Face Wall Research Articles

Abstract 4481: Topical application of the dual PDPK1/AKT inhibitor PHT-427 inhibits signaling and growth of human breast cancer cutaneous metastases in mice

Abstract Despite advances in the treatment of breast cancer between 10 to 15% of patients develop cutaneous metastatic disease (CMD) most frequently on the face, neck and chest wall, usually in later stages of the disease as a harbinger of metastasis that will occur in other organs 1 to 3 years later. CMD is not life threatening but can significantly impact patients’ quality of life and is a cause of anxiety, pain, discomfort, and a portal for infection. CMD could also be a seed for metastases at other sites. Surgery or radiotherapy is used for single or localized CMD. Topical (epicutaneous) therapy with molecularly targeted agents provides an attractive modality for treatment of more widespread breast CMD. PHT-427 is a dual pleckstrin homology (PH) domain inhibitor of PDPK and AKT, two key enzymes of PI3K signaling that is frequently activated in breast cancer. We report here PHT-427's topical activity in CMD. MCF-7 human breast cancer (mutant PIK3CA) 106 cells in 20 μI were injected intradermaly in the flank of estradiol pelleted female nu/nu mice. When tumors reached 40-200 mm3 groups of 5 mice were treated twice a day with 0.1 ml vehicle or vehicle with 50 mg/ml PH-427, applied to a 1 cm patch of skin over the tumor. Mice were housed individually with collars to prevent them ingesting applied drug. After 10 days mice were euthanized 4 hr after the last application and blood, tumor and overlying skin were removed for analyses. Topical PHT-427 gave 89 % inhibition of tumor growth (p = 0.017, 3/5 no measurable tumor). There was no change in body weight and no apparent skin toxicity. Western blotting showed that PHT-427 inhibited p-AKT Thr308/Ser473 in skin and tumor, and decreased total AKT in skin but not tumor. p-PDPK1 Ser241 was inhibited in tumor but not skin, as was the downstream target pPKC Thr410 and pMAPK Thr202/Tyr204. Measurement of PHT-427 by HPL-MS showed very high levels in the skin at the site of application, levels of ∼50 μg/g in tumor and 5.5 μg/ml in plasma. In vitro levels of PHT-427 of 5 μg/ml are required for killing of sensitive cell lines. Thus, topical application of PHT-427 can deliver active drug levels to skin and tumor, inhibiting PDPK1 and AKT, and significantly inhibiting tumor growth without adverse effects on normal skin. Topical PHT-427 could have use in skin conditions driven by PDPK/AKT such as prevention of sun damage and skin cancer, and in the personalized therapy of breast CMD. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4481. doi:10.1158/1538-7445.AM2011-4481

Hereditary Angioedema in Childhood

Hereditary angioedema (HAE) is an inherited disorder characterized by recurrent, circumscribed, non-pitting, non-pruritic, and rather painful subepithelial swelling of sudden onset, which fades during the course of 48-72 hours, but can persist for up to 1 week. Lesions can be solitary or multiple, and primarily involve the extremities, larynx, face, esophagus, and bowel wall. Patients with HAE experience angioedema because of a defective control of the plasma kinin-forming cascade that is activated through contact with negatively charged endothelial macromolecules leading to binding and auto-activation of coagulation factor XII, activation of prekallikrein to kallikrein by factor XIIa, and cleavage of high-molecular-weight kininogen by kallikrein to release the highly potent vasodilator bradykinin. Three forms of HAE have currently been described. Type I and type II HAE are rare autosomal dominant diseases due to mutations in the C1-inhibitor gene (SERPING1). C1-inhibitor mutations that cause type I HAE occur throughout the gene and result in truncated or misfolded proteins with a deficiency in the levels of antigenic and functional C1-inhibitor. Mutations that cause type II HAE generally involve exon 8 at or adjacent to the active site, resulting in an antigenically intact but dysfunctional mutant protein. In contrast, type III HAE (also called estrogen-dependent HAE) is characterized by normal C1-inhibitor activity. The diagnosis of HAE is suggested by a positive family history, the absence of accompanying pruritus or urticaria, the presence of recurrent gastrointestinal attacks of colic, and episodes of laryngeal edema. Estrogens may exacerbate attacks, and in some patients attacks are precipitated by trauma, inflammation, or psychological stress. For type I and type II HAE, diminished C4 concentrations are highly suggestive for the diagnosis. Further laboratory diagnosis depends on demonstrating a deficiency of C1-inhibitor antigen (type I) in most kindreds, but some kindreds have an antigenically intact but dysfunctional protein (type II) and require a functional assay to establish the diagnosis. There are no particular laboratory findings in type III HAE. Prophylactic administration of either 17alpha-alkylated androgens or synthetic antifibrinolytic agents has proven useful in reducing the frequency or severity of attacks. Plasma-derived C1-inhibitor concentrate, recombinant C1-inhibitor, ecallantide (DX88; a plasma kallikrein inhibitor) and icatibant (a bradykinin B(2) receptor antagonist) have demonstrated significant efficacy in the treatment of acute attacks, whereas the C1-inhibitor concentrate has also provided a significant benefit as long-term prophylaxis. However, these drugs are not licensed in all countries and are not always readily available.

Pneumoretroperitoneum und beidseitiger Pneumothorax nach endoskopischer Sphinkterotomie

A 39-year-old obese woman underwent endoscopic retrograde cholangiopancreatography with elective endoscopic biliary sphincterotomy (papillotomy) for symptomatic retained stones in the common bile duct which were extracted completely after added lithotripsy. Three hours later the patient developed profound subcutaneous emphysema of the face, neck and chest wall and shortness of breath, but had no abdominal pain. Physical examination revealed bilaterally diminished breath sounds and a distended and hyper-resonant abdomen, but no evidence of peritonitis. The patient was afebrile and hemodynamically stable. An emergency contrast-enhanced computed tomography (CT) of the chest and abdomen was performed. It demonstrated a bilateral pneumothorax, pneumomediastinum, pneumoperitoneum and pneumoretroperitoneum, in addition to extensive subcutaneous emphysema. There was no evidence of extraluminal leakage of contrast medium or intraperitoneal fluid on the CT. Because of the increasing respiratory distress an intercostal drain was placed in the left pneumothorax and broad-spectrum antibiotics were administered. No drain was placed in the right lung. A follow-up CT after three days showed decreasing pneumomediastinum, pneumoperitoneum and pneumoretroperitoneum as well as resolution of the bilateral pneumothorax. The patient made an uneventful recovery and was discharged home seven days after the intervention. Pneumothorax after endoscopic biliary sphincterotomy is a rare but serious complication that should be kept in mind after postinterventional development of shortness of breath.

Caving thickness effects of surrounding rocks macro stress shell evolving characteristics

In order to explore the influence of different caving thicknesses on the MSS distribution and evolving characteristics of surrounding rocks in unsymmetrical disposal and fully mechanized top-coal caving (FMTC), based on unsymmetrical disposal characteristics, the analyses of numerical simulation, material simulation and in-situ observation were synthetically applied according to the geological and technical conditions of the 1151(3) working face in Xieqiao Mine. The results show that the stress peak value of the MSS-base and the ratio of MSS-body height to caving thickness are nonlinear and inversely proportional to the caving thickness. The MSS-base width, the MSS-body height, the MSS-base distance to working face wall and the rise distance of MSS-base beside coal pillar are nonlinear and directly proportional to the caving thickness. The characteristics of MSS distribution and its evolving rules of surrounding rocks and the integrated caving thickness effects are obtained. The investigations will provide lots of theoretic references to the surrounding rocks’ stability control of the working face and roadway, roadway layout, gas extraction and exploitation, and efficiency of caving, etc.

Science of Composite Tissue Allotransplantation

The science of composite tissue allotransplantation (CTA) is rooted in progressive thinking by surgeons, fueled by innovative solutions, and aided by understanding the immunology of tolerance and rejection. These three factors have allowed CTA to progress from science fiction to science fact. Research using preclinical animal models has allowed an understanding of the antigenicity of complex tissue transplants and mechanisms to promote graft acceptance. As a result, translation to the clinic has shown that CTA is a viable treatment option well on the way of becoming a standard of care for those who have lost extremities and suffered large tissue defects. The field of CTA has been progressing exponentially over the past decade. Transplantation of hands, larynx, vascularized knee, trachea, face, and abdominal wall has been performed. Several important observations have emerged from translation to the clinic. Although it was predicted that rejection would pose a major limitation, this has not proven true. In fact, steroid-sparing protocols for immunosuppression that have been successfully used in renal transplantation are sufficient to prevent rejection of limbs. Although skin is highly antigenic when transplanted alone in animal models, when part of a CTA, it has not proven to be. Chronic rejection has not been conclusively demonstrated in hand transplant recipients and is difficult to induce in rodent models of CTA. This review focuses on the science of CTA, provides a snapshot of where we are in the clinic, and discusses prospects for the future to make the procedures even more widely available.

The challenge of dermatopathological diagnosis of composite tissue allograft rejection: a review

Advances in immunosuppressive treatments and microsurgical techniques have rendered allotransplantation of composite tissues (i.e. heterogeneous, non-organ tissues) possible in humans. Most of these allografts (hands, face and abdominal wall) contain skin that may be the target of rejection, the diagnosis of which relies mainly on clinicopathological monitoring of the skin. Rejection of allografted skin manifests with changes that are characteristic but not very specific. Although composite tissue allografts are still in their infancy, they have opened a new era in the field of transplantation surgery and pathology, so that (dermato) pathologists may occasionally be faced with the challenge of diagnosing skin rejection of a composite tissue allograft. The diagnostic difficulties that may be encountered in the pathological evaluation of skin in this setting are discussed in this review.

Shewanella soft tissue infection: case report and literature review

To better understand the clinical characteristics of soft tissue infections caused by Shewanella in humans. We report a case of Shewanella soft tissue infection and review the English literature from a search of PubMed. A total of 27 adults (mean age 61.1+/-16.0 years) with soft tissue infections caused by Shewanella were included for analysis. Limb involvement was found in 22 (81.5%) patients, while scalp, face, perineum, lacrimal sac, and abdominal wall involvement were each found in one patient. Chronic ulcer over the leg (14 cases (51.9%)), steroid use (four cases (14.8%)), and liver cirrhosis (three cases (11.1%)) were the major underlying conditions. Shewanella bacteremia was found in 14 out of 22 patients with soft tissue infections involving the limbs. Two patients died of septicemia, giving a mortality rate of 7.4%. Shewanella soft tissue infections usually develop in immunocompromised patients with a preexisting cutaneous ulcer (particularly over the legs) after marine environment or seawater exposure. In view of the possible catastrophic consequences, education on the prevention of Shewanella soft tissue infections in at-risk people (e.g., the immunocompromised or elderly with a cutaneous ulcer) relating the need to avoid exposure to the marine environment or seawater may be of importance.

Numerical study of influences of hard particles in lubricant on tribological performances of the piston ring

Influences of hard particles lying in the lubrication region between piston ring face and cylinder wall, including the effects of a non-contact particle and contact particle, on tribological performances of the piston ringwere numerically analysed. A modified Reynolds equation incorporating a non-contact particle effect was presented. The total friction force, deformation, and contact stress of the ring, with a non-contact particle and contact particle consideration, were solved separately by using finite-element program code of the authors and software ANSYS 5.7. The numerical results show that obvious changes in the total friction force and deformation of the ring can occur, if the diameter and height across the film thickness of a non-contact particle and axial velocity difference between the non-contact particle and ring are considered. The maximum contact stress of the ring is obviously affected by the contact particle's interfering time and velocity, and hardness value of the plastically deformed particle.

Surgical debridement of craniocervical necrotizing fasciitis: the window of opportunity

Craniocervical necrotizing fasciitis (CCNF) has a potentially high morbidity and mortality. Late presentation, shock and disseminated intravascular coagulation are associated with a particularly poor prognosis. Early recognition and aggressive treatment is advised. A case report is presented of a late presentation of necrotizing fasciitis of the face, neck and anterior thoracic wall. Despite adverse prognostic indicators, surgical debridement was performed. Intensive medical treatment included continuous renal replacement therapy and intravenous immunoglobulin. Survival in this case illustrates that the window of opportunity for surgically treating CCNF extends to the advanced stages of the disease, albeit with increased morbidity.

Right Arm Pyomyositis and Necrotizing Fasciitis Complicated With Subcutaneous Emphysema and Pneumomediastinum in a Patient With Diabetes Mellitus and Iatrogenic Cushing Syndrome

We report a case of subcutaneous emphysema and pneumomediastinum secondary to pyomyositis and necrotizing fasciitis over the right arm of a woman with underlying diabetes mellitus and iatrogenic Cushing syndrome. Gas produced by the culprit pathogen extensively dissected the subcutaneous fat and fascia of the patient's right arm and distantly spread to her face, neck, back, and thoracic wall and penetrated the soft tissue cephalically bordering her sternum, resulting in pneumomediastinum. The patient improved-with antimicrobial therapy and localized debridement and fasciotomy over her right arm.

Lifting of dust particles behind a reflected shock wave sliding above a particle layer

The paper presents results of mathematical simulation of particle lifting behind a shock wave reflected from the face wall and sliding above the particle layer. It is shown that particle lifting occurs in a vortex initiated in the gas when the shock wave is reflected from the wall.

Hereditary Angioneurotic Edema: Review of the Literature

Congenital C1-inhibitor deficiency, or hereditary angioneurotic edema (HAE), is a rare autosomal dominant disease due to alterations in the C1 inhibitor gene that results in a deficiency of antigenic and/or functional C1-INH. Affected patients are heterozygous, and their deficiency is incomplete, many of them having up to 20% of the normal amount of the inhibitor. The disease is characterised by recurrent, circumscribed, non-pitting, and non-pruritic subepithelial swellings of sudden onset, which fade during the course of 48-72 hours, but can persist up to 1 week. Lesions can be solitary or multiple and primarily involve the extremities, larynx, face, and bowel wall. Bradykinin is believed to be the main, but certainly not the sole, mediator responsible for the bouts of edema in HAE. The diagnosis is suggested by family history, the lack of accompanying pruritus or urticaria, the presence of recurrent gastrointestinal attacks of colics, and episodes of laryngeal edema. Diminished C4 concentrations during symptomatic periods are highly suggestive for the diagnosis. Further laboratory diagnosis depends on demonstrating a deficiency of C1-INH antigen (type I) in most kindreds, but some kindreds have an antigenically intact but dysfunctional protein (type II) and require a functional assay to establish the diagnosis. Prophylactic administration of either attenuated androgens or protease inhibitors has proved useful in reducing frequency or severity of attacks. Infusions of a vapour-heated C1-INH concentrate are safe and effective means of both preventing and treating attacks. Nevertheless, this treatment is expensive and this extract is not readily available. It is emphasised that administration of angiotensin converting enzyme inhibitors is contraindicated in patients suffering from protease inhibitor deficiency states.

A CASE OF RECTAL CANCER WITH SUBCTANEUS EMPHYSEMA CAUSING PERFORATION OF THE SIGMOID COLON

A 60-year-old woman visited another hospital because of no bowel movement and a stomach-ache lasting for 5 days, and was conveyed to the hospital with a diagnosis of peritonitis. Blood pressure was 86/34mmHg, and pulse was 112/min. There were muscular defense in the abdomen, and subcutaneus enphysema in the face, neck, and chest wall. Plain chest and abdominal X-ray examinations, and CT scan showed subcutaneus enphysema and a large quantity of free air. Emergency operation was carried out with a diagnosis of panperitonitis due to perforation of the colon. Ascites accompanied with stench and stool were found out in the abdominal cavity. There was a rectal cancer, and the sigmoid colon was perforated in the mesenterium side. The rectal cancer and sigmoid colon was resected, and the peritoneal cavity was washed with 35 liter of warm saline. Colostomy was attempted on the oral side colon. The patient became septic shock at the operation, but recovered from septic shock after the operation. Chemotherapy was started on the 39th hospital day, and the patient was discharged from the hospital on the 84th hospital day.

Piston-Ring Lubrication Problems for Refrigeration Compressors Considering Combined Effects of Supply Oil Quantity and Surface Roughness

Reciprocating-type compressors are widely used for refrigeration systems, and an understanding of piston-ring lubrication in the compressor is vital for designers in reducing the energy losses due to friction because a substantial portion of friction in the compressors is attributable to the piston-ring assembly. This study aimed at developing a one-dimensional analysis for lubrication between the piston-ring and cylinder of refrigeration compressors considering the combined effects of supply oil quantity and surface roughness on piston-ring face and cylinder wall. In the theoretical model, the piston-ring is treated as a one-dimensional dynamically loaded bearing with combined sliding and squeezing motion. The one-dimensional modified Reynolds equation based on the average flow model by Patir and Cheng is used as a governing equation. In the analysis of the modified Reynolds equation, two-types of inlet boundary conditions, flooded condition and starvation condition, are applied at the leading edge according to the supply oil quantity, and the Reynolds boundary condition is applied at the trailing edge. A numerical procedure is then developed to estimate the cyclic variation of minimum film thickness, inlet and outlet positions of lubrication film and friction force, and the combined effects of supply oil quantity and surface roughness height are examined for a typical refrigeration compressor. It is clarified from the numerical results that the supply oil quantity and surface roughness affect significantly the friction force of the piston-ring for refrigeration compressors.

FE analysis of grid reinforced embankment system on soft Bangkok clay

The behavior of a reinforced embankment on soft Bangkok clay has been analyzed by plane strain finite element method. The finite element analysis considers the selection of proper soil/reinforcement properties according to the relative displacement pattern of upper and lower interface elements. The large deformation phenomenon is simulated by updating the node coordinates, including those of the embankment elements above the current construction level, which ensures that the applied fill thickness simulates the actual field value. A full scale test reinforced embankment with a vertical face (wall) on Bangkok clay has been analyzed by the proposed finite element method, and the numerical results are compared with the field data. The response of a reinforced embankment on soft ground is principally controlled by the interaction between the reinforced soil mass and soft ground and the interaction between the grid reinforcement and the backfill soil. The tension in reinforcement and lateral displacement of the wall face varied during consolidation of foundation soil. The maximum tension force occurred in the reinforcement layer placed at the base of reinforced mass, due to bending of the reinforced mass resulting from differential settlements. It is considered necessary to account for the permeability variation of the soft ground foundation in the finite element analysis.

Some aspects of the flow in S-shaped diffusing ducts

The circular cross-sectional Royal Aerospace Establishment (RAE) 2129 S-shaped intake diffusing duct series, shown in Fig. 1, which has an offset of the inlet and exit centerline of 0·3 and 0·45 of the axial length of the duct, was designed at the RAE (Bedford) and tested at British Aerospace Filton, at low forward speeds (freestream Mach no. range from 0 – 0·2 but a range of duct inlet Mach numbers up to choking speeds) in the last two decades to fulfil the objectives of collecting systematic experimental data on engine face pressure recovery, total pressure flow distortion and wall static pressures for computational fluid dynamics validation. Some of the measurements have been presented, as for example, by Willmer, Brown & Goldsmith. The measurements from one version of Model 2129 (the 0·3 length offset S-duct geometry) have been used to compare with calculated results from a number of CFD programs, as for example, by Anderson, Horton and by the AGARD Working Group 13. The series of comparison also highlight the need for measurements other than the engine face total pressure and wall static pressure which have already been made.

Flows in the Vaneless Radial Diffuser Operating at Lower Flow Rates. (1st Report. Flow Visualization and Pressure Variations in the Radial Diffuser without Volute Casing.).

Experiments for water flows using flow visualization techniques and for air flows using some conventional instruments were conducted on the vaneless diffusers. The rotating stall cells were confirmed in the region of lower flow rates in the vaneless radial diffuser, and the flow characteristic parameters of existence of the rotating stall cells were attained for various space widths between the impeller open face and lower diffuser side wall. The relationships between the variations in pressure and the traveling speeds of the stall cells were also shown. The pressure distributions in the vaneless diffuser can be represented by an empirical relation for the outer range of normal operating flow rates.

A CASE OF GAS GANGRENE OF THE DEEP NECK

Gas gangrene, which is a severe and life-threatening disease, has been very rare in the head and neck region. A case of gas gangrene spreading within the bilateral cheek, oral floor, neck and upper mediastinum is reported. A 51-year-old man having a history of liver cirrhosis was admitted to Nagoya City University Hospital, due to persistent swelling and pain in his neck following gingibitis of his lower jaw, in spite of medical treatments involving antibiotics. He had high fever and jaundice. Severe swelling and redness were observed in his face, neck and upper chest wall. Macroscopic hematuria, leukocytosis, thrombocytopenia were also observed. He was recovered after transient shock with three times complementary surgical drainages and debridements under general anesthesia, supported by effective antibiotics. The foci of abscess were successfully oriented by computed tomography at every operation. Thus the computed tomography was very useful to determine the indication and suitable method of drainage and debridement of gas gangrene.

Water pressures on rigid gravity dams with finite reservoir during earthquakes

AbstractAn approximate analytical solution is presented for earthquake‐induced hydrodynamic pressures on rigid gravity dams with a finite reservoir and incompressible fluid. Using the Trefftz‐Mikhlin method, the solution is constructed with function expansions of solutions of the problem's governing equation which satisfy boundary conditions at the bottom and free surface. Unknown coefficients of the linear combinations are obtained from a continuous least‐squares treatment of the remaining boundary conditions at the upstream dam face and reservoir wall. Numerical results are presented for different geometries of the dam‐water and wall‐water interfaces. Out‐of‐phase motion at the end of the reservoir is considered. When the upstream dam face and reservoir wall are vertical, the known solution for in‐phase dam and wall movement is recovered.

Tension Pneumothorax during Dental Anesthesia

Subcutaneous emphysema of the face or neck which may extend into the mediastinum can complicate the use of high-speed air-turbine dental drills (1-5) or dental extractions (1). Pneumopericardium with subcutaneous emphysema has also occurred after maxillary surgery (6). Pneumopericardium, where air may have forced its way through a tear in the mucous membrane of the upper respiratory passages, has been reported to have occurred during a high-speed ride on a motorcycle (7). This case report describes the development of subcutaneous emphysema of the face, neck, and chest wall with mediastinal emphysema and tension pneumothorax that occurred during conservative dentistry using an air-turbine dental drill.