Disorders of Blood Pressure Regulation—Role of Catecholamine Biosynthesis,Release, and Metabolism

Catecholamines (epinephrine and norepinephrine) are synthesised and produced by the adrenal medulla and postganglionic nerve fibres of the sympathetic nervous system. It is known that essential hypertension has a significant neurogenic component, with the rise in blood pressure mediated at least in part by overactivity of the sympathetic nervous system. Moreover, novel therapeutic strategies aimed at reducing sympathetic activity show promise in the treatment of hypertension. This article reviews recent advances within this rapidly changing field, particularly focusing on the role of genetic polymorphisms within key catecholamine biosynthetic enzymes, cofactors, and storage molecules. In addition, mechanisms linking the sympathetic nervous system and other adverse cardiovascular states (obesity, insulin resistance, dyslipidaemia) are discussed, along with speculation as to how recent scientific advances may lead to the emergence of novel antihypertensive treatments.     

Receptor for Advanced Glycation End Products (RAGE) and Implications for the Pathophysiology of Heart Failure

The receptor for advanced glycation end products (RAGE) is expressed in the heart in cardiomyocytes, vascular cells, fibroblasts, and in infiltrating inflammatory cells. Experiments in murine, rat, and swine models of injury suggest that RAGE and the ligands of RAGE are upregulated in key injuries to the heart, including ischemia/reperfusion injury, diabetes, and inflammation. Pharmacological antagonism of RAGE or genetic deletion of the receptor in mice is strikingly protective in models of these stresses. Data emerging from human studies suggest that measurement of levels of RAGE ligands or soluble RAGEs in plasma or serum may correlate with the degree of heart failure. Taken together, the ligand-RAGE axis is implicated in heart failure and we predict that therapeutic antagonism of RAGE might be a unique target for therapeutic intervention in this disorder.     

Long term efficacy of gastric electrical stimulation in intractable nausea and vomiting

BackgroundAlthough the efficacy of gastric electrical stimulation has been reported in short-term studies, there is a lack of data on the long-term improvement of nausea and vomiting by gastric electrical stimulation in patients with delayed or normal gastric emptying.MethodsThirty-one patients were implanted at our centre for medically refractory severe and chronic nausea and/or vomiting. Patients were evaluated at baseline, 6 months then 5 years after implantation (mean follow-up 80 ± 4 months) using a symptomatic and quality of life scores.Key resultsAmongst the 31 patients, 4 were lost to follow-up, 6 explanted due to lack of improvement, and 1 patient died. Out of the 20 patients evaluated over 5 years, the quality of life score showed 27% improvement (p < 0.01), including nausea (62%; p < 0.01), vomiting (111%; p = 0.03), satiety (158%; p < 0.01), bloating (67%; p < 0.01) and epigastric pain (43%; p = 0.03). Over 5 years, 15/20 patients reported a 50% improvement with a global satisfaction rated at 64 ± 6%. Therefore, 15/27 patients (56%) were improved by gastric electrical stimulation over 5 years in intention to treat. Improvement of nausea 6 months after implantation was predictive of 5-year success of gastric electrical stimulation (p = 0.04). Finally, patients with delayed gastric emptying or with normal gastric emptying rate before surgery were similarly improved over 5 years (60% versus 50% respectively).ConclusionGastric electrical stimulation is safe and effective in the long term in patients with medically refractory nausea and vomiting, with an efficacy over 50% beyond 5 years in intention to treat. Gastric emptying measured before implantation did not influence the response rate over 5 years.     

Too tight to give birth? Assessment of pelvic floor muscle function in 277 nulliparous pregnant women

Introduction and hypothesis

Theoretically, tight or strong pelvic floor muscles may impair the progress of labor and lead to instrumental deliveries. We aimed to investigate whether vaginal resting pressure, pelvic floor muscle strength, or endurance at midpregnancy affect delivery outcome.

Methods

This was a prospective cohort study of women giving birth at a university hospital. Vaginal resting pressure, pelvic floor muscle strength, and endurance in 300 nulliparous pregnant women were assessed at mean gestational week 20.8 (±1.4) using a high precision pressure transducer connected to a vaginal balloon. Delivery outcome measures [acute cesarean section, prolonged second stage of labor (> 2 h), instrumental vaginal delivery (vacuum and forceps), episiotomy, and third- and fourth-degree perineal tear) were retrieved from the hospital’s electronic birth records.

Results

Twenty-three women were lost to follow-up, mostly because they gave birth at another hospital. Women with prolonged second stage had significantly higher resting pressure than women with second stage less than 2 h; the mean difference was 4.4 cmH₂O [95 % confidence interval (CI) 1.2–7.6], p?<?0.01, adjusted odds ratio 1.049 (95 % CI 1.011–1.089, p?=?0.012). Vaginal resting pressure did not affect other delivery outcomes. Pelvic floor muscle strength and endurance similarly were not associated with any delivery outcomes.

Conclusions

While midpregnancy vaginal resting pressure is associated with prolonged second stage of labor, neither vaginal resting pressure nor pelvic floor muscle strength or endurance are associated with operative delivery or perineal tears. Strong pelvic floor muscles are not disadvantageous for vaginal delivery.     

Subjective and objective results of arthroscopic debridement of ulnar-sided TFCC (Palmer type 1B) lesions with stable distal radio-ulnar joint

Purpose

The purpose of this study was to determine functional and subjective results of patients who received arthroscopic debridement for their TFCC Palmer 1B lesions and to compare their results with those of arthroscopic suture repair.

Methods

Between March 2007 and August 2011, 36 patients were diagnosed with Palmer type 1B tears and underwent arthroscopic debridement. 31 patients (15 males and 16 females) were followed up for an average of 26.7 months (±17.4 months) postoperatively. Their average age was 36.7 years (±12.7 years). Follow-up included the determination of range of motion (ROM), grip strength, pain, and wrist scores (modified Mayo wrist score (MMWS), Disabilities of the Arm, Shoulder and Hand questionnaire (DASH score)).

Results

Postoperative ROM averaged 99.2 % for the extension/flexion arc, 95.5 % for the radial/ulnar deviation arc, and 99.4 % for the pronation/supination arc of motion when compared with the contralateral wrist. The MMWS was rated excellent in 48 % of patients, good in 39 %, fair in 13 %, and poor in 0 %. The average DASH score was 17.02 (±14.92). There was a significant reduction in pain. The grip strength was 96.7 % (±15.8), pulp-to-pulp pinch 101.9 % (±17.4), and the ulnar variance ?0.12 ± 1.69 mm.

Conclusions

Arthroscopic debridement of Palmer type 1B lesions in stable DRUJ yields satisfactory to excellent results. Our study showed similar results compared with the studies of arthroscopic suture repair with shorter postoperative care and fewer complications.     

Serum Vitamin D Increases with Weight Loss in Obese Subjects 6 Months After Roux-en-Y Gastric Bypass

Background

Malabsorptive surgical procedures lead to deficiencies in fat-soluble vitamins. However, results concerning serum vitamin D (25OHD) after gastric bypass (GBP) are controversial. The aim of the study was to assess the influence of GBP on 25OHD and calcium metabolism.

Methods

Parameters of calcium metabolism were evaluated in 202 obese subjects before and 6 months after GBP. Thirty of them were matched for age, gender, weight, skin color, and season with 30 subjects who underwent sleeve gastrectomy (SG). A multivitamin preparation that provides 200 to 500 IU vitamin D3 per day was systematically prescribed after surgery.

Results

In the 202 patients after GBP, serum 25OHD significantly increased from 13.4?±?9.1 to 22.8?±?11.3 ng/ml (p?<?0.0001), whereas parathyroid hormone (PTH) did not change. Despite a decrease in calcium intake (p?<?0.0001) and urinary calcium/creatinine ratio (p?=?0.015), serum calcium increased after GBP (p?<?0.0001). Preoperatively, 91 % of patients had 25OHD insufficiency (<30 ng/ml), 80 % deficiency (<20 ng/ml), and 19 % secondary hyperparathyroidism (>65 pg/ml) vs. 76, 44, and 17 %, respectively, following GBP. Serum 25OHD was negatively correlated with BMI at 6 months after GBP (R?=??0.299, p?<?0.0001). In the two groups of 30 subjects, serum 25OHD and PTH did not differ at 6 months after GBP or SG.

Conclusions

At 6 months after GBP, serum 25OHD significantly increased in subjects supplemented with multivitamins containing low doses of vitamin D. These data suggest that weight loss at 6 months after surgery has a greater influence on vitamin D status than malabsorption induced by GBP.