ERCP and MRCP--when and why

Since the introduction of endoscopic retrograde cholangiopancreatography (ERCP) in the 1970s, gastroenterologists have a wide spectrum of diagnostic and therapeutic options in the biliopancreatic ductal system at their disposal. With its arrival in the 1990s, magnetic resonance cholangiopancreatography (MRCP) developed as a potent diagnostic tool in biliopancreatic pathology. Currently, MRCP is widely replacing diagnostic ERCP and thereby avoiding complications related to endoscopic technique.We summarize evidence-based data and demonstrate indications and differential indications for MRCP and ERCP in pancreatic disease. Complications related to the procedures and possible medical prevention are discussed. The feasibility of interventional endoscopy in pancreatic disease is reported in detail. The role of gastroenterologists in performing MRCP is outlined on the basis of practical examples.     

Convection and permeation and albumin between plasma and interstitium.

Nonequilibrium thermodynamics is combined with compartmental analysis to interpret albumin sieving and tracer experiments in terms of a permeability-surface product PS (permeation) and a solvent drag reflection coefficient σ_f (convection) for various blood-tissue barriers. The human whole-body albumin data of Lassen, Parving, and Rossing (Lassen, Parving, and Rossing, Microvasc. Res.7, i–iv (1974)), modified for nonliver tissues by Johnson and Levitt (Johnson &; Levitt, Microvasc. Res.9, 141 (1975)) lead to P ～ 1.8 × 10^?8 cm sec^?1 (based on a surface area per unit plasma volume of 700 cm^?1) and to σ_f ～ 0.9, which imply, in agreement with Johnson and Levitt, that permeation is the dominant nonliver blood-tissue transport mechanism for albumin in the normal resting human. Similar values are derived from the dog paw muscle data of Garlick and Renkin (Garlick and Renkin, Amer. J. Physiol.219, 1595–1605 (1970)). The Casley-Smith (Casley-Smith, Microvasc. Res.9, 43–48 (1975)) mechanism of uphill albumin transport is verified as possible. It is tentatively inferred that lymph formation in resting tissue does not result from a small difference between a large fluid (volumetric) filtration and an almost equally large fluid reabsorption, either in the same capillary (Starling) or between different capillaries (Zweifach) (Zweifach, Circ. Res.34, 858–866 (1974)). Rather, reabsorption is negligibly small relative to filtration, and lymph flow is comparable to volumetric filtration.     

Micronutrients and infection: interactions and implications with enteric and other infections and future priorities

Symposium presentations have focused on the elegant molecular science and the biologic mechanisms by which micronutrients play critical roles in cellular and humoral immune responses, cellular signaling and function, and even in the evolution of microbial virulence. The concluding session examined the practical issues of how best to evaluate the nutritionally at-risk host, especially in the areas of greatest need-an analytical model of nutrient-immune interactions, implications of nutritional modulation of the immune response for disease, and the implications for international research and child health. This overview illustrated how malnutrition may be a major consequence of early childhood diarrhea and enteric infections, as enteric infections may critically impair intestinal absorptive function with potential long-term consequences for growth and development. The potentially huge, largely undefined DALY (disability-adjusted life years) impact of early childhood diarrheal illnesses demonstrates the importance of quantifying the long-term functional impact of largely preventable nutritional and infectious diseases, especially in children in developing areas.     

Leptin and cellular and innate immunity in abstinent alcoholics and controls

BACKGROUND: Basic studies indicate that in vitro and in vivo doses of leptin modulate cellular immune responses. Given evidence that concentrations of leptin are altered in alcoholics who also show immune abnormalities, this study examined the relationships between circulating levels of leptin and markers of cellular and innate immunity. METHODS: Circulating levels of leptin, natural killer cell (NK) activity, interleukin-2 (IL-2)-stimulated NK activity, and concanavalin A-stimulated production of IL-2, IL-6, IL-10, and IL-12 were compared between abstinent DSM-IV alcohol-dependent men (n = 27) and age- and gender-matched controls (n = 34). RESULTS: As compared with controls, alcoholics showed lower NK activity (p < 0.01) and a trend for lower levels of leptin (p = 0.055). In the total sample, leptin predicted NK activity (beta = 0.33; p < 0.05) after controlling for the confounding influence of body mass index, alcohol intake, and smoking. Leptin was not correlated with any of the cytokine measures. To examine whether the effects of leptin were mediated by its direct action on NK, additional studies examined in vitro effects of leptin on NK activity in healthy volunteers (n = 10); leptin doses (0.1, 1, and 10 nM) yielded levels of NK activity comparable to those with media alone. CONCLUSIONS: These data show that circulating levels of leptin are associated with NK activity in humans and suggest that abnormal in vivo concentrations of leptin may contribute to the declines of NK activity in alcoholics who are at risk for infectious diseases.     

Sex and Gender and Allostatic Mechanisms of Cardiovascular Risk and Disease

Cardiovascular diseases are leading causes of mortality and morbidity in adults worldwide. Multiple studies suggest that there are clinically relevant sex differences in cardiovascular disease. Women and men differ substantially in terms of prevalence, presentation, management, and outcomes of cardiovascular disease. To date, however, little is known about why cardiovascular disease affects women and men differently. Because many studies do not differentiate the concept of sex and gender, it is sometimes difficult to discriminate sociocultural vs biological contributors that drive observed clinical differences. Female sex has some biological advantages in relation to cardiovascular disease, but many of these advantages seem to disappear as soon as women develop cardiovascular risk factors (eg, type 2 diabetes, hypertension, dyslipidemia). Furthermore, stress and allostatic load could play an important role in the relationship between sex/gender and cardiovascular diseases. In this narrative review, we argue that chronic stress and psychosocial factors might better encompass the patterns of allostatic load increases seen in women, while biological risk factors and unhealthy behaviours might be more important mechanisms that drive increased allostatic load in men. Indeed, men show allostatic load patterns that are more associated with impaired anthropometric, metabolic, and cardiovascular functioning and women have greater dysregulation in neuroendocrine and immune functioning. Thus gender-related factors might contribute to the pathogenesis of cardiovascular disease especially through stress mechanisms. It is important to continue to study the mechanisms by which gender influences chronic stress, because chronic stress could influence modifiable gendered factors to promote cardiovascular disease prevention.     

Medical and Psychology Students' Knowledge and Attitudes Regarding Aging and Sexuality

The current study surveys medical and doctoral psychology students (N = 100) from an urban northeastern university regarding knowledge and attitudes toward elderly sexuality and aging using the Facts on Aging Quiz, the Aging Sexuality Knowledge and Attitudes Scale, and measures of interest in gerontology, academic/clinical exposure to aging and sexuality, and contact with elders. The current study found that psychology students demonstrated greater aging knowledge than medical students; however, both groups showed gaps in knowledge about sexuality. Married students had greater academic/clinical exposure and greater knowledge about aging but less permissive attitudes toward elderly sexuality. Generally, knowledge about aging was the strongest correlate of knowledge about sexuality. Level of knowledge about sexuality was not associated with attitudes. Attitudes toward sexuality and aging may be more strongly tied to demographic variables reflective of religious beliefs or adherence to sociocultural norms.     

Diabetes and Clinical and Subclinical CVD

Diabetes mellitus is a major cardiovascular risk factor and its prevalence has been increasing globally. This review examines the contributions of the MESA (Multi-Ethnic Study of Atherosclerosis), a diverse American cohort (6,814 adults ages 45 to 84, recruited from 2000 to 2002, 50% female, 62% nonwhite) toward understanding the relationship between diabetes and clinical and subclinical cardiovascular disease. People with diabetes have a high burden of subclinical vascular disease as measured by coronary artery calcification (CAC), carotid artery intima-media thickness, valvular calcification, and alterations in left ventricular structure. CAC substantially improves cardiovascular risk prediction. Among adults with diabetes, 63% had CAC >0; above CAC >400 Agatston units the event rate was 4% annually, whereas an absence of CAC was a marker of a very low cardiovascular disease rate (0.4% to 0.1% annually). These stark differences in rates may have implications for screening and/or targeted prevention efforts based on CAC burden. MESA has also provided insight on diabetes epidemiology.     

Platelet and leukocyte adhesion and activation in unstable angina and post-PTCA

BACKGROUND: Unstable atherosclerotic plaques activate blood cells which may adhere to the coronary endothelium causing vessel occlusion. However, it is unknown if different clinical syndromes associated with plaque rupture induce similar blood cell activation and adhesion to the endothelium. METHODS: We studied changes in adhesion molecule expression of platelets (GPIIb/IIIa), neutrophils--CD18, CD11b and L-selectin--and monocytes (CD14) after interaction with active lesions of patients with stable angina subjected to PTCA and patients with unstable angina (UA). Generation of superoxide (SO) radicals from PMNs and PMN sequestration in the coronary circulation were also assessed. Blood samples were collected from the aorta (Ao) and coronary sinus (CS) before and 15 min after PTCA (n=13) and within the first 48 h of UA (n=12). RESULTS: PTCA induced a marked up-regulation of CD18, CD11b, CD14 and GPIIb/IIIa with L-selectin shedding and reduced SO formation, whereas only minor L-selectin down-regulation and decreased SO production indicated activation in UA. However, a significant decrease in neutrophil count in the CS compared to the Ao was only observed in UA. CONCLUSIONS: The magnitude of cellular activation depends on the underlying clinical setting and just partially contributes to cell adhesion to the endothelium which might be modulated by different extent of vascular occlusion and shear forces.     

Serum Alkaline Phosphatase and Phosphate and Risk of Mortality and Hospitalization

Background and objectives: Elevated alkaline phosphatase (AlkPhos) and phosphate levels are associated with cardiovascular morbidity and mortality in patients receiving dialysis. A retrospective cohort study was conducted to test these associations in outpatients with an estimated GFR ≥60 ml/min/1.73 m².Design, setting, participants, & measurements: Patients with serum AlkPhos and phosphate levels measured between 2000 and 2002 (n = 10,743) at Montefiore Medical Center (MMC) clinics were followed through September 11, 2008 (median 6.8 years). Mortality data were obtained via Social Security Administration records (n = 949 deaths). Hospitalization data were obtained from MMC records.Results: The mean age was 51 years, 64% were women, 22% were white, 26% were non-Hispanic black, 16% were Hispanic, 13% had a diagnosis of hypertension, 9% had diabetes mellitus, and 8% had cardiovascular disease at baseline. AlkPhos and phosphate were independently associated with mortality and cardiovascular-related hospitalization after multivariable adjustment. Comparing patients in the highest (≥104 U/L) versus lowest quartile of AlkPhos (≤66 U/L), the adjusted hazard ratio (HR) for mortality was 1.65 (P trend across quartiles <0.001). For the highest compared with the lowest quartile of serum phosphate (≥3.8 mg/dl versus ≤3.0 mg/dl), the adjusted HR for mortality was 1.29 (P trend across quartiles = 0.008). High AlkPhos but not phosphate levels were also associated with all-cause, infection-related, and fracture-related hospitalization.Conclusions: Higher levels of serum AlkPhos and phosphate were associated with increased mortality and cardiovascular-related hospitalization in an inner-city clinic population. Further studies are needed to elucidate mechanisms underlying these associations.Individuals with ESRD experience increased cardiovascular morbidity and mortality compared with the general population (1). ESRD patients are at high risk for vascular calcification, a highly regulated process that appears to be partially mediated by disorders of mineral metabolism (2). In response to various stimuli, vascular smooth muscle cells undergo a phenotypic change characterized by expression of proteins that promote bone formation, including alkaline phosphatase (AlkPhos) (3). Phosphate induces this phenotypic change in vitro (2) and upregulates AlkPhos activity (4). Thus AlkPhos and phosphate have been directly implicated in the pathogenesis of vascular calcification and subsequent cardiovascular disease (CVD).In patients with ESRD and in the general population, higher serum levels of AlkPhos and phosphate are associated with increased all-cause and cardiovascular mortality (5–13). Recent studies support the hypothesis that these associations are mediated by vascular calcification (14,15), although medial calcification is seen almost exclusively in patients with advanced kidney disease and diabetes and not in the general population (16). These findings are clinically relevant because medial and intimal vascular calcification have been shown to predict cardiovascular risk in dialysis patients (17) and the general population (18). In addition, several studies have demonstrated an association between vascular calcification and low bone density (19–21), suggesting a role for bone mineral parameters as a marker of both processes.On the basis of these data, we evaluated the association between AlkPhos and phosphate and subsequent mortality and hospitalizations in patients with an estimated GFR (eGFR) ≥60 ml/min/1.73 m² in a large medical system in the Bronx, New York.     

Leucine and alpha-ketoisocaproate metabolism and interconversions in fed and fasted sheep

Fed and three-day-fasted sheep were infused with [1-14C] alpha-ketoisocaproate (KIC), L-[1-14C] leucine, and [14C] bicarbonate for determination of their whole-body turnovers, interconversions, and oxidation. Protein synthesis (PS), protein degradation (PD), net tissue metabolism, unidirectional utilization, and production rates also were estimated for the portal-drained viscera, liver, and hindquarters. KIC and leucine arterial concentrations (6.5 and 95 mumol X L-1) both increased with fasting. KIC turnover (9 mumol X min-1) also increased but leucine turnover (108 mumol X min-1) decreased. About 40% of KIC and 15% of leucine were oxidized, but they contributed less than 1% of whole-body CO2 production. The portal-drained viscera released KIC and leucine into the blood only in fed sheep. Hepatic net utilization of KIC and leucine (approximately 2 and 12 mumol X min-1) changed only little with fasting; thus, total splanchnic tissues utilized both in fasted sheep. Net metabolism by the hindquarters (representative of skeletal muscle) was always opposite to splanchnic metabolism. Thus, muscle must produce both KIC and leucine during fasting. In fed sheep whole-body PS, expressed as mumol X min-1 of leucine, was 92 +/- 6 and PD was 71 +/- 5. After fasting, PS decreased by 27%. Calculated liver protein metabolism was unaffected by the fast; PS (fixed and plasma) remained at about 25 and PD at about 15 mumol X min-1. However, protein metabolism by the hindquarters was sensitive to fasting; PS decreased from 30 +/- 4 in fed sheep to 20 +/- 3 mumol X min-1 after fasting and PD increased from 27 +/- 2 to 35 +/- 6 mumol X min-1. Thus, hepatic PS was maintained at the expense of muscle. If the total muscle mass of the body is considered, muscle PS contributed more than one half of whole-body PS.