Quantitative diagnosis of stress-induced myocardial ischemia using analysis of contrast echocardiographic parametric perfusion images.

AIMS: Parametric imaging of myocardial perfusion provides useful visual information for the diagnosis of coronary artery disease (CAD). We developed a technique for automated detection of perfusion defects based on quantitative analysis of parametric perfusion images and validated it against coronary angiography. METHODS AND RESULTS: Contrast-enhanced, apical 2-, 3- and 4-chamber images were obtained at rest and with dipyridamole in 34 patients with suspected CAD. Images were analyzed to generate parametric perfusion images of the standard contrast-replenishment model parameters A, beta and A.beta. Each parametric image was divided into six segments, and mean parameter value (MPV) was calculated for each segment. Segmental MPV ratio between stress and rest was defined as a flow reserve index (FRI). Receiver operating characteristics (ROC) analysis was used in a Study group (N=17) to optimize FRI threshold and the minimal number of abnormal segments per vascular territory (LAD and non-LAD), required for automated detection of stress-induced perfusion defects. The optimized detection algorithm was then tested prospectively in the remaining 17 patients (Test group). LAD and non-LAD stenosis >70% was found in 19 and 17 patients, respectively. In the Study group, FRI threshold was: LAD=0.95 and non-LAD=0.68, minimal number of abnormal segments was four and two, correspondingly. Sensitivity, specificity and accuracy in the Test group were: 75%, 67% and 71% in the LAD, and 75%, 75% and 75% in the non-LAD territories. CONCLUSION: Automated quantitative analysis of contrast echocardiographic parametric perfusion images is feasible and may aid in the objective detection of CAD.     

Isolation, purification, and cytotoxicity of 5-methoxypodophyllotoxin, a lignan from a root culture of Linum flavum.

A method has been developed for the large scale isolation of 5-methoxypodophyllotoxin [1] from a high-producing root culture derived from Linum flavum. A closely related lignan, 5'-demethoxy-5-methoxypodophyllotoxin [2], was also present in the root culture and was the cause of the main isolation difficulties. Essential steps in the isolation procedure are CH2Cl2 and XAD-4 extraction and XAD-8 cc followed by Si gel chromatography, using two different mobile phases. The isolated 5-methoxypodophyllotoxin [1] was very pure (greater than 99%) and possessed the desired stereochemical configuration, namely (-)-5-methoxypodophyllotoxin [1]. The in vitro cytotoxicity of 5-methoxypodophyllotoxin [1] against EAT and HeLa cells was determined and compared with those of podophyllotoxin [3], etoposide (VP-16-213) [4], teniposide (VM-26) [5], and 5-methoxypodophyllotoxin-4-beta-D-glucoside [6]. It appeared that 5-methoxypodophyllotoxin [1] has about the same cytotoxic potency as podophyllotoxin [3].     

Circulating hydroxy fatty acids in familial Mediterranean fever.

Episodes of fever, serositis, and arthritis in familial Mediterranean fever (FMF) suggested circulating mediators of acute inflammation (e.g., neutrophil activation). The mean serum neutrophil-aggregating activity of 51 FMF patients was 2.5 +/- 0.2 cm2/min, compared to 1.0 +/- 0.1 cm2/min in 20 normal controls (P less than 0.0002). Lipid extracts of FMF sera retained neutrophil-aggregating activity and had UV absorbance peaks at 269 and 279 nm, indicating the presence of lipids with a conjugated triene structure. Chromatography of extracts yielded peaks that were coeluted with reference dihydroxyicosatetraenoic acids, had UV absorbance peaks at 259, 269, and 279 nm, and possessed neutrophil-aggregating activity. The presence of leukotriene B4 was excluded by chromatography following methyl-esterification. Monohydroxy compounds identified in FMF extracts by gas chromatography/mass spectrometry included 5-hydroxyicosatetraenoic acid, and 9- and 13-hydroxyoctadecadienoic acids. Hydroxy acids were present in 19 of 31 FMF sera and absent in extracts of sera from 8 patients with active systemic lupus erythematosus, 7 with fever from infection, and 12 normal controls. The finding of circulating mono- and dihydroxy fatty acids in FMF suggests that defects in the formation or elimination of these compounds might play a role in the pathogenesis of FMF.     

Pulmonary mycobacteriosis due to Mycobacterium chelonei: a report on a new case (authors' transl)]

Mycobacterium chelonei is a saprophytic germ usually devoid of pathogenic activity. Over a period of about the last ten years, however, several cases have been reported, including twelve cases of bronchopulmonary affections, in which it has been the infecting organism. The radiographic appearance is in every respect similar to that observed in pulmonary tuberculosis. A positive diagnosis of infection due to this germ can be made by the absence of Kuch's bacillus the lack of therapeutic effect of antituberculous medication, a positive skin reaction to specific antigens, and positive Mycobacterium Chelonei cultures from biopsy specimens. A new case of this infection is reported.     

Assessing fluid-responsiveness by a standardized ventilatory maneuver: the respiratory systolic variation test

Respiratory-induced changes in arterial blood pressure predict fluid responsiveness. However, the accuracy of these variables is affected by the preset tidal volume and by the early inspiratory increase in arterial blood pressure. We have therefore calculated the slope produced by the minimal systolic blood pressures (plotted against the respective airway pressures) during a ventilatory maneuver consisting of four incremental, successive, pressure-controlled breaths, termed the Respiratory Systolic Variation Test (RSVT). In 14 ventilated patients, after major vascular surgery, the slope of the RSVT decreased significantly after intravascular fluid administration and correlated with the end-diastolic area and with changes in cardiac output better than filling pressures. This preliminary study suggests that a standardized ventilatory maneuver may be useful in guiding fluid therapy in ventilated patients.     

Pediatric poisoning from trimedoxime (TMB4) and atropine automatic injectors

OBJECTIVE: To describe the effects of combined trimedoxime (TMB4) and atropine poisoning from automatic injectors (AI) in children. STUDY DESIGN: Data was collected from two sources: calls to the Israel Poison Information Center (IPIC) during a 1-year period and a cohort of children who presented to pediatric emergency departments (EDs) after unintentional injection of an AI. Demographic data and data regarding the type of AI, site and time of injection, and the clinical manifestations were abstracted. RESULTS: Data were available for 142 patients. The median age was 8.5 years (range 1.25-18 years). The dose of atropine and TMB4 was higher than the recommended dose for age in 22 (15.5%) cases. There were few side effects attributable to atropine: dilated pupils (26.7%), dryness of mucous membranes (24.6%), and tachycardia (22.5%). Compared with children injected with an age-appropriate dose, children injected with an AI that contained a dose that exceeds the recommended one were more likely to be symptomatic ( P = .029). There were no side effects characteristic to oximes, and no specific medical intervention was required. CONCLUSIONS: Unintentional pediatric atropine and TMB4 injection, even an adult dose in a small child, does not cause significant side effects.     

Confirmation of the association between male pattern baldness and the androgen receptor gene

Male pattern baldness (MPB) is a common phenomenon with a complex mode of inheritance. A recent report has implicated the androgen receptor gene in MPB, but this result has not been confirmed. We analyzed a silent polymorphism in the androgen receptor gene (AR) in a group of 41 bald males and 39 non-bald males, and found a significant association (p < 0.0026), thus confirming the previously reported association between MPB and the AR gene.     

Biochemical subtyping of amyloid in formalin-fixed tissue samples confirms and supplements immunohistologic data

The systemic amyloidoses are a heterogeneous group of congophilic fibrillar protein deposition diseases that should be subtyped chemically by immunohistologic methods. Biochemical methods sometimes are required to confirm or identify the amyloid type in unfixed or informalin-fixed tissue samples. We report the results of formic acid extraction and immunochemical and biochemical characterization of deposits informalin-fixed tissue samples from 10 cases of amyloidosis and 3 from nonamyloid monoclonal immunoglobulin light chain deposition disease. The results in 11 of 13 cases demonstrated concordance with the previous immunohistochemical and/or biochemical data obtained in unfixed tissue samples from the same specimens, and in 2 of 13, the protein deposits that previously could not be classified by standard immunohistochemical methods were identified by amino acid sequence. An additional new finding of constant-region rather than variable-region fragments as the major constituent protein in 1 case of lambda light chain amyloidosis demonstrated the value of the method and its importance for future applications.