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Biomedical subjects

W Richards

Publications and source records attributed to W Richards.

At least 37 records · Page 2Linked to original sources
PubMed1998

Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients: clinical implications.

PURPOSE: To retrospectively construct a comprehensive multivariate model of cancer recurrence and to design a molecular pathologic substaging system in stage I non-small-cell lung cancer (NSCLC). METHODS: All patients with stage I NSCLC resected at Brigham and Women's Hospital (Boston, MA) between 1984 and 1992 with adequate clinical follow-up were studied. The importance of three demographic characteristics, surgical extent, 11 pathologic features, and seven molecular factors on cancer-free survival was examined. RESULTS: Two hundred forty-four patients were studied, with 25 noncancer deaths and 80 patients with recurrent disease. Significant univariate predictors (P < .05) of cancer recurrence were age older than 60 years, male sex, wedge resection, World Health Organization (WHO) adenocarcinoma subtype solid tumor with mucin, lymphatic invasion, and p53 expression. Multivariate analysis identified nine independent predictors of recurrence: solid tumor with mucin, a wedge resection, tumor diameter of 4 cm or greater, lymphatic invasion, age older than 60 years, male sex, p53 expression, K-ras codon 12 mutation, and absence of H-ras p21 expression. Multivariate cancer-free survival (CFS) analysis in the 180 patients who underwent lobectomy or pneumonectomy led to the elimination of sex and age, which left six independent factors. CONCLUSION: Lobectomy or pneumonectomy should be performed in stage I NSCLC. Using the six independent factors for recurrent disease, we propose a pathologic molecular substaging system. Patients with two factors or less are graded Ia, with a 5-year CFS rate of 87%; those with three factors are graded Ib, with a 5-year CFS rate of 58%; and those with four factors or more are graded Ic, with a 5-year CFS rate of 21%.

Adult↗
PubMed1998

Mesenteric afferent sensitivity to cholecystokinin and 5-hydroxytryptamine.

The present electrophysiological investigation examines the effect of CCK and 5-hydroxytryptamine on gastrointestinal afferent fibre discharge. 5-HT markedly stimulated mesenteric afferents. The response was transient (< 10s) and mediated by 5-HT3 receptors as demonstrated by the action of 2-methyl-5-HT and antagonism by granisetron. CCK was also a potent stimulus to mesenteric afferents causing a long-lasting (> 30s) increase in excitability. The response to CCK was mediated via the CCKA receptor as shown by the antagonistic action of devazepide. At doses of granisetron and devazepide which completely block the response to exogenous 5-HT and CCK, the afferent fibres still responded to both mechanical and chemical stimulation of the mucosa. Thus products of enteroendocrine cells can have profound effects on mucosal afferent sensitivity but do not play an obligatory role in afferent signal transduction.

Animals↗
PubMed1996

Sensitivity of vagal mucosal afferents to cholecystokinin and its role in afferent signal transduction in the rat.

1. Extracellular recordings from rat mesenteric paravascular nerve bundles were made in order to characterize the responses of different populations of afferents supplying the small intestine to intravenous cholecystokinin (CCK; in the form of sulphated CCK8). 2. Approximately 70% of mesenteric nerve bundles contained CCK-sensitive afferent fibres. Responsive afferents had low spontaneous discharge (1.6 +/- 0.3 impulses s-1) and showed a 14-fold increase in firing at the peak of the response to 50 pmol CCK with the overall response lasting several minutes. The onset of the response occurred after a latency of (3.9 +/- 0.1 s) following i.v. administration of CCK, which corresponds largely to the circulation delay in these animals. The threshold dose of CCK was < 5 pmol. 3. The response to 100 pmol CCK was completely abolished by devazepide (0.5 mg kg-1) and by chronic subdiaphragmatic vagotomy performed 10-14 days prior to experimentation, indicating that CCK sensitivity was via CCKA receptors and exclusively mediated via vagal afferents rather than splanchnic or enteric afferents. 4. Evidence that CCK-sensitive afferents had mucosal receptive fields was indicated by the lack of any response to luminal distension and the sensitivity of the CCK response to luminal anaesthesia. Furthermore, CCK-sensitive afferents responded to luminal hydrochloric acid (50 mM) in a slowly adapting manner. The response to acid was significantly reduced (P < 0.005), but not abolished, by devazepide at a time when the response to exogenous CCK had been completely eliminated. 5. The exquisite sensitivity of some vagal mucosal afferents to CCK suggests that they may play a physiological role in the reflex and behavioural consequences of CCK release from the small intestine, possibly acting in a paracrine fashion. However, this sensitivity to CCK represents only one aspect of the broad chemosensitivity of these mucosal afferents and is not an obligatory component of the signal transduction pathway.

Afferent Pathways↗
PubMed1996

Attentional frames, frame curves and figural boundaries: the inside/outside dilemma.

Attended and unattended regions of the image array are viewed often as binary complements to one another, with a well-defined boundary between them. A simple experiment shows otherwise: if the contour of a simple convex shape is perturbed to create a distinctive texture, it is typically the outside of the contour that provides the basis for similarity judgement, not the inside. The introduction of the appropriate task, however, can make the inside part of the contour become more salient. A similar result occurs for concave shapes, such as a C, where notions of containment are not easily specified. These observations suggest that figure boundaries are difficult to define objectively and that the setting of an attentional reference frame plays a key role in object description. We propose that this frame is part of a virtual, transparent blackboard or "clearboard", bound to the scene, not to the image.

Attention↗
PubMed1996

Oral ill-health in a general dental practice in south Wales.

PURPOSE OF STUDY: To establish and report oral health status data by measuring social impact in conjunction with clinical impact. Oral health status encompassed functional, experiential and psychosocial impact measures in addition to clinical measures. POPULATION STUDIED: Registered dental patients over 18 years of age attending for routine care at a general dental practice. METHOD: A self-complete questionnaire based on the work of Locker was administered to consecutive patients as an ongoing survey evaluating service delivery and outcome. In addition clinical data were taken from the clinical examination and patient record card. Between December 1994 and June 1995, 997 patients provided a stratified sample representing the population studied. FINDINGS: 96.7% were dentate leaving only 3.3% edentulous. A total of 15.1% were unable to chew one or more foods, 43.3% reported oral or facial pain in the previous four weeks and 62.9% experienced one or more other symptoms. Problems with eating and communication/social interaction were reported by 47.5%, 45% worried a great deal about their oral health and 26.3% were dissatisfied with some aspect of their oral health status. CONCLUSION: There is merit in using social impact measures in conjunction with clinical impact measures. Clinical outcome measures exceed national oral health targets set for 2002 by the Welsh Office. Social impact is weighted differently in different groups within the practice; for the elderly edentulous physical disability is the main burden whereas discomfort is the main problem for the younger dentate patients. Regular attenders benefit from regular care.

Adult↗
PubMed1995

Reciprocal Rb inactivation and p16INK4 expression in primary lung cancers and cell lines.

cdk4-mediated phosphorylation of the retinoblastoma susceptibility protein (Rb) is stimulated by cyclin D1, an oncogene, and inhibited by p16, a candidate tumor suppressor. We examined these proteins in non-small cell lung cancer (NSCLC), which is predominantly Rb positive, and small cell lung cancer (SCLC), which is Rb negative. Most NSCLC and SCLC resection specimens and cell lines overexpress cyclin D1 (indicating that cyclin D1 overexpression and Rb inactivation can coexist in SCLC). However, 9 of 9 Rb-positive NSCLC cell lines have absent or low p16, while an Rb-negative NSCLC line and 5 of 5 SCLC cell lines have high levels of p16. In primary resection specimens, p16 was undetectable in 18 of 27 NSCLC samples and abundant in 4 of 5 SCLC samples. Our data confirm the predicted reciprocity between Rb inactivation and p16 expression in a common human malignancy and define differential p16 expression as a fundamental distinction between NSCLC and SCLC.

Blotting, Southern↗
PubMed1995

Trajectory mapping: a new nonmetric scaling technique.

Trajectory mapping is a new scaling technique designed to recover the parameterizations, axes, and paths used to traverse a feature space. Unlike with multidimensional scaling, there is no assumption that the space is homogeneous or metric. Although some metric ordering information is obtained with trajectory mapping, the main output is the feature parameterizations that partition the given domain of object samples into different categories. After an introductory example, the technique is further illustrated by using first a set of colors and then a collection of textures.

Color Perception↗
PubMed1994

The termination of a randomized clinical trial for poor Hispanic children.

OBJECTIVE: To conduct a randomized clinical trial of the Spanish version of an educational program designed to be an adjuvant to adequate medical care of children with asthma. DESIGN: Randomized, clinical trial. SETTING: Los Angeles County, Calif. PARTICIPANTS: One hundred thirty-eight Hispanic children, ages 7 to 12 years, from disadvantaged families. All had used emergency facilities of major local hospitals in the previous year. MEASUREMENT/MAIN RESULTS: As the study proceeded, it became apparent that subjects were receiving inadequate medical and nursing care and had numerous barriers to applying knowledge and self-care skills gained from the program. Realizing this, we considered it unethical to allow the control children to suffer for the duration of the trial (1 year). Therefore, all children received "adequate" care from the research staff, and the randomized clinical trial, as originally designed, was ended. The emergency department/hospital use by both groups was significantly reduced compared with previous experience. CONCLUSION: Those researchers conducting randomized trials involving poor children should be aware of the potential ethical problems inherent in such ventures.

Asthma↗
PubMed1994

Chaos in percepts?

Multistability in perceptual tasks has suggested that the mechanisms underlying our percepts might be modeled as nonlinear, deterministic systems that exhibit chaotic behavior. We present evidence supporting this view, obtaining an estimate of 3.5 for the dimensionality of such a system. A surprising result is that this estimate applies for a rather diverse range of perceptual tasks.

Eye Movements↗
PubMed1994

Sinusitis in status asthmaticus.

The relationship between sinusitis and status asthmaticus (SA) remains obscure. The purposes of this study were to determine the prevalence of abnormal sinus radiographs (SXRs) and investigate possible risk factors among unselected children admitted with SA. Eighty-eight patients over 2 years of age (range 2 to 16 years) consecutively admitted with SA were studied. The principal investigator, blinded to SXR findings, interviewed and examined the patients with respect to 10 physical parameters and 14 historical parameters. Two staff radiologists, blinded to the clinical findings, interpreted the SXRs. Relationship of historical and physical findings with positive SXRs was determined by statistical analysis. Twenty-seven percent of patients were found to have abnormal SXRs, manifesting two thirds or greater opacification of the sinuses. The mean age, sex, and race of patients with abnormal SXRs was not significantly different from those with normal films. A history of two or more admissions per year for SA, and, in children under 5 years of age, a history of chronic otitis media, and the physical finding of otitis media were significantly more frequent among patients with abnormal SXRs. Although not found to be statistically significant, a history of sinusitis and cough occurred more frequently in association with abnormal SXRs.

Adolescent↗
PubMed1994

Relaxation of human bronchial smooth muscle by S-nitrosothiols in vitro.

S-Nitrosothiols (RS-NO) relax tracheal smooth muscle from a variety of animal species, and may have physiological relevance. We therefore studied their effects on human bronchial smooth muscle. S-Nitroso adducts of glutathione, cysteine, N-acetylcysteine and bovine serum albumin relaxed tissues contracted with methacholine with mean IC50 +/- S.E.M. of 3.3 (+/- 14), 22 (+/- 45), 25 (+/- 22) and 36 (+/- 7.1) microM, respectively; they were more potent as inhibitory agonists than the corresponding reduced thiol, NaNO2, or theophylline, but less potent than isoproterenol (P < .001). Despite large differences in their molecular weights and dissociation kinetics, the IC50 of these RS-NO did not differ significantly from one another, from nitric oxide (NO.) or from sodium nitroprusside. Consistent with the role of cyclic GMP (cGMP) in mediating relaxation responses, S-nitroso-N-acetyl cysteine (S-NO-AC) (100 microM) increased tissue cGMP levels 4-fold, and 8-bromo-cGMP caused modest tissue relaxation which was potentiated by the phosphodiesterase inhibitor, dipyridamole (1 microM). However, the guanylyl cyclase inhibitors, methylene blue (100 microM) and LY 83583 (50 microM), failed to modify the relaxation response to S-NO-AC (sodium nitroprusside and NO.), while altering the accumulation of cGMP. Further, hemoglobin (100 microM) failed to inhibit relaxation by S-NO-AC.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchi↗
PubMed1993

Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma.

PURPOSE: We studied a multimodality approach using extrapleural pneumonectomy, chemotherapy, and radiotherapy in patients with malignant pleural mesothelioma. PATIENTS AND METHODS: From 1980 to 1992, 52 selected patients, underwent treatment. Median age was 53 years (range, 33 to 69). Initial patient evaluation was performed by a multimodality team. Pathologic diagnosis was reviewed and confirmed before therapy. Patients with no medical contraindication and potentially resectable mesothelioma on computed tomography (CT) (magnetic resonance imaging [MRI] when it became available) received extrapleural pneumonectomy, cyclophosphamide, doxorubicin, and cisplatin (CAP) chemotherapy, and radiotherapy. RESULTS: Perioperative morbidity and mortality rates were 17% and 5.8%, respectively. The overall median survival duration is 16 months (range, 1 month to 8 years). The 32 patients with epithelial histologic variant had 1-, 2-, and 3-year survival rates of 77%, 50%, and 42%, respectively. Patients with mixed and sarcomatous cell disease had 1- and 2-year survival rates of 45% and 7.5%; no patient lived longer than 25 months (P < .01). At resection, positive regional mediastinal lymph nodes were found in 13. Positive lymph nodes were associated with poorer survival than were negative nodes (P < .01). Patients with epithelial variant and negative mediastinal lymph nodes had a survival rate of 45% at 5 years. CONCLUSION: Multimodality therapy including extrapleural pneumonectomy has acceptable morbidity and mortality for selected patients. Prolonged survival occurred in patients with epithelial histologic variant and negative mediastinal lymph nodes. These data provide a rationale for a revised staging system for malignant pleural mesothelioma; furthermore, they permit stratification of patients into groups likely to benefit from aggressive multimodality treatment.

Adult↗
PubMed1993

A review of the results of laparoscopic versus open appendectomy.

Proponents of laparoscopic appendectomy emphasize the advantages of laparoscopic operation--decreased hospitalization, paralytic ileus, postoperative pain and wound complications, including infection. This study compared open laparoscopic appendectomy with laparoscopic appendectomy. To compare the two techniques, patients undergoing laparoscopic appendectomy at four hospitals were compared with patients undergoing open appendectomy during a six month period. Excluded were incidental appendectomies and patients with perforated appendicitis. An equal number of pediatric patients undergoing laparoscopic and open procedures were included in the analysis to avoid bias, because most of the laparoscopic appendectomies were performed in the adult patient population (age of more than 16 years). A University Medical Center, a Veterans Administration and two community hospitals were the settings. Patients undergoing laparoscopic appendectomy (n = 54) had an average age of 25.7 +/- 1.5 (range of six to 59 years). These patients were compared with 121 patients undergoing open appendectomy whose average age was 23.7 +/- 1.8 (range of three to 83 years). The race and gender distribution were similar in the two groups. Traditional open appendectomy was compared with a group of patients undergoing laparoscopic appendectomy. Variables evaluated were operating room time, number of patients who reported nausea, days until patient tolerated a regular diet, days of hospitalization, postoperative pain medication and wound infection rate. Results are expressed as the mean plus or minus standard error of the mean. Analysis of variance was used to compute continuous variables and Fischer's exact test was used for discrete variables. The laparoscopic approach was attempted in 61 patients and completed in 54 patients. Open appendectomy was performed upon 121 patients. Nineteen patients (18 who underwent open operation and one patient who underwent laparoscopic operation) were excluded from further analysis because of perforated appendicitis. The open procedure took less time (p < 0.05). However, there were more wound infections than in the laparoscopic group (seven of 103 versus zero of 53; p = 0.09). Patients with acute appendicitis recuperated more quickly from the laparoscopic procedure, as evidenced by the time until eating regular diet, period of hospitalization, incidence of nausea and pain medications on postoperative day one (p < 0.05). The absence of wound infections after laparoscopic appendectomy can be attributed to the practice of placing the appendix in a sterile bag or into the trocar sleeve before removal from the abdomen. Laparoscopic appendectomy reduces the period of hospitalization, postoperative ileus, nausea and postoperative pain in patients with acute appendicitis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗