tbuckley/cabot-search huggingface dataset:
Glomic cells and blood vessels in the hyperplastic carotid bodies of spontaneously hypertensive rats
Authors: P. SMITH, R. JAGO, D. HEATH
Journal: Cardiovascular Research (1984)

Carotid bodies from 21 normotensive Wistar albino rats were compared with those from 20 spontaneously hypertensive rats of the Okamoto strain. From serial histological sections the volume of the carotid bodies was estimated by Simpson's rule. Differential and absolute cell counts were also performed on the chief and elongated cells which surround them. The glomic vasculature was examined by light and electron microscopy. Although the carotid bodies of Okamoto rats were nearly three times as large as those of Wistar rats of comparable body weight, there was no difference in the proportion of the two types of cell. The organisation of glomic cells was also similar in the two strains. The main carotid body artery consists of a muscular tube with a valve-like cushion at its orifice. In the Okamoto rats branches of this artery were occluded by intimal proliferations of myofibroblasts embedded within a copious, loose matrix of acid mucopolysaccharide ground substance. These proliferations appeared to originate from intimal pads situated at the origins of many glomic arteries and arterioles. These findings are in sharp contrast to those in the hyperplastic human carotid body.
LKM autoantibodies in autoimmune hepatitis, APS1 and chronic hepatitis C: quantification of anti-CYP2D6 autoantibodies with 35S-labeled recombinant protein and comparison of target proteins
Authors: P. Obermayer-Straub, A. Kayser, S. Braun, S. Loges, B. Lüttig, J. Perheentupa, M.P. Manns
Journal: Journal of Hepatology (1998)
Abstract 752: The effect of food on the pharmacokinetics of tivozanib
Authors: Monette M. Cotreau, Thomas King, Lisa Massmanian, Andrew Strahs, William Slichenmyer, Dennis Vargo
Journal: Cancer Research (2012)

Abstract Background: Tivozanib, a potent, selective, long-half-life tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, has demonstrated antitumor activity in a Phase II study in patients with renal cell carcinoma (RCC), and is currently being studied in clinical trials in patients with RCC and other solid tumors. The goal of this study was to investigate the effect of food on the pharmacokinetics (PK) of a single 1.5 mg dose of tivozanib in healthy subjects. Methods: This was a single-center, open-label, randomized, two-period, crossover Phase I trial. Subjects were admitted to the clinical research unit (CRU) 1 day before dosing, fasted ∼10 hours, and were randomized to fed (standard high-fat breakfast)/fasted or fasted/fed sequence. In each phase of the sequence, subjects received a single oral dose of tivozanib 1.5 mg with a 6-week washout period between doses. Subjects remained at the CRU for at least 48 hours post dose for blood sample collection and safety monitoring, and were assessed on an outpatient basis for up to 504 hours post dose. PK data were analyzed by non-compartmental methods. The effect of food on PK was assessed using standard criteria for bioequivalence based on the exposure parameters AUC0-α and Cmax. If the 90% confidence intervals for the fed/fasted AUC0-α and Cmax fell within the range of 80% to 125%, it was concluded that food had no effect on exposure. Results: Thirty healthy volunteers were enrolled (19M/11F; mean age 39 years [range 22-53 years]). There was no significant difference in AUC0-α of serum tivozanib between the fed and fasted states (107.4%; Table 1). Food caused a significant decrease in serum tivozanib levels vs fasted state (Cmax: 77.5%). Conclusions: These results indicate that dosing tivozanib with food decreases maximal concentrations by ∼ 23%, but does not affect overall exposure. As tivozanib is dosed chronically in oncology patients and accumulates ∼6 to 7 times single-dose levels when at steady-state, these results are not likely to affect dosing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 752. doi:1538-7445.AM2012-752
Medical Responsibility and Global Environmental Change
Authors: Michael McCally
Journal: Annals of Internal Medicine (1990)

Global environmental change threatens the habitability of the planet and the health of its inhabitants. Toxic pollution of air and water, acid rain, destruction of stratospheric ozone, waste, species extinction and, potentially, global warming are produced by the growing numbers and activities of human beings. Progression of these environmental changes could lead to unprecedented human suffering. Physicians can treat persons experiencing the consequences of environmental change but cannot individually prevent the cause of their suffering. Physicians have information and expertise about environmental change that can contribute to its slowing or prevention. Work to prevent global environmental change is consistent with the social responsibility of physicians and other health professionals.
In Vivo Association Between Alcohol Intoxication, Aggression, and Serotonin Transporter Availability in Nonhuman Primates
Authors: Andreas Heinz, J. Dee Higley, Julia G. Gorey, Richard C. Saunders, Douglas W. Jones, Daniel Hommer, Kristin Zajicek, Stephen J. Suomi, Klaus-Peter Lesch, Daniel R. Weinberger, Markku Linnoila
Journal: American Journal of Psychiatry (1998)

Studies on brain serotonin metabolism in human and nonhuman primates have indicated that dysfunction of serotonin transmission may play a role in the biological vulnerability to dependence on alcohol. Among young men, low sensitivity to alcohol intoxication predicts subsequent alcohol abuse and dependence.The authors used single photon emission computed tomography and the radioligand [(I)123]beta-CIT ([(I)123]methyl 3beta-(4-iodophenyl) tropane-2-carboxylate) to measure the availability of serotonin transporters in 11 male rhesus monkeys, and the monkeys were genotyped for a functional polymorphism of the serotonin transporter gene. The 11 monkeys had experienced parental separation after birth; their behavior and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in CSF had been assessed regularly.In the 5-year-old monkeys, there was a significant negative correlation between beta-CIT binding to serotonin transporters in the brainstem and 5-HIAA concentrations in CSF. Animals with greater beta-CIT binding and low CSF 5-HIAA concentrations displayed greater aggressiveness and were less sensitive to alcohol-induced intoxication. The genetic constitution of the serotonin transporter promoter gene did not significantly contribute to the availability of brainstem serotonin transporters as measured by beta-CIT binding.In adult nonhuman primates who underwent early developmental stress, variables indicating a low serotonin turnover rate were associated with behavior patterns similar to those predisposing to early-onset alcoholism among humans.
Binding of 125I-insulin to the isolated glomeruli of rat kidney.
Authors: K Kurokawa, F J Silverblatt, K L Klein, M S Wang, R L Lerner
Journal: Journal of Clinical Investigation (1979)

To investigate a possible action of insulin on the glomerulus, the binding 125I-insulin to the isolated glomeruli prepared from rat kidney was examined. When incubated at 22 degrees C, 125I-insulin binding proceeded with time and reached a steady state at 45 min at which time nonspecific binding was less than 25% of total binding. A small fraction of 125I-insulin was degraded during incubation. This binding was specific to insulin in that it was inhibited by unlabeled porcine and beef insulins and to a lesser extent by porcine proinsulin and desalanine-desasparagine insulin, but not by glucagon, parathyroid hormone, vasopressin, calcitonin, and angiotensin II. Increasing concentrations of nonlabeled insulin displaced 125I-insulin binding in a dose-dependent fashion. Scatchard plot of the data was curvilinear consistent with either two classes of receptors with different affinities or a single class of receptors that demonstrate negative cooperativity. The addition of excess nonlabeled insulin to the glomeruli preincubated with 125I-insulin resulted in a rapid dissociation of approximately or equal to 70% of bound 125I-insulin. Insulin decreased the increments in glomerular cyclic AMP levels by epinephrine and by prostaglandin E2, but not those by histamine. These data showed the presence of specific insulin receptors in the glomeruli, and that insulin action may be, at least in part, through modulation of glomerular cyclic AMP concentrations. Such action of insulin may underlie the alteration in glomerular ultrafiltration and the glomerular ultrafiltration and the development of glomerular lesions in diabetes mellitus, a disease in which insulin deficiency or the tissue resistance to insulin exists.
Outpatient antibiotics for pelvic inflammatory disease
Authors: J. D C Ross
Journal: BMJ (2001)

Standing at the therapeutic crossroads trying to choose a path for outpatients with pelvic inflammatory disease, a clinician may find his or her evidence based map lacking in detail. Not only is pelvic inflammatory disease hard to diagnose; once it has been diagnosed it is not clear what the best outpatient treatment is.

Pelvic inflammatory disease remains a condition with imprecise diagnostic criteria where the clinical features are neither sensitive nor specific1 and where the “gold standard” of laparoscopy lacks standardisation and is not routinely available in clinical practice. Non-invasive diagnosis using magnetic resonance imaging has potential and may be comparable with laparoscopy and superior to transvaginal ultrasound,2 but data and access are both limited.

Once the diagnosis of pelvic inflammatory disease has been made what outcomes are realistic after treatment? Rapid resolution of symptoms, preservation of fertility, and low rates of ectopic pregnancy are all desirable outcomes, but only the first, short term control of symptoms, has …
Genetic or pharmaceutical blockade of p110δ phosphoinositide 3-kinase enhances IgE production
Authors: Ting-ting Zhang, Klaus Okkenhaug, Baher F. Nashed, Kamal D. Puri, Zachary A. Knight, Kevan M. Shokat, Bart Vanhaesebroeck, Aaron J. Marshall
Journal: Journal of Allergy and Clinical Immunology (2008)
Abstract 2730: Anti-Her2/neu immunotoxins: Impact of monovalent and bivalent designs on <i>in vitro</i> and <i>in vivo</i> antitumor efficacy
Authors: Yu Cao, John W. Marks, Zhigang Liu, Lawrence H. Chueng, Walter N. Hittelman, Michael G. Rosenblum
Journal: Cancer Research (2012)

Abstract Immunotoxins and designed fusion constructs have significant potential for improved cancer therapy and reduced toxic side effects. We compared the efficacy of anti-Her2/neu immunotoxins containing recombinant gelonin (rGel) in either monovalent or bivalent formats. The bivalent conjugate was Herceptin/rGel chemical conjugate and the monovalent constructs were Herceptin-derived scFv (4D5) fused to rGel in two orientations: 4D5/rGel and rGel/4D5. All three immunotoxins retained the affinity and specificity of the original antibody as well as the biological activity of rGel toxin. Cytotoxicity studies against a panel of Her2/neu expressing tumor cell lines revealed significant differences among these constructs. Both Herceptin/rGel conjugate and rGel/4D5 displayed the best cytotoxicity and specificity whereas 4D5/rGel was the least potent. IC50 values ranged from 0.1-1nM for Herceptin/rGel conjugate and rGel/4D5, but were 10-1000 fold higher for 4D5/rGel. BT474 M1 HR cells with acquired resistance to Herceptin, either by constitutive Akt activation or external factor stimulation, remained sensitive to these constructs compared to the parental cells. The cytotoxicity of all constructs was generally restricted to cells expressing high levels of Her2/neu indicating that Herceptin-based immunotoxins may not be toxic to normal tissues with endogenous (low or medium) levels of Her2/neu. Treatment of nude mice bearing well-developed SKOV3 tumor xenografts with either Herceptin/rGel or rGel/4D5 resulted in impressive tumor inhibition compared to either Herceptin or 4D5/rGel. These studies demonstrate that engineered fusion constructs are competitively effective compared with chemically-generated immunotoxins with longer plasma circulation times. Further characterization of the constructs on Her2/neu overexpressing tumor cells with MDR/MRP resistance is currently ongoing. In conclusion, our studies suggested that smaller, engineered monovalent fusion constructs have excellent, comparable activity compared to intact bivalent antibody conjugates. In addition, the orientation of rGel/scFv vs scFv/rGel can significantly impact the in vitro and in vivo therapeutic activity and should be a consideration in design optimization. Research conducted, in part, by the Clayton Foundation for Research. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2730. doi:1538-7445.AM2012-2730
Effect of colchicine and vinblastine on rat intestinal water transport and Na-K-ATPase activity.
Authors: D Rachmilewitz, R Fogel, F Karmeli
Journal: Gut (1978)

The hypothesis that colchicine and vinblastine, which are commonly used for therapeutic purposes and known to cause diarrhoea, decrease intestinal water transport by inhibition of Na-K-ATPase activity was tested in rats. Net fluid transport by jejunal segments was measured four hours after intraperitoneal injection of either 0.15 M NaCl (0.5 ml/100 g), colchicine (0.5 mg/100 g b.w.), or vinblastine (1.0 mg/100 g b.w.). Colchicine and vinblastine decreased net fluid transport: 3.0 +/- 0.9 (SE) and 4.6 +/- 0.4 (SE) respectively, as compared to that transported by segments from rats injected with 0.15 M NaCl, 8.6 +/- 0.7 (SE) g fluid/hour/g. Methylprednisolone (3.0 mg/100 g b.w.) abolished the inhibitory effect of cholchicine and vinblastine on fluid transport. Colchicine and vinblastine were found to decrease significantly mucosal Na-K-ATPase activity, 18.2 +/- 4.9 (SE); 25.2 +/- 2.4 (SE) respectively, as compared to that measured in rats injected with saline 40.6 +/- 3.4 (SE) mumol/mg protein/hour. Pretreatment with methylprednisolone prevented the decrease in enzyme activity observed in rats injected with colchicine and vinblastine. The degree of inhibition in intestinal Na-K-ATPase activity was similar to that observed in fluid transport following colchicine and vinblastine. It is thus suggested that colchicine-induced inhibition of water transport is caused by inhibition of Na-K-ATPase activity, an effect which can be prevented by pretreatment with methyl-prednisolone.
PTU-001 Refeeding Syndrome: is our Knowledge Deficient?: Abstract PTU-001 Table
Authors: A Mohanaruban, J Landy, C Gouveia, C Collins
Journal: Gut (2013)

<h3>Introduction</h3> The 2006 NICE guidelines on “Nutrition support in adults” recommend screening and identification of patients at risk of refeeding syndrome (RS). Despite the implementation of local hospital policies, RS still occurs. This may, in part, be due to a lack of awareness amongst clinicians responsible for at risk patients. We aimed to assess the knowledge and awareness of RS amongst medical doctors in our Trust. <h3>Methods</h3> We conducted a questionnaire survey of doctors’ practises between April and August 2008. In total 68 doctors, working in medical specialities, from FY1 to Consultants, were surveyed. <h3>Results</h3> The overall response rate was 40 (59%). Only 10% were unaware of RS (all FY doctors). However, only 35% were aware of the importance of correcting electrolyte imbalance when commencing enteral feeding. 30% would not monitor electrolytes daily with 25% of the respondents unaware of the important electrolytes to monitor. Although 90% of respondents recognised thiamine as important supplementation, only 20% indicated they would prescribe this to all at risk patients. Only 58% stated they would provide Vitamin B Co-strong and only 63% multivitamins or trace element supplements. <h3>Conclusion</h3> RS is potentially fatal. It is essential that clinicians are aware and able to identify at risk patients. This survey highlights that, although many clinicians are familiar with RS and its effects, there is a lack of awareness regarding the NICE guidelines and practise aimed at its prevention in those patients at high risk. Most strikingly, 65% of the doctors surveyed did not consider starting enteral feed prior to or alongside correcting any electrolyte imbalances. Delaying the onset of enteral feed may put patients at greater risk of malnutrition. Further education and training about RS are necessary for all grades, particularly junior doctors. <h3>Disclosure of Interest</h3> None Declared <h3>References</h3> Mehanna HM, Moledina J, Travis J, Refeeding syndrome: what it is, and how to prevent and treat it. BMJ 2008; 336:1495–1498 NICE guidelines for nutritional support in adults. http://www.nice.org.uk/cg32
Canadians win award over breast implants
Authors: D. Spurgeon
Journal: BMJ (1998)

About 3000 women in Ontario and Quebec have won a compensation settlement of US$15.3m (£9.5m) in a suit involving silicone gel breast implants.

The settlement involves women who claim that their health has been adversely affected by implants manufactured by a United States firm, Heyer-Schulte Corporation, which is …
Henry de Chair Baker
Authors: Philip F Roberts
Journal: BMJ (2004)

Former consultant pathologist Norfolk and Norwich University Hospital (b London 1924; q Manchester 1948; MD, FRCPath), died from prostate cancer on 5 February 2004.​2004.




Figure 1




Henry's first consultant post was at Dudley Hospital, but his principal career was as a consultant histopathologist and director of pathology services at the Norfolk and Norwich group of hospitals from 1967 to 1983. He reorganised the pathology services in the north east quadrant of East Anglia, reducing the number of laboratories to four and redesigning the new laboratories in Norwich; he also appointed the first full time pathologist to Great Yarmouth and Lowestoft hospitals. He was a first class racing dinghy sailor, later in life becoming a keen cruising sailor. He leaves a wife, Charmian; three children; and five grandsons.
Blood Pressure in Obesity
Authors: Robert W. Vaughan
Journal: JAMA (1973)

To the Editor.—  Burch and Shewey in their recent article, Sphygmomanometric Cuff Size and Blood Pressure Recordings (225:1215, 1973), reemphasized the importance of the width of the cuff bladder as opposed to the length, and supported the continued use of the current standard cuff of 12-to 14-cm width for an adult human arm. Their findings were based on a series of adult patients of apparently normal weight, where the largest circumference of the right arm at the brachium ranged between 20.5 and 39 cm, with an average of 26.8 cm.  I would like to report on a series of 25 patients undergoing jejunoileal small bowel bypass; right brachial arterial blood pressure was measured, using a standard clinical mercury manometer with one of two self-adhering cuffs. The smaller measured 23 × 12.5 cm, while the larger was 38 × 18.5 cm. We employed the usual rule of thumb, ie, the inflatable
ln-111 Leukocytes Confirm Lymphatic Spread of Infection
Authors: DONALD S. SCHAUWECKER
Journal: Clinical Nuclear Medicine (1992)

A 55-year-old woman with diabetes had an ulcer in the soft tissues under the fifth metatarsal, and a request was made to rute out osteomyelitis. Discussion with the patient revealed marked left groin pain of recent onset. A combined three-phase bone/in-111 leukocyte study confirmed osteomyelitis of the fifth metatarsal. In addition, there was intense uptake in the lymph nodes of the left groin region representing lymphatic spread of infection. After 6 weeks of antibiotic therapy, the patient became asymptomatic. A repeat in-111 leukocyte study at that time showed no uptake in the groin.
Lepirudin for anticoagulation in patients with heparin‐induced thrombocytopenia treated with continuous renal replacement therapy
Authors: Ajeet Gajra, Neerja Vajpayee, Arienne Smith, Bernard J. Poiesz, Sriram Narsipur
Journal: American Journal of Hematology (2006)

Abstract Lepirudin is a potent, direct thrombin inhibitor used for anticoagulation in patients with heparin‐induced thrombocytopenia type II (HIT). The half‐life of lepirudin is prolonged in patients with renal insufficiency. Preliminary studies suggest that it is safe to use lepirudin in patients being treated with intermittent hemodialysis but information regarding its use with continuous renal replacement therapy (CRRT) is scarce. CRRT is used in acute care settings to remove fluid and uremic toxins in patients with renal failure with hemodynamic instability. Patients with HIT, renal failure, and hemodynamic instability pose a complex situation for clinical management. These patients require anticoagulation with nonheparin agents with simultaneous CRRT. There are no guidelines in the literature regarding the management of this patient group. We report our experience with lepirudin at managing four such patients with HIT, being treated with CRRT. Am. J. Hematol., 2007. © 2006 Wiley‐Liss, Inc.
Controlling Costs by Expanding the Medicare Acute Care Episode Demonstration
Authors: Maura Calsyn, Ezekiel J. Emanuel
Journal: JAMA Internal Medicine (2014)

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