Peripheral intravenous myocardial contrast echocardiography using a 2% dodecafluoropentane emulsion: identification of myocardial risk area and infarct size in the canine model of ischemia.

OBJECTIVES: This study assessed the accuracy of 2% dodecafluoropentane (EchoGen), an intravenous echocardiographic contrast agent, in identifying myocardial area at risk and infarct size in the canine model of myocardial ischemia. BACKGROUND: Myocardial contrast echocardiography allows determination of myocardial area at risk and infarct size but requires intracoronary injection in humans. The development of agents that can be delivered by peripheral intravenous injection could enable bedside myocardial contrast echocardiographic assessment of risk area, infarct size and reperfusion. METHODS: Two protocols were used. Protocol 1 assessed the accuracy of myocardial contrast echocardiography using intravenous dodecafluoropentane in defining myocardial area at risk and infarct size in the canine model of regional myocardial ischemia versus gross pathologic specimens stained with monastral blue to determine area at risk and triphenyltetrazolium chloride to determine the area of necrosis. Protocol 2 assessed the effects of repeated injections of dodecafluoropentane (0.5 ml/kg body weight, four doses 30 min apart or eight doses 10 min apart) on myocardial blood flow and hemodynamic variables. RESULTS: Myocardial contrast echocardiography accurately defined area at risk and infarct size (r = 0.96 vs. triphenyltetrazolium chloride). Myocardial blood flow remained stable after multiple serial injections of dodecafluoropentane. However, a significant increase in pulmonary artery pressure and pulmonary vascular resistance, along with a decrease in arterial oxygen saturation and cardiac output, was seen in dogs that received eight injections at 10-min intervals. CONCLUSIONS: Myocardial contrast echocardiography using intravenous dodecafluoropentane accurately defined myocardial area at risk and infarct size. Hemodynamic variables and regional myocardial blood flows remained stable when dodecafluoropentane was injected at 30-min intervals for up to four doses; more frequent administration led to cardiopulmonary deterioration. Dodecafluoropentane offers the potential for reliable, noninvasive assessment of reperfusion after therapeutic interventions.

Aldehydes potentiate alpha(2)(I) collagen gene activity by JNK in hepatic stellate cells.

Hepatic stellate cells (HSCs) are responsible for type I collagen deposition in liver fibrosis that leads to cirrhosis. The purpose of this study was to examine potential molecular signals that lead to increased alpha(2)(I) collagen gene expression by acetaldehyde, the primary metabolite of alcohol and malondialdehyde (MDA), a lipid peroxidation product known to be associated with chronic liver injury. MDA and the combination of MDA and acetaldehyde were employed to determine the effect on alpha(2)(I) collagen gene expression as assessed by transient transfection analysis and reverse transcriptase polymerase chain reaction (RT-PCR). Immunoblot and subsequent immunoprecipitation analysis examined stress-activated protein kinase (SAPK) activity. Cotransfection with a dominant negative mutant for c-jun nuclear kinase (dnJNK1) was also employed with the alpha(2)(I) collagen promoter. MDA increased alpha(2)(I) collagen gene expression nearly 2.5- to 3-fold, however there was no synergistic effect of the combination of acetaldehyde and MDA on alpha(2)(I) collagen gene activation and expression. Acetaldehyde, MDA, or both significantly increased JNK activity when compared to untreated stellate cells. The dnJNK1 expression vector abrogated alpha(2)(I) collagen transgene activity. In conclusion, JNK activation appears to be critical in the signaling cascade of oxidative metabolites of chronic alcohol-related liver injury and collagen gene activation.

Complications of herpes zoster ophthalmicus.

Of 86 patients with herpes zoster ophthalmicus seen at the Mayo Clinic, Rochester, Minn, from 1975 to 1980, 61 had some form of ocular involvement. Corneal disease was seen in 47, uveitis in 37, postherpetic neuralgia in 15, scleritis in three, and ocular motor palsies in three. No case of optic nerve or retinal involvement was found. Of serious concern were four patients with neurologic complications, including two with contralateral hemiplegia and two with segmental cerebral arteritis. Because the neurologic complications occur several months after the episode of herpes zoster ophthalmicus, the association is often overlooked and the opportunity to treat with corticosteroids for systemic effect is missed.

A training procedure for remediating WCST deficits in chronic psychotic patients: an adaptation of errorless learning principles.

Although a number of studies have demonstrated that psychiatric patients' performance deficits on the Wisconsin Card Sorting Test (WCST) can be modified through intervention, relatively little evidence exists to support the long-term durability of training effects. The present study tested the effectiveness and durability of a training procedure based on errorless learning principles, and in addition sought to determine the effect of previously committed errors on training and post-training performance. Twenty-three chronic psychotic inpatients were randomly assigned to an Initial Error (n = 11) or No Initial Error (n = 12) group. The Initial Error group received two standard administrations of the WCST prior to training (where they were expected to commit many errors); the No Initial Error group had no prior exposure to the WCST. All subjects received training on the WCST which was followed by immediate, 1-, 2-, and 4-week post-tests. Results supported the effectiveness of training and the durability of effects, but previous error history showed no clear relationship to post-training performance.

Pro-alpha 2(V) collagen gene; pairwise analysis of the amino-propeptide coding domain, and cross-species comparison of the promoter sequence.

Type V collagen is a minor represented and poorly characterized fibrillar collagen type. Previous cDNA cloning experiments showed that the amino-propeptide of the pro-alpha 2(V) chain shares structural features in common with pro-alpha 1(I), pro alpha 1(II) and pro-alpha 1(III) collagens. In the present paper, this analysis was extended to the gene level. Accordingly the exon/intron arrangement of the amino-propeptide coding domain was compared among pro-alpha 1(I) (COL1A1), pro alpha 1(II) (COL2A1), pro-alpha 1(III) (CO13A1) and pro-alpha 2(V) (COL5A2) collagen genes. This revealed that COL3A1 is the most closely related gene to COL5A2. Based on the assumption that critical regulatory elements might be phylogenetically conserved, we also compared the promoter sequences of the mouse and human COL5A2 genes. This revealed the highest level of sequence homology (97%) in a 52-bp segment which was previously shown to be essential in conferring cell type specificity to the human promoter.

Evaluation of two commercially available carbon dioxide sampling nasal cannulae.

Our study compared two commercially available carbon dioxide sampling nasal cannulae for efficacy of oxygenation and relationship of end-tidal carbon dioxide (PETCO2) to arterial carbon dioxide (PaCO2). The two-prong nasal cannula (2PNC) has one prong dedicated to delivering O2 via one naris and the second prong dedicated to sampling exhaled gases via the other naris. The four-prong nasal cannula (4PNC) delivers O2 via a prong in each naris, and samples exhaled gases via another set of prongs in each naris. Forty six patients were divided into three groups, which received either 2 (n = 15), 3 (n = 16), or 4 (n = 15) L/min O2, respectively, and were studied sequentially with standard nasal cannula (SNC), the 2PNC, and then the 4PNC. At each O2 flow rate, PaO2 was equivalent regardless of whether the SNC, 2PNC, or 4PNC was used. Seventy-four percent (34/46) of the 2PNC and 0% (0/46) of the 4PNC PETCO2 values were within +/- 4 torr of the PaCO2 value. The authors conclude that the 2PNC and 4PNC are equally effective compared with an SNC in oxygenating patients, but the PETCO2 measured by the 2PNC provides a superior quantitative estimate of the PaCO2 than that obtained by the 4PNC.

Acetaldehyde enhances murine alpha2(I) collagen promoter activity by Ca2+-independent protein kinase C activation in cultured rat hepatic stellate cells.

Protein kinase C (PKC) inhibitors decrease alpha1(I) collagen mRNA in stellate cells exposed to 200 micromol/liter of acetaldehyde. The purpose of these studies was to determine whether PKC activation plays a role in transcriptional activation of the alpha2(I) collagen gene. Cultured stellate cells were exposed to 200 micromol/liter of acetaldehyde. PKC, inositol triphosphate, diacylglycerol (DAG), and intracellular free calcium (Ca2+i) were measured. Alpha1(I) and alpha2(I) collagen messages were determined by reverse transcriptase-polymerase chain reaction. Activation of the alpha2(I) collagen promoter was determined in transiently transfected stellate cells. Acetaldehyde exposure enhanced PKC activity translocation to the particulate fraction at 20 min. Acetaldehyde did not increase Ca2+i, or inositol triphosphate but increased DAG levels at 20 min and 3 hr. Acetaldehyde increased both the alpha1(I) and alpha2(I) collagen messages in stellate cells. Calphostin C, a specific PKC inhibitor, which blocks DAG binding, eliminated both activation of the alpha2(I) collagen promoter by acetaldehyde and mRNA production by reverse transcriptase-polymerase chain reaction analysis. Similarly, D609, an inhibitor of DAG production, also inhibited alpha2(I) collagen gene expression. This study shows that collagen production by acetaldehyde is mediated by a calcium-independent PKC mechanism.

Transdifferentiation of rat hepatic stellate cells results in leptin expression.

Leptin is a peptide hormone that appears critical in regulating Fat metabolism. Recently, circulating leptin levels were reported higher in patients with alcoholic cirrhosis. In health, hepatic stellate cells store retinoids, but following liver injury they transdifferentiate into myofibroblast-like cells with loss of the retinoid stores. Leptin expression was demonstrated by detection of leptin mRNA by RT-PCR analysis and by immunohistochemistry viewed with confocal microscopy in transdifferentiated stellate cells after 14 days, or more, of culture. Leptin expression was not found in freshly isolated quiescent stellate cells. Leptin expression was not demonstrated in freshly isolated or cultured Kupffer cells. Treatment of activated stellate cells with either 1 microM retionic acid or 10 microM retinol acetate resulted in the inhibition of leptin mRNA expression. The observation that activated stellate cells in culture can express leptin has implications for understanding adipocyte biology in liver disease and treatment of malnutrition in cirrhotics.