Ethics: responsible scientific conduct

Body composition and measures of obesity were evaluated in 59 subjects with myelomeningocele (MMC), aged 0.3-29 y, by anthropometry and measures of body cell mass (BCM) and intra- and extracellular water (ICW and ECW), derived from total body potassium and deuterium-isotope dilution; these results were compared with reference data. Body composition was normal in preambulatory children with MMC. Beyond ages 3-4 y there was significant depletion of BCM and total body water, with maldistribution of water (increased ECW and decreased ICW) and increased percentage body fat above that expected for age and sex. These findings were more pronounced in females and in those with high lesions, and were less pronounced in those who remained ambulatory. These changes may result in metabolic and nutritional maladaption during stress. The relation of BCM, total body water depletion and increased ECW to decreasing ambulatory activity suggests that early nutritional and mobility programs warrant further study.     

Warfarin for dilated cardiomyopathy: a bloody tough pill to swallow?

Although current recommendations for the treatment of dilated cardiomyopathy include long-term anticoagulation to diminish the likelihood of systemic embolization, there have been no clinical trials examining the effectiveness of anticoagulation in preventing systemic embolization in these patients. Furthermore, those recommendations do not address the issue of the quality of life associated with long-term warfarin therapy. Using decision analysis, the authors examined the benefits and risks of long-term anticoagulation for patients 35 to 75 years of age who have dilated cardiomyopathy. The results show that anticoagulant therapy increases quality-adjusted life expectancy by 76 to 128 days, depending on the patient's age. Sensitivity analysis, however, demonstrates that the outcome is dependent on the disutility associated with long-term warfarin therapy. Interestingly, anticoagulation exerts most of its benefit by preventing pulmonary embolization, not systemic embolization. The authors conclude that the current recommendation to anticoagulate these patients, although probably correct for many patients, should take into consideration the change in lifestyle imposed by long-term anticoagulant therapy. For some patients, the benefit may not outweigh the sacrifice.     

Differences in triage thresholds for patients presenting with possible acute coronary syndromes: more than meets the eye.

BACKGROUND: Many studies have shown differences in cardiac care by racial/ethnic groups without accounting for institutional factors at the location of care. OBJECTIVE: Exploratory analysis of the effect of hospital funding status (public vs private) on emergency department (ED) triage decision making for patients with symptoms suggestive of acute coronary syndromes (ACSs) and on the likelihood of ED discharge for patients with confirmed ACS. STUDY DESIGN AND SETTING: Secondary analysis of data from a randomized controlled trial of 10,659 ED patients with possible ACS in five urban academic public and five private hospitals. The main outcome measures were the sensitivity and specificity of hospital admission for the presence of ACS at public and private hospitals and the adjusted odds of a patient with ACS not being hospitalized at public versus private hospitals. RESULTS: Of 10,659 ED patients, 1,856 had confirmed ACS. For patients with suspected ACS, triage decisions at private hospitals were considerably more sensitive (99 vs 96%; p<.001) but less specific (30 vs 48%; p<.001) than at public hospitals. The difference between hospital types persisted after adjustment for multiple patient-level and hospital-level characteristics. CONCLUSION: Significant differences in triage for patients with suspected ACS exist between public and private hospital EDs, even after adjustment for multiple patient demographic, clinical, and institutional factors. Further studies are needed to clarify the causes of the differences.     

A study comparing biopharmaceutic characteristics of four once daily controlled release diltiazem preparations

Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)¹, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (c_min), the maximum plasma concentration (c_max), the time to reach that concentration (t_max), the time interval during which the plasma concentration exceeds 50% of c_max (t₅₀), the area under the plasma concentration-time curve (AUC_72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC_72–96 (AUC_NDM and AUC_DAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL^-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated.     

Segmental intestinal muscular thinning: a possible cause of intestinal obstruction in the newborn

Intestinal obstruction proximal to a transition zone without an interposed physical barrier usually indicates Hirschsprung disease. The authors report one case of focal small bowel muscular thinning just distal to a transition zone that produced clinical and radiographic findings that simulated long-segment Hirschsprung disease in a 2-day-old infant.     

HHF35, a muscle actin-specific monoclonal antibody. II. Reactivity in normal, reactive, and neoplastic human tissues.

Monoclonal antibody HHF35 has previously been characterized biochemically as recognizing isotypes of actin (alpha and gamma) which are specific to muscle cells. In this study, the authors have investigated the normal and pathologic tissue distribution of HHF35-positive cells using the avidin-biotin immunoperoxidase method on methacarn-fixed, paraffin-embedded sections of human tissue. In addition to muscle tissues (smooth, skeletal, and cardiac) the antibody localizes to myoepithelium, as well as most of the capsular cells of several parenchymal organs, including liver, kidney, and spleen, with extension of the latter cells into the splenic trabeculaes. In pathologic tissues, the antibody localizes to cells, identified by some investigators as "myofibroblasts," in the stroma of certain tumors, within hyperplastic fibrous tissue responses ("fibromatoses") such as Dupuytren's contracture, and within fibrotic lung tissue. HHF35 also localizes to cells that proliferate within the intima in lesions of atherosclerosis and to a unique population of reactive mesothelial and submesothelial cells. Among tumors, it is positive only on leiomyomas, leiomyosarcomas, and rhabdomyosarcomas, and negative on all nonmuscle sarcomas. This antibody thus shows great potential utility as a diagnostic reagent in various pathologic conditions, most especially in the diagnosis of tumors of muscle origin.