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Establishment of adult Parelaphostrongylus tenuis, patent infections, and acquired immunity after experimental infection of white-tailed deer (Odocoileus virginianus) and red deer (Cervus elaphus elaphus).

Experimental Parelaphostrongylus tenuis infections were established in white-tailed deer (Odocoileus virginianus) and an atypical host, red deer (Cervus elaphus elaphus). Groups of deer were fed 10, 25, or 100 third-stage larvae (L3) of P. tenuis and received a single equivalent challenge exposure at varying intervals. Infections were monitored up to 6 yr in white-tailed deer and up to 2.8 yr in red deer. The prepatent period in white-tailed deer varied from 91 to 1,072 days (381 +/- 374) and in red deer from 105 to 358 days (167 +/- 77). Adult worms lived for up to 6 yr in white-tailed deer. Although most had patent infections until necropsy, latent periods were observed regardless of season. Adult worms lived for up to 2.8 yr in red deer, and patent infections persisted for 20-363 days (152 +/- 106). Patent infections were correlated with the presence of adult worms in blood vessels and sinuses of both deer species. Worms were restricted to the subdural space in all deer with latent and occult infections. Adult worm recovery in white-tailed deer fed 10 or 25 L3 corresponded to the mean intensities reported in natural infections of white-tailed deer Recovery from deer fed 100 L3 was not typical of natural infection intensities. Adult P. tenuis established in all groups of red deer, but neurologic disease was restricted to animals fed 100 L3. Acute neurologic disease was associated with subdural hemorrhage and occurred at 11 mo postinfection in 2 red deer. The absence of postchallenge patent periods and the persistence of occult infections indicated that challenge exposures did not establish. These data indicate that acquired immunity to P. tenuis was established by 6 mo postinfection in both white-tailed and red deer. Latent periods in white-tailed deer and latent infections in red deer reinforce the need for a reliable diagnostic assay.

Animals↗

Patent urachus with subsequent joint infection in a free-living Grevy's zebra foal.

A free-living, female Grevy's zebra (Equus grevyi) foal was found lethargic, lame, with swollen joints, pyrexia, and urine dripping from the umbilicus. It died 2 days later despite intensive care. Gross examination revealed patent urachus and suppurative arthritis. Swabs were taken from the joints, the patent urachus, and urine for bacteriology. The dominant isolate was Escherichia coli. The joint infection was probably secondary to septicemia, resulting from the patent urachus. To our knowledge, this is the first report of neonatal patent urachus in a wild equid.

Animals↗

Contrast echocardiography and transcranial Doppler sonography for detection of a patent foramen ovale.

We report the case of a patient, in whom a patent foramen ovale was detected. For the detection of a patent foramen ovale simulation of Valsalva's manoeuvre with a positive airway pressure of 20 cm H2O was applied. Change of ventilation manoeuvre by ventilation with positive airway pressure of 35/30/15 cm H2O at a tidal volume of 1200 ml make a distinct increase in passage of contrast medium from the right to the left atrium. These findings were detected by contrast transesophageal echocardiography and indirectly by transcranial Doppler sonography and were reproducible. This may stress the importance of preoperative screening of patent foramen ovale in patients to be operated on in the sitting position. Contrast echocardiography and the ventilatory manoeuvre with high airway pressure and PEEP might increase the detection rate of patent foramen ovale with a right to left shunt during general anaesthesia.

Echocardiography↗

Patent foramen ovale in underwater medicine.

The foramen ovale, between the right and left atria, exists in the foetal heart as a vital physiological communication. Haemodynamic closure occurs in the neonatal period with most people having permanent fusion of the foramen. In up to a third of adults the closure is functional only and a potential right to left atrial communication persists as a patent foramen ovale. Studies in patients with decompression illness after diving suggest a consistent increase in the prevalence of patent foramen ovale, as detected by transthoracic contrast echocardiography. The association is strongest for those patients with early onset of neurological decompression illness, particularly those cases occurring in the absence of other risk factors traditionally associated with decompression illness. However, patent foramen ovale is a common finding in the general population and the absolute risk of decompression illness, even in the presence of a patent foramen ovale, remains very low.

Decompression Sickness↗

[The way for carrying medicine and its containers (X): "patent medicine and carrying it in the Edo Period"].

A patent medicine and prescribed one coexisted in the Edo period, as they do in these days. A patent medicine was generally taken for curing slight illness and a prescribed one was used for curing serious one. As the former was more useful for carrying and taking it than the latter, a patent medicine was spread not only in town, but also in the country. Manufacturers of a patent medicine were eager to develop new markets for it and they were also active to innovate new preparations which were convenient for taking it and carrying it.

Drug Packaging↗

Non-HIV antivirals - a review of the recent patent literature.

This review covers the non-HIV antiviral patent literature from December 2001 to April 2002. Most of the patent applications describe new compounds for the treatment of hepatitis C virus (HCV) by inhibition of the NS3 serine protease. Several examples of both nucleoside and non-nucleoside inhibitors of the HCV polymerase NS5B have been reported. Hepatitis B virus (HBV) therapy continues to be dominated by nucleoside analogs, but several non-nucleoside HBV polymerase inhibitors have also been reported. In addition, a number of patents describing non-nucleoside inhibitors of the human cytomegalovirus (HCMV), the herpes simplex virus (HSV-1 and HSV-2) and the varicella zoster virus (VZV) DNA polymerase are also reviewed. A number of patents that appeared in 2002 hold promise for the treatment of respiratory syncytial virus (RSV) with small molecule inhibitors. Various approaches to the treatment of hepatitis D virus (HDV), picornaviruses and the human papilloma virus (HPV) are also described.

Journal Article↗

[Percutaneous closure of patent foramen ovale: preliminary experience with the PFO Star].

This article reports the experience of percutaneous closure of patent foramen ovale with the PFO Star device. Between January 2000 and December 2002, 44 consecutive patients with a mean age of 53 years were included in this registry. The implantation of the prosthesis was successful in 43 patients (98%): in 1 patient the atrial septum could not be crossed at operation. An early complication was observed in 3 patients (7%): one had transient amnesia and two patients had temporary ST elevation in the inferior ECG leads. Four patients (7%) had late complications: there was one case of spontaneously regressive atrial fibrillation, two recurrences of stroke (one in the patient without an implanted prosthesis and the other in a patient in whom the patent foramen ovale had been closed). Finally, one patient developed a fistula between the aorta and right atrium which occluded spontaneously when the anticoagulants were stopped. Complete closure of the patent foramen ovale was confirmed at 1 year in 92% of patients. The authors conclude that this preliminary experience shows that closure of patent foramen ovale with this device is effective and safe.

Adult↗

[Behavioral situation at onset of paradoxical brain embolism due to patent foramen ovale].

The goal of this study was to determine whether there was difference in behavioral situation at onset of stroke between the patients with right-to-left shunt whose stroke was diagnosed as paradoxical brain embolism according to the new criteria proposed by Strategies against Stroke Study for Young Adults in Japan (SASSY-Japan) and whose stroke was not. Among 365 consecutive patients with possible acute ischemic stroke who underwent transesophageal echocardiography, we compared clinical profiles of the following three patient groups: patients with patent foramen ovale whose stroke was diagnosed as paradoxical brain embolism (group A), patients with patent foramen ovale whose stroke was not diagnosed as paradoxical brain embolism (group B), and patients without patent foramen ovale whose stroke was diagnosed as cardiogenic brain embolism (group C). Patent foramen ovale was present on echocardiogram in 76 of 365 patients (21%). Among them, 19 patients were classified into group A and 34 into group B. Group C was composed of 69 patients. At stroke onset, 3 patients in group A took behavior with positive Valsalva maneuver, 2 in group B, and 1 in group C. Similarly at stroke onset, 4 patients in group A just stood up from long-time sitting position, 1 in group B, and 1 in group C. In all, stroke onset following Valsalva maneuver or long-time sitting position was positive in 37% of group A, 9% of group B, and 3% of group C, and was most frequent in group A (p < 0.0001). In group A, the frequency of Valsalva maneuver or long-time sitting position at stroke onset was higher than the frequency of detection of venous thrombus (21%). The result indicates that Valsalva maneuver and long-time sitting position contribute to occurrence of paradoxical brain embolism. We think that these behavioral situations are appropriate diagnostic criteria for paradoxical brain embolism.

Aged↗

Antiparasitics - a review of the recent patent literature.

A total of 45 patents relating to chemical substances with antiparasitic activity appeared during the last quarter of 1999 and the first quarter of 2000. While ten were concerned with specific formulations of registered drugs, nine alluded to the antiparasitc activity in a general way but without substantiating such effect. The majority of the 26 remaining patents reflected the further exploration of chemical groups with known antiparasitic activity. All patents covering antimalarials relate to artemisinin analogs, some of which may offer pharmacodynamic advantages over currently available commercial products. Only two patents concern candidate compounds against human and animal infections by members of the Trypanosomatidae family. In contrast, ectoparasitoses of livestock animals received greater attention with new developments in the area of avermectins, nodulosporins, marcfortines and paraherquamides, with pyrazole analogs obviously reflecting a major veterinary medical interest. As a result of molecular biological research, two new approaches to antiparasitic therapy were identified and two new screening methods were developed for application in antiparasitic and antifungal screening.

Journal Article↗

[Percutaneous closure of patent foramen ovale, as secondary prevention of cryptogenic cerebral event].

In patients with patent foramen ovale and cryptogenic stroke, the risk of recurrent event is about 4-5% yearly, despite of the antithrombotic treatment. Transcatheter closure of patent foramen ovale has been shown to decrease risk of recurrence. This report summarizes the first experiences in Hungary and the medium term follow up of our patients. Thirty-three patients were selected for closure. All the patients had at least one ischemic stroke, transitory ischemic attack or peripheral embolus. In 31 of them the stroke was confirmed by computer tomographic or magnetic resonance imaging. Patent foramen ovale with right-to-left shunt was diagnosed by transesophageal echocardiography. Transcatheter closure was performed under fluoroscopic and transesophageal echocardiographic control. Closure was successful in 31 patients. Passage of atrial septum did not succeed in two cases. An AV fistula at puncture site was the only early complication. There was no late complication. No device dislocation, periprocedural arrhythmia or embolic event was detected. No residual shunt could be found. During follow up of 11.3 (1-30) months no recurrent embolus was detected. Transcatheter closure of patent foramen ovale is a safe and efficient procedure to decrease the risk of recurrent ischemic events.

Adult↗

[Presence of patent foramen ovale in different heart diseases: incidence in 211 consecutive patients studied by transesophageal echocardiography].

BACKGROUND: Contrast echocardiography during the decompression phase of the Valsalva manoeuvre in course of transesophageal echo study is the ideal method to identify patent foramen ovale. METHODS: In order to evaluate the incidence of patent foramen ovale in patients with different cardiac diseases we performed contrast injection in 211 consecutive pts submitted to TEE (Transesophageal Echocardiography) in our laboratory between march 1991 and march 1993. RESULTS: Fiftythree of 211 pts (25%) presented a patent foramen ovale. The incidence in the different cardiac diseases was as follows: 0% in rheumatic mitral disease, 23% in aortic valve disease, 17% in mitral and/or aortic valve prosthesis, 29% in congenital heart disease other than interatrial septal defect, 44% in mitral valve prolapse and 92% in atrial septal aneurysm. CONCLUSIONS: This study indicates that patent foramen ovale is a common finding in different cardiac pathologies and frequent in mitral valve prolapse and even more in atrial septal aneurysm. In case of peripheral embolism of likely cardiac origin, the patency of the foramen ovale must be recognized, especially when these two latter cardiac anomalies are identified.

Aged↗

[Asymptomatic cerebral infarction associated with a patent foramen ovale and atrial septal aneurysm].

We reported two young adults (a 42-year-old female and a 45-year-old male) with tension type headache who had a patent foramen ovale and atrial septal aneurysm demonstrated by transesophageal echocardiography, associated with asymptomatic cerebral infarctions. There were multiple subcortical infarctions in the frontal and parietal lobes in case 1, and cerebral infarctions in the right corona radiata, head and body of the caudate nucleus, and putamen in case 2. The two cases did not have hypertension, diabetes mellitus, hyperlipidemia, cardiac diseases detected by electrocardiography and transthoracic echocardiography, and abnormality of intracranial and extracranial arteries by ultrasound sonography and cerebral angiography. Transeosophageal echocardiography revealed atrial septal aneurysm, and showed right-to-left shunt (patent foramen ovale) by Valsalva maneuver. Two cases were diagnosed as paradoxical cerebral embolism associated with a patent foramen ovale. If asymptomatic cerebral infarctions are cryptogenic stroke, a patent foramen ovale and atrial septal aneurysm should be examined by transesophageal echocardiography with Valsalva maneuver.

Adult↗

How can you patent genes?

What accounts for the continued lack of clarity over the legal procedures for the patenting of DNA sequences? The patenting system was built for a "bricks-and-mortar" world rather than an information economy. The fact that genes are both material molecules and informational systems helps explain the difficulty that the patent system is going to continue to have.

Access to Information↗

The patents-based pharmaceutical development process: rationale, problems, and potential reforms.

The pharmaceutical industry is facing substantial criticism from many directions, including financial barriers to access to drugs in both developed and developing countries, high profits, spending on advertising and marketing, and other issues. Underlying these criticisms are fundamental questions about the value of the current patent-based drug development system. Six major problems with the patent system are (1) recovery of research costs by patent monopoly reduces access to drugs; (2) market demand rather than health needs determines research priorities; (3) resources between research and marketing are misallocated; (4) the market for drugs has inherent market failures; (5) overall investment in drug research and development is too low, compared with profits; and (6) the existing system discriminates against US patients. Potential solutions fall into 3 categories: change in drug pricing through either price controls or tiered pricing; change in drug industry structure through a "buy-out" pricing system or with the public sector acting as exclusive research funder; and change in development incentives through a disease burden incentive system, orphan drug approaches, or requiring new drugs to demonstrate improvement over existing products prior to US Food and Drug Administration approval. We recommend 4 complementary reforms: (1) having no requirement to test new drug products against existing products prior to approval but requiring rigorous comparative postapproval testing; (2) international tiered pricing and systematic safeguards to prevent flow-back; (3) increased government-funded research and buy-out for select conditions; and (4) targeted experiments using other approaches for health conditions in which there has been little progress and innovation over the last few decades.

Developing Countries↗

Transcatheter closure of the patent ductus arteriosus: a comparative study between occluding coils and the Rashkind umbrella device.

This study was performed to evaluate the efficacy of transcatheter coil closure of the patent ductus arteriosus in comparison to our experience with the Rashkind umbrella device. Transcatheter coil closure of the patent ductus arteriosus has been reported with encouraging results. We present our experience with ducti up to 5.0 mm in diameter and report the short-term follow-up. We compare the results with our previous experience with the Rashkind umbrella device. Seventy-one patients underwent transcatheter coil closure. Median age was 3.1 years, and median weight was 13.6 kg. Mean ductus diameter was 2.0 +/- 1.1 mm. These were compared with 105 patients who underwent transcatheter closure using a single Rashkind umbrella device. The median age was 3.2 years and the median weight was 14.0 kg. The mean ductus diameter for this group was 2.1 +/- 0.6 mm. The ductus murmur in the coil group disappeared in all patients. Immediate (< or = 24h), complete closure was achieved in 89% of the coil group as compared to 71% for the Rashkind umbrella device group (P < 0.005). Closure rate for the coil group was 97% at the 6-month follow-up, vs. 82% for the Rashkind umbrella device group at the 6-12 month follow-up (P < 0.05). In almost all patients requiring more than one coil, the ductus was crossed serially from the aortic end. All patients with ductus diameter > or = 3.0 mm required two or more coils. Eleven coils in six patients embolized to the pulmonary arteries. All coils except one were retrieved with subsequent successful foil placement. Sixty-seven patients (94%) in the coil group were discharged in < or = 24 h. Transcatheter closure of the patent ductus arteriosus using multiple coils is a more effective technique than the Rashkind umbrella closure and has excellent short-term results. This can be performed safely as an outpatient procedure.

Adolescent↗

Molecular determinants of atrial and ventricular septal defects and patent ductus arteriosus.

Septation defects and patent ductus arteriosus are the most common human cardiovascular malformations (CVMs). Genetic factors play a major part in the origin of these malformations. Recent molecular analyses have shed light on several mendelian forms. In the autosomal dominant Holt-Oram syndrome, both atrial and ventricular septal defects are inherited in association with limb deformity as a result of mutations in the gene encoding the TBX5 transcription factor. Mutations in the NKX2.5 transcription factor gene cause autosomal dominant familial atrial septal defects in association with progressive atrioventricular block as well as complex congenital heart disease. Common atrial syndromes in autosomal dominant Ellis-van Creveld syndrome arise in the context of axial skeletal and limb malformation as a result of mutations in the EVC gene, whose function is unknown. Patent ductus arteriosus occurs in several syndromic forms of congenital heart disease, including Holt-Oram syndrome. Recent analyses of autosomal dominant Char syndrome, which includes, with variable penetrance, patent ductus arteriosus as well as craniofacial and hand malformations, have shown that the syndrome is caused by mutations in the TFAP2B transcription factor gene. Ongoing analyses are poised to determine the contribution of these genes as well as others yet to be identified to common, sporadic forms of congenital heart disease.

Abnormalities, Multiple↗

Pulmonary arteriography through patent ductus arteriosus with preformed catheters.

Selective pulmonary arteriography was performed successfully with new preformed catheters in eight consecutive patients with pulmonary atresia or severe stenosis and patent ductus arteriosus. The catheters were inserted percutaneously into the femoral artery and passed into the patent ductus arteriosus very easily within a few minutes. Pulmonary arteriography was performed with biplane cineangiography. All eight patients showed either stenosis or secondary atresia in the central pulmonary artery. The obstructive lesions occurred at the junction of either a patent ductus arteriosus or a surgically anastomosed subclavian artery.

Adult↗

Enhanced funding of pharmacoepidemiology through patenting the disclosure of adverse event information.

PURPOSE: Known drug adverse events have been estimated to be between the 4th and 6th leading cause of death in the US (1). There are currently insufficient funds to perform the quantity and quality of studies necessary to ensure all drug adverse events are discovered in a timely fashion. METHODS/RESULTS: One approach to attract capital for pharmacoepidemiology studies is to patent the discoveries from the studies. Potential investors, whether executives of branded pharmaceutical companies or not, will consider funding pharmacoepidemiology studies if they can expect to receive competitive returns on their investments. Pharmacoepidemiolists who desire to patent their discoveries should seek novel drug-drug and drug-food interactions or negative interactions between drugs and certain phenotypes, genotypes or preexisting comorbidities. CONCLUSION: These discoveries can lead to safer, and patentable, use of the drug by avoiding these interactions.

Drug Industry↗