Branchio-oculo-facial syndrome in a newborn caused by a novel TFAP2A mutation.

We present an 18-day old boy with bilateral cervical cutaneous defect in the retroauricular region, low-set and posteriorly rotated ears, bilateral microphtalmia and bilateral pseudocleft of the upper lip. Histopathological evaluation of cervical cutaneous defect showed ulceration on the surface and ectopic thymus tissue in the deep dermis with cortex, medulla and Hassal's corpuscles. Clinical findings led to the diagnosis of Branchio-oculo-facial syndrome, characterized by branchial defects (erythematous cutaneous defects in cervical region), ocular anomalies (microphthalmia, anophthalmia, lacrimal duct obstruction, coloboma, cataract, ptosis) and facial defects (cleft lip and/or palate, pseudocleft or abnormal philtrum). DNA sequencing showed a novel heterozygous mutation, c.731T>C (p.L244P), in TFAP2A gene confirming the diagnosis of this rare autosomal dominant developmental disorder with variable clinical findings.

Langerhans Cell Histiocytosis: Single Center Experience of 25 Years.

OBJECTIVES: To review a single center outcome of patients with Langerhans Cell Histiocytosis diagnosed at a tertiary referral hospital from Turkey.Methods: The files between 1989 and 2015 of 80 patients with LCH were retrospectively analyzed. RESULTS: During the 25 years, 80 patients were diagnosed with LCH. The median age at diagnosis was 53 months (2-180 months) and the median follow-up time of patients was 10 years and 9 months (24 months-25 years). Bone was the most frequently affected organ (n:60, 75%). Initially, 43 patients (54%) had single system (SS) disease, 20 patients (25%) had multisystem (MS) disease without risk organ involvement (MS-RO-), and 17 patients (21%) had a multisystem disease with risk-organ involvement (MS-RO+). The overall survival (OS) rate was 91%, and event-free survival (EFS) rate was 67% at 10 years. 10-year OS rate was lower for patients with MS-RO+ (65%) when compared to those with, MS-RO-, and SS (100%, 97%, p value=<0.001). The overall survival rate was also lower in patients with lack of response to systemic chemotherapy on 12th week (p=<0.001), younger age (<2 years) at presentation (p=<0.02), skin involvement (<0.001) and lack of bone lesions at presentation (<0.001). DISCUSSION: In the group with MS-RO+, OS is significantly low compared to other groups. Further efforts are warranted to improve survival in MS-RO+ patients.

Epidural metastasis of Ewing's sarcoma: a rare localisation.

Epidural spinal metastasis of Ewing's sarcoma is rarely observed. We report on a rare case of purely epidural spinal metastasis of Ewing's sarcoma with pain and paraplegia, and describe the treatment and final outcome of the patient.

An unusual long-term complication of burn injury: malignant fibrous histiocytoma developed in chronic burn scar.

Development of malignant tumors in chronic burn wounds is a well-known complication. These tumors are almost always squamous cell carcinomas, although other types of malignancies such as basal cell carcinoma, malignant melanoma and sarcomas can be seen rarely. There are only three previously reported cases of malignant fibrous histiocytoma developed in chronic burn scar in the literature. Two cases with malignant fibrous histiocytoma developed in chronic, badly treated burn wounds are presented. One of the tumors was multifocal and overexpression of the p53 gene was present. Both tumors were excised widely and skin grafted. Regional lymph node dissection was performed in one case. One of the patients died due to tumor recurrence and lymphatic metastases. These cases represent a very uncommon complication of burn injury and indicate the importance of the appropriate primary treatment of the burn wound.

A dynamic study of the thermal components in electrical injury mechanism for better understanding and management of electric trauma: an animal model.

The thermal effects of acute electric trauma to living cells show some variation patterns and kinetics for different body components (muscle, bone, blood-vein and skin). Thermal energy transfer is random with no preferred directions, but electrical energy transfer is vectorial in the direction of the current. In the present study, a total 50 white male Wistar Albino rats, body weight 250-300 g, have been used to study electrical injury mechanism with subsequent change in muscle perfusion at different post-traumatic stages. The muscle temperature was found to increase with a sudden jump from 35.3+/-1.2 to 75.2+/-7.6 degrees C. The bone temperature increased from 35.2+/-1.4 to 45.8+/-1.2 degrees C and decayed slowly within 600+/-90 s. The venous blood curves show a similar pattern to that of muscle with a sudden jump of temperature from 36.4+/-.9 to 40.5+/-3.1 degrees C. The core temperature showed a flat pattern with a slight increase from 36.1+/-0.8 to 37.3+/-0.6 degrees C and the peak temperature was found after 70+/-10 s. From the scintigraphic study, muscle perfusion was found to be a minimum 72 h after electric shock. The right hind limbs of all the rats (ground) exhibited more intense histopathological damages (electric burns) than the left fore limb (source).

Congenital short bowel syndrome associated with appendiceal agenesis and functional intestinal obstruction.

Congenital short bowel with functional intestinal obstruction and absence of appendix vermiformis is a very rare condition with poor prognosis. Seventeen cases of congenital short bowel have been reported previously in the literature. The etiology is unknown. In this report, a case of congenital short bowel, combined with functional intestinal obstruction, mal-rotation, and absence of the appendix vermiformis, is presented and the pathogenesis discussed.

Endoscope assisted removal of cementoossifying fibroma in the paranasal sinuses in a five-year-old girl.

We report a five-year-old girl with a sinonasal cementoossifying fibroma with CT findings that reveal the invasion of all paranasal sinuses and the remodeling of facial bones. It was possibly a congenital lesion and caused a slowly progressive nasal obstruction and anosmia. Tumor removal with transnasal endoscopic approach was applied and total removal of the mass was accomplished. It was found out to be the cementoossifying fibroma of the paranasal sinuses when the results of the pathological examinations were obtained.

The sex hormone receptors in the bladder in childhood - I: preliminary report in male subjects.

The sex hormone receptors (oestrogen, androgen, progesterone) in the bladder were demonstrated in clinical studies by various authors in adult patients. But the presence of these receptors in childhood had not been investigated. The aim of this study was to assess the presence of sex hormone receptors in the bladder of male subjects in childhood. The study included 20 bladder biopsies from a total of 15 children. Biopsies were taken during open surgery and/or cystoscopic procedures for various indications from the bladder dome, trigonum and in the region of the bladder neck. All biopsies were routinely fixed and processed for histopathological assessment and investigated immunohistochemically to determine the sex hormone receptors in the bladder. The sex hormone receptors were demonstrated with different densities and locations. In particular, sex hormone receptors were found very frequently in biopsies taken from the bladder neck. Overall receptor positivity in the specimens was 90 % for progesterone, 65 % for androgen and 25 % for oestrogen. There was no receptor expression in the deeper tissues of the bladder wall. This preliminary study demonstrated: 1. Sex hormone receptors are present in children; 2. There was a female sex hormone (progesterone, oestrogen) receptor expression in male subjects; 3. The receptors are mainly localised at the bladder neck and in transitional epithelium of the bladder wall. We think that the sex hormone receptor map may be useful in the evaluation of lower urinary tract and specially bladder neck disorders in childhood in the future.

Changes in the threshold voltage and alterations of smooth-muscle physiology after bladder outlet obstruction.

The purpose of this study was to determine the resultant changes in the bladder function after partial bladder outlet obstruction (BOO), with particular emphasis on the threshold voltage and on the role of NO. A total of 12 adult rabbits were used in the study. New Zealand-type rabbits were subjected to no intervention and 3 weeks duration of a partial outlet obstruction. They underwent an in vivo cystometric evaluation before and after the BOO, histological studies, bladder-strip stimulation studies using acetylcholine, electrical field stimulation, and relaxation studies using NO donor nitroprusside. Statistical significance was determined by two-way ANOVA for multiple variations and Student's t-test. Histology sections demonstrated smooth-muscle hypertrophy, hyperemia of the vessels in the wall and widely set mononuclear cell infiltration in the rabbits with partial BOO. Cystometry showed markedly decreased bladder capacities, and decrease of compliance from 4.3 +/- 1.8 to 1.6 +/- 0.3 in the obstructed group. Tissue bath studies demonstrated no meaningful change with cholinergic stimulation, increased contractility in response to electrical field stimulation, and increased threshold voltage values from 57.5 to 93.3 compared to controls. Nitroprusside did not induce relaxation of the neostigmine and acetylcholine-precontracted bladder in all animals. Hypertrophy was observed due to adaptation of the detrusor against the obstruction. During this adaptation period, bladder capacity decreases and the elasticity disappears, thus causing higher pressures with lesser volumes. In other words, compliance decreases. The neurogenic damage can be shown with increasing values of threshold voltage, and higher voltages are needed to start a contraction. Nitroprusside has no inhibitory effect on smooth-muscle tone in the rabbit bladder.

Lymphangiosarcoma in chronic lymphoedema. Stewart-Treves syndrome.

A case of post-mastectomy lymphangiosarcoma is reported. Lymphangiosarcoma is an extremely rare but highly lethal complication of chronic lymphoedema. Our patient was treated by amputation and died 6 months later. Treatment of post-mastectomy lymphangiosarcoma is still unsatisfactory. Early recognition and radical ablative surgery seem to provide best chance for survival.

Congenital generalized infantile myofibromatosis and neonatal hemochromatosis. An autopsy case report.

An autopsy case of congenital infantile myofibromatosis and neonatal hemochromatosis is reported. A thirty-six-hour-old baby girl had multiple subcutaneous nodules in addition to multiple visceral involvement of heart, lungs, pharynx, larynx, stomach, small bowel, large bowel, pancreas, kidneys, spleen, thyroid, adrenal glands, lymph nodes, peripheral nerves, meninges and soft tissues. In these tumoral nodules, three types of histological patterns were observed: 1-hemangiopericytoma-like, 2-mixed, and 3-pure spindle cell. Tumor cells were immunohistochemically positive for actin, and negative for desmin, muscle-specific antigen, and estrogen, related protein. The histological and immunohistochemical findings of the case suggested that a close relationship may exist between infantile myofibromatosis and infantile hemangiopericytoma. In addition to infantile myofibromatosis, neonatal hemochromatosis characterized by iron deposition in parenchymatous organs such as liver, pancreas, lungs, thyroid, and adrenal glands was another important characteristic of the case.

Causes of fetal and neonatal death.

Autopsy was performed on 601 out of 654 (91.9%) fetus and newborn cases of death which occurred during a four-year period between 1988-1991 at Istanbul University Cerrahpasa Faculty of Medicine, Gynecology Department and Neonatal Unit. According to autopsy findings, among the main causes of death in newborns were infection, hyaline membrane disease, congenital anomalies, perinatal hypoxia and immaturity, and in the fetal period, perinatal hypoxia, asphyxia and congenital anomalies. In these cases, when pathologic and clinical findings were examined, it was observed that in 204 out of 301 newborn cases (67.8%) the clinical findings were well correlated with the autopsy findings; in 97 (32.2%) of the remaining cases the main disease and primary causes of death could not be determined through clinical findings; in 69 (23%) cases, in addition to the clinical diagnosis on autopsy, minor defects were determined on autopsy which were not directly related to death. When clinical and autopsy findings were compared, diagnoses with the highest discordance were pulmonary hemorrhage infection and intracranial hemorrhage.

Maternal cocaine abuse resulting in necrotizing enterocolitis--an experimental study in a rat model.

The aim of this study was to assess the relation between the use of cocaine during pregnancy and development of necrotizing enterocolitis in a rat model. Different doses of cocaine HCl were given to pregnant Wistar Albino rats during gestation. Total number of live births, mean birth weight, mean placental weight and histopathological examination of the maternal uterus, placenta, embryonal G-I tract and liver were investigated. These results were compared with a control group and showed that the number of live births, mean birth weight and mean placental weight were lower than in non-cocaine controls. Histopathologic examinations revealed severe inflammation and vascular changes in the uterus and placenta. We also observed focal necrosis, necrobiosis, cellular debris, haemorrhage, inflammatory reactions in the G-I tract of embryos. These findings indicate that maternal cocaine abuse should probably be considered a major risk factor for development of NEC in baby rats and embryos.

The roles of extracellular matrix proteins, apoptosis and c-kit positive cells in the pathogenesis of ureteropelvic junction obstruction.

AIM: To investigate histopathological changes in ureteropelvic junction obstruction (UPJO) from an etiological perspective. PATIENTS AND METHODS: Medical records of patients with UPJO were reviewed and pathological specimens collected. Nephrectomy materials from forensic autopsies were taken as controls. Specimens were assessed with light microscopy. Fibronectin, type 4 collagen, laminin, Bax and Bcl-2 expression for apoptosis, together with interstitial cells of Cajal determination with c-kit were determined immunohistochemically. Staining scores were evaluated semiquantitatively. Results were evaluated using Mann-Whitney U-test. RESULTS: Control group comprised 14 children (median age, 3.5 years; 6 months-17 years). Study group comprised 22 children with UPJO (median age, 9 months; 1 month-10 years). Light microscopy revealed non-specific inflammation, epithelial proliferation and atrophy with fibrosis in the smooth muscle of the UPJ in all patients. Fibronectin, type 4 collagen and laminin were found to be significantly increased in UPJO at the intrafascicular space of smooth muscle and the matrix of stroma. Bcl-2 expression was increased in UPJO. c-Kit was unable to stain interstitial cells of Cajal, but staining for mast cells was significant. CONCLUSIONS: High expression of fibronectin, laminin and type 4 collagen may indicate a relation to the pathogenesis of UPJO. Defective kidney morphogenesis, during branching and tubulogenesis of ureteric bud, may be responsible for this congenital pathology.

Expression of estrogen and androgen receptors in children with hypospadias: preliminary report.

This investigation was conducted to evaluate the presence of estrogen and androgen receptors in penile tissues of patients with hypospadias. The biopsy specimens from prepuce, glans, and urethral plate were sampled during the hypospadias surgery in five patients and were analyzed immunohistochemically. Twelve specimens were investigated for the presence of estrogen or androgen receptors (n: 24); the result was negative in 9 (37%) and positive in 15 (63%). Estrogen receptors were present in 10 specimens (42%) (prepuce: 5, glans: 3, and urethral plate: 2). Androgen receptors were present in 5 specimens (21%) (prepuce: 3, glans: 1, and urethral plate: 1). There was expression of both estrogen and androgen receptors in 5 specimens and only estrogen receptors in the remaining 5. Dominant expression of estrogen receptors in penile tissues of children with hypospadias may be the postnatal finding of disrupted estrogen and androgen receptor interaction during the intrauterine development of external genitalia.

Appendix interposition in the treatment of severe posterior urethral injuries.

The aim of this study was to investigate the applicability of the Mitrofanoff principle in the treatment of severe posterior urethral injuries and determine the feasibility of this technique with its early and late postoperative results. A total of 27 New Zealand rabbits (12 male and 15 female) was used (mean weight 2,272 +/- 343 gm.). Using general anesthesia the proximal part of the posterior urethra was transected completely and a 1 cm. segment was excised. A 2 cm. segment of appendix with its intact vascular pedicle was meticulously mobilized and anastomosed to the proximal and distal site of the urethra. Excretory urograms, voiding cystourethrograms, urodynamic investigation and histopathological examination were performed postoperatively. The fertility of the male rabbits was examined in the late postoperative period as well. These results were compared with those of a control group. There was no problem concerning voiding patterns in the pedicled appendiceal flap group. Excretory urograms revealed a properly functioning urinary system. Voiding cystourethrograms showed a normal bladder capacity and voiding pattern, and an intact urethra. Urodynamic analysis was within normal limits except for a decrease in bladder volume. An intact urethral lumen without any strictures or fibrosis was demonstrated histopathologically. No calculus, mucus formation or urinary tract infection was observed in the late postoperative period. Fertility problems were noted in male rabbits. This animal experiment suggested that the pedicled appendiceal flap technique could be used for the treatment of severe forms of posterior urethral injuries.

Rectus abdominis muscle flap (RAMF) technique for the management of large bladder defects: urodynamic findings in a rabbit model.

OBJECTIVE: To investigate the efficacy of the rectus abdominis muscle flap (RAMF) technique for the closure and augmentation of small, inelastic bladder extrophies using a rabbit model with a large bladder defect. MATERIALS AND METHODS: Fifteen New Zealand White rabbits were studied in two groups; nine rabbits in group 1 underwent resection of 65% of the bladder and then bladder augmentation using a full-thickness RAMF, including peritoneum, and six rabbits in group 2 (control) underwent a similar bladder resection but the bladder remnant was closed primarily. Urodynamic investigations were carried out in both groups preoperatively and 4 weeks after surgery. Intravenous pyelography (IVP), voiding cystourethrography (VCUG), urodynamic and histopathological investigations were also carried out for up to 4 months after surgery. RESULTS: As assessed by IVP, the urinary system appeared normal, with no signs of upper urinary tract dilatation and VCUG showed a normal voiding pattern. After surgery, the bladder capacity and compliance decreased in both groups, but both variables partially recovered in group 1, although not significantly. CONCLUSIONS: This animal model indicates that the RAMF technique is a suitable alternative for the management of large bladder defects and bladder exstrophies with small, inelastic, non-compliant bladders.

Urodynamic investigations in reversed ileal seromuscular enterocystoplasty: an experimental study in a rabbit model.

OBJECTIVE: To investigate the efficacy of the reversed ileal seromuscular enterocystoplasty (RISMEC) technique and assess the urodynamic findings. MATERIALS AND METHOD: A large bladder defect was created in 12 New Zealand White rabbits: in six the bladder was closed primarily (control group) and in the remaining six the bladder was augmented using the RISMEC technique combined with omentoplasty. The results were assessed using intravenous pyelography (IVP), voiding cysto-urethrography (VCUG), histopathological investigations and urodynamic studies after 4 and 12 weeks. RESULTS: The IVP and VCUG revealed an apparently normal urinary system and voiding pattern in both groups. Histopathologically, in all rabbits undergoing RISMEC, the serosal surface of the reversed ileum was lined with transitional urinary epithelium; there was no evidence of severe fibrosis, inflammation, stone or mucus-production. Urodynamic studies showed a significant decrease in the mean bladder capacity in the controls, but no significant change in the RISMEC group. The mean bladder compliance decreased from 5.85 to 1.36 mL/cmH2O in the controls (P < 0.02) but there was no significant decrease in compliance in the RISMEC group. CONCLUSION: The results suggest that in this rabbit model, the RISMEC technique combined with omentoplasty increases bladder capacity with minimal graft shrinkage; the peritoneal surface is rapidly covered with transitional epithelium and the integrity of the kidneys preserved. Urodynamic investigations showed neobladders with adequate storage capacity, low intravesical pressures and improved compliance rates.

Nucleolar organizer regions in pituitary gland adenomas.

Nucleolar organizer regions are DNA segments concerned with the synthesis of ribosomal RNA (rRNA). Some specific proteins related to NORs can be demonstrated by a silver technique and are then referred to as Ag-NORs. The mean number of Ag-NORs per cell has been used as a marker of cell proliferation in recent years and there is some evidence to suggest that Ag-NOR counts can be used to differentiate between normal and neoplastic cells. Paraffin block sections of 42 pituitary gland adenomas and 24 normal adult pituitary glands have been examined using the Ag-NOR staining technique. Touch imprints of nine adenomas and 12 normal adult pituitary glands were also examined using the same Ag-NOR staining technique. Using light microscopy at x2000 magnification, the Ag-NORs were located as black dots in the cell nuclei and the mean number of Ag-NORs per cell was determined. No significant difference was observed between blocked sections and imprints of adenomas or between imprints and paraffin sections of normal glands. However, a significant difference was observed between the mean number of Ag-NORs in pituitary gland adenomas and normal glands in paraffin block sections and touch preparations (P less than 0.001). The modified Ag-NOR technique can be a useful aid in the differential diagnosis between normal pituitary gland tissue and pituitary adenomas, especially during surgical operations.

Effects of some nonsteroidal anti-inflammatory drugs on articular cartilage of rats in an experimental model of osteoarthritis.

We evaluate the chondrotoxic effects of some nonsteroidal anti-inflammatory drugs (NSAIDs) on articular cartilage in an experimental model of osteoarthritis (OA). Each of 40 Sprague-Dawley rats weighing 0.250 kg and 12 weeks old received weekly injections of sodium iodoacetate (1 mg/0.1 ml NaCl) in the right knees for 8 weeks to induce an experimental model of OA. The left knees served as controls. Four groups were formed of ten rats each. The control group received no medicine. In the other three groups, tiaprofenic acid, diclofenac, and indomethacin were given orally for 12 weeks. At the end of the 20th week, the complete groups were sacrificed and histologic evaluation performed. In the right knees of the control group, specific morphologic changes for OA were observed. Of the three NSAIDs tested, indomethacin was found to have deleterious effects on articular cartilage of both left and right knees. Diclofenac caused a statistically significant increase in the severity of most of the osteoarthritic parameters that were examined in the right knees, whereas tiaprofenic acid was observed to have some beneficial influences on the articular cartilage of right knees. Both diclofenac and tiaprofenic acid displayed the same deleterious effects on articular cartilage of left knees. We conclude that, in the prescription of NSAIDs for OA, it would be appropriate to choose a drug with a protective effect on chondrocytes and articular cartilage.