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Biomedical subjects

P Lucas

Publications and source records attributed to P Lucas.

At least 73 records · Page 4Linked to original sources

Refinement of the HEPAR expert system: tools and techniques.

Methods and tools for the static and dynamic verification and validation of software systems are commonplace in the field of software engineering. In the field of expert systems, where it is more difficult to ensure that a system meets the specifications and expectations than in traditional software engineering, such tools are generally not available. In this paper, the need for more support of the development process by methods and tools is illustrated by the approach taken in building the HEPAR system, a rule-based expert system that can be used as a supportive tool in the diagnosis of disorders of the liver and biliary tract. At a certain stage in the development of this system an incremental development methodology has been adopted, in which implementation of parts of the expert system was followed by dynamic validation. For this purpose, a collection of software tools were implemented as extensions to a rule-based expert-system shell. These tools provide valuable information about the effects of modification of the HEPAR knowledge base, and indicate places in the knowledge base for refinement. It is believed that similar software tools may prove helpful in the development of other expert systems as well.

Artificial Intelligence↗

The representation of medical reasoning models in resolution-based theorem provers.

First-order predicate logic essentially is a language to express knowledge concerning objects and relationships between objects in a domain. Many medical problems can be cast naturally in such terms. In this paper the suitability of logic as a knowledge-representation formalism for building medical expert systems is investigated. In particular, we investigate the logical representation of three typical reasoning models in medicine: diagnostic, anatomical and causal reasoning. It turns out that each of these models has its own characteristic logical structure. Furthermore, the pragmatics of using theorem-proving techniques in consulting such logic-based medical expert systems is discussed. In particular, attention is paid to the use of a meta-level architecture to improve the applicability of theorem-proving techniques in building expert systems.

Anatomy↗

The psychological benefit of orthodontic treatment. Its relevance to dental health education.

In March 1989 the third stage of a major longitudinal survey examining the psychological, social and dental effects of malocclusion and the effectiveness of orthodontic treatment was undertaken. The aim of the research was to assess the benefit of receiving dental treatment with a particular interest in orthodontic treatment. The benefits investigated were dental, psychological and social. The project has involved researchers in several professional disciplines from locations in Britain and Europe.

Child↗

Pirarubicin in advanced breast cancer: a French cooperative phase II study.

79 patients with advanced breast cancer were given Pirarubicin 20-25 mg/m2 during 3 consecutive days every 3 or 4 weeks. 78 were evaluable for response (41 without previous chemotherapy and 37 with only one previous regimen). The overall response rate was 35% (95% CI 24-45) and the complete response rate was 8%. In previously untreated patients, the response rate reached 41.5%. The limiting toxicity was a non-cumulative granulocystopenia, sometimes severe at these high doses, with a prompt recovery. The non-haematological toxicities were mild, and included 13% with grade 3 alopecia.

Adult↗

Developmental changes of Ca2+, PO4, and calcitriol metabolism in spontaneously hypertensive rats.

We have measured Ca and P balance, serum calcitriol, and vitamin D-dependent intestinal calcium-binding protein (CaBP9k) in the spontaneously hypertensive rat (SHR) and its normotensive control, the Wistar-Kyoto rat (WKY) at 4-5 and again at 13-14 wk of age. In rats on a 1% Ca diet, P balance was significantly more positive in the 5-wk-old SHR than WKY (P less than 0.01); Ca balance tended to be greater in the 5-wk-old SHR. In contrast, in the 14-wk-old SHR, P and Ca balance were less positive than in the WKY (P was 5.8 +/- 1.3 vs. 13 +/- 1.7 mg/day, P less than 0.01, and Ca was 53 +/- 4.6 vs. 67 +/- 2.7 mg/day, P less than 0.05). On the 1% Ca diet, plasma calcitriol levels of the 5-wk-old SHR were higher than those of the WKY (58 +/- 3.2 vs. 40 +/- 2.1 pg/ml, P less than 0.002), whereas at 12 wk there was no difference. On Ca-deficient (0.1%) diets, plasma calcitriol was increased in 5-wk-old and 12-wk-old SHR and WKY, compared with the 1% Ca diet (P less than 0.001). Calcitriol metabolic clearance rate was the same in the 13-wk-old SHR and WKY on either Ca diet. Intestinal CaBP9k content of the 5-wk-old (38 +/- 2.6 vs. 40 +/- 3.9 micrograms/mg) and the 12-wk-old (11 +/- 1.6 vs. 14 +/- 1.4 micrograms/mg) SHR and WKY were similar on the 1% Ca diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Interdisciplinary perspectives on mechanisms and management of low back pain.

Chronic low back pain (CLBP) is one of the most pervasive and costly problems facing medicine today. In addition to personal suffering, CLBP accounts for a greatly disproportionate amount of consumer health care over-utilization, employee absenteeism, lowered work productivity, disability and compensation payments. Recent research in the area has called attention to the complex nature of the problem and the need for an interdisciplinary approach to identification and management. Toward this end, a panel of health care professionals with skill in the assessment and treatment of chronic pain was convened on November 17, 1988. Sponsored by the Institute for Behavioral Medicine in Providence and with funding from the National Institute for Neurological Disorders and Stroke, Stroke and Trauma Program, the purpose of the panel discussion was to bring together clinicians and researchers from distinctly different specialties but who all work with CLBP patients. Topics of discussion included etiology, current status of medical diagnostics and treatments for chronic pain, conceptual and systems issues, and directions for future research.

Back Pain↗

Vitamin D3 and glucose-6-phosphate dehydrogenase in rat duodenal epithelial cells.

A microdensitometric method was employed to determine enzyme activities in situ in undisrupted tissue rat duodenum. The effect of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] on glucose-6-phosphate dehydrogenase (G6PD) activity and on the two utilization pathways of synthesized NADPH, H1 (mixed function oxidation) and H2 (biosynthesis), was studied. In normal animals, a crypt-to-villus gradient of G6PD activity and of both NADPH utilization pathways was observed. A high level of NADPH utilization occurred predominantly via the H2 pathway. In vitamin D-deficient rat animals, G6PD activity in the middle part of the villus was approximately 60% lower than in normal animals [10.05 +/- 0.35 vs. 3.95 +/- 0.26 (means +/- SE) A585.min-1.micron-3 X 10(5), P less than 0.001] with reduced NADPH utilization via the H2 pathway (8.39 +/- 0.49 vs. 2.73 +/- 0.43 A585.min-1.micron-3 X 10(5), P less than 0.001) but not the H1 pathway (1.65 +/- 0.17 vs. 1.22 +/- 0.19 A585.min-1.micron-3 X 10(5), P = NS). Intraperitoneal administration of 1,25(OH)2D3 (500 pmol) to vitamin D-deficient animals resulted in increased G6PD activity within 30 min (4.09 +/- 0.38 vs. 5.51 +/- 0.39 A585.min-1.micron-3 X 10(5), P less than 0.05), attaining normal levels within 2 h. The H2 but not the H1 pathway of NADPH utilization increased significantly in response to 1,25(OH)2D3. This increase is essentially located in the basal and middle parts of the villus. Thus 1,25(OH)2D3 may influence biosynthesis in the duodenum via stimulation of G6PD activity and the H2 pathway of NADPH utilization.

Animals↗

Common epitope in human immunodeficiency virus (HIV) I-GP41 and HLA class II elicits immunosuppressive autoantibodies capable of contributing to immune dysfunction in HIV I-infected individuals.

We previously reported the identification of highly conserved homologous regions located in the carboxy terminus of the HIV I gp41-envelope (aa 837-844), and the amino-terminal of the beta chain of all human HLA class II antigens (aa 19-25). Murine monoclonal antibodies, raised against synthetic peptides from these homologous regions, bound not only to the isolated peptides, but also to the native gp160 and class II molecules. In this study one-third of sera from HIV I-infected individuals, at different disease stages, were found to react with both the gp41 and class II-derived peptides. These sera also reacted with "native" HLA class II molecules. The potential affects of such autoantibodies on normal immune functions were examined. It was found that in the presence of class II-cross-reactive (but not control) sera, the proliferative responses of normal CD4+ T cells to tetanus toxoid and allogeneic stimuli were markedly decreased. In addition, these sera could eliminate class II-bearing cells by antibody dependent cellular cytotoxicity. Similar affects were seen with affinity-purified IgG antibodies from patients' sera. Thus, the "molecular mimicry" between HIV I and HLA class II antigens, may lead to the generation of autoantibodies in HIV I-infected individuals that may contribute to the early functional impairment of CD4+ T cell observed in many HIV I-infected individuals.

Acquired Immunodeficiency Syndrome↗

Sequential trial of initial chemotherapy for advanced cancer of the head and neck. DDP versus DDP + 5-fluorouracil.

The study, which compares DDP to DDP + FU, was planned to detect an increase by 60% in efficacy and by 5% in toxicity (2a = B = 5%) for DDP + FU. In a previous trial DDP produced 15% of responders and 5% of high-level toxic manifestations. The eligible patients with an advanced head and neck cancer were paired off successively on the basis of the tumour site and the UICC stage. DDP (100 mg/m2; day 1) was administered with hyperhydration, alone in the first protocol and followed by a 5-day continuous infusion of 5-FU (1 g/m2) in the second one. Courses were repeated every three weeks. Assessment was carried out after three courses or two, in cases of toxic manifestations. Seventy-four patients, who were paired off, entered the trial. The median age was 55 years and the median Karnofsky index was 90. The tumor site was as follows: 28 hypopharynx, 28 oropharynx, 8 oral cavity, and 10 multiple primary cancers. According to the UICC stage, there were 14 T1/T2 N3, 60 T3/T4 with among them 45 N3, and they were all MO. Comparisons were made through sequential closed plans. The combination chemotherapy was more efficacious than DDP with a difference that could be appreciated by the sequential analysis as high as 60% (95% confidence interval, 38% to 82%). The high-level toxicity appeared more significant (+25%) for the association. After radiation therapy 11 of 37 patients (30%) achieved a complete response in the arm with DDP versus 18 of 37 (49%) in that with DDP + FU. The median survival times were 9 and 11.5 months, respectively, and were not statistically different.

Adult↗

Alprazolam augmentation of the antipsychotic effects of fluphenazine in schizophrenic patients. Preliminary results.

Alprazolam was added, under double-blind conditions, to stable fluphenazine hydrochloride regimens in 12 symptomatic, chronically ill inpatients with schizophrenia. The addition of alprazolam was associated with significant, albeit modest, reductions in global psychosis, thought disorder, and paranoia ratings, with a return to pretreatment levels on discontinuation of alprazolam treatment. Improvement in "negative symptoms" such as emotional withdrawal paralleled the changes in "positive symptoms" but did not, in itself, reach statistical significance. There were no significant changes in group mean plasma levels of homovanillic acid or 3-methoxy-4-hydroxyphenylglycol during alprazolam treatment, although group mean serum cortisol levels were significantly decreased by alprazolam treatment. Patients who responded favorably to alprazolam treatment were significantly more psychotic or anxious before treatment, were older, showed significant alprazolam-associated reductions in plasma levels of homovanillic acid, and had significantly more prominent prefrontal cortex atrophy on computed tomographic scans than patients in whom alprazolam was without therapeutic effect. These preliminary data, based on a small sample, suggest that some patients with schizophrenia who are only partially responsive to standard neuroleptic treatment may benefit from the addition of triazolobenzodiazepines, such as alprazolam.

Adult↗

The effects of unstable clients in adolescent treatment: contagion versus continuity.

This study examined the effects of integrating an unstable group of seriously disturbed adolescents into an existing day treatment program. Behavioral data were collected for an established group of subjects who were in treatment one year prior to and one year after the arrival of a new group of severely disturbed adolescents. It was found that the disruptive behavior displayed by the new admission subjects was not imitated by the subjects of the established group. Rather, there was a significant decrease in aggression and in the overall number of psychiatric events for the established group. The treatment milieu was seen to be resistant to the effects of the new admissions largely due to the structured form of treatment.

Adolescent↗