Semi-automated entry of clinical temporal-abstraction knowledge.

OBJECTIVES: The authors discuss the usability of an automated tool that supports entry, by clinical experts, of the knowledge necessary for forming high-level concepts and patterns from raw time-oriented clinical data. DESIGN: Based on their previous work on the RESUME system for forming high-level concepts from raw time-oriented clinical data, the authors designed a graphical knowledge acquisition (KA) tool that acquires the knowledge required by RESUME. This tool was designed using Protégé, a general framework and set of tools for the construction of knowledge-based systems. The usability of the KA tool was evaluated by three expert physicians and three knowledge engineers in three domains-the monitoring of children's growth, the care of patients with diabetes, and protocol-based care in oncology and in experimental therapy for AIDS. The study evaluated the usability of the KA tool for the entry of previously elicited knowledge. MEASUREMENTS: The authors recorded the time required to understand the methodology and the KA tool and to enter the knowledge; they examined the subjects' qualitative comments; and they compared the output abstractions with benchmark abstractions computed from the same data and a version of the same knowledge entered manually by RESUME experts. RESULTS: Understanding RESUME required 6 to 20 hours (median, 15 to 20 hours); learning to use the KA tool required 2 to 6 hours (median, 3 to 4 hours). Entry times for physicians varied by domain-2 to 20 hours for growth monitoring (median, 3 hours), 6 and 12 hours for diabetes care, and 5 to 60 hours for protocol-based care (median, 10 hours). An increase in speed of up to 25 times (median, 3 times) was demonstrated for all participants when the KA process was repeated. On their first attempt at using the tool to enter the knowledge, the knowledge engineers recorded entry times similar to those of the expert physicians' second attempt at entering the same knowledge. In all cases RESUME, using knowledge entered by means of the KA tool, generated abstractions that were almost identical to those generated using the same knowledge entered manually. CONCLUSION: The authors demonstrate that the KA tool is usable and effective for expert physicians and knowledge engineers to enter clinical temporal-abstraction knowledge and that the resulting knowledge bases are as valid as those produced by manual entry.

Knowledge-based temporal abstraction in diabetes therapy.

We suggest a general framework for solving the task of creating abstract, interval-based concepts from time-stamped clinical data. We refer to this problem-solving framework as the knowledge-based temporal-abstraction (KBTA) method. The KBTA method emphasizes explicit representation, acquisition, maintenance, reuse, and the sharing of knowledge required for abstraction of time-oriented clinical data. We describe the subtasks into which the KBTA method decomposes its task, the problem-solving mechanisms that solve these subtasks, and the knowledge necessary for instantiating these mechanisms in a particular clinical domain. We have implemented the KBTA method in the RESUME system and have applied it to the task of monitoring the care of insulin-dependent diabetics.

Parathyroid imaging. Use of dual isotope scintigraphy for the localization of adenomas before surgery.

Seventy-nine patients with primary hyperparathyroidism, whose average preoperative blood calcium level was 11.6 mg/dl, underwent thallium-technetium dual isotope scintigraphy of the thyroid and parathyroids. For patients who had surgery, the detection and localization rate of parathyroid disease or the sensitivity was low (0.53), but the positive predictive value for the location was high (0.80). Correct localization correlated positively with the weight of the tumor but not significantly with the parathyroid hormone blood level nor with the blood calcium level. Unprocessed data alone were sufficient to predict correctly the location in two thirds of the detected cases. Computer processing increased the sensitivity without decreasing the specificity. Those results, at variance with earlier published data but congruent with another more recent study, require a reevaluation of the role of this scintigraphic technique in the management of hyperparathyroidal patients.

Iodine-131 MIBG uptake in metastatic medullary carcinoma of the thyroid. A patient treated with somatostatin.

A 47-year-old man with multiple endocrine neoplasia (MEN) type 2a syndrome in whom metaiodobenzylguanidine (MIBG) concentrated in lesions from metastatic medullary carcinoma of the thyroid is reported. A somatostatin analogue (Sandostatin SMS 201-995) alleviated the symptoms of flushing and diarrhea associated with the elevated calcitonin levels but it did not alter either the course of the disease or the MIBG images. A review of the literature is presented of the noncatecholamine secreting tumors associated with MIBG uptake. Similarities between this case and metastatic carcinoid syndrome are discussed.

Tricuspid valve obstruction due to intravenous leiomyomatosis.

A case is discussed of a 65-year-old woman who presented with tricuspid stenosis. She was evaluated with multiple imaging techniques including gated radionuclide angiography, cardiac sector scanning, and abdominal CT imaging. A review of the literature of the entity known as intravenous leiomyomatosis is presented.

Intensive plasmapheresis in the treatment of diabetic retinopathy.

Two insulin-dependent diabetic patients with advanced nonproliferative and early proliferative retinopathy showed regression of diabetic retinopathy after three weeks of intensive plasmapheresis. Because of the sudden unexplained death in one patient, the study was stopped. However, these observations in this pilot study suggest that factors mediated through plasma contribute to the pathogenesis of diabetic microangiopathy.

Photopenic lesions in bone scintigraphy.

Three cases with photopenic lesions on bone scintigraphy due to metastases from osteogenic sarcoma are presented.

Splanchnic metabolism of free fatty acids and production of triglycerides of very low density lipoproteins in normotriglyceridemic and hypertriglyceridemic humans.

Transport of free fatty acids from the blood into the splanchnic region and their conversion to triglycerides of very low density lipoproteins, together with estimates of splanchnic oxidation of free fatty acids to ketones and to carbon dioxide and water, have been made in the postabsorptive state in seven normolipemic subjects, six with primary endogenous hyperlipemia and one each with primary dysbetalipoproteinemia and mixed hyperlipemia. Net systemic transport of free fatty acids into the blood was the same in normolipemic and hyperlipemic groups, but a greater fraction was taken up in the splanchnic region in the latter. Transport into the blood in very low density lipoproteins of triglyceride fatty acids derived from free fatty acids was proportional and bore the same relationship to splanchnic uptake of free fatty acids in the two groups. In normolipemic subjects, near equilibration of specific activities after 4 hr infusion of palmitate-1-(14)C showed that almost all triglyceride fatty acids of very low density lipoproteins and acetoacetate were derived from free fatty acids taken up in the splanchnic region. In the hyperlipemic subjects, equilibration of free fatty acidcarbon with acetoacetate was almost complete, but not with triglyceride fatty acids, owing at least in part to increased pool size. Comparison of the rate of equilibration of triglyceride fatty acids-(14)C with rate of inflow transport from the splanchnic region, together with other data, indicated that most of the circulating triglyceride fatty acids of very low density lipoproteins in hyperlipemic subjects were also derived from free fatty acids. Although mean inflow transport of triglyceride fatty acids was greater in the hyperlipemic subjects, it correlated poorly with their concentration and it appeared that efficiency of mechanisms for extrahepatic removal must be a major determinant of the concentration of triglycerides in blood plasma of the normolipemic as well as the hyperlipemic subjects. Estimates of splanchnic respiratory quotient supported the concept that oxidation of free fatty acids accounts for almost all of splanchnic oxygen consumption in the postabsorptive state. Splanchnic oxygen consumption was greater in the hyperlipemics, but fractional oxidation of free fatty acids to ketones was higher in normolipemic subjects. Calculations of splanchnic balance indicate that a larger fraction of free fatty acids was stored in lipids of splanchnic tissues in the hyperlipemics. No differences were found between the two groups in net splanchnic transport of glucose, lactate, or glycerol.

Hepatic metabolism of free fatty acids in normal and diabetic dogs.

Fasted dogs prepared with catheters in the femoral artery, portal vein, and hepatic vein and infused intravenously with palmitate-1-(14)C were used to estimate uptake of free fatty acids in liver and their conversion to major metabolic products secreted into hepatic venous blood. Animals were studied under ordinary conditions and when fat mobilization was increased abruptly by infusing norepinephrine or for a prolonged period by withdrawing insulin from depancreatized dogs. 80% of hepatic blood flow was assumed to be derived from the portal vein. Hepatic uptake was proportional to net outflow transport of plasma free fatty acids in the three groups and, in each, hepatic extraction fraction was about 25%. Since specific activity of free fatty acids entering and leaving the liver was equal and their composition was closely similar in the three sites sampled, it was concluded that palmitate is a representative tracer for free fatty acids entering the liver and that the liver does not release free fatty acids into the blood. In norepinephrine-infused dogs, the fraction of free fatty acids secreted in triglycerides (13%) was similar to that of control animals, so that transport of triglycerides was increased. In diabetic dogs no increased transport could be demonstrated since an average of only 2% of free fatty acids was converted to plasma triglyceride fatty acids; the hyperlipemia uniformly observed therefore appeared to result from defective removal of triglycerides from the blood.A similar fraction of free fatty acids was converted to ketones in normal and norepinephrine-infused dogs. This fraction was somewhat higher in diabetic animals and, in addition, a substantial quantity of ketones was derived from unlabeled precursors. Fractional conversion of free fatty acids to CO(2) was similar in normal and norepinephrine-infused dogs, but reduced in the diabetics.