Atrial natriuretic peptide receptor subtype determination and biological actions of atrial natriuetic peptided in bovine cardiac muscle and hypertensive rat liver

Atrial natriuretic peptide (ANP) has previously been shown to bind to specific ANP receptors and increase intracellular cGMP levels in purified rat cardiac sarcolemmal membranes. Experiments described in this thesis were performed to investigate the binding characteristics of ANP in bovine ventricular sarcolemmal membranes and in plasma membranes isolated from the liver of hypertension-resistant and hypertension-sensitive Dahl rats fed on two dietary salt regimes one of 0.8% NaCl and the other 8% NaCl. Additional experiments utilising ANP analogues in radio-receptor assays and radio-receptor crosslinking assays were performed to determine the precise nature of the ANP receptor population present in these membrane preparations. In bovine ventricular cardiac sarcolemmal membranes, ANP bound specifically to one class of ANP receptor with a Kd of approximately 44 pM and a Bmax of approximately 49 fmol/mg protein. ANP produced a 1.8-fold stimulation of manganese-dependent guanylate cyclase activity with an EC50 value of approximately 1 nM. Receptor binding using the des-ANP analogue indicated the predominant presence of the ANP-B receptor subtype. Radioreceptor crosslinking experiments did not entirely agree with these experiments. Radio-receptor crosslinking indicated the presence of two ANP receptors one of 60 kDa and one of 120 kDa, equivalent to the molecular weights of ANP receptors found in other tissues. Collectively these experiments indicate that bovine ventricular sarcolemmal membranes possess ANP receptors, at least a proportion of which are coupled to guanylate cyclase (ANP-B receptors). In plasma membranes from the liver of Dahl-Resistant (Dahl-R) and Dahl-Sensitive (Dahl-S) rats, ANP bound specifically to one class of ANP receptor with Kd values ranging from 245 to 288 pM and Bmax values ranging from 104 to 217 fmol/mg protein. ANP produced a 3.8 to 6.15-fold stimulation of manganese-dependent guanylate cyclase activity with an EC50 values ranging from 2.3 to 7.4 nM, dependent on the strain of Dahl rat and the dietary salt regime used. In liver membranes isolated from rats sensitive to salt-induced hypertension results indicated increases in Bmax with no change in Kd for ANP binding to receptors and higher basal and ANP-stimulated guanylate cyclase levels. Receptor binding using the des-ANP analogue indicated the presence of 13-33% ANP-C receptors with a majority of ANP-B receptors in plasma membranes isolated from the liver of Dahl-R and Dahl-S rats. However, radio-receptor crosslinking experiments were unable to support these results. Collectively these experiments indicate that in plasma membranes isolated from the liver of Dahl-R and Dahl-S rats possess ANP receptors, at least a majority of which are coupled to guanylate cyclase (ANP-B receptors) and that sensitivity to hypertension induced by a high salt dietary regime increases the density of ANP receptors coupled to guanylate cyclase

Documentation of antipsychotic-related adverse drug reactions: An educational intervention

Antipsychotic agents are associated with harmful adverse reactions which impact negatively on patient adherence and clinical management. Accurate and complete documentation of signs and symptoms in the clinical notes is an important means of communication between healthcare providers, and an essential component in the management of antipsychotic-induced adverse drug reactions. To determine the impact of an educational intervention on the incidence and extent of antipsychotic-induced adverse drug reaction documentation in patient medical records

Endoscopic Management of Cavernous Carotid Surgical Complications: Evaluation of a Simulated Perfusion Model

Objective—Endoscopic surgical treatment of pituitary tumors, lateral invading tumors, or aneurysms requires surgeons to operate adjacent to the cavernous sinus. During these endoscopic endonasal procedures, the carotid artery is vulnerable to surgical injury at its genu. The objective of this simulation model was to evaluate trainees regarding management of a potentially lifethreatening vascular injury. Methods—Cadaveric heads were prepared in accordance with the Oregon Health & Science University body donation program. An endoscopic endonasal approach was used, and a perfusion pump with a catheter was placed in the ipsilateral common carotid artery at its origin in the neck. Learners used a muscle graft to establish vascular control and were evaluated over 3 training sessions. Simulation assessment, blood loss during sessions, and performance metric data were collected for learners. Results—Vascular control was obtained at a mean arterial pressure of 65 mm Hg using a muscle graft correctly positioned at the arteriotomy site. Learners improved over the course of training, with senior residents (n = 4) performing better across all simulation categories (situation awareness, decision making, communications and teamwork, and leadership); the largest mean difference was in communication and teamwork. Additionally, learner performance concerning blood loss improved between sessions (t = 3.667, P \u3c 0.01). Conclusions—In this pilot endoscopic endonasal simulation study, we successfully demonstrate a vascular complication perfusion model. Learners were able to gain direct applicable expertise in endoscopic endonasal techniques, instrumentation use, and teamwork required to optimize the technique. Learners gained skills of vascular complication management that transcend this model

Hypercoagulability and Risk of Venous Thromboembolic Events in Endogenous Cushing's Syndrome: A Systematic Meta-Analysis

Background: Hypercortisolism has been implicated in the development of venous thromboembolic events (VTE). We aimed to characterize VTE risk in endogenous Cushing's syndrome (CS) patients, compare that risk to other pathologies, and determine if there are any associated coagulation factor changes.Methods: Medline and Scopus search for “hypercortisolism” and “thromboembolic disease” from January 1980 to April 2017 to include studies that reported VTE rates and/or coagulation profile of CS patients. A systematic review and meta-analysis were performed.Results: Forty-eight studies met inclusion criteria. There were 7,142 CS patients, average age was 42 years and 77.7% female. Odds ratio of spontaneous VTE in CS is 17.82 (95%CI 15.24–20.85, p < 0.00001) when comparing to a healthy population. For CS patients undergoing surgery, the odds ratio (both with / without anticoagulation) of spontaneous VTE is 0.26 (95%CI 0.07–0.11, p < 0.00001)/0.34 (0.19–0.36, p < 0.00001) when compared to patients undergoing hip fracture surgery who were not treated with anticoagulants. Coagulation profiles in patients with CS showed statistically significant differences compared to controls, as reflected by increases in von Willebrand factor (180.11 vs. 112.53 IU/dL, p < 0.01), as well as decreases in activated partial thromboplastin time (aPTT; 26.91 vs. 30.65, p < 0.001) and increases in factor VIII (169 vs. 137 IU/dL, p < 0.05).Conclusion: CS is associated with significantly increased VTE odds vs. general population, but lower than in patients undergoing major orthopedic surgery. Although exact timing, type, and dose of anticoagulation medication remains to be established, clinicians might consider monitoring vWF, PTT, and factor VIII when evaluating CS patients and balance advantages of thromboprophylaxis with risk of bleeding

Recent Progress in the Medical Therapy of Pituitary Tumors

Management of pituitary tumors is multidisciplinary, with medical therapy playing an increasingly important role. With the exception of prolactin-secreting tumors, surgery is still considered the first-line treatment for the majority of pituitary adenomas. However, medical/pharmacological therapy plays an important role in controlling hormone-producing pituitary adenomas, especially for patients with acromegaly and Cushing disease (CD). In the case of non-functioning pituitary adenomas (NFAs), pharmacological therapy plays a minor role, the main objective of which is to reduce tumor growth, but this role requires further studies. For pituitary carcinomas and atypical adenomas, medical therapy, including chemotherapy, acts as an adjuvant to surgery and radiation therapy, which is often required to control these aggressive tumors. In the last decade, knowledge about the pathophysiological mechanisms of various pituitary adenomas has increased, thus novel medical therapies that target specific pathways implicated in tumor synthesis and hormonal over secretion are now available. Advancement in patient selection and determination of prognostic factors has also helped to individualize therapy for patients with pituitary tumors. Improvements in biochemical and “tumor mass” disease control can positively affect patient quality of life, comorbidities and overall survival. In this review, the medical armamentarium for treating CD, acromegaly, prolactinomas, NFA, and carcinomas/aggressive atypical adenomas will be presented. Pharmacological therapies, including doses, mode of administration, efficacy, adverse effects, and use in special circumstances are provided. Medical therapies currently under clinical investigation are also briefly discussed

Awareness of diabetes mellitus among African traditional healers in the Nelson Mandela Metropole

Diabetes mellitus, a chronic illness, affects approximately 8% of black South Africans. Traditional healers are an integral part of the lifestyle of the African people. Opsomming Diabetes mellitus, 'n chroniese siekte, affekteer na raming 8% van Suid-Afrika se swart bevolking. Tradisionele genesers is 'n integrale deel van die lewenswyse van dié bevolkingsgroep. *Please note: This is a reduced version of the abstract. Please refer to PDF for full text

Awarness of diabetes mellitus among African traditional healers in the Nelson Mandela Metropole: research

Diabetes mellitus, a chronic illness, affects approximately 8% of black South Africans. Traditional healers are an integral part of the lifestyle of the African people. Approximately 80% of black patients consult a western doctor only after having consulted a traditional healer, yet traditional healers remain an untapped resource in South Africa. The primary objective of the study was to determine the clinical knowledge pertaining to diabetes mellitus of traditional healers in the Nelson Mandela Metropole (NMM), and to educate the healers on diabetes mellitus through the medium of interactive workshops. Three workshops were held with the healers over a seventeen-month period. The target population consisted of all traditional healers of the NMM interested in participating in the research project. The results obtained indicated that healers of the NMM had a basic knowledge about diabetes and a willingness to learn more about conventional aspects of the disease. At a feedback workshop the healers indicated that they were using the information gained during preceding workshops and that they have begun imparting the knowledge gained to other traditional healers and to their apprentices. A relationship has been established between healers of the NMM and the University of Port Elizabeth (UPE) and Port Elizabeth Technicon. Diabetes mellitus, ๋n chroniese siekte, affekteer na raming 8% van Suid-Afrika se swart bevolking. Tradisionele genesers is ๋n integrale deel van die lewenswyse van diศ bevolkingsgroep. Bykans 80% van alle swart pasiฮnte besoek ๋n tradisionele geneser voor hulle hul tot ๋n westerse geneesheer wend. Ten spyte hiervan bly tradisionele genesers ๋n onbenutte hulpbron in Suid-Afrika. Die primอre doelwitte van diศ navorsing was om die kliniese kennis van tradisionele genesers ten opsigte van diabetes te bepaal en om hulle verder oor diabetes te onderrig deur middel van interaktiewe werkswinkels. Drie werkswinkels is oor ๋n tydperk van sewentien maande gehou. Die teikengroep was ๋n groep genesers wat geิnteresseerd was om aan die navorsing deel te neem. Die navorsing toon dat genesers in die NMM oor ๋n basiese kennis van diabetes mellitus beskik en gewillig was om meer van die konvensionele aspek van diabetes te leer. In ๋n terugvoerbespreking het die genesers te kenne gegee dat die inligting wat hulle tydens die werkswinkels verkry het, aktief deur hulle gebruik word, asook oorgedra word aan ander genesers en vakleerlinge. Die navorsing het die basis vir ๋n goeie verstandhouding tussen die tradisionele genesers, die Universiteit van Port Elizabeth and die Port Elizabeth Technikon gelอ. Key Words: Traditional healer, Diabetes mellitus, Interactive workshops, Nelson Mandela Metropole, South Africa Health SA Gesondheid Vol.9(1) 2004: 27-3