the frequency, associated risk factors or surveillance measures undertaken to identify subluxation or dislocation of the hip in children with cerebral palsy. Assessment of the quality of the methodology was undertaken independently by two researchers. Four studies described the natural history, incidence and risk factors for dislocation of the hip. Two reported their surveillance results. Approximately 60% of children who were not walking by five years of age were likely to develop subluxation of the hip, with the greatest risk in those with severe neurological involvement. The introduction of surveillance programmes allowed earlier identification of subluxation and reduced the need for surgery on dislocated hips. Surveillance can identify children most at risk of subluxation using radiological methods which are widely available.

Adolescent↗
PubMed2001

A phase II trial of 9-aminocaptothecin (9-AC) as a 120-h infusion in patients with non-small cell lung cancer.

In a previous phase II trial of the synthetic topoisomerase I inhibitor, 9-aminocamptothecin (9-AC), given as a 72-h infusion, we identified modest single agent activity of 9% in patients with previously untreated advanced non-small cell lung cancer (NSCLC). Preclinical studies suggested that a more prolonged continuous infusion of the drug might lead to greater antitumor activity. A phase I study recommended a phase II dose of 25 microg/m2/hr for 120 h (3000 microg/m2 over 5 days), administered for 2 consecutive weeks of a 3-week cycle. We utilized this schedule and enrolled 13 chemotherapy-naïve patients with Stage IIIB and IV NSCLC in this trial: median age 67 (range 57-74); 46% male; 92% stage IV; and median performance status 1. Twelve patients are available for response and toxicity evaluation after 2 cycles of therapy. One patient achieved a partial response. Four patients had stable disease while seven patients had progressive disease. Patients with stable or progressive disease after two cycles received no additional 9-AC, and were offered conventional chemotherapy. The median survival time was 10.2 months and the one-year survival rate 28% (95% confidence interval, 5-58%). Significant toxicities included myelosuppression, fatigue, and anorexia. One patient had grade 4 neutropenia following the first week of cycle 2, and did not receive additional therapy. There were no neutropenia-related infections. These data suggest that this prolonged schedule is unlikely to increase 9-AC's very modest activity in NSCLC above that seen with the simpler 72-h administration schedule. Further evaluation of 9-AC in NSCLC is not recommended.

Aged↗
PubMed2000

DNA segregation in bacteria.

Segregation of DNA in bacterial cells is an efficient process that assures that every daughter cell receives a copy of genomic and plasmid DNA. In this review, we focus primarily on observations in recent years, including the visualization of DNA and proteins at the subcellular level, that have begun to define the events that separate DNA molecules. Unlike the process of chromosome segregation in higher cells, segregation of the bacterial chromosome is a continuous process in which chromosomes are separated as they are replicated. Essential to separation is the initial movement of sister origins to opposite ends of the cell. Subsequent replication and controlled condensation of DNA are the driving forces that move sister chromosomes toward their respective origins, which establishes the polarity required for segregation. Final steps in the resolution and separation of sister chromosomes occur at the replication terminus, which is localized at the cell center. In contrast to the chromosome, segregation of low-copy plasmids, such as Escherichia coli F, P1, and R1, is by mechanisms that resemble those used in eukaryotic cells. Each plasmid has a centromere-like site to which plasmid-specified partition proteins bind to promote segregation. Replication of plasmid DNA, which occurs at the cell center, is followed by rapid partition protein-mediated separation of sister plasmids, which become localized at distinct sites on either side of the division plane. The fundamental similarity between chromosome and plasmid segregation-placement of DNA to specific cell sites-implies an underlying cellular architecture to which both DNA and proteins refer.

Cell Compartmentation↗
PubMed2000

A phase I study of STEALTH cisplatin (SPI-77) and vinorelbine in patients with advanced non small-cell lung cancer.

STEALTH cisplatin (SPI-77) is a liposomal formulation of cisplatin that has activity in animal models of non small-cell lung cancer (NSCLC). Vinorelbine has documented clinical activity in NSCLC. The purpose of this study was to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of SPI-77 when administered in combination with a fixed dose of vinorelbine to patients with stage IIIB or IV NSCLC refractory to or recurrent following previous chemotherapy. SPI-77 was given on day 1 in combination with vinorelbine at a fixed dose of 25 mg/m2 on days 1 and 8 of a 3-week treatment cycle. Dose escalation of SPI-77 progressed as follows: 20, 40, 80, 100, 120, and 140 mg/m2. Twenty patients were entered (11 men and nine women; median age, 63 years). Sixty-four complete cycles of therapy were administered, and 19 of 20 patients completed at least 1 cycle of combination chemotherapy. Neutropenia was dose limiting at a SPI-77 dose of 140 mg/m2. Neuropathy and nephrotoxicity were minimal and not dose related. A partial response was observed in three of 17 patients eligible for a response evaluation and response duration ranged from 6 weeks to 5 months. In conclusion, treatment with combination SPI-77 and vinorelbine was well tolerated, and our recommended phase II dose is 120 mg/m2 of SPI-77 in combination with vinorelbine at 25 mg/m2. Activity was observed in this patient population, and additional phase II testing of this regimen in a less extensively pretreated cohort of patients with NSCLC is indicated.

Journal Article↗
PubMed1999

Chemoradiation for locally advanced, unresectable NSCLC. New standard of care, emerging strategies.

The optimal therapy for locally advanced, unresectable, stage III non-small-cell lung cancer (NSCLC) continues to evolve. The critical determinants of overall survival include local tumor control and the eradication of subclinical micrometastatic disease. Historically, standard radiation therapy resulted in a median survival of 7 to 10 months. In a randomized trial, the Cancer and Leukemia Group B (CALGB) established the superiority of induction cisplatin (Platinol) and vinblastine chemotherapy followed by radiation therapy. Additional studies revealed that induction chemotherapy improved survival rates by decreasing metastatic disease progression. Three independent meta-analyses confirmed the survival benefit afforded by cisplatin-based induction chemotherapy followed by radiotherapy, and helped to establish this as the new standard of care. Other investigators have demonstrated improvements in local tumor control and survival with either concurrent chemoradiotherapy or hyperfractionated radiotherapy. Most recently, attention has focused on radiation dose intensity and the utilization of newer, highly active chemotherapeutic agents with concurrent or sequential radiation therapy. These newer drugs, including paclitaxel (Taxol), docetaxel (Taxotere), gemcitabine (Gemzar), vinorelbine (Navelbine), and irinotecan (Camptosar), enhance radiation cytotoxicity and, when administered in systemically active dosages, may also control micrometastatic disease. Phase I and II studies of novel chemoradiation regimens continue to demonstrate encouraging results, and several large randomized clinical trials are currently enrolling patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Chromosome and low copy plasmid segregation in E. coli: visual evidence for distinct mechanisms.

We have investigated DNA segregation in E. coli by inserting multiple lac operator sequences into the chromosome near the origin of replication (oriC), in the hisC gene, a terminus marker, and into plasmids P1 and F. Expression of a GFP-LacI fusion protein allowed visualization of lac operator localization. oriC was shown to be specifically localized at or near the cell poles, and when duplicated, one copy moved to the site of new pole formation near the site of cell division. In contrast, P1 and F localized to the cell center and on duplication appeared to move rapidly to the quarter positions in the cell. Our analysis suggests that different active processes are involved in movement and localization of the chromosome and of the two plasmids during segregation.

Cell Cycle↗
PubMed1997

A survey of lamotrigine and vigabatrin treatment in children with severe epilepsy.

A retrospective survey was carried out of add-on treatment with lamotrigine (LTG) and vigabatrin (GVG) in 109 children with severe epilepsy, treated between 1987 and 1994, identified from a total population of 300 patients seen annually, in a tertiary referral outpatient clinic in Cardiff, Wales. Of 79 patient treatments with LTG and 86 with GVG, 42 patients were treated with add-on LTG, 52 with add-on GVG and 20 with both drugs simultaneously. A Kaplan-Meier curve, applied to each of the two index drugs, indicated that 71 and 62% of patients would be expected to continue taking LTG or GVG, respectively after 40 months. Improved seizure control (> or = 50%) at the time of audit was seen in 65% of LTG and 58% of GVG patient treatments for all epilepsy syndromes, but there was a higher proportion of patients with generalized epilepsy improved by LTG (28/41, 68%) than that improved by GVG (8/20, 40%), and only those with generalized epilepsy treated with LTG became seizure free (8/38, 21%). Similar proportions of patients discontinued LTG (16%) and GVG (15%) due to an adverse experience, but a higher proportion discontinued GVG (18%) compared with LTG (6%) because of lack of efficacy. This study supports the relative clinical effectiveness of LTG and GVG in the real world, where children with severe epilepsy are treated in clinical practice and serves to generate hypotheses to enable design of prospectively controlled trials, which should enable more rational use of these two drugs in the paediatric population with epilepsy.

Adolescent↗
PubMed1995

Thinness at birth and glucose tolerance in seven-year-old children.

Adults who had low birthweight and were thin at birth have an increased risk of Type 2 diabetes and impaired glucose tolerance. To discover whether thinness at birth is associated with reduced glucose tolerance in children, 250 7-year-old children underwent an abbreviated oral glucose tolerance test. Children who were thin at birth, as measured by a low ponderal index (birthweight length-3) had higher plasma glucose concentrations. Plasma glucose concentration 30 min after a glucose load rose by 0.07 mmol l-1 (95% confidence interval 0.00 to 0.14; p = 0.04) for every unit (kg m-3) fall in ponderal index. Children in the lowest quarter of the distribution of ponderal index (23 kg m-3 or less) had a mean 30 min plasma glucose concentration of 8.49 mmol l-1 compared to a mean of 7.97 mmol l-1 for those in the highest quarter (> 27.5 kg m-3). These associations were independent of duration of gestation, gender, social class or the child's current weight. This is consistent with the hypothesis that Type 2 diabetes originates in utero.

Adult↗
PubMed1995

Intracranial tumours during the first two years of life: presenting features.

Between 1979 and 1994, 21 children (nine females, 12 males) with intracranial tumours diagnosed before the age of 2 years (range 2-23 months) were treated at the University Hospital of Wales. The commonest presenting symptoms were vomiting (n = 9) and unsteadiness (n = 8); the commonest presenting sign was enlarged occipitofrontal circumference (> 97th centile in 16 and > 90th centile in a further two). In five cases with signs of raised intracranial pressure, meningitis was the clinical diagnosis, and a lumbar puncture was performed. For cases with long delays in diagnosis, multiple other disorders had been considered and the significance of head enlargement had not been recognised. In very early childhood, intracranial tumours are uncommon and can mimic other disorders, especially meningitis. Early neuroimaging is advised when a child presents with recent onset of neurological symptoms and a disproportionately large head.

Astrocytoma↗
PubMed1993

Hospital drug formularies and use of hospital services.

Many hospitals have introduced formularies to reduce hospital pharmacy expense, among other reasons. This study provides empirical evidence of the influence of hospital formulary restrictions on pharmacy charges, all other hospital charges, and on length of stay, using a survey of hospital drug policies and hospital discharge data from Washington State in 1989. Limiting the number of drugs in particular therapeutic categories reduced total charges incurred for gastrointestinal disease and asthma patients, increased total charges for cardiovascular disease patients, and had no effect on charges for infectious diseases patients. Restricting availability of drugs reduced pharmacy charges, but these savings tended to be offset by increases in other charges. Combining the categories, we found that restricting availability of drugs did not affect charges. We conclude that across-the-board restrictions do not result in cost savings, although savings may be realized for particular drug categories.

Aged↗
PubMed1991

Charges for comprehensive obstetric care at teaching and nonteaching hospitals. A comparison.

We compared total charges for obstetric care at a major teaching hospital and faculty group practice with those at 3 nonteaching centers in western Washington. The patients were all enrollees of an employee-based health maintenance organization. Charges were used as a proxy for costs and included all outpatient, inpatient, and physician charges. In the teaching system, patients were cared for by faculty and house staff; in the nonteaching settings, they received care from private physicians. No significant differences in total charges were found between the teaching and the nonteaching settings for all deliveries ($4,652 [N = 90] versus $4,530 [N = 335], P greater than .5). In the teaching setting, vaginal deliveries were slightly more expensive ($4,178 [n = 75] versus $3,768 [n = 250], P = .15), as were cesarean deliveries ($7,024 [n = 15] versus $6,771 [n = 85], P greater than .5). The rate of cesarean deliveries was lower in the teaching setting (17% versus 25%, P = .10), partially accounting for the similarity in total charges. The length of stay was similar in the teaching hospital (3.29 versus 3.14 days, P greater than .5). We conclude that the academic medical center as a total system of care can provide obstetric care as cost-effectively as nonteaching systems under the constraints of prepaid care.

Cesarean Section↗
PubMed1989

Intranasal administration of deferoxamine to iron overloaded patients.

We examined the effect of intranasal administration of deferoxamine on iron excretion in seven patients with iron overload secondary to chronic transfusion therapy. Deferoxamine was administered in doses of 0.75 to 3.0 gm given over 12 hours in a variety of dosing schedules. There was a probable, though not significant, dose response relationship between the amount of iron excreted and the dose administered. The amount of iron excreted was 10%-15% of that obtained using the same dosage of deferoxamine given by the subcutaneous route over the same time period. Hourly administration was more effective than less frequent administration. Addition of taurodeoxycholate to deferoxamine did not increase its absorption as measured by the levels of iron excretion. Side effects were few and consisted mainly of mild nasal irritation and a bad taste in the mouth. Nasal administration of deferoxamine may be a useful adjunct to iron chelation in patients receiving chronic transfusion therapy, particularly in those who are noncompliant with parenteral means of administration.

Administration, Intranasal↗
PubMed1988

Treatment of theophylline poisoning with haemoperfusion.

Two patients who had taken overdoses of theophylline were treated initially with oral activated charcoal. Owing to continued toxic plasma levels of theophylline, haemoperfusion was used to reduce rapidly theophylline levels. Both patients recovered rapidly.

Adult↗