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P Wall

Publications and source records attributed to P Wall.

At least 19 recordsLinked to original sources
PubMed2002

Sensitization to the neuroendocrine, central monoamine and behavioural effects of murine tumor necrosis factor-alpha: peripheral and central mechanisms.

Systemic administration of murine tumour necrosis factor-alpha (mTNF-alpha; 0.1-2.0 microg, i.p.) dose-dependently increased plasma corticosterone and augmented monoamine utilization within the paraventricular nucleus of the hypothalamus (PVN), locus coeruleus, medial prefrontal cortex (PFC), central and medial amygdala. A time-dependent sensitization was induced in mice, wherein reexposure to mTNF-alpha 28 days (but not 1 day) following the initial cytokine treatment provoked marked signs of illness (diminished activity, ptosis, piloerection) and increased plasma corticosterone levels. Serotonin (5-HT) activity was augmented upon mTNF-alpha reexposure at the 1- or 28-day intervals in the PFC and medial amygdala, respectively. Intracerebroventricular (i.c.v.; 1-500 ng) mTNF-alpha did not promote illness, but modestly increased plasma corticosterone levels. Neither the illness nor the corticosterone changes were subject to a sensitization upon i.c.v. cytokine reexposure. Acute i.c.v. mTNF-alpha increased norepinephrine (NE), 5-HT and dopamine (DA) activity within the PVN and median eminence/arcuate nucleus complex (ME/ARC), and NE utilization within the central amygdala. Subsequent i.c.v. mTNF-alpha further enhanced the hypothalamic monoamine variations. Finally, systemic (i.p.) mTNF-alpha pretreatment did not proactively influence sickness or corticosterone responses upon later i.c.v. cytokine challenge, but augmented locus coeruleus NE activity and 5-HT and DA utilization within the ME/ARC. It is suggested that the sensitization with respect to sickness and corticosterone activity in response to mTNF-alpha reflect the involvement of peripheral mechanisms. Moreover, it appears that mTNF-alpha promotes central neurochemical plasticity through independent central and peripheral mechanisms.

Animals↗
PubMed2001

Monitoring gastrointestinal intraluminal PCO2: problems with airflow methods.

UNLABELLED: Gastrointestinal intraluminal PCO2 (PiCO2) information is used to assess the adequacy of trauma patient resuscitation and to assist in choosing resuscitative interventions. Therefore, determining the limitations and potential caveats of different PiCO2 monitoring systems is clinically important. This study compared two PCO2 monitoring systems. The airflow device adds and then removes air samples to quantitate PCO2, whereas the fiber-optic device does not. METHODS: Airflow (TRIP Tonometer/Tonocap) and fiber-optic (Neotrend) systems were used. In vitro they were compared with each other and to two end-tidal CO2 monitors measuring the PCO2 of humidified air containing 5% and then 10% CO2. In vivo the two systems' catheters were surgically juxtaposed in 15 dogs' stomachs; paired PiCO2 readings were taken throughout hemorrhage and resuscitation. RESULTS: In vitro, paired PCO2 values from the airflow and fiber-optic devices correlated with each other (r = 0.99) and with end-tidal values (r = 0.99 with airflow, r = 0.95 with fiber-optic). In vivo, paired values differed significantly (P < 0.0001), correlating poorly for two devices simultaneously measuring the same variable (r = 0.61). Fiber-optic PiCO2 values were higher than airflow values (mmHg +/- SEM): 69.3 +/- 4.8 vs. 61.3 +/- 5.6 at the start of hemorrhage, 141.3 +/- 12.9 vs. 87.7 +/- 7.9 by end of hemorrhage, and 104.3 +/- 9.6 vs. 82.8 +/- 7.0 by end of resuscitation for fiber-optic and airflow, respectively. CONCLUSIONS: Despite agreement in vitro, airflow methods can influence PiCO2 values obtained in vivo. Passive sensing methods used to monitor PiCO2, such as fiber-optic methods, are preferable because they neither deliver O2 to, nor remove CO2 from the local microenvironment.

Animals↗
PubMed2001

Analysis of outbreaks of infectious intestinal disease in Ireland: 1998 and 1999.

Surveillance of general outbreaks of infectious gastroenteritis was introduced in 1998 by the Food Safety Authority of Ireland (FSAI), in co-operation with the eight health boards. A total of 67 general outbreaks of gastroenteritis in Ireland were reported to the FSAI in 1998 and 1999. Over 1900 people were ill as a result of these outbreaks. Four percent required hospitalisation and there were two deaths. The duration of the outbreaks varied between one day and 38 days. Salmonellae (44%) and small round structured viruses (SRSV) (12%) were the most commonly reported pathogens. In 25% of the outbreaks the aetiology was unknown. The commonest settings were restaurants, hotels and take-aways, which accounted for 45% (30/67) of all outbreaks. Sixteen percent of all outbreaks occurred in hospitals and residential institutions. Over half of the outbreaks were reported to be foodborne, 63% of which were due to various serotypes of Salmonella enterica. Eggs were implicated as the vehicle of infection in 13% of all outbreaks. An infected food handler was identified in almost one third of outbreaks, although it could not be established if this had contributed directly to the outbreak.

Cross Infection↗
PubMed1999

An international outbreak of Vero cytotoxin-producing Escherichia coli O157 infection amongst tourists; a challenge for the European infectious disease surveillance network.

In March 1997, an outbreak of Vero cytotoxin-producing Escherichia coli O157 (VTEC) infection occurred amongst holidaymakers returning from Fuerteventura, Canary Islands. For the investigation, a confirmed case was an individual staying in Fuerteventura during March 1997, with either E. coli O157 VTEC isolated in stool, HUS or serological evidence of recent infection; a probable case was an individual with bloody diarrhoea without laboratory confirmation. Local and Europe-wide active case finding was undertaken through national centres, Salm-Net and the European Programme of Intervention Epidemiology, followed by a case-control study. Fourteen confirmed and one probable case were identified from England (7), Finland (5), Wales (1), Sweden (1) and Denmark (1) staying in four hotels. Three of the four hotels were supplied with water from a private well which appeared to be the probable vehicle of transmission. The case-control study showed illness was associated with consumption of raw vegetables (OR 8.4, 95% CI 1-5-48.2) which may have been washed in well water. This investigation shows the importance of international collaboration in the detection and investigation of clusters of enteric infection.

Adolescent↗
PubMed1999

Cerebral near infrared spectroscopy: emitter-detector separation must be increased.

We have compared the effect of increasing optode separation (range 0.7-5.5 cm) on the sensitivity of near infrared spectroscopy (NIRS) to discrete reductions in scalp and cerebral oxygenation in 10 healthy men (mean age 32, range 26-39 yr) using multichannel NIRS. During cerebral oligaemia (a mean reduction in middle cerebral artery flow velocity of 47%) induced by a mean reduction in end-tidal PCO2 of 2.4 kPa, the decrease in oxyhaemoglobin detected by NIRS became significantly greater with increasing optode separation (P < 0.0001). In response to scalp hyperaemia induced by inflation and release of a pneumatic scalp tourniquet, increases in oxyhaemoglobin became significantly smaller with increasing optode separation (P < 0.0002). These results are consistent with theoretical models of the behaviour of NIR light in the adult head and support the concept of using multi-detector NIRS to separate intra- and extracranial NIR signal changes. However, the emitter-detector separation used by currently available cerebral oximeters is not large enough to provide optimal spatial resolution.

Adult↗
PubMed1999

An estimate of the proportion of diarrhoeal disease episodes seen by general practitioners attributable to rotavirus in children under 5 y of age in England and Wales.

Mean weekly incidence rates for a 4-week period of new episodes of infectious intestinal disease (IID) and laboratory reports of faecal isolations in children under 5 y of age presenting in general practice were used to estimate the incidence of IID due to rotavirus infection in England and Wales. Between January 1992 and December 1996, a total of 92452 new episodes of IID were seen at sentinel general practices and reported to the Royal College of General Practitioners (RCGP) Research Unit in Birmingham, UK. Of these 32% (29592) were in children under 5 y of age. During the same period the Communicable Disease Surveillance Centre (CDSC) in London, UK received 159532 reports of faecal identifications in children under 5 y of age; 69219 (43%) of these were due to rotavirus. By modelling RCGP data and laboratory reports, the proportion of episodes attributable to rotavirus infection was estimated to be 29% (95% CI: 24% to 34%). By extrapolation of RCGP data it was estimated that rotavirus accounted for 762000 of new episodes of IID nationally in children under 5 y of age between January 1992 and December 1996. Implementation of a rotavirus vaccination programme could substantially reduce the incidence of childhood diarrhoea.

Child, Preschool↗
PubMed1998

Diagnostic delay in breast disease: a system analysis of a public urban hospital.

OBJECTIVE: To analyze the diagnostic process in 146 women referred to a breast clinic in an urban setting between January 1, 1994, and December 31, 1996. DESIGN: We devised the "diagnostic delay index (DDI)," defined as the time between the medical system's awareness of a diagnostic need and the completion of the diagnostic process. The time awaiting breast clinic consultation and the diagnostic events experienced--including clinic visits, imaging studies, and biopsies--were recorded. We stratified patients in 2 pathways (palpable masses and mammogram-identified lesions) and by benign or malignant outcome. RESULTS: Patients in pathways 1 (n = 85) and 2 (n=61) had a mean (+/-SD) DDI of 68.4 (+/-46.9) days and 71.9 (+/-35.2) days, respectively. Patients in both pathways who had a malignant outcome had a significantly lower DDI than those who had a benign outcome (47.5+/-30.9 days vs 78.6+/-42.6) (P<.001); this advantage was most pronounced in patients with palpable lumps. The average patient waited more than 3 weeks for both an initial clinic consultation and operating room access. Quartile analysis of the DDI revealed statistically significant differences in clinic access time, number of visits, diagnostic events per visit, and operating room access time. Regression analysis demonstrates the relationship between DDI and measured process variables: DDI= -21.11+0.09 age+1.86 pathway-12.18 outcome+1.08 clinic access+11.91 visits+0.94 operating room access (R2=61.5%). CONCLUSIONS: In a public hospital, diagnostic delay is related to inadequate access to surgical consultation and a delay in operating room access. Regression analysis demonstrates the relationships between these components of system diagnostic delay and suggests strategies for reducing the DDI.

Adolescent↗
PubMed1998

Sensitivity of near infrared spectroscopy to cerebral and extra-cerebral oxygenation changes is determined by emitter-detector separation.

OBJECTIVE: To examine the effect of two emitter-detector separations (2.7 and 5.5 cm) on the detection of changes in cerebral and extra-cerebral tissue oxygenation using near infrared spectroscopy (NIRS). METHODS: Two NIR detectors were placed on the scalp 2.7 and 5.5 cm from a single NIR emitter. Changes in deoxyhaemoglobin (HHb), oxyhaemoglobin (O2Hb),oxidised cytochrome C oxidase (Cyt) and total haemoglobin (tHb) were recorded from each detector during the induction of cerebral oligaemia (transition from hypercapnia to hypocapnia) and scalp hyperaemia (following release of a scalp tourniquet). RESULTS: Cerebral oligaemia (mean decrease in middle cerebral artery blood flow velocity of 44%) induced by a mean reduction in end tidal CO2 of 18 mmHg was accompanied by a significant increase in the spectroscopic signal for HHb and a decrease in the O2Hb signal. The signal change per unit photon path length detected at 5.5 cm was significantly greater for HHb (p = 0.007) than that detected at 2.7 cm. In contrast, the increase in all chromophores detected at 5.5 cm during scalp hyperaemia was significantly less than that detected at 2.7 cm (p<0.001). CONCLUSIONS: The differing sensitivity of the proximal and distal channels to changes in cerebral and extracerebral oxygenation is compatible with theoretical models of NIR light transmission in the adult head and may provide a basis for spatially resolving these changes. The optimal emitter-detector separation for adult NIRS requires further investigation and may differ between individuals.

Adult↗
PubMed1997

Defining the roles of high dose rate endobronchial brachytherapy and laser resection for recurrent bronchial malignancy.

Endobronchial therapy is commonly used in the palliative management of malignant disease, but the optimal combinations of treatment modalities (laser, brachytherapy, external beam radiotherapy) have not been defined. We have undertaken a prospective analysis of symptom response, duration of response, and prognostic factors for 117 patients treated with brachytherapy at a single centre, to identify hypotheses suitable for prospective randomised studies. All but one patient had received previous treatment. The percentage of patients with scores of 0 or 1 (none or mild) for each symptom pre-treatment and at 3 months were as follows: cough 62% to 77% (43% improving by at least one grade, N.S.); dyspnoea 32% to 56% (50% improvement by at least one grade, P = 0.0063); haemoptysis 78% to 97%; performance status 65% to 84% (54% by at least one grade, P = 0.0417). An actuarial risk of fatal haemoptysis at 2 years of 20% was associated with prior laser resection (P = 0.048). Death before 2 months was associated with dyspnoea scores of 3 or 4. Suggestions for randomised studies are made to address some of the uncertainties revealed by the analysis.

Brachytherapy↗
PubMed1997

Changes in tissue oxyhaemoglobin concentration measured using multichannel near infrared spectroscopy during internal carotid angiography.

OBJECTIVE: To develop an in vivo model for testing spatially resolved spectroscopy and quantified near infrared spectroscopy (NIRS) cerebral blood flow measurements. METHOD: Multiple detector NIRS has been used to study changes in tissue oxyhaemoglobin (O2Hb) concentration during selective internal carotid angiography. A significant reduction in O2Hb occurred in tissue interrogated by detectors situated between 0.7 and 4.1 cm from the NIRS light source. RESULTS: The time course of O2Hb concentration change was consistent with displacement of oxygenated blood by the radiocontrast medium from vascular beds of differing flow and NIR light attenuation. Increasing changes in O2Hb concentration per unit photon path length--predicted to occur at greater emitter-detector separations if those changes had occurred predominantly in cerebral tissue--were found in the first four seconds after injection of radiocontrast medium. However, later changes (6-10 s) were larger and were not proportional to emitter-detector separation. CONCLUSION: The findings indicate that simple assumptions regarding the distribution of the internal carotid artery blood supply to cerebral and extracerebral tissues, the photon path length through those tissues, and their relative contributions to attenuation of NIR light may not be justified.

Brain↗
PubMed1996

Identification of intermediate-risk prostate cancer patients treated with radiotherapy suitable for neoadjuvant hormone studies.

We undertook a retrospective review of patients presenting with apparently localised prostatic carcinoma to a single practitioner for consideration of radiation therapy to clarify the characteristics of those patients who might benefit from the use of neo-adjuvant androgen deprivation. Of 133 patients referred between January 1989 and June 1994, 85 were considered suitable for radical therapy, of whom 31 were treated with hormone therapy prior to radiotherapy, frequently on the basis of an elevated PSA. Increasing PSA levels (p = 0.0016) and Gleason grade (p = 0.026) were independent variables for relapse. It was possible to define three prognostic groups of patients, on the basis of initial PSA and Gleason grade. Those of intermediate risk (PSA < 10 micrograms/l, Gleason score 8-10; PSA 10-25 micrograms/l, Gleason 5-7 or 8-10; PSA > 25 micrograms/l, Gleason score 2-4) had a superior duration of disease-free survival if given initial hormone therapy. This group of patients is potentially the most likely to benefit from such an approach and should be enrolled in prospective randomised studies of neoadjuvant androgen deprivation.

Aged↗
PubMed1995

[The use of amphotericin B in a general hospital].

BACKGROUND: Amphotericin B (AmB) remains the standard treatment for most systemic mycosis. In addition to the ordinary deoxycholate formulation (AmB-DC), liposomal AmB (AmB-LP) is available in the United Kingdom. The aim of this study was to determine the patterns of usage of AmB in the present situation. METHODS: A 3 month prospective audit (August-October 1992) and a 3 year retrospective analysis of usage and expenditure in a United Kingdom University Hospital were carried out. RESULTS: A total of 42 courses and 564 days of treatment with AmB were analysed during the prospective audit. The total cost of AmB was 38,000 pounds (roughly 7,600,000 pesetas). AmB-LP accounted for 92% of the expenditure on AmB and 72% of the total expenditure on antifungals during the survey period. In 60% of the courses AmB was given as an empiric treatment. Only 65% of the days of treatment with AmB-LP were used according to the institution guidelines. The estimated cost of the days of treatment with AmB-LP that did not follow the institution guidelines was 9,500 pounds (roughly 1,800,000 pesetas). The retrospective analysis revealed a striking increase in the expenditure on AmB since the release of AmB-LP. There was an steady growth in the usage of both AmB-DC and AmB-LP over the 3 year period analysed. CONCLUSIONS: AmB is being increasingly used, mainly as an empiric treatment. The release of AmB-LP has had a great impact on the AmB budget. The current prescriptions habits of AmB-LP could be improved. To ensure an appropriate usage a direct control of AmB-LP might be advisable.

Amphotericin B↗
PubMed1995

Cardiac troponin C as a target protein for a novel calcium sensitizing drug, levosimendan.

The role of cardiac troponin C (cTnC) as a target protein for the calcium sensitization by levosimendan, pimobendan, MCI-154 and EMD 53998 was evaluated using purified recombinant human cTnC. For determination of calcium- and magnesium-dependent binding of the compounds to cTnC a new type of cTnC-HPLAC column was used. Furthermore, dansylated cTnC was utilized to study the effect of the calcium sensitizing compounds on calcium-induced conformation of cTnC. Only levosimendan showed calcium-dependent and to a lesser extent magnesium-dependent retention in the cTnC column. The findings indicate that levosimendan binds both to the N-terminal and C-terminal domains of cTnC. In agreement with this, only levosimendan shifted the calcium-induced fluorescence curve of dansylated cTnC to the left. In the control experiments Ca50 and KCa2+ were calculated to be 2.73 microM and 4 x 10(5) M-1, respectively. Levosimendan at 3 microM decreased the value of Ca50 to 1.19 microM. In conclusion, it is suggested that the mechanism of calcium sensitizing effect of levosimendan, unlike that of the other calcium sensitizers, is based on calcium-dependent binding to the N-terminal domain of cTnC. This is proposed to amplify the trigger of contraction induced by cTnC in the cardiac muscle.

Calcium↗