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A Parry

Publications and source records attributed to A Parry.

At least 19 recordsLinked to original sources
PubMed2003

Beta-Interferon treatment does not always slow the progression of axonal injury in multiple sclerosis.

Progression of disability in multiple sclerosis (MS) appears related to axonal damage, which is at least in part associated with white matter lesions. Beta-interferon (BIFN) substantially reduces new inflammatory activity in MS and a recent report suggested that it may reverse a component of axonal injury. To test the generalisability of this conclusion, particularly in a population with relatively active disease, we used magnetic resonance spectroscopy measures to test whether BIFN can reverse or arrest progression of axonal injury in patients with MS. Eleven patients with a history of active (median, 1.5 relapses/year) relapsing-remitting MS were treated with BIFN and responses to treatment were monitored with serial MRI and single voxel magnetic resonance spectroscopic measurements of relative concentrations of brain N-acetylaspartate (NAA), a measure of axonal integrity from a central, predominantly white matter brain region. BIFN treatment was associated with a significant reduction in relapse rate (p = 0.007) and white matter water T2 relaxation time (p = 0.047) over 12 months. Also consistent with a treatment effect, white matter T2-hyperintense lesion loads did not increase. However, the central white matter NAA/creatine ratio (NAA/Cr, which was reduced over 16 % in patients relative to healthy controls at the start of treatment), continued to decrease in the patients over the period of observation (mean 6.2 % decrease, p = 0.02). For individual patients the magnitude of the NAA/Cr decrease was correlated with the frequency of relapses over the two years prior to treatment (r = -0.76, p = 0.006). These data suggest that reduction of new inflammatory activity with BIFN does not invariably halt progression of axonal injury. Nonetheless, there appears to be a relationship between the rate of progression of axonal injury and relapse rate over the previous two years. The consequences of reduced inflammation on pathological progression relevant to disability therefore may be present, but substantially delayed. Alternatively, distinct mechanisms may contribute to the two processes.

Adult↗
PubMed2002

White matter and lesion T1 relaxation times increase in parallel and correlate with disability in multiple sclerosis.

Previous studies have established the clinical relevance of hypointense lesions ("black holes") on T1-weighted MRI as a surrogate marker for pathological change [36]. In contrast to measuring the volume of "black holes", the direct measurement of T1 values allows an objective assessment of the changes contributing to hypointensity both in the focal lesions and in the normal appearing white matter (NAWM). The aims of this study were first, to determine the relationship between T1 values in the NAWM and in discrete lesions, second, to test the relationship between white matter T1 changes and measures of disability and third, to determine whether pathology leading to T1 change occurred in thalamic grey matter of patients with multiple sclerosis. 24 patients with clinically definite multiple sclerosis (13 with relapsing-remitting multiple sclerosis and 11 with secondary progressive multiple sclerosis) and 11 controls participated. White matter T1 histograms and mean T1 values for the thalamus were generated from whole brain T1 relaxation time maps measured using a novel echo-planar imaging based MRI sequence at 3Tesla. Tissue segmentation based on T2- and T1-weighted images allowed independent study of changes in lesions and NAWM. White matter T1 histograms from the patient group showed a reduced peak height and a shift towards higher T1 values (p = 0.028) relative to controls. The mean thalamic T1 was greater for secondary progressive patients than for healthy controls (p = 0.03). Mean white matter T1 values correlated significantly with disability (r = 0.48, p = 0.02). The mean T1 value in the T1-hypointense lesions correlated strongly with the mean T1 value in the NAWM (r = 0.80, p < 0.001). No significant relationship was found between mean white matter T1 value and cerebral volume (r = -0.23, p = 0.31). The T1 measurements extend previous observations suggesting that changes in the NAWM occur in parallel with pathology in lesions of MS. T1 measurements of either the total or NAWM therefore may provide a potentially observer- and scanner- independent marker of pathology relevant to disability in MS.

Adult↗
PubMed2002

Is subjective shortening in human memory unique to time representations?

Three experiments compared forgetting of the duration of a bar-like visual stimulus with forgetting of its length. The main aim of the experiments was to investigate whether subjective shortening (a decrease in the subjective magnitude of a stimulus as its retention interval increased) was observable in length judgements as well as in time judgements, where subjective shortening has been often observed previously. On all trials of the three experiments, humans received two briefly presented coloured bars, separated by a delay ranging from 1 to 10 s, and the bars could differ in length, duration of presentation, or both. In Experiment 1 two groups of subjects made either length or duration judgements, and subjective shortening-type forgetting functions were observed only for duration. Experiments 2 and 3 used the same general procedure, but the stimuli judged could differ both in length and duration within a trial, and different subject groups (Experiment 2) or the same subjects in two conditions (Experiment 3) made either length or duration judgements of stimuli, which were on average physically identical. Subjective shortening was only found with duration, and never with length, supporting the view that subjective shortening may be unique to time judgements.

Adult↗
PubMed2001

A phase I study in paediatric patients to evaluate the safety and pharmacokinetics of SPI-77, a liposome encapsulated formulation of cisplatin.

Pre-clinical studies indicate that cisplatin encapsulated in STEALTH((R))liposomes (SPI-77) retains anti-tumour activity, but has a much reduced toxicity, compared to native cisplatin. A phase I study was conducted to determine the toxicity and pharmacokinetics of SPI-77 administered to children with advanced cancer not amenable to other treatment. Paediatric patients were treated at doses ranging from 40 to 320 mg m(-2)by intravenous infusion every 4 weeks. Blood samples taken during, and up to 3 weeks after, administration and plasma and ultrafiltrate were prepared immediately. Urine was collected, when possible, for 3 days after administration. SPI-77 administration was well tolerated with the major toxicity being an infusion reaction which responded to modification of the initial infusion rate of SPI-77. Limited haematological toxicity and no nephrotoxicity were observed. No responses to treatment were seen during the course of this phase I study. Measurement of total plasma platinum showed that cisplatin was retained in the circulation with a half life of up to 134 h, with maximum plasma concentrations approximately 100-fold higher than those reported following comparable doses of cisplatin. Comparison of plasma and whole blood indicated that cisplatin was retained in the liposomes and there was no free platinum measurable in the ultrafiltrate. Urine recovery was less than 4% of the dose administered over 72 h. Results from this phase I study indicate that high doses of liposomal cisplatin can safely be given to patients, but further studies are required to address the issue of reformulation of liposomally bound cisplatin.

Adolescent↗
PubMed2001

Age-dependent and hypoxia-related differences in myocardial protection during pediatric open heart surgery.

BACKGROUND: Current cardioplegic protection techniques used in pediatric cardiac surgery do not take into consideration age and cyanotic differences. The aim of the present work was to address this question by monitoring clinical outcome, myocardial metabolism, and reperfusion injury in pediatric patients protected by cold-crystalloid cardioplegia. METHODS AND RESULTS: Fifty-eight patients (31 children and 27 infants) with or without hypoxic stress (cyanosis) undergoing open heart surgery with cold-crystalloid cardioplegia were included in the study. Clinical outcome measures assessed included inotropic and ventilatory support, intensive care, and hospital stay. Ischemia-induced changes in metabolism (adenine nucleotides, purines, lactate, and amino acids) were determined in ventricular biopsies collected at the beginning and end of ischemic time (cross-clamp time). Reperfusion injury was assessed by measuring postoperative serial release of troponin I. Evidence was observed of ischemic stress during cardioplegic arrest in children and infants as shown by significant changes in cellular metabolites. Compared with infants, children had significantly less reperfusion injury and better clinical outcome, and these factors were related to duration of ischemic time. Cyanosis did not influence outcome in infants, but cyanotic children showed worse reperfusion injury and clinical outcome than acyanotic children. CONCLUSIONS: Extent of myocardial protection with cold-crystalloid cardioplegia in pediatric open heart surgery is dependent on age and degree of cyanosis.

Age Factors↗
PubMed2001

Influence of cellular factors and pharmacokinetics on the formation of platinum-DNA adducts in leukocytes of children receiving cisplatin therapy.

The formation of platinum (Pt)-DNA adducts is thought to be crucial to the antitumor activity of cisplatin, and relationships between adduct formation in peripheral blood leukocytes (PBLs) and response to cisplatin therapy have been reported. The current study directly tests, for the first time, whether pharmacokinetic or other factors predominantly determine the drug-target interaction of cisplatin in a pediatric patient population. Cisplatin pharmacokinetics and Pt-DNA adduct formation in PBLs were determined in 10 children in parallel with measurement of adduct levels after incubation of pretreatment blood samples with cisplatin in vitro. Total and unbound plasma Pt concentrations were determined by atomic absorption spectrophotometry and adduct measurements performed by competitive ELISA. Pt-DNA adduct levels determined after cisplatin treatment showed considerable interindividual variation (peak levels at 24 h ranged from 0.15 to 1.31 nmol/g DNA) and correlated strongly with adduct levels determined after incubation of pretreatment whole blood with cisplatin (r = 0.92; P = 0.0002). No significant correlation was observed between in vivo adduct formation and either unbound or total cisplatin plasma concentrations (r = 0.14 and 0.18, respectively). A correlation was also observed between the degree of myelosuppression, as determined by WBC nadirs measured over a 14-day period after cisplatin treatment, and the extent of adduct formation, with greater WBC toxicity observed in patients with higher levels of Pt-DNA adducts (P = 0.010). These preliminary results provide evidence that interpatient variation in formation of Pt-DNA adducts in PBLs of children is determined by host-specific factors other than cisplatin pharmacokinetics. These results imply that analysis of adducts in PBLs after incubation of pretreatment blood samples with cisplatin may be used to predict in vivo adduct levels, leukopenia, and, potentially, response to cisplatin therapy.

Adolescent↗
PubMed2000

Placental growth hormone (GH), GH-binding protein, and insulin-like growth factor axis in normal, growth-retarded, and diabetic pregnancies: correlations with fetal growth.

We previously described significant changes in GH-binding protein (GHBP) in pathological human pregnancy. There was a substantial elevation of GHBP in cases ofnoninsulin-dependent diabetes mellitus and a reduction in insulin-dependent diabetes mellitus. GHBP has the potential to modulate the proportion of free placental GH (PGH) and hence the impact on the maternal GH/insulin-like growth factor I (IGF-I) axis, fetal growth, and maternal glycemic status. The present study was undertaken to investigate the relationship among glycemia, GHBP, and PGH during pregnancy and to assess the impact of GHBP on the concentration of free PGH. We have extended the analysis of specimens to include measurements of GHBP, PGH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 and have related these to maternal characteristics, fetal growth, and glycemia. The simultaneous measurement of GHBP and PGH has for the first time allowed calculation of the free component of PGH and correlation of the free component to indexes of fetal growth and other endocrine markers. PGH, free PGH, IGF-I, and IGF-II were substantially decreased in IUGR at 28-30 weeks gestation (K28) and 36-38 weeks gestation (K36). The mean concentration (+/-SEM) of total PGH increased significantly from K28 to K36 (30.0 +/- 2.2 to 50.7 +/- 6.2 ng/mL; n = 40), as did the concentration of free PGH (23.4 +/- 2.3 to 43.7 +/- 6.0 ng/mL; n = 38). The mean percentage of free PGH was significantly less in IUGR than in normal subjects (67% vs. 79%; P < 0.01). Macrosomia was associated with an increase in these parameters that did not reach statistical significance. Multiple regression analysis revealed that PGH/IGF-I and IGFBP-3 account for 40% of the variance in birth weight. IGFBP-3 showed a significant correlation with IGF-I, IGF-II, and free and total PGH at K28 and K36. Noninsulin-dependent diabetes mellitus patients had a lower mean percentage of free PGH (65%; P < 0.01), and insulin-dependent diabetics had a higher mean percentage of free PGH (87%; P < 0.01) than normal subjects. Mean postprandial glucose at K28 correlated positively with PGH and free PGH (consistent with the hyperglycemic action of GH). GHBP correlated negatively with both postprandial and fasting glucose. Although GHBP correlated negatively with PGH (r = -0.52; P < .001), free PGH and total PGH correlated very closely (r = 0.98). The results are consistent with an inhibitory function for GHBP in vivo and support a critical role for placental GH and IGF-I in driving normal fetal growth.

Adult↗
PubMed1999

The contribution of donor management and modified cold blood lung perfusate to post-transplant lung function.

BACKGROUND: Donor organ availability remains the major limiting factor in the treatment of patients with end-stage lung disease by lung transplantation. Maximising the use of available organs is therefore crucial. Details available at the time of organ referral may give a misleading impression of their quality. Intensive donor management may improve the quality of the organs thereby improving the quality of the outcome. METHODS: We performed 56 heart-lung and 5 double lung transplants between November 1990 and September 1993; 49 had adequate documentation for analysis. All organs were preserved with modified cold blood solution with an ischemic time of 197 (117-297) minutes. Assessment of lung function post-implantation was performed using an acute lung injury score as this gives a more accurate indication of overall lung function. Donors were treated intensively by bronchoscopy, optimal fluid management and appropriate lung expansion. RESULTS: Careful management improved donor quality so that the alveolar-arterial oxygen gradient fell significantly from 185 (+/-20) mmHg at arrival to 80 (+/-11) mmHg (p < .0001) immediately prior to harvesting 190 minutes later. This improvement was maintained following harvesting using the modified cold blood preservation solution so that lung injury was assessed as "mild" according to the acute lung injury criteria post-transplantation. There was one instance of primary lung failure following transplantation which was neither related to the quality of the organ at harvesting nor to the method of lung preservation. CONCLUSIONS: Intensive donor management significantly improves the quality of donor organs, providing an improvement in immediate post-transplantation lung function. This improvement is maintained using modified cold blood lung preservation solution.

Adolescent↗
PubMed1996

The management of post-cardiac transplantation coronary artery disease.

OBJECTIVE: Allograft coronary artery disease remains the single greatest limitation to long term survival after cardiac transplantation. It is peculiarly aggressive in its behavior and diffuse in its nature. The role of conventional approaches to coronary artery revascularisation were studied in a selected group of cardiac transplant recipients. METHODS: Of the 557 patients undergoing cardiac transplantation at our unit between January 1979 and December 1993, all were screened for the development of allograft coronary artery disease routinely after 2 years and yearly thereafter or after 4 years. Twenty patients with allograft coronary artery disease were considered suitable for treatment by conventional means 17 of whom had undergone transplantation for ischaemic cardiomyopathy and the others for dilating cardiomyopathy. Percutaneous transluminal coronary angioplasty was performed in 18, 25-103 months after transplantation (mean 60 months) all of whom had severe proximal stenoses and reversible defects on perfusion scans. None suffered chest pain. Coronary artery bypass grafting was performed in 5, 95-105 months after transplantation (mean 101 months) 2 of whom had post-infarction unstable angina and 3 had severe triple vessel disease, dyspnoea, and perfusion abnormalities. RESULTS: The primary success rate for PTCA was 84% (16/19). Two lesions restenosed and 3 patients had progressive disease which necessitated coronary revascularisation. No patient died. Of the 5 patients undergoing coronary artery surgery 2 died perioperatively, one from acute left ventricular failure and one from acute rejection. All 18 survivors have improved perfusion scans. Following surgery, all survivors had improvement in dyspnoea and relief of angina. Five late deaths a mean of 89 months after transplantation were from coronary artery disease (4) and lung malignancy (1). CONCLUSIONS: Revascularisation by PTCA and CABG is feasible and successful in selected cardiac transplant recipients. Further study is required to determine the effect of revascularisation on prognosis.

Adult↗
PubMed1995

Age-related geriatric medicine: relevance of special skills of geriatric medicine to elderly people admitted to hospital as medical emergencies.

This study was carried out to find out how many patients aged 75 and over admitted to hospital as medical emergencies had features appropriate to care by physicians in geriatric medicine and to examine the extent of use of specialist facilities by these patients. The purpose was to examine criticisms of age-related admission policies which have focused on misplacement of patients with single diagnoses and lack of access to specialist care. An analysis was made of admission, process and discharge characteristics relevant to the special skills of geriatric medicine, multiple pathology and use of specialist services by 554 patients aged 75 and over. These were collected prospectively, consecutively admitted as medical emergencies via the accident and emergency department of a large district general hospital with an age-related (75 and over) medical admissions policy. 84 patients (15%) had single pathology and no characteristics suggesting the need for specialist geriatric care. 177 (32%) had single pathology and one or more specialized characteristics. 66 (12%) had multiple pathology alone. 227 (41%) had multiple pathology and specialized characteristics. There were 142 specialist referrals in 121 patients (22% of the whole sample). We concluded that the special skills of general physicians specializing in the medical and associated community problems of elderly people are highly relevant to patients aged 75 and over presenting as medical emergencies. There was no evidence of lack of involvement of specialists in their care.

Aged↗
PubMed1994

Cardiac involvement in seatbelt-related and direct sternal trauma: a prospective study and management implications.

The study set out to assess the incidence and consequences of pericardial and myocardial involvement in seatbelt-related sternal injury. Comparison was made with that from direct sternal trauma and implications for patient management were examined. The study was designed as a prospective sequential single centre study of 60 patients, from a total of 63 consecutive admissions over a 13 month period, admitted with blunt central chest trauma or multiple injuries involving the torso. Clinical status, correlated with echocardiographic, ECG and cardiac enzyme abnormalities were the main outcome measures. The study showed that 25% of 32 patients with seatbelt-related chest injury and 30% of 10 patients with multiple injuries had clinically unsuspected pericardial effusions detected by echocardiography. Pericardial effusion was not associated with an adverse outcome in the seatbelt-related injuries. Abnormalities of ECG or CK-MB isoenzyme levels were non-specific and did not correlate with the presence of pericardial effusion. From these data it is concluded that seatbelt-related sternal trauma is usually relatively benign. Echocardiography detects unsuspected pericardial effusion in a significant minority but ECG and cardiac enzyme estimations are of limited value. The routine admission to hospital of all patients with isolated seatbelt-related sternal trauma for cardiological monitoring is unnecessary. Inpatient treatment should be reserved for patients whose clinical condition, social circumstances or other injuries necessitate admission.

Accidents, Traffic↗
PubMed1994

Periductal inflammation and cigarette smoke.

BACKGROUND: Cigarette smoking has been implicated in the etiology of periductal mastitis. The mechanism by which it causes inflammation around the mammary ducts is unknown. STUDY DESIGN: Inflammation and dilatation of the mammary ducts were compared in two groups of women with proven histologic diagnoses of periductal mastitis (PDM, n = 133) and intraductal papilloma (IDP, n = 98) over an eight year period. This study was done to determine if the number of cigarettes smoked correlated with the amount of periductal inflammation seen in PDM. Duct dilatation, periductal inflammation, and squamous metaplasia were assessed objectively by two pathologists without knowledge of the clinical parameters. RESULTS: Women with PDM were significantly more likely to be smokers than women with IDP (p < 0.001). Women with severe periductal inflammation were more likely to be younger (p < 0.05) whereas those with duct dilatation were more likely to be older (p < 0.02). Women with PDM who were heavy smokers (more than ten cigarettes per day) had more periductal inflammation (p = 0.0006) and squamous metaplasia of the lactiferous ducts (p < 0.02) compared with light or nonsmokers. Duct dilatation did not correlate with smoking habits. CONCLUSIONS: Cigarette smoking appears to be an important etiologic factor in periductal mastitis and appears to have direct toxic effects on the mammary ducts.

Adult↗
PubMed1993

Does modern cardiac surgery require conventional intensive care?

We considered that, with modern perfusion equipment and mildly hypothermic cardiopulmonary bypass, protracted post-operative ventilation in an intensive care unit (ITU) is no longer required after most cardiac operations. We used a three-bedded cardiac recovery area (CRA) within the operating suite for 1,000 patients between January 1990 and June 1991. Forty-five patients with special needs were managed in the ITU. The time to extubation (T50%; range) for coronary bypass, aortic valve, mitral valve, and double-valve patients was 2.0 (0-42), 2.5 (0-12), 3.0 (0-15), and 3.0 (1-36) hours, respectively. Recovery beds were re-used allowing 5-6 operations daily. The difference in nursing staff complement for a CRA versus ITU bed was 4.5/7.8. Patient management was by nurse specialists supported by cardiac surgeons. Intervention by cardiac anaesthetists or intensivists was limited to specific ventilatory problems or renal failure. The early extubation policy failed in ten patients (five coronary, three aortic, one mitral and one double-valve patient) through poor pre-operative respiratory function, left ventricular failure or intra-operative events. The overall mortality in CRA was 1.4%. The mean duration of post-operative stay was 7 days (range 5-12). We conclude that a CRA staffed by nurse practitioners provides a safe and effective alternative to the anaesthetist-managed ITU. A rapid turnover of CRA beds removes the constraints of ITU bed availability.

Adolescent↗
PubMed1993

Replacement of the thoracic aorta with collagen-impregnated woven Dacron grafts. Early results.

We used the collagen-impregnated woven double-velour Dacron graft in 120 patients undergoing 122 aortic reconstructions. Seventy-nine aortic root, ascending, or arch replacements were performed during cardiopulmonary bypass with or without circulatory arrest; 53 of the 79 were for acute aortic dissection. In addition, three infants and one child underwent repair of truncus arteriosus. There were no deaths caused by hemorrhage or bleeding-related complications. For aortic root replacement, the impervious nature of the collagen-impregnated woven double velour Dacron graft allowed elimination of wrap-around techniques. Eight deaths occurred as a result of multisystem organ failure, which followed late diagnosis of type A dissection. Two patients underwent reoperation for late complications of type A dissection. Thirty-nine patients underwent treatment for disease of the descending aorta; eight of these patients underwent a central cannulation technique with profound hypothermic cardiopulmonary bypass. The other 31 underwent repair with aortic crossclamping without bypass. Four of these patients died: two as a result of multisystem organ failure, one as a result of uncontrolled bleeding from the native dissected aorta, and one as a result of intestinal necrosis. Follow-up studies for 2 months to 5 years revealed three late deaths caused by the rupture of a persistent aneurysmal false lumen after type A dissection. The intraoperative advantages of the collagen-impregnated woven double velour Dacron graft represent an important advance in vascular graft technology. Its handling and suturing characteristics are excellent, and the graft is completely impervious in its originally manufactured state. Needle holes self-seal rapidly. Medium-term follow-up by clinical, angiographic, computed tomographic, and magnetic resonance imaging techniques showed no late graft complications--specifically, no dilatation or thrombus formation.

Adult↗