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J Williams

Publications and source records attributed to J Williams.

At least 163 records · Page 9Linked to original sources

Validation of electrode placement in neonatal electrogastrography.

Electrogastrography (EGG) is the transcutaneous measurement of gastric electrical activity. The aims of this study were to validate the electrode placement position in neonatal electrogastrography using ultrasonography to localise the stomach, and to describe the observed EGG frequency characteristics. Fifteen neonates with no known abdominal disorder were studied. Two bipolar EGG recordings were obtained from each subject, the first from electrodes placed at sites localized by ultrasound and the second from electrodes placed at the currently recommended sites. Paired sample t tests were used to compare electrode positioning and electrogastrographic data. There were 15 subjects with a mean age of 36 days (range 1-95). While there was a significant difference in the position of electrodes at each site, the EGG recordings did not differ. The 3-cycle/minute (2.6-3.7cpm) activity ranged from 30% to 84% of recorded time (mean at sites localized with ultrasound was 53%, and at currently recommended sites it was 50%; difference not significant, P = 0.155). Bradygastria (<2.6 cpm) was observed in the range of 2-29% of recorded time (mean at sites localised with ultrasound was 12.9%, and at currently recommended sites it was 11.7%; difference not significant, P = 0.40). Tachygastria (3.2-10 cpm) was shown to be in the range of 10-58% of recorded time (mean at sites localized with ultrasound was 33.3%, and at currently recommended sites it was 38.7%; difference not significant; P = 0.044). In conclusion, there was no significant difference between EGG recordings taken from electrode sites localized by ultrasound and those recommended by manufacturers of the electrogastrogram, thus confirming the validity of the manufacturer's recommended electrode positioning. The pattern of electrical control activity in the normal neonatal stomach appears to be different from that demonstrated in adults. Bradygastria and tachygastria are seen more frequently, with fewer periods of 3 cpm activity.

Electrodiagnosis↗

CD34-positive cellular blue nevi.

BACKGROUND: Although cellular blue nevi (CBN) are well known and characterized, the histopathologic and clinical spectrum of these tumors continues to evolve. We report four CBN with a distinctive histologic and immunohistochemical pattern. METHODS: The histologic features and immunohistochemical staining for S-100 protein, HMB-45, Bcl-2 and CD34 of four CBN with distinctive features were evaluated using routine methods and compared to common CBN. RESULTS: All four of these distinctive CBN where known to be congenital, and all showed aggregates of plump spindled cells with round to oval nuclei in aggregates and more slender spindled cells with thin wavy nuclei. The slender, spindled cells showed an infiltrative pattern laterally into the dermis and deep into the subcutaneous fat. All four tumors showed diffuse expression of an immunohistochemical stain for CD34, as well as for S-100 protein, Bcl-2, and HMB-45. CONCLUSION: Positive immunohistochemical staining with the progenitor marker CD34 defines a subset of CBN. These tumors appear to fit within the spectrum of neurocristic cutaneous hamartomas and may arise from more primitive neurocristically derived cells. Further follow-up of these tumors will be necessary to determine whether this subset of CBN defines a subset with a characteristic biologic behavior.

Adolescent↗

Metastatic adenocarcinoma of the esophagus to the skin: new patterns of tumor recurrence and alternate treatments for palliation.

BACKGROUND: Esophageal cancer, particularly adenocarcinoma of the esophagus (ACE), has been steadily increasing in incidence in the United States. In the past, patients usually died rapidly with locoregional disease that leads to inanition and aspiration. However, today when patients with ACE are treated successfully with induction chemotherapy and radiation therapy, followed by surgical excision, ACE usually does not recur locally, but presents with metatastic disease. We present a 62-year-old white male with ACE, which was treated with induction chemotherapy and radiation therapy followed by surgical excision. After approximately 1 year with no evidence of locoregional recurrence, the patient presented with diffuse cutaneous metastatic disease. METHODS: In addition to routine staining immunohistochemical stains for CK(AE1/AE3), CK7, CK 20, EMA, alpha-smooth muscle (SM) actin, S-100 protein, CD34, P53, Bcl-2, c-erbB-2 were performed. RESULTS: The immunohistochemical profile was consistent with an esophageal origin showing positive staining with CK20 and CK7 as well as AE1/AE3 and EMA. In addition, there was marked nuclear expression of p53, as well as membrane expression of c-erb-B2; consistent with progression of the disease and poor response to further cytotoxic therapeutic regimes. CONCLUSIONS: With new therapeutic protocols, we can expect to see more metastatic disease with recurrences of ACE. The histopathologic features and the immunohistochemical profile of the recurrent tumors may be helpful in determining alternate forms of therapy that either alone or in combination could be useful in palliation and delaying progression.

Adenocarcinoma↗

Salvage abdominal surgery in patients with a retained rectal stump after restorative proctocolectomy and stapled anastomosis.

BACKGROUND: The introduction of surgical stapling instruments has widened the use of restorative proctocolectomy. Too high a distal transection of the rectum can, however, produce a retained rectal stump, which may cause symptoms. A study of the operative and functional data in a consecutive series of patients undergoing salvage surgery for retained rectal stump was undertaken. METHODS: Twenty-five patients referred between January 1990 and September 2000 for pouch dysfunction were identified as having a retained rectal stump. Twenty-two underwent abdominoanal revision. The hospital notes were reviewed and function was assessed during outpatient visits, by postal questionnaire and by telephone interview. RESULTS: Median operating time was 225 (range 170-340) min and median hospital stay was 15 (range 8-48) days. There was no operative death. Five pouches were excised. Seventeen patients were available for functional assessment. Median follow-up was 22.5 (range 4-114) months. Median 24-h frequency before and after operation was 12 (range 4-20) and 6 (range 3-12) respectively, and median night-time frequency was 4 (range 0-8) and 0.5 (range 0-4) respectively. Fifteen patients reported marked subjective improvement in pouch function and quality of life. CONCLUSION: Major revisional surgery for symptomatic retained rectal stump after restorative proctocolectomy with stapled anastomosis was successful in 15 of 22 patients. These results are worse than the outcome following first-time restorative proctocolectomy with anastomosis constructed at the anal level. Pouch-rectal anastomosis should be avoided.

Adenomatous Polyposis Coli↗

Enteric-release glyceryl trinitrate in active Crohn's disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Mucosal ischaemia may contribute to the pathogenesis of Crohn's disease. Microvascular abnormalities have been found in colonic resection specimens, and mucosal levels of constitutive nitric oxide synthase are reduced. AIM: To assess the efficacy of a novel, enteric-release formulation of the nitric oxide donor, glyceryl trinitrate, aimed at increasing the mucosal circulation and relaxing smooth muscle in the affected bowel. METHODS: The trial was randomized, double-blind and placebo-controlled. Baseline disease activity was assessed by a structured symptom diary, with blood tests and a quality of life assessment. Patients with a Crohn's disease activity index of > or = 150 and < 450 were randomized to receive 12 weeks of either glyceryl trinitrate (initially 6 mg twice daily, increasing to 9 mg twice daily after 6 weeks) or an identical placebo. Assessments were repeated at 6 and 12 weeks. RESULTS: Seventy patients (22 male) entered the study; 34 were given glyceryl trinitrate and 36 placebo. At 12 weeks, there were no differences between the treatment groups in terms of Crohn's disease activity index, pain, stool frequency, inflammatory markers or quality of life scores. CONCLUSIONS: Enteric-release glyceryl trinitrate did not benefit patients with mild to moderately active Crohn's disease. Whilst ischaemia may contribute to the pathogenesis of Crohn's disease, our results fail to provide supportive evidence for this hypothesis.

Administration, Oral↗

Antineutrophil cytoplasm antibody-induced neutrophil nitric oxide production is nitric oxide synthase independent.

BACKGROUND: Antineutrophil cytoplasm antibodies (ANCAs) are implicated in the pathogenesis of systemic vasculitis. We asked whether ANCA could induce nitric oxide (NO) release from human neutrophils and, if so, whether this NO production was dependent on NO synthase (NOS) activity. METHODS: Neutrophil NO production was measured using a chemiluminescence assay, and NOS activity was determined by the conversion of [(14)C] L-arginine to [(14)C] L-citrulline and NOS mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Human neutrophils isolated from healthy donors were incubated at 37 degrees C with human ANCA, normal human IgG, murine monoclonal myeloperoxidase ANCA, murine proteinase-3 ANCA, or their respective isotypic controls for 6 to 12 hours in RPMI. Both human and monoclonal ANCA led to a dose-dependent increase of NO compared with control IgG. Neutrophils, either freshly isolated or incubated for seven hours with murine monoclonal myeloperoxidase ANCA, proteinase-3 ANCA, or a mixture of interleukin-1 beta, tumor necrosis factor-alpha, interferon-gamma plus lipopolysaccharide showed no NOS activity with low conversion rates of [(14)C] L-arginine to [(14)C] L-citrulline, which could not be inhibited by N(G)-monomethyl-L-arginine (NOS inhibitor). To detect NOS mRNA expression, RT-PCR was performed using oligonucleotide primers derived from mRNA sequences of either human constitutive endothelial NOS (eNOS), constitutive neuroneal NOS (nNOS), or human hepatocyte inducible NOS (iNOS). There was no expression of either eNOS, nNOS, or iNOS in untreated, human and murine monoclonal ANCA-treated, or cytokine-treated neutrophils. CONCLUSION: These data suggest that human neutrophils produce NO in response to ANCA but in a NOS-independent way. NO can be generated from a nonenzymatic interaction between hydrogen peroxide and arginine. We postulate that this is the predominant pathway of NO synthesis in neutrophils, since ANCAs are capable of inducing reactive oxygen species production from neutrophils.

Antibodies, Antineutrophil Cytoplasmic↗

Association of prolonged hyperglycemia with glomerular hypertrophy and renal basement membrane thickening in the Goto Kakizaki model of non-insulin-dependent diabetes mellitus.

The aim of the current study was to characterize the effects of prolonged hyperglycemia on renal structure and function using a model of non-insulin-dependent diabetes mellitus: the Goto Kakizaki (GK) rat, which does not have confounding variables, such as hyperlipidemia, obesity, or elevated blood pressure. The data show that hyperglycemia in this model was not associated with the development of significant proteinuria, but it was associated with the development of definitive age-dependent renal structural changes. These changes consisted of thickening of glomerular basement membrane at 35 weeks and tubular basement membrane. This thickening was accompanied by marked glomerular hypertrophy resulting from a parallel increase in total capillary luminal volume and mesangial volume, but fractional capillary and mesangial volumes remained unchanged. There was evidence of podocyte injury, as assessed by de novo expression of desmin. In contrast, there was no evidence of mesangial cell activation, as assessed by their de novo expression of alpha-SMA. Interstitial monocyte/macrophage influx increased significantly in GK rats at 12 weeks compared with Wistar controls. Glomerular macrophage infiltration was elevated significantly in 35-week GK rats. The structural changes described in the GK rat are similar to those described in prolonged non-insulin-dependent diabetes mellitus patients who have not developed overt renal disease. This model allows us to investigate further the mechanisms involved in the pathogenesis of the consequences of prolonged hyperglycemia.

Aging↗

Cholangiocytic apoptosis in chronic ductopenic rejection.

The significance of cholangiocytic apoptosis as a mechanism of ductopenia in liver rejection remains controversial. In a previous study, the presence but not the extent of ductal apoptosis was assessed by electron microscopy. Other previously published studies using an in situ hybridization method (in situ end labeling) produced conflicting results (no apoptosis v massive apoptosis). We studied 47 liver needle biopsies from 8 patients with chronic ductopenic rejection confirmed by pathologic examination of the failed grafts. These biopsies were performed because of graft dysfunction, during a period of several months before retransplantation, and they showed cholangiocytic injury with progressive ductal paucity. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) was used to detect apoptosis (tissue digestion with proteinase K 20 microg/mL for 20 minutes). The interlobular bile ducts did not show labeling, even in lymphocytic cholangitis with obvious epithelial injury. However, there was minimal staining of ductular nuclei. Lymphocytic nuclei were also labeled. Apoptosis was not detectable in the vanishing interlobular bile ducts, even when more representative samples were studied and a more sensitive method was used. Unless apoptosis of cholangiocytes is an exceptionally rapid process escaping detection by conventional methods, ductopenia results mainly from ordinary, nonprogrammed cholangiocytic death. Apoptosis could still be involved in the pathogenesis of ductopenia by depleting cholangiocytic precursors, generally presumed to reside in ductules. This is a possible mechanism suggested by the following: (1) the established role of apoptosis in the homeostatic control of immature/progenitor cells, (2) the paucity of ductular proliferation in chronic rejection, (3) the previously reported decrease of ductular bcl-2 expression in rejection, and (4) the sporadic ductular TUNEL labeling seen in this study.

Apoptosis↗

A comparison of three disease-specific and two generic health-status measures to evaluate the outcome of pulmonary rehabilitation in COPD.

The use of health status as an outcome measure is becoming more widespread in pulmonary rehabilitation. There are a number of health status measures but the choice remains uncertain. Three disease specific measures and two generic measures of health status were employed to observe their relative sensitivity to a 7-week course of pulmonary rehabilitation. Patients with stable chronic obstructive pulmonary disease (COPD) were recruited into a rehabilitation programme. They completed a shuttle-walking test and three disease-specific questionnaires: the Chronic Respiratory Questionnaire (CRQ), the St. George's Hospital Respiratory Questionnaire (SGRQ) and the Breathing Problems Questionnaire (BPQ). Patients also completed two generic questionnaires: a global quality-of-life scale and an activity checklist. Ninety-seven patients [58 male mean (SD) age 67 (8.7) years] completed the course over a 12-month period. The mean pre-rehabilitation (SD) FEV1 was 1.06 (0.59) l. The shuttle-walking test and the treadmill-endurance test increased significantly after rehabilitation (P<0.001). All three disease-specific questionnaires improved significantly (the CRQ and SGRQ improved beyond minimum clinically important difference). The global score improved significantly whilst the 'things people do' decreased. All three disease-specific measures were responsive to pulmonary rehabilitation. However the operator-led CRQ appears to be the most sensitive short-term outcome measure.

Aged↗

Short-term results of the M2a-taper metal-on-metal articulation.

A polyethylene-free, metal-on-metal acetabular system (M2a-taper [Biomet, Inc., Warsaw, IN]) was designed in an effort to improve total hip arthroplasty (THA) longevity. Minimum 2-year follow-up results involving 72 polyethylene liner THAs and 78 metal liner THAs from a multicenter, randomized, controlled, investigational device exemption study are reported. Mean Harris hip scores of 95.54 (polyethylene liner group) and 95.23 (metal liner group) were reported at mean follow-up intervals of 3.29 and 3.23 years. Radiographic evaluation revealed no evidence of early failure. No acetabular components have been revised or are pending revision. No statistically significant differences in the data were calculated between liner types except for the immediate postoperative (P=.0415) and minimum 2-year follow-up (P=.0341) angles of inclination. The M2a-taper metal-on-metal articulation may represent a viable alternative for THA in younger, higher demand patients.

Adolescent↗

Pharmacokinetics and pharmacodynamics of sotalol in a pediatric population with supraventricular and ventricular tachyarrhythmia.

OBJECTIVE: This pharmacokinetic-pharmacodynamic study was designed to define the steady-state relationship between pharmacologic response and dose or concentration of sotalol in children with cardiac arrhythmias, with an emphasis on neonates and infants. METHODS: The treatment consisted of an upward titration with unit doses of 10, 30, and 70 mg of sotalol per square meter of body surface area. The patients received 3 doses at each dose level. The dosing interval was 8 hours. The Class III and beta-blocking activities of sotalol were derived from the QT and R-R intervals, respectively, of the surface electrocardiogram, which was recorded at 6 scheduled times before and after the third, sixth, and ninth doses. During these three dose intervals, 4 scheduled blood samples were also collected. Drug concentrations were measured with a validated nonstereoselective liquid chromatographic tandem mass spectrometric detection assay. Pharmacokinetic and pharmacodynamic parameters were obtained with standard methods. RESULTS: Twenty-one centers enrolled 25 patients in the study: 7 were neonates, 9 were infants, and 11 were children between the ages of 2 years and 12 years. The area under the drug concentration-time curve increased proportionately with dose. The apparent oral clearance of sotalol was linearly correlated with body surface area and creatinine clearance. The smallest children (body surface area <0.33 m2) displayed greater drug exposure than the larger children. The increase of QTc and R-R intervals was dose dependent. At the 70-mg/m(2) dose level, the mean (+/- standard deviation) maximum increase for the QTc interval was 14% +/- 7% and the average Class III effect during a dose interval was 7% +/- 5%. At the same dose level, the mean maximum increase of the R-R interval was 25% +/- 15% and the average beta-blocking effect during a dose interval was 12% +/- 13%. The effects tended to be larger in the smallest children. The Class III response and the plasma concentrations of sotalol were linearly related. The treatment was well tolerated. CONCLUSIONS: The steady-state pharmacokinetics of sotalol were dose proportionate. Pharmacologically important beta-blocking effects were observed at the 30-mg/m2 and 70-mg/m2 dose levels. Important Class III effects were seen at the 70-mg/m2 dose level. The Class III effect was linearly related to the drug concentration.

Anti-Arrhythmia Agents↗

Patterns of memory performance in children with controlled epilepsy on the CVLT-C.

Decreased memory skills have been reported in children with epilepsy. However, standardized instruments to evaluate learning and memory in children have been unavailable until recently. The present study was designed to assess memory patterns in children with epilepsy based on the California Verbal Learning Test-Children's Version (CVLT-C). The test was administered to 44 children with complex partial seizures and 21 children with generalized seizures between 8 and 13 years of age. Children in the study had been treated for epilepsy for at least 6 months, had well-controlled seizures on monotherapy, and had no evidence of anticonvulsant toxicity. Children with head injuries, learning disabilities, or hyperactivity were excluded. Test results did not reflect differences in memory performance based on seizure type. Scores for the entire sample indicated intact new learning, decreased intrusions and perseverative responses, and better short-term than long-term delayed recall. Recognition skills were stronger than long-term delayed recall skills and suggested that memory performance may be improved for these children when a multiple-choice format is available in academic settings.

Child↗

Context dependent latent inhibition in adult humans.

Learning the association between one stimulus (a condition stimulus, CS) and another (unconditioned stimulus, US) can be impaired by prior exposure to the CS alone--latent inhibition (LI). Current theories attempting to elucidate the cognitive deficit in schizophrenia have used the abolition of LI in schizophrenia as an indicator of attentional dysfunction. However, it has always been unclear if human and animal LI are measuring the same psychological processes. It is obviously important to clarify this relationship so that theoretical and experimental developments in the rat do not mislead the investigation of brain-behaviour relationships in schizophrenia. LI in the rat is strongly dependent upon context. Our aim was to examine the context specificity of LI in humans and specifically to: (1) investigate whether participants' belief that they are in a different context is sufficient to abolish LI, even though there is no physical change in the environment; (2) produce a context manipulation that is immune to alternative interpretation in terms of stimulus generalization decrement; and (3) investigate whether a "tonic" change of context reduces or abolishes human LI, thus complementing previous reports using a "phasic" change of context. In two experiments we manipulated context in either the real world or a virtual world, and showed that LI is abolished by a change of context in adult humans.

Adolescent↗

An overview of tritium behaviour in the Severn Estuary (UK).

Measurements of tritium (3H) activity in marine species in the Severn Estuary (UK) show concentrations significantly above those predicted by standard models. Concentration factors of 10(4) between seawater and marine species are observed; standard models assume a concentration factor of 1. In addition, the vast majority of activity is present in the form of organically bound tritium (OBT). The critical group dose from tritium--to consumers of local flounder--is estimated as approximately 36 microSv per annum. The measurements are related to the authorised release of wastes, via the sewer system, from the Amersham plc plant at Cardiff. The radiochemical plant manufactures a wide range of isotopically labelled compounds for use in life science research. The elevated levels of tritium observed in marine species have led to a programme of investigative work by specialist organisations. This paper describes the various definitions, measurements and significance of the term OBT. It also outlines the environmental observations and preliminary conclusions from the investigative programme to date.

Animals↗

A profile of PMS salaried GP contracts and their impact on recruitment.

BACKGROUND: Personal medical services (PMS) pilot sites aim to use salaried GP schemes to improve GP recruitment and retention and enhance the quality of service provision, particularly in underserved areas. OBJECTIVES: Our objectives were to (i) compare the work incentives of salaried compared with standard GP contracts; (ii) assess recruitment success to salaried posts; and (iii) describe the types of GPs attracted to these new posts. METHOD: All first wave PMS pilot sites with salaried GP posts known to be 'live' in October 1998 were included in the analysis of employment contracts and job descriptions. Information on recruitment was obtained by a questionnaire survey of PMS sites that were intending to recruit a salaried GP. RESULTS: The mean full-time equivalent salary was 43,674 pounds sterling with additional benefits in terms of sick leave, maternity leave and paid expenses. Eighty-nine percent of posts were eligible for the NHS pension scheme. Posts were mainly full time (40.8 hours per week). GPs were responsible for providing services equivalent in scope to general medical services. One-fifth of contracts freed GPs from out-of-hours responsibility and most freed them from practice management. Forty-three of the pilot sites actively recruited to fill 63 salaried posts, which involved a total of 51 recruitment 'rounds', with some pilots advertising more than once. There were 291 applications. The median number of applicants per post was three and the median time to recruitment was 6 weeks. Eighty-five percent of sites were satisfied with the quality of their applicants and 64% with the quantity. Eighty-five percent of applicants previously had been working in general practice, most in locum or salaried posts. Applicants tended to be young and male. Sixty posts were filled. CONCLUSIONS: Salaried contracts offer positive incentives to recruitment in terms of reduced hours of work and freedom from administrative responsibility. Recruitment success was similar to that achieved by inner city practices generally. This modest achievement might be enhanced by the addition of professional development schemes and increased flexible/part-time working.

Adult↗

The clinical and histologic spectrum of cutaneous fibrous perineuriomas.

Cutaneous fibrous perineuriomas (CFPs) and the closely related sclerotic perineuriomas are recently reported tumors. We present nine additional cases of CFPs. All tumors were small nodules on the extremities; however, they were not limited to a distal acral location as previously reported. In addition to tabulation of the histologic features, we performed a battery of immunohistochemical stains, including S-100 protein, CD34, cytokeratin, epithelial membrane antigen (EMA), KP-1, and collagen type IV. Histologically, these tumors presented with sharp circumscription of their deep aspect, as previously reported, or were not circumscribed on any side. The cells ranged from plump and spindled with one or more nuclei to thin, elongated, spindled cells with slender nuclei. A variably fibrotic stromal matrix surrounded these components. Immunohistochemical staining showed EMA-positive staining of the cellular component, with collagen type IV-positive staining surrounding the cells. The tumor cells were negative for S-100 protein, factor XIIIa, CD34, cytokeratin, and KP-1. The tumors reported here add to the clinical and histopathologic spectrum of CFPs.

Adult↗