PubMed Health⌕ Search

Biomedical subjects

A McInnes

Publications and source records attributed to A McInnes.

At least 19 recordsLinked to original sources
PubMed2002

A phase I and pharmacokinetic study of capecitabine in combination with epirubicin and cisplatin in patients with inoperable oesophago-gastric adenocarcinoma.

BACKGROUND: The purpose of this study was to evaluate the dose-limiting toxicity (DLT) and maximum tolerated dose of capecitabine when used in combination with epirubicin and cisplatin (ECC) in patients with oesophageal or gastric adenocarcinoma. Response rate, progression-free survival (PFS) and overall survival were also determined, and the effect of previous oesophago-gastric surgery or concurrent oesophago-gastric cancer on the absorption and metabolism of capecitabine was evaluated. PATIENTS AND METHODS: Patients with inoperable oesophago-gastric adenocarcinoma received up to six cycles of epirubicin (50 mg/m(2) i.v., 3-weekly), cisplatin (60 mg/m(2) i.v., 3-weekly) and capecitabine, the latter administered orally in an intermittent schedule (14 days treatment; 7-day rest period) at 3-weekly intervals. Patients were recruited into one of four escalating dose cohorts (500, 825, 1000 and 1250 mg/m(2) bd). Dose escalation occurred after six patients had completed at least one cycle of chemotherapy at the previous dose level, with DLT assessed on the toxicity of the first cycle only. Blood sampling for pharmacokinetic analyses was performed over the first 10 h of day 1 of cycle 1. RESULTS: Thirty-two patients, median age 63 years (range 32-76 years), ECOG performance status < or =2 with locally advanced (10) or metastatic (22) disease were recruited and were evaluable for toxicity. Two of five patients experienced DLT at 1250 mg/m(2) bd with grade II stomatitis (one patient) and grade III diarrhoea with febrile neutropenia (one patient). Cumulative toxicity for all cycles (n = 140) (worst grade per patient) includes grade IV oesophagitis (one patient), grade III diarrhoea (five), grade IV neutropenia with infection (seven), grade II stomatitis (four) and grade IV thrombocytopenia (one). Of 29 patients with evaluable disease, there was one complete response and six partial responses [24% response rate [95% confidence interval (CI) 10% to 44%]], a median PFS of 22 weeks (95% CI 17-27 weeks) and median overall survival of 34 weeks (95% CI 19-49 weeks). Capecitabine was rapidly absorbed after oral administration, with a t(max) of 1-2 h for capecitabine, DFCR (5'-deoxy-5-fluorocytidine) and DFUR (5'-deoxy-5-fluorouridine). The C(max) and AUC(0-)( infinity ) for capecitabine, DFCR and DFUR were similar to those observed in previous monotherapy studies of capecitabine taken after food. CONCLUSION: A dose of 1000 mg/m(2) bd of capecitabine is recommended for use on an intermittent schedule in combination with these doses and schedule of epirubicin and cisplatin. This regimen is tolerable and active in oesophago-gastric adenocarcinoma. A randomised phase III comparison with ECF is justified.

Adenocarcinoma↗
PubMed2001

Striatal cannabinoid CB1 receptor mRNA expression is decreased in the reserpine-treated rat model of Parkinson's disease.

High levels of both endocannabinoids and endocannabinoid receptors are present in the basal ganglia. Attention has recently focused on the role of endocannabinoids in the control of movement and in movement disorders of basal ganglia origin such as Parkinson's disease. We investigated CB1 cannabinoid receptor mRNA expression in the reserpine-treated rat model of Parkinson's disease using in situ hybridization. Reserpine treatment caused a topographically organized reduction in CB1 receptor mRNA expression in the striatum (ranging from 11.6% medially to 53.6% laterally and dorsally). No change in CB1 receptor mRNA expression was observed in the cerebral cortex or septum. This reduction in CB1 receptor mRNA expression may be secondary to increased endocannabinoid stimulation of the receptor as increased basal ganglia endocannabinoid levels have been shown to occur in this model of Parkinson's disease. The data support the idea that cannabinoid receptor antagonists may provide a useful treatment for the symptoms of Parkinson's disease.

Animals↗
PubMed2001

A phase II study of epirubicin, cisplatin and raltitrexed combination chemotherapy (ECT) in patients with advanced oesophageal and gastric adenocarcinoma.

BACKGROUND: The aim of this study was to evaluate the efficacy of the combination of epirubicin, cisplatin and ralitrexed (Tomudex). ECT, in patients with advanced oesophageal or gastric adenocarcinoma. Efficacy was assessed primarily as response rate and secondarily in terms of toxicity, time to progression and survival. PATIENTS AND METHODS: Twenty-one patients with histologically and/or cytologically proven unresectable (7) or metastatic (14) gastro-oesophageal adenocarcinoma, who had bi-dimensionally measurable disease, with ECOG performance status < or = 2. with adequate haematological, hepatic and renal function received first-line chemotherapy with epirubicin (50 mg/m2). cisplatin (60 mg/m2) and Tomudex (2.5 mg/m2), ECT, at three-weekly intervals. Treatment consisted of three cycles of chemotherapy, with a further three cycles if there was disease response or stabilisation. RESULTS: ECT is an active regimen in the treatment of advanced gastro-oesophageal adenocarcinoma with an overall intention-to-treat response rate of 29% (95% confidence intervals (CI): 11%-52%). In addition, 4 (19%) patients had stable disease. Median time to progression was 19 weeks (95% CI: 7-31 weeks). Median overall survival was 18 weeks (95% CI: 11-24 weeks). Seventeen patients failed to complete the six cycles of treatment due to disease progression (5). toxicity (3), non-toxic death (1 pulmonary embolism, 1 cardiac), severe allergy to epirubicin (1), patient decision (1) and five patients after the study was discontinued early due to toxicity. There were three toxic deaths: two due to sepsis complicating neutropaenia and one due to cardiorespiratory failure following drug induced enteritis. Nine patients experienced grade 3 or 4 neutropaenia, two patients experienced grade 3 or 4 nausea and vomiting and one patient had grade 4 diarrhoea. CONCLUSIONS: The combination of epirubicin, cisplatin and tomudex is active against advanced gastro-oesophageal adenocarcinoma but the toxicity suggests that further evaluation in a randomised comparison to ECF is not appropriate.

Adenocarcinoma↗
PubMed1999

Limited joint mobility in the hands and feet of adolescents with Type 1 diabetes mellitus.

AIMS: Limited joint mobility (LJM) in the foot has not been assessed in adolescents with Type 1 diabetes mellitus (DM) but is associated with neuropathic ulceration in adults. This study was designed to determine the presence of LJM in adolescents with Type 1 DM and its association with microvascular disease. METHODS: The hands, feet and hips were examined in 302 diabetic adolescents and 51 nondiabetic controls (aged 11.5-20 years). LJM was defined as less than the fifth percent reference for controls. RESULTS: Reduced motion was found in 35% of diabetic adolescents at the subtalar (ST) joint, 18% at the first metatarsophalangeal (MTP) joint, 26% at the fifth metacarpophalangeal (MCP) joint and 13% had limited passive extension of the interphalangeal (IP) joints of the hands. Limited passive IP joint extension of the hands was not present in the controls. Limited active IP joint extension, a positive 'prayer sign', occurred in 35% of diabetic adolescents and 14% of controls. Diabetic adolescents showing LJM in any of these areas, except the prayer sign, were more likely to have retinopathy (odds ratio 2.53, CI: 1.53-4.18). Those with LJM in the foot were more likely to have albumin excretion rates >7.5 microg/min (OR 2.06, CI: 1.16-3.68). CONCLUSION: LJM in the feet of adolescents with Type 1 DM is associated with microvascular disease and is a useful routine clinical measure.

Adolescent↗
PubMed1998

British Diabetic Association guidelines on genetic and immune screening for type 1 diabetes mellitus.

The following article is a report from the Chairman of the Professional Advisory Committee of the British Diabetic Association. The committee, with the help of a number of experts currently working in the field, produced a set of guidelines intended for use by health care professionals on the issues around genetic screening for Type 1 diabetes mellitus. The guidelines were approved by the Board of Management of the British Diabetic Association and we publish them here.

Autoantibodies↗
PubMed1998

The at-risk foot: the role of the primary care team in achieving St Vincent targets for reducing amputation.

Foot ulceration and ultimately amputation are major complications associated with diabetes mellitus, the occurrence of which can be substantially reduced by appropriate care. This article provides a brief overview of the problem and a simple scheme for use in primary care diabetes clinics to contribute to the reduction in this particular form of diabetes-related morbidity and mortality.

Amputation, Surgical↗
PubMed1998

Bolus/infusional 5-fluorouracil and folinic acid. A report on two prospective, consecutive phase II studies with 5-fluorouracil dose escalation.

We have used a relatively new trial methodology, the group sequential design, to prospectively evaluate two dose levels of bolus/infusional 5-fluorouracil (5-FU) and folinic acid in 192 consecutive-patients with advanced colorectal carcinoma. On day 1, all patients received 200 mg m(-2) of folinic acid infusion over 2 h. Cohort A (n = 102 patients) received 500 mg m(-2) 5-FU by i.v. 15-min infusion followed by an infusion of 500 mg m(-2) 5-FU over 22 h. Treatment was repeated on day 2 and further cycles given 2-weekly. After sequential analysis excluded a response rate of over 40%, cohort B (n = 90 patients) received an increased dose of 600 mg m(-2) 5-FU bolus and infusion. Patients had received no prior 5-FU therapy and the two cohorts had similar demographic features. In 179 evaluable patients, the overall response rate was 18% (95% CI 12-24%) with CR of 6% and PR of 12%, with no difference between the two cohorts. Overall median survival was 34 weeks (95% CI 30-39) with no significant difference between cohorts (median survival 32 and 37 weeks in cohort A and B respectively; P = 0.27). On multivariate analysis, poor performance status, elevated initial WBC and alkaline phosphatase and low serum albumin were associated with reduced survival (P < 0.05), and initial raised WBC showed an association with reduced likelihood of response (P = 0.002). Overall toxicity was low with CTC grade 3 mucositis, diarrhoea, nausea or vomiting in < or = 6% of patients and no treatment-related deaths. Significant (grade 3 or above) leucopenia was more common in cohort B than in cohort A (9% and 1% respectively); there were more dose reductions, and the median administered dose intensity was lower in cohort B than in cohort A (89% and 97% respectively; P = 0.006). In this group of relatively unselected patients, we have confirmed a relatively low objective response rate and median survival of 7.8 months with this regimen. There was no significant difference in outcome between the two dose levels but the higher dose of 5-FU was associated with more dose reductions and greater toxicity.

Adult↗
PubMed1989

Prevalence of spina bifida occulta in patients with functional disorders of the lower urinary tract and its relation to urodynamic and neurophysiological measurements.

OBJECTIVE: To determine the relation between neurophysiological abnormalities and the radiological detection of spina bifida occulta in patients with dysfunction of the lower urinary tract. DESIGN: Blind assessment and subsequent decoding of mixed batch of abdominal radiographs from patients with and without urological symptoms for evidence of spina bifida occulta and comparison of results with those of previous control series. SETTING: Review study among tertiary referrals to an incontinence clinic of a city hospital. PATIENTS: One hundred and thirty eight adults with proved urodynamic abnormalities in whom neurophysiological measurements were available. INTERVENTIONS: None. END POINT: Correlation of neurophysiological abnormalities in lower urinary tract dysfunction with presence and type of spina bifida occulta and level of opening of posterior sacral arcs. MEASUREMENTS AND MAIN RESULTS: On decoding radiographs those from patients without urological symptoms showed a similar prevalence of spina bifida occulta to that in the control series (631/2707 controls; 23%). By contrast, patients with urological symptoms had a significantly increased prevalence of spina bifida occulta at S1 and S2 and a higher level of opening of posterior sacral arcs. The increased prevalence of the bony defect was particularly striking in men with urgency and instability and in women with stress incontinence. No significant correlation was found between any particular neurophysiological abnormality and the presence of spina bifida. CONCLUSIONS: In patients with dysfunction of the lower urinary tract neurophysiological abnormalities may be associated with congenital dysraphic lesions in the lower lumbar spine and sacrum. There appears to be no direct causal relation between the radiological and neurophysiological abnormalities but the findings suggest a common aetiological factor.

Adult↗
PubMed1989

Neurological defects of the voiding reflex arcs in chronic urinary retention and their relation to spina bifida occulta.

A group of 37 patients (24 female and 13 male) with chronic urinary retention and without demonstrable mechanical obstruction had neurophysiological measurements of their lower urinary tracts to detect any neurological abnormality which might relate to the disorder. These consisted of measurements of the electrosensitivity of the dorsal nerve of the penis/clitoris and of the urethra, measurement of the sacral reflex latencies (SRL) from dorsal nerve to urethra and to anus and between urethra and anus and EMG studies of the urethral and anal sphincters. The results suggest that female patients in particular have significant neurogenic defects in the voiding reflex arcs which find their clinical expression in detrusor underactivity with urinary retention. Plain X-rays of the renal tracts (KUB films) were also studied for the presence of spina bifida occulta. The prevalence of this defect was significantly higher than in normal controls, suggesting that in some of these patients the nerve defect might be related to a tethered cord in association with spina bifida occulta.

Adult↗
PubMed1989

Electrophysiological studies in cervical spondylosis.

This paper reports a study of 57 patients with cervical spondylosis who underwent nerve conduction velocity (NCV), cervical somatosensory evoked potentials (CSEP), and concentric needle electromyography (EMG) as an aid to diagnosis. The results were analyzed in two groups. In Group I, there were 24 patients with radiological changes of cervical spondylosis in the absence of clear neurological signs. Nine patients in this group had abnormal electrophysiological recordings. In Group II, there were 33 patients with clinical signs, and 22 had abnormal electrophysiological recordings. The CSEP was abnormal in 12 of 14 patients who had evidence of nerve root filling defects on myelography. It is concluded that NCV, CSEP, and concentric needle electromyography are useful tests in distinguishing between root lesions and peripheral entrapment neuropathy. Although the methods available are not sufficiently precise to localize the level involved, they can be used as a screen prior to myelography or enhanced computed tomography (CT) scanning if surgery is proposed.

Adult↗