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Biomedical subjects

G Phillips

Publications and source records attributed to G Phillips.

At least 37 records · Page 2Linked to original sources

Influence of ingesting a carbohydrate-electrolyte solution on endurance capacity during intermittent, high-intensity shuttle running.

The aim of this study was to examine the effects of ingesting a carbohydrate-electrolyte solution on endurance capacity during a prolonged intermittent, high-intensity shuttle running test (PIHSRT). Nine trained male games players performed two exercise trials, 7 days apart. On each occasion, they completed 75 min exercise, comprising of five 15-min periods of intermittent running, consisting of sprinting, interspersed with periods of jogging and walking (Part A), followed by intermittent running to fatigue (Part B). The subjects were randomly allocated either a 6.9% carbohydrate-electrolyte solution (CHO) or a non-carbohydrate placebo (CON) immediately prior to exercise (5 ml kg-1 body mass) and every 15 min thereafter (2 ml kg-1 body mass). Venous blood samples were obtained at rest, during and after each PIHSRT for the determination of glucose, lactate, plasma free fatty acid, glycerol, ammonia, and serum insulin and electrolyte concentrations. During Part B, the subjects were able to continue running longer when fed CHO (CHO = 8.9 +/- 1.5 min vs CON = 6.7 +/- 1.0 min; P < 0.05) (mean +/- S.E.M.). These results show that drinking a carbohydrate-electrolyte solution improves endurance running capacity during prolonged intermittent exercise.

Adult

An in vitro study of fusidic acid susceptibility amongst isolates from conjunctival swabs.

The aim of this study was to examine the in vitro activity of fusidic acid against bacterial isolates from conjunctival swabs. Conjunctival swabs from 213 patients with conjunctivitis were examined. One or more pathogens were grown from 73 patients. Forty per cent of isolates were resistant to fusidic acid on disc sensitivity testing. Reduced sensitivity was detected by minimum inhibitory concentration testing in many isolates of H. influenzae and an isolate of S. pneumoniae. In addition, the in vitro activity of fusidic acid was determined against upper respiratory tract isolates of H. influenzae, S. pneumoniae and M. catarrhalis; this showed that many isolates had a reduced sensitivity to fusidic acid. Topical fusidic acid may not be optimal empiric therapy of bacterial conjunctivitis.

Anti-Bacterial Agents

Techniques of partial hysterectomy: an overview.

With the advent of endometrial ablation and resection, and the laparoscopic techniques for hysterectomy, there has been renewed interest in subtotal or partial hysterectomy. A number of unsubstantiated claims have been made for these new techniques and these are critically reviewed. There appears to be no reason to advocate a change from total hysterectomy to partial hysterectomy on the basis of the currently available evidence.

Cervix Uteri

Accelerated healing of chronic sickle-cell leg ulcers treated with RGD peptide matrix. RGD Study Group.

Leg ulcers are a chronic manifestation of sickle-cell disease (SCD) and are often painful, disabling, and difficult to treat. RGD peptide matrix treatment is a novel therapy designed to provide a topical synthetic extracellular matrix that can act as a temporary substitute for the damaged natural matrix at the ulcer site. In this randomized, placebo-controlled, double-blind, prospective, multicenter investigation, SCD patients with full-thickness leg ulcers were treated with standard therapy plus RGD peptide matrix or saline placebo once weekly for up to 10 weeks. Healing in patients with chronic ulcers (2 months or greater in duration) was significantly accelerated (P = .0085) in RGD peptide matrix recipients compared with the placebo group. In these chronic ulcer cases, the average percent ulcer closure (decrease in ulcer surface area) in the RGD peptide matrix group (54.4% +/- 8.9%) exceeded that in the placebo group (19.0% +/- 24.3%) nearly threefold by study endpoint. Furthermore, RGD peptide matrix was equally effective in promoting healing of long persistent ulcers and ulcers of shorter duration. In contrast, standard therapy plus placebo was significantly less effective (P = .001) in promoting healing for ulcers of progressively greater duration. The results of this study provide preliminary evidence that RGD peptide matrix treatment may significantly accelerate healing of chronic sickle-cell leg ulcers.

Adolescent

Intensive conditioning regimen for bone marrow transplantation in children with high-risk haematological malignancies.

Between September 1987 and May 1991, 21 children aged 10 months to 15 years (median 9 years) underwent bone marrow transplantation (BMT) for advanced haematological malignancies using a conditioning regimen consisting of total body irradiation (TBI), etoposide 1.8 g/m2 by continuous infusion, and cyclophosphamide 2 g/m2 on 3 consecutive days. The patients included 14 with acute lymphoblastic leukaemia (ALL), 1 with chronic myeloid leukaemia (CML), 1 with juvenile CML, 4 with non-Hodgkin's lymphoma and 1 with acute nonlymphocytic leukaemia. Eleven had an allogeneic BMT from an HLA-matched sibling, and 1 from an unrelated donor. Nine patients received 4-hydroperoxycyclophosphamide purged autologous marrow. Median time to myeloid engraftment (ANC > 500/microliters) was 19 days in allogeneic BMT patients and 28 days in autologous BMT patients (P < .01). Mucositis was the major regimen-related toxicity (RRT). GI toxicity in the form of diarrhoea affected ten patients and five had veno-occlusive disease of the liver. Two patients had mild bladder toxicity and one died of renal toxicity. There was no CNS or cardiac toxicity. There was no significant difference in the incidence of toxicity according to the type of BMT (autologous or allogeneic), total dose, or sequence of TBI. With a median follow-up of 44 months, ten patients are alive (6/12 allogeneic BMT patients and 4/9 autologous BMT patients). Of the 11 deaths, four were related to toxicity (2 aspergillus, 1 haemorrhage following liver biopsy, and 1 from haemolytic-uraemic syndrome), and 4/12 allogeneic and 4/9 autologous BMT patients died from relapsed disease. This conditioning regimen is well tolerated in children, demonstrating mild and reversible RRT.

Adolescent

Persistence of microflora in biofilm within fluid pathways of contemporary haemodialysis monitors (Gambro AK-10).

Growth of bacteria within a biofilm, visible macroscopically as a yellow coating, was seen on the interior walls of semi-transparent plastic dialysis monitor fluid pipes. The level of bacterial growth along the water/dialysis fluid pathway, and the effect of in-line bacterial filters, on colony counts in reverse osmosis reject water and monitor effluent were examined. Little difference in colony counts was seen at either sampling point in monitors fitted with and without filters. Because of the increasing use of high-flux dialysis, and its potential for transmembrane transport of endotoxin and bacteria into patients, staff should be aware that dialysis fluid pathways may be colonized with viable bacteria, which are not readily killed by conventional heat and chemical cleaning processes.

Bacteria

Observation of pain behaviors during episodes of sickle cell disease pain.

OBJECTIVE: To assess the utility of a brief behavioral observation method to quantify pain. DESIGN: Correlational study. PATIENTS: 31 sickle cell disease (SCD) patients first seen in an outpatient clinic in painful crisis. OUTCOME MEASURES: Observed pain behaviors, physician rating of patient pain on a 0 to 10 scale, patient rating of pain on a 0 to 10 scale, and patient pain report from the McGill Pain Questionnaire. RESULTS: High interrater reliability for the brief behavioral observation was found, and observed pain behavior was found to correlate significantly with physician ratings of pain. CONCLUSIONS: This study is an important first step toward developing a systematic behavior-observation methodology for the analysis of SCD pain. The current methodology was found to be reliable and easily implemented in a busy, outpatient clinic.

Adult

The value of ultrasound-guided fine needle aspiration in the assessment of solid breast lumps.

To assess the value of routine ultrasound-guided fine needle aspiration (US-FNA) of solid mass lesions of the breast, all such patients presenting to the breast clinic over a 5 month period were offered US-FNA in addition to standard imaging. One thousand, three hundred and eight-six consecutive patients were assessed and 77 solid mass lesions identified. US-FNA was performed in 49 of these. Sixteen demonstrated cytological features of malignancy that was confirmed at surgery. US-FNA did not diagnose malignancy in cases with typical benign imaging features. It did alter diagnosis from an equivocal suspicious mass lesion to a definite diagnosis of malignancy in four cases (25%). It also altered diagnosis from an equivocal, probably benign, diagnosis to a more confident diagnosis of benign disease in 18 (58%) of benign cases. US-FNA confirmed the diagnosis of malignancy in four cases where a suspicious mass could only be imaged by ultrasound. US-FNA is simple, rapid and, unlike large Tru-Cut biopsies, is not associated with complications. It causes only minimal discomfort to both patient and operator. We recommend that US-FNA becomes a routine component of the imaging workup of breast mass lesions both to exclude malignancy in equivocal cases and to confirm malignancy when this is expected.

Adolescent

Thalidomide in the management of chronic graft-versus-host disease in children following bone marrow transplantation.

Chronic graft-versus-host disease (GVHD) is the major complication in patients surviving > 100 days post-allogeneic bone marrow transplantation and occurs in 30% of pediatric patients. It is most prevalent 1-2 years post-transplant. Treatment involves corticosteroids and other immunosuppressive therapy which may affect growth and increase the likelihood of infectious complications. We report five children with severe corticosteroid-dependent chronic GVHD treated with thalidomide 12-25 mg/kg/day. Response to therapy was based on resolution of symptoms of chronic GVHD and withdrawal of other immunosuppressive therapy. All the children showed clinical response to thalidomide with cessation or diminution in other immunosuppressive medication. Side-effects were minimal and no patient developed peripheral neuropathy. All patients are alive 48-65 months post-transplantation. Thalidomide is a safe and effective drug for the treatment of chronic GVHD in children and may avoid the use of long-term corticosteroid therapy.

Adolescent

Synthesis and biological activity of cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro- 3-propyl-1H-benz[e]indole-9-carboxamide: a potent and selective 5-HT1A receptor agonist with good oral availability.

The synthesis and biological activity of cis-(3aR)-(-)-2,3,3a,4,5,9b- hexahydro-3-propyl-1H-benz[e]indole-9-carboxamide ((-)-3a), U93385, is described. The cis racemate and its enantiomer as well as the corresponding trans enantiomers were also synthesized and evaluated. The synthesis of these analogs was achieved via either a four-step conversion of the 9-hydroxy precursor into 9-carboxamide or an alternative synthesis using the (R)-alpha-methylbenzyl group as the chiral auxiliary. The cis racemate (+/-)-3a, was found to be a selective and potent 5-HT1A receptor agonist with the activity residing in the cis-(3aR)-enantiomer, (-)-3a. The cis-(3aS)-enantiomer (+)-3a and trans-(3aR)-enantiomer (-)-3b displayed partial 5-HT1A agonist activity whereas the other trans-(3aS)-enantiomer (+)-3b showed no activity. The enantiomer (-)-3a was found to be selective in both in vitro and in vivo biochemical/behavioral assays. This compound potently reduced rectal temperature in mice, decreased the firing rate of rat midbrain serotonergic neurons, and suppressed rat brain 5-HT synthesis. This compound also reduced sympathetic nerve discharge and blood pressure in the anesthetized cat and showed activity in the forced swim assay in mice. It exhibited good oral activity in behavioral and biochemical assays and, in fact, had a 46% oral availability in the rat when comparing blood levels of parent drug after iv and po administration. This compound has demonstrated a potential for anxiolytic and antidepressant activity and is currently undergoing clinical evaluation.

Administration, Oral

Centrally acting serotonergic and dopaminergic agents. 2. Synthesis and structure-activity relationships of 2,3,3a,4,9,9a-hexahydro-1H-benz[f]indole derivatives.

The conformationally restricted linear tricyclic analogs of 5- and 8-hydroxy-2-(di-n-propylamino)-tetralins were investigated for their serotonergic and dopaminergic properties. These cis and trans analogs of 2,3,3a,4,9,9a-hexahydro-1H-benz[f]indole (3), where a five-membered ring is fused between the nitrogen and C-3 carbon of 2-aminotetralin, were synthesized from 5-methoxy- and 8-methoxytetralones. The enantiomers of trans-5-methoxy-N-n-propyl and -N-allyl analogs were obtained via fractional recrystallization of their di-p-toluoyl-L (or D) tartaric acid salts. All analogs were evaluated in the in vitro 5-HT1A and D2 binding assays and selected analogs were investigated further in biochemical and behavioral tests. In the 5-substituted series (R1 in 3), the trans isomers were found to possess higher levels of pharmacological activity then the corresponding cis isomers. The trans-5-methoxy analogs showed selective 5-HT1A receptor activity in vitro but displayed mixed 5-HT1A and D2 agonist properties in vivo. The corresponding trans-5-hydroxy analogs were found to be potent D2 agonists with full intrinsic activity. An examination of nitrogen substitution (R2 in 3) revealed that analogs with either an allyl or an n-propyl group displayed equipotent activities. Substitution with a cyclopropylmethyl or benzyl group resulted in reduced activity. Among the resolved analogs tested, the activity was found to reside exclusively in the (3aS)-(-)-enantiomers. In the 8-substituted series (R1 in 3), only 8-methoxy-N-allyl analogs were synthesized and evaluated. In this case, both cis and trans isomers showed equally weak in vitro 5-HT1A receptor agonist activity devoid of dopaminergic effects. The presence of an additional methyl group at the C-2 position (R3 in 3) of the cis-(+/-)-8-methoxy-N-n-propyl analog resulted in enhancement of in vitro 5-HT1A receptor binding affinity, with the (2 beta,3a alpha,9a alpha)-(+/-)-isomer displaying potency 35 times greater than the (2 alpha,3a alpha,9a alpha)-(+/-)-isomer.

Animals