Decreased insulin binding to cultured cells from a patient with the Rabson-Mendenhall syndrome: dichotomy between studies with cultured lymphocytes and cultured fibroblasts.

[125I]Insulin binding has been studied with cultured cells from an insulin-resistant patient with the Rabson-Mendenhall syndrome. Previously, this patient has been demonstrated to have decreased insulin binding to circulating blood cells. Similarly, [125I]insulin binding to cultured lymphocytes and cultured fibroblasts was markedly decreased. Whereas the decrease in [125I]insulin binding to cultured lymphocytes appeared to result from a decrease in receptor number in cultured lymphocytes, there appeared to be a reduction in the affinity of [125I]insulin binding to cultured fibroblasts. This discrepancy between the observations with the two cell types is a general phenomenon which has been described in patients with a variety of syndromes of extreme insulin resistance. It is possible that the interpretation of the studies with the fibroblasts is complicated by the confounding influence of receptors for insulin-like growth factors on the surface of those cells. If the number of insulin receptors is sufficiently reduced on fibroblasts from the patient with extreme insulin resistance, then the low level of residual [125I]insulin binding may involve primarily receptors for insulin-like growth factors, which bind insulin with relatively low affinity.

PaperChase: computerized bibliographical retrieval for the physician.

PaperChase is a computer program that permits any physician or scientist to search the National Library of Medicine's MEDLINE data base of references to the biomedical literature. Written for the clinician rather than for the search librarian, PaperChase permits the user to search the entire MEDLINE collection of over 5,000,000 references published in 4,000 biomedical journals dating back to 1966. PaperChase is now available throughout the world to anyone who has a computer terminal or personal computer, and a modem. No special training is needed for a successful search. There is no user's manual. Users can search by title word, Medical Subject Heading, author's name, journal title, year of publication, language of publication, or any combination of the above. Users can read abstracts online, and they can request that a photocopy of the full text of any article be mailed to them.

Bringing the medical literature to physicians. Self-service computerized bibliographic retrieval.

Seven years ago physicians at the Beth Israel Hospital in Boston began doing their own searches of the medical literature. They used PaperChase, a computer program written especially for end users rather than for search librarians. The data base was initially limited to the journals shelved in the library of the Beth Israel Hospital, but it has since been expanded to include the entire MEDLINE collection of the National Library of Medicine-nearly 5 million references published in 3,400 biomedical journals dating back to 1966.PaperChase is now available throughout the United States and Canada to anyone who has a computer terminal or personal computer and a modem. No special training is needed for a successful search and there is no user's manual. Users can search by title word, "medical subject heading," author's name, journal title, year of publication, language of publication or any combination of the above. They can read abstracts on line, and they can request that a photocopy of the full text of any article be mailed to them.

A protein activator for the adenylate cyclase of Bordetella pertussis.

The activity of Bordetella pertussis extracytoplasmic adenylate cyclase is 100-fold higher in organisms grown on blood agar than in those grown in synthetic medium. This increase in activity is due to in vivo activation of the enzyme by a factor present in erythrocytes. Activation also occurs in killed or disrupted organisms. The activator can be separated from heme proteins and has been purified approximately 100-fold from erythrocytes, yielding material of approximately 105,000 daltons. It is sensitive to trypsin and alpha-chymotrypsin and exhibits considerable heat stability. Activation of cyclase in intact B. pertussis organisms exhibits a lag of 3 to 4 min and is not reversed by washing. Response to the activator decreases with increasing purification of the adenylate cyclase and is absent in the pure enzyme. The activation does not appear to be proteolytic and does not appear to change access to the substrate, ATP. The activator has no effect on a number of eukaryotic cyclases. We conclude that this is a new type of activation and that the activator differs from all those previously described.

ClinQuery: a system for online searching of data in a teaching hospital.

We designed a user-friendly computer program that permits physicians to search the clinical database of Boston's Beth Israel Hospital by clinical and demographic descriptors. For example, the user can identify all admissions in which diabetic ketoacidosis was diagnosed, the serum bicarbonate level was under 12 mmol/L, and the length of stay exceeded 7 days. Once particular admissions are identified, all data stored in the computerized record can be displayed. Authorized persons can also request the patient's complete medical record for further study. Over a 30-month period, 530 doctors, nurses, medical students, and administrators used the program to search the hospital's clinical database 1786 times. They displayed detailed information on 30,851 patients and requested the complete medical record 5319 times. In 1389 of the 1786 searches completed, the searcher responded to a computer-based questionnaire about motivation for the search. Responses indicated that 32% of the searches were for clinical research, 17% for patient care, 17% for teaching and education, 11% for hospital administration, and 12% for general exploration. In 58% of the searches, respondents indicated definite or probable success in finding the desired information. We conclude that physicians and allied personnel will repeatedly obtain, view, and analyze aggregate clinical information if they are provided with appropriate tools. We believe that such access to clinical information is an important resource for patient care, teaching, and clinical research.

Hypoglycemia associated with antibodies to the insulin receptor.

Antibodies to the insulin receptor are insulinomimetic in vitro, although they generally induce insulin resistance in vivo. We report the novel case of a patient who presented with fasting hypoglycemia as the sole manifestation of autoantibodies to the insulin receptor. Prednisone therapy (120 mg per day) produced a rise in fasting glucose to more than 100 mg per deciliter (6 mmol per liter) within 48 hours, although there was no detectable change in the titer of antireceptor antibodies. After 10 weeks of therapy, the titer of antireceptor antibodies had fallen approximately 100-fold, and prednisone could be discontinued without recurrence of hypoglycemia. This case demonstrates that antireceptor antibodies must be considered in the differential diagnosis of hypoglycemia, especially in patients with other manifestations of autoimmunity.

ClinQuery: searching a large clinical database.

We designed a user-friendly computer program that permits physicians to use clinical and demographic descriptors to search a hospital's clinical database for purposes of patient care, teaching, and research. For example, the user can identify all admissions in which diabetic ketoacidosis was diagnosed, the serum bicarbonate level was under 12 mmol/liter, and the length of stay exceeded 7 days. Once particular admissions have been identified, all data stored in the computerized record can be displayed. Authorized persons can also request the patient's complete medical record for further study. Over a 5-year period, 895 doctors, nurses, medical students, and hospital administrators used Clin-Query to search the clinical database of Boston's Beth Israel Hospital 3724 times. They displayed detailed information on 72,489 patients and requested the complete medical record 5477 times. Responses to a computer-based questionnaire indicated that 16% of the searches were performed for patient care, 38% for clinical research, 16% for teaching and education, 12% for hospital administration, and 18% for general exploration. We conclude that physicians and allied personnel will repeatedly examine and analyze aggregate clinical information when they are provided with the appropriate tools.