Circulating adrenomedullin and B-type natriuretic peptide do not predict blood pressure fluctuations during pheochromocytoma resection: a cross-sectional study

Background: Despite adequate presurgical management, blood pressure fluctuations are common during resection of pheochromocytoma or sympathetic paraganglioma (PPGL). To a large extent, the variability in blood pressure control during PPGL resection remains unexplained. Adrenomedullin and B-type natriuretic peptide, measured as MR-proADM and NT-proBNP, respectively, are circulating biomarkers of cardiovascular dysfunction. We investigated whether plasma levels of MR-proADM and NT-proBNP are associated with blood pressure fluctuations during PPGL resection. Methods: Study subjects participated in PRESCRIPT, a randomized controlled trial in patients undergoing PPGL resection. MR-proADM and NT-proBNP were determined in a single plasma sample drawn before surgery. Multivariable linear and logistic regression analyses were used to explore associations between these biomarkers and blood pressure fluctuations, use of vasoconstrictive agents during surgery as well as the occurrence of perioperative cardiovascular events. Results: A total of 126 PPGL patients were included. Median plasma concentrations of MR-proADM and NT-proBNP were 0.51 (0.41-0.63) nmol/L and 68.7 (27.9-150.4) ng/L, respectively. Neither MR-proADM nor NT-proBNP were associated with blood pressure fluctuations. There was a positive correlation between MR-proADM concentration and the cumulative dose of vasoconstrictive agents (03B2 0.44, P = 0.001). Both MR-proADM and NT-proBNP were significantly associated with perioperative cardiovascular events (OR: 5.46, P = 0.013 and OR: 1.54, P = 0.017, respectively). Conclusions: plasma MR-proADM or NT-proBNP should not be considered as biomarkers for the presurgical risk assessment of blood pressure fluctuations during PPGL resection. Future studies are needed to explore the potential influence of these biomarkers on the intraoperative requirement of vasoconstrictive agents and the perioperative cardiovascular risk.Diabetes mellitus: pathophysiological changes and therap

Solubilization of Proteins in 2DE: An Outline

Protein solubilization for two-dimensional electrophoresis (2DE) has to break molecular interactions to separate the biological contents of the material of interest into isolated and intact polypeptides. This must be carried out in conditions compatible with the first dimension of 2DE, namely isoelectric focusing. In addition, the extraction process must enable easy removal of any nonprotein component interfering with the isoelectric focusing. The constraints brought in this process by the peculiar features of isoelectric focusing are discussed, as well as their consequences in terms of possible solutions and limits for the solubilization process

Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers

Germline mutations in succinate dehydrogenase subunit B and D (SDHB and SDHD) are predisposed to hereditary paraganglioma (PGL) and pheochromocytoma (PHEO). The phenotype of pathogenic variants varies according to the causative gene. In this retrospective study, we estimate the mortality of a nationwide cohort of SDHB variant carriers and that of a large cohort of SDHD variant carriers and compare it to the mortality of a matched cohort of the general Dutch population. A total of 192 SDHB variant carriers and 232 SDHD variant carriers were included in this study. The Standard Mortality Ratio (SMR) for SDHB mutation carriers was 1.89, increasing to 2.88 in carriers affected by PGL. For SDHD variant carriers the SMR was 0.93 and 1.06 in affected carriers. Compared to the general population, mortality seems to be increased in SDHB variant carriers, especially in those affected by PGL. In SDHD variant carriers, the mortality is comparable to that of the general Dutch population, even if they are affected by PGL. This insight emphasizes the significance of DNA-testing in all PGL and PHEO patients, since different clinical risks may warrant gene-specific management strategies

Hand and wrist problems in general practice - Patient characteristics and factors related to symptom severity

Objectives. Hand and wrist problems are common, but little is known about characteristics of patients consulting the general practitioner (GP) for these problems. The objectives are: (i) to describe wrist and hand problems presented to the GP in terms of severity of symptoms, and their impact on physical, emotional and social functioning; (ii) to describe patient and disease characteristics across different diagnostic categories; and (iii) to study factors related to the severity of hand or wrist problems. Methods. Patients consulting their GP with hand or wrist problems were sent a questionnaire containing questions on socio-demographic variables, characteristics of the complaint, physical activity and psychosocial factors. The GP recorded information on symptoms, signs and medical diagnosis. We studied the cross-sectional association between a variety of factors and severity of hand or wrist problems, using the Symptom Severity Scale as the outcome measure. Results. Mean age of the 267 participants was 49.3 yrs and 74% were female. The three most frequently recorded diagnoses were osteoarthritits (17%), tenosynovitis (16%) and nerve entrapment (12%). The characteristics of patients varied slightly across diagnostic categories. Patients who did not have paid work, had longer duration of symptoms, diagnosis of entrapment, higher pain intensity, higher body mass index and higher scores on worrying reported significantly higher scores on severity of hand or wrist problems (P-value <0.10). Conclusion. Primary care patients with hand or wrist problems report pain and reduced function. Impact on other aspects of perceived health is limited. Severity seems to be associated with socio-demographic, physical and psychosocial factors, more than with medical diagnosis

Intricacies of the Molecular Machinery of Catecholamine Biosynthesis and Secretion by Chromaffin Cells of the Normal Adrenal Medulla and in Pheochromocytoma and Paraganglioma

The adrenal medulla is composed predominantly of chromaffin cells producing and secreting the catecholamines dopamine, norepinephrine, and epinephrine. Catecholamine biosynthesis and secretion is a complex and tightly controlled physiologic process. The pathways involved have been extensively studied, and various elements of the underlying molecular machinery have been identified. In this review, we provide a detailed description of the route from stimulus to secretion of catecholamines by the normal adrenal chromaffin cell compared to chromaffin tumor cells in pheochromocytomas. Pheochromocytomas are adrenomedullary tumors that are characterized by uncontrolled synthesis and secretion of catecholamines. This uncontrolled secretion can be partly explained by perturbations of the molecular catecholamine secretory machinery in pheochromocytoma cells. Chromaffin cell tumors also include sympathetic paragangliomas originating in sympathetic ganglia. Pheochromocytomas and paragangliomas are usually locally confined tumors, but about 15% do metastasize to distant locations. Histopathological examination currently poorly predicts future biologic behavior, thus long term postoperative follow-up is required. Therefore, there is an unmet need for prognostic biomarkers. Clearer understanding of the cellular mechanisms involved in the secretory characteristics of pheochromocytomas and sympathetic paragangliomas may offer one approach for the discovery of novel prognostic biomarkers for improved therapeutic targeting and monitoring of treatment or disease progression