Exaggerated pulmonary hypertension and right ventricular dysfunction in high-altitude dwellers with patent foramen ovale.

BACKGROUND There is considerable interindividual variability in pulmonary artery pressure among high-altitude (HA) dwellers, but the underlying mechanism is not known. At low altitude, a patent foramen ovale (PFO) is present in about 25% of the general population. Its prevalence is increased in clinical conditions associated with pulmonary hypertension and arterial hypoxemia, and it is thought to aggravate these problems. METHODS We searched for a PFO (transesophageal echocardiography) in healthy HA dwellers (n = 22) and patients with chronic mountain sickness (n = 35) at 3,600 m above sea level and studied its effects (transthoracic echocardiography) on right ventricular (RV) function, pulmonary artery pressure, and vascular resistance at rest and during mild exercise (50 W), an intervention designed to further increase pulmonary artery pressure. RESULTS The prevalence of PFO (32%) was similar to that reported in low-altitude populations and was not different in participants with and without chronic mountain sickness. Its presence was associated with RV enlargement at rest and an exaggerated increase in right-ventricular-to-right-atrial pressure gradient (25 ± 7 mm Hg vs 15 ± 9 mm Hg, P < .001) and a blunted increase in fractional area change of the right ventricle (3% [-1%, 5%] vs 7% [3%, 16%], P = .008) during mild exercise. CONCLUSIONS These findings show, we believe for the first time, that although the prevalence of PFO is not increased in HA dwellers, its presence appears to facilitate pulmonary vasoconstriction and RV dysfunction during a mild physical effort frequently associated with daily activity. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov.

Patent Foramen Ovale Closure in Obstructive Sleep Apnea Improves Blood Pressure and Cardiovascular Function.

UNLABELLED Obstructive sleep apnea (OSA) is a frequent syndrome characterized by intermittent hypoxemia and increased prevalence of arterial hypertension and cardiovascular morbidity. In OSA, the presence of patent foramen ovale (PFO) is associated with increased number of apneas and more severe oxygen desaturation. We hypothesized that PFO closure improves sleep-disordered breathing and, in turn, has favorable effects on vascular function and arterial blood pressure. In 40 consecutive patients with newly diagnosed OSA, we searched for PFO. After initial cardiovascular assessment, the 14 patients with PFO underwent initial device closure and the 26 without PFO served as control group. Conventional treatment for OSA was postponed for 3 months in both groups, and polysomnographic and cardiovascular examinations were repeated at the end of the follow-up period. PFO closure significantly improved the apnea-hypopnea index (ΔAHI -7.9±10.4 versus +4.7±13.1 events/h, P=0.0009, PFO closure versus control), the oxygen desaturation index (ΔODI -7.6±16.6 versus +7.6±17.0 events/h, P=0.01), and the number of patients with severe OSA decreased significantly after PFO closure (79% versus 21%, P=0.007). The following cardiovascular parameters improved significantly in the PFO closure group, although remained unchanged in controls: brachial artery flow-mediated vasodilation, carotid artery stiffness, nocturnal systolic and diastolic blood pressure (-7 mm Hg, P=0.009 and -3 mm Hg, P=0.04, respectively), blood pressure dipping, and left ventricular diastolic function. In conclusion, PFO closure in OSA patients improves sleep-disordered breathing and nocturnal oxygenation. This translates into an improvement of endothelial function and vascular stiffening, a decrease of nighttime blood pressure, restoration of the dipping pattern, and improvement of left ventricular diastolic function. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01780207.

Denkschrift über die Aufhebung des Gesetzes vom 13. Juli 1836, betreffend die bäuerliche Erbfolge in Westphalen: Nach dem Publikations-Patent vom 9. September 1814, durch welches das Allgemeine Landrecht in die mit dem Staat wieder vereinigten Provinzen eingeführt wurde ...

Welsch (Projektbearbeiter): Die Bevorzugung des Anerbenrechtes zuungunsten der Realteilung verstößt gegen den Grundsatz der staatsbürgerlichen Freiheit und Gleichheit. Da das fragliche Gesetz darüberhinaus - vorzugsweise von bäuerlicher Seite - abgelehnt wird, ist seine Aufhebung die natürliche Folge

Percutaneous closure of the patent foramen ovale, easy does it.

Closure of the patent foramen ovale does not benefit from echocardiographic guidance in the majority of cases. Guiding these procedures with fluoroscopy only reduces procedure time, radiation exposure, and amount of contrast medium. There is a clear trend to abandon echocardiographic guidance for this procedure over time and with growing experience.

Patent-Schnell-Darre

von J. Keidel

Patent, Daß zu Küstern Und Schulmeistern Auf dem platten Lande, Ausser Schneidern, Rademachern und Zimmerleuten, Sonst keine andere Handwercker angenommen werden sollen

[Fr. Wilhelm]

Patent und Declaration, Daß Die Bürger und Wirthe in denen Städten nicht schuldig seyn sollen, weder der Infanterie noch Cavallerie Das so genandte Sauer und Süß, oder Saltz, Pfeffer und Eßig ohnentgeldtlich zu reichen

[Fr. Wilhelm]

An meine lieben Berliner! : Durch mein Einberufungs-Patent vom heutigen Tage habt Ihr das Pfand der treuen Gesinnung Eures Königs zu Euch und zum gesammten teutschen Vaterlande empfangen ...

Welsch (Projektbearbeiter): Darstellung der Geschehnisse des 18. März 1848 (Aufstand in Berlin und Barrikadenkämpfe gegen das Militär) aus der Sicht Friedrich Wilhelms IV. Aufruf zur Niederlegung der Barrikaden, Versprechen des Truppenrückzuges von den öffentlichen Straßen und Plätzen

Indian Patent Policy and Publich Health : implications from the Japanese Experience

The introduction of pharmaceutical product patents in India and other developing countries is expected to have a significant effect on public health and local pharmaceutical industries. This paper draws implications from the historical experience of Japan when it introduced product patents in 1976. In Japan, narrow patents and promotion of cross-licensing were effective tools to keep drug prices in check while ensuring the introduction of new drugs. While the global pharmaceutical market surrounding India today differs considerably from that of the 1970's, the Japanese experience offers a policy option that may profitably be considered by India today. The Indian patent system emphasizes the patentability requirement in contrast to the Japanese patent policy which relied on narrow patents and extensive licensing. R&D by local firms and the development of local products may be promoted more effectively under the Japanese model.

Who Develops Innovations in Medicine for the Poor? Trends in Patent Applications Related to Medicines for HIV/AIDS, Tuberculosis, Malaria and Neglected Diseases

Who invents medicines for the poor of the world? This question becomes very important where the WTO allows low income countries to be unbound by the TRIPS agreement. This agreement concerns medicines for infectious diseases such as HIV/AIDS, tuberculosis and malaria. These diseases cause serious damage to low income countries. Under these circumstances, some scholars wonder if anyone will continue innovative activities related to treating these diseases. This paper sought to answer this question by collecting and analyzing patent data of medicines and vaccines for diseases using the database of the Japan Patent Office. Results indicate that private firms have led in innovation not only for global diseases such as HIV/AIDS but also diseases such as malaria that are spreading exclusively in low income countries. Innovation for the three infectious diseases is diverse among firms, and frequent patent applications by high-performing pharmaceutical firms appear prominent even after R&D expenditure, economies of scale, and economies of scope are taken into account.

Patent policy and public health in developing countries: lessons from Japan

The introduction of pharmaceutical product patents in India and other developing countries is expected to have a significant effect on public health and local pharmaceutical industries. This paper draws implications from the historical experience of Japan when it introduced product patents in 1976. In Japan, narrow patents and promotion of cross-licensing were effective tools to keep drug prices in check while ensuring the introduction of new drugs. While the global pharmaceutical market surrounding India today differs considerably from that of the 1970's, the Japanese experience offers a policy option that may profitably be considered by India today. The Indian patent system emphasizes the patentability requirement in contrast to the Japanese patent policy which relied on narrow patents and extensive licensing. R&D by local firms and the development of local products may be promoted more effectively under the Japanese model.

Innovation networks in China, Japan, and Korea : evidence from Japanese patent data

The growing importance of innovation in economic growth has encouraged the development of innovation capabilities in East Asia, within which China, Japan, and Korea are most important in terms of technological capabilities. Using Japanese patent data, we examine how knowledge networks have developed among these countries. We find that Japan's technological specialization saw little change, but those of Korea and China changed rapidly since 1970s. By the year 2009, technology specialization has become similar across three countries in the sense that the common field of prominent technology is "electronic circuits and communication technologies". Patent citations suggest that technology flows were largest in the electronic technology, pointing to the deepening of innovation networks in these countries.

Innovation networks in China, Japan, and Korea : further evidence from U.S. patent data

The growing importance of innovation in economic growth has encouraged the development of innovation capabilities in East Asia, within which China, Japan, and Korea are most important in terms of technological capabilities. Using U.S. patent data, we examine how knowledge networks have developed among these countries. We find that Japan's technological specialization saw gradual changes, but those of Korea and China changed rapidly since 1970s. By the year 2009, technology specialization has become similar across three countries in the sense that the common fields of prominent technology are electronics and semiconductors. Patent citations suggest that technology flows were largest in the electronics technology, pointing to the deepening of innovation networks in these countries. Together with our prior work, the Japanese and U.S. data produce similar conclusions about innovation networks.

Use of prediction methods for patent and trademark applications in Spain

Patent and trademark offices which run according to principles of new management have an inherent need for dependable forecasting data in planning capacity and service levels. The ability of the Spanish Office of Patents and Trademarks to carry out efficient planning of its resource needs requires the use of methods which allow it to predict the changes in the number of patent and trademark applications at different time horizons. The approach for the prediction of time series of Spanish patents and trademarks applications (1979e2009) was based on the use of different techniques of time series prediction in a short-term horizon. The methods used can be grouped into two specifics areas: regression models of trends and time series models. The results of this study show that it is possible to model the series of patents and trademarks applications with different models, especially ARIMA, with satisfactory model adjustment and relatively low error.