EON: a component-based approach to automation of protocol-directed therapy

Provision of automated support for planning protocol-directed therapy requires a computer program to take as input clinical data stored in an electronic patient-record system and to generate as output recommendations for therapeutic interventions and laboratory testing that are defined by applicable protocols. This paper presents a synthesis of research carried out at Stanford University to model the therapy-planning task and to demonstrate a component-based architecture for building protocol-based decision-support systems. We have constructed general-purpose software components that (1) interpret abstract protocol specifications to construct appropriate patient-specific treatment plans; (2) infer from time-stamped patient data higher-level, interval-based, abstract concepts; (3) perform time-oriented queries on a time-oriented patient database; and (4) allow acquisition and maintenance of protocol knowledge in a manner that facilitates efficient processing both by humans and by computers. We have implemented these components in a computer system known as EON. Each of the components has been developed, evaluated, and reported independently. We have evaluated the integration of the components as a composite architecture by implementing T-HELPER, a computer-based patient-record system that uses EON to offer advice regarding the management of patients who are following clinical trial protocols for AIDS or HIV infection. A test of the reuse of the software components in a different clinical domain demonstrated rapid development of a prototype application to support protocol-based care of patients who have breast cancer.     

Botulinum toxin for neurological disorders in a movement disorders clinic in Singapore

AIM OF STUDY: This study was done to examine the usefulness of botulinum toxin A injections in treating various neurological disorders such as hemifacial spasm, blepharospasm, focal dystonia and task-specific dystonia. METHODS: This was a prospective, open-labelled trial of patients seen in a Movement Disorders Clinic with dyskinesias potentially treatable with botulinum toxin. All patients were assessed before and after injections using clinical rating scales, and those with focal and task-specific dystonias were also recorded on videotape. RESULTS: There were 102 patients with hemifacial spasm, 3 with blepharospasm, 13 with neck dystonia, 6 with writer's cramp, I with musician's cramp, and I with jaw dystonia. All patients with hemifacial spasm and blepharospasm obtained good results, while 77% of those with cervical dystonia received substantial benefit. Only half of those with writer's cramp improved. Hemifacial spasm seems more prevalent in Singapore compared with Western populations. CONCLUSION: Injections of botulinum toxin are useful in treating the various neurological disorders studied. This is an advancement in the treatment of these dyskinesias which respond poorly to oral medications.     

Influence of the major histocompatibility complex on age at onset of chronic lymphoid leukaemia

Goodpasture syndrome is an often fatal autoimmune disease associated with glomerulonephritis and/or pulmonary hemorrhage. The clinical manifestations of this disease correlate well with the presence of circulating antiglomerular basement membrane (GBM) autoantibodies. The primary target antigen in glomerular and alveolar basement membranes is thought to be the alpha 3 chain of type IV collagen. Nearly all that is known about anti-GBM antibodies in humans comes from work on unbound circulating antibody. We recently had the unique and rare opportunity to obtain early postmortem antibody and tissues from a patient who died with catastrophic Goodpasture syndrome. The specificity of circulating, kidney-bound and lung-bound autoantibodies from this patient was evaluated against a variety of purified basement membrane constituents. The results indicate that the primary target for the circulating and tissue-bound autoantibodies is the NC1 domain of the alpha 3(IV) chain of type IV collagen. Additionally, all the antibodies recognize a cryptic epitope/s on the alpha 3(IV)NC1 hexamer. Furthermore, tissue-bound and circulating antibodies compete with one another for overlapping epitopes on the antigen. These findings demonstrate that circulating autoantibodies in Goodpasture syndrome are highly representative of those bound to organ tissues, strengthening the notion that pathogenic autoantibodies are targeted to the alpha 3(IV)NC1 collagen, and that previous reports of findings in the circulation may be applicable to tissue injury.     

Rheumatic heart disease in India

A cross-sectional study was carried out in rural areas of Jawan Block, District Aligarh, Uttar Pradesh, India, covering a total population of 3760 drawn from 11 villages. The total number of confirmed cases of rheumatic heart disease was 24 with a prevalence rate of 6.4 per 1000 of the general rural population. The prevalence of rheumatic heart disease increased with age until the age of 25 years. Females were more prone to rheumatic heart disease compared to males. Socio-economic class had a direct impact on the occurrence of rheumatic heart disease.     

Don't confuse dental soft tissues with odontogenic tumors

Surgical pathologists are cautioned against the misinterpretation of immature dental tissues (dental papillae and follicles) and dental pulp as odontogenic tumors, especially odontogenic myxomas and fibromas. The close histologic similarity of the immature tissues to tumors may require a clinical-radiologic correlation with the histopathologic specimen in order to distinguish the locally aggressive tumors from innocuous dental tissues.     

Hypothermic ischaemia of the liver: a re-perfusion phenomenon

BACKGROUND: The effects of hypothermic injury to the liver were investigated on an isolated perfusion circuit by comparing porcine livers with varying degrees of preservation injury. METHODS: A group of unstored livers (n = 5) were compared to livers stored in University of Wisconsin (UW) solution for 18 h (n = 5), and a group of livers stored in Hartmann's solution for 18 h (n = 5). RESULTS: We observed that the degree of platelet sequestration was directly related to the severity of the preservation injury. After 2 h of isolated liver perfusion, the perfusate platelet count fell from 148 +/- 14 x 10(9)/L to 84 +/- 13 x 10(9)/L for control livers. In comparison for livers stored in UW solution, the platelet count fell from 173 +/- 43 x 10(9)/L to 61 +/- 14 x 10(9)/L representing a 64.8% fall, while for those stored in Hartmann's solution, an even more profound fall from 152 +/- 36 x 10(9)/L to 19 +/- 9 x 10(9)/L (87.5% fall) was observed. The difference between the UW-stored and Hartmann's-stored livers was significant (P < 0.05). However, using this model, the degree of leukocyte sequestration did not differentiate the groups. Both histological and ultrastructural examination of liver biopsies taken immediately following revascularization demonstrated that for mild degrees of preservation injury following hypothermic storage, changes occur to the sinusoidal lining cells well before changes to the parenchymal elements. CONCLUSIONS: These findings substantiate the hypothesis that the primary injury associated with hypothermia involves the sinusoidal lining cells (non-parenchymal elements), that it is predominantly a reperfusion phenomenon and that efforts at improving preservation should therefore be targeted primarily at these cells and not the hepatocytes.