The molecular and clinical impact of hepatocyte growth factor, its receptor, activators, and inhibitors in wound healing

Wound healing involves a number of cellular and molecular events, many of which are controlled by soluble growth factors. In the process of healing, hepatocyte growth factor, a cytokine known to act as mitogen, motogen, and morphogen, has been postulated to play multiple roles during several stages of this complex biological process. Produced primarily by stromal fibroblasts, hepatocyte growth factor regulates angiogenesis, vascular permeability, cell migration, matrix deposition and degradation, and other biological processes. The current article discusses recent progress in understanding the multiple roles played by this growth factor in tissue repair.     

Use of an in vitro model of tissue-engineered human skin to study keratinocyte attachment and migration in the process of reepithelialization

To produce a stable epidermis, keratinocytes need to be firmly attached to the basement membrane. However, following wounding, keratinocytes are required to develop a migratory phenotype in order to reepithelialize the wound. To investigate some of the issues underlying reepithelialization, we have developed a three-dimensional in vitro model of tissue-engineered skin, comprising sterilized human dermis seeded with human keratinocytes and dermal fibroblasts. Using this model, we have shown that the inclusion of fibroblasts within the model increases the stability of keratinocyte attachment. We have also demonstrated that keratinocyte migration occurs most effectively in the absence of a basement membrane and following the inclusion of fibroblasts in the model. In addition, subjecting the keratinocyte layer to mechanical trauma induces a migratory phenotype. We conclude that this three-dimensional in vitro wound model can be used to increase our understanding of the factors that enhance keratinocyte migration and hence wound healing in vivo.     

Is herniography useful?

Herniography has been used for 25 years in the diagnosis of occult herniation but has not gained widespread acceptance in the UK, despite studies confirming its high sensitivity and specificity for occult hernias and an excellent record of safety and patient acceptability. The traditional approach in the UK to suspected occult groin herniation has been surgical exploration. This study examined the use of herniography in a single district general hospital to assess its impact in limiting unnecessary groin explorations and allowing discharge of patients without hernias. The case notes of 90 successive patients referred for herniography by the department of general surgery in a single UK district general hospital over an 18-month period were reviewed. Eighty-seven completed examinations were analysed in which 23 hernias were diagnosed in 20 patients. Thirteen patients have undergone hernia repair with resolution of symptoms. There were no false positive examinations, although two inguinal hernias were incorrectly diagnosed radiologically as femoral hernias; there were two false negative examinations where additional hernias were found at laparoscopic repair. There were no reported complications. Twenty-four patients were discharged directly from the surgical clinic after a negative herniogram. Thirty patients were referred to other specialities. No patient had undergone groin exploration after a negative herniogram. Herniography is a useful tool in assessing obscure groin pain and potential occult herniation. It can reliably rule out the presence of a hernia and avoid the need for surgical exploration. Many patients with a negative herniogram can be reassured and discharged, whilst others may be referred on to other specialities safe in the knowledge that an occult hernia has been excluded.     

Ovulationshemmer bei Risikogruppen

Severe adverse effects during the use of ovulation inhibitors occur mostly in women who have an elevated risk for the development of certain diseases owing to hereditary or acquired factors. By means of a careful personal or family history analysis as well as specific laboratory examinations, an existing predisposition may frequently be diagnosed and the individual risk associated with the use of oral contraceptive inhibitors may be estimated. The present contribution describes the potential effects of treatment with ovulation inhibitors on women with thrombophilia, cardiovascular disease, diabetes mellitus, dyslipidemia, overweight or underweight, tumors, psychiatric and neurological diseases and autoimmune disease. The hormonal methods and non-hormonal alternatives available for contraception are elucidated according to existing lesions and risk factors and the advantages and disadvantages are discussed.     

Vitamin D receptor genotype and risk of osteoporotic hip fracture in elderly women of Utah: an effect modified by parity

Introduction The associations between vitamin D receptor (VDR) Bsm I and Fok I genotypes, parity, and risk of osteoporotic hip fracture were evaluated in a statewide population-based case-control study in Utah.Methods Women age 50–89 years with hip fracture (n=882) were ascertained via surveillance of 18 Utah hospitals from 1997 to 2001. Age-matched controls were randomly selected (n=897). Participants were interviewed in their homes, and blood samples were collected for genotyping.Results In logistic regression analyses that controlled for multiple confounders, Bsm I VDR genotype but not Fok I genotype was associated with risk of osteoporotic hip fracture (OR bb vs. BB genotype: 0.68; 95% CI: 0.50, 0.95). In similar analyses, no overall association was observed between parity status and risk of osteoporotic hip fracture. However, the effect of VDR genotype was modified by parity status. Among nulliparous women (n=140), Bsm I genotype was not associated with risk of hip fracture (OR bb vs. BB: 0.82; 95% CI: 0.28, 2.4); among primiparous women (n=133), bb genotype was associated with increased risk of hip fracture (OR bb vs. BB: 3.30; 95% CI: 0.96, 11.29); among multiparous women (n=1,400), bb genotype was associated with decreased risk of hip fracture (OR bb vs. BB: 0.59; 95% CI: 0.42, 0.84).Conclusion VDR Bsm I genotype was associated with risk of hip fracture in Utah women, and this effect was modified by parity status. Hormonal or lifestyle factors related to parity may underlie this interaction.     

灾难的时代错误:灾害医学的过去、现在和将来(一)

灾难,特别是地震、火山、洪水以及与战争有关的事件如饥饿和流行性传染病,是人类有记录的经历的一部分。从意大利庞贝的火山爆发,到约翰斯顿的洪水、第二次世界大战和黑色瘟疫,到西班牙流感,都发生了灾难,这不会被传说和历史书籍长期忘却。不过,在20世纪中叶以前,那些灾难的发生相对较少,且相距时间较长。从20世纪中叶以来,灾难的本质发生了变化。从恐怖分子使用“新技术”,到与气候有关的导致亿万美元经济损失的事件,表明这个世界正在发生变化。仅仅在最近的50~60年间,造成多种多样的伤亡事件,其危险性和频率的增加引人注目,并且注定要在接…