What's best for the patient?
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Decision Making↗
Biomedical subjects
D Waller
Publications and source records attributed to D Waller.
Towards a biological staging model for operable non-small cell lung cancer.
Non-small cell lung cancer is the most common cause of cancer-related death in North America and Europe. Despite improvements in the diagnosis and treatment of the disease the prognosis remains poor, the overall 5-year survival being 4-14%. An increased understanding of the molecular biology of the disease may identify novel targets for drug development. We evaluated epidermal growth factor receptor (EGFR), HER-2/neu, matrix metalloproteinase (MMP)-2, MMP-9, p53 and bcl-2 expression and microvessel density (MVD) in patients who underwent surgery with curative intent in our department between 1991 and 1996. Co-expression of EGFR/MMP-9, MVD and bcl-2 were found to be independent prognostic variables, which allowed prediction of patient outcome independent of surgical stage. Other prognostic factors identified in our series were gender, surgical stage, platelet count, extent of necrosis, the hypoxia marker carbonic anhydrase-9 and beta-catenin. In collaboration with groups in Oxford and Greece, we were also able to establish the angiogenic growth factors vascular endothelial growth factor and platelet-derived endothelial growth factor as prognostic variables. The inter-relationships between these factors are currently being examined in an expanded patient series. Through this work we hope to be able to construct an integrated biological prognostic model which can be tested in prospective studies. This work has identified several potential targets for novel therapeutic agents currently in development.
Adult↗
Spatial representations of virtual mazes: the role of visual fidelity and individual differences.
Twenty-four people learned three versions of a room-sized maze: a wire-frame desktop virtual environment (VE), a normal surface-rendered desktop VE, and a real-world maze. Differences among the mental representations formed from each environment were measured with pointing and distance estimation tasks in a real-world version of each maze. People were more accurate at pointing after having learned the real and wire-frame VE maze than the surface-rendered VE maze; however, this effect was small compared with the effect of individual differences. Differences in gender, spatial ability, and prior computer experience were significantly related to the ability to acquire spatial information from the desktop VE. There was a high correlation between spatial knowledge when it was measured in the VE and spatial knowledge measured in the real world. Actual or potential applications include the design of effective VE training systems.
Adolescent↗
Individual differences in spatial learning from computer-simulated environments.
A multivariate study examined relationships between the following factors: paper-and-pencil assessments of verbal and spatial ability, ability to form an accurate spatial representation of a large real-world environment, gender, computer attitudes and experience, proficiency with the navigational interface of a virtual environment (VE), and the ability to acquire and transfer spatial knowledge from a VE. Psychometrically assessed spatial ability and proficiency with the navigational interface were found to make substantial contributions to individual differences in the ability to acquire spatial information from a VE. Gender influenced many VE-related tasks, primarily through its relationship with interface proficiency and spatial ability. Measures of spatial knowledge of a VE maze were highly predictive of subsequent performance in a similar real-world maze, suggesting that VEs can be useful for training people about real-world spaces.
Adult↗
The paradox of voluntary motherhood.
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Abortion, Induced↗
Study of the vaginal tolerance to Acidform, an acid-buffering, bioadhesive gel.
Vaginal tolerance tests were performed with a new potential microbicidal and spermicidal product, an acid-buffering vaginal gel (Acidform) without or with nonoxynol-9 (N-9). The potential advantages over other vaginal products include keeping a low pH, decrease of the irritating effect of N-9 on the cervix or vaginal mucosa associated with greater retention of the product after application, and decreasing "messiness" as compared to other vaginal products. Three groups of six women were admitted and randomly assigned to use Acidform with 0%, 2.5%, and 5% N-9. Colposcopic evaluation for vulvar, vaginal, and cervical signs of irritation was performed and photographs were taken, following a specific World Health Organization protocol, at time 0, and after 24 h and 6 days of application of the gel. No irritation or symptom was reported by users of Acidform without N-9. A generalized and intense erythema in cervix was observed in 10 of 12 Acidform/N-9 users and abrasion occurred in nine of them. Vulvar irritation was seen in seven of these 10 volunteers. N-9 concentration in the gel (2.5% or 5.0%) was not related to the findings. No ulcer, exulceration, or de-epithelialization was observed. Acidform without N-9 was well tolerated by volunteers, but it was unable to protect the cervix, vagina, and vulva from the N-9 effects.
Adult↗
Cardiomyoplasty after implantation of a pacemaker and cardioverter/defibrillator.
Presently, a combination of two surgical methods improves the survival of patients with advanced ventricular dysfunction: implantable cardioverter/defibrillator implantation (which prevents sudden cardiac death) and cardiomyoplasty (which prevents further dilatation of the heart and provides additional cardiac assistance). We report the clinical course of a patient who had cardiomyoplasty after cardioverter/defibrillator implantation and pacemaker insertion. It is a rare case in which three different devices cardioverter/defibrillator, pacemaker, and cardiomyostimulator) are functioning together without crosstalk.
Adult↗
Is there a role for video-assisted thoracoscopy in the staging of non-small cell lung cancer?
OBJECTIVE: To evaluate the role of video-assisted thoracoscopy (VAT) in the staging of non-small cell lung cancer (NSCLC). METHODS: In 30 patients (18 male, 12 female, median age 62 (50-78) years) VAT was used to assess the operability of NSCLC in cases where doubt existed after conventional staging investigations had been performed. RESULTS: VAT was used to assess direct tumour invasion of adjacent organs in 17 patients (mediastinal invasion in 14 and chest wall invasion in 3 patients). In 4 patients with limited respiratory reserve, VAT confirmed the need only for lobectomy prior to thoracotomy. Mediastinal lymph node biopsy was performed in 5 patients with significant (> 1.5 cm) lymphadenopathy on CT scan. VAT was also used to assess bilateral lesions in 4 patients with suspected synchronous tumours. Conversion to thoracotomy was necessary in 4 patients for technical reasons. Successful resection was possible in 17 of the remaining 26 cases, while unnecessary thoracotomy was avoided in 9 patients (30%) with unresectable or benign disease. In 4 patients deemed inoperable on CT scan, VAT staging enabled subsequent resection. CONCLUSIONS: Video-assisted thoracoscopy appears to have a complementary role in staging NSCLC when other methods are equivocal. It has the potential for increased sensitivity over conventional staging methods.
Aged↗
Post-malaria neurological syndrome.
BACKGROUND: Neurological signs and symptoms are common in malaria, but observations in Vietnam and Thailand have pointed to a discrete transient neurological syndrome after recovery from severe infections. METHODS: A prospective study of the post-malaria neurological syndrome (PMNS) was conducted at two centres in Vietnam over four years. Criteria for inclusion were recent symptomatic malaria infection with parasites cleared from blood (and in cases of cerebral malaria full recovery of consciousness), and development of neurological or psychiatric symptoms within two months after the acute illness. Half of the patients with severe falciparum malaria had been taking part in a randomised trial of antimalarials. FINDINGS: Of 18,124 patients with falciparum malaria treated (1176 of whom had severe infections) 19 adults and three children had subsequent PMNS; in one patient it followed uncomplicated malaria and in 21 it followed severe malaria. The overall incidence (95% confidence interval) of PMNS after falciparum malaria at the main study centre was 1.2 per 1000 (0.7 to 1.8 per 1000) and relative risk (95% CI) for developing PMNS after severe versus uncomplicated falciparum malaria was 299 (40 to 2223). 13 patients had an acute confusional state or psychosis, six had one or more generalised convulsions, two had generalised convulsions followed by a long period of acute confusion, and one developed a fine tremor. At the time of PMNS diagnosis all patients were aparasitaemic. The syndrome was self-limiting, median duration 60 h (range 24-240). PMNS was associated with the use of oral mefloquine. In the randomised trial 4.4% (10/228) of patients with severe malaria who received mefloquine after parenteral treatment developed PMNS compared with 0.5% (1/210) of those who received quinine; relative risk 9.2 (95% CI 1.2 to 71.3, p = 0.012). INTERPRETATION: Mefloquine is not the only risk factor for PMNS but it is a strong one. Where an effective alternative drug is available, mefloquine should not be used after treatment of severe malaria.
Adolescent↗
A controlled trial of artemether or quinine in Vietnamese adults with severe falciparum malaria.
BACKGROUND: Artemisinin (qinghaosu) and its derivatives are rapidly effective antimalarial drugs derived from a Chinese plant. Preliminary studies suggest that these drugs may be more effective than quinine in the treatment of severe malaria. We studied artemether in Vietnam, where Plasmodium falciparum has reduced sensitivity to quinine. METHODS: We conducted a randomized, double-blind trial in 560 adults with severe falciparum malaria. Two hundred seventy-six received intramuscular quinine dihydrochloride (20 mg per kilogram of body weight followed by 10 mg per kilogram every eight hours), and 284 received intramuscular artemether (4 mg per kilogram followed by 2 mg per kilogram every eight hours). Both drugs were given for a minimum of 72 hours. RESULTS: There were 36 deaths in the artemether group (13 percent) and 47 in the quinine group (17 percent; P = 0.16; relative risk of death in the patients given artemether, 0.74; 95 percent confidence interval, 0.5 to 1.11). The parasites were cleared more quickly from the blood in the artemether group (mean, 72 vs. 90 hours; P < 0.001); however, in this group fever resolved more slowly (127 vs. 90 hours, P < 0.001), the time to recovery from coma was longer (66 vs. 48 hours, P = 0.003), and the hospitalization was longer (288 vs. 240 hours, P = 0.005). Quinine treatment was associated with a higher risk of hypoglycemia (relative risk, 2.7; 95 percent confidence interval, 1.7 to 4.4; P < 0.001), but there were no other serious side effects in either group. CONCLUSIONS: Artemether is a satisfactory alternative to quinine for the treatment of severe malaria in adults.
Adolescent↗
Treating bulimia nervosa in primary care: a pilot study.
OBJECTIVE: To develop and evaluate a simplified and condensed cognitive behavioral treatment for bulimia nervosa suitable for use in primary care. METHOD: Once developed, the treatment was tested on a consecutive series of 11 patients. RESULTS: Six patients did well, 3 were nonresponders, and in the other 2 external events interfered with progress. DISCUSSION: This form of treatment may benefit a significant proportion of those patients with bulimia nervosa who are seen in primary care. It can be administered by nonspecialist therapists.
Adolescent↗
The acute effects of intravenous frusemide on the renal kallikrein kinin system in man: relationship to dose.
Frusemide (f) is a potent natriuretic and diuretic that acts mainly on the luminal side of the ascending loop of Henle (Schlatter et al. (1983) Pflug. Arch. 396: 210-217). F increases the urinary excretion of prostaglandin (PG) E (Mackay et al. (1984) Contr. Nephrol. 41: 160-162) and its diuretic and natriuretic effects are blunted by indomethacin, suggesting that PGs are involved in the cellular action of this drug (Chennavasin et al. (1980) J. Pharmacol. Exp. Ther. 215: 77-81; Waller et al. (1987) Arch. Pharmacodyn. Ther. 290: 145-150). Several investigators have shown a rapid but short-lived rise in urinary kallikrein (UK) excretion after F administration in man, which could represent a 'wash-out' phenomenon rather than indicating a direct involvement of the kallikrein-kinin system (KKS) in mediating the action of F (Zschiedrich et al. (1979) Clin. Sci. 57: 247-250; Waller et al. (1987); Waller et al. (1990) Clin. Sci. 79: 117-121). However, using a mouse model, 5 days treatment with F has been shown to stimulate renal cortical tubular messenger RNA for tissue kallikrein (Penchow and Coghlan (1994) J. Hypertension 12 (Suppl. 3): 887). Urinary excretion of the components of the KKS is believed to reflect the intra-renal activity of the system (Bhoola et al. (1992) Am. Soc. Pharmacol. Exp. Ther. 44: 1-80). Therefore, if the KKS is directly involved in the natriuretic action of F, a dose-related release of the active components of the system would be expected. This study was designed to examine the effect of three intravenous (i.v.) doses of F on the urinary excretion of components of the renal KKS and the relationships of these components with the excretion of water, electrolytes and F.
Adult↗
Clinical features and outcome of severe malaria in Gambian children.
The clinical and laboratory features of severe falciparum malaria in 180 Gambian children were studied between 1985 and 1989. Of the 180 children, 118 (66%) presented with seizures, 77 (43%) had cerebral malaria, 35 (20%) had witnessed seizures after admission, 29 (16%) were hypoglycemic, and 27 (15%) died. Respiratory distress was a common harbinger of a fatal outcome. The differences in admission parasite counts in the blood, hematocrit, and opening cerebrospinal pressures for patients who died and survivors were not significant. A multiple logistic regression model identified neurological status (coma, particularly if associated with extensor posturing), stage of parasite development on the peripheral blood film, pulse rate of > 150 or respiratory rate of > 50, hypoglycemia, and hyperlactatemia (plasma lactate level, > 5 mmol/L) as independent indicators of a fatal outcome. Biochemical evidence of hepatic and renal dysfunction was an additional marker of a poor prognosis, but, in contrast to severe malaria in adults, none of these children with severe malaria had acute renal failure.
Adult↗
Comparison of artemether and chloroquine for severe malaria in Gambian children.
Artemether is an oil-soluble methyl ether of artemesinin (qinghaosu). It has been studied extensively in China, where it has been shown to be rapidly effective in severe falciparum malaria. Nearly all the patients studied previously were adults. We have investigated the efficacy of artemether in children with moderate or severe falciparum malaria. In the preliminary study of moderately severe malaria, 30 Gambian children were randomised in pairs to receive either intramuscular artemether (4 mg/kg loading dose followed by 2 mg/kg daily) or intramuscular chloroquine ('Nivaquine') 3.5 mg base/kg every 6 h. Both drugs were well tolerated and rapidly effective. The times to parasite clearance were significantly shorter in the artemether recipients (mean 36.7 [SD 11.3] vs 48.4 [16.8] h, p less than 0.05). 43 children with severe malaria were then randomised to receive intramuscular treatment with the same regimens of artemether (n = 21) or chloroquine (n = 22) as used in the preliminary study. 8 children (19%) died. There were no significant differences between the two groups in the clinical, haematological, biochemical, or parasitological measures of therapeutic response in survivors and there was no evidence of local or systemic toxicity. Despite similar parasite counts on admission, clearance times overall were longer in severe malaria than in moderate malaria. Artemether is a well tolerated and rapidly effective parenteral treatment for severe malaria in children, and would be especially valuable in areas with chloroquine-resistant P falciparum.
Animals↗
Brief report: a double-blind study of naltrexone in infantile autism.
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Adolescent↗
Neuropsychological function in young children who have undergone liver transplantation.
Presented neuropsychological data from 20 patients between the ages of 4 and 9 years, who had undergone liver transplantation at least 12 months prior to study participation, and compared them to a control group of 20 children with cystic fibrosis. The liver transplant group showed deficits in VIQ, PIQ, visual-spatial and abstraction/reasoning skills, but not in alertness/concentration, motor, or sensory-perceptual functions. On motor and sensory-perceptual tests, no differences were found in direction of lateralization of deficits. Visual-spatial deficits found in this study sample are similar to those found in adults with end-stage liver disease and in a previous report of an overall older group of children following liver transplantation. However younger children have greater evidence of generalized impairment and VIQ deficits which have not been found in older groups. Findings are discussed in relation to possible etiology, location of brain damage, and clinical implications.
Brain Damage, Chronic↗
[Major methodologic shortcomings in the article on the treatment of alcoholism].
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Alcohol Drinking↗