Effect of epinephrine on cerebral and myocardial perfusion in an infant animal preparation of cardiopulmonary resuscitation

We assessed the efficacy of conventional cardiopulmonary resuscitation (CPR) in 2-week-old piglets. We determined intrathoracic vascular pressures, cerebral (CBF) and myocardial blood flows (MBF), and cerebral oxygen uptake during conventional CPR in this infant animal preparation and contrasted these results with those of previous work on adult animals. We further examined the effects of the infusion of epinephrine on these pressures and flows and on cerebral oxygen uptake, which has not been previously evaluated in adult preparations. Conventional CPR was performed on pentobarbital-anesthetized piglets with a 20% sternal displacement with the use of a pneumatic piston compressor. Chest recoil was incomplete, leading to an 18% to 27% reduction in anteroposterior diameter during the relaxation phase. Aortic and right atrial pressures in excess of 80 mm Hg were generated. These pressures are greater than those generally obtained in adult animals with similar percent pulsatile displacements. CBF and MBF were also initially greater than those reported in adult animals undergoing conventional CPR. However, when CPR was prolonged beyond 20 min, aortic pressure fell and CBF and MBF declined to the near-zero levels seen in adult preparations. At 5 min of CPR, CBF and MBF were 24 +/- 7 and 27 +/- 7 ml . min-1 x 100 g-1 (50% and 17% of the values during cardiac arrest), respectively. With the continuous infusion of epinephrine (4 micrograms/kg/min) in another group of animals, MBF was significantly greater at 20 min of CPR and CBF and cerebral O2 uptake were greater at 35 min of CPR as a result of higher perfusion pressures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Estrogen, testosterone, and gender differences

The purpose of this report is to gain some current perspective on the definition, bases, and trends for research associated with gender differences. To accomplish this goal an analysis on the number of citations from a 1994–2004 Medline search with the terms estrogen, testosterone, gender differences, sex differences as well as the combinations of these terms was performed. Other combinations of terms included separate searches of estrogen, testosterone, and their combination within males or females, and an analysis of gender and sex differences with the terms human and animal. The salient results from this survey include: (1) An overall greater ratio of estrogen:testosterone citations when these terms were searched alone or in combination with gender differences; (2) an overall greater ratio of testosterone:estrogen citations when these terms were combined with sex differences or conducted separately within males or females, although this trend was shifting toward decreased testosterone and increased estrogen citation numbers toward the latter years of the survey; (3) a trend for increasing numbers of estrogen and gender differences citations over the period of the survey; (4) a clear indication for the term gender differences to be associated with the search term human; and (5) a very small number of citations when the terms estrogen and testosterone were combined. Interpretations and implications of these results are discussed.     

Aneurysm of a saphenous vein bypass graft associated with aneurysms of native coronary arteries

Aneurysm formation in saphenous vein aortocoronary bypass grafts is an extremely rare complication of coronary artery bypass surgery. Aneurysms of native coronary arteries are found in a small percentage of patients at autopsy. Reported is a case with multiple coronary artery aneurysms in which a dissecting aneurysm of the saphenous vein bypass graft also developed following coronary artery bypass surgery. This is the first report of such association.     

DRD2 Dopamine Receptor Genotype, Linkage Disequilibrium, and Alcoholism in American Indians and Other Populations

We defined interpopulation differences in the frequency of the dopamine D2 receptor DRD2/Taq1 A1 allele, which has previously been associated with alcoholism. Frequencies of the A1 allele in unrelated subjects were 0.18 to 0.20 (se = 0.02 to 0.03) in several Caucasian populations previously assessed, 0.38 (±0.05) in American Blacks ( n = 44), 0.63 (±0.07) in Jemez Pueblo Indians ( n = 23), and 0.80 (± 0.04) in Cheyenne Indians ( n = 52). The existence of large interpopulation differences in the frequency of the Taq1 alleles suggests that associations to disease status could readily be generated or masked if disease and control groups were uneven in ethnic composition. To address the possibility that the 4-fold higher frequency of the A1 allele in Cheyenne Indians was related to an increased vulnerability to alcoholism in that population, 47 Cheyenne Indians were psychiatrically interviewed and blind-rated. However, there was no significant difference between interviewed controls (0.73 ± 0.06, n = 24), subjects with alcoholism and/or drug abuse (0.74 ± 0.06, n = 23) and noninterviewed population controls (0.87 ± 0.05, n = 20). Legitimate association of the DRD2/Taq1 allele to alcoholism would presumably require it to be in linkage disequilibrium (nonrandom association) with a functional mutation at DRD2 or elsewhere. The level of disequilibrium would vary between populations and could place an upper bound on the strength of an association. To provide a model for the extent and variation of disequilibrium at DRD2, the level of linkage disequilibrium between the Taq1 RFLP and a second DRD2 polymorphism, the SSCP variant in the immediate 3'region of the gene, was determined in three populations. The normalized disequilibrium values were 0.36 In U.S. Caucasians ( n = 48), 0.34 in Finns ( n = 86), and 0.78 in Cheyenne Indians ( n = 34).     

Therapeutic treatment of canine osteoarthritis with glycosaminoglycan polysulfuric acid ester

The therapeutic effect of glycosaminoglycan polysulfuric acid ester (GAGPS) was studied using the Pond-Nuki model of canine osteoarthritis. The clinical setting was simulated by permitting 4 weeks ambulation without treatment, following anterior cruciate transection. Animals were then injected with GAGPS, 4 mg/kg intramuscularly, twice weekly during weeks 4-8. Control animals received intramuscular saline. The study was terminated 4 weeks after completion of the GAGPS or saline regimen (i.e., 12 weeks postoperatively). Cartilage from the medial femoral condyle was analyzed for collagen integrity (swelling properties), hydroxyproline, uronic acid, active and total proteoglycan (PG)-degrading metalloproteinase, PG-degrading serine proteinase, and histopathology (Mankin score). Condylar cartilage from animals treated with GAGPS demonstrated less cartilage swelling, less total and active metalloproteinase, and lower histopathologic scores than were found in cartilage from saline-treated animals. GAGPS was able to suppress PG-degrading enzyme activity and maintain a more normal-appearing cartilage. It is proposed that GAGPS suppressed PG breakdown by decreasing synthesis of metalloproteinase or by directly inhibiting metalloproteinase in cartilage, rather than by increasing synthesis of PG by chondrocytes.     

Mast cells and mastocytosis

Mast cells have been recognized for well over 100 years. With time, human mast cells have been documented to originate from CD34+ cells, and have been implicated in host responses in both innate and acquired immunity. In clinical immunology, they are recognized for their central role in IgE-mediated degranulation and allergic inflammation by virtue of their expression of the high-affinity receptor for IgE and release of potent proinflammatory mediators. In hematology, the clinical disease of mastocytosis is characterized by a pathologic increase of mast cells in tissues, often associated with mutations in KIT, the receptor for stem cell factor. More recently, and with increased understanding of how human mast cells are activated through receptors including the high-affinity receptor for IgE and KIT, specific tyrosine kinase inhibitors have been identified with the potential to interrupt signaling pathways and thus limit the proliferation of mast cells as well as their activation through immunoglobulin receptors.     

The influence of balloon inflation duration on the acute angiographic result of percutaneous transluminal coronary angioplasty

This study was performed to evaluate the importance of the duration of balloon inflation during PTCA, by comparing two common inflation durations. Patients were randomized to a 30-second inflation protocol (group I, 83 procedures, 109 lesions), or a 60-second protocol (group II, 83 procedures, 115 lesions). There were no differences in baseline characteristics between the two groups, and no subsequent differences in mean inflation number (3.4 +/- 1.6 vs 3.1 +/- 1.6), residual stenosis (34% +/- 17% vs 33% +/- 16%), presence of dissection (29% vs 34%), or clinical success (89% vs 84%), group I versus group II, respectively. The 30-second inflations caused significantly less chest pain score (147 +/- 239 vs 399 +/- 516, P less than 0.001), and ST segment alteration (75 +/- 94 seconds vs 136 +/- 163, P less than 0.05). These results indicate that 60-second inflations do not produce a superior result to 30-second inflations. Furthermore, shorter inflations are much better tolerated.     

Polymorphisms in metalloproteinase-9 are associated with the risk for asthma in Mexican pediatric patients

Asthma is characterized by chronic airway inflammation, which induces airway remodelling of the extracellular matrix over time. Matrix metalloproteinases (MMPs) are involved in this process, and single-nucleotide polymorphisms (SNPs) in MMP genes may influence their mRNA expression levels or abilities to bind substrates and inhibitors, thereby contributing to asthma predisposition and severity. MMP-9 is highly expressed in airways and many studies support its involvement in asthma pathogenesis; however the contribution of MMP-9 SNPs is controversial. To investigate whether MMP-9 SNPs are associated with childhood-onset asthma in Mexican patients we conducted a case-control study including 403 children with clinical asthma diagnoses and 426 healthy controls from Mexico. The cases and controls were matched by ethnicity and gender. We found that the SNPs rs2274755, rs17577, and rs3918249 were associated with asthma risk. The most significant associations were with rs2274755 (OR = 2.10, 95% CI 1.31–3.39, P = 0.001) and rs17577 (OR = 2.07, 95% CI 1.29–3.30, P = 0.001); which were in strong linkage disequilibrium. Both SNPs were also associated with atopic asthma (OR = 2.38, 95% CI 1.44–3·96, P = 0.0005). The SNP rs3918249 exhibited a female gender-dependent association with asthma (OR = 1.66, 95% CI 1.14–2.43, P = 0.007). Our results suggest that MMP-9 polymorphisms could play a role in the susceptibility to childhood-onset asthma.