Effect of local injection of mesenchymal stem cells on healing of sutured gastric perforation in an experimental model.

BACKGROUND: Mesenchymal stem cells are proposed to facilitate repair of organ injuries. The aim of this study was to investigate whether local injection of mesenchymal stem cells could accelerate healing of sutured gastric perforations. METHODS: Sutured gastric perforations in rats were treated either with local injection of mesenchymal stem cells (injected MSC group) or by topically spraying with fibrin glue containing mesenchymal stem cells (sprayed MSC group). Controls were treated by local injection of saline or topical spray of fibrin glue without mesenchymal stem cells. Healing of sutured gastric perforations was assessed on days 3, 5 and 7. RESULTS: Local injection of mesenchymal stem cells significantly promoted the healing of gastric perforations, with the highest pneumatic bursting pressure (mean(s.e.m.) 112·3(30·2) mmHg on day 5 versus 71·2(17·4) mmHg in saline controls; P = 0·001), minimal wound adhesions, and lowest incidence of wound dehiscence (3, 6, 5 and 1 animal on day 5 in control, fibrin, sprayed MSC and injected MSC groups respectively; n = 10 per group) and abdominal abscess (2, 2, 1 and no animals respectively on day 5). Histological examination showed that gastric perforations in the injected MSC group displayed reduced inflammation, and increased granulation and re-epithelialization. Sutured gastric perforations in the injected MSC group showed decreased expression of interleukin 6, and increased expression of transforming growth factor ß1 and epithelial proliferating cell nuclear antigen, compared with the other groups. CONCLUSION: Local injection of mesenchymal stem cells was more effective than topical application, and enhanced the healing of sutured gastric perforations by an anti-inflammatory process, enhanced cellular proliferation and earlier onset of granulation. Surgical relevance Abnormal healing of gastric perforation may cause morbidity and increase the risk of death. Adipose tissue-derived mesenchymal stem cells have been found to promote the healing of organ injuries through cellular differentiation and secretion of cytokines that stimulate cellular proliferation and angiogenesis, and suppress inflammation. This study explored the therapeutic potential of such mesenchymal stem cells for promotion of the healing of sutured gastric perforations. Mesenchymal stem cells delivered by local injection significantly enhanced the healing of gastric perforations with reduced severity of wound adhesion, and a decreased incidence of wound dehiscence and abdominal abscess. The increased expression of transforming growth factor ß1, proliferating cell nuclear antigen and reduced level of interleukin 6 provide evidence for enhancement of the healing process. Engrafted mesenchymal stem cells expressed α-smooth muscle actin as a marker of myofibroblasts. This preclinical study indicates that local injection of allogeneic adipose tissue-derived mesenchymal stem cells may have a potential therapeutic role in enhancing the healing of peptic ulcer disease and prevention of ulcer-related complications.

Suicidal gene therapy in the effective control of primary human hepatocellular carcinoma as monitored by noninvasive bioimaging.

Hepatocellular carcinoma (HCC) is usually refractory to the available treatments. For cancer gene therapy purposes, real-time imaging of therapeutic gene expression is of great importance because there are multiple factors that modulate the therapeutic gene expression in a complex tumor microenvironment. As a consequence, multiple doses of therapeutic viral vectors may be required for improved efficacy. In the present study, the luciferase reporter gene and the yeast cytosine deaminase (yCD) genes were bicistronically expressed using the foot-and-mouth disease virus 2A peptide under the regulation of the cytomegalovirus (CMV) promoter. The effectiveness of the yCD/5-FC (5-fluorocytosine) killing efficacy mediated by the herpes simplex virus type 1 (HSV-1) amplicon viral vector was shown using HCC and non-HCC cell lines in vitro. In addition, in vivo experiment also showed tumor regression of a primary HCC 26-1004 tumor xenograft in tumor expressing high levels of the yCD gene (as determined by noninvasive imaging) after intratumoral injection of 1.5 × 10(6) TU HGCX-L2C HSV-1 amplicon viral vector and 5-FC administration. The HSV-1 amplicon viral vector coupled with the yCD/5-FC prodrug activated suicide gene could potentially be of use in clinical gene therapy for HCC.

Clinical trial of oral malodor treatment in patients with periodontal diseases.

BACKGROUND AND OBJECTIVE: Only a few clinical research studies have assessed different therapeutic approaches to oral malodor in subjects affected by periodontal diseases. The aim of this study was to evaluate the effects of periodontal treatment and tongue cleaning on oral malodor parameters in periodontitis and gingivitis patients. MATERIAL AND METHODS: The subjects were 102 periodontitis and 116 gingivitis patients with oral malodor. Oral malodor was measured by organoleptic test and Oral Chroma™. Oral health status, including tooth conditions, periodontal health, tongue coating and proteolytic activity of the BANA test in tongue coating were assessed. Subjects in each periodontal disease group were randomly assigned into two subgroups depending on the sequence of treatment: periodontal treatment and tongue cleaning. Oral malodor and oral health parameters were compared by groups and sequence of treatment. RESULTS: For subjects in the periodontitis group, there were statistically significant reductions in oral malodor after periodontitis treatment or tongue cleaning; however, major reductions were found after periodontitis treatment. For those in the gingivitis group, there were also statistically significant reductions in oral malodor after gingivitis treatment or tongue cleaning, but the most marked reductions were observed after tongue cleaning. At the completion of treatment, all oral malodor parameters fell below the threshold levels in all subgroups. CONCLUSION: The present study indicated that periodontal treatment played an important role and tongue cleaning contributed to a lesser extent to reduction in oral malodor in periodontitis patients. In contrast, tongue cleaning alone can be the primary approach to reduce oral malodor in gingivitis patients.

Oral Health Indicators for Risk of Malnutrition in Elders.

OBJECTIVES: Using both clinical parameters and subjective measures of oral health, this study aimed to identify useful oral health indicators for the risk of malnutrition in elders. DESIGN: Cross-sectional study. SETTING: Five community centers run by non-government organizations (NGOs). PARTICIPANTS: 195 community dwelling elders (65 or above). MEASUREMENTS: An interviewer-administered questionnaire was completed to collect information on elders' socio-demographic background and oral health perception and practice. Their number of teeth, number of occluding tooth pairs, dental caries, and periodontal condition were examined. General Oral Health Assessment Index (GOHAI), an instrument for assessing oral health related quality of life (OHQoL), was used as a subjective measure of oral health. The elders' nutritional status was evaluated by using the Mini-Nutritional Assessment (MNA). RESULTS: The mean (SD) DFT was 3.3 (3.1). Over 60% of elders had periodontal pockets; 33% had fewer than 20 teeth and 6% were edentulous. The mean (SD) of occluding tooth pairs was 7.1 (4.8). The mean (SD) total GOHAI score was 56.4 (8.0); 60% reported negative impact of oral health on their quality of life. The mean (SD) MNA score was 25.0 (2.9); 30% had malnutrition or were at risk. After controlling for socio-demographic factors, none of the clinical indicators (dental caries, periodontal status, number of teeth, and number of occluding tooth pairs) were associated with risk of malnutrition (all p>0.05). Poorer OHQoL indicated a higher chance for malnutrition in both adjusted models (OR of 0.914; 95% CI of 0.850-0.982; p=0.014 and OR of 0.915; 95% CI of 0.852-0.984; p=0.017). Tooth loss and untreated decayed teeth (DT) were significant/marginally significant determinants of poor OHQoL. CONCLUSION: Elders' tooth loss and unmet treatment need for dental caries were associated with compromised quality of life, which indicated increased likelihood for malnutrition.

48 weeks pegylated interferon alpha-2a is superior to 24 weeks of pegylated interferon alpha-2b in achieving hepatitis B e antigen seroconversion in chronic hepatitis B infection.

BACKGROUND/AIM: Although 48-week therapy with pegylated-interferons has been shown to be effective for the treatment of chronic hepatitis B virus infection, the efficacy of a shorter duration of therapy with pegylated interferons is unknown. METHOD: We reviewed 53 hepatitis B e antigen positive Chinese patients treated with 48 weeks of pegylated interferon alpha-2a or 24 weeks of pegylated interferon alpha-2b. Sustained virological response was defined as hepatitis B e antigen seroconversion and hepatitis B virus DNA <10(5) copies/mL at week 72. RESULTS: Twenty-nine patients were treated with 48 weeks of pegylated-interferon-alpha-2a and 24 patients with 24 weeks of pegylated-interferon-alpha-2b. At the end-of-therapy, hepatitis B e antigen seroconversion and hepatitis B virus DNA <10(5) copies/mL were similar between the two groups of patients [9/29 (31.0%) vs. 2/24 (8.3%), respectively, P = 0.09]. At week 72, 10 of the 29 patients (34.5%) treated with 48 weeks of pegylated-interferon-alpha-2a compared with two of the 24 patients (8.3%) treated with 24 weeks of pegylated-interferon-alpha-2b had sustained virological response (P = 0.04). By logistic analysis, 48 weeks of pegylated-interferon-alpha-2a was independently associated with sustained virological response (P = 0.04 adjusted hazards-ratio 9.37). CONCLUSION: Further studies are required to determine the optimal duration of therapy with pegylated interferons in chronic hepatitis B.

Effect of metal reconstruction plates on cobalt-60 dose distribution: a predictive formula and clinical implications.

PURPOSE: We sought to create a predictive formula for the dose perturbations caused by head and neck reconstruction plates in the delivery of postoperative radiotherapy with 60Co beams. MATERIALS AND METHODS: The dose perturbation effects of Vitallium and Titanium reconstruction plates and flat metal plates of aluminum (13Al), stainless steel (26Fe), tin (50Sn) and lead (82Pb) irradiated with a 60Co beam were measured in polystyrene phantoms using a film dosimetry system. We then used these results to create formulas to predict the effect of a metal reconstruction plate dependent upon its effective atomic number. RESULTS: Percentage dose increases secondary to back scattering were 10% at 1 mm in front of the Vitallium plate and 40% at the plate while the percentage dose decrease was 29% at the plate and 10% 1 mm behind the plate. For the Titanium plate, the percentage dose increase was 5% at 1 mm in front the plate and 25% at the plate while the percentage dose decrease was 20% at the plate and 5% 1 mm behind the plate. For flat plates the percentage dose increases and decreases, respectively, at the plate surfaces were: 13Al (8%, 6%), 26Fe (35%, 16%), 50Sn (60%, 24%), and 82Pb (85%, 13%). A second order polynomial predicting the back scatter and shadowing effects was created, Y = a + bZ + cZ2, where Z is the effective atomic number of the plate while a, b, and c are the following constants: for back scatter a = 0.854 +/- 0.082, b = 0.0212 +/- 0.0044, c = -0.00011 +/- 0.00004 and for shadowing a = 1.108 +/- 0.021, b = -0.0141 +/- 0.0011, c = 0.00014 +/- 0.00001. CONCLUSIONS: It is possible to predict the effect of a metal reconstruction plate upon the delivered postoperative radiotherapy dose. The dose perturbations around the plate only exist for a few millimeters, but this is substantially greater than the thickness of a normal tissue or tumor cell. Perhaps a coating of a low effective atomic number, biologically inert, substance might allow for greater dose homogeneity and decrease the risks of plate failure or tumor recurrence.

Evaluation of artificial skin (Integra) in a rodent model.

The biocompatibility of artificial skin (Integra) has been investigated in clean surgical wounds of 20 guinea-pigs. A rectangular 3 x 3 cm full-thickness skin defect with excision carried down to the panniculus carnosus was prepared on the dorsal area of the guinea-pig. A thin layer of silver sulfadiazine cream was applied and artificial skin was placed to cover the wound. At day 14, the uppermost silicone layer was removed. Good take of the artificial skin was observed in 18 of 20 animals. Microscopy showed good vascular ingrowth in 14 of the 18 animals. The remaining four animals showed necrotic tissue, absence of vascularization and haemorrhage in the wound bed. Two of the 20 wounds showed purulent discharge. In this animal model, clinical 'take' of the neodermis was achieved in 18/20 animals (90 per cent), while vascular ingrowth was observed in only 14/20 animals (70 per cent). These results suggested that artificial skin in clean surgical wound is readily biologically incorporated into surrounding viable tissue.

A comparison of mussels (Perna viridis) and semi-permeable membrane devices (SPMDs) for monitoring chlorinated trace organic contaminants in Hong Kong coastal waters.

A comparison of mussels (Perna viridis) and semi-permeable membrane devices (SPMDs) was carried out at five sites, representing a gradient of contaminant concentrations, in Hong Kong coastal waters. Mussels, originally collected from a "clean" location, were deployed along with SPMDs at each site for 30 days. Analyses for chlorinated pesticides and polychlorinated biphenyls (PCBs) indicated that SPMDs have potential as monitoring tools, and to some extent can overcome the problems associated with mussels, such as natural variability, differing age, sex, and physical condition. However, in most cases, SPMDs failed to rank the sites in the same order as mussels in terms of contaminant concentrations. Nonetheless, in localities where mussels cannot survive--as shown at Kwun Tong in the present experiment--SPMDs may be valuable in providing an indication of potentially bio-available lipophilic pollutants.

In vitro cytotoxicity testing of a nanocrystalline silver dressing (Acticoat) on cultured keratinocytes.

Acticoat is a polyethylene mesh coated with nanocrystalline silver. It has been used widely as a dressing for chronic wounds, acute partial-thickness burn wounds and donor sites. In this study, the in vitro cytotoxicity of Acticoat on cultured keratinocytes is tested. Human keratinocytes are cultivated on a pliable hyaluronate-derived membrane (Laserskin) using dermal fibroblasts as the feeder layer. When the cultured Laserskin (CLS) is subconfluent it is covered by Acticoat, which is exposed to water (Group 1), phosphate-buffered saline (Group 2) or culture medium (Group 3). The control group is not exposed to the Acticoat. After 30 minutes incubation at 37 degrees C, the inhibitory effect of the nanocrystalline silver on keratinocyte growth is measured by an MTT assay. Compared with the control, the relative viability of the CLS dropped to 0%, 0% and 9.3%, respectively. Thus, Acticoat is cytotoxic to cultured keratinocytes and should not be applied as a topical dressing on cultured skin grafts.

Using restorations borne totally by anterior implants to preserve the edentulous mandible.

BACKGROUND: This study quantifies the changes in bone height of the posterior area of the edentulous mandible when the load of complete dentures is borne entirely by anteriorly placed osseointegrated implants. METHODS: Thirty-three patients, of whom there were radiographs from the beginning of implant loading and from a follow-up visit at least three years later (a mean of 6.6 years later), were included in the study. Working with panoramic radiographs, the authors took height measurements in the premolar area (15 millimeters distal to the most distal implants). A valid correction factor was available because implants of known length were proximal to the area being evaluated. RESULTS: The authors calculated descriptive statistics using means, standard deviations, medians and proportions as appropriate. A P-value of less than .05 was considered significant. Of the 33 subjects, most showed increases in bone height--29 (87.9 percent) on the right side and 28 (84.9 percent) on the left side. The mean change in all subjects was +1.0 mm (range -0.8 to +3.3 mm). A comparison of mandibular height at implant placement vs. follow-up showed a statistically significant increase bilaterally (P < .001). CONCLUSIONS: This study demonstrates that dentures for edentulous mandibles that are borne totally by implants in the anterior area conserve or enhance the bone of the posterior portion of the mandible. An important future study should test the effect of implant-assisted restorations for the edentulous mandible that load the posterior ridge (a bar clasp, for example). CLINICAL IMPLICATIONS: One of the considerations in planning treatment for the edentulous mandible should be the preserving effect of totally implant-borne restorations vs. the continued resorption of the body of the mandible with conventional dentures.

Unilateral ptosis correction with mersilene mesh frontalis sling in infants: thirteen-year follow-up report.

PURPOSE: To assess surgical, visual, refractive, and aesthetic outcomes 13 years after mersilene mesh frontalis sling (MMFS) operation for severe unilateral congenital ptosis performed in 10 infants before 1 year of age. METHODS: Longitudinal follow-up of an interventional case series by structured ocular examinations, external photographs, and questionnaire-based interviews. RESULTS: Mean age at surgery was 6.9+/-2.7 months. After a mean follow-up of 13.0+/-0.6 years, one patient (10%) had recurrent ptosis with the upper lid 2 mm below the superior limbus at 3 months postoperatively. Best-corrected visual acuities were within two Snellen lines between the two eyes in all patients. Astigmatic errors were 1.20+/-1.00 D and 1.10+/-1.70 D between operated and unoperated eyes. Four patients had 2 mm lid lag on down-gaze and one of them had 2 mm lagophthalmos. Mean satisfaction scores (scale of 1 to 100) for lid position, cosmesis, function, and to the procedure were 83.3+/-11.8, 77.0+/-22.9, 89.4+/-5.5, and 86.8+/-6.3, respectively. No case of overcorrection, sling extrusion, stitch granuloma, or exposure keratopathy was noted. CONCLUSIONS: In view of the low recurrence rate (10%) and absence of serious complication or need for revision after 13 years, the use of MMFS seems effective and feasible in infants less than 1 year old. Achieving compatible long-term stability, satisfactory aesthetic, and visual outcomes, MMFS may offer an alternative to delaying operations for autogenous fascia lata harvesting in infants requiring early ptosis correction.

Nanosized bioceramic particles could function as efficient gene delivery vehicles with target specificity for the spleen.

We have compared the ability of several nanosized bioceramic particles including negatively charged silica (SiO(2)), neutrally charged hydroxyapatite (HA) and positively charged zirconia (ZrO(2)) nanoparticles as non-viral vectors for efficient in vivo gene delivery. A mixture of highly monodispersed aqueous suspension of HA or SiO(2) nanoparticles, coated with protamine sulfate (PS), complexed efficiently with plasmid DNA and significantly enhanced transgene expression in vitro. In comparison, ZrO(2) nanoparticles gave poor transfection efficiency under similar conditions tested. It was also determined that, under the same conditions, PS-SiO(2)-DNA, but not PS-HA-DNA-nanoplexes, were able to mediate efficient transgene expression in vitro in the presence of 50% serum. Intraperitoneal injections of PS-SiO(2)-luciferase DNA nanoplexes targeted the highest level of transgene expression in the spleen of recipient mice that lasted for more than 48 h. Injection of PS-SiO(2)-pNGVL-hFLex-MUC-1 nanoplexes was able to mediate the production of Flt-3L in the sera of recipient mice. Simultaneously, the production of Flt-3L was accompanied by the stimulation of IL-2 and interferon-gamma (IFN-gamma). Most importantly, the injection of PS-SiO(2)-pNGVL-hFLex-MUC-1 nanoplexes could mount potent anti-tumour specific immune responses that led to the subsequent regression of parental tumor cells containing the muc-1 determinant.

Alkaline digestion and solid phase extraction method for perfluorinated compounds in mussels and oysters from South China and Japan.

Perfluorinated compounds (PFCs), such as perfluorooctane sulfonate (PFOS), have been identified in the coastal waters of China and Japan. An alkaline digestion method, coupled with solid-phase extraction (SPE), and high-performance liquid chromatography interfaced with high-resolution electrospray tandem mass spectrometry was developed to determine PFCs in mussel and oyster samples from coastal waters of South China and Japan. These techniques produced adequate recoveries and reporting limits with small quantities of PFCs. Concentrations of individual PFCs in mussels and oysters from South China and Japan ranged from 113.6 to 586.0 pg/g, wet weight (ww) for PFOS, 63.1 to 511.6 pg/g, ww for perfluorohexane sulfonate, 9.3 to 30.1 pg/g, ww for perfluorobutane sulfonate and 37.8 to 2957.0 pg/g, ww for perfluorooctane sulfonamide. The quantification of perfluorinated carboxylates was compromised by interferences from carboxylates in the procedural blanks. Perfluoroundecanoate and perfluorononanoate had relatively great blank interferences, which resulted in relatively poor limits of quantification for these compounds. Some PFCs were only identified in a limited number of samples: perfluorododecanoate in samples from Tokyo Bay, Japan (195.9 pg/g, ww); and perfluorodecanoate in Fuzhou, China (131.7 pg/g, ww) and Tokyo Bay (118.6 pg/g, ww). The greatest concentrations of perfluorooctanoate, perfluoroheptanoate, and perfluorohexanoate were observed in samples from Tokyo Bay and Bei Hai, South China.

Mandibular asymmetry and condylar position in children with unilateral posterior crossbite.

The purpose of this retrospective study was to determine if condylar position in children with functional unilateral crossbites was different from that found in children with Class I noncrossbite malocclusions and if there was a change in condylar position after correction of the crossbite by palatal expansion. Mandibular asymmetry in children with functional unilateral posterior crossbite was also compared to that of a Class I noncrossbite group. Thirty-one children aged 6 to 14 years (mean, 9.3 years; standard deviation, 2.2) with functional unilateral crossbites were compared to 31 children aged 9.5 to 14.1 years (mean, 11.9 years; standard deviation, 1.3) exhibiting Angle Class I noncrossbite malocclusions. Pretreatment submentovertex radiographs were used to study mandibular skeletal, dental, and positional asymmetries with reference to cranial floor and mandibular coordinate systems. In addition, the anterior, superior, and posterior joint spaces were measured to determine differences between the groups with the use of pretreatment and posttreatment horizontally corrected tomograms of the temporomandibular joints. Finally, the distances of the mesiobuccal cusp of the upper first molar relative to the buccal groove of the lower first molar were measured in both groups before treatment. Univariate analyses revealed that the mandibles of children in the functional unilateral posterior crossbite group exhibited asymmetry in both anteroposterior and transverse dimensions when compared with the Class I noncrossbite group (P <. 05). These asymmetries were the result of a functional deviation of the mandible that was present in all subjects in the crossbite group. This deviation was manifested occlusally by a Class II subdivision on the crossbite side as indicated from the study model analysis (P <.05). Examination of condylar position as evidenced by horizontally corrected tomograms demonstrated a large standard deviation, resulting in an inability to detect any significant differences within or between groups at both T1 and T2 (P >.05). This study raised the question of the appropriateness of measuring joint spaces for routine diagnostic purposes.

Identical twins treated differently.

This case study is intended to demonstrate the effects of two different orthodontic treatment methods on one set of identical twins.

A new technique to resurface wounds with composite biocompatible epidermal graft and artificial skin.

BACKGROUND: The incorporation of cultured epidermal autograft on the neodermis of artificial skin (Integra, Integra LifeSciences, Plainsboro, NJ) has been met with some difficulties. A new engraftment technique to resurface the wounds with Integra and composite biocompatible epidermal graft (CBEG) has been successfully applied on three patients for elective reconstructive procedures. METHODS: A small skin biopsy was taken from the normal edge of the lesion for keratinocytes and dermal fibroblast cultures 2 weeks before surgery. When sufficient cells were grown, the patient was admitted for the excision of the lesions or scars. The wounds of the patients, ranging from 125 to 250 cm2, were covered with Integra. When the neodermis of the Integra was fully vascularized, the silicone membrane of the Integra was removed and replaced with the CBEG, which consisted of autologous keratinocytes cultivated on a hyaluronate-derived membrane (Laserskin; Fidia Advanced Biopolymers, Abano Terme, Italy)) using human dermal fibroblasts as a feeder layer. RESULTS: Clinically, there was good initial "take" of the CBEGs in these three patients, ranging from 50% to 100%. Biopsy specimens of the grafted wounds were taken 1 to 3 weeks after the application of the CBEGs. Epithelialization was noted in all patients. CONCLUSION: This engraftment technique has several advantages. The CBEG is much easier to handle than the conventional cultured epidermal autograft. It eliminates the invasive second procedure for skin harvesting, with resulting pain and scarring. The application of the CBEG can be easily performed at the bedside.