CDKN2A mutations and melanoma risk in the Icelandic population.

BACKGROUND: Germline CDKN2A mutations have been observed in 20-40% of high risk, melanoma prone families; however, little is known about their prevalence in population based series of melanoma cases and controls. METHODS: We resequenced the CDKN2A gene, including the p14ARF variant and promoter regions, in approximately 703 registry ascertained melanoma cases and 691 population based controls from Iceland, a country in which the incidence of melanoma has increased rapidly. RESULTS: We identified a novel germline variant, G89D, that was strongly associated with increased melanoma risk and appeared to be an Icelandic founder mutation. The G89D variant was present in about 2% of Icelandic invasive cutaneous malignant melanoma cases. Relatives of affected G89D carriers were at significantly increased risk of melanoma, head and neck cancers, and pancreatic carcinoma compared to relatives of other melanoma patients. Nineteen other germline variants were identified, but none conferred an unequivocal risk of melanoma. CONCLUSIONS: This population based study of Icelandic melanoma cases and controls showed a frequency of disease related CDKN2A mutant alleles ranging from 0.7% to 1.0%, thus expanding our knowledge about the frequency of CDKN2A mutations in different populations. In contrast to North America and Australia where a broad spectrum of mutations was observed at a similar frequency, in Iceland, functional CDKN2A mutations consist of only one or two different variants. Additional genetic and/or environmental factors are likely critical for explaining the high incidence rates for melanoma in Iceland. This study adds to the geographic regions for which population based estimates of CDKN2A mutation frequencies are available.

Alternating tip splitting in directional solidification.

We report experimental results on the tip splitting dynamics of seaweed growth in directional solidification of succinonitrile alloys. Despite the random appearance of the growth, a tip splitting morphology was observed in which the tip alternately splits to the left and to the right. The tip splitting frequency f was found to be related to the growth velocity V as a power law f~V1.5. This finding is consistent with the predictions of a tip splitting model that is also presented. Small anisotropies are shown to lead to different kinds of seaweed morphologies.

Clinical experience with the Unilink/3M Precise microvascular anastomotic device.

The Unilink/3M Precise anastomotic device for microvascular anastomoses has been evaluated in 38 critical anastomoses in 26 selected patients. The microvascular anastomosis was usually completed within three minutes by a single surgeon. There was only one failure, when an arterial anastomosis clotted because of a technical error. In all patients tissue survival was dependent on patent mechanical anastomoses (critical anastomoses) and the follow-up period was more than three years.

Long term evaluation of the unilink anastomotic system. A study with light and scanning electron microscopy.

The long term effects of the Unilink mechanical microvascular anastomosis in terms of anastomotic patency and histological changes in the vessel wall were evaluated in 10 rabbits. Both carotid arteries and facial veins were divided and reanastomosed with the Unilink device. At death two years later all 40 anastomoses were fully patent, with histological changes similar to those described previously after 16 weeks, that is, normal endothelial lining, but almost total atrophy of the media at the anastomotic site. The thinning of the vessel wall at the anastomosis caused neither occlusions nor aneurysms during the observation period.

Effects of public posting on driving speed in Icelandic traffic.

We replicated a study by Van Houten, Nau, and Marini (1980) that had revealed reductions in vehicle speeding following the posting of percentages of drivers not speeding on a sign at roadside. Our subjects were drivers entering a residential area where the speed limit changed from 90 km/hr (55.9 mph) to 60 km/hr (37.3 mph). A total of 4,409 vehicle speeds were taken from two observation sessions per day for 20 consecutive weekdays. The intervention consisted of a single posting condition, in which a hypothetical daily percentage of drivers not speeding was posted on a feedback sign, followed by a double posting condition, in which a sign posting a best result was erected beyond the feedback sign. Results revealed a significant speed reduction from an average of 69.0 km/hr (42.9 mph) during baseline to 63.4 km/hr (39.4 mph) during single posting. Average speed during double posting was 62.9 km/hr (39.1 mph). The percentage of drivers exceeding 70 km/hr (43.5 mph) dropped from 41.0 during baseline to 20.5 during single posting. The significant speed reductions add to the generality of findings of similar studies in Canada and Israel and offer possible explanations for the failure of feedback posting to reduce speed in the U.S.

Microvascular anastomoses in irradiated vessels: a comparison between the Unilink system and sutures.

A new mechanical device (the Unilink system) was compared to conventional suture anastomoses in irradiated microvessels. Twenty rabbits received a single radiation dose of 20 Gy from a 7-MeV electron source through an anterior neck field. One and 6 months following irradiation, the carotid arteries and facial veins were divided and anastomosed on one side with the Unilink system and on the other side with suture technique. At sacrifice 4 weeks postoperatively, all vessels were evaluated for patency and histologic changes associated with radiation and anastomotic trauma. Histology disclosed severe radiation changes. Also, intimal hyperplasia was consistently found at the anastomotic sites in the arteries, while it was totally absent in the venous anastomoses. Occlusive thrombosis was found in two arteries, one anastomosed with the Unilink system and one sutured. Two other arteries, one from each group, had subtotal occlusions at the anastomotic site. No occlusions occurred in any of the venous anastomoses. The overall patency in this study was 97.5 percent, with no difference between the two techniques.

Microvenous grafts to arterial defects. The use of mechanical or suture anastomoses.

A mechanical microvascular anastomotic device, the Unilink system, was compared with sutures in terms of patency, anastomotic time, and histologic changes when a microvenous graft is placed in an arterial defect. Twenty rabbits underwent grafting of a 1.0-cm defect in both carotid arteries with a 1.5-cm reversed femoral vein graft. Anastomoses were performed with the Unilink system on one side and sutures on the other. Animals were killed at 2 weeks (10 animals) and 16 weeks (10 animals) with the vein grafts being assessed with clinical patency tests and then fixated for histologic evaluation. All 20 grafts (100%) interposed with the Unilink system were fully patent while 17 (85%) of the 20 grafts interposed with sutures were fully patent. The grafting procedure with the Unilink anastomoses averaged 12.5 minutes while the sutured anastomoses averaged 41.9 minutes. No differences in the histologic appearance of the vein grafts were noted between the two types of anastomoses. All grafts showed endothelialization at 2 weeks with intimal hyperplasia or "arterialization" being a constant finding.

Microvenous end-to-side anastomosis: an experimental study comparing the Unilink system and sutures.

A method for mechanical microvascular end-to-side anastomosis is presented and compared to conventional suture technique. Twenty rabbits had their facial veins divided from the jugular veins and reanastomosed end-to-side to the jugular veins, 2 cm cranially to the original bifurcation. The anastomoses were performed on one side of the neck with the Unilink system and on the other side with sutures. At sacrifice at two weeks (10 animals) and at 16 weeks (10 animals), all anastomoses were tested for patency and histologically evaluated. All 40 anastomoses were fully patent. The time required for completion of a mechanical anastomosis was on the average one-fourth the time required for suture anastomosis. No thrombus formation was noted in any of the specimens, but a slight narrowing because of intimal hyperplasia was noted in the recipient vessels in two mechanical anastomoses. It was demonstrated that mechanical anastomoses of small veins end-to-side can be performed in a rapid and safe manner with the Unilink system.

Arterial end-to-side anastomosis with the UNILINK system.

A new technique for mechanical end-to-side anastomoses using the UNILINK anastomotic system is presented. The technique, based on the concept of vessel wall eversion over paired ring pins, is described as is a new device for vessel expansion. To evaluate the technique of end-to-side anastomosis, we detached the left renal artery in 18 rabbits and then reanastomosed them end-to-side to the aorta using the UNILINK anastomotic system. Renal blood flow was evaluated before and after anastomoses with a laser Doppler flowmeter. Animals were separated into three groups of 6 and were killed at 24 hours, 2 weeks, and 16 weeks, respectively. To evaluate the acute effects of vessel expansion, 7 additional rabbits underwent expansion of the aorta without subsequent anastomosis. All vessels were evaluated with light and scanning electron microscopy. A patency rate of 100% was achieved in the 18 animals; histological changes at the anastomotic site were comparable to those described previously for this mechanical anastomotic system. The animal model demonstrates that it is both technically possible and efficacious to perform end-to-side anastomoses of arteries with the UNILINK anastomotic system.

Microvascular anastomosis of interpositional vein grafts with the UNILINK system. A comparative experimental study.

Vein segments from the posterior facial vein of the rabbit were surgically isolated and re-anastomosed, either by manual suture technique or by the use of a new mechanical anastomotic device, the UNILINK apparatus. The purpose of the study was to compare anastomotic patency and time required for an orthotopic vein grafting procedure, when the two techniques were used. In the grafts anastomosed with the UNILINK technique, both clinical and histological evaluation showed 100% patency, while 20% of the sutured grafts showed impaired flow as a result of occlusive thrombosis. When the mechanical device was used, the full procedure was completed within one third of the time, as compared to suture anastomoses.

Strength of microvascular anastomoses: comparison between the unilink anastomotic system and sutures.

The Unilink system, a mechanical anastomotic device, was compared with standard suture techniques in terms of anastomotic strength under conditions of uniaxial loading. Twenty-five rabbits underwent Unilink and suture anastomosis of both carotid arteries and facial veins. Animals were sacrificed at 1 hour (five animals), 2 weeks (10 animals), and 16 weeks (10 animals), and all vessels were tested by constant loading in a material testing machine. The maximum load required to disrupt the anastomosis as well as the site of vessel failure were recorded. All 100 anastomoses were fully patent as evaluated by clinical testing. At 1 hour and 2 weeks, the Unilink arterial anastomoses were consistently and significantly stronger than the sutured anastomoses. At 16 weeks the sutured arterial anastomoses were significantly stronger than Unilink. The Unilink anastomoses, however, remained approximately 50% stronger than unoperated normal vessels. No statistical differences were observed in the strength of venous anastomoses at any of the intervals tested. There were no statistical differences in the sites of failure of the vessels under loading (i.e., at the anastomosis or proximal or distal to it) between the two techniques.

The UNILINK system for mechanical microvascular anastomosis in hand surgery.

A new mechanical anastomotic device--the UNILINK system--for small vessels, designed for work under the operating microscope was used in four patients for microvascular, hand surgical operations. All procedures were successful with regard to tissue survival and wound healing. Basal skin temperature and systolic blood pressure distal to the mechanical anastomoses were normal 12 to 26 months after the operation. Doppler investigation also confirmed that all mechanical anastomoses were patent. At the time of this report, 32 to 45 months after the operations, no adverse effects of the method have been found. The device offers increased safety and speed in microvascular operations.