Influence of magnesium substitution therapy on blood lipid composition in patients with ischemic heart disease. A double-blind, placebo controlled study

In a double-blind, placebo-controlled study, 47 patients with ischemic heart disease and acute myocardial infarction were allocated to 3 months' treatment with peroral magnesium (15 mmol/d) or placebo. Before, during, and after treatment, blood samples were taken to determine serum concentrations of cholesterol; triglyceride; high-density, low-density, and very-low-density lipoprotein; apolipoprotein A1 and B; and magnesium. We found a 13% increase in molar ratio of apolipoprotein A1:apolipoprotein B after magnesium treatment, as compared with a 2% increase in the placebo group (for mean differences between changes of the magnesium and the placebo groups). This increase was caused by a decrease in apolipoprotein B concentrations, which were reduced by 15% from 1.44 to 1.23 mmol/L in the magnesium group as compared with a slight increase in the placebo group. Triglyceride, and thereby very-low-density lipoprotein concentrations decreased by 27% after magnesium treatment (from 2.41 to 1.76 mmol/L, and from 1.1 to 0.79 mmol/L, respectively) as compared with much smaller decrements in the placebo group. Likewise, we found tendencies toward an increase in high-density lipoprotein cholesterol and in high-density lipoprotein cholesterol ratio/(low-density lipoprotein cholesterol:very-low-density lipoprotein cholesterol) after magnesium treatment. The observed findings support the hypothesis that magnesium deficiency might be involved in the pathogenesis of ischemic heart disease by altering the blood lipid composition in a way that disposes to atherosclerosis.     

Long-Term Function After Restorative Proctocolectomy

PURPOSE Early functional outcome after restorative proctocolectomy and formation of an ileoanal pouch is known to be good, but there are minimal data on the long-term function of the pouch. The aim of this study was to look at the long-term functional outcome in patients who had undergone restorative proctocolectomy and formation of an ileoanal pouch.METHODS A total of 151 consecutive patients (96 males, 55 females) who underwent ileoanal pouch surgery between April 1983 and May 1993 were identified. Functional outcomes from the previous 12 months were appraised by a standardized questionnaire.RESULTS The median age at surgery was 31 years (range, 6–63 years), with a median follow-up of 142 months (range, 100–221 months). Eighteen patients have had their pouches excised, with another patient being defunctioned. Therefore 19 patients (13 percent) had suffered pouch failure. Altogether, 115 patients were available for follow-up, and 98 patients (85 percent) returned questionnaires. The median pouch-emptying frequency was five times (range, 1–17) during the day and one time (range, 0–6) at night. A total of 74 percent of patients had perfect continence during the day. Most of the patients had no life-style restrictions related to the pouch, and 98 percent of patients would recommend a pouch to others.CONCLUSIONS Long-term functional outcome after ileoanal pouch surgery is good in most patients. For patients requiring proctocolectomy, ileoanal pouch surgery can now be recommended as an excellent long-term option.Presented at the Association of Coloproctology of Great Britain and Ireland, Manchester, United Kingdom, July 2 to 5, 2002 Reprints are not available.     

Case report: chylous ascites and carcinoid tumors: possible association of two rare disorders

Three cases of chylous ascites are reported in a series of 275 patients with carcinoid tumor. All three patients had diarrhea and elevated serotonin production. The literature is reviewed and the possible causes of the chylous ascites are discussed. It is suggested that a history of clinically significant diarrhea in a patient with chylous ascites should lead to biochemical tests for carcinoid tumors.     

Cardiomyocyte-specific knockout and agonist of peroxisome proliferator-activated receptor-gamma both induce cardiac hypertrophy in mice

Peroxisome proliferator-activated receptor (PPAR)-gamma is required for adipogenesis but is also found in the cardiovascular system, where it has been proposed to oppose inflammatory pathways and act as a growth suppressor. PPAR-gamma agonists, thiazolidinediones (TZDs), inhibit cardiomyocyte growth in vitro and in pressure overload models. Paradoxically, TZDs also induce cardiac hypertrophy in animal models. To directly determine the role of cardiomyocyte PPAR-gamma, we have developed a cardiomyocyte-specific PPAR-gamma-knockout (CM-PGKO) mouse model. CM-PGKO mice developed cardiac hypertrophy with preserved systolic cardiac function. Treatment with a TZD, rosiglitazone, induced cardiac hypertrophy in both littermate control mice and CM-PGKO mice and activated distinctly different hypertrophic pathways from CM-PGKO. CM-PGKO mice were found to have increased expression of cardiac embryonic genes (atrial natriuretic peptide and beta-myosin heavy chain) and elevated nuclear factor kappaB activity in the heart, effects not found by rosiglitazone treatment. Rosiglitazone increased cardiac phosphorylation of p38 mitogen-activated protein kinase independent of PPAR-gamma, whereas rosiglitazone induced phosphorylation of extracellular signal-related kinase 1/2 in the heart dependent of PPAR-gamma. Phosphorylation of c-Jun N-terminal kinases was not affected by rosiglitazone or CM-PGKO. Surprisingly, despite hypertrophy, Akt phosphorylation was suppressed in CM-PGKO mouse heart. These data show that cardiomyocyte PPAR-gamma suppresses cardiac growth and embryonic gene expression and inhibits nuclear factor kappaB activity in vivo. Further, rosiglitazone causes cardiac hypertrophy at least partially independent of PPAR-gamma in cardiomyocytes and through different mechanisms from CM-PGKO.     

Growth responses to patterned GH delivery

We have investigated the effects of different patterns of administration of recombinant human growth hormone (rhGH) on weight gain, organ growth, serum GH binding protein (GHBP) and insulin-like growth factor-l (IGF-1) levels in a series of studies using hypophysectomized (Hx) or GH-deficient dwarf (dw/dw) rats. Animals were given rhGH either by subcutaneous (s.c.) injections (1 or 2 per day) or s.c. infusions and rhlGF-1 (2 mg/kg/day) by s.c. infusion. In Hx rats, all rhGH regimes increased body weight, tibial epiphyseal plate width, and organ weights in a dose-related manner. Dwarf rats showed a smaller growth response to rhGH than Hx rats, whereas rhGH induced greater elevations in serum GHBP in drarf rats. Growth responses depended on the pattern of rhGH administration (twice daily injections > continuous infusions > daily injections). The shape of the body growth curves also differed; rhGH injections increased weight gain linearly, whereas infusions gave an initial rapid weight gain which slowed with time (a curvilinear response). For both regimens, tibial epiphyseal plate width increased linearly with rhGH dose but infusions were 5-fold more potent than daily injections. Spleen and thymus weights were markedly increased by rhGH and were also affected by the pattern of GH exposure. At 5 mg rhGH/kg/day, thymus weights were 390±35 mg for injectionsvs. 613 ± 34 mg for infusions (P<0.001) compared with 248 ± 16 mg in vehicle-treated Hx controls. Infusions of rhlGF-1 also stimulated specific organ growth but caused less weight gain. RhlGF-1 additively increased the weight gain caused by rhGH injections but not by rhGH infusions. Circulating IGF-1 and GHBP levels were increased in a dose-dependent manner by rhGH infusion, whereas daily injections were ineffective. Thus, differential organ growth could be related to the higher serum IGF-1 concentrations induced by continuous rhGH administration. These studies show that whole body growth is best maintained by intermittent rhGH exposure, whereas, paradoxically, differential organ growth is most pronounced with continuous rhGH administration.     

Real-time assessment of right and left ventricular volumes and function in children using high spatiotemporal resolution spiral bSSFP with compressed sensing

Background

Real-time cardiovascular magnetic resonance (CMR) assessment of ventricular volumes and function enables data acquisition during free-breathing. The requirement for high spatiotemporal resolution in children necessitates the use of highly accelerated imaging techniques.

Methods

A novel real-time balanced steady state free precession (bSSFP) spiral sequence reconstructed using Compressed Sensing (CS) was prospectively validated against the breath-hold clinical standard for assessment of ventricular volumes in 60 children with congenital heart disease. Qualitative image scoring, quantitative image quality, as well as evaluation of biventricular volumes was performed. Standard BH and real-time measures were compared using the paired t-test and agreement for volumetric measures were evaluated using Bland Altman analysis.

Results

Acquisition time for the entire short axis stack (~?13 slices) using the spiral real-time technique was ~?20 s, compared to ~?348 s for the standard breath hold technique. Qualitative scores reflected more residual aliasing artefact (p?<?0.001) and lower edge definition (p?<?0.001) in spiral real-time images than standard breath hold images, with lower quantitative edge sharpness and estimates of image contrast (p?<?0.001).There was a small but statistically significant (p?<?0.05) overestimation of left ventricular (LV) end-systolic volume (1.0?±?3.5 mL), and underestimation of LV end-diastolic volume (??1.7?±?4.6 mL), LV stroke volume (??2.6?±?4.8 mL) and LV ejection fraction (??1.5?±?3.0%) using the real-time technique. We also observed a small underestimation of right ventricular stroke volume (??1.8?±?4.9 mL) and ejection fraction (??1.4?±?3.7%) using the real-time imaging technique. No difference in inter-observer or intra-observer variability were observed between the BH and real-time sequences.

Conclusions

Real-time bSSFP imaging using spiral trajectories combined with a compressed sensing reconstruction showed good agreement for quantification of biventricular metrics in children with heart disease, despite slightly lower image quality. This technique holds the potential for free breathing data acquisition, with significantly shorter scan times in children.

     

Plasma Aluminum Concentrations in Pediatric Patients Receiving Long‐Term Parenteral Nutrition

Background: Patients receiving long‐term parenteral nutrition (PN) are at increased risk of aluminium (Al) toxicity because of bypass of the gastrointestinal tract during PN infusion. Complications of Al toxicity include metabolic bone disease (MBD), Al‐associated encephalopathy in adults, and impaired neurological development in preterm infants. Unlike the United States, there are no regulations regarding Al content of large‐ and small‐volume parenterals in Canada. We, therefore, aimed to present our data on plasma Al concentration and Al intake from our cohort of pediatric patients receiving long‐term PN. Methods: Plasma Al concentration was retrospectively gathered from the patient charts of all 27 patients with intestinal failure (IF) receiving long‐term PN at The Hospital for Sick Children, Toronto, Canada, and compared with age‐ and sex‐matched controls recruited for comparison. In addition, Al concentration was measured in PN samples collected from 10 randomly selected patients with IF and used to determine their Al intake. Results: The plasma Al concentration of patients with IF receiving long‐term PN was significantly higher than that of control participants (1195 ± 710 vs 142 ± 63 nmol/L; P < .0001). In the subgroup of 10 patients for whom Al intake from their PN solution was determined, mean ± SD Al intake from PN was 15.4 ± 15 µg/kg, 3 times the Food and Drug Administration upper recommended intake level, and Al intake was significantly related to plasma Al concentration (P = .02, r² = 0.52). Conclusion: Pediatric patients receiving long‐term PN for IF in Canada are at risk for Al toxicity.     

Using the wisdom of the crowds to find critical errors in biomedical ontologies: a study of SNOMED CT

Objectives The verification of biomedical ontologies is an arduous process that typically involves peer review by subject-matter experts. This work evaluated the ability of crowdsourcing methods to detect errors in SNOMED CT (Systematized Nomenclature of Medicine Clinical Terms) and to address the challenges of scalable ontology verification.Methods We developed a methodology to crowdsource ontology verification that uses micro-tasking combined with a Bayesian classifier. We then conducted a prospective study in which both the crowd and domain experts verified a subset of SNOMED CT comprising 200 taxonomic relationships.Results The crowd identified errors as well as any single expert at about one-quarter of the cost. The inter-rater agreement (κ) between the crowd and the experts was 0.58; the inter-rater agreement between experts themselves was 0.59, suggesting that the crowd is nearly indistinguishable from any one expert. Furthermore, the crowd identified 39 previously undiscovered, critical errors in SNOMED CT (eg, ‘septic shock is a soft-tissue infection’).Discussion The results show that the crowd can indeed identify errors in SNOMED CT that experts also find, and the results suggest that our method will likely perform well on similar ontologies. The crowd may be particularly useful in situations where an expert is unavailable, budget is limited, or an ontology is too large for manual error checking. Finally, our results suggest that the online anonymous crowd could successfully complete other domain-specific tasks.Conclusions We have demonstrated that the crowd can address the challenges of scalable ontology verification, completing not only intuitive, common-sense tasks, but also expert-level, knowledge-intensive tasks.