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Biomedical subjects

J Williams

Publications and source records attributed to J Williams.

At least 181 records · Page 10Linked to original sources

Metastatic meningioma to the lung with multiple pleural metastases.

Meningiomas with both malignant clinical behavior and cytology are rare. Meningiomas comprise approximately 15% of the primary brain tumors. The majority are benign; less than 1% metastasize, most commonly to the lung (61%) followed by liver, lymph node, and bone. Approximately 130 cases of extracranial metastatic meningiomas have been described. Only 13% had more than three metastases, with few cases reported with extensive pleural involvement. We report an interesting case of a malignant meningioma that invaded through the skull in the frontal sinus that later metastasized to the left lung with multiple pulmonary and pleural nodules.

Aged↗

Microcystic adnexal carcinoma: an immunohistochemical study including markers of proliferation and apoptosis.

Microcystic adnexal carcinoma (MAC) is the prototype for a subset of locally aggressive adnexal carcinomas (LAACs). Ultraviolet radiation (UVR) and UVB signature p53 mutations are implicated in the etiology of the most common cutaneous carcinomas. However in MACs, the role of UVR and p53 mutations is unknown. In addition, controversy still exists regarding the patterns of differentiation within these tumors. The objective of this study was to determine the expression patterns of immunohistochemical markers for p53, Ki-67, c-erbB-2, and Bcl-2 in MACs, and to compare these patterns with two MAC histologic stimulants: sclerosing type basal cell carcinomas (sBCCs) and desmoplastic trichoepitheliomas (dTEs). Other objectives were to compare expression patterns of cytokeratin (CK) AE1/AE3, CK7, CD20, endothelial membrane antigen (EMA), Ber-EP4, CD34, alpha-smooth muscle actin (SMA), and S-100 protein in MACs with its histologic simulators, and to determine the usefulness of all the immunohistochemical studies in diagnosis. Immunohistochemical markers were performed on 10 MACs, 10 sBCCs, and four dTEs. They included p53, Ki-67, c-erbB-2, Bcl-2, CK AE1/AE3, CK7, CD20, EMA, Ber-EP4, CD34, S-100 protein, and alpha-SMA. MACs expressed p53 in less than 25% of the tumor cells in only two cases (20%), and both cases showed only moderately intense staining, whereas 80% of the sBCCs were positive and showed intense staining, and all dTEs were negative. In MACs, less than 5% of the tumor cells were Ki-67 positive, whereas the sBCCs showed 20% to 40% Ki-67-positive tumor cells and dTEs showed rare Ki-67-positive cells. Bcl-2 was expressed focally in MACs, diffusely in sBCCs, and in scattered cells in dTEs. All tumors were negative for c-erbB-2. CD34, CK7, EMA, Ber-EP4, S-100 protein, and alpha-SMA all showed a distinctive pattern of staining in MACs. Although MACs arise commonly in chronically sun-exposed skin, increased expression of p53 is not found frequently. Overexpression of c-erbB-2 does not appear to be a factor in the development and progression of these adnexal tumors. Bcl-2 is expressed in MACs, but not diffusely as in sBCCs. The low level of Ki-67 supports a low proliferative rate, and other immunohistochemical markers support divergent patterns of adnexal differentiation in MACs. Immunohistochemical studies may help to differentiate MAC from sBCCs and dTEs.

Adult↗

Use of V4R in patients who sustain blunt chest trauma.

OBJECTIVE: In blunt chest trauma, the right ventricle is more vulnerable than the left. The purpose of this study was to determine whether recording V4R in patients with blunt chest trauma would provide additional useful information to that already obtained from the standard 12-lead electrocardiogram (ECG). METHODS: Forty-five patients with blunt chest trauma and 40 unmatched control subjects without blunt chest trauma had standard 12-lead ECG and right precordial leads recorded. The ECGs were read blindly by three physicians. RESULTS: Patients with chest trauma were distinguishable from controls on the basis of the left-sided ECGs (odds ratio, 2.9; 95% confidence interval, 1.71-4.90). This was not the case using V4R (odds ratio, 1.23; 95% confidence interval, 0.59-2.0). CONCLUSION: Patients with a significant mechanism and physical findings of blunt chest trauma were more likely than controls to have an abnormal ECG. They were not more likely to have abnormalities in V4R. We recommend that a 12-lead ECG, but not V4R, be routinely obtained on these patients.

Adolescent↗

Relation between dosage of carbamazepine and concentration in hair and plasma samples from a compliant inpatient epileptic population.

Compliance is a problem in all areas of therapeutic medicine. Methods for its assessment are classified as either indirect or direct. Indirect assessment is based on criteria such as pill counts, questionnaires, and self-reporting; direct methods involve the analytic measurement of the drugs in biologic fluids such as plasma or urine. Drugs taken either therapeutically or recreationally become incorporated into hair. This prospective study investigated the relation between the daily intake of the antiepileptic drug carbamazepine and both its trough plasma and hair concentrations in a highly supervised inpatient population of patients with epilepsy during a period of 6 months. Results showed that although there was a significant variation between patients resulting from the substantial range in the daily intake of carbamazepine (800-2400 mg/day), the intrapatient variation in both trough plasma and hair concentrations during the 6-month period were not significantly different. The mean intrapatient percentage coefficient of variation in total plasma and hair concentrations of carbamazepine was 11.5 +/- 4.7 and 15.0 +/- 5.2, respectively, both of which were independent of the daily dosage. This relatively small intrapatient variation in hair concentration over time and its close relation to the plasma concentration suggests that hair analysis may be a complementary and useful technique in monitoring drug-taking behavior.

Adult↗

Role of alginate and its O acetylation in formation of Pseudomonas aeruginosa microcolonies and biofilms.

Attenuated total reflection/Fourier transform-infrared spectrometry (ATR/FT-IR) and scanning confocal laser microscopy (SCLM) were used to study the role of alginate and alginate structure in the attachment and growth of Pseudomonas aeruginosa on surfaces. Developing biofilms of the mucoid (alginate-producing) cystic fibrosis pulmonary isolate FRD1, as well as mucoid and nonmucoid mutant strains, were monitored by ATR/FT-IR for 44 and 88 h as IR absorbance bands in the region of 2,000 to 1,000 cm(-1). All strains produced biofilms that absorbed IR radiation near 1,650 cm(-1) (amide I), 1,550 cm(-1) (amide II), 1,240 cm(-1) (P==O stretching, C---O---C stretching, and/or amide III vibrations), 1,100 to 1,000 cm(-1) (C---OH and P---O stretching) 1,450 cm(-1), and 1,400 cm(-1). The FRD1 biofilms produced spectra with an increase in relative absorbance at 1,060 cm(-1) (C---OH stretching of alginate) and 1,250 cm(-1) (C---O stretching of the O-acetyl group in alginate), as compared to biofilms of nonmucoid mutant strains. Dehydration of an 88-h FRD1 biofilm revealed other IR bands that were also found in the spectrum of purified FRD1 alginate. These results provide evidence that alginate was present within the FRD1 biofilms and at greater relative concentrations at depths exceeding 1 micrometer, the analysis range for the ATR/FT-IR technique. After 88 h, biofilms of the nonmucoid strains produced amide II absorbances that were six to eight times as intense as those of the mucoid FRD1 parent strain. However, the cell densities in biofilms were similar, suggesting that FRD1 formed biofilms with most cells at depths that exceeded the analysis range of the ATR/FT-IR technique. SCLM analysis confirmed this result, demonstrating that nonmucoid strains formed densely packed biofilms that were generally less than 6 micrometer in depth. In contrast, FRD1 produced microcolonies that were approximately 40 micrometer in depth. An algJ mutant strain that produced alginate lacking O-acetyl groups gave an amide II signal approximately fivefold weaker than that of FRD1 and produced small microcolonies. After 44 h, the algJ mutant switched to the nonmucoid phenotype and formed uniform biofilms, similar to biofilms produced by the nonmucoid strains. These results demonstrate that alginate, although not required for P. aeruginosa biofilm development, plays a role in the biofilm structure and may act as intercellular material, required for formation of thicker three-dimensional biofilms. The results also demonstrate the importance of alginate O acetylation in P. aeruginosa biofilm architecture.

Acetylation↗

Normal light response, photoreceptor integrity, and rhodopsin dephosphorylation in mice lacking both protein phosphatases with EF hands (PPEF-1 and PPEF-2).

Rhodopsin dephosphorylation in Drosophila is a calcium-dependent process that appears to be catalyzed by the protein product of the rdgC gene. Two vertebrate rdgC homologs, PPEF-1 and PPEF-2, have been identified. PPEF-1 transcripts are present at low levels in the retina, while PPEF-2 transcripts and PPEF-2 protein are abundant in photoreceptors. To determine if PPEF-2 alone or in combination with PPEF-1 plays a role in rhodopsin dephosphorylation and to determine if retinal degeneration accompanies mutation of PPEF-1 and/or PPEF-2, we have produced mice carrying targeted disruptions in the PPEF-1 and PPEF-2 genes. Loss of either or both PPEFs has little or no effect on rod function, as mice lacking both PPEF-1 and PPEF-2 show little or no changes in the electroretinogram and PPEF-2-/- mice show normal single-cell responses to light in suction pipette recordings. Light-dependent rhodopsin phosphorylation and dephosphorylation are also normal or nearly normal as determined by (i) immunostaining of PPEF-2-/- retinas with the phosphorhodopsin-specific antibody RT-97 and (ii) mass spectrometry of C-terminal rhodopsin peptides from mice lacking both PPEF-1 and PPEF-2. Finally, PPEF-2-/- retinas show normal histology at 1 year of age, and retinas from mice lacking both PPEF-1 and PPEF-2 show normal histology at 3 months of age, the latest time examined. These data indicate that, in contrast to loss of rdgC function in Drosophila, elimination of PPEF function does not cause retinal degeneration in vertebrates.

Alleles↗

Case-control study of the health of those looked after by local authorities.

AIMS: To assess the health needs and provision of health care to school age children in local authority care. METHODS: A total of 142 children aged 5 to 16 in local authority care, and 119 controls matched by age and sex were studied. Main outcome measures were routine health care, physical, emotional, and behavioural health, health threatening and antisocial behaviour, and health promotion. RESULTS: Compared with children at home, those looked after by local authorities were significantly more likely to: experience changes in general practitioner; have incomplete immunisations; receive inadequate dental care; suffer from anxieties and difficulties in interpersonal relationships; wet the bed; smoke; use illegal drugs; and have been cautioned by police or charged with a criminal offence. They also tend to receive less health education. They were significantly more likely to have had a recent hearing or eye sight test, and reported significantly less physical ill health overall. CONCLUSIONS: The overall health care of children who have been established in care for more than six months is significantly worse than for those living in their own homes, particularly with regard to emotional and behavioural health, and health promotion. In contrast to uncontrolled observational studies we have not found evidence of problems with the physical health of these children.

Adolescent↗

Ulcer associated cell lineage glands expressing trefoil peptide genes are induced by chronic ulceration in ileal pouch mucosa.

BACKGROUND: Chronic ulcerative conditions in the gastrointestinal tract result in the appearance of the ulcer associated cell lineage (UACL). The glands of this new cell lineage secrete epidermal growth factor, transforming growth factor alpha, and the trefoil factor family (TFF) peptides, which are known to participate in repair processes. Pouchitis is the most frequent complication of ileal pouch-anal anastomosis. AIM: Our aim was to determine whether the mucosal ulceration present in pouchitis can induce the development of UACL glands. METHODS: Biopsies from ileal pouches with pouchitis (n=10), healthy pouches (n=5), and normal terminal ileum (n=5) were studied. Expression of TFF mRNA was assessed by in situ hybridisation. TFF1 and TFF2 proteins were localised by immunochemistry. RESULTS: UACL glands containing TFF1 and TFF2 were observed in six patients with pouchitis. In some glands, there was TFF3 mRNA as has been reported for Crohn's UACL. None of the biopsies from ileal reservoirs without pouchitis showed UACL glands (p<0.05). Neither TFF1 nor TFF2 expression was detected in ileal reservoirs without pouchitis. CONCLUSION: UACL glands arise de novo in ileal pouch mucosa of patients with pouchitis and express all three TFF peptide genes. Chronic inflammation alone, present in healthy pouches, is not enough to stimulate the growth of the UACL, and additional stimuli consequent on ulceration may be needed.

Autoradiography↗

Formal education programmes for senior house officers: comparison of experience in three hospital specialties.

This study was designed to compare the attendance rate of senior house officers (SHOs) in three specialties at formal educational events, examine experiences of protected time, use of educational objectives, and perceived barriers to attendance and evaluate differences found in the context of variations in training practice within each specialty. A quantitative questionnaire survey was completed by Trent region SHOs in obstetrics and gynaecology, general medicine, and accident and emergency posts. An independent researcher visited a selection of educational programme events over a two month span, recorded attendances, and administered the questionnaire. Attendance rates ranged from 40.8% of those in obstetrics and gynaecology jobs to 55.4% of those in accident and emergency jobs. The questionnaire findings found that service commitments were a major obstacle to attendance for the majority of those in obstetrics and gynaecology and general medicine jobs, while relatively few of the accident and emergency SHOs specified any barriers. SHOs in accident and emergency jobs had significantly more protected time for education and found educational objectives to be more widely used by senior staff. The findings suggest that the planned integration of formal education programmes with appropriate working pattern systems--in this case full shifts within accident and emergency departments--will result in SHOs receiving a better deal in terms of provision and structure of education.

Education, Medical↗

A randomised controlled trial of four weeks versus seven weeks of pulmonary rehabilitation in chronic obstructive pulmonary disease.

BACKGROUND: Pulmonary rehabilitation programmes have been shown to improve both exercise tolerance and health status in patients with chronic obstructive pulmonary disease (COPD). The optimal duration for a pulmonary rehabilitation programme is, however, unknown. To assess whether the current pulmonary rehabilitation programme could be shortened a randomised controlled trial was conducted in 44 patients with COPD who were allocated to either a seven week or a four week course. METHODS: Patients were randomised to either our standard seven week twice weekly outpatient based programme or a comparable but shortened four week course. They were assessed at baseline and at completion by the Chronic Respiratory Questionnaire (CRQ), the Breathing Problems Questionnaire (BPQ), the incremental shuttle walking test (SWT), and the treadmill endurance test (TET). RESULTS: Twenty one patients (61% men) of mean (SD) age 68 (9.2) years and forced expiratory volume in one second ( FEV(1)) 1.08 (0.4) l completed a conventional seven week course and 23 (67% men) of mean (SD) age 69 (8.8) years and FEV(1) 1.03 (0.3) l completed a shortened four week course. Patients who completed the seven week rehabilitation programme had greater improvements in all outcome measures than those undertaking the four week course. These differences reached clinical and statistical significance for the total CRQ score, which was the primary outcome variable (mean difference (95% confidence intervals (CI) of difference) -0.61(-0.15 to -1.08), p<0.05), and the CRQ domains of dyspnoea (-0.80 (95% CI -0.13 to -1.48), p<0.05), emotion (-0.89 (95% CI -0.33 to -1.45), p<0.005), and mastery (-0.84 (95% CI -0.10 to -1.58), p<0.05). There were also trends towards greater improvements in exercise assessments in the seven week group but the differences did not reach statistical significance (SWT: mean difference -16.9 (95% CI 24.8 to -58.6), p=0.41; TET: geometric mean difference -1.21 (95% CI -0.60 to -2.47), p=0.56). CONCLUSIONS: A seven week course of pulmonary rehabilitation provides greater benefits to patients than a four week course in terms of improvements in health status. Larger prospective studies are required to determine the optimal duration of a pulmonary rehabilitation programme.

Aged↗

Effects of maturation and acute hypoxia on receptor-IP(3) coupling in ovine common carotid arteries.

Whereas previous studies have established that many mechanisms mediating pharmacomechanical coupling are subject to regulation, evidence of physiological regulation of the coupling efficiency between receptor activation and second-messenger production is scarce. The present studies address the hypothesis that acute hypoxia and maturation can influence the mass of second-messenger production for each activated agonist-bound receptor ("receptor gain"). For this assessment, receptor density and agonist affinity values were used to calculate 5-hydroxytryptamine (5-HT) concentrations that would produce standardized numbers of bound receptors (8.5 fmol/mg protein) in each experimental group and thus minimize effects of age or hypoxia on receptor density or agonist affinity. After 3 min of exposure to these 5-HT concentrations, normoxic magnitudes of contraction were similar (as %potassium maxima) in fetal (50 +/- 14%) and adult (40 +/- 9%) arteries, but hypoxia (PO(2) approximately 9--12 Torr for 30 min) depressed contractile tensions with a significantly different time course and magnitude in fetal (30 +/- 10%) and adult (17 +/- 11%) arteries (P < 0.05). Basal inositol 1,4,5-trisphosphate (IP(3)) values (in pmol/mg protein) were significantly greater in fetal (94 +/- 16) than in adult (44 +/- 6) arteries, and integrated areas above baseline for the IP(3) time courses (in nmol-s/mg protein) were significantly greater in fetal than in adult arteries both in normoxic (14.3 +/- 1.8 vs. 9.1 +/- 1.6) and hypoxic (15.0 +/- 2.1 vs. 8.6 +/- 1.2) conditions (P < 0.05). Hypoxia altered the IP(3) time courses both in the fetus and the adult but had no significant effect on IP(3 )mobilization or receptor gain. These data demonstrate that for the 5-HT(2a) receptor predominant in this preparation, receptor gain can be experimentally determined, is not influenced by acute hypoxia, but is greater in fetal than in adult ovine carotid arteries.

Animals↗

Genetic changes in contralateral bronchioloalveolar carcinomas of the lung.

OBJECTIVE: The pattern of metastases and recurrence of bronchioloalveolar carcinoma (BAC) differs from adenocarcinoma of the lung, occurring more frequently within the lung without extrapulmonary involvement. Analyses of genetic differences of contralateral BACs may help to explain these clinical differences. METHODS: We compared paired tumors from 5 patients with contralateral metachronous BACs for loss of heterozygosity (LOH) on 6 chromosomal arms (2q, 3p, 5q, 9p, 13q and 17p) and mutational analysis of p53 and K-ras. RESULTS: Two patients, patients 1 and 2, had discordant patterns of LOH on 2 and 3 of the chromosome arms, respectively. In addition, patient 2 had a detectable K-ras mutation in his initial tumor but not in his second. These results suggest that in patients 1 and 2, the contralateral tumors were clonally unrelated. Patient 3 had no mutations in the K-ras or p53 gene and no LOH on any of the 5 informative chromosome arms. Patient 4 had LOH of 9p and mutated K-ras in both the first and the second tumor, with a mutation in the p53 gene in the first but not in the second tumor. Patient 5 had LOH of 17p and the same p53 mutations in both the first and the second tumor, with a mutation of K-ras in the first tumor but not in the second. CONCLUSIONS: The preponderance of evidence suggests that in patients 3, 4 and 5, the paired tumors were clonally related. The different patterns of LOH and mutations in clinically similar contralateral metachronous BACs provide evidence of genetic heterogeneity in the tumors of this patient group.

Adenocarcinoma, Bronchiolo-Alveolar↗

Inducible nuclear translocation of a STAT protein in Dictyostelium prespore cells: implications for morphogenesis and cell-type regulation.

Dd-STATa, the Dictyostelium STAT (signal transducer and activator of transcription) protein, is selectively localised in the nuclei of a small subset of prestalk cells located in the slug tip. Injection of cAMP into the extracellular spaces in the rear of the slug induces rapid nuclear translocation of a Dd-GFP:STATa fusion protein in prespore cells surrounding the site of injection. This suggests that cAMP signals that emanate from the tip direct the localised nuclear accumulation of Dd-STATa. It also shows that prespore cells are competent to respond to cAMP, by Dd-STATa activation, and it implies that cAMP signalling is in some way limiting in the rear of the slug. Co-injection of a specific inhibitor of the cAR1 serpentine cAMP receptor almost completely prevents the cAMP-induced nuclear translocation, showing that most or all of the cAMP signal is transduced by cAR1. Dd-GFP:STATa also rapidly translocates into the nuclei of cells adjoining the front and back cut edges when a slug is bisected. Less severe mechanical disturbances, such as pricking the rear of a slug with an unfilled micropipette, also cause a more limited nuclear translocation of Dd-GFP:STATa. We propose that these signalling events form part of a repair mechanism that is activated when the migrating slug suffers mechanical damage.

Animals↗

Nurse referrals of children to social services.

This literature review examines current referral systems and processes used by community nurses when making referrals of children in need and children in need of protection to social services departments. The problems surrounding definitions of need, children in need and children in need of protection are considered. The ambiguity of the language used and the difficulties encountered by community nursing staff in trying to identify criteria and thresholds for referral are highlighted. The review focuses on research exploring the assessment and referral processes used by community nurse, in particular by health visitors, and draws attention to the lack of research concerning these areas. Government recognition of the problems encountered by agencies working in this field is acknowledged in recent Department of Health publications.

Child↗

Photodynamic therapy for patients with advanced non-small-cell carcinoma of the lung.

Patients with advanced non-small-cell lung carcinoma (NSCLC) have poor prognoses and experience negative sequelae of disease. Patients often suffer from dyspnea and/or hemoptysis, with overall pulmonary compromise. Patients with advanced, inoperable disease have limited options for treatment. This study summarizes our early experience and findings using photodynamic therapy (PDT) as an effective modality in the palliation of hemoptysis, dyspnea, and physical airway obstruction in cases of inoperable lung cancer. A retrospective review was conducted for the first 10 patients diagnosed with stage III/IV obstructive NSCLC who underwent PDT at our institution. Endobronchial lesions were identified by bronchoscopy. Treatments were initiated 48 hours after intravenous injection of 2 mg/kg of the photosensitizing agent porfimer sodium (Photofrin, QLT PhotoTherapeutics, Vancouver, BC). The porfimer sodium was then activated by illumination with a 630 nm wavelength light using a Coherent argon ion laser through a flexible bronchoscope. Repeated bronchoscopies were performed 1-3 days following initial PDT for evaluation and airway debridement. In 8 cases, a second treatment of PDT was administered within 72 hours of the first injection. One patient received a third treatment several months later. Three patients also received endobronchial stents after PDT. Overall, all 10 patients responded to PDT. Physical airway obstruction was reduced in all patients, with a noted improvement in bronchoscopic luminal diameter. Acute hemoptysis resolved in all 7 symptomatic patients. Median survival was 5.5 months post-PDT, while median survival postdiagnosis was 10.5 months. Three patients are alive at the time of this review at 5-21 months following therapy. Patients with unresectable late-stage NSCLC have few options for treatment. Our early experience with PDT indicates effective relief of hemoptysis, dyspnea, and airway obstruction and improves their quality of life.

Journal Article↗

Breakthrough bargaining.

Unspoken, subtle parts of a bargaining process--also known as the shadow negotiation--can set the tone for a successful negotiation. Deborah Kolb and Judith Williams, whose book The Shadow Negotiation was the starting point for this article, say there are three strategies businesspeople can use to guide these hidden interactions. Power moves are used when two negotiating parties hold unequal power--for instance, subordinates and bosses; new and existing employees; and people of different races, ages, or genders. These strategies, such as casting the status quo in an unfavorable light, can help parties realize that they must negotiate: they will be better off if they do and worse off if they don't. Process moves affect how negotiation issues are received by both sides in the process, even though they do not address substantive issues. Working outside of the actual bargaining process, one party can suggest ideas or marshal support that can shape the agenda and influence how others view the negotiation. Appreciative moves alter the tone or atmosphere so that a more collaborative exchange is possible. They shift the dynamics of the shadow negotiation away from the adversarial--helping parties to save face--and thus build trust and encourage dialogue. These strategic moves don't guarantee that all bargainers will walk away winners, but they help to get stalled negotiations moving--out of the dark of unspoken power plays and into the light of true dialogue.

Commerce↗