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.     

Prevention of Descending Pneumonia in Rats with Perflubron-delivered Tobramycin

OBJECTIVES: Patients undergoing emergent endotracheal intubation are at increased risk for developing pneumonia. Although numerous strategies have been investigated to reduce ventilator-associated pneumonia (VAP), the incidence of VAP and its associated mortality remains high. This investigation tested the hypothesis that LiquiVent (Alliance Pharmaceutical, San Diego, CA-LV) delivered antibiotics (via spray-dried microspheres-SDM) would improve survival in a rat model of descending gram-negative pneumonia. METHODS: Wistar rats (n = 49) were randomized to receive prophylaxis with 1). nothing (controls); 2). intramuscular (IM) tobramycin, 3). intratracheal LV plus SDM shells (vehicle), 4). intratracheal LV plus SDM shells plus IM tobramycin, or 5). intratracheal LV plus SDM containing 1 mg/kg of tobramycin. All interventions were given 24 hours before a bacterial challenge with 10(8) colony-forming units of intratracheal Klebsiella pneumoniae. Mortality at ten days was the sole outcome measure. Survival in individual groups was compared with controls by Fisher's exact test with Bonferroni correction for multiple comparisons. RESULTS: All animals in the control group died of pneumonia within ten days of bacterial inoculation (0% survival). Prophylaxis with either IM tobramycin or SDM vehicle plus IM tobramycin provided no protection (0% survival). This is in sharp contrast to the cohort receiving pretreatment with tobramycin-containing SDM delivered via LV, in which 60% of the animals survived to study completion (p < 0.05). CONCLUSIONS: Prophylaxis with SDM containing antibiotics delivered in low-dose LV provided significant protection in a rat model of descending gram-negative pneumonia. These data support the hypothesis that perfluorocarbon-delivered intratracheal antimicrobials may be useful in the prevention of VAP.     

腰椎管狭窄症术后下肢残留麻木的发生率及影响因素

[目的]探讨腰椎管狭窄症术后下肢残留麻木的发生率和影响因素。[方法]2001年1月～2003年2月手术治疗56例腰椎管狭窄症患者，术后随访10d，1、3个月、1年和2年，记录患者神经功能和残留症状。[结果]术前82．1％的患者有下肢麻木，术后10d，1、3个月、1年和2年分别有43．6％、39．I％、36．6％、35．3％和35．7％的患者下肢残留麻木，与病程、术前JOA评分和椎管狭窄类型有关，与年龄和神经根直径无关。[结论]腰椎管狭窄症患者术后1个月内下肢麻木恢复最快，术后1年和2年下肢麻木发生率为35．3％和35．7％，推测神经组织的潜在恢复能力影响下肢麻木的发生率。     

The distally based sural fasciomusculocutaneous flap for foot reconstruction.

Finding appropriate soft-tissue to cover a wound located over the middle or distal portion of the foot can be challenging. A distally based sural fasciomusculocutaneous flap including the sural nerve and a midline cuff of the gastrocnemius muscle can be used for this purpose. This flap is designed on the proximal third of the posterior calf and is nourished in a retrograde manner by the lower peroneal septocutaneous perforators, through the vascular axis of the sural nerve to the musculocutaneous perforators of the gastrocnemius muscle. Between October of 2002 and January of 2004, this flap was applied in nine individuals, including four diabetic patients. The skin defects all resulted from trauma, osteomyelitis or chronic ulcer, and combined with bone or tendon exposure. One flap developed distal necrosis. The other flaps survived fully and provided good contour. In our series, diabetes mellitus seemed not to compromise the vascularity of the flap. The distally based sural fasciomusculocutaneous flap is very useful for lower limb reconstruction, particularly for the foot, because of its long vascular pedicle and the availability of the skin portion of the proximal calf based on direct branches between the musculocutaneous perforators and the neurovascular axis of the sural nerve. This is an important variant of the sural neurocutaneous flap and it appears to be a good alternative to free flaps for resurfacing the foot.     

Intrapulmonary metastasis developing eighteen years after complete resection of thymoma

We present a case of intrapulmonary metastasis developing 18 years after complete resection of thymoma. An 8 mm nodule in the lower lobe of the left lung was noted on chest X-ray in a 76-year-old woman who had undergone complete resection of Masaoka’s stage II thymoma 18 years earlier. Since the nodule grew to 17 mm during a 2-year follow-up, wedge resection was performed. The lesion was histologically diagnosed as an intrapulmonary metastasis from thymoma. Extremely late recurrence after complete resection of thymoma is discussed.     

伴有LADD综合征的角膜缘干细胞缺乏

泪管-耳-牙-指（趾）（LADD）综合征是一种具有多种表现的常染色体显性遗传疾病。最初在1967年由Levy报道。1例双侧泪液系统缺失、杯状耳、干嘴，以及牙、手臂和指（趾）异常的单发病例。之后一些新发现的临床表现，如肾脏异常、唾液腺缺乏、先天性髋脱位、先天性裂孔疝和横膈疝、感觉性耳聋和传导性耳聋、牙发育不全、四肢异常、口腔干燥和眼干都被报道与此综合征有关。