Immersion technique for brain removal in perinatal autopsies

Perinatal autopsies present forensic patholgists with a variety of challenges, not the least of which involves the removal and examination of very small and sometimes fragile organs. Removal of the immature brain can be particularly troublesome. Even if great care is taken during brain removal, one is often left with no more than a semifluid amorphous mass of softened tissue by the time the brain is ready to be fixed in formalin. We describe a method of perinatal brain removal which helps to preserve brain shape and integrity. By removing the brain while the head (and body) is totally immersed in water, we find that the brain is easier to remove and less apt to destruction. Subsequent fixation in formalin results in well-preserved, intact specimens, allowing for optimal examination and sectioning.     

Global and specific migration of antioxidants from polypropylene films into food simulants

Global migration and specific migration of antioxidants (AOs--Irgafos 168 [tris(2,4-di-tert-butylphenyl) phosphite], Irganox 1076 [octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl-propionate], and Hostanox SE2 (distery thiodipropionate)--from polypropylene (PP) films into food simulants (water, 3% acetic acid, 95% ethanol, olive oil, and heptane) were studied. Films (50, 100, and 200 microns thick) were exposed to simulants at temperature-time conditions simulating migration under retorting and long-term storage. Global migration into aqueous simulants was independent of film thickness and conditions of exposure, so it seems as if the migration process was limited to the dissolution of migrants on the contacting surface. Global migration to fatty food simulants was dependent on simulant, conditions of exposure, and in some cases film thickness. Specific AO migration was analyzed from dry residues obtained from global migration analysis. Migration of AOs into aqueous simulants was below the detection limit (0.01 mg/dm2). Migration into fatty food simulants was dependent on the simulant. The extractive power of simulants was similar to that observed in global migration studies. Specific migration into heptane was independent of the polymer mass, though dependent on the thickness. Migration into ethanol was dependent on both mass and thickness. A theoretical discussion about the controversial effect of thickness on migration results, based on the kinetics of the process, is presented.     

Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication

Cilostazol is an antiplatelet agent and vasodilator marketed in Japan for treatment of ischemic symptoms of peripheral vascular disease. It is currently being evaluated in the United States for treatment of symptomatic intermittent claudication (IC). Cilostazol has been shown to improve walking distance in patients with IC. In addition to its reported vasodilator and antiplatelet effects, cilostazol has been proposed to have beneficial effects on plasma lipoproteins. We examined the effect of cilostazol versus placebo on plasma lipoproteins in 189 patients with IC. After 12 weeks of therapy with 100 mg cilostazol BID, plasma triglycerides decreased 15% (P<0.001). Cilostazol also increased plasma high density lipoprotein cholesterol (HDL-C) (10%) and apolipoprotein (apo) A1 (5.7%) significantly (P<0.001 and P<0.01, respectively). Both HDL3 and HDL2 subfractions were increased by cilostazol; however, the greatest percentage increase was observed in HDL2. Individuals with baseline hypertriglyceridemia (>140 mg/dL) experienced the greatest changes in both HDL-C and triglycerides with cilostazol treatment. In that subset of patients, HDL-C was increased 12.2% and triglycerides were decreased 23%. With cilostazol, there was a trend (3%) toward decreased apoB as well as increased apoA1, resulting in a significant (9.8%, P<0.002) increase in the apoA1 to apoB ratio. Low density lipoprotein cholesterol and lipoprotein(a) concentrations were unaffected. Cilostazol treatment resulted in a 35% increase in treadmill walking time (P=0.0015) and a 9.03% increase in ankle-brachial index (P<0.001). These results indicate that in addition to improving the symptoms of IC, cilostazol also favorably modifies plasma lipoproteins in patients with peripheral arterial disease. The mechanism of this effect is currently unknown.     

Evaluation of universal preenrichment broth for the recovery of foodborne pathogens from milk and cheese

The use of universal preenrichment broth for the recovery of verotoxigenic Escherichia coli, Salmonella spp., and Listeria monocytogenes from milk and cheese was examined. Universal preenrichment broth supported the growth of low inoculum levels (10 cfu/ml) of these organisms in pure cultures and in mixed cultures containing higher levels of other pathogens or bacterial flora from raw milk. This medium also supported the recovery and growth of heat-injured Salmonella spp., L. monocytogenes, and verotoxigenic E. coli at inoculum levels of 10(2) cfu/ml to yield cell levels of 10(8) cfu/ml in pure cultures and at least 10(5) cfu/ml in the presence of high levels of known competitive pathogens or microflora of cheese samples after 24 h of incubation. Universal preenrichment broth performed better than Listeria enrichment broth in supporting the recovery and growth of heat-injured L. monocytogenes and equally as well as buffered peptone water or trypticase soy broth in supporting the growth of uninjured L. monocytogenes, Salmonella spp., and verotoxigenic E. coli. Coenrichment of these pathogens in universal preenrichment broth reduced the quantity of milk or cheese samples that were required for analysis and also reduced the cost and labor involved in preparing and processing separate preenrichment media.     

Use of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) to assist with triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia. A multicenter, controlled clinical trial

BACKGROUND: Approximately 6 million U.S. patients present to emergency departments annually with symptoms suggesting acute cardiac ischemia. Triage decisions for these patients are important but remain difficult. OBJECTIVE: To test whether computerized prediction of the probability of acute ischemia, used with electrocardiography, improves the accuracy of triage decisions. DESIGN: Controlled clinical trial. SETTING: 10 hospital emergency departments in the midwestern, southeastern, and northeastern United States. PATIENTS: 10689 patients with chest pain or other symptoms suggestive of acute cardiac ischemia. INTERVENTION: The probability of acute ischemia predicted by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI), either automatically printed or not printed on patients' electrocardiograms. MEASUREMENTS: Emergency department triage to a coronary care unit (CCU), telemetry unit, ward, or home. Other measurements were the bed capacity of the CCU relative to that of the telemetry unit; training or supervision status of the triaging physician; and patient diagnoses and outcomes based on clinical, electrocardiographic, and creatine kinase data. RESULTS: For patients without cardiac ischemia, in hospitals with high-capacity CCUs and relatively low-capacity cardiac telemetry units, use of ACI-TIPI was associated with a reduction in CCU admissions from 15% to 12%, a change of -16% (95% CI, -30% to 0%), and an increase in emergency department discharges to home from 49% to 52%, a change of 6% (CI, 0% to 14%; overall P=0.09). Across all hospitals, for patients evaluated by unsupervised residents, use of ACI-TIPI was associated with a reduction in CCU admissions from 14% to 10%, a change of -32% (CI, -55% to 3%); a reduction in telemetry unit admissions from 39% to 31%, a change of -20% (CI, -34% to -2%); and an increase in discharges to home from 45% to 56%, a change of 25% (CI, 8% to 45%; overall P=0.008). Among patients with stable angina, in hospitals with high-capacity CCUs, use of ACI-TIPI was associated with a reduction in CCU admissions from 26% to 13%, a change of -50% (CI, -70% to -17%), and an increase in discharges to home from 20% to 22%, a change of 10% (CI, -29% to 71%; overall P=0.02). At hospitals with high-capacity telemetry units, use of ACI-TIPI was associated with a reduction in telemetry unit admissions from 68% to 59%, a change of -14% (CI, -27% to 1%), and an increase in emergency department discharges to home from 10% to 21%, a change of 100% (CI, 22% to 230%; overall P=0.02). Among patients with acute myocardial infarction or unstable angina, use of ACI-TIPI did not change appropriate admission (96%) to the CCU or telemetry unit at hospitals with high-capacity CCUs or telemetry units. CONCLUSIONS: Use of ACI-TIPI was associated with reduced hospitalization among emergency department patients without acute cardiac ischemia. This result varied as expected according to the CCU and cardiac telemetry unit capacities and physician supervision at individual hospitals. Appropriate admission for unstable angina or acute infarction was not affected. If ACI-TIPI is used widely in the United States, its potential incremental impact may be more than 200000 fewer unnecessary hospitalizations and more than 100000 fewer unnecessary CCU admissions.     

Fungal beta-tubulin, expressed as a fusion protein, binds benzimidazole and phenylcarbamate fungicides

Benzimidazoles are important antitubulin agents used in veterinary medicine and plant disease control. Resistance is a practical problem correlated with single amino acid changes in beta-tubulin and is often linked to greater sensitivity to phenylcarbamates. This negative cross-resistance creates opportunities for durable antiresistance strategies. Attempts to understand the molecular basis of benzimidazole resistance have been hampered by the inability to purify tubulin from filamentous fungi. We have overcome some of these problems by expressing beta-tubulin as a fusion with a maltose binding protein. This fusion protein is soluble, and we confirm for the first time using a gel filtration assay that benzimidazoles indeed bind to beta-tubulin. This binding is reduced by the mutation Glu198-->Gly198, which also confers resistance. Binding of phenylcarbamates is the complete opposite, reflecting their biological activity and the negative cross-resistance. This suggests that the fungicide binding sites fold correctly in the fusion protein.     

Development of attitude strength over the life cycle: surge and decline

This article explores the relation of age to manifestations and antecedents of attitude strength. Three studies demonstrate that susceptibility to attitude change is greater during early and late adulthood than during middle adulthood. Three additional studies demonstrate that attitude importance, certainty, and perceived quantity of attitude-relevant knowledge are greater in middle adulthood than during early or late adulthood. These antecedents may therefore explain life cycle shifts in susceptibility to change. Susceptibility to change, importance, certainty, and perceived knowledge differ from one another in terms of their correlations with education, gender, and race, challenging the notion that attitude strength is a unitary construct. Evidence that people incorrectly believe that susceptibility to change declines steadily over the life course reinforces the distinction between operative and meta-attitudinal measures of attitude strength.     

Diagnostic assignment of criteria: clinicians and DSM-IV

Keratocytes are useful in the study of locomotion because they move rapidly (up to 1 micron/second) while maintaining an almost uniform shape, speed and direction. The smooth gliding motion of the keratocyte requires a precise coordination between adhesion, contractility, and retraction. To ask what role integrins play in keratocyte adhesion and locomotion, either RGD peptides or an anti-beta1 integrin mAb that binds to an ectodomain epitope and inhibits adhesion formation was added to the culture media of moving keratocytes. The response to these reagents depended on three interrelated factors: the dose of RGD/mAb, the apparent adhesion strength of the keratocyte to the substratum and the cell speed. High doses cause keratocytes to quickly and irreversibly round up. At intermediate RGD/mAb doses, keratocytes reestablish adhesion after treatment and briefly resume locomotion until partial detachment recurs. At the lowest doses, disruption of beta1 integrin-mediated adhesion formation destabilizes the lamella, temporarily preventing lamellar extension and forward movement of the cell. With increasing culture time, there is an increase in apparent adhesion and a corresponding marked decrease in locomotory velocity. Under these conditions, high doses of RGD/mAb do not cause keratocytes to detach or even produce detectable lamellar instabilities. We postulate that RGD/mAb competitively inhibits new beta1 integrin mediated adhesion formation that is required to support the rates of lamellar extension necessary for rapid locomotion.     

Specific serological diagnosis of leprosy with a recombinant Mycobacterium leprae protein purified from a rapidly growing mycobacterial host

In this report we demonstrate the utility of an monoclonal antibody inhibition enzyme-linked immunosorbent assay based on the Mycobacterium leprae 35-kDa protein, purified from the rapidly growing host Mycobacterium smegmatis, for the serodiagnosis of multibacillary leprosy. The assay proved highly specific (97.5%) and sensitive (90%) and compared favorably with two other established methods routinely utilized for leprosy serodiagnosis.