Angiogenesis in Myocardial Laser "Revasculiarization"

The clinical and experimental data relevant to the theoretical mechanisms and clinical results of laser myocardial "revascularization" are reviewed. Both transmyocardial (TMR) and percutaneous (PMR) approaches are considered. Special attention is paid to the issue of TMR-induced angiogenesis. Both TMR and PMR result in a reduction in angina symptoms in patients refractory to conventional therapy and are likely to act through common pathways. TMR-induced angiogenesis appears to result from the up-regulation of vascular growth factors. However, the available data suggest that the angiogenic response is not a unique consequence of laser revascularization. Rather, the angiogenesis associated with TMR is likely to be a non-specific response of the myocardium to injury. Zusammenfassung Die Idee, die Myokardperfusion mittels eingebrachter Kannäle zu verbessern, ist sehr alt und beruht auf experimentellen und klinischen Befunden. Vineberg implantierte die Arteria mammaria interna direkt in das Myokard und konnte zum Teil exzellente Langzeitergebnisse über 20 Jahre demonstrieren. Pifarré modifizierte das Konzept und implantierte autologe Venen. Weitere Interventionen zur Modifikation des Konzeptes wurden durchgeführt. Selbst die Verwendung von Akupunkturnadeln oder T-Stücken wurde eingesetzt. Mirhoseini verwandte schließlich einen CO₂-Laser im Hundemodell zur Behandlung der Ischämie und konnte eine Steigerung der Durchblutung des Myokards nachweisen. Diese experimentellen Vorstellungen wurden auf die Klinik übertragen und zunächst transmurale und später perkutane Myokardlaserrevaskularisationen mittels CO₂-Laser, Holmium: Yag-Laser und Excimer-Laser durchgeführt. Die Bildung von neuen Kapillaren um die gebildeten Kannäle wurden nachgewiesen, so dass der Aspekt der Angiogenese erhebliches Interesse gewann. Es konnte nachgewiesen werden, dass auch der angiogenetische Faktor VEGF nach Laserbehandlung anstieg. Erhöhte Spiegel für die mRNA wurden erfasst. Derzeit muss man aber davon ausgehen, dass die induzierte Angiogenese eher eine unspezifische Antwort auf die Myokardschädigung darstellt. Eine laserspezifische Angiogenese konnte niemals sicher identifiziert werden. Ein Nachweis der Steigerung der Myokardperfusion konnte experimentell nicht sicher erfasst werden. Auch hierbei zeigte sich ein eher unspezifischer Effekt. Klinisch wurde die Thalium-SPECT-Szintigraphie und Positronenemissions-tomographie benutzt, um Patienten vor und nach Laserrevaskularisation zu untersuchen. Dabei konnten Verbesserungen der regionalen Myokardperfusion erfasst werden. Diese Ergebnisse sind aber von anderen Autoren nicht bestätigt worden. Die meisten klinischen Studien zeigen keine Verbesserung der regionalen oder globalen Myokardfunktion. Ein weiterer wichtiger Effekt des Lasers scheint die Zerstörung von Nervenfasern zu sein, die die behandelte Myokardregion durchlaufen. Die transmurale Myokardlaserrevaskularisation und die perkutane Myokardlaserrevaskularisation führen zu einer Reduktion der Angina pectoris bei Patienten mit Symptomen, die mit konventionellen Therapiemaßnahmen nicht beherrscht werden können.     

Perception of pitch contours in single words in alaryngeal speech.

The perception and production of pitch contours were investigated in single words produced by two groups of alaryngeal speakers: tracheo-oesophageal (TE) and oesophageal (E) speakers. High quality tape-recordings of three tonal patterns by four oesophageal and eight tracheo-oesophageal speakers in monosyllabic words were judged by a group of six speech and language therapy listeners. The results indicated that tonal patterns can be produced with a relatively high level of reliability for both speaker groups. Some individual speakers from both groups approached predicted normal levels. These findings emphasise the importance of providing the opportunity for patients to acquire either of these speech modes in alaryngeal rehabilitation, rather than simply being provided with an artificial larynx, particularly in countries where tone languages are used. The high variability between groups also suggests that other variables apart from alaryngeal speech mode may be relevant in determining ability to signal tonal patterns.     

Acceptability ratings and intelligibility scores of alaryngeal speakers by three listener groups.

Acceptability and intelligibility of three groups of alaryngeal speakers were examined: four oesophageal speakers, four tracheo-oesophageal puncture speakers using a tracheostoma valve and four tracheo-oesophageal puncture speakers using digital occlusion. Speakers were video-taped producing samples from the Assessment of Intelligibility of Dysarthric Speech, in addition to a section of spontaneous speech. Three groups of listeners were used: nine speech and language therapists, five ENT surgeons and ten na?ve listeners. Specific variables including fluency, rate, quality, intensity, extraneous noise, effort required, pitch and general acceptability were rated on a 7-point scale. Overall no significant difference was found between the speaker groups but listener groups did obtain significantly different intelligibility scores with speech and language therapists scoring highest and ENT surgeons lowest. Analysis suggests that speech and language therapist listeners cope equally well with all speaker groups but ENT surgeons and na?ve listeners cope best with tracheo-oesophageal puncture speakers using the tracheostoma valve; only the data from ENT surgeons showed a significant difference between scores for the different speaker groups.     

Long-Term Effects of Pesticide Exposure at Various Life Stages of the Southern Leopard Frog (Rana sphenocephala)

Amphibian larvae are commonly exposed to low levels of pesticides during their development. Chronic studies generally examine the effects of long-term exposure, but they often disregard the importance of the individual life stage at which tadpoles are exposed. I determined the point during development at which carbaryl effects are manifested by exposing southern leopard frog tadpoles (Rana sphenocephala) to the pesticide carbaryl at five different times during development. Metamorphs exposed throughout the tadpole stage and throughout development (egg, embryo, tadpole) experienced significant mortality at all chemical levels. Although the length of the larval period was the same for all experimental groups, metamorphs exposed during the egg stage were smaller than their corresponding controls, independent of whether they were exposed at any other stage. Nearly 18% of individuals exposed to carbaryl during development exhibited some type of developmental deformity (including both visceral and limb malformities), compared to a single deformed (< 1%) control tadpole, demonstrating that a chemical hypothesis for amphibian deformities remains viable. Because exposure to nonpersistent chemicals may last for only a short period of time, it is important to examine the long-term effects that short-term exposure has on larval amphibians and the existence of any sensitive life stage. Any delay in metamorphosis or decrease in size at metamorphosis can impact demographic processes of the population, potentially leading to declines or local extinction. Received: 18 June 1999/Accepted: 13 January 2000     

Decreased antibody response among nursing home residents who received recalled influenza vaccine and results of revaccination, 1996-97

In November 1996, 11 lots of one U.S. manufacturer's 1996-97 trivalent influenza vaccine were voluntarily recalled because of decreasing potency of the A/Nanchang/933/95 (H3N2) component. Because the elderly are at high risk of developing influenza-related complications, we assessed the postvaccination antibody titers of nursing home residents who received recalled vaccine and assessed the antibody response to revaccination. Blood samples were collected 3 weeks after vaccination from 86 residents at three nursing homes who received recalled vaccine and 86 residents at three other nursing homes who received a different manufacturer's vaccine. Medical records were reviewed. Residents of one nursing home were later revaccinated. Blood samples were collected on the day of revaccination and again in 3 weeks. Serum was tested by hemagglutination inhibition for antibody to all three components of the 1996-97 influenza vaccine. The geometric mean antibody titer (GMT) (33 vs 55; p=0.01) and the percentage of residents with an antibody titer > or = 1:40 (52 vs 67%; p=0.04) to the A/Nanchang/933/95 component were lower among residents who received recalled vaccine compared to those who received non-recalled vaccine, but had similar GMTs against the other two vaccine components. After revaccination, the GMT to A/Nanchang/933/95 increased from 24 on the day of revaccination to 39 (p=0.01) in residents from one nursing home. Therefore, vaccination with the recalled vaccine was associated with lower postvaccination antibody titers to A/Nanchang/933/95, but not against the other two vaccine components. Revaccination was moderately effective in increasing antibody titers. With annual changes in influenza vaccine strains, routine post-release stability testing of influenza vaccine should continue.     

Addressing risk preferences in cost-effectiveness analyses

Cost-effectiveness analysis is a form of economic evaluation that compares that compares the costs and effectiveness of health interventions, where effectiveness is measured in a single scale. Despite the growth in the popularity of cost-effectiveness analysis, very few cost-effectiveness analyses adequately measure and account for uncertainty. In the health economics literature, two schools of thought are emerging. The first takes a statistical approach to uncertainty by focusing on the likelihood that a decision making error will be made. The second approach applies and develops economic theories of risk preference that consider the welfare implications for a patient when they are presented with interventions that have uncertain health outcomes. Cost-effectiveness analyses need to account for risk preferences if they claim to be increasing patient welfare.     

Homograft aortic root replacement during pregnancy

Operative cardiac interventions have been performed on pregnant women with varying degrees of success since the late 1950s. Currently, reported maternal mortality for cardiac operations is similar to the mortality rate for nonpregnant female patients. However, fetal mortality remains high, at approximately 20%. Aortic root replacement with an aortic homograft in a 34-year-old pregnant woman with bacterial endocarditis at 18 weeks gestation is presented. Fetal echocardiography during and after bypass was employed.     

The significance of heavy pornography involvement for romantic partners: research and clinical implications

This article presents a paradigm case portrait of female romantic partners of heavy pornography users. Based on a sample of 100 personal letters, this portrait focuses on their often traumatic discovery of the pornography usage and the significance they attach to this usage for (a) their relationships, (b) their own worth and desirability, and (c) the character of their partners. Finally, we provide a number of therapeutic recommendations for helping these women to think and act more effectively in their very difficult circumstances.     

Comparison of mucosal and systemic humoral immune responses after transcutaneous and oral immunization strategies

In order to compare the ability of transcutaneous and oral immunization strategies to induce mucosal and systemic immune responses, we inoculated mice transcutaneously with cholera toxin (CT) or the non-toxic B subunit of cholera toxin (CtxB), or orally with Peru2(pETR1), an attenuated vaccine strain of Vibrio cholerae expressing CtxB. In addition, we also evaluated dual immunization regimens (oral inoculation with transcutaneous boosting, and transcutaneous immunization with oral boosting) in an attempt to optimize induction of both mucosal and systemic immune responses. We found that transcutaneous immunization with purified CtxB or CT induces much more prominent systemic IgG anti-CtxB responses than does oral inoculation with a vaccine vector strain of V. cholerae expressing CtxB. In comparison, anti-CtxB IgA in serum, stool and bile were comparable in mice either transcutaneously or orally immunized. Overall, the most prominent systemic and mucosal anti-CtxB responses occurred in mice that were orally primed with Peru2(pETR1) and transcutaneously boosted with CT. Our results suggest that combination oral and transcutaneous immunization strategies may most prominently induce both mucosal and systemic humoral responses.