Variable impairment of wound healing in the heterozygous collagenase-resistant mouse

Collagen undergoes dramatic reorganization during wound repair. Matrix metalloproteinases degrade and remodel collagen in a tightly controlled process. The collagenase-resistant mouse, Col1a1(tm1Jae), produces type I collagen, which is resistant to degradation by human matrix metalloproteinase 1. These mice grow normally but develop thickened skin with age. We have previously reported that the early wound repair response in homozygous mutant (Col1a1(r/r)) mice is delayed compared to wild type (Col1a1(+/+)). However, the late-stage scar of Col1a1(r/r) wounds was not significantly altered compared to Col1a1(+/+). Here we have investigated the response of heterozygous mice (Col1a1(+/r)) to wounding, not previously reported. Wound reepithelialization was delayed to a similar degree to wounds in the Col1a1(r/r) mice. However, the recovery of impaired wound contraction was faster in Col1a1(+/r) than in Col1a1(r/r) mice, but still slower than in wild-type animals. Analysis of wound protein extracts showed expression of some matrix metalloproteinases was prolonged in both the Col1a1(r/r) and Col1a1(+/r) wounds compared to wild type. We suggest the partial resistance of collagen to collagenase-mediated degradation in the heterozygous animals causes equivalent impairment of keratinocyte migration compared to homozygous collagenase-resistant mice, but that wound contraction during late-stage healing is only partially retarded.     

Where patients with cancer die in South Australia

In a sample of 1582 deaths among South Australian patients with cancer (795 deaths in 1981 and 787 deaths in 1985), 67% of deaths occurred in a hospital, 9% of deaths in a hospice, 10% of deaths in a nursing home, and 14% of deaths in a private residence. More patients died in a hospice or nursing home in 1985 than in 1981, and fewer died in a hospital. With increasing age, fewer patients died in a hospital and more in a nursing home. Compared with men, women were less likely to die at a private residence and more likely to die in a nursing home. A greater proportion of men with a living wife died at a private residence than was so among single or widowed men. However, conjugal status was not associated with the place of death of women. Patients who lived in the more affluent metropolitan suburbs tended more to die at a private residence than did those from poorer suburbs or country areas. Patients with haematological malignancies died in major metropolitan public hospitals more frequently than did patients with other tumours. Possible explanations are given for these findings.     

Automatic Intracranial Space Segmentation for Computed Tomography Brain Images

Craniofacial disorders are routinely diagnosed using computed tomography imaging. Corrective surgery is often performed early in life to restore the skull to a more normal shape. In order to quantitatively assess the shape change due to surgery, we present an automated method for intracranial space segmentation. The method utilizes a two-stage approach which firstly initializes the segmentation with a cascade of mathematical morphology operations. This segmentation is then refined with a level-set-based approach that ensures that low-contrast boundaries, where bone is absent, are completed smoothly. We demonstrate this method on a dataset of 43 images and show that the method produces consistent and accurate results.     

CD molecules 2006--human cell differentiation molecules

The Human Leucocyte Differentiation Antigens Workshops (HLDA) have since 1984 provided a forum for the characterization and study of leucocyte surface molecules and antibodies against them. HLDA devised the CD nomenclature, which is sanctioned by IUIS. The HLDA Council reviewed and modified the objectives of HLDA in 2004, and changed the name of the organization to Human Cell Differentiation Molecules (HCDM) to reflect the broader objectives. Workshop studies under the HCDM banner proceeded during 2005 and early 2006, culminating in a meeting in May 2006. At that meeting the Council, acting as Nomenclature Committee, approved a number of new CD designations and changes to some pre-existing CD designations, which are summarized in this report.     

Avoiding coagulopathy in vascular surgery

The possibility of coagulopathy can be minimized by attending to certain general perioperative details to avoid hypothermia, hypotension-shock, and multiple transfusions. In this paper, we present our protocol for avoiding coagulopathy in vascular surgery. In the past 1 1/2 years, we have used perioperative plasmapheresis in 204 patients undergoing cardiac or aortic peripheral vascular surgery. Autologous platelet-rich plasma is transfused at the completion of the operation after heparin reversal. Our data show an approximate 50% reduction in homologous blood product requirement. Seventy-five percent of patients having aortic surgery received no homologous blood products during their hospital stay. For those undergoing cardiac surgery, there has been about a 45% reduction in the use of homologous blood products. In our experience, autologous platelet-rich plasma not only decreases the risk of transmittable disease, but promotes hemostasis.     

Plasmid DNA vaccines: tissue distribution and effects of DNA sequence, adjuvants and delivery method on integration into host DNA

A variety of factors could affect the frequency of integration of plasmid DNA vaccines into host cellular DNA, including DNA sequences within the plasmid, the expressed gene product (antigen), the formulation, delivery method, route of administration, and the type of cells exposed to the plasmid. In this report, we examined the tissue distribution and potential integration of plasmid DNA vaccines following intramuscular administration in mice and guinea pigs. We compared needle versus Biojector (needleless jet) delivery, examined the effect of aluminum phosphate adjuvants, compared the results of different plasmid DNA vaccines, and tested a gene (the human papilloma virus E7 gene) whose protein product is known to increase integration frequency in vitro. Six weeks following intramuscular injection, the vast majority of the plasmid was detected in the muscle and skin near the injection site; lower levels of plasmid were also detected in the draining lymph nodes. At early time points (1-7 days) after injection, a low level of systemic exposure could be detected. Occasionally, plasmid was detected in gonads, but it dissipated rapidly and was extrachromosomal - indicating a low risk of germline transmission. Aluminum phosphate adjuvant had no effect on the tissue distribution and did not result in a detectable increase in integration frequency. Biojector delivery, compared with needle injection, greatly increased the uptake of plasmid (particularly in skin at the injection site), but did not result in a detectable increase in integration frequency. Finally, injection of a plasmid DNA vaccine containing the human papilloma virus type 16 E7 gene, known to increase integration in vitro, did not result in detectable integration in mice. These results suggest that the risk of integration following intramuscular injection of plasmid DNA is low under a variety of experimental conditions.     

Polytetrafluoroethylene vein composite grafts across the knee

Fifteen Gore-tex vein composite femoral-popliteal artery bypass procedures were performed during the four year period of December 1975 to December 1979. Nine were performed for salvage of the limb and six, for incapacitating claudication. Preoperatively, all patients had an arteriographic evaluation of the outflow tract. CPR by the life-table method was 63 per cent at six years. Early failures were three occlusions within two months in patients with poor outflow. One late occlusion occurred at 16 months, and the limb was salvaged with a femoral tibial bypass graft. Another late occlusion was treated by thrombectomy at 24 months with continued patency. Late revision was carried out in one patient at seven months. This consisted of repair of a stenosis of the distal popliteal artery with salvage of the graft. Only two of ten grafts available for evaluation beyond one year have become occluded. All patients operated upon for claudication or with good runoff have patent grafts. On the contrary, none of the grafts to an isolated popliteal segment remained patent. When there is not sufficient autogenous saphenous vein available for femoral-popliteal bypass, the ready availability of a synthetic graft makes it an attractive choice. Nevertheless, our 63 per cent CPR at six years strongly suggests that the composite graft is a durable option.