Aneurysm of the Superior Posterior Pancreatic-Duodenal Artery Presenting with Recurrent Syncopes

We present a 61-year-old woman with hypovolemic shock due to a ruptured aneurysm of the superior posterior pancreatic-duodenal artery in whom recurrent syncopes were the first presenting sign of pancreatic-duodenal artery aneurysm (PDAA). PDAA is a rare but life-threatening condition. The widely varying symptomatology may lead to a delay in diagnosis and treatment. Patients with atypical symptoms, such as vague abdominal pain, recurrent dizziness or syncope, may actually suffer from a sentinel bleeding of the vascular malformation. Radiological imaging, especially selective angiography, may provide a diagnostic as well as a therapeutic tool in these patients

Resistance Training and Bone Mineral Density During Growth

This study examined the efficacy of two different resistance training programs in enhancing bone modeling and bone mineral density (BMD) in maturating rats. One exercise mode involved lifting a lighter weight with more repetitions (LI), while the other regimen involved lifting a heavier weight with fewer repetitions (HI) where the total volume of work between exercise programs was equivalent by design. Twenty-three male rats were randomly divided into control (Con, n = 8), LI (n = 7), and HI (n = 8) groups. The LI and HI groups were conditioned to climb a vertical ladder with weights appended to their tail 4 days/wk for 6 wks. After training, serum osteocalcin (OC) was significantly (p \u3c 0.05) higher in both HI (45.2 +/- 1.7 ng/ml) and Ll (39.1 +/- 2.2 ng/ml) when compared to Con (29.9 +/- 0.9 ng/ml). Left tibial BMD was significantly (p \u3c 0.05) greater for HI (0.231 +/- 0.004 g/cm(2)) when compared to both LI (0.213 +/- 0.003 g/cm(2)) and Con (0.206 +/- 0.005 g/cm(2)) with no significant difference between Ll and Con. The results indicate that both HI and LI are effective in elevating serum OC, implicating an osteogenic response; however, only HI resulted in a significant elevation in BMD

Does weight impact anidulafungin pharmacokinetics?

Pharmacolog

Higher Midazolam Clearance in Obese Adolescents Compared with Morbidly Obese Adults

Background The clearance of cytochrome P450 (CYP) 3A substrates is reported to be reduced with lower age, inflammation and obesity. As it is unknown what the overall influence is of these factors in the case of obese adolescents vs. morbidly obese adults, we studied covariates influencing the clearance of the CYP3A substrate midazolam in a combined analysis of data from obese adolescents and morbidly obese adults. Methods Data from 19 obese adolescents [102.7 kg (62–149.5 kg)] and 20 morbidly obese adults [144 kg (112–186 kg)] receiving intravenous midazolam were analysed, using population pharmacokinetic modelling (NONMEM 7.2). In the covariate analysis, the influence of study group, age, total body weight (TBW), developmental weight (WTfor age and length) and excess body weight (WTexcess = TBW − WTfor age and length) was evaluated. Results The population mean midazolam clearance was significantly higher in obese adolescents than in morbidly obese adults [0.71 (7%) vs. 0.44 (11%) L/min; p < 0.01]. Moreover, clearance in obese adolescents increased with TBW (p < 0.01), which seemed mainly explained by WTexcess, and for which a so-called ‘excess weight’ model scaling WTfor age and length to the power of 0.75 and a separate function for WTexcess was proposed. Discussion We hypothesise that higher midazolam clearance in obese adolescents is explained by less obesity-induced suppression of CYP3A activity, while the increase with WTexcess is explained by increased liver blood flow. The approach characterising the influence of obesity in the paediatric population we propose here may be of value for use in future studies in obese adolescents

Morbidly Obese Patients Exhibit Increased CYP2E1-Mediated Oxidation of Acetaminophen

Introduction: Acetaminophen (paracetamol) is mainly metabolized via glucuronidation and sulphation, while the minor pathway through cytochrome P450 (CYP) 2E1 is held responsible for hepatotoxicity. In obese patients, CYP2E1 activity is reported to be induced, thereby potentially worsening the safety profile of acetaminophen. The aim of this study was to determine the pharmacokinetics of acetaminophen and its metabolites (glucuronide, sulphate, cysteine and mercapturate) in morbidly obese and non-obese patients. Methods: Twenty morbidly obese patients (with a median total body weight [TBW] of 140.1 kg [range 106–193.1 kg] and body mass index [BMI] of 45.1 kg/m2 [40–55.2 kg/m2]) and eight non-obese patients (with a TBW of 69.4 kg [53.4–91.7] and BMI of 21.8 kg/m2 [19.4–27.4]) received 2 g of intravenous acetaminophen. Fifteen blood samples were collected per patient. Population pharmacokinetic modelling was performed using NONMEM. Results: In morbidly obese patients, the median area under the plasma concentration–time curve from 0 to 8 h (AUC0–8h) of acetaminophen was significantly smaller (P = 0.009), while the AUC0–8h ratios of the glucuronide, sulphate and cysteine metabolites to acetaminophen were significantly higher (P = 0.043, 0.004 and 0.010, respectively). In the model, acetaminophen CYP2E1-mediated clearance (cysteine and mercapturate) increased with lean body weight [LBW] (population mean [relative standard error] 0.0185 L/min [15 %], P < 0.01). Moreover, accelerated formation of the cysteine and mercapturate metabolites was found with increasing LBW (P < 0.001). Glucuronidation clearance (0.219 L/min [5 %]) and sulphation clearance (0.0646 L/min [6 %]) also increased with LBW (P < 0.001). Conclusion: Obesity leads to lower acetaminophen concentrations and earlier and higher peak concentrations of acetaminophen cysteine and mercapturate. While a higher dose may be anticipated to achieve adequate acetaminophen concentrations, the increased CYP2E1-mediated pathway may preclude this dose adjustment

Influence of Morbid Obesity on the Pharmacokinetics of Morphine, Morphine-3-Glucuronide, and Morphine-6-Glucuronide

Perioperative Medicine: Efficacy, Safety and Outcom