Day: 11/09/2010

The immense potential of xenotransplantation in surgery

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There is a limited availability of deceased human organs and cells for the purposes of clinical transplantation. Genetically-engineered pigs may provide an alternative source. Although several immune barriers need to be overcome, considerable progress has been made in experimental models in recent years, largely through the increasing availability of pigs with new genetic modifications.

Pig heterotopic heart graft survival in nonhuman primates has extended for 8 months, with orthotopic grafts supporting life for almost 2 months. Life-supporting kidney transplants have functioned for almost 3 months. The current barriers are related to coagulation dysfunction between pig and primate that results in thrombotic microangiopathy and/or a consumptive coagulopathy, which may in part be related to molecular incompatibilities in the coagulation systems of pigs and primates. Current efforts are concentrated on genetically-modifying the organ- or islet-source pigs by the introduction of ‘anticoagulant’ or ‘anti-thrombotic’ genes to provide protection from the recipient coagulation cascade and platelet activation.

Progress with pig islet xenotransplantation has been particularly encouraging with complete control of glycemia in diabetic monkeys extending in one case for >12 months. Other areas where experimental data suggest the possibility of early clinical trials are corneal xenotransplantation and pig neuronal cell xenotransplantation, for example, in patients with Parkinson’s disease.

With the speed of advances in genetic engineering increasing steadily, it is almost certain that the remaining problems will be overcome within the foreseeable future, and clinical allotransplantation will eventually become of historical interest only.

source: science direct

leflunomide in rheumatoid arthritis and psoriatic arthritis

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Jones PBB et al. – Recent trials have shown that leflunomide can be used safely with biologic DMARDs, including antitumor necrosis factor agents and rituximab as part of the treatment algorithm in place of methotrexate as a cotherapy. Leflunomide has demonstrated efficacy as a monotherapy in psoriatic arthritis, and it also has a beneficial effect in psoriasis. Postmarketing studies have shown that retention on treatment with leflunomide is equal to methotrexate and superior to other DMARDs. In general, its side effect profile is acceptable compared with other DMARDS, with nausea, diarrhea, and hair fall occurring commonly, but only rarely leading to discontinuation. Liver toxicity is the most significant problem in clinical use although it is uncommon. Peripheral neuropathy, hypertension, pneumonitis, and cytopenia occur more rarely. Leflunomide is contraindicated in pregnancy and should be used with caution in women during child–bearing years. In this review, the place of leflunomide in therapy is discussed and practical advice informed by evidence is given regarding dosing regimens, safety monitoring, and managing side effects. Leflunomide remains one of the most useful of the nonbiologic DMARDs.

Sperm-Associated Antigen 9: A Novel Diagnostic Marker for Thyroid cancer

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Garg M et al. – SPAG9 expression may play a role in cellular growth and thyroid carcinogenesis. These findings support a potential role for SPAG9 as diagnostic biomarker as well as a possible therapeutic target in thyroid cancer treatment.

The Evolving Epidemiology of Hepatitis A in the United States

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Background The incidence of hepatitis A virus (HAV) disease is the lowest ever in the United States. We describe recent incidence and characteristics of cases of HAV disease from 6 US sites conducting hepatitis surveillance in the Emerging Infections Program.

Methods Health departments conducted enhanced, population-based surveillance for HAV from 2005 through 2007. Demographic and risk factor data were collected on suspected cases (persons with a positive IgM anti-HAV result) using a standard form. Remnant serum specimens from a convenience sample of cases were tested by polymerase chain reaction, followed by sequencing the 315-nucleotide segment of the VP1-P2B junction.

Results There were 1156 HAV cases reported during 2005 through 2007. The combined population under surveillance was 29.8 million in 2007. The overall annual incidence rate was 1.3 per 100 000 population (range by site, 0.7-2.3). Of reported cases, 53.4% were male, 42.4% were white, 44.7% were aged 15 to 39 years, and 91.4% resided in urban areas. Reported risk factors were international travel (45.8%), contact with a case (14.8%), employee or child in a daycare center (7.6%), exposure during a food or waterborne common-source outbreak (7.2%), illicit drug use (4.3%), and men who had sex with men (3.9%). Genotypes among the 271 case specimens were IA (87.8%), IB (11.4%), and IIIA (0.7%). Of the 271 polymerase chain reaction–positive specimens, 131 (48.3%) were from cases reporting travel or exposure to a traveler; 58 of the 131 cases reported travel to Mexico, and 53 of the 58 were within the US-IA1 cluster.

Conclusions International travel was the predominant risk factor for HAV transmission. Health care providers should encourage vaccination of at-risk travelers.

source: JAMA