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Biomedical subjects

P Thompson

Publications and source records attributed to P Thompson.

At least 19 recordsLinked to original sources

Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide.

Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28-81 years), male 81%, Child-Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0-9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways.

Adult↗

Blood splash from different diathermy instruments during tonsillectomy.

OBJECTIVE: To compare the potential risk of blood contamination of the surgeon's conjunctiva during tonsillectomy using disposable bipolar diathermy and reusable monopolar diathermy. DESIGN: A prospective, single-blind, randomized, controlled trial. METHODS: Elective tonsillectomy was performed using either disposable bipolar diathermy or reusable monopolar diathermy. The operating surgeon wore a ViewsafeTM protective eyeshield which was later examined under an operating microscope by a blinded observer and the number of blood spots counted. RESULTS: One hundred and sixty-eight patients were enrolled. The relative risk of conjunctival contamination of the surgeon using disposable bipolar diathermy was 2.8 times that with reusable monopolar diathermy (chi-squared test, p < 0.0005). A previous history of peritonsillar abscess and additional adenoidectomy were associated with increased blood splatter. CONCLUSION: The use of disposable bipolar diathermy for haemostasis during tonsillectomy poses a greater risk of conjunctival contamination for the surgeon than using reusable monopolar diathermy.

Adolescent↗

Comparison of physician- and self-collected genital specimens for detection of human papillomavirus in men.

There is currently no consensus regarding the most appropriate methods of sampling for the detection of genital human papillomavirus (HPV) in men. We employed a recently developed collection method involving abrasion and moistened swabbing of the genital skin surface for the detection of HPV in a cohort of 136 university-affiliated males in Hawaii. Genital specimens collected by physicians using this method were compared with self-collected specimens from the same individuals obtained 24 h later. Self-collected specimens yielded a greater proportion of sufficient specimens than physician-collected specimens. HPV detection was comparable in physician- and self-collected specimens; detection was highest in the penile shaft (51.2% and 51.5%, respectively, P = 0.96), followed by the scrotum (41.2% and 46.2%, P = 0.43), the glans/coronal sulcus (31.9% and 33.1%, P = 0.84), and the foreskin (33.3% and 28.6%, P = 0.74). Site-specific agreement in HPV detection between paired physician- and self-collected samples ranged from 67.2% (kappa = 0.34) for the penile shaft to 95.0% (kappa = 0.89) for the foreskin. There was a high degree of concordance in HPV genotypes in HPV-positive pairs. The most common type was HPV type 84, which comprised approximately 15% of the specimens. The emery paper-swab method offers an efficient sampling method for genital HPV DNA detection in men that could be used both within and outside of the clinical setting.

Adolescent↗

Distinct phenotype associated with a cryptic subtelomeric deletion of 19p13.3-pter.

Telomeres are gene rich regions with a high recombination rate. Cryptic subtelomeric rearrangements are estimated to account for 5% of mental retardation/malformation syndromes. Here we present the first patient with a deletion of 19p13.3, identified by subtelomeric FISH analysis. His features included a distinctive facial appearance, cleft palate, hearing impairment, congenital heart malformation, keloid scarring, immune dysregulation, and mild learning difficulties. Subtelomeric FISH analysis identified a deletion of 19p13.3-pter. The deletion size was determined to be 1.2 Mb by FISH analysis. It extended from within the chromosomal region covered by BAC RP11-50C6 to 19pter. The deleted area encompassed approximately 60 genes. Fifteen possible candidate genes were considered with respect to the phenotype, including follistatin-related precursor 3 (FSTL3) and serine-threonine kinase 11 (STK-11).

Abnormalities, Multiple↗

An African American family with early-onset Alzheimer disease and an APP (T714I) mutation.

The occurrence of an APP T174I mutation is described in a large American family of African descent with Alzheimer disease. The clinical characteristics were an unusually early onset of disease (early 30s), similar to a previously reported age at onset of this mutation in an Austrian family. Distinct from that family, seizures and myoclonus were prominent features of the disease in this kindred.

Adult↗

Therapeutic efficacy as predicted by quantitative assessment of murine RIF-1 tumour pH and phosphorous metabolite response during hyperthermia: an in vivo 31P NMR study.

Described herein are the initial findings from an 'in-magnet' 31P NMR compatible hyperthermia system capable of concurrently heating and monitoring the metabolic response of murine tumours; the murine radiation induced fibrosarcoma (RIF-1) was employed for these studies. At thermal doses sufficient to raise tumour temperature to 41.5 and 43 degrees C for a period of 30 min, a marked and rapid decrease in nucleoside triphosphate concentration and in pH was observed during the heating period, while inorganic phosphate concentration increased significantly but more gradually. These 31P NMR determined metabolic indices remained depressed/elevated throughout a 1.5 h post-hyperthermia monitoring period. Importantly, these metabolic indices correlated significantly with specific growth delay. This suggests a possible role for NMR spectroscopy in early assessment, and perhaps control, of therapeutic response to hyperthermia.

Animals↗

Phenytoin toxicity due to fluoropyrimidines (5FU/capecitabine): three case reports.

Interactions between phenytoin and the fluoropyrimidine derivatives, 5 fluorouracil (5FU) and capecitabine, are not commonly documented or widely recognised. As more people with significant medical comorbidities are now being considered for chemotherapy, it is increasingly likely that people receiving phenytoin will be prescribed treatment with fluoropyrimidines. We present two cases of clinical phenytoin toxicity occurring after starting treatment with 5-fluorouracil/folinic acid (5FU/FA) and a third who developed clinical phenytoin toxicity after starting capecitabine (an orally administered prodrug of fluorouracil).

Adenocarcinoma↗

Performance of phase plates on the XMaS beamline at the ESRF.

Two phase plates, a 0.78 mm-thick natural diamond and a 0.3 mm-thick synthetic diamond, were used to convert linearly polarized X-rays into a circularly polarized beam, to cover an energy range of 3-9 keV. The performance of these plates followed theoretical predictions as indicated by polarization analyses and X-ray magnetic circular dichroism measurements. The use of the device is illustrated by resonant magnetic reflectivity measurements on UAs/Co multilayers.

Journal Article↗

Transfemoral implantation of the Wagner SL stem. The abolition of subsidence and enhancement of osteotomy union rate using Dall-Miles cables.

BACKGROUND: The Wagner SL uncemented revision stem has been utilised successfully for revision hip surgery where marked loss of proximal bone stock co-exists or where there is a periprosthetic fracture. Implanted via the transfemoral approach, one significant difficulty appears to be a tendency for implant subsidence, which in some cases has been troublesome enough to necessitate early revision (usually to a larger prosthesis). METHODS: A change in our operative practice allowed us to review the effects of using either wire cerclages or 2.0 mm Dall-Miles cables for prophylactic wiring of the distal femur. Seventeen Wagner SL stems, inserted via the transfemoral approach, were studied in 16 patients. RESULTS: We found those patients prophylactically wired with Dall-Miles cables demonstrated no subsidence in comparison with those in whom heavy wire cerclage had been utilised (mean subsidence 6 mm; p=0.001). In addition, we found that closure of the proximal osteotomy with wires conferred a more reliable rate of union in comparison with those closed with heavy sutures. CONCLUSION: We recommend the use of Dall-Miles cables for distal cerclage and osteotomy closure for the Wagner prosthesis.

Aged↗

Acute and chronic regulation of pituitary receptors for vasopressin and corticotropin releasing hormone.

At least two hypothalamic peptides, corticotropin releasing hormone (CRH) and vasopressin (VP), are important in regulating adrenocorticotropin (ACTH) release from the anterior pituitary. Both are secreted in a pulsatile manner and stimulate ACTH secretion by interacting with G protein-coupled receptors (GPCRs), namely the type 1 CRH receptor and V1b receptor, respectively. Repeated or prolonged stimulation with either peptide can cause reduced ACTH responsiveness or desensitisation, both in vivo and in vitro. Desensitisation of perifused sheep anterior pituitary cells to VP was found to be rapid and occurred following treatment with 5 nM VP for 5 min. This is within the range of concentrations and durations of VP pulses seen in sheep portal blood during acute stress. In contrast, significant desensitisation of the ACTH response to CRH required pre-treatment for longer than 25 min with a CRH concentration of 1 nM, suggesting that endogenous pulses may not elicit desensitisation. Although rapid GPCR desensitisation involves uncoupling of receptors from their G proteins, commonly mediated by receptor phosphorylation, and internalisation of receptors, desensitisation of neither the CRH nor VP receptor was mediated by PKA or PKC, respectively. Desensitisation of the response to VP was found to be dependent upon receptor internalisation, and resensitisation could be delayed by treatment with a protein phosphatase 2B inhibitor. The rapid kinetics of desensitisation of the ACTH response to VP suggest that this process is important in regulating the response to acute rather than chronic stress. If, as has been suggested, CRH acts in a permissive way to set corticotrope gain, desensitisation to CRH could also be important in long term regulation of ACTH secretion.

Adrenal Glands↗

Women with HIV infection: a model of university-based care, training and research.

The growth of human immunodeficiency virus type-1 (HIV) infection among women in the USA has been coincident with an international momentum to better address the specific health care needs of women. This paper provides an overview of a demonstration model for comprehensive HIV care of adolescent and adult women in an academic setting. The paper contains a descriptive summary of a university-based demonstration model of comprehensive care for women with HIV infection. During 1997-1998, there were 279 urban and rural Midwest adolescent and adult women with HIV infection in care at this model programme. Medical care encompassed subspecialty HIV care, obstetrical and gynaecological care, primary care of non-HIV comorbidities, mental health assessments and family planning in a safe, university-based environment. For 279 women during the two-year period, health services included the detection and treatment of sexually transmitted diseases (56%) and cervical dysplasia (35%), perinatal care (12%) and screening and referral for substance abuse treatment (30%). There was no mother-to-child HIV transmission among 33 pregnant women enrolled in the Center prior to delivery, and transmission by three of nine women enrolled after delivery. Only 167 (60%) women were compliant with biannual medical visits during 1997-1998. Integral to the health services delivery was the provision of ancillary support services intended to enhance optimal medical care for this cohort of women. This university-based model of care also incorporated HIV provider training and formative HIV research. Structured medical and public health experiential learning opportunities occurred for medical and social work students, medicine residents, infectious diseases fellows, nurses and other professional health care workers. Clinical investigations of adolescent and adult women have complemented care and training, with funded research in HIV medication adherence and health services research. In follow-up, 71% of these women remained active in care in 1999. Retention of vulnerable populations in care may be a big challenge over the next decade, despite the availability of potent antiretroviral therapies.

Adolescent↗

Adherence to statin treatment and readmission of patients after myocardial infarction: a six year follow up study.

OBJECTIVE: To investigate patients' adherence to statin treatment prescribed following their first myocardial infarction (MI) and to estimate the effect of adherence to statins on recurrence of MI and all cause mortality. DESIGN: Cohort study using a record linkage database. SETTING: Tayside, Scotland, UK. PATIENTS: Patients who experienced their first MI between January 1990 and November 1995. MAIN OUTCOME MEASURES: Percentage of statin use and adherence to statins by patients after an MI and the relative risk of hospitalisation for recurrent MI. The effect of adherence on all cause mortality was also examined. The covariates used were age, sex, socioeconomic deprivation, serum cholesterol concentration, diabetes mellitus, cardiovascular drug use, and other hospitalisations. RESULTS: Of 5590 patients who experienced an incident MI, 717 (12.8%) experienced at least one further MI. Only 7.7% of patients used statins after an MI during the study period. Compared with those not taking statins, those who had 80% or better adherence to statin treatment had an adjusted relative risk of recurrent MI of 0.19 (95% confidence interval (CI) 0.08 to 0.47) and all cause mortality of 0.47 (95% CI 0.22 to 0.99). There was no significant reduction in either end point for those who were less than 80% adherent to statins. CONCLUSIONS: Despite the infrequent use of statin during the study period, good adherence to statin treatment was associated with lower risk of recurrent MI.

Adult↗

An optimized individual target brain in the Talairach coordinate system.

The goal of regional spatial normalization is to remove anatomical differences between individual three-dimensional brain images by warping them to match features of a single target brain. Current target brains are either an average, suitable for low-resolution brain mapping studies, or a single brain. While a single high-resolution target brain is desirable to match anatomical detail, it can lead to bias in anatomical studies. An optimization method to reduce the individual anatomical bias of the ICBM high-resolution brain template (HRBT), a high-resolution MRI target brain image used in many laboratories, is presented. The HRBT was warped to all images in a group of 27 normal subjects. Displacement fields were averaged to calculate the "minimal deformation target" (MDT) transformation for optimization. The greatest anatomical changes in the HRBT, following optimization, were observed in the superior precentral and postcentral gyri on the right, the right inferior occipital, the right posterior temporal lobes, and the lateral ventricles. Compared with the original HRBT, the optimized HRBT showed better anatomical matching to the group of 27 brains. This was quantified by the improvements in spatial cross-correlation and between the group of brains and the optimized HRBT (P < 0.05). An intended use of this processing is to create a digital volumetric atlas that represents anatomy of a normal adult brain by optimizing the HRBT to the group consisting of 100+ normal subjects.

Adult↗

Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study.

PURPOSE: To compare the efficacy and safety of orally administered capecitabine (Xeloda; Roche Laboratories, Inc, Nutley, NJ), a novel fluoropyrimidine carbamate designed to mimic continuous fluorouracil (5-FU) infusion but with preferential activation at the tumor site, with that of intravenous (IV) 5-FU plus leucovorin (5-FU/LV) as first-line treatment for metastatic colorectal cancer. PATIENTS AND METHODS: We prospectively randomized 602 patients to treatment with capecitabine 1,250 mg/m(2) administered twice daily days 1 to 14 every 3 weeks, or to the 4-weekly Mayo Clinic regimen (5-FU/LV) until disease progression or unacceptable toxicity. RESULTS: The primary objective, to demonstrate at least equivalent response rates in the two treatment groups, was met. The overall response rate was 18.9% for capecitabine and 15.0% for 5-FU/LV. In the capecitabine and 5-FU/LV groups, respectively, median time to disease progression was 5.2 and 4.7 months (log-rank P =.65); median time to treatment failure was 4.2 and 4.0 months (log-rank P =.89); and median overall survival was 13.2 and 12.1 months (log-rank P =.33). The toxicity profiles of both treatments were typical of fluoropyrimidines. However, capecitabine led to significantly lower incidences (P <.00001) of stomatitis and alopecia, but a higher incidence of cutaneous hand-foot syndrome (P <.00001). Capecitabine also resulted in lower incidences (P <.00001) of grade 3/4 stomatitis and neutropenia, leading to a lower incidence of grade 3/4 neutropenic fever and sepsis. Only grade 3 hand-foot syndrome (P <.00001) and uncomplicated grade 3/4 hyperbilirubinemia (P <.0001) were reported more frequently with capecitabine. CONCLUSION: Oral capecitabine achieved an at least equivalent efficacy compared with IV 5-FU/LV. Capecitabine demonstrated clinically meaningful safety advantages and the convenience of an oral agent.

Adenocarcinoma↗

The XMaS beamline at ESRF: instrumental developments and high-resolution diffraction studies.

The beamline, which is situated on a bending magnet at ESRF, comprises a unique combination of instrumentation for high-resolution and magnetic single-crystal diffraction. White-beam operation is possible, as well as focused and unfocused monochromatic modes. In addition to an eleven-axis Huber diffractometer, which facilitates simple operation in both vertical and horizontal scattering geometries, there is an in-vacuum polarization analyser and slit system, mirrors for harmonic rejection, sub 4.2 K and 1 Tesla magnetic field sample environment, plus a diamond phase plate for polarization conditioning. The instrumentation developed specifically for this beamline is described, and its use illustrated by recent scientific results.

Journal Article↗

A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM).

Motivated by the vast amount of information that is rapidly accumulating about the human brain in digital form, we embarked upon a program in 1992 to develop a four-dimensional probabilistic atlas and reference system for the human brain. Through an International Consortium for Brain Mapping (ICBM) a dataset is being collected that includes 7000 subjects between the ages of eighteen and ninety years and including 342 mono- and dizygotic twins. Data on each subject includes detailed demographic, clinical, behavioural and imaging information. DNA has been collected for genotyping from 5800 subjects. A component of the programme uses post-mortem tissue to determine the probabilistic distribution of microscopic cyto- and chemoarchitectural regions in the human brain. This, combined with macroscopic information about structure and function derived from subjects in vivo, provides the first large scale opportunity to gain meaningful insights into the concordance or discordance in micro- and macroscopic structure and function. The philosophy, strategy, algorithm development, data acquisition techniques and validation methods are described in this report along with database structures. Examples of results are described for the normal adult human brain as well as examples in patients with Alzheimer's disease and multiple sclerosis. The ability to quantify the variance of the human brain as a function of age in a large population of subjects for whom data is also available about their genetic composition and behaviour will allow for the first assessment of cerebral genotype-phenotype-behavioural correlations in humans to take place in a population this large. This approach and its application should provide new insights and opportunities for investigators interested in basic neuroscience, clinical diagnostics and the evaluation of neuropsychiatric disorders in patients.

Adult↗