Comparison of Esophageal Manometric Characteristics in Asymptomatic Subjects and Symptomatic Patients with High-Amplitude Esophageal Peristaltic Contractions

The aim of this study was to examine systematically the manometric characteristics of symptomatic patients with high-amplitude peristaltic esophageal contractions, or the nutcracker esophagus (n = 20), in comparison to normal subjects (n = 30). In both normals and patients, amplitude and duration of contractions were more at 5 cm than at 10 cm above the lower esophageal sphincter. The patients differed significantly from normals not only in amplitude at 5 cm, but also at 10 cm and in duration at both sites. Bipeaked waves were seen more frequently in patients than in normals at either 5 or 10 cm above the sphincter. Two patients, but none of the normal subjects, had triple-peaked waves. Lower esophageal sphincter pressure was significantly elevated in patients as compared to normals. Although percent relaxation of the sphincter was the same in patients and normals, the postrelaxation residual, or nadir, sphincter pressure was higher in patients. We conclude that patients with high-amplitude peristaltic contractions may also have abnormalities in duration of contractions, percent bipeaked waves, triple-peaked waves, or in parameters of the lower esophageal sphincter.     

Diagnostic criteria for computer-aided electrocardiographic 15-lead system. Evaluation using 12 leads and Frank orthogonal leads with vector display.

The criteria for the diagnosis of myocardial infarction and ischaemic heart disease by an automated 15-lead computer-aided electrocardiographic system were examined using electrocardiograms of 543 patients. Errors in the electrocardiographic diagnosis were evaluated for each lead system (Frank orthogonal 3-lead, 12-lead, and hybrid 15-lead) using clinical and catheterization data for definitive diagnosis before review of the electrocardiograms and their reports. The effects of combinations of these diagnoses and additional ventricular conduction defects were also studied. Myocardial infarction and left ventricular hypertrophy were more reliably diagnosed using 3-lead and 12-lead systems together than with either system alone. The most sensitive criteria for anterior infarction were a Q/R ratio in Z less than 0-1 and loss of the first 20 ms of anterior forces in the horizontal and sagittal planes of the vectorcardiogram. However, false positive results were frequent, particularly in association with left ventricular hypertrophy, non-specific intraventricular conduction defects, and left bundle branch system block. Our V lead criteria were more specific whether or not these associated conditions were present. No single criterion with an acceptable false positive rate could be found to be sensitive for inferior infarction in all situations. Our most sensitive criteria were those based on the limb leads, and the presence of superior forces for the first 30 ms in the frontal plane of the vectorcardiogram, but these were better in combination. Limb lead criteria were the most specific. False positive results for inferior infarction were more frequent in the presence of left ventricular hypertrophy or ventricular conduction defects other than left anterior hemiblock. ST and T wave abnormalities were more apparent in the 12 leads than in the orthogonal leads. Specificity and sensitivity of criteria were poor, and specificity was decreased and sensitivity was not significantly improved by combining 3-lead with 12-lead criteria. Because of frequent measurement errors of ST, T, and also Q waves by the computer programme, in practice we have achieved increased sensitivity in the diagnosis of ischaemia and infarction with the combination of 3-lead and 12-lead systems. It is concluded that errors of diagnosis by a computer-aided system can be reduced by using multiple leads and that both 12-lead and orthogonal 3-lead systems are necessary for optimal computer diagnosis of left ventricular hypertrophy, myocardial infarction, and ischaemia.     

Insight into the molecular basis of pathogen abundance: group A Streptococcus inhibitor of complement inhibits bacterial adherence and internalization into human cells

Streptococcal inhibitor of complement (Sic) is a secreted protein made predominantly by serotype M1 Group A Streptococcus (GAS), which contributes to persistence in the mammalian upper respiratory tract and epidemics of human disease. Unexpectedly, an isogenic sic-negative mutant adhered to human epithelial cells significantly better than the wild-type parental strain. Purified Sic inhibited the adherence of a sic negative serotype M1 mutant and of non-Sic-producing GAS strains to human epithelial cells. Sic was rapidly internalized by human epithelial cells, inducing cell flattening and loss of microvilli. Ezrin and moesin, human proteins that functionally link the cytoskeleton to the plasma membrane, were identified as Sic-binding proteins by affinity chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis. Sic colocalized with ezrin inside epithelial cells and bound to the F-actin-binding site region located in the carboxyl terminus of ezrin and moesin. Synthetic peptides corresponding to two regions of Sic had GAS adherence-inhibitory activity equivalent to mature Sic and inhibited binding of Sic to ezrin. In addition, the sic mutant was phagocytosed and killed by human polymorphonuclear leukocytes significantly better than the wild-type strain, and Sic colocalized with ezrin in discrete regions of polymorphonuclear leukocytes. The data suggest that binding of Sic to ezrin alters cellular processes critical for efficient GAS contact, internalization, and killing. Sic enhances bacterial survival by enabling the pathogen to avoid the intracellular environment. This process contributes to the abundance of M1 GAS in human infections and their ability to cause epidemics.     

Evidence for an insulin receptor substrate 1 independent insulin signaling pathway that mediates insulin-responsive glucose transporter (GLUT4) translocation.

Interaction of the activated insulin receptor (IR) with its substrate, insulin receptor substrate 1 (IRS-1), via the phosphotyrosine binding domain of IRS-1 and the NPXY motif centered at phosphotyrosine 960 of the IR, is important for IRS-1 phosphorylation. We investigated the role of this interaction in the insulin signaling pathway that stimulates glucose transport. Utilizing microinjection of competitive inhibitory reagents in 3T3-L1 adipocytes, we have found that disruption of the IR/IRS-1 interaction has no effect upon translocation of the insulin-responsive glucose transporter (GLUT4). The activity of these reagents was demonstrated by their ability to block insulin stimulation of two distinct insulin bioeffects, membrane ruffling and mitogenesis, in 3T3-L1 adipocytes and insulin-responsive rat 1 fibroblasts. These data suggest that phosphorylated IRS-1 is not an essential component of the metabolic insulin signaling pathway that leads to GLUT4 translocation, yet it appears to be required for other insulin bioeffects.     

Comparison of five measures of motivation to quit smoking among a sample of hospitalized smokers

OBJECTIVE: To compare the predictive validity of several measures of motivation to quit smoking among inpatients enrolled in a smoking cessation program. METHODS: Data collected during face-to-face counseling sessions included a standard measure of motivation to quit (stage of readiness [Stage]: precontemplation, contemplation, or preparation) and four items with responses grouped in three categories: “How much do you want to quit smoking” (Want), “How likely is it that you will stay off cigarettes after you leave the hospital” (Likely), “Rate your confidence on a scale from 0 to 100 about successfully quitting in the next month” (Confidence), and a counselor assessment in response to the question, “How motivated is this patient to quit?” (Motivation). Patients were classified as nonsmokers if they reported not smoking at both the 6-month and 12-month interviews. All patients lost to follow-up were considered smokers. MAIN RESULTS: At 1 year, the smoking cessation rate was 22.5%. Each measure of motivation to quit was independently associated with cessation (p<.001) when added individually to an adjusted model. Likely was most closely associated with cessation and Stage was least. Likely had a sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio of 70.2%, 68.1%, 39.3%, 88.6%, and 2.2, respectively. CONCLUSIONS: The motivation of inpatient smokers to quit may be as easily and as accurately predicted with a single question as with the series of questions that are typically used.     

A randomized, double-blind trial of filgrastim (granulocyte colony-stimulating factor) versus placebo following allogeneic blood stem cell transplantation

Blood stem cell transplantation (BSCT) results in rapid hematopoietic recovery in both the allogeneic and autologous transplant settings. Because of the large numbers of progenitor cells in mobilized blood, the administration of growth factors after transplantation may not provide further acceleration of hematopoietic recovery. A randomized, double-blind, placebo-controlled study was performed to determine the effects of filgrastim (granulocyte colony-stimulating factor; G-CSF) administration on hematopoietic recovery after allogeneic BSCT. Fifty-four patients with hematologic malignancies undergoing a related, HLA-matched allogeneic BSCT were randomly assigned to receive daily filgrastim at 10 microg/kg or placebo starting on the day of transplantation. A minimum of 3 x 10(6) CD34(+) cells/kg in the allograft was required for transplantation. All patients received a standard preparative regimen and a standard regimen for the prevention of graft-versus-host disease (GVHD). The median time to achieve an absolute neutrophil count greater than 0.5 x 10(9)/L was 11 days (range, 9-20 days) for patients who received filgrastim compared with 15 days (range, 10-22 days) for patients who received placebo (P =.0082). The median time to achieve a platelet count greater than 20 x 10(9)/L was 13 days (range, 8-35 days) for patients who received filgrastim compared with 15.5 days (range, 8-42 days) for patients who received placebo (P =.79). There were no significant differences for red blood cell transfusion independence, the incidence of acute GVHD, or 100-day mortality between the groups. The administration of filgrastim appears to be a safe and effective supportive-care measure following allogeneic BSCT.     

The effects of carbon dioxide on oxygenation and systemic, cerebral, and pulmonary vascular hemodynamics after the bidirectional superior cavopulmonary anastomosis

OBJECTIVES: We investigated the effects of different CO(2) tensions on oxygenation, pulmonary blood flow (Qp), cerebral blood flow, and systemic blood flow (Qs) after the bidirectional superior cavopulmonary anastomosis (BCPA). BACKGROUND: Hypoxemia refractory to management of a high pulmonary vascular resistance index (PVRI) may complicate recovery from the BCPA. METHODS: After BCPA, CO(2) was added to the inspired gas of mechanically ventilated patients. The Qp, Qs, PVRI, and systemic vascular resistance index (SVRI) were calculated from oxygen consumption, intravascular pressures, and oxygen saturations. Cerebral blood flow was estimated by near infrared spectroscopy and transcranial Doppler. RESULTS: In nine patients (median age 7.1, range 2 to 23 months), arterial oxygen tension increased significantly (p < 0.005) from 36 +/- 6 mm Hg to 44 +/- 6 to 50 +/- 7 mm Hg at arterial carbon dioxide tensions (PaCO(2)) of 35, 45, and 55 mm Hg, respectively and decreased to 40 +/- 8 mm Hg at PaCO(2) 40 mm Hg. At a PaCO(2) of 55 and 45 compared with 35 mm Hg, Qp, cerebral blood flow, and Qs increased significantly, PVRI, Qp/Qs, and the ratio of Qp to inferior vena caval blood flow were unchanged, but SVRI decreased. CONCLUSIONS: We have demonstrated that after the BCPA, systemic oxygenation, Qp, Qs, and cerebral blood flow increased and SVRI decreased at CO(2) tensions of 45 and 55 mm Hg compared with 35 mm Hg. We suggest that hypoxemia after the BCPA is ameliorated by a higher PaCO(2) and that low PaCO(2) or alkalosis may be detrimental. Hypercarbic management strategies may allow earlier progression to the BCPA, which may contribute to reducing the interval morbidity in patients with a functional single ventricle.     

Reduced bone mineral density in bulimia as well as anorexia nervosa

We conducted a case controlled study to examine bone mineral density (BMD) in 47 women with bulimia nervosa, 51 with anorexia nervosa, 45 women recovered from past eating disorders, and 40 healthy controls. Lumbar spine and whole body BMD were measured by dual energy X‐ray absorptiometry. In contrast with previous studies, we found that subjects with active bulimia nervosa, even with no previous history of anorexia, had lower whole body and lumbar spine BMD than controls, although higher than in anorexia. Non‐traumatic spinal fractures were detected in two anorexic subjects and two bulimic subjects, but none of the controls. Assessment of BMD should be considered in patients with severe bulimia as well as anorexia nervosa. Copyright © 2004 John Wiley & Sons, Ltd and Eating Disorders Association.     

Animal antibiotic use has an early but important impact on the emergence of antibiotic resistance in human commensal bacteria

Antibiotic use is known to promote the development of antibiotic resistance, but substantial controversy exists about the impact of agricultural antibiotic use (AAU) on the subsequent emergence of antibiotic-resistant bacteria among humans. AAU for animal growth promotion or for treatment or control of animal diseases generates reservoirs of antibiotic-resistant (AR) bacteria that contaminate animal food products. Mathematical models are an important tool for understanding the potential medical consequences of this increased exposure. We have developed a mathematical model to evaluate factors affecting the prevalence of human commensal AR bacteria that cause opportunistic infections (e.g., enterococci). Our analysis suggests that AAU hastens the appearance of AR bacteria in humans. Our model indicates that the greatest impact occurs very early in the emergence of resistance, when AR bacteria are rare, possibly below the detection limits of current surveillance methods.