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.

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.

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.

Genetic variations of BRCA1 and BRCA2 genes in dogs with mammary tumours.

Mammary tumours are the most common tumour type in female dogs. The formation of the mammary tumours is multifactorial but the high incidence of tumour disease in certain canine breeds suggests a strong genetic component. BRCA1 and BRCA2 are the most important genes significantly associated with mammary tumours. The aim of this study was to determine the association between the variations of these two genes and canine mammary tumours. 5'-untranslated region, intron 8 and exon 9 of BRCA1 and exons 12, 24, 27 of BRCA2 were sequenced in order to detect the genetic variations. In addition to six previously identified polymorphisms, six novel single nucleotide polymorphisms (SNPs) were detected. Five of the coding SNPs were synonymous and three of them were non-synonymous. The comparison of the sequences from 25 mammary tumour bearing and 10 tumour free dogs suggested that the two SNPs in intron 8 and exon 9 of BRCA1 and two SNPs in exon 24 and exon 27 of BRCA2, which are firstly identified in this study, might be associated with mammary tumour development in dogs. Especially one SNP in exon 9 of BRCA1 and one SNP in exon 24 of BRCA2 were found to be significantly associated with canine mammary tumours.

The role of ischemia modified albumin in acute pulmonary embolism.

BACKGROUND: Acute pulmonary embolism (PE) is a life-threatening and a relatively common cardiovascular pathology. Although the pathogenesis of PE is well defined, there is no ideal diagnostic biochemical marker. Previous studies showed an increased ischemia modified albumin (IMA) levels in acute PE; however, the relationship between IMA and right ventricular (RV) dysfunction has not been examined. The aim of this study was to evaluate the diagnostic value of IMA and the relationship with RV dysfunction in acute PE. MATERIALS AND METHODS: A total of 145 patients (70 females) with suspected acute PE was enrolled to the study. Eighty-nine patients were diagnosed with acute PE via computed tomographic pulmonary angiography. Sixty-five patients with similar demographic and clinical characteristics were assigned to the control group. All patients were evaluated for RV dysfunction using transthoracic echocardiography. RESULTS: Serum IMA levels were significantly increased in acute PE compared with control group (0.41 ± 0.06 vs. 0.34 ± 0.11, P = 0.001). There was no relationship between serum IMA levels and RV dysfunction. IMA levels were positively correlated with shock index and heart rate. Receiver operating curve analysis demonstrated that serum IMA levels higher than 0.4 put the diagnosis at sensitivity of 53.85% and at specificity of 85.96%. CONCLUSIONS: Although IMA levels are increased in patients with acute PE, it failed to predict RV dysfunction.

Microwave-assisted synthesis and spasmolytic activity of 4-indolylhexahydroquinoline derivatives.

In the present study a microwave-assisted one-pot method was applied for the synthesis of 18 novel condensed 1,4-dihydropyridines carrying the indole moiety. The compounds were achieved by the reaction of appropriate 1,3-cyclohexanedione, substituted indole carboxaldehyde derivative, alkyl acetoacetate and ammonium acetate in methanol, according to a modified Hantzsch reaction. The structure elucidation of the compounds was carried out by spectral methods including X-ray studies. Their spasmolytic activities through calcium channel blockade were assayed on isolated rat ileum. The obtained results indicated that the introduction of the brom atom on the indole ring altered the mentioned activity positively.

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.

Synthesis of cyclopentapyridine and thienopyridine derivatives as potential calcium channel modulators.

In this study, novel condensed 1,4-dihydropyridines bearing cyclopentanone (1-21) or tetrahydrothiophene-1,1-dioxide ring (22-42) with various ester substituents were synthesized via a modified Hantzsch reaction and their calcium channel modulator activities were investigated on isolated rat ileum and rat thoracic aorta. The introduction of a cyclopentanone ring fused to the 1,4-dihydropyridine nucleus and methyl, ethyl and allyl moieties to the ester group led to more active calcium modulators.

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.

Mutation spectrum of fumarylacetoacetase gene and clinical aspects of tyrosinemia type I disease.

Tyrosinemia type I (OMIM 276700) is a rare, autosomal recessive disorder caused by a deficiency in the fumarylacetoacetate hydrolase (FAH) enzyme. This study examined the spectrum of FAH gene mutation in 32 patients with tyrosinemia type I. In addition, clinical and biochemical findings were evaluated to establish a genotype-phenotype relationship in the patients. Mutation screening was performed using a 50K custom-designed resequencing microarray chip (TR_06_01r520489, Affymetrix) and sequencing analysis. Of the 12 different mutations found, 6 are categorized as novel. Three of the mutations-IVS6-1G>A, D233V, and IVS3-3C>G-are the most common in Turkish patients, comprising 25%, 17.1%, and 12.5% of mutant alleles, respectively.Clinical evaluations suggest that the spectrum of symptoms observed in the patients with very early and early disease were of the more nonspecific form, whereas the patients with late-presenting disease had more of the distinctive form over the course of the disease. This study adds support to the notion that the D233V mutation is specific to the Turkish population.

A preliminary trial to determine whether prevention of dark adaptation affects the course of early diabetic retinopathy.

UNLABELLED: This study was designed to determine whether a new form of treatment of diabetic retinopathy (DR) was acceptable to patients and whether reduction in the maximal activity of rods in diabetes could affect the progress of DR. METHODS: In 12 patients, trans-lid retinal illumination of one eye was employed during sleep to prevent the depolarisation of rods and thus reduce their metabolic activity. TECHNIQUES: A headband was used to place a source of chemical light over one eye, with its fellow as a control. MEASUREMENTS: Colour contrast thresholds were measured before and after a period of treatment in treated eyes, and the changes were compared to those in untreated fellow eyes, and areas of 'dark retinal anomalies' (microaneurysms, dot haemorrhages) were measured at the same time points. RESULTS: Patients found this intervention to be acceptable, and no adverse effects were noted. In the majority of cases, and for each outcome measure, the treated eyes improved relative to their fellows. The intervention significantly reduced the tritan thresholds in treated eyes relative to their fellows (P=0.03), and the area of dark retinal anomalies decreased in treated eyes and increased in untreated eyes, with a similar probability. CONCLUSIONS: The study showed that this intervention is safe. Although the study was not powered to study efficacy, the results are promising and consistent with other reports that indicate the retina in DR is suffering from hypoxia; however, further trials should be undertaken.

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.

Sequential expressions of Notch1, Jagged2 and Math1 in molar tooth germ of mouse

The Notch signaling pathway is an evolutionary conserved mechanism that plays an important role in cell-cell communication and cell fate in a wide range of tissues. The mammalian family of Notch receptors consists of 4 members: Notch1/2/3/4. The Notch ligand family consists of 5 members: Delta1/3/4 and Jagged1/2. Math1 encodes a murine Basic helix-loop-helix (bHLH) transcription factor that acts as positive regulator of cell differentiation. Recently, links between Notch and Math1 pathways were demonstrated in various tissues. Expression of Notch1, Jagged2 and Math1 were analyzed in the mouse molar tooth germ during embryonic stage (E) 13 and E15 and during postnatal stage (PN) 1, PN3, PN5, PN10 and PN14 by using in situ hybridization. Positive Notch1 expression was found at the tooth bud during embryonic stages, but its expression was absent from the basal cells in contact with the dental mesenchyme. Jagged2 and Math1 were strongly expressed in differentiated ameloblasts and odontoblasts and Math1 strong expression was even maintained until PN14 stage. Math1 showed the strongest expression. Our results suggest that the Notch1 signaling pathway through Jagged2 could be importantly related to Math1, directing the process of odontogenesis toward cell differentiation.

Sequential expressions of Notch1, Jagged2 and Math1 in molar tooth germ of mouse

The Notch signaling pathway is an evolutionary conserved mechanism that plays an important role in cell-cell communication and cell fate in a wide range of tissues. The mammalian family of Notch receptors consists of 4 members: Notch1/2/3/4. The Notch ligand family consists of 5 members: Delta1/3/4 and Jagged1/2. Math1 encodes a murine Basic helix-loop-helix (bHLH) transcription factor that acts as positive regulator of cell differentiation. Recently, links between Notch and Math1 pathways were demonstrated in various tissues. Expression of Notch1, Jagged2 and Math1 were analyzed in the mouse molar tooth germ during embryonic stage (E) 13 and E15 and during postnatal stage (PN) 1, PN3, PN5, PN10 and PN14 by using in situ hybridization. Positive Notch1 expression was found at the tooth bud during embryonic stages, but its expression was absent from the basal cells in contact with the dental mesenchyme. Jagged2 and Math1 were strongly expressed in differentiated ameloblasts and odontoblasts and Math1 strong expression was even maintained until PN14 stage. Math1 showed the strongest expression. Our results suggest that the Notch1 signaling pathway through Jagged2 could be importantly related to Math1, directing the process of odontogenesis toward cell differentiation.(AU)

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.