Intravenous epinephrine in life-threatening asthma

STUDY OBJECTIVE: Intravenous epinephrine is a potentially vital therapy for patients with life-threatening asthma but is often avoided because of concerns about its safety. We evaluated the safety of intravenous epinephrine in a series of adults with life-threatening asthma. METHODS: We performed an explicit retrospective chart review on a case series of 27 emergency department patients aged 19 to 58 years (mean 25 years) who were treated with intravenous epinephrine for a life-threatening exacerbation of asthma between 1989 and 1997. Explicit criteria for adverse effects, including cardiac arrhythmia or ischemia, hypotension or hypertension, neurologic injury, and death, were defined before chart review. RESULTS: No patient had an arrhythmia other than sinus tachycardia, and there were no cases of cardiac ischemia, hypotension, neurologic deficit, or death. CONCLUSION: Intravenous epinephrine was safe in this small series of younger adults with acute life-threatening asthma. A prospective trial of its use to better define an efficacy and risk-benefit relationship is justified.     

Effects of age on responses to isometric exercise. Isometric handgrip in noninvasive screening for cardiovascular disease.

Isometric handgrip (IHG) imposes an acutely increased afterload on the left ventricle. Utilizing systolic time intervals, we studied various responses to IHG, measured as changes from resting values with near-maximum IHG, in old normal (ON) subjects, young normal (YN) subjects, and old patients with hypertensive heart disease (HHD) and patients with coronary artery disease (CAD). There were no differences in responses to IHG between ON and patients with HHD or patients with CAD. However, there were clear differences between the responses of ON and YN subjects. Increase in heart rate (HR) was much more prominent in YN (ON vs. YN = +11.6 +/- 2.6 vs. +15.6 +/- 5.7 beats per minute p less than 0.001). Pre-ejection period (PEP) end isovolumic contraction time (IVCT) increased in ON but decreased in YN (PEP + 6.2 +/- 1.7 vs. -11.0 +/- 3.7 msec., p less than 0.001; IVCT +8.1 +/- 2.2 vs. -13.8 +/- 3.4 msec., p less than 0.001. Shortening of LVET was much more marked in YN (-6.5 +/- 4.1 VS. -63.3 +/- 9.9 msec. p less than 0.001), but this was entirely due to the HR differences since there was no difference in ejection time index (+ 5.1 +/- 3.4 vs. -0.4 +/- 7.3 msec. p greater than 0.5). IHG produced no significant differences between ON and YN in the timing of the "mitral" component of the first heart sound (q-Im), in the ratio PEP/LVET, or in pulse transmission time (PTT). By contrast, resting control PTT was markedly short in ON, especially those with CAD. Resting PTT in ON was 27.1 +/- 2.6 msec.; in YN 43.7 +/- 1.4 msec.; in CAD patients 20.7 +/- 1.3 msec. We conclude that even near-maximal IHG does not seem to be an adequate noninvasive screening test for cardiovascular disease in that age alone seems to have the most significant influence on the responses.     

Supplementation with tetrahydrobiopterin prevents the cardiovascular effects of angiotensin II-induced oxidative and nitrosative stress

OBJECTIVE: The pteridine cofactor tetrahydrobiopterin (BH4) has emerged as a critical determinant of endothelial nitric oxide synthase (eNOS) activity. When BH4 availability is limited, eNOS does not produce nitric oxide (NO) but instead generates superoxide. BH4 may reverse endothelial dysfunction due to cardiovascular disease, including atherosclerosis, coronary artery disease and hypertension. In this study, the influence of BH4 on cardiovascular parameters and the production of free radicals following angiotensin II (Ang II) infusion was assessed. METHODS: BH4 (20 mg/kg per day in drinking water) was administered with Ang II (300 ng/kg per min subcutaneously, osmotic pump) for 7 days in Sprague-Dawley rats. In addition, BH4 was also given in vehicle-infused rats. RESULTS: Treatment with BH4 significantly prevented some of the effects of Ang II, such as impaired vascular responses to acetylcholine, hypertension and increases in heart weight index values. Treatment with BH4 also significantly reduced Ang II-induced increases in inducible NO synthase expression, nitrotyrosine immunostaining, NO production and superoxide anion formation in rats. CONCLUSION: These results indicate that BH4 might prevent the development of hypertension and myocardial hypertrophy, as well as the Ang II-induced production of superoxide and NO, thereby reducing the production of peroxynitrite. Therefore, BH4 may protect against the cardiovascular manifestations of oxidative and nitrosative stress in this experimental model of Ang II-mediated hypertension.     

Synthesis,Properties, and Doping Behavior of Optically Active Polythiophenes Bearing a Bornyl Group

Polythiophenes bearing a bornyl group as a side chain are synthesized. The polymers, which consist of multiple thiophenes and a substituted aromatic ring in the repeat unit, demonstrate right‐handed helicity in the film state. Results of energy level measurements show good agreement with the density functional theory calculation results for the model compounds. In situ electron spin resonance (ESR) studies indicate that increasing the number of unsubstituted thiophene units in the repeat unit increases susceptibility for the dopants. The chiral charge carriers are confirmed with ESR and circular dichroism spectroscopy measurements.

     

Comparative genomic hybridization analysis for pancreatic cancer specimens obtained by endoscopic ultrasonography-guided fine-needle aspiration

Background Comparative genomic hybridization (CGH) analysis of pancreatic cancer has been done exclusively for surgical and autopsy specimens, because of the difficulty of tissue sampling without surgery. To overcome this difficulty, we applied CGH technology to cells obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA).Methods In the present study, we performed EUS-FNA for 17 patients with pancreatic cancer before surgery. Tumor cells were selected by microdissection. DNA was extracted from the cells and amplified by degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR). Then CGH was carried out.Results In the 15 patients with tubular adenocarcinoma, the most common loci of gains (including amplification) were 5p, 8q, and 20q (60% of the patients); and 1q, 7p, and 12p (27%). The most frequent losses were 17p (73%); 9p, 18q, and 19p (47%); and 8p (33%). These findings were similar to our previously reported data. Both of the patients with acinar cell carcinoma showed gains of 2q and 5p, and losses of 1p, 9p, 9q, 11p, 11q, 14q, 17p, 17q, and 18q.Conclusions The results of this study suggest that comprehensive genetic analysis is possible for EUS-FNA biopsy specimens, with a combination of microdissection and DOP-PCR. This analytical strategy will enable us to evaluate the biological characteristics of pancreatic cancer before treatment.     

Changes in Expression of Connexin 32, Bile Canaliculus-Like Structures,and Localization of Alkaline Phosphatase in Primary Cultures of Fetal Rat Hepatocytes

We devised an experimental design in primary cultures of fetal rat hepatocytes for studying hepatocyte differentiation over a short period. In the present study, hepatocytes were first cultured for 3 days in dexamethasone-supplemented medium and then for an additional 3 days in dexamethasone- or epidermal growth factor-supplemented medium. In hepatocytes cultured continuously in dexamethasone-supplemented medium, the expression of connexin 32 increased and bile canaliculus-like structures and localization of alkaline phosphatase in the plasma membrane around bile canaliculus-like structures were maintained. Few cells incorporated bromodeoxyuridine. On the other hand, in most of the hepatocytes cultured in epidermal growth factor-supplemented medium, the expression of connexin 32 was minimally recognized, bile canaliculus-like structures were shortened or eliminated, and alkaline phosphatase was localized as numerous fine spots throughout the cytoplasm. More than 20% of all hepatocytes incorporated bromodeoxyuridine.The present study suggests that in hepatocytes, there is a close relationship among connexin 32 expression, the maintenance of bile canaliculus-like structures, and the localization of alkaline phosphatase to the plasma membrane around the bile canaliculus-like structures, and this indicates that the present experimental model is useful for studying hepatocyte differentiation over a short period.     

Acute Limited Intimal Tears of the Thoracic Aorta

Background

Limited intimal tears (LITs) of the aorta (Class 3 dissection variant) are the least common form of aortic pathology in patients presenting with acute aortic syndrome (AAS). LITs are difficult to detect on imaging and may be underappreciated.