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1.
Open Med (Wars) ; 19(1): 20230851, 2024.
Article in English | MEDLINE | ID: mdl-38584825

ABSTRACT

The role of hepatic venous pressure gradient (HVPG) measurement in risk stratification before liver resection is an ongoing area of debate. This study examines the impact of preoperative HVPG levels on overall survival (OS)/time to recurrence (TTR) and postoperative complications after hepatic resection of hepatocellular carcinoma (HCC). Thirty-eight HCC patients undergoing HVPG measurement before liver resection at Cambridge University Hospitals NHS Foundation Trust between January 2014 and April 2022 were retrospectively analysed. Statistical analysis comprised univariable/multivariable Cox/logistic regression to identify risk factors of reduced OS/TTR or 90-day post-resection complications and Kaplan-Meier estimator, log-rank, chi-squared, Fisher's exact, and Mann-Whitney U test, or Student's t-test for survival/subgroup analysis. The median HPVG was 6 (range: 0-14) mmHg. The HVPG was an independent risk factor for poorer TTR in the overall cohort (cut-off: ≥7.5 mmHg (17.18/43.81 months; P = 0.009)). In the subgroup analysis of cirrhotic patients (N = 29 (76%)), HVPG was additionally an independent risk factor for lower OS (cut-off: ≥8.5 mmHg [44.39/76.84 months; P = 0.012]). The HVPG had no impact on OS/TTR in non-cirrhotic patients (N = 9 (24%)), nor was it associated with postoperative complications in any cohort. In conclusion, preoperative HVPG levels are useful predictors for TTR and OS in cirrhotic HCC patients undergoing hepatic resection.

2.
Gut ; 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38627031

ABSTRACT

Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service.

3.
BJR Case Rep ; 10(2): uaae006, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38433767

ABSTRACT

Vascular Ehlers-Danlos Syndrome (vEDS) is a rare and potentially life-threatening inherited connective tissue disorder. Patients with vEDS can present with spontaneous arterial dissections and ruptured aneurysms. There are previous reports of large artery dissections and vessel rupture following conventional catheter diagnostic angiography. We present the case of a patient with vEDS who had a spontaneous carotid-cavernous fistula (CCF) and visceral aneurysms, associated with a normal variant of corona mortis. A CCF was successfully treated with a transvenous approach with detachable coils.

5.
BMJ ; 383: e077164, 2023 12 21.
Article in English | MEDLINE | ID: mdl-38128958

ABSTRACT

OBJECTIVE: To investigate the behaviour of common healthcare related objects in a 3 tesla (T) MRI (magnetic resonance imaging) scanner, examining their ability to self-propel towards the scanner bore and their potential for tissue penetration. DESIGN: Prospective in situ experimental study. SETTING: Clinical 3 T MRI scanner. Customised rig designed and built to guide objects towards the scanner bore. PARTICIPANTS: 12 categories of objects commonly found in hospitals, or on patients or healthcare professionals, or near an MRI scanning room. Human tissue penetration simulated with ballistic gel (Federal Bureau of Investigation and North Atlantic Treaty Organisation graded). MAIN OUTCOME MEASURES: SANTA (site where applied newtonian mechanics triggers acceleration) measurements and depth of tissue penetration of the objects. RESULTS: SANTA measurements ranged from 0 cm for the 20 pence, 50 pence, and £2 coins to 152-161 cm for a knife and the biscuit tins. One penny, two pence, five pence, and 10 pence coins showed self-propulsion and acceleration towards the scanner bore at a distance >100 cm from the gantry entry point. Linear regression analysis showed no apparent correlation between the weight of the objects and their SANTA measurements (R2<0.1). Only five objects penetrated the ballistic gel (simulated human tissue). The deepest penetration was by the knife (5.5 cm), closely followed by the teaspoon (5.0 cm), fork (4.0 cm), spoon (3.5 cm), and a 10 pence coin (0.5 cm). Although the biscuit tins did not penetrate the simulated human tissue, they exerted substantial impact force which could potentially cause bone fractures. A smartphone, digital thermometer, metallic credit card, and pen torch remained fully functional after several passes into the MRI scanner. No discernible loss of image quality for the MRI scanner after the experiments was found. CONCLUSIONS: The study highlights the potential for harm (major tissue damage and bone fractures) when commonly found objects in a healthcare setting are unintentionally brought into the MRI scanner room. Patients and healthcare professionals need to be aware of the dangers associated with bringing ferromagnetic objects into the MRI environment.


Subject(s)
Fractures, Bone , Health Facilities , Humans , Prospective Studies , Magnetic Resonance Imaging/methods , Delivery of Health Care
8.
Front Med (Lausanne) ; 9: 867536, 2022.
Article in English | MEDLINE | ID: mdl-35602494

ABSTRACT

Background: Capnography has been associated with a reduced incidence of events related to respiratory compromise during procedural sedation. Methods: A prospective service evaluation was conducted at a large United Kingdom (UK) teaching hospital to assess the impact of capnography on patient safety within four speciality services: bronchoscopy, endoscopy, interventional cardiology, and interventional radiology. Events were defined as provided by the World Society of Intravenous Anaesthesia. One thousand four hundred one patients were enrolled in the evaluation, with 666 patients before and 735 after implementation of capnography. Data was entered as a convenience sample on site in an offline data-collection tool. Results were assessed for the relative reduction in the incidence and resulting adjusted odds ratio for the combined incidence of oxygen desaturation (75-90% for <60s), severe oxygen desaturation (<75% at any time) or prolonged oxygen desaturation (<90% for >60s), bradycardia (>25% from baseline) and tachycardia (>25% from baseline). The adjusted odds ratio was controlled for both procedure and patient characteristics. Results: After implementation of capnography, a significant reduction (43.2%, p ≤ 0.05) in adverse events was observed: 147 adverse events occurred during 666 procedures without capnography compared with 93 adverse events that occurred during 735 procedures with capnography. The adjusted odds ratio for the occurrence of the target adverse events was 0.57 (95% CI: 0.42-0.77). Multivariable linear regression indicated that capnography was a significant predictor (p 0.001) of reduced adverse events. Conclusion: These results suggest improved patient safety following capnography implementation.

10.
Cardiovasc Intervent Radiol ; 44(10): 1625-1632, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34254176

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the predictive value of a 'Modified Karnofsky Scoring System' on outcomes and provide real-world data regarding the UK practice of biliary interventions. MATERIALS AND METHODS: A prospective multi-centred cohort study was performed. The pre-procedure modified Karnofsky score, the incidence of sepsis, complications, biochemical improvement and mortality were recorded out to 30 days post procedure. RESULTS: A total of 292 patients (248 with malignant lesions) were suitable for inclusion in the study. The overall 7 and 30 day mortality was 3.1% and 16.1%, respectively. The 30 day sepsis rate was 10.3%. In the modified Karnofsky 'high risk' group the 7 day mortality was 9.7% versus 0% for the 'low risk' group (p = 0.002), whereas the 30 day mortality was 28.8% versus 13.3% (p = 0.003). The incidence of sepsis at 30 days was 19% in the high risk group versus 3.3% at the low risk group (p = 0.001) CONCLUSION: Percutaneous biliary interventions in the UK are safe and effective. Scoring systems such as the Karnofsky or the modified Karnofsky score hold promise in allowing us to identify high risk groups that will need more careful consideration and enhanced patient informed consent but further research with larger studies is warranted in order to identify their true impact on patient selection and outcomes post biliary interventions.


Subject(s)
Biliary Tract Surgical Procedures , Cholestasis , Cholestasis/surgery , Cohort Studies , Drainage , Humans , Prospective Studies , Treatment Outcome
11.
Science ; 371(6531): 839-846, 2021 02 19.
Article in English | MEDLINE | ID: mdl-33602855

ABSTRACT

Organoid technology holds great promise for regenerative medicine but has not yet been applied to humans. We address this challenge using cholangiocyte organoids in the context of cholangiopathies, which represent a key reason for liver transplantation. Using single-cell RNA sequencing, we show that primary human cholangiocytes display transcriptional diversity that is lost in organoid culture. However, cholangiocyte organoids remain plastic and resume their in vivo signatures when transplanted back in the biliary tree. We then utilize a model of cell engraftment in human livers undergoing ex vivo normothermic perfusion to demonstrate that this property allows extrahepatic organoids to repair human intrahepatic ducts after transplantation. Our results provide proof of principle that cholangiocyte organoids can be used to repair human biliary epithelium.


Subject(s)
Bile Duct Diseases/therapy , Bile Ducts, Intrahepatic/physiology , Bile Ducts/cytology , Cell- and Tissue-Based Therapy , Epithelial Cells/cytology , Organoids/transplantation , Animals , Bile , Bile Ducts/physiology , Bile Ducts, Intrahepatic/cytology , Common Bile Duct/cytology , Epithelial Cells/physiology , Gallbladder/cytology , Gene Expression Regulation , Humans , Liver/physiology , Liver Transplantation , Mesenchymal Stem Cell Transplantation , Mice , Organoids/physiology , RNA-Seq , Tissue and Organ Procurement , Transcriptome
12.
Aliment Pharmacol Ther ; 50(9): 1049-1058, 2019 11.
Article in English | MEDLINE | ID: mdl-31489698

ABSTRACT

BACKGROUND: Anticoagulation alone in acute, extensive portomesenteric vein thrombosis (PVT) does not always result in spontaneous clot lysis, and leaves the patient at risk of complications including intestinal infarction and portal hypertension. AIM: To develop a new standard of care for patients with acute PVT and evidence of intestinal ischaemia. METHODS: We present a case series of patients with acute PVT and evidence of intestinal ischaemia plus ongoing symptoms despite initial systemic anticoagulation, who were treated with a thrombolysis protocol between 2014 and 2019. This stepwise protocol initially uses low-dose systemic alteplase, and in patients with ongoing abdominal pain, and no evidence of radiological improvement, is followed by local clot dissolution therapy (CDT) through a TIPSS. Outcomes and safety were assessed. RESULTS: Twenty-two patients were included. The mean age was 44.6 (standard deviation [SD] 16.0) years, and 64% had an identifiable prothrombotic risk factor. All patients had intestinal wall oedema and 77% had complete occlusion of all portomesenteric veins. Systemic thrombolysis was started 18.7 (SD 11.2) days after the onset of symptoms. 55% of patients underwent TIPSS insertion for CDT. At the end of treatment, symptoms resolved in 91% of patients and recanalisation in 86%. Only one patient required resection for intestinal ischaemia, and there were no deaths. Major complications occurred in two patients (9%). CONCLUSIONS: Our stepwise protocol is effective, resulting in good recanalisation rates. It can be commenced early while organising transfer to a centre capable of performing local CDT.


Subject(s)
Intestinal Diseases/therapy , Ischemia/therapy , Portal Vein/pathology , Portasystemic Shunt, Transjugular Intrahepatic , Thrombolytic Therapy/methods , Venous Thrombosis/therapy , Acute Disease , Adult , Anticoagulants/therapeutic use , Female , Humans , Intestinal Diseases/complications , Intestines/blood supply , Intestines/pathology , Ischemia/complications , Male , Mesenteric Ischemia/complications , Mesenteric Ischemia/therapy , Middle Aged , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Portasystemic Shunt, Transjugular Intrahepatic/methods , Retrospective Studies , Risk Factors , Treatment Outcome , Venous Thrombosis/complications , Venous Thrombosis/pathology
13.
J Vasc Interv Radiol ; 30(8): 1185-1192, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31255499

ABSTRACT

PURPOSE: To evaluate the safety and efficacy of yttrium-90 transarterial radioembolization (TARE) for the treatment of unresectable, chemotherapy-refractory intrahepatic cholangiocarcinoma (ICC). METHODS: A prospective, observational study was carried out in 10 centers between 2013 and 2017. TARE plus standard care was delivered to patients with unresectable, chemotherapy-refractory or chemotherapy-intolerant ICC. Primary outcome was overall survival. Secondary outcomes included safety, progression-free survival (PFS), and liver-specific progression-free survival (LPFS). RESULTS: Sixty-one patients were treated with TARE. Patients were 53% male; median age was 64 years; 91% had performance status 0/1; 92% had received prior chemotherapy; and 59% had no extrahepatic disease. Median follow-up was 13.9 months (95% confidence interval [CI], 9.6-18.1). Overall survival was 8.7 months (95% CI, 5.3-12.1), and 37% of patients survived to 12 months. PFS was 2.8 months (95% CI, 2.6-3.1), and LPFS was 3.1 months (95% CI, 1.3-4.8). One severe complication (abdominal pain) occurred at the time of the TARE procedure. Thirty patients experienced a total of 49 adverse events, of which 8% were grade ≥3; most common were grade 1-2 fatigue and abdominal pain. A total of 77 abnormal laboratory value events were recorded, of which 4% were grade ≥3. CONCLUSIONS: Patients with advanced ICC have limited therapeutic options and a poor prognosis. This prospective study examined the survival of patients with unresectable, chemotherapy-refractory primary ICC treated with TARE in real-world practice. The results demonstrate that this treatment merits further investigation in this patient cohort in a larger study, including collection of patient-reported outcomes.


Subject(s)
Bile Duct Neoplasms/radiotherapy , Cholangiocarcinoma/radiotherapy , Drug Resistance, Neoplasm , Embolization, Therapeutic/methods , Radiopharmaceuticals/administration & dosage , Yttrium Radioisotopes/administration & dosage , Aged , Bile Duct Neoplasms/diagnostic imaging , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Cholangiocarcinoma/diagnostic imaging , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Disease Progression , Embolization, Therapeutic/adverse effects , Embolization, Therapeutic/mortality , England , Female , Humans , Male , Middle Aged , Progression-Free Survival , Prospective Studies , Radiopharmaceuticals/adverse effects , Risk Factors , Time Factors , Yttrium Radioisotopes/adverse effects
15.
Diagn Interv Radiol ; 23(4): 318-320, 2017.
Article in English | MEDLINE | ID: mdl-28498107

ABSTRACT

Transjugular intrahepatic portosystemic shunt (TIPS) insertion is commonly performed for refractory ascites or variceal bleeding. However, TIPS dysfunction can be seen in both early and late settings, with shunt thrombosis a particular problem. Treatment of shunt dysfunction commonly involves angioplasty and re-lining, with or without embolectomy, mechanical thrombectomy, or thrombolysis. Ultrasound-assisted thrombolysis has been shown to be successful for treatment of pulmonary embolism, deep vein thrombosis, and peripheral arterial thromboembolism, but has not been described before for TIPS occlusion. Ultrasound is theorized to lead to a shortened duration of thrombolysis due to thinning of the fibrin clot and exposing plasminogen receptor sites. In this technical report, we describe the first published use of ultrasound-assisted thrombolysis in the declotting of an occluded TIPS. We found that the use of ultrasound-assisted thrombolysis allowed a relatively short duration of thrombolytic therapy, with removal of thrombus extending into the portal vein, facilitating stent re-lining. No complications were observed, in particular no bleeding complications. The TIPS remains patent at 8 months postprocedure.


Subject(s)
Portasystemic Shunt, Transjugular Intrahepatic , Thrombolytic Therapy/methods , Thrombosis/drug therapy , Ultrasonography, Interventional/methods , Female , Humans , Middle Aged , Thrombosis/diagnostic imaging , Treatment Outcome
16.
Cardiovasc Intervent Radiol ; 40(8): 1155-1163, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28275827

ABSTRACT

PURPOSE: Intraprocedural distal embolization is an accepted complication of femoropopliteal angioplasty. The purpose of this study is to assess the use of below-the-knee stents in the "bail-out" of conventional methods. MATERIALS AND METHODS: We retrospectively reviewed 1485 of femoropopliteal angioplasties that were performed in our centre in a 4-year period and analysed 12 cases (<1%) where distal embolization that required further intervention occurred. In all cases lesions were chronic and 75% suffered from critical limb ischaemia. The target vessel was the SFA in all of the cases with a long (>10 cm) occlusion in 50%. A three-vessel run-off was present in only 25%. Patients that received a stent as a limb salvage attempt were analysed. Outcome measures were technical success, clinical success and procedure-related complications. Multivariate regression analysis of the factors related to stenting was also performed. RESULTS: In 41% of the cases with distal embolization, recanalization with aspiration, thrombolysis or angioplasty offered a satisfactory result. In 59%, conventional methods were ineffective; a stent was deployed in 85%, whereas in 15% surgical embolectomy was required. Technical and clinical success of the stent cases was 100% without any procedure-related complications. There was significance (p < 0.05) between critical limb ischaemia and stenting; single-vessel run-off has also shown a positive trend (p = 0.88). CONCLUSION: Stents appear as a valid salvage option for infragenicular distal embolization when conventional methods fail; the likelihood of having to use a stent is higher for patients with critical limb ischaemia and a single-vessel run-off.


Subject(s)
Angioplasty/adverse effects , Embolism/surgery , Femoral Artery/surgery , Limb Salvage/methods , Popliteal Artery/surgery , Stents , Aged , Aged, 80 and over , Female , Humans , Leg/blood supply , Leg/surgery , Male , Middle Aged , Retrospective Studies , Treatment Outcome
17.
Can Assoc Radiol J ; 65(3): 242-52, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24325923

ABSTRACT

Kidney was the first and is the most frequently transplanted organ. Despite improved surgical techniques and transplantation technology, complications do occur and, if left untreated, may lead to catastrophic consequences. Renal transplantation complications may be vascular (eg, renal artery and vein stenosis and thrombosis, arteriovenous fistula, and pseudoaneurysms); urologic (eg, urinary obstruction and leak, and peritransplantation fluid collections, including hematoma, seroma, lymphocele, and abscess formation); and nephrogenic, including acute tubular necrosis, graft rejection, chronic allograft nephropathy, and neoplasm. Early diagnosis and treatment of these complications are paramount to prevent graft failure and other significant morbidities to the patients. Radiology plays a pivotal role in the diagnosis and treatment of these complications, with minimally invasive percutaneous techniques. In this article, we reviewed renal transplantation anatomy, a wide range of complications that may occur after renal transplantation surgery, typical imaging appearances of the complications on varies imaging modalities, and percutaneous interventional techniques that are used in their treatment.


Subject(s)
Diagnostic Imaging , Kidney Transplantation/adverse effects , Radiography, Interventional , Ultrasonography, Interventional , Contrast Media , Diagnosis, Differential , Humans
18.
Magn Reson Med ; 70(6): 1644-52, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23440691

ABSTRACT

PURPOSE: To report the initial experience and diagnostic performance applying a novel flow-dependent non-contrast-enhanced MR angiography (NCE-MRA) method, in patients with suspected peripheral vascular disease, in comparison with established contrast-enhanced MRA (CE-MRA). METHODS: The lower legs of 34 patients were imaged at 1.5 T with both NCE-MRA and CE-MRA. The NCE-MRA method consisted of a cardiac-gated balanced-SSFP sequence with controllable flow-suppression preparation. Flow-suppressed and unsuppressed datasets were subtracted to obtain angiograms. Two experienced radiologists assessed both NCE-MRA and CE-MRA images, first independently and then in consensus to resolve significant disagreements. Signal loss, vessel conspicuity, vascular disease, venous contamination, artifacts, and diagnostic confidence were assessed. RESULTS: Using the CE-MRA as the "gold standard," the per-segment sensitivity and specificity for detection of significant disease were 81.7% and 90.9%, respectively. Mean diagnostic confidence (scale 0-4) was 3.4 for NCE-MRA and 3.9 for CE-MRA. Most vessel segments were well visualized but the popliteal arteries often suffered some technique-related signal loss. CONCLUSIONS: The NCE-MRA method was able to visualize most vessel segments with good or excellent confidence, few artifacts, and excellent background suppression, giving moderate agreement with CE-MRA. However, some segments were poorly visualized, probably due to flow profile distortion in these patients.


Subject(s)
Algorithms , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Lower Extremity/blood supply , Magnetic Resonance Angiography/methods , Peripheral Vascular Diseases/pathology , Adult , Aged , Contrast Media , Female , Humans , Lower Extremity/pathology , Male , Pilot Projects , Reproducibility of Results , Sensitivity and Specificity
19.
Int J Surg Case Rep ; 3(11): 555-8, 2012.
Article in English | MEDLINE | ID: mdl-22922358

ABSTRACT

INTRODUCTION: Portal venous aneurysms are a rare finding. The reported incidence is on the rise with increasing use of modern imaging techniques in clinical practice. However, there is still much to be elicited regarding their aetiology, natural history, and management. PRESENTATION OF CASE: An 80-year-old woman presented with abdominal pain and nausea. Investigations showed a hypoechoic area in the region of the head of pancreas on ultrasound, which was found to be a portal venous aneurysm on CT. In view of her multiple comorbidities, a conservative approach was taken. DISCUSSION: Portal venous aneurysms represent approximately 3% of all venous aneurysms with a reported prevalence of 0.43%. They may be congenital, due to failure of complete regression of the right vitelline vein, or acquired secondary to portal hypertension. The primary presentation of portal vein aneurysm is abdominal pain, followed by incidental detection on imaging, with a minority of patients presenting with gastrointestinal bleeding. Complications of PVA include thrombosis, biliary tract obstruction, inferior vena cava obstruction, and duodenal compression. On the whole PVAs are stable and have a low risk of complications with 88% of patients showing no progression of aneurysm size or complications on subsequent follow up scans. CONCLUSION: We recommend that portal venous aneurysms be assessed using colour Doppler ultrasonography in the first instance with CT scans reserved for indeterminate cases or symptomatic patients. Due to the slow progression of such aneurysms, surgery is recommended only for symptomatic patients or those with complications secondary to portal venous aneurysms.

20.
N Engl J Med ; 360(1): 44-52, 2009 Jan 01.
Article in English | MEDLINE | ID: mdl-19092146

ABSTRACT

BACKGROUND: Weight gain and weight loss are associated with changes in blood pressure through unknown mechanisms. Central melanocortinergic signaling is implicated in the control of energy balance and blood pressure in rodents, but there is no information regarding such an association with blood pressure in humans. METHODS: We assessed blood pressure, heart rate, and urinary catecholamines in overweight or obese subjects with a loss-of-function mutation in MC4R, the gene encoding the melanocortin 4 receptor, and in equally overweight control subjects. We also examined the effects of an MC4R agonist administered for 7 days in 28 overweight or obese volunteers. RESULTS: The prevalence of hypertension was markedly lower in the MC4R-deficient subjects than in the control subjects (24% vs. 53%, P=0.009). After the exclusion of subjects taking antihypertensive medications, blood-pressure levels were significantly lower in MC4R-deficient subjects than in control subjects, with mean (+/-SE) systolic blood pressures of 123+/-14 mm Hg and 131+/-12 mm Hg, respectively (P=0.02), and mean diastolic blood pressures of 73+/-10 mm Hg and 79+/-7 mm Hg, respectively (P=0.03). As compared with control subjects, MC4R-deficient subjects had a lower increase in heart rate on waking (P=0.007), a lower heart rate during euglycemic hyperinsulinemia (P<0.001), and lower 24-hour urinary norepinephrine excretion (P=0.04). The maximum tolerated daily dose of 1.0 mg of the MC4R agonist led to significant increases of 9.3+/-1.9 mm Hg in systolic blood pressure and of 6.6+/-1.1 mm Hg in diastolic blood pressure (P<0.001 for both comparisons) at 24 hours, as compared with placebo. Differences in blood pressure were not explained by changes in insulin levels; there were no significant adverse events. CONCLUSIONS: Results of our genetic and pharmacologic studies implicate melanocortinergic signaling in the control of human blood pressure through an insulin-independent mechanism.


Subject(s)
Blood Pressure/physiology , Hypertension/metabolism , Mutation , Overweight/metabolism , Receptor, Melanocortin, Type 4/metabolism , Signal Transduction , Adult , Autonomic Nervous System/physiology , Blood Pressure/drug effects , Blood Pressure/genetics , Catecholamines/urine , Cross-Over Studies , Dose-Response Relationship, Drug , Double-Blind Method , Female , Genotype , Heart Rate/genetics , Heart Rate/physiology , Heterozygote , Humans , Hypertension/complications , Hypertension/genetics , Male , Obesity/complications , Obesity/genetics , Obesity/metabolism , Overweight/complications , Overweight/genetics , Prevalence , Receptor, Melanocortin, Type 4/agonists , Receptor, Melanocortin, Type 4/deficiency , Receptor, Melanocortin, Type 4/genetics , Sleep/physiology
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