tbuckley/cabot-search huggingface dataset:
Phenytoin-valproate interaction: importance of saliva monitoring in epilepsy.
Authors: C Knott, A Hamshaw-Thomas, F Reynolds
Journal: BMJ (1982)

Sodium valproate is often used with phenytoin when epilepsy cannot be controlled by a single drug. Sodium valproate depresses phenytoin protein binding and so invalidates plasma phenytoin monitoring as a means of determining precise phenytoin dosage requirements. Plasma and saliva phenytoin and plasma valproate concentrations were measured in 42 patients with epilepsy receiving both drugs. Phenytoin protein binding was also measured by ultrafiltration in 19 of these patients and 19 patients taking phenytoin alone. Saliva phenytoin concentration bore the same close correlation to unbound (therapeutically active) phenytoin in patients receiving both drugs as it did in patients receiving phenytoin alone, whereas plasma total phenytoin did not. The same therapeutic range for saliva phenytoin (4-9 mumol/1; 1-2 microgram/ml) was therefore valid in both groups. The depression of phenytoin binding was directly related to the plasma concentration of valproate both in random samples taken from the 42 patients and in samples taken throughout the day in two of these patients. This was confirmed in vitro. Even when the concentration of valproate is known the degree of binding cannot be predicted. Saliva rather than plasma monitoring of phenytoin treatment is therefore valuable in the presence of valproate and with reduced phenytoin binding from any cause.
Role of transforming growth factor-beta in maintenance of function of cultured neonatal cardiac myocytes. Autocrine action and reversal of damaging effects of interleukin-1.
Authors: A B Roberts, N S Roche, T S Winokur, J K Burmester, M B Sporn
Journal: Journal of Clinical Investigation (1992)

The three isoforms of transforming growth factor-beta (TGF-beta) have previously been implicated in embryonic development of the heart as well as in repair of myocardial damage after ischemia/reperfusion injury. TGF-beta 1 has also been localized intracellularly to both mitochondria and contractile filaments of cardiac myocytes, although its role in these structures has not been defined. We now report that exogenous TGF-beta stabilizes the beating rate of neonatal rat cardiac myocytes cultured on fibroblast matrix, and sustains their spontaneous rhythmic beating in serum-free medium. Moreover, using blocking antibodies to TGF-beta, we show that endogenous TGF-beta secreted by these myocytes acts in an autocrine fashion to maintain their beating rate. In contrast, IL-1 beta, an inflammatory mediator secreted by immune cells during myocardial injury, inhibits the beating of cardiac myocytes, and TGF-beta can overcome this inhibition. The antagonistic effects of TGF-beta and IL-1 were not observed when the myocytes were cultured on gelatin, as compared to native fibroblast matrix. The data indicate that TGF-beta is an important regulator of contractile function of the heart and have significant implications for understanding cardiac physiology in health and disease.
DANGERS IN THE USE OF ADRENAL PREPARATIONS.
Authors: F. C. BENNETT
Journal: JAMA (1906)

In an article inThe Journal, Oct 13, 1906, Dr. B. H. Potts, of Philadelphia, warns the profession of some of the dangers of suprarenal preparations. The following case illustrates a danger in the indiscriminate use of the drug: A negro, aged 26, male, very rugged and healthy, had a stricture of the urethra. After some difficulty I succeeded in passing a No. 24 French sound. When the sound was withdrawn considerable blood followed it, which greatly alarmed the patient. Thinking to quiet his fears I injected into the urethra about half a dram of adrenalin chlorid (1-1000). In about thirty seconds the patient became restless and moved about, staggered and was laid on the couch. He complained of intense pain about the heart and his breathing was labored and very rapid. The heart beat was so fast that I could not count it. The conjunctiva was blanched. Profuse perspiration
Improvement of Basal Hepatic Glucose Production ana Fasting Hyperglycemia of Type I Diabetic Patients Treated With Human Recombinant Ultralente Insulin
Authors: Antonio Riccio, Angelo Avogaro, Anna Valerio, Anna Zappella, Antonio Tiengo, Stefano Del Prato
Journal: Diabetes Care (1994)

OBJECTIVE To test whether a suppertime injection of human ultralente insulin in patients with type I diabetes would result in a larger inhibition of basal hepatic glucose production (HGP) and improvement in fasting and mean daily plasma glucose levels. RESEARCH DESIGN AND METHODS We studied 16 type I diabetic patients (41 ± 4 years of age; body mass index [BMI] = 23.3 ± 0.3 kg/m2; diabetes duration &amp;gt;3 years) with a crossover protocol of therapy with an intermediate and ultralente insulin. All patients were already treated with three injections per day of regular insulin in addition to intermediate-acting (NPH) insulin at suppertime. After a 14-day run-in period, patients were randomly assigned to treatment with equivalent doses (10.8 ± 0.8 U, at 1900) of intermediate (Humulin 1) or ultralente (Humulin U) insulin. After 1 month of treatment, patients were crossed over. No change of the insulin dosage was performed during the study period. Basal HGP was measured by β-glucose infusion. Plasma glucose concentration was measured in the fasting state and monitored during the day. RESULTS Before starting the study period, fasting plasma glucose was 13.4 ±1.1 mM and plasma free-insulin was 48.0 ± 4.8 pM. Daily plasma glucose concentration averaged 10.3 ± 0.3 mM and the area under the curve (AUC) was 1.41 ± 0.05 mol/14 h. NPH insulin, given at suppertime for a month, did not induce significant changes in fasting plasma insulin (40.2 ± 4.8 pM), glucose concentration (14.0 ± 0.9 mM) or HGP (20.2 ± 2.2 jamol · kg–1 · min–1). Accordingly, no change occurred in the average daily plasma glucose (10.3 ± 0.3 mM) or AUC (1.41 ± 0.9 mol/14 h). Glycated hemoglobin also was not affected (8.2 ± 0.4 vs. 8.2 ± 0.3%). On the contrary, a 4-week treatment with ultralente insulin, also given at suppertime, was associated with a decline in the basal HGP (16.0 ±1.3 /Ltmol · kg–1 · min–1), fasting (11.3 ± 0.9 mM) and average daily (9.4 ± 0.3 mM) plasma glucose concentrations, and AUC (1.29 ± 0.07 mol/14 h) of plasma glucose level (all P &amp;lt; 0.05). Glycated hemoglobin was reduced (7.9 ± 0.4%). In each condition, fasting plasma glucose concentration was correlated with the average daily plasma glucose level (basal = 0.78; intermediate = 0.89; ultralente = 0.62; all P &amp;lt; 0.05), which suggests that ultralente insulin likely induces the improvements of metabolic control through reducing fasting plasma glucose. CONCLUSIONS Our results suggest that treating type I diabetic patients with ultralente insulin at suppertime provides a better modulation of basal HGP so that lower fasting plasma glucose levels are ensured. The reduction of fasting hyperglycemia is likely to affect positively aily plasma glucose control.
Human eosinophils express CD4 protein and bind human immunodeficiency virus 1 gp120.
Authors: D R Lucey, D I Dorsky, A Nicholson-Weller, P F Weller
Journal: The Journal of Experimental Medicine (1989)

The CD4 glycoprotein, expressed on leukocytes belonging to subsets of T lymphocytes and to cells of monocyte/macrophage lineage, participates in the functioning of T cells and serves as a receptor for HIV-1 and HIV-2. Human eosinophils, a class of granulocytic leukocytes, have been found to express CD4. With anti-CD4 mAbs CD4 was demonstrable on eosinophils from both normal and eosinophilic donors. Eosinophils synthesized a 55-kD CD4 polypeptide immunoprecipitable with two anti-CD4 mAbs. Eosinophil CD4 bound HIV-1 gp120 as assessed by competition for anti-OKT4A, but not anti-OKT4, mAb binding. Eosinophils, normally rich in gastrointestinal and genitourinary tract tissues, increase in numbers in patients with metazoan parasitic infections. In these sites and diseases, CD4 expression by eosinophils may be pertinent to their immunologic functions and could make these cells susceptible to HIV infection.
THE QUANTITATION OF KERATINIZATION IN HUMAN FOETAL TISSUES
Authors: A. JARRETT, W. WYK
Journal: British Journal of Dermatology (1972)

Journal Article THE QUANTITATION OF KERATINIZATION IN HUMAN FOETAL TISSUES Get access A. JARRETT, A. JARRETT Dermatology Department, University College Hospital Medical School, University Street, London, W.C.1 Search for other works by this author on: Oxford Academic Google Scholar W. VAN WYK W. VAN WYK Dermatology Department, University College Hospital Medical School, University Street, London, W.C.1 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 86, Issue 5, 1 May 1972, Pages 508–512, https://doi.org/10.1111/j.1365-2133.1972.tb16104.x Published: 01 May 1972 Article history Accepted: 07 January 1972 Published: 01 May 1972
Doctors of mirth
Authors: J. O. Drife
Journal: BMJ (2010)

A sense of humour was never the leading prerequisite for a medical career, but now it has slipped off the list completely. Interviews for medical school have become earnest, scripted affairs, and the days of hospital revues are long gone. Soon postgraduate centres will have notices like those at airports, warning that if you make a joke you will be arrested.

Doctors used to enjoy a bit of fun, but you have to go back a long way to find …
Neuroblastoma, Its Natural History and Prognosis: A Study of 487 Cases
Authors: L. M. K. Wilson, G. J. Draper
Journal: BMJ (1974)

The natural history of neuroblastoma and factors affecting survival for this disease were studied in an unselected group of children notified to cancer registries in Britain during 1962-7. The three-year survival rate based on 487 cases was 23%; many of the cases were followed up for more than five years, and this made it possible to calculate long-term survival and recurrence rates. There were only five deaths among 110 cases followed for more than three years, 64 of the survivors having been followed for more than five years. Factors affecting the prognosis included age at diagnosis, site, histological grade at diagnosis, and the sex of the child. The interrelationship between these factors together with their effect on prognosis were analysed, and in particular we attempted to elucidate factors which might explain our observation that girls have a significantly better survival rate than boys. Direct histological evidence and also the analyses of survival and recurrence rates seem to support the suggestion that the likelihood of maturation for this tumour is greater for girls than for boys.
Multistate Evaluation of Anonymous HIV Testing and Access to Medical Care
Authors: Andrew B. Bindman
Journal: JAMA (1998)

Context.—Infection with the human immunodeficiency virus (HIV) is the only infectious disease for which anonymous testing is publicly funded, an exception that has been controversial.Objective.—To assess whether anonymous HIV testing was associated with earlier HIV testing and HIV-related medical care than confidential HIV testing.Design.—Retrospective cohort.Setting.—Arizona, Colorado, Missouri, New Mexico, North Carolina, Oregon, and Texas.Participants.—Probability sample of 835 new acquired immunodeficiency syndrome (AIDS) cases reported to the state health department's HIV/AIDS Reporting System from May 1995 through December 1996. All had responded to the AIDS Patient Survey; 643 had been tested confidentially for HIV, and 192 had been tested anonymously.Main Outcome Measures.—First CD4+ cell count; number of days from HIV-positive test result to first HIV-related medical care, from first HIV-related medical care to AIDS, and from first HIV-positive test result to AIDS.Results.—Persons tested anonymously sought testing and medical care earlier in the course of HIV disease than did persons tested confidentially. Mean first CD4+ cell count was 0.427×109/L in persons tested anonymously vs 0.267×109/L in persons tested confidentially. Persons tested anonymously experienced an average of 918 days in HIV-related medical care before an AIDS diagnosis vs 531 days for persons tested confidentially. The mean time from learning they were HIV positive to the diagnosis of AIDS was 1246 days for persons tested anonymously vs 718 days for persons tested confidentially. After adjustment for the subject's age, sex, race/ethnicity, education, income, insurance status, HIV exposure group, whether the respondent had a regular source of care or symptoms at the time of the HIV test, and state residence, anonymous testing remained significantly associated with earlier entry into medical care (P&lt;.001).Conclusion.—Anonymous testing contributes to early HIV testing and medical care.
Mcm2, Geminin, and KI67 Define Proliferative State and are Prognostic Markers in Renal Cell Carcinoma
Authors: Tim J. Dudderidge, Kai Stoeber, Marco Loddo, Geraldine Atkinson, Thomas Fanshawe, David F. Griffiths, Gareth H. Williams
Journal: Clinical Cancer Research (2005)

The origin licensing factors minichromosome maintenance 2 (Mcm2) and Geminin have recently been identified as critical regulators of growth and differentiation. Here we have investigated the regulation of these licensing factors together with Ki67 to further elucidate the cell cycle kinetics of renal cell carcinoma (RCC). Furthermore, we have examined the role of Ki67, Mcm2, and Geminin in disease-free survival after nephrectomy in patients with localized RCC.Tissue sections from 176 radical nephrectomy specimens were immunohistochemically stained with Mcm2, Geminin, and Ki67 antibodies. Labeling indices (LI) for these markers were compared with clinicopathologic parameters (median follow-up 44 months).In RCC, Mcm2 is expressed at much higher levels than Ki-67 and Geminin, respectively [medians 41.6%, 7.3%, and 3.5% (P < 0.001)] and was most closely linked to tumor grade (P < 0.001). For each marker, Kaplan-Meier survival curves provided strong evidence that increased expression is associated with reduced disease-free survival time (P < 0.001). Additionally, an Mcm2-Ki67 LI identified a unique licensed but nonproliferating population of tumor cells that increased significantly with tumor grade (P = 0.004) and was also of prognostic value (P = 0.01). On multivariate analysis, grade, vascular invasion, capsular invasion, Ki67 LI >12%, and age were found to be independent prognostic markers.Although Ki67 is identified as an independent prognostic marker, semiquantitative assessment is difficult due to the very low proliferative fraction identified by this marker. In contrast, Mcm2 identifies an increased growth fraction that is closely linked to grade, provides prognostic information, and is amenable to semiquantitative analysis in routine pathologic assessment.
Nucleus-targeted Dmp1 transgene fails to rescue dental defects in Dmp1 null mice
Authors: Shu-Xian Lin, Qi Zhang, Hua Zhang, Kevin Yan, Leanne Ward, Yong-Bo Lu, Jian-Quan Feng
Journal: International Journal of Oral Science (2014)

Dentin matrix protein 1 (DMP1) is essential to odontogenesis. Its mutations in human subjects lead to dental problems such as dental deformities, hypomineralization and periodontal impairment. Primarily, DMP1 is considered as an extracellular matrix protein that promotes hydroxyapatite formation and activates intracellular signaling pathway via interacting with αvβ3 integrin. Recent in vitro studies suggested that DMP1 might also act as a transcription factor. In this study, we examined whether full-length DMP1 could function as a transcription factor in the nucleus and regulate odontogenesis in vivo. We first demonstrated that a patient with the DMP1 M1V mutation, which presumably causes a loss of the secretory DMP1 but does not affect the nuclear translocation of DMP1, shows a typical rachitic tooth defect. Furthermore, we generated transgenic mice expressing NLSDMP1, in which the endoplasmic reticulum (ER) entry signal sequence of DMP1 was replaced by a nuclear localization signal (NLS) sequence, under the control of a 3.6 kb rat type I collagen promoter plus a 1.6 kb intron 1. We then crossbred the NLSDMP1 transgenic mice with Dmp1 null mice to express the NLSDMP1 in Dmp1-deficient genetic background. Although immunohistochemistry demonstrated that NLSDMP1 was localized in the nuclei of the preodontoblasts and odontoblasts, the histological, morphological and biochemical analyses showed that it failed to rescue the dental and periodontal defects as well as the delayed tooth eruption in Dmp1 null mice. These data suggest that the full-length DMP1 plays no apparent role in the nucleus during odontogenesis. A protein involved in tooth mineralization, although found in the nucleus, does not seem to play a role there during tooth formation. Dentin matrix protein 1 (DMP1) is present both in the nucleus and in the cytoplasm of odontoblasts, cells that form part of the dental pulp. To examine DMP1's role during embryonic tooth development, a team led by Jian-Quan Feng of the Texas A&M University Baylor College of Dentistry, USA, bred transgenic mice that only express DMP in the nucleus. These mice displayed dental defects and delayed tooth eruption similar to the defects seen in mouse strains with no functional versions of DMP1 in the nucleus or the cytoplasm. A human patient with a DMP1 gene mutation that causes only nuclear protein localization also exhibited tooth abnormalities consistent with rickets.
Imaging of Multiple Bilateral Parotid Gland Oncocytomas
Authors: ELMER C. SAN PEDRO, MORDECHAI LORBERBOYM, JOSEF MACHAC, PETER SOM, JOEL SHUGAR
Journal: Clinical Nuclear Medicine (1995)

Oncocytoma of the salivary glands is a rare tumor that usually follows a benign course and, in most cases, can be cured by surgical resection. The authors report a rare case of multiple bilateral parotid oncocytomas that presented clinically with two palpable parotid masses. Both CT and MRI scans demonstrated multiple masses in each parotid gland. The tumors exhibited intense uptake and prolonged retention of Tc-99m pertechnetate. The diagnosis was confirmed by fine needle aspiration. Sialoscintigraphy is a simple and noninvasive procedure that can usually separate benign entities like Warthin tumor and oncocytoma of the salivary glands from malignant tumors, and significantly affect the course of treatment.
SNARE Protein Recycling by αSNAP and βSNAP Supports Synaptic Vesicle Priming
Authors: Andrea Burgalossi, Sangyong Jung, Guido Meyer, Wolf J. Jockusch, Olaf Jahn, Holger Taschenberger, Vincent M. O'Connor, Tei-ichi Nishiki, Masami Takahashi, Nils Brose, Jeong-Seop Rhee
Journal: Neuron (2010)
Progress in the Development of Trauma Systems in the United States
Authors: Gloria J. Bazzoli
Journal: JAMA (1995)

To examine the status of trauma system development and key structural and operational characteristics of these systems.National survey of trauma systems with enabling state statute, regulation, or executive orders and for which designated trauma centers were present.Trauma system administrators and directors of 37 state and regional organizations that had legal authority to administer trauma systems, which represented a response rate of 90.2%.Trauma system components that had been implemented or were under development.From 1988 to 1993, the number of states meeting one set of criteria for a complete trauma system criteria increased from two to five. The most common deficiency in establishing trauma systems was failure to limit the number of designated trauma centers based on community need. Although most existing trauma systems have developed formal processes for designating trauma centers, prehospital triage protocols to allow hospital bypass, and centralized trauma registries, several systems lack standardized policies for interhospital transfer and systemwide evaluation.State and regional organizations have accomplished a great deal but still have substantial work ahead in developing comprehensive trauma systems. Research is needed to better understand the relationship between trauma volume and outcomes of care as well as the impact of trauma system structure and operational characteristics on care delivery. Improved measures of patient outcome are also needed so that effective system evaluation can take place.
Plasma oestrogens in men with chronic liver disease.
Authors: J R Green, N A Mowat, R A Fisher, D C Anderson
Journal: Gut (1976)

A highly specific radioimmunoassay was used to measure the total plasma concentrations of the three principal unconjugated oestrogens: oestrone E1, oestradiol E2, and oestriol E3 in normal males and in 21 males with various forms of chronic liver disease. In addition, the unbound concentration of plasma E2 was established in the same group. About half of the patients with liver disease had overt feminising changes. Total and unbound plasma E2 concentrations were within the normal range in all patients. Total plasma E1 was significantly elevated only in those patients with liver disease and gynaecomastia, and a similar trend was seen for total plasma E3.
"Concepts" in Diabetes Mellitus
Authors: ROBERT MATZ
Journal: Annals of Internal Medicine (1975)

Comments and CorrectionsJune 1, 1975"Concepts" in Diabetes MellitusROBERT MATZ, M.D., F.A.C.P.ROBERT MATZ, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-82-6-853_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: It is unfortunate that "concepts" remain entrenched in medicine while facts are ignored until they overwhelm the concept. I refer to the editorial note by Molnar and Service (1) in the December 1974 issue.In 1962 Shaw and associates (2) showed that low doses of insulin were just as effective as high doses in correcting diabetic ketoacidosis. In 1954 Smith and Martin (3) reported that the time required to lower the blood sugar to 300 mg/100 ml and to raise the serum bicarbonate to 20 meq/litre was not influenced by changes in insulin dosage from 80 to...References1. MOLNARSERVICE GF: Low-dosage continuous insulin infusion for diabetic coma. Ann Intern Med 81:853-854, 1974 LinkGoogle Scholar2. SHAWHURWITZSCHMUKLER CGM: A clinical and laboratory study of insulin dosage in diabetic acidosis: comparison with small and large doses. Diabetes 11:23-30, 1962 MedlineGoogle Scholar3. SMITHMARTIN KH: Response of diabetic coma to various insulin dosages. Diabetes 3:287-294, 1954 CrossrefMedlineGoogle Scholar4. MATZ R: Diabetic coma: guidelines in therapy. NY State J Med 74:642-648, 1974 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics June 1, 1975Volume 82, Issue 6Page: 853-853KeywordsBicarbonatesBlood sugarComaInsulin Issue Published: June 1, 1975 PDF DownloadLoading ...