Multiple idiopathic external cervical root resorption in patient treated continuously with denosumab: a case report.

BACKGROUND: External root resorption is an irreversible loss of dental hard tissue as a result of odontoclastic action. Multiple external cervical root resorptions in permanent teeth are rare. The exact cause of external cervical root resorption is unclear. It is currently well established that RANK/RANKL signaling is essential for osteoclastogenesis and osteoclast-mediated bone resorption. Denosumab is an anti-RANKL antibody used for the treatment of postmenopausal osteoporosis. RANK/RANKL pathway suppression by denosumab is expected to suppress the activity of clastic cells responsible for hard tissue resorption involving both osteoclasts and odontoclasts. CASE PRESENTATION: This case report demonstrates aggressive and generalized idiopathic external cervical root resorption that started and advanced during ongoing antiresorptive therapy with the human monoclonal RANKL-blocking antibody denosumab without discontinuation of therapy in a 74-year-old female patient treated for postmenopausal osteoporosis. The extent of resorptive defects was too large and progressively led to fractures of the teeth. The number of teeth involved and the extend of destruction excluded conservative treatment. The affected teeth had to be extracted for functional prosthetic reconstruction. CONCLUSIONS: This finding suggests that treatment with denosumab may be associated with severe and aggressive odontoclastic resorption of multiple dental roots despite an adequate inhibitory effect on osteoclasts in the treatment of osteoporosis. The RANKL-independent pathways of clastic cell formation are likely to be involved in this pathological process.

Newly Developed Psoriasis in a Patient with Telangiectasia Macularis Eruptiva Perstans and Systemic Mastocytosis Treated with Interferon.

The authors present a rare case of a patient with telangiectasia macular eruptiva perstans, with confirmed D816V mutation which later progressed to systemic mastocytosis confirmed by trepanobiopsy. First-line treatment - phototherapy - had to be stopped, and systemic treatment with interferon alpha-2a was initiated. The treatment was successful with regression of skin lesions as well as mast cell infiltrates in the bone marrow. However, the treatment was complicated by the onset of psoriasis lesions.

Insulinoma presenting with postprandial hypoglycemia and a low body mass index: A case report.

BACKGROUND: Insulinomas are the most common type of functioning endocrine neoplasms of the pancreas presenting hypoglycemic symptoms. Patients characteristically develop symptoms while fasting, but some patients have reported symptoms only in the postprandial state. Repeated and prolonged hypoglycemic episodes can reduce the awareness of adrenergic symptoms, and patients may have amnesia, which delays diagnosis. CASE SUMMARY: We describe a case of a 24-year-old underweight patient who showed hypoglycemic symptoms for almost 6 years. Although patients with insulinoma characteristically develop symptoms while fasting, this young man had hypoglycemic symptoms up to one hour postprandially, especially after high-sugar meals and after physical activity. The fasting tests and imaging methods performed at local hospitals were evaluated as negative for abnormal results. However, brown adipose tissue exhibited increased metabolic activity, and some muscle groups had histological changes as indicated by positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography. Glycogen deficiency was also histologically confirmed. The patient's symptoms progressed over the years and occurred more frequently, i.e., several times a month, and the patient had reduced awareness of adrenergic symptoms. The follow-up fasting test was positive, and the imaging results showed a tumor in the head of the pancreas. The patient underwent laparotomy with enucleation of the insulinoma. CONCLUSION: Weight gain and fasting hypoglycemia are not necessarily characteristics of insulinoma. In prolonged cases, adrenergic symptoms can be suppressed.

Gossypiboma mimicking recurrent mandibular tumor: case report.

Gossypiboma is not a commonly known surgical complication. It is a tumorous lesion usually caused by hemostatic material used in surgery. Such lesions are most commonly described after abdominal surgery. In this case report, the authors describe a case of a 17 year old female patient, operated for a mandible tumor. Histopathologically it was an ameloblastoma. The patient was treated lege artis, with the use of Surgicel® felt (Surgicel FibrillarTM Absorbable Hemostat). After two months, the young woman returned to clinics with a tumorous lesion at the same location. On the CT scan the lesion appeared to be a recurrence of the originally diagnosed ameloblastoma. Histopathologically, the lesion consisted of a foreign material with surrounding granulation tissue and massive inflamation. The foreign material had an atypical structure. Subsequent consultations and consensus at the clinic confirmed that it was a haemostatic foreign material with a surrounding hyper-inflammatory response mimicking a tumor, known in the literature under various names, most often as gossypiboma or textiloma.

Antineoplastic effects of clove buds (Syzygium aromaticum L.) in the model of breast carcinoma.

It is supposed that plant functional foods, rich in phytochemicals, may potentially have preventive effects in carcinogenesis. In this study, the anticancer effects of cloves in the in vivo and in vitro mammary carcinoma model were assessed. Dried flower buds of cloves (CLOs) were used at two concentrations of 0.1% and 1% through diet during 13 weeks after the application of chemocarcinogen. After autopsy, histopathological and immunohistochemical analyses of rat mammary carcinomas were performed. Moreover, in vitro evaluation using MCF-7 cells was carried out. Dietary administered CLO caused the dose-dependent decrease in tumour frequency by 47.5% and 58.5% when compared to control. Analysis of carcinoma cells in animals showed bcl-2, Ki67, VEGFA, CD24 and CD44 expression decrease and Bax, caspase-3 and ALDH1 expression increase after high-dose CLO administration. MDA levels were substantially decreased in rat carcinomas in both CLO groups. The evaluation of histone modifications revealed increase in lysine trimethylations and acetylations (H4K20me3, H4K16ac) in carcinomas after CLO administration. TIMP3 promoter methylation levels of CpG3, CpG4, CpG5 islands were altered in treated cancer cells. An increase in total RASSF1A promoter methylation (three CpG sites) in CLO 1 group was found. In vitro studies showed antiproliferative and pro-apoptotic effects of CLO extract in MCF-7 cells (analyses of cytotoxicity, Brdu, cell cycle, annexin V/PI, caspase-7, Bcl-2 and mitochondrial membrane potential). This study showed a significant anticancer effect of clove buds in the mammary carcinoma model in vivo and in vitro.

Microvascular changes in relation to inflammation and epidermal hyperplasia in chronic cutaneous lesions of psoriasis vulgaris.

Epidermal proliferation, inflammatory changes and microvascular augmentation are prominent features of chronic cutaneous psoriatic lesions. The objective of this study was the investigation of blood and lymphatic microvascular changes in relation to epidermal changes and inflammatory infiltration in dermis. Immunohistochemical analysis with antibodies to CD34, podoplanin, vascular endothelial growth factors - A and C (VEGF-A and C) and morphometric software were used for quantification of the following parameters: blood and lymphatic vessel area (BVA and LVA), VEGF - A and VEGF-C positive area, inflammatory cell infiltration in dermis (CIA) and epidermal area (EA). In comparison to healthy skin psoriatic lesions showed remarkable elevation of all measured parameters with the following average increase: BVA (2.8-times increased), LVA (2.6-times increased), VEGF-A and VEGF-C area (in epidermis 29-times and 19- times increased, in dermis 25-times and 15- times increased, respectively ), and EA (3-times increased). Statistical analysis revealed significant positive correlation between CIA and EA in psoriatic samples. Blood vessels area and VEGF - A expression in epidermis showed mild positive correlation with epidermal hyperplasia and weak positive correlation with dermal inflammatory infiltration. VEGF - A expression in epidermis also significantly correlated with blood vessels area. As for the lymphatic microcirculation we found a statistically significant positive correlation between lymphatic vessels area and the cellular infiltration in dermis but only weak correlation with epidermal hyperplasia. We hypothesize that angiogenesis in psoriasis is to a greater extent responding to epidermal hyperplasia and in a lesser way to inflammatory infiltration in dermis. However, lymphangiogenesis is significantly related to dermal inflammatory infiltration.

Treatment of Ormond Disease and Idiopathic Membranous Glomerulonephritis by using Rituximab.

Treatment of retroperitoneal fibrosis usually involves corticosteroids with or without other immunomodulating medications or tamoxifen.  Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving complete remission of proteinuria in patients with idiopathic membranous nephropathy. We describe a case of a 45 years old man with idiopathic membranous glomerulonephritis (with proteinuria of more than 30 grams/24 hours) and simultaneously with idiopathic retroperitoneal fibrosis (with large number of cells CD20 in the histologic image). The patient did not tolerate the treatment by cyclophosphamide, and as rescue therapy, administration of rituximab was indicated with excellent effect. We recorded promptreduction of proteinuria and significant reduction of retroperitoneal fibrosis. Rituximab is effective in treatment of idiopathic retroperitonea lfibrosis with positivity of CD20 cells, as well as in treatment of idiopathic membranous glomerulonephritis.

[Lungs "Hassalloid´s-like" bodies in children with epidermolysis bullosa junctionalis and bart´s syndrome]. / "Hassalloidné" telieska v plúcach u dietata s epidermolysis bullosa junctionalis a s Bartovým syndrómom.

Epidermolysis bullosa and Bart´s syndrome are fairly accurately documented diseases by histopathology. In the article the authors describe interesting and hitherto undescribed phenomenon in the lungs male infant with epidermolysis bullosa junctionalis and Barts syndrome, who died 17 days after birth and 13 days after surgery for pyloric atresia, on multiorgan failure within basic congenital diseases.Histologically in lung alveoli was found to the massive presence of foamy macrophages and numerous globoid formations resembling morphological and immunohistochemical "Hassall´s" bodies in a thymus of the newborn. It was a acidophillic spherical bodies concentric tracks in the connective tissue with focal presence of fibrin, as a unique proof CKAE1/AE3 and CKHMW positive epithelial cells and CD68-positive histiocytic elements. An interesting finding was the follicular skin structure in the center "hassalloid´s-like" body, which suggests an aspiration components of the skin during intrauterine life.Normal Apgar score at birth of the child (10/10/10 s.) and severe histological features on the death of the child testify for the first pathogenetic formation "hassalloid´s-like" bodies in the lungs during the 17-day life of a disabled child.

[Skin cell response after jellyfish sting]. / Kozná bunková reakcia po popálení medúzou.

INTRODUCTION: Jellyfish burning is not commonly part of the professional finding in the central Europe health care laboratory. Holiday seaside tourism includes different and unusual presentations of diseases for our worklplaces. Sea water-sports and leisure is commonly connected with jellyfish burning and changes in the skin, that are not precisely described. AIM: Authors focused their research on detection of morphological and quantitative changes of some inflammatory cells in the skin biopsy of a 59-years-old woman ten days after a jellyfish stinging. Because of a comparison of findings the biopsy was performed in the skin with lesional and nonlesional skin. METHODS: Both excisions of the skin were tested by imunohistochemical methods to detect CD68, CD163, CD30, CD4, CD3, CD8, CD20 a CD1a, to detect histiocytes, as well as several clones of lymphocytes and Langerhans cells (antigen presenting cells of skin), CD 117, toluidin blue and chloracetase esterase to detect mastocytes and neutrophils. Material was tested by immunofluorescent methods to detect IgA, IgM, IgG, C3, C4, albumin and fibrinogen. Representative view-fields were documented by microscope photocamera Leica DFC 420 C. Registered photos from both samples of the skin were processed by morphometrical analysis by the Vision Assistant software. A student t-test was used for statistical analysis of reached results. RESULTS: Mean values of individual found cells in the sample with lesion and without lesion were as follows: CD117 -2.64/0.37, CD68-6.86/1.63, CD163-3.13/2.23, CD30-1.36/0.02, CD4-3.51/0.32, CD8-8.22/0.50, CD3-10.69/0.66, CD20-0.56/0.66, CD1a-7.97/0.47 respectively. Generally mild elevation of eosinofils in lesional skin was detected. Increased values of tested cells seen in excision from lesional skin when compared with nonlesional ones were statistically significant in eight case at the level p = 0.033 to 0.001. A not statistically significant difference was found only in the group of CD163+ histiocytes. CONCLUSION: Authors detected numbers of inflammatory cells in lesional skin after the stinging by a jellyfish and compared them with the numbers of cells in the nonlesional skin of the same patient. Statistically significant differences were seen in the level of selected inflammation cells and numerically documented changes of cellularity in the inflammatory focus were caused by a hypersensitivity reaction after jellyfish injury in the period of 10 days after attack.

Quantitative comparison of angiogenesis and lymphangiogenesis in cutaneous lichen planus and psoriasis: immunohistochemical assessment.

Recent experimental studies revealed that angiogenesis and lymphangiogenesis are closely related to chronic inflammation. The present study aims to evaluate quantitative changes of blood and lymphatic microcirculatory beds in cutaneous lichen planus (CLP) and psoriatic lesions using immunohistochemical analysis with antibodies to CD34, D2-40 and VEGF. Morphometric software was used to determine the area of blood and lymphatic vessels (BVA and LVA) and also the VEGF positive area. Statistical analysis of these parameters confirmed a significant enlargement of both the blood and lymphatic microcirculatory beds in psoriatic and CLP lesions. BVA in CLP lesions was increased by 56% however this augmentation was not as great as in psoriatic lesions where BVA was increased by 123%. Interestingly, LVA in psoriatic and CLP lesions was increased equally by 85%. The strongest VEGF expression was detected in psoriatic lesions, with lower, but still significant, overexpression in CLP lesions. VEGF-C was significantly increased in both psoriatic and CLP lesions in comparable level. Noticeably higher VEGF and VEGF-C expression was observed in the epidermis than in the dermis. Finally, our results indicate that the level of angiogenesis is considerably greater in psoriatic lesions than in CLP lesions, but the level of lymphangiogenesis is equal in both psoriatic and CLP lesions.

Quantitative immunohistochemical assessment of blood and lymphatic microcirculation in cutaneous lichen planus lesions.

Latest advances have brought to light the hypothesis that angiogenesis and lymphangiogenesis are tightly connected to some chronic inflammatory diseases. The present study focuses on immunohistochemical assessment of the quantitative changes in the blood and lymphatic microcirculatory bed in common chronic dermatosis - cutaneous lichen planus. Double immunohistochemistry with CD34 and podoplanin antibodies was used to detect blood and lymphatic endothelium, while anti-human VEGF was used for the observation of a key angiogenesis and lymphangiogenesis inducer. Morphometric analysis was performed with QuickPhoto Micro image analysis software. Results confirmed statistically significant enlargement of both the blood and lymphatic microcirculatory beds. Compared to healthy skin, cutaneous lichen planus lesions revealed 1.6 times enlarged blood microcirculatory bed and 1.8 times enlarged lymphatic microcirculatory bed. Vascular endothelial growth factor (VEGF) expression in lesional skin was significantly higher in the epidermis (19.1 times increase) than in the dermis (10.3 times increase). These findings indicate a tight association of angiogenesis and lymphangiogenesis with the pathogenesis of cutaneous lichen planus.

Combination of Pitavastatin and melatonin shows partial antineoplastic effects in a rat breast carcinoma model.

Our previous results indicated significant tumor-suppressive effects of different statins in rat mammary carcinogenesis. The purpose of this experiment was to examine the chemopreventive effects of Pitavastatin alone and in combination with the pineal hormone melatonin in the model of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female Sprague-Dawley rats. Pitavastatin was administered dietary (10mg/kg) and melatonin in an aqueous solution (20µg/ml). Chemoprevention began 7 days prior to carcinogen administration and subsequently continued for 15 weeks until autopsy. At autopsy, mammary tumors were removed and prepared for histopathological and immunohistochemical analysis. Compared to controls, Pitavastatin alone reduced average tumor volume by 58% and lengthened latency by 8 days; on the other hand, the drug increased tumor frequency by 23%. Combined administration of Pitavastatin with melatonin decreased tumor frequency by 23%, tumor volume by 44% and lengthened tumor latency by 5.5 days compared to control animals. The analysis of carcinoma cells showed significant increase in caspase-3 expression in both treated groups and a tendency of increased caspase-7 expression after Pitavastatin treatment alone. Significant expression decrease of Ki67 was found in carcinoma cells from both treated groups. Compared to control carcinoma cells, Pitavastatin alone increased VEGF expression by 41%, however melatonin totally reversed its undesirable effect. Pitavastatin combined with melatonin significantly increased femur compact bone thickness in animals. Pitavastatin alone decreased plasma triglycerides and total cholesterol levels, however it significantly increased levels of glucose. In summary, our results show a partial antineoplastic effect of Pitavastatin combined with melatonin in the rat mammary gland carcinoma model.

[Bart´s syndrome associated with epidermolysis bullosa junctionalis and with pyloric atresia. An autopsy case report]. / Bartov syndróm asociovaný s epidermolysis bullosa junctionalis a s atréziou pyloru. Nekroptická kazuistika.

Barts syndrome, in literature also known under the name CLAS (Congenital Localised Absence of Skin), first described by Bart in 1966 as congenital localized absence of skin, epidermolysis bullosa congenita and nail abnormalities. The authors present a macroscopic and histological findings of a newborn with Barts syndrome, with epidermolysis bullosa junctionalis and atresia pylori, who died 17 days after birth and 13 days after surgery for pyloric stenosis.

Melatonin potentiates the anti-tumour effect of pravastatin in rat mammary gland carcinoma model.

Previous studies in the field of cancer research have suggested a possible role for statins in the reduction of risk in certain malignancies. The purpose of these studies was to examine the chemopreventive effects of pravastatin alone and in combination with pineal hormone melatonin in the N-methyl-N-nitrosourea-induced mammary carcinogenesis model. Pravastatin was given orally (1 00 mg/kg) and melatonin was added to the water (20 µg/ml). Chemoprevention began seven days prior to carcinogen administration and subsequently continued for 15 weeks until autopsy. At autopsy, mammary tumours were removed and prepared for histopathological and immunohistochemical analysis. Parameters of experimental carcinogenesis, mechanism of action (biomarkers of apoptosis, angiogenesis and proliferation) and side effects after long-term treatment in animals were assessed. Pravastatin alone suppressed tumour frequency by 20.5% and average tumour volume by 15% compared with controls. Combined administration of the drugs decreased tumour frequency by 69% and lengthened tumour latency by nine days compared with control animals. The ration between high and low grade carcinomas was apparently reduced in both treated groups. The analysis of carcinoma cells showed significant expression increase in caspase-3 and caspase-7 after pravastatin treatment; however, combined treatment even more pronounced increase in the expression of both caspases. Regarding VEGFR-2 expression, a small effect in carcinomas of both treated groups was found. In plasma metabolism evaluation, pravastatin alone significantly decreased levels of glucose and triacylglycerols. Our results suggest a mild anti-neoplastic effect of pravastatin in this rat mammary gland carcinoma model. Statins co-administered with other suitable drug (e.g. melatonin) should be further evaluated for tumour-preventive properties.

Giant cell myocarditis and endomyocardial calcification in a 2.5-month-old infant triggered by excessive maternal alcohol abuse: case study of an unusual association.

This report describes an unusual case of a 2.5-month-old infant's sudden death secondary to giant cell myocarditis and endomyocardial calcification, both unusual entities in pediatric patients. The mother had a history of excessive alcohol consumption during pregnancy and the postnatal period. No infectious etiologies, hypersensivity, or autoimmune disorders were identified. Therefore, the authors assume that alcohol exposure might be responsible for the inflammatory giant cell process complicated with endomyocardial calcification in susceptible infants. This report is the first to describe the rare form of noninfectious myocarditis complicated with endomyocardial calcification possibly triggered by a toxic agent. The authors discuss the possible interaction between these processes that led to the infant's sudden death.

Preventive effects of fluvastatin in rat mammary carcinogenesis.

On the basis of preclinical and clinical evidence, statins lead to risk reduction of several types of neoplasia including breast cancer. This study is the first report on the preventive effects of fluvastatin in experimental breast cancer in vivo. In this experiment, the antineoplastic effects of fluvastatin in the chemoprevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female rats were evaluated. The effects of fluvastatin on selected parameters of apoptosis, proliferation, and angiogenesis in mammary tumor cells were determined. The drug was dietary administered at two concentrations of 20 and 200 mg/kg. The experiment was terminated 17 weeks after carcinogen administration; mammary tumors were removed and prepared for histomorphological and immunohistochemical analysis. The basic parameters of experimental carcinogenesis, chosen metabolic variables, and side effects after long-term fluvastatin treatment in animals were assessed. Fluvastatin at higher concentrations suppressed tumor frequency by 63% and tumor incidence by 33% in comparison with the controls. After fluvastatin treatment, immunohistochemical analysis of tumor cells showed a decrease in vascular endothelial growth factor receptor-2 expression by 86% and an increase in caspase-3 by 8.5%. Fluvastatin in both treated groups significantly increased the parameters of serum lipid metabolism and significantly decreased femur compact bone thickness and body weight in animals. Our results suggest that fluvastatin and other statins should be further evaluated for tumor-preventive characteristics.

Quantitative changes of the capillary bed in aging human skin.

The present study focuses on the quantitative changes of the capillary bed in aging human skin. Forty-five skin samples were excised from the anterior thoracic region of cadavers of caucasian origin in the age range 33-82 years. The immunohistochemical method with anti-human CD34 was used for the detection of the capillary endothelium. Morphometric analysis was done by Vision Assistant software. The capillary bed was quantified by two parameters: capillary area (CA) and intercapillary distance (ID) in 6 age groups. Results revealed no quantitative changes of the capillary bed up to the age of 60 years. In the papillary dermis a significant reduction of the capillary area was seen in the 7th, 8th and 9th decennium. A considerable decrease, by 33%, was determined in the 7th decennium. During the 8th and 9th decennium the capillary area was reduced by a further 19% and 13%. In total from the 4th till the 9th decennium, the capillary bed in the papillary dermis was diminished by 65%. The intercapillary distance in the papillary dermis singnificantly increased during the 8th decennium. On the basis of the mutual evaluation of both the observed parameters, CA and ICD, the authors supposed that the reduction of the capillary bed in the papillary dermis during the 7th decennium was probably caused only by the shortening of the capillary loops, which copied flattened dermal papillae, and during the 8th decennium also by the decreased number of the capillary loops. In the reticular dermis the capillary bed remained unchanged.

Recurrent basal cell carcinoma: a clinicopathological study and evaluation of histomorphological findings in primary and recurrent lesions.

BACKGROUND: Basal cell carcinoma (BCC) of the skin is now the most common malignancy in the human population. One of the most negative features of this disease is frequent tumor recurrence. Unfortunately, all of the traditional diagnostic criteria have failed to definitively predict which patients should be considered at high risk of recurrence. OBJECTIVE: The aim of this study was to evaluate the prevalence, topographical localization, and histomorphological features of recurrent BCCs. METHODS: Biopsy samples and clinical data from 30 consecutive patients (15 women and 15 men) with 31 recurrent BCCs diagnosed from January 2007 to September 2010 were analyzed retrospectively. The mean age of the individuals at the time of diagnosis of recurrence was 68.2 years (range 32 to 97 years). Histological types and other pathological findings of original and relapsing BCCs, as well as the time between them, were able to be compared in 24 cases. RESULTS: Recurrent carcinomas represented 4.9% of all diagnosed cases during the observed period. Recurrence time varied from 4 to 105 months with a mean time of 31.2 months. The majority of recurrences occurred within 3 years after the primary treatment. The topographic localization of tumors was as follows: auricles (n = 5), cheeks (n = 4), medial canthus (n = 4), periauricular regions (n = 3), temporal areas (n = 3), paranasal regions (n = 3), nose (n = 3), forehead (n = 1), lower eyelid (n = 1), mandible (n = 1), chin (n = 1), neck (n = 1), and back (n = 1). Histologically, 50% of primary and 54.8% of recurrent BCCs demonstrated at least partial aggressive-growth features. Comparing primary and corresponding relapsing BCCs, 50% of them showed an identical type, in 16.7% the recurrent tumor had developed a more aggressive histological picture, and in 20.8% the histomorphology had became more benign. Of all primary tumors previously removed by total extirpation, 54.5% were resected completely and 45.5% incompletely. CONCLUSIONS: BCC recurrences may vary considerably with respect to various tumor- and host- -related factors, and so it is impossible to predict them precisely. Although aggressive histological types and positive excision margins are considered the strongest predictors, we demonstrated that half of the primary cancers had shown an indolent character, and that more than half of them had appeared to be completely resected. We can conclude that all patients that have had BCCs removed should be re-examined regularly even after microscopically adequate excisions, or lesions with an indolent histomorphology. Careful monitoring must be undertaken for at least 3 years; however, the most appropriate course is a lifetime of regular follow-up.