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J Phillips

Publications and source records attributed to J Phillips.

At least 55 records · Page 3Linked to original sources

Nonlinear PCA: characterizing interactions between modes of brain activity.

This paper presents a nonlinear principal component analysis (PCA) that identifies underlying sources causing the expression of spatial modes or patterns of activity in neuroimaging time-series. The critical aspect of this technique is that, in relation to conventional PCA, the sources can interact to produce (second-order) spatial modes that represent the modulation of one (first-order) spatial mode by another. This nonlinear PCA uses a simple neural network architecture that embodies a specific form for the nonlinear mixing of sources that cause observed data. This form is motivated by a second-order approximation to any general nonlinear mixing and emphasizes interactions among pairs of sources. By introducing these nonlinearities principal components obtain with a unique rotation and scaling that does not depend on the biologically implausible constraints adopted by conventional PCA. The technique is illustrated by application to functional (positron emission tomography and functional magnetic resonance imaging) imaging data where the ensuing first- and second-order modes can be interpreted in terms of distributed brain systems. The interactions among sources render the expression of any one mode context-sensitive, where that context is established by the expression of other modes. The examples considered include interactions between cognitive states and time (i.e. adaptation or plasticity in PET data) and among functionally specialized brain systems (using a fMRI study of colour and motion processing).

Acoustic Stimulation↗

Oral folate reduces plasma homocyst(e)ine levels in hemodialysis patients with cardiovascular disease.

INTRODUCTION: Hyperhomocyst(e)inemia (plasma homocyst(e)ine concentration >16.0 micromol/l) is an independent risk factor for atherosclerosis, and is ubiquitous in patients with end-stage renal disease (ESRD). Oral folate supplementation in the non-ESRD population has been demonstrated to reduce plasma homocyst(e)ine (Hcy) concentration, and may reduce atherosclerotic morbidity. This study was undertaken to evaluate the efficacy of folate supplementation in reducing Hcy in patients with ESRD and cardiovascular disease. METHODS: Twenty-eight chronic hemodialysis patients with demonstrated hyperhomocyst(e)inemia (mean Hcy 35.2+/-13.3 micromol/l) were enrolled in the study. The presence of atherosclerosis was documented by history, physical examination, or ultrasonographic criteria. Hcy was determined initially and following six weeks' supplementation with 5.0mg folate and multvitamins. RESULTS: Hcy fell a mean of 15.0+/-10.4 micromol/l (38.9+/-19.9%) following supplementation (p<0.0005, paired t-test). In patients whose Hcy 'normalized' (n=10) Hcy fell a mean of 51+/-14% compared to a reduction of 32+/-20% in 18 patients whose Hcy remained >16.0 micromol/l (p=0.02). A significant positive correlation was observed between initial Hcy and both absolute and percent reduction after folate supplementation (r=0.87, p<0.005 and 0.53, p<0.005, respectively). Seven patients with documented atherosclerosis were older (68+/-8 yr vs 51+/-5 yr, p=0.007) an tended to have lower initial and final Hcy than the 21 patients without atherosclerosis (26.8+/-9.9 vs. 38.0+/-13.3 micromol/l, p=0.051 and 16.5+/-5.0 vs. 21.3+/-6.7, p=0.06, respectively). The presence of atherosclerosis was not associated with significant alteration in the response to folate. CONCLUSIONS: Supplementation with high-dose folate significantly reduces plasma Hcy in patients with and without atherosclerosis, and the presence of atherosclerosis does not impact on patients' response to folate and multivitamin supplementation. Hcy remained >16.0 micromol/l in the majority of patients, however, despite large absolute reductions in Hcy. Doses of folate greater than 5mg, or additional therapy may be required to further reduce Hcy in the majority of ESRD patients.

Adult↗

Current practice in the management of acute cholecystitis

AIMS: Several recent papers have advocated emergency cholecystectomy for patients with acute cholecystitis, stating that it is safe, cost effective and leads to less time off work. This study was designed to assess current practice in the management of acute cholecystitis in the UK. METHODS: A postal questionnaire was sent to 357 consultant surgeons who were thought to be involved in a general surgical on-call rota, to ascertain their current management of patients with acute cholecystitis. Replies were received from 250 consultants (70 per cent) of whom 242 (68 per cent) were involved in a general surgical take. Sixteen of these consultants, however, handed their patients with acute cholecystitis on to a different team the following day for further management. RESULTS: Twenty-seven consultants (12 per cent) routinely treat their patients by emergency cholecystectomy whenever possible, with 24 stating that they would do this within 72 h. Limiting factors to this practice were stated to be availability of surgical staff (15), theatre space (nine) and radiological investigations (four). The remaining consultants (n = 199) routinely manage their patients conservatively initially and providing they settle, either (1) book directly for cholecystectomy (n = 94, 47 per cent), (2) reassess as an outpatient (n = 65, 33 per cent), (3) either of above (n = 21; 11 per cent) or (4) refer on to a colleague (n = 19, 10 per cent). The commonest indications for acute cholecystectomy stated by consultants whose initial treatment policy is conservative are spreading peritonitis due to bile leak (93 per cent), empyema (89 per cent), unexpected space on a theatre list (28 per cent) and failure of an acute episode to settle (21 per cent). The laparoscopic method is the commonest for both elective and emergency cholecystectomy, but the percentage of consultants using an open method rises dramatically from 9 per cent in the elective situation to 48 per cent for emergency cholecystectomy. CONCLUSIONS: Despite evidence to support the increased use of emergency cholecystectomy, this practice is routinely carried out by only 12 per cent of consultants. However, of the consultants who treat their patients conservatively, 28 per cent are prepared to undertake emergency cholecystectomy if an unexpected space appears on the theatre list.

Journal Article↗

pH-dependent protein profiles of Helicobacter pylori analyzed by two-dimensional gels.

BACKGROUND: Helicobacter pylori survives transient exposure to extreme acid prior to adherence and growth on the gastric epithelium at neutral pH. MATERIALS AND METHODS: The effect of pH stress on protein profiles of H. pylori was observed using two-dimensional gel electrophoresis (2-D gels). H. pylori 26695 was grown microaerobically in tryptone-yeast extract broth, 3% fetal bovine serum. Growth in acid alkalinized the medium, whereas growth in base caused acidification. For 2-D gel analysis of protein profiles, cultures were grown in media buffered at pH 5.7 and at pH 7.5. RESULTS: Under all pH conditions, the most abundant proteins observed were the urease structural subunit UreB and the chaperonin GroEL. Growth in acid significantly increased the abundance of UreB. Thus, urease expression is not completely constitutive, as reported previously, but shows regulation by pH. Another protein observed only at low pH was identified as mammalian apolipoprotein A-I, possibly taken up by H. pylori from bovine serum in the growth medium. This finding, if confirmed, suggests that uptake of high-density lipoprotein from the human host may facilitate acquisition of cholesterol, required for formation of the unique cholesteryl glucosides in the membrane of H. pylori. In growth above pH 7, three stress proteins were induced: GroES (HspA), GroEL (HspB), and the antioxidant AhpC homolog TsaA. In addition, N-terminal sequence analysis identified five additional proteins that had not previously been reported on 2-D gels of H. pylori (FMN, SodB, TrxB, TsaA, and Tsr). CONCLUSIONS: In summary, our 2-D gel study reveals expression of several proteins dependent on growth pH.

Bacterial Proteins↗

Gender differences in state-wide EMS transports.

There are gender differences in emergency medical services (EMS) transports and management based on diagnosis. Data were extracted from the EMS State Ambulance Transport database. This database exists because of a legal requirement that all EMS transports generated by 911 calls and all interhospital transports be reported to the State EMS Bureau. All ambulance transports reported to the State EMS Division during 1995 were evaluated. Cases were excluded if they were aborted, admission or discharge transports, outpatient transports, or cases listed as "other" without a diagnosis. Gender-related treatment differences were determined for problems for which EMTs have specific treatment options. These were cardiac arrest, chest pain, allergic reactions, and extremity fractures. Results were compared using a two-tailed Chi squared or Fischer's Exact with significance at P < .05. Odds Ratios (OR) and 95% confidence intervals (CIs) were calculated. There were a total of 164,595 ambulance transports reported to the State EMS Division. Of these 76,074 (46%) were men and 88,521 (54%) were women. Of these, 50,211 were excluded. This left 52,607 injury transport and 61,777 illnesses transport. Men were significantly more likely than women to have injuries related to all-terrain vehicle accidents, motorcycle accidents, RV accidents, burns, gunshot wounds, and stab wounds. Men were significantly more likely than women to have illnesses related to cardiac arrest, dead on arrivals (DOAs), drowning, and smoke inhalation. For cardiac arrest transports, significantly more male patients presented ventricular fibrillation, more males received defibrillation, lidocaine, and bicarbonate, but more women received atropine. Male chest pain patients were more likely to receive oxygen and morphine and less likely to receive nitroglycerin. Male allergic reaction patients were more likely to receive an i.v. and subcutaneous epinephrine. Male extremity fracture patients were more likely to get an i.v. line, but there was no difference in morphine use or splinting. There are numerous disease-specific gender differences in the demographics of illness and injury transported by EMS. The use of various medications and procedures may also be related to gender. Understanding these differences may help in preparing EMS professionals for patient management.

Blood Pressure↗

Transnasal penetrating brain injury with a ball-pen.

We report a case of a 44-year-old man with 1 day's history of epistaxis. He was an in-patient in a psychiatric ward with a history of depression. He had CSF rhinorrhoea, was confused and had no focal neurological deficits. A full length pencil was removed from his left nostril in the emergency department. CT of the brain revealed a tract, but also suggested another foreign body in the inter-hemispheric space. He had a para-sagittal craniotomy and a 14 cm ball-point pen was found lying between the two cerebral hemispheres. This was removed and the patient made an uneventful recovery. This is the first report of an attempted suicide by transnasal insertion of a ballpoint pen intracranially.

Adult↗

The impact of aspirin therapy and anticoagulation on the prevalence of spontaneous subdural haematoma.

A retrospective analysis was performed of all patients who received operative intervention for subdural haematoma at the Beaumont neurosurgical unit between 1994 and 1997 inclusive. There were 123 spontaneous (mean age 74 +/- 5 years) and 77 traumatic haematomas (mean age 43 +/- 23 years) in the series. Ninety three patients (76%) in the spontaneous group were on antiplatelet agents or anticoagulants (78 aspirin, 15 warfarin) and the indication for their use was unknown in twenty four patients (19%). The re-operation rate in the group on aspirin and anticoagulants was twice that in the non aspirin / non anticoagulant group. These results highlight a significant medical problem and emphasise the need for cautious use of antiplatelet and anticoagulant agents, particularly in the elderly.

Adult↗

Expression of Epstein-Barr virus lytically related genes in African Burkitt's lymphoma: correlation with patient response to therapy.

A study on the Epstein-Barr virus (EBV)-associated malignancy (endemic) Burkitt's lymphoma (BL) was initiated on fine-needle-aspiration biopsies from 46 proven BL cases in Malawi. Gene expression that might correlate with patient serology (where high levels of antibodies to lytically related genes are commonly observed) was explored. In two-thirds of the cases, we identified the EBV BZLF1 replication activator intermediate early protein ZEBRA in varying quantities and to varying extents in cells by immuno-cytochemistry. The early lytic-cycle gene transcript BHLF1 was assessed positively by solid-phase hybridisation in over half of the same tumours. Evidence of transcription of these genes was confirmed on a smaller number of surgically removed fresh biopsies by RT-PCR. We asked whether our findings, which are generally counter to the established notion that EBV gene expression in BLs is restricted to the latent function, EBNA1, might offer some explanation for the differential responses to chemotherapy observed among African patients. Where the duration of follow-up was sufficient to assign the cases (37 in number) to one of 3 categories, namely, complete, partial or no response, a significant correlation between expression of the viral function ZEBRA and a positive patient response to treatment was found. Lack of this was associated with poor prognosis. Clinical data and EBV gene expression results support the postulate of subgroups of African BLs, the intermediate early antigen providing a marker of potential use in patient management.

Adolescent↗

Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial.

BACKGROUND: We and others have previously reported significant changes in chloride transport after cationic-lipid-mediated transfer of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to the nasal epithelium of patients with cystic fibrosis. We studied the safety and efficacy of this gene transfer to the lungs and nose of patients with cystic fibrosis in a double-blind placebo-controlled trial. METHODS: Eight patients with cystic fibrosis were randomly assigned DNA-lipid complex (active) by nebulisation into the lungs followed 1 week later by administration to the nose. Eight control patients followed the same protocol but with the lipid alone (placebo). Safety was assessed clinically, by radiography, by pulmonary function, by induced sputum, and by histological analysis. Efficacy was assessed by analysis of vector-specific CFTR DNA and mRNA, in-vivo potential difference, epifluorescence assay of chloride efflux, and bacterial adherence. FINDINGS: Seven of the eight patients receiving the active complex reported mild influenza-like symptoms that resolved within 36 h. Six of eight patients in both the active and placebo groups reported mild airway symptoms over a period of 12 h following pulmonary administration. No specific treatment was required for either event. Pulmonary administration resulted in a significant (p<0.05) degree of correction of the chloride abnormality in the patients receiving active treatment but not in those on placebo when assessed by in-vivo potential difference and chloride efflux. Bacterial adherence was also reduced. We detected no alterations in the sodium transport abnormality. A similar pattern occurred following nasal administration. INTERPRETATION: Cationic-lipid-mediated CFTR gene transfer can significantly influence the underlying chloride defect in the lungs of patients with cystic fibrosis.

Adult↗

Development of autologous human dermal-epidermal composites based on sterilized human allodermis for clinical use.

The aim of this study was to identify a sterilization technique for the preparation of human allodermis which could be used as a dermal component in wound healing and as the dermal base for production of dermal-epidermal composites for one-stage grafting in patients. We report that it is possible to produce dermal-epidermal composites which perform well in vitro and in vivo using a standard ethylene oxide sterilization methodology. Prevention of ethylene oxide-induced damage to the dermis was achieved using gentle dehydration of the skin prior to ethylene oxide sterilization. The issue of whether viable fibroblasts are required for composite production was examined in comparative studies using glycerol vs. ethylene oxide sterilized dermis. Where good collagen IV retention was achieved following preparation of acellular de-epidermized dermis there was no advantage to having fibroblasts present in vitro or in vivo; however, where collagen IV retention was poor or where keratinocytes were initially expanded in culture then there was a significant advantage to introducing fibroblasts to the composites during their preparative 10-day period in vitro. The requirement for fibroblasts became less evident when composites were grafted on to nude mice. In conclusion, we report a protocol for the successful sterilization of human allodermis to achieve an acellular dermis with good retention of collagen IV. This acellular dermis would be appropriate for clinical use as a dermal replacement material. It can also be used for the production of dermal-epidermal composites using autologous keratinocytes (with or without fibroblasts).

Adult↗

Screening for familial intracranial aneurysm: resource implications.

In this descriptive study, we estimate the resource implications of screening 18-65 year-old first degree relatives of patients with a first degree family history of intracranial aneurysm (IA). A postal survey of 374 patients who underwent operative clipping of IA between July 1994 and June 1997 was performed, enquiring about first degree family history of IA and first degree family structure. The response rate was 68.2% (255/374). Thirty-five out of 255 patients (14.0%) reported IAs in first degree relatives and 21 (8.2%) in second degree relatives giving a total of 57 (22.0%) with a reported family history. The average number of screenable relatives currently living in Ireland was 5.6 per high-risk family. Assuming a national prevalence of 0.45% for ruptured IA, these data give a point prevalence for high-risk families of 816 in the Republic of Ireland (1996 census population 3.6 x 10(6). Thus, the number of currently screenable relatives (5.6 per family) is 4814. A 15% yield has previously been reported from screening of first degree relatives in Northern Ireland. A national screening programme should thus detect over 700 individuals with asymptomatic IAs. The time required to screen the screenable population once would be 2.3 years by digital subtraction angiography (DSA) and 1.1 years by magnetic resonance angiography (MRA). In order to detect de novo aneurysms, screening has been suggested in this suspect population at 6-monthly to 5-yearly intervals after the initial study. In the absence of a biological marker, the results of our survey suggest that screening for familial IA disease would pose a significant logistical burden and have major financial implications for health care services.

Adolescent↗

State regulation and the hazards of milk, 1900-1939.

This examination of milk safety before the Second World War focuses on the manner in which government regulation was shaped by the agricultural lobby, acting through the Ministry of Agriculture. Dairy farmers used their market strength to resist the introduction of many regulations which were regarded as desirable and even essential from a public health perspective. These included compulsory pasteurization, favoured by the Ministry of Health and the BMA, but successfully resisted by farmers in the 1930s on commercial grounds and so not actually realized until 1949. This episode crystallized the three related conflicts of interest--between rural and urban areas, the needs of agriculture and public health, and the Ministries of Agriculture and Health--which restricted the expansion of state regulation, ensuring that milk still remained a potentially hazardous and occasionally lethal commodity in the late 1930s.

Agriculture↗