Ectodermal dysplasia: important role of complex dental care in its interdisciplinary management.

AIM: Despite the fact that ectodermal dysplasia (ED) is a rare disease, it is often seen in a tertiary clinic. ED affects ectodermal tissues such as skin, hair, teeth, nails, and sweat glands. Patients usually have sparse light hair, deformed nails, and dry skin. They suffer from dental abnormalities such as oligodontia (absence of 6 or more teeth) or complete anodontia; salivation can also be affected. The absence of teeth can be the overriding problem for both patients and their parents, and lead to substantial social ostracisation. This study aims to summarise the facts about the disease, especially dental treatment options based on data drawn from a representative Czech cohort. MATERIALS: The present article summarises the facts about ectodermal dysplasia (ED) in a cohort of 13 patients, where the following were evaluated: clinical manifestations of ED, pathogenic variants detected in selected candidate genes and dental treatment options from child removable dentures to fixed crowns and implants insertion. Three cases are described in detail and demonstrate approaches for different age groups. CONCLUSION: Early diagnosis and active cooperation between the geneticist and dentist will facilitate cooperation with parents and patients and assure secondary prevention. It is preferable that the geneticist understands dental treatment options and can discuss these with patients/parents.

Analysis of DNA methylation and microRNA expression in NUT (nuclear protein in testis) midline carcinoma of the sinonasal tract: a clinicopathological, immunohistochemical and molecular genetic study.

The aim of this study was a detailed clinicopathological investigation of sinonasal NUT midline carcinoma (NMC), including analysis of DNA methylation and microRNA (miRNA) expression. Three (5%) cases of NMC were detected among 56 sinonasal carcinomas using immunohistochemical screening and confirmed by fluorescence in situ hybridization. The series comprised 2 males and 1 female, aged 46, 60, and 65 years. Two tumors arose in the nasal cavity and one in the maxillary sinus. The neoplasms were staged pT1, pT3, and pT4a (all cN0M0). All patients were treated by radical resection with adjuvant radiotherapy. Two patients died 3 and 8 months after operation, but one patient (pT1 stage; R0 resection) experienced no evidence of disease at 108 months. Microscopically, all tumors consisted of infiltrating nests of polygonal cells with vesicular nuclei, prominent nucleoli and basophilic cytoplasm. Abrupt keratinization was present in only one case. Immunohistochemically, there was a diffuse expression of cytokeratin (CK) cocktail, CK7, p40, p63, and SMARCB1/INI1. All NMCs tested negative for EBV and HPV infection. Two NMCs showed methylation of RASSF1 gene. All other genes (APC, ATM, BRCA1, BRCA2, CADM1, CASP8, CD44, CDH13, CDKN1B, CDKN2A, CDKN2B, CHFR, DAPK1, ESR1, FHIT, GSTP1, HIC1, KLLN, MLH1a, MLH1b, RARB, TIMP3, and VHL) were unmethylated. All NMCs showed upregulation of miR-9 and downregulation of miR-99a and miR-145 and two cases featured also upregulation of miR-21, miR-143, and miR-484. In summary, we described three cases of sinonasal NMCs with novel findings on DNA methylation and miRNA expression, which might be important for new therapeutic strategies in the future.

Zirconocene-assisted remote cleavage of C-C and C-O bonds: application to acyclic stereodefined metalated hydrocarbons.

The molding of molecules through remote functionalisation has increasingly become popular as it provides original and flexible synthetic alternatives to classical retrosynthetic analysis. In this Perspective article, we summarise more than a decade of studies in the specific field of remote activation of inert C-C and C-O bonds using the unique abilities of organozirconocene species mainly from our own research group. By demonstrating that these reactions represent novel and powerful entries towards acyclic stereodefined reactive organometallic species, we aim to show the vast opportunities this concept-driven methodology discovery offers.

Copper mediated carbometalation reactions.

Since the first discovery of carbocupration of alkynes in the 1970s a tremendous amount of research has been carried out in this field. The exceptionally high selectivities obtained attribute to the great synthetic value of carbocupration reactions. This tutorial review will present the most important features of carbocupration of alkynes and highlight the most relevant reviews. Then a comprehensive review of copper mediated carbometalation of cyclopropenes will follow. The latter method has received much attention over the last decade as it allows the highly selective construction of poly-substituted cyclopropanes which can be transformed into acyclic derivatives bearing one or multiple tertiary or quaternary carbon stereocenters.

[Phosphate Intoxication after Application of Enema--a Life-threatening Iatrogenic Complication]. / Phosphatintoxikation nach Klysmagabe--eine lebensgefährliche iatrogene Komplikation.

INTRODUCTION: Enemas are used in pediatric patients with constipation. Retention of phosphate containing enemas with prolonged resorption or reduced renal elimination of phosphate can result in life-threatening hyperphosphatemia with subsequent lethal hypocalcemia and acidosis. CASE PRESENTATION: We report the case of a 6-month-old child who received phosphate-containing enema to treat acute aggravation of constipation. The used enema here was not licensed for this age group. Phosphate intoxication resulted (phosphate 19.87 mmol/l) and presented like a sepsis. Hyperphosphatemia was treated by hemodialysis. A non-diagnosed Hirschsprung disease had led to prolonged resorption of phosphate containing enema and to an ileus and toxic megacolon that had to be operated. CONCLUSION: Insufficient elimination of phosphate containing enema can result in lethal or life threatening hyperphosphatemia, hypocalcemia and metabolic acidosis. These can be treated efficaciously by hemodialysis. Because of the high risk of intoxication in using enemas containing phosphate in infants or in patients with gastrointestinal or renal comorbidities, physicians treating constipation should choose enemas without phosphate but with ingredients with lower risk like glycerol or sorbitol in this age group.

The placental mTOR-pathway: correlation with early growth trajectories following intrauterine growth restriction?

Idiopathic intrauterine growth restriction (IUGR) is a result of impaired placental nutrient supply. Newborns with IUGR exhibiting postnatal catch-up growth are of higher risk for cardiovascular and metabolic co-morbidities in adult life. Mammalian target of rapamycin (mTOR) was recently shown to function as a placental nutrient sensor. Thus, we determined possible correlations of members of the placental mTOR signaling cascade with auxologic parameters of postnatal growth. The protein expression and activity of mTOR-pathway signaling components, Akt, AMP-activated protein kinase α, mTOR, p70S6kinase1 and insulin receptor substrate-1 were analysed via western blotting in IUGR v. matched appropriate-for-gestational age (AGA) placentas. Moreover, mTOR was immunohistochemically stained in placental sections. Data from western blot analyses were correlated with retrospective auxological follow-up data at 1 year of age. We found significant catch-up growth in the 1st year of life in the IUGR group. MTOR and its activated form are immunohistochemically detected in multiple placental compartments. We identified correlations of placental mTOR-pathway signaling components to auxological data at birth and at 1 year of life in IUGR. Analysis of the protein expression and phosphorylation level of mTOR-pathway components in IUGR and AGA placentas postpartum, however, did not reveal pathognomonic changes. Our findings suggest that the level of activated mTOR correlates with early catch-up growth following IUGR. However, the complexity of signals converging at the mTOR nexus and its cellular distribution pattern seem to limit its potential as biomarker in this setting.

The use of Tenckhoff catheters for draining of symptomatic lymphoceles: a review of literature and our experience.

BACKGROUND: Lymphoceles are one of the common complications of kidney transplantations. While small, asymptomatic lypmhoceles do not require intervention, however, larger, high-pressure cases can lead to graft dysfunction and are thus an indication for decompression. The aim of this study is to present the drainage using a Tenckhoff catheter as effective treatment for recurrence of symptomatic lymphoceles based on both a single center's experience as well as existing literature. MATERIALS AND METHODS: In our database, two patients were operated with a Tenckhoff catheter for the recurrence of symptomatic lymphocele. A review of MEDLINE in search of cases with lymphoceles treated with Tenckhoff catheterization yielded only five articles published between 1990 and 2014. The reports covered 15 cases in which 11 patients were treated for a primary lymphocele whereas 4 were treated for a recurring lymphocele. RESULTS: There was no evidence of lymphocele recurrence or infections after Tenckhoff catheterization in either the material review or our database. CONCLUSIONS: Intraperitoneal drainage with a Tenckhoff catheter seems to be an effective and safe method for treating recurrent, symptomatic lymphoceles after renal transplantation.

Quinazoline-based tricyclic compounds that regulate programmed cell death, induce neuronal differentiation, and are curative in animal models for excitotoxicity and hereditary brain disease.

Expanding on a quinazoline scaffold, we developed tricyclic compounds with biological activity. These compounds bind to the 18 kDa translocator protein (TSPO) and protect U118MG (glioblastoma cell line of glial origin) cells from glutamate-induced cell death. Fascinating, they can induce neuronal differentiation of PC12 cells (cell line of pheochromocytoma origin with neuronal characteristics) known to display neuronal characteristics, including outgrowth of neurites, tubulin expression, and NeuN (antigen known as 'neuronal nuclei', also known as Rbfox3) expression. As part of the neurodifferentiation process, they can amplify cell death induced by glutamate. Interestingly, the compound 2-phenylquinazolin-4-yl dimethylcarbamate (MGV-1) can induce expansive neurite sprouting on its own and also in synergy with nerve growth factor and with glutamate. Glycine is not required, indicating that N-methyl-D-aspartate receptors are not involved in this activity. These diverse effects on cells of glial origin and on cells with neuronal characteristics induced in culture by this one compound, MGV-1, as reported in this article, mimic the diverse events that take place during embryonic development of the brain (maintenance of glial integrity, differentiation of progenitor cells to mature neurons, and weeding out of non-differentiating progenitor cells). Such mechanisms are also important for protective, curative, and restorative processes that occur during and after brain injury and brain disease. Indeed, we found in a rat model of systemic kainic acid injection that MGV-1 can prevent seizures, counteract the process of ongoing brain damage, including edema, and restore behavior defects to normal patterns. Furthermore, in the R6-2 (transgenic mouse model for Huntington disease; Strain name: B6CBA-Tg(HDexon1)62Gpb/3J) transgenic mouse model for Huntington disease, derivatives of MGV-1 can increase lifespan by >20% and reduce incidence of abnormal movements. Also in vitro, these derivatives were more effective than MGV-1.

Endoscopic drainage/debridement of walled-off pancreatic necrosis--single center experience of 112 cases.

BACKGROUND: Endoscopic drainage of the pancreatic pseudocysts has been accepted as a valid alternative to surgical and percutaneous drainage. Endoscopic treatment of the symptomatic walled-off necrosis was not, however, univocally accepted by all authors. THE AIM: The aim of this study was to assessed the effectiveness and safety of the endoscopic drainage of walled-off necrosis. METHODS AND MATERIAL: Between 2001 and 2011 one hundred and twelve patients with symptomatic walled-off necrosis were treated in the Department of Gastroenterology and Hepatology of the Medical University of Gdansk, using endoscopic drainage. The drainage system was set up by introducing endoprostheses and drains through gastric and duodenal fistulas, transpapillary, and additionally--in cases when the necrosis was spreading outside of the lesser sac--percutaneously. The results and complications of the endoscopic treatment were assessed retrospectively. RESULTS: Initial success was achieved in 104/112 (92.9%) patients. Long term success was achieved in 94/112 (83.9%) patients in intention to treat analysis and 94/102 (90.4%) patients in per protocol analysis. Recurrence of pancreatic fluid collection was observed in 19/97(19.6%) patients. Procedure-related complications were observed in 29/112 patients (25.9%). Most of them were treated conservatively. Procedure-related mortality was 1.8%. CONCLUSIONS: In a large group of selected patients with symptomatic walled-off necrosis, endoscopic drainage enables high success rate with acceptable complication rate and low procedure-related mortality.

Intrauterine growth retardation aggravates the course of acute mesangioproliferative glomerulonephritis in the rat.

Intrauterine growth retardation (IUGR) aggravates the course of acute mesangioproliferative glomerulonephritis (GN) in the rat. Observational studies in children suggest that IUGR may be associated with a severe course of kidney diseases such as IgA nephropathy. We tested the hypothesis that IUGR leads to aggravation of acute mesangioproliferative GN in former IUGR rats. IUGR was induced in Wistar rats by isocaloric protein restriction in pregnant dams. Litter size was reduced to six male neonates in low protein animals (LP) and normal protein animals (NP). At 8 weeks GN was induced by injection of an anti-Thy-1.1 antibody. Rats were killed on days 4 and 14 after induction of GN and kidneys were investigated for inflammation and sclerosis using real-time polymerase chain reaction and histological methods. On day 4 after induction of GN, LP animals showed more glomerulosclerosis and tubulointerstitial lesions. On day 14, inflammatory markers (expression of monocyte chemoattractant protein 1, osteopontin, tumor necrosis factor and interleukin-6), extracellular matrix accumulation and markers of sclerosis (plasminogen activator inhibitor-1 expression, transforming growth factor-beta1 expression, score for glomerulosclerosis, glomerular deposition of collagen I and collagen IV) were more severe in LP animals. Some degree of induction of inflammatory and profibrotic markers was also present in non-nephritic LP animals. However, these rats did not display marked glomerulosclerosis or interstitial fibrosis. We conclude that after IUGR inflammatory damage is aggravated and the reparation of the kidney is impaired during the course of acute mesangioproliferative GN, leading to more sclerotic lesions.

[Experiences in the treatment of benign prostatic hyperplasia with high power potassium-titanyl-phosphate (KTP) laser]. / Wlasne doswiadczenia w leczeniu lagodnego rozrostu stercza wysokoenergetycznym laserem potasowo-tytanowo-fosforowym KTP.

UNLABELLED: Benign prostatic hyperplasia (BPH) exist in about 70% men after 60 years old. High power KTP laser is a new tool for the treatment of BPH. MATERIAL AND METHOD: 49 men were treated by photoselective vaporisation of the prostate (PVP) from August 2003 to May 2004. Thirty patients with follow-up period longer than 12 weeks (12 to 26 weeks) were analyzed. Preoperative prostate volume ranged from 31 to 136 cc. PSA range, estimated before treatment, was normal in all patients (pts). International Prostate Symptom Score (I-PSS) estimated before treatment was over 24 and Quality of Life (QoL) was over 3 in all pts. The maximum peak urinary flow (Qmax) before treatment ranged from 7.2 to 14.1 ml/s. RESULTS: One patient was catheterized with Foley catheter at the finish of the procedure. Two pts required catheterization in the first day after treatment. In two pts increasing of body temperature to 38 degrees C was observed in the first day after treatment. Twenty four hours after treatment haematuria required catheterization was observed in one patient. Seven days after treatment in 4 pts massive haematuria was observed (two required hospitalisation). In one patient because of urinary retention 4 weeks after PVP transurethral resection of the prostate was performed. Four weeks after PVP I-PSS decreased from 24 to 20 and after 12 weeks to 15. The Qmax increased and ranged from 11.3 ml/s to 17.1 ml/s 4 weeks after PVP and 12 weeks after PVP ranged from 15.1 to 22.8 ml/s. CONCLUSIONS: Photoselective vaporization of the prostate reduces I-PSS in all patients 12 weeks after procedure. Short follow-up period and a limited number of patients in study group cannot lead to ultimate conclusions. However the results encourage to undertaking further studies on PVP for the treatment of BPH.

[Value of the photodynamic method in the diagnosis of superficial bladder tumors]. / Znaczenie metody fotodynamicznej w rozpoznawaniu powierzchownych nowotworów pecherza moczowego.

Photodynamic diagnosis (PDD) is one of most precise method of neoplasms recognition. The aim of the study was to estimate the value of 5-amino levulinic acid in diagnosis of superficial bladder tumours. Since 1996 to March 2004, 597 cystoscopies were performed with 5-amino levulinic acid in 151 patients with superficial bladder tumours (102 men and 49 women) aged 19-87 years old. 132 pts were treated by PDD after transurethral resection of bladder tumours (TURB). 749 specimens were taken from mucosa during PDD. Before PDD 50 ml of of 5-amino levulinic acid solution was instilled into bladder. As a source of ultraviolet light (UV) D--Light Storz xenon lamp (405 nm) was used. In 16 pts single PDD was performed in 38 double and in 97 PDD was performed three or more times (3 to 7). All pts were observed 12 months before and after PDD. In 102 from 151 pts in white light cystoscopy (WL) no changes in the bladder mucosa were found. In both kind of light (WL and UV) changes were not observed in 44 pts (29.1%). In 58 pts in WL no changes were observed but in UV places of neoplastic changes in the mucosa were found. In these cases the presence of superficial bladder tumours was confirmed. These changes were pathologically confirmed only in UV in 26 pts. Ta (G1 and G2) changes were confirmed in 52 pts (21 in WL and additionally 31 in UV). T1 changes were confirmed in UV in 26 pts but in WL in 25 pts. In 3 pts T2 changes were confirmed in both UV and WL. Cystoscopy in ultraviolet light (photodynamic diagnosis--PDD) with 5 amino levulinic acid gives more precise diagnosis of superficial bladder tumours then the one in standard white light. Cystoscopy performed to diagnose bladder tumours and early recurrence and new focus of tumours recognition without PDD is less effective. Introduction of superficial bladder tumours photodynamic diagnosis into health care system reduced recurrences and improves results of treatment.

New allene synthesis via carbocupration-zinc carbenoid homologation and beta-elimination sequence.

[reaction: see text] Polysubstituted propadienes are obtained in good to excellent yields by the consecutive carbocupration-homologation-beta-elimination reactions on the easily accessible alkynyl sulfoxides or sulfones. This one-pot reaction also allows the preparation of functionalized allenes.

[Morphology of analgesic nephropathy and its incidence in Czechoslovakia]. / Morfologiia anal'geticheskoi nefropatii i ee chastota v ChSSR.

Basing on the data obtained at 10433 autopsies performed from 1972 to 1981, cases of secondary kidney cirrhosis (chronic pyelonephritis, glomerulonephritis and interstitial nephritis) and renal pelvis cancer were thoroughly analysed. Analgetic nephropathy was found in 13.5% of all chronic interstitial and tubulo-interstitial inflammatory renal diseases, and in cases of bilateral lesions--in 17.2%. The conclusion was made on the basis of morphologic criteria ("chronic" papillary necroses and capillarosclerosis of renal pelvis). There was 41 patient with analgetic nephropathy, who died of chronic renal insufficiency, i.e. 10.6% out of the total number of patients deceased of the same reason for the period mentioned. In the biopsy material reviewed for the same period, that mainly consisted of cases with renal pelvis cancer, analgetic nephropathy was found in 15.7%.