Efficiency and clinical results of bleomycin injection in the treatment of lymphatic malformations.

Background: Lymphatic malformations (LMs) are rare congenital anomalies. The traditional treatment is surgical excision, but intralesional sclerosing agent injection is also preferred as the first-choice treatment because of postoperative frequent recurrences, poor cosmetic results, and high complication rate. We aimed to evaluate the efficacy of sclerosing agent injection used in the treatment of LMs in children. Materials and Methods: We retrospectively analyzed the children who were treated for LM between January 2011 and January 2022. The lesion sizes of the patients who were injected with sclerosant (Bleomycin) under sedation anesthesia, measured by ultrasound before and after the treatment, were recorded, and the difference between them was statistically evaluated. Results: Fifteen patients were retrospectively analyzed. The mean age was 45.2 ± 14.1 months. Of these, ten (66.6%) were male and five (33.3%) were female (F/M = 1/2). The mean age of male patients was 55 ± 20.1 months; the mean age of female patients was 25.8 ± 11. Seven patients had a single dose, two had twice, and six had three and more. The mean measurable size of macrocystic lesions before treatment was 55.2 ± 28.4 mm; after treatment, it was 23.8 ± 18.2 mm. Although no measurable shrinkage was detected in microcystic lesions, it was observed that the lesion shrank to allow surgical resection. With the statistical analysis, it was seen that there was a statistically significant difference between the dimensions before and after the treatment (P < 0.05) and the sclerosant injection had a great effect on the treatment (R: 0.89). Conclusion: Intralesional injection of bleomycin is less effective for microcystic or mixed-type LMs, but provides an effective reduction for a safe surgical procedure. It is an effective treatment for macrocystic lesions.

Effect of hypericin on the ADAMTS-9 and ADAMTS-8 gene expression in MCF7 breast cancer cells.

AIM: To investigate the effects of hypericin which is obtained from the plant Hypericum perforatum on the expression and the regulation of ADAMTS8 and ADAMTS9 genes in MCF7 breast cancer cells and on the viability of these cells. MATERIALS AND METHODS: MCF7 cells were cultured and were separately exposed to 2, 10 and 50 µl/mL of hypericin. After 24 hours, RNA was isolated from these cells and converted to cDNA. The expression levels of ADAMTS8 and ADAMTS9 genes were evaluated using the Reverse Transcription Polymerase Chain Reaction. XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide, disodium salt) cell viability assay was used to determine cytotoxicity. RESULTS: ADAMTS9 expression in MCF7 cells were increased 1.8 and 3.6 fold with the use of 2 and 10 µl/mL of hypericin, respectively; and decreased 0.7 fold with the use of 50 µl/mL of hypericin. There was no significant change in the ADAMTS8 expression. Rapid cell death was observed in the cancer cells when hypericin was used at a dose of ≥ 50 µl/mL. CONCLUSIONS: The increase in ADAMTS9 expression can be a useful factor in the prevention of possible metastasis in breast cancer and for the occurrence of a tumor suppressive effect. Hypericin increases the expression of ADAMTS9, therefore, it may show its antitumoral and antiapoptotic effects by means of ADAMTS9.

Comparing anterior palatoplasty and modified uvulopalatopharyngoplasty for primary snoring patients: preliminary results.

OBJECTIVES: To evaluate and compare the long-term efficacy of modified uvulopalatopharyngoplasty (mUP3) and anterior palatoplasty (AP) techniques for treating snoring in a prospective clinical trial. METHODOLOGY: Patients with total apnea-hypopnea index values < 5/per hour sleep were included in the study. Patients completed the Epworth sleepiness scale (ESS) and snoring visual analogue scale (VAS) before and 24 months after surgery, and a VAS for pain after the operation. RESULTS: Twenty-four patients were in the mUP3 group with a mean age of 42.1 +/- 11.8 years, and 26 in AP group with a mean age of 43.2 +/- 10.4 years. Snoring VAS values were significantly decreased after surgery in both groups (p < 0.025), but changes between operative groups were not statistically significant (p > 0.05). Patients' ESS scores in both groups significantly decreased (p < 0.025), but ESS score changes between groups were not significantly different (p > 0.05). Two years postoperatively, patient satisfaction was 85% in the AP group, and 70% in the mUP3 group. Pain VAS values were significantly lower in the AP group than in the mUP3 group (p < 0.001). Eight patients (33.3%) in the mUP3 group and one (7.7%) in the AP group reported nasal regurgitation of liquids upon swallowing during the first week postoperatively. Two years after the operation, 10 patients (41.6%) in the mUP3 group and 9 (34.6%) in AP group still had a lump sensation in the throat. CONCLUSIONS: We compared the efficacy of the mUP3 and AP techniques to treat patients with primary snoring and found less morbidity and more patient satisfaction in the AP group.

An infantile case of Zellweger syndrome presented with Kabuki-like phenotype.

Zellweger syndrome is a peroxisomal disorder resulting from the mutations in PEX genes generally presenting in the neonatal period with profound hypotonia seizures, inability to feed, liver cysts with hepatic dysfunction, chondrodysplasia punctata. Kabuki make-up syndrome is a multiple congenital anomalies and mental retardation syndrome with characteristic facial appearance, skeletal abnormalities, dermatoglyphic abnormalities, mental retardation and short stature. Abnormal liver functions and some atypical findings were also reported in some patients with Kabuki syndrome. In this report a case with late onset Zellweger syndrome who had some phenotypical findings which are also seen in Kabuki Syndrome will be presented. The inclusion of Zellweger syndrome into the differential diagnosis of the patients with Kabuki-like phenotype in addition to abnormal liver functions is emphasized.

Structural and functional motor cortex asymmetry in unilateral lower limb amputation with phantom limb pain.

OBJECTIVE: The role of motor cortex reorganization in the development and maintenance of phantom limb pain (PLP) is still unclear. This study aims to evaluate neurophysiological and structural motor cortex asymmetry in patients with PLP and its relationship with pain intensity. METHODS: Cross-sectional analysis of an ongoing randomized-controlled trial. We evaluated the motor cortex asymmetry through two techniques: i) changes in cortical excitability indexed by transcranial magnetic stimulation (motor evoked potential, paired-pulse paradigms and cortical mapping), and ii) voxel-wise grey matter asymmetry analysis by brain magnetic resonance imaging. RESULTS: We included 62 unilateral traumatic lower limb amputees with a mean PLP of 5.9 (SD = 1.79). We found, in the affected hemisphere, an anterior shift of the hand area center of gravity (23 mm, 95% CI 6 to 38, p = 0.005) and a disorganized and widespread representation. Regarding voxel-wise grey matter asymmetry analysis, data from 21 participants show a loss of grey matter volume in the motor area of the affected hemisphere. This asymmetry seems negatively associated with time since amputation. For TMS data, only the ICF ratio is negatively correlated with PLP intensity (r = -0.25, p = 0.04). CONCLUSION: There is an asymmetrical reorganization of the motor cortex in patients with PLP, characterized by a disorganized, widespread, and shifted hand cortical representation and a loss in grey matter volume in the affected hemisphere. This reorganization seems to reduce across time since amputation. However, it is not associated with pain intensity. SIGNIFICANCE: These findings are significant to understand the role of the motor cortex reorganization in patients with PLP, showing that the pain intensity may be related with other neurophysiological factors, not just cortical reorganization.

Cortical plasticity in phantom limb pain: A fMRI study on the neural correlates of behavioral clinical manifestations.

The neural mechanism of phantom limb pain (PLP) is related to the intense brain reorganization process implicating plasticity after deafferentation mostly in sensorimotor system. There is a limited understanding of the association between the sensorimotor system and PLP. We used a novel task-based functional magnetic resonance imaging (fMRI) approach to (1) assess neural activation within a-priori selected regions-of-interested (motor cortex [M1], somatosensory cortex [S1], and visual cortex [V1]), (2) quantify the cortical representation shift in the affected M1, and (3) correlate these changes with baseline clinical characteristics. In a sample of 18 participants, we found a significantly increased activity in M1 and S1 as well as a shift in motor cortex representation that was not related to PLP intensity. In an exploratory analyses (not corrected for multiple comparisons), they were directly correlated with time since amputation; and there was an association between increased activity in M1 with a lack of itching sensation and V1 activation was negatively correlated with PLP. Longer periods of amputation lead to compensatory changes in sensory-motor areas; and itching seems to be a protective marker for less signal changes. We confirmed that PLP intensity is not associated with signal changes in M1 and S1 but in V1.

Comparison of intrathecal magnesium, fentanyl, or placebo combined with bupivacaine 0.5% for parturients undergoing elective cesarean delivery.

BACKGROUND: Intrathecal (i.t.) administration of magnesium has been reported to potentiate opioid antinociception in rats and humans. In this prospective, randomized, double-blind, study, we investigated the sensory, motor, and analgesic block characteristics of i.t. magnesium 50 mg compared with fentanyl 25 microg and saline when added to 0.5% bupivacaine (10 mg). METHODS: Ninety ASA I or II adult patients undergoing cesarean section were randomly allocated to receive 1.0 ml of 0.9% sodium chloride in group S, 50 mg of magnesium sulfate (1.0 ml) 5% in group M, or 25 microg of fentanyl (1.0 ml) in group F following 10 mg of bupivacaine 0.5% i.t. We recorded the following: onset and duration of sensory and motor block, maximal sensory block height, the time to reach the maximal dermatomal level of sensory block, and the duration of spinal anesthesia. RESULTS: Magnesium did not shorten the onset time of sensory and motor blockade or prolong the duration of spinal anesthesia. The duration of sensory (P<0.032) and motor (P<0.002) blockade was significantly shorter in M and S groups than in the F group. The time to reach the maximal dermatomal level of sensory block was significantly shorter in the F group than in the S and M groups (P<0.002). CONCLUSION: In patients undergoing cesarean section with spinal anesthesia, the addition of magnesium sulfate (50 mg) i.t. to 10 mg of spinal bupivacaine (0.5%) did not shorten the onset time of sensory and motor blockade or prolong the duration of spinal anesthesia, as seen with fentanyl.

Early initiation of extracorporeal photochemotherapy increases response for chronic graft versus host disease following steroid failure.

OBJECTIVES: Chronic graft versus host disease (GVHD) is one of the major obstacles to achieve success in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Extracorporeal photochemotherapy (ECP) has been demonstrated to be an effective modality for the treatment of GVHD in previous studies but they vary in terms of initiation and duration. Our aim is to demonstrate the characteristics of our patients who received ECP for chronic GVHD to clarify the best treatment scheme. MATERIAL AND METHODS: In this study, we retrospectively evaluated 34 patients with steroid refractory chronic GVHD (n=34) who were treated with ECP between 2001 and 2015. The initiation of ECP was determined according to patient status and the physician's preference. RESULTS: ECP was initiated early (≤3months) as the preferred second-line treatment after failure of methylprednisolone treatment in 12 patients (35%), 22 steroid refractory patients (65%) received ECP later. In all cohorts, 10 (29%) and 14 (41%) of 34 patients achieved complete response (CR) and partial response (PR), respectively, with an overall response rate (ORR) of 70. Early initiation of ECP after chronic GVHD diagnosis (≤3months vs more than 3months) was associated with increased rates of response (92% vs 59%, P=0.046) in which the severity of diseases were similar. Patients with skin involvement in early treatment group had statistically better response. Mild side effects were detected in only 6 patients (16%). CONCLUSION: ECP is a safe treatment modality and particularly effective when initiated soon after steroid failure in chronic GVHD.

Stromal cells promote bone invasion by suppressing bone formation in ameloblastoma.

AIMS: To study the stromal variation and role of stromal-tumour cell interaction in impaired bone formation as well as enhanced bone resorption in ameloblastoma. METHODS AND RESULTS: Four types of stroma were observed histologically; fibrous, desmoplastic, myxoid and myxoid with hyalinization. Osteoblast and osteoclast were counted using haematoxylin and eosin sections and immunohistochemistry with CD68. After histomorphometric analysis, only fibrous and myxoid types of stroma were distinctly identified. Secreted frizzled-related peptide (sFRP)-2, transforming growth factor-beta 1 and receptor activator of nuclear factor-kappaB ligand (RANKL) revealed strong expression in myxoid type compared with the normal stroma. Bone morphogenetic protein (BMP)-2 was negative in myxoid type, but positive in normal stroma. Fibrous-type stroma showed weak expression of all antigens except RANKL compared with myxoid type. CONCLUSIONS: The results suggest that stroma does not act only in bone resorption, but also in the suppression of new bone formation. sFRP-2 is the main factor for impaired bone formation. The expression of markers related to osteoclastogenesis and suppression of osteoblast formation is higher in myxoid-type than in fibrous-type stroma. Tumour cells create a favourable environment for impaired bone formation by secreting sFRP-2 as well as bone resorption by secreting RANKL and interleukin-6.

Expression of human beta-defensin -1, -2, and -3 in non-inflamed pseudocyst, mucoceles.

OBJECTIVES AND DESIGN: The expressions of human beta defensin-1 (HBD-1), -2 (HBD-2) and -3 (HBD-3) in non-inflamed pseudocysts such as mucoceles were investigated immunohistochemically in this study. MATERIALS AND METHODS: Mucocele specimens were obtained from 21 patients. The expression of HBDs was studied immunohistochemically by using antibodies directed against HBD-1, -2, and -3. Statistical analyses were carried out on serial sections stained with antibodies. RESULTS: Cells expressing HBDs were found in mucoceles. The expression of HBD-2 was observed in floating cells in all the specimens, whereas HBD-1 and HBD-3-expressing cells were detected in 93% and 73% of the mucoceles, respectively. The HBD-2 signal was the most intense and the HBD-3 signal intensity was weaker than that of HBD-1. HBDs were expressed in neutrophils and in other floating cells. Interestingly, the signal intensity and the population of positive cells located close to the centers of cysts were higher than those located in the peripheral areas of cysts. CONCLUSION: The expression of HBDs was found even in non-inflamed pseudocysts such as mucoceles. These results suggest that an unknown mechanism not involved in biophylaxis for the expression of HBDs may exist.

Deletion mapping of chromosome 4q22-35 and identification of four frequently deleted regions in head and neck cancers.

Head and neck squamous cell carcinoma (HNSCC) is a diverse group of cancers that are frequently aggressive in their biologic behavior. Inactivation of tumor suppressor gene (TSG) is one of the most critical steps leading to HNSCC. Loss of heterozygosity analysis is very sensitive method for the detection of frequent allelic loss in a chromosomal locus. This method has been considered as an important evidence for the localization of TSGs. We analyzed loss of heterozygosity (LOH) at chromosome 4q22-35 region by using 14 polymorphic microsatellite markers in 83 matched normal and HNSCC tissues. LOH was detected at least in one location in 71 of 83 (86%) tumor tissues. Frequent deletions were detected at the location of microsatellite markers, D4S2909 (46%), D4S2623 (51%), D4S406 (48%), D4S1644 (45%) and D4S2979 (40%). Four different frequently deleted regions at 4q22, 4q25, 4q31 and 4q34-35 were observed. These regions include several putative TSGs such as Caspase-6, SMARCAD1, SMARCA5, SAP30 and ING2. Further molecular analysis of each gene should be performed to clarify their roles in head and neck squamous cell carcinogenesis.

Lack of B-RAF mutations in head and neck squamous cell carcinoma.

B-RAF is one of the most commonly mutated oncogenes in human cancer. However, the mutation status of B-RAF has not been established completely in HNSCC. We have analysed the mutation status of the kinase domain of the B-RAF gene (exons 11 and 15) in 91 Japanese HNSCC patients as well as 12 HNSCC cell lines. DNA was extracted and amplified by PCR. Mutations were then analysed by SSCP mutation detection method. Since V600EB-RAF constitutes 90 % of the mutations identified in B-RAF in human cancers, we also used MASA analysis to specifically detect this mutation in exon 15 of B-RAF. Using both methods, no mutation was found in both exon 11 and 15 in all patients and cell lines. Mu tations are absent or rare in the kinase domain of B-RAF in Japanese HNSCC. However, more studies are still needed to determine its usefulness as a target for molecular therapy in these patients.

Genomic structure of the human ING1 gene and tumor-specific mutations detected in head and neck squamous cell carcinomas.

We characterized the genomic structure of the human ING1 gene, a candidate tumor suppressor gene, and found that the gene has three exons. We also demonstrated that four mRNA variants were transcribed from three different promoter regions. Of 34 informative cases of head and neck squamous cell carcinoma, 68% of tumors showed loss of heterozygosity at chromosome 13q33-34, where the ING1 gene is located. Here we present the first report that three missense mutations and three silent changes were detected in the ING1 gene in 6 of 23 tumors with allelic loss at the 13q33-34 region. These missense mutations were found within the PHD finger domain and nuclear localization motif in ING1 protein, probably abrogating the normal function.

TNF combined with IFN-alpha accelerates NF-kappaB-mediated apoptosis through enhancement of Fas expression in colon cancer cells.

Immunostaining and EMSA revealed that NF-kappaB was activated strongly by TNF/IFN-alpha compared to TNF alone in a human colon adenocarcinoma cell line, RPMI4788. Although inhibition of activated NF-kappaB, by using an NF-kappaB decoy, reduced cell viability after treatment with TNF only, NF-kappaB decoy resulted in recovery of cell viability after TNF/IFN-alpha treatment. Caspase-3 activity was increased in cells induced by TNF/IFN-alpha, while suppression of caspase-3 activity was observed in cells transfected with NF-kappaB decoy and then treated by TNF/IFN-alpha. On the other hand, Fas expression was strongly enhanced by TNF/IFN-alpha, and inhibition of TNF/IFN-alpha-induced NF-kappaB activation, by using NF-kappaB decoy, decreased Fas expression. Cell viability and caspase-3 activity decreased in cells treated with TNF/IFN-alpha and anti-FasL antibody. Taken together, our findings suggest that activated NF-kappaB induced by the crosstalk between TNF and IFN-alpha is a novel pro-apoptotic signal acting via enhancement of Fas expression.

Heparanase expression correlates with malignant potential in human colon cancer.

PURPOSE: Heparanase cleaves carbohydrate chains of heparan sulphate proteoglycans and is an important component of the extracellular matrix. This study was designed to determine the relation between heparanase expression and prognosis of patients with colon cancer. METHODS: The study included 54 patients (35 males and 19 females) who underwent colorectal resection for colorectal cancer between January 1992 and December 1994. Expression of heparanase protein and mRNA were determined and correlated with various clinicopathological parameters. In vitro studies were also performed to examine tumor invasion and to test the effects of heparanase inhibition, and in vivo studies were performed to examine tumor metastasis and prognosis. RESULTS: Heparanase expression was detected in the invasion front of the tumor in 37 of 54 (69%) colon cancer samples, whereas 17 of 54 (31%) tumors were negative. Expression of heparanase was significantly more frequent in tumors of higher TNM stage (P=0.0481), higher Dukes stage (P=0.0411), higher vascular infiltration (P=0.0146), and higher lymph vessel infiltration (P=0.0010). Heparanase expression in colon cancers correlated significantly with poor survival (P=0.0361). Heparanase-transfected colon cancer cells exhibited significant invasion compared with control-transfected colon cancer cells (P=0.001), and the peritoneal dissemination model also showed the malignant potential of heparanase-transfected cells, as assayed by number of nodules (P=0.017) and survival (P=0.0062). Inhibition of heparanase significantly reduced the invasive capacity of cancer cells (P=0.003). CONCLUSIONS: Heparanase is a marker for poor prognosis of patients with colon cancer and could be a suitable target for antitumor therapy in colon cancer.

A comparative study of continuous positive airway pressure (CPAP) and intermittent positive pressure ventilation (IPPV) in patients with flail chest.

INTRODUCTION: The role of non-invasive positive pressure ventilation delivered through a face mask in patients with flail chest is uncertain. We conducted a prospective, randomised study of continuous positive airway pressure (CPAP) given via a face mask to spontaneously breathing patients compared with intermittent positive pressure ventilation (IPPV) with endotracheal intubation (ETI) in 52 patients with flail chest who required mechanical ventilation. METHOD: The 52 mechanically ventilated patients were randomly divided into two treatment groups: the ET group (n = 27) received mechanical ventilation with ETI, whereas patients in the CPAP group (n = 25) received CPAP via a face mask with patient controlled analgesia (PCA). Major complications, arterial blood gas levels, length of intensive care unit (ICU) stay and ICU survival rate were recorded. RESULTS: Nosocomial infection was diagnosed in 10 of 21 patients in the ET group, but only in 4 of 22 in the CPAP group (p = 0.001). Mean PO(2) was significantly higher in the ET group in the first 2 days (p<0.05). There were no significant differences in length of ICU stay between groups. Twenty CPAP patients survived, but only 14 of 21 intubated patients who received IPPV (p<0.01). CONCLUSION: Non-invasive CPAP with PCA led to lower mortality and a lower nosocomial infection rate, but similar oxygenation and length of ICU stay. The study supports the application of CPAP at least as a first line of treatment for flail chest caused by blunt thoracic trauma.

Effect of enteral and parenteral nutrition on growth parameters of hospitalized Turkish children.

This study was conducted to investigate growth and the complications in the hospitalized pediatric patients receiving either enteral (n = 26) or parenteral (n = 15) nutrition. Anthropometric measures as well as the results of biochemical analyses and complete blood counts were recorded. Weight, height and weight for height were expressed in z scores. The improvement in z scores for the 26 children receiving enteral nutrition in weight for age (P = 0.001), height for age (P = 0.002) and weight for height (P = 0.008) were all statistically significant. There were also significant correlations between the changes in weight for age (r2 = 0.15, P = 0.0049) and height for age (r2 = 0.64 and P = 0.0001) z scores and the time for follow up. Corresponding z scores in the parenteral nutrition group were not statistically significant. This study indicated that enteral nutrition provides significant improvement not only in weight but also height of sick hospitalized pediatric patients.

Localization of type IV collagen a 1 to a 6 chains in basement membrane during mouse molar germ development.

The dental basement membrane (BM) putatively mediates epithelial-mesenchymal interactions during tooth morphogenesis and cytodifferentiation. Type IV collagen alpha chains, a major network-forming protein of the dental BM, was studied and results disclosed distinct expression patterns at different stages of mouse molar germ development. At the dental placode and bud stage, the BM of the oral epithelium expressed alpha 1, alpha 2, alpha 5 and alpha 6 chains while the gubernaculum dentis, in addition to the above four chains, also expressed a 4 chain. An asymmetrical expression for alpha 4, alpha 5 and alpha 6 chains was observed at the bud stage. At the early bell stage, the BM associated with the inner enamel epithelium (IEE) of molar germ expressed alpha 1, alpha 2 and alpha 4 chains while the BM of the outer enamel epithelium (OEE) expressed only alpha 1 and a 2 chains. With the onset of dentinogenesis, the collagen a chain profile of the IEE BM gradually disappeared. Howeverfrom the early to late bell stage, the gubernaculum dentis consistently expressed alpha 1, alpha 2, alpha 5 and a 6 chains resembling fetal oral mucosa. These findings suggest that stage- and position-specific distribution of type IV collagen alpha subunits occur during molar germ development and that these changes are essential for molar morphogenesis and cytodifferentiation.

nm23 Protein expression in larynx cancer and the relationship with metastasis.

The nm23 gene, which encodes nucleoside diphosphate (NDP) kinase, is proposed as a metastatic suppressor gene and has been demonstrated to correlate inversely with metastatic potential in several tumours. To elucidate the role of nm23 in larynx carcinomas, we examined using immunohistochemistry the expression of the nm23 protein in matched sets of primary tumours and metastatic lymph nodes. nm23 Protein was expressed in all the carcinomas as well as in non-neoplastic larynx mucosa. Overexpression of nm23 protein was found in the majority of primary tumours compared with corresponding normal mucosa, while decreased expression was associated with poor differentiation and distant metastasis and/or recurrence. No significant difference in age, sex and stage was found between primary tumours with high and low nm23 protein expression. These results suggest that decreased nm23 protein expression may play a role in metastasis and/or recurrence in larynx cancer and therefore could be used as a prognostic factor.