Tempol-nebivolol therapy potentiates hypotensive effect increasing NO bioavailability and signaling pathway.

Nebivolol is a third generation beta blocker with endothelial nitric oxide synthase (eNOS) agonist properties. Considering the role of reactive oxygen species (ROS) in the uncoupling of eNOS, we hypothesized that the preadministration of an antioxidant as tempol, could improve the hypotensive response of nebivolol in normotensive animals increasing the nitric oxide (NO) bioavailability by a reduction of superoxide (O2(•-)) basal level production in the vascular tissue. Male Sprague Dawley rats were given tap water to drink (control group) or tempol (an antioxidant scavenger of superoxide) for 1 week. After 1 week, Nebivolol, at a dose of 3 mg/kg, was injected intravenously to the control group or to the tempol-treated group. Mean arterial pressure, heart rate, and blood pressure variability were evaluated in the control, tempol, nebivolol, and tempol nebivolol groups, as well as, the effect of different inhibitor as Nß-nitro-l-arginine methyl ester (L-NAME, a Nitric oxide synthase blocker) or glybenclamide, a KATP channel inhibitor. Also, the expression of α,ß soluble guanylate cyclase (sGC), phospho-eNOS, and phospho-vasodilator-stimulated phosphoprotein (P-VASP) were evaluated by Western Blot and cyclic guanosine monophosphate (cGMP) levels by an enzyme-linked immunosorbent assay (ELISA) commercial kit assay. We showed that pretreatment with tempol in normotensive rats produces a hypotensive response after nebivolol administration through an increase in the NO bioavailability and sGC, improving the NO/cGMP/protein kinase G (PKG) pathway compared to that of the nebivolol group. We demonstrated that tempol preadministration beneficiates the response of a third-generation beta blocker with eNOS stimulation properties, decreasing the basal uncoupling of eNOS, and improving NO bioavailability. Our results clearly open a possible new strategy therapeutic for treating hypertension.

Patients from across Europe have similar views on patient-centred care: an international multilingual qualitative study in infertility care.

BACKGROUND: International patient centredness concepts were suggested but never conceptualized from the patients' perspective. Previously, a literature review and a monolingual qualitative study defined 'patient-centred infertility care' (PCIC). The present study aimed to test whether patients from across Europe value the same aspects of infertility care. METHODS: An international multilingual focus group (FG) study with 48 European patients from fertility clinics in Austria, Spain, the UK and Belgium, with deductive content analysis. RESULTS: All specific care aspects important to participants from all countries could be allocated to the 10 dimensions of PCIC, each discussed in every FG, including: 'information provision', 'attitude of and relationship with staff', 'competence of clinic and staff', 'communication', 'patient involvement and privacy', 'emotional support', 'coordination and integration', 'continuity and transition', 'physical comfort' and 'accessibility'. Most specific care aspects (65%) were discussed in two or more countries and only a few new codes (11%) needed to be added to the previously published coding tree. Rankings from across Europe clearly showed that 'information provision' is a top priority. CONCLUSIONS: The PCIC-model is the first patient-centred care (PCC) model based on the patients' perspective to be validated in an international setting. Although health-care organization and performance differ, the similarities between countries in the infertile patients' perspective were striking, as were the similarities with PCC models from other clinical conditions. A non-condition specific international PCC model and a European instrument for the patient centredness of infertility care could be developed. European professionals can learn from each other on how to provide PCC.

Stroke in young people: the increasing role of advanced imaging.

Ischemic stroke in young people is an unexpected event due to a wider variety of causes compared to the older population. This study highlights the increasing role of neuroimaging in the diagnosis, prognosis and treatment of young stroke patients. Thirty young adult patients (age range, 15-45 years) with acute ischemic stroke diagnosis were retrospectively included and studied at our institution during 2009. The mean age of patients was 35 years and 50% were men. The stroke etiology was established in 86% of cases (n=26), 7% (n=2) were due to atherosclerosis of the main vessels, 10% (n=3) were related to cardioembolism, 27% (n=8) were due to arterial dissection and 43% (n=13) responded to miscellaneous etiologies. The cause remained unexplained in 14% (n=4) of cases. The aims of neuroimaging in the challenging study of young stroke patients are to confirm the ischemic nature of the lesion, to determine its location, and to verify the patency of major neck and intracranial arteries. Both MRI and MSCT offer the best sensitivity and spatial resolution.

MR imaging findings in 56 patients with Wernicke encephalopathy: nonalcoholics may differ from alcoholics.

BACKGROUND AND PURPOSE: Wernicke encephalopathy (WE) is a severe neurologic disorder resulting from dietary vitamin B(1) deficiency. This study was undertaken to analyze and compare MR imaging findings and neurologic manifestations at clinical presentations of patients with WE with and without a history of alcohol abuse. MATERIALS AND METHODS: WE patients were identified using diagnostic neurologic data bases. Fifty-six patients (29 females, 27 males) diagnosed between 1999 and 2008 with WE who improved within 1 month from the onset of thiamine administration were included in the analysis. Patients' records were reviewed for clinical manifestations and imaging studies' findings. MR imaging was performed in the acute phase of the disease at a field strength of 1T (16 patients) and 1.5T (40 patients). All MR images were of acceptable to good quality and were retrospectively reviewed. We compared imaging findings and clinical presentation in the alcoholic (AL) group versus the non-alcoholic (NA) group using the 2-tailed Fisher exact test and the Phi coefficient as appropriate. RESULTS: Forty-three percent of the patients were in the AL group, whereas 57% were in the NA group. Eighty-nine percent showed changes in consciousness, 75% had ocular manifestations, and 54% had ataxia. On MR imaging, 80% of the patients had evidence of symmetric lesions in the medial thalami and in the periventricular region of the third ventricle; 59%, in the periaqueductal area; 45%, in the mamillary bodies; 36%, in the tectal plate; and 7%, in the periventricular gray matter located anteriorly to the fourth ventricle. Signal-intensity alterations in areas considered atypical for the disease were noted only in the NA group and always in association with the typical findings. Contrast enhancement of the thalamus and mamillary bodies was significantly associated with alcohol abuse. CONCLUSIONS: Contrast enhancement in the mamillary bodies and thalamus is a typical finding of the disease in AL patients. Atypical MR imaging findings characterize NA patients.

Tubulopapillary hidradenoma-like tumor of the mandible: clinicopathologic and immunohistochemical features.

Tubulopapillary hidradenoma is a benign sweat gland tumor that appears as a well-defined, superficially located dermal nodule. It combines ductal as well as apocrine and eccrine glandular differentiation. Microscopically, the tumor is composed of tubular structures that characteristically show intraluminal non-villous papillary projections and a peripheral myoepithelial cell layer. A tumor that is histologically and immunohistochemically identical to tubulopapillary hidradenoma occurred in the mandible of a 73-year-old man and resulted in considerable diagnostic difficulty. The neoplasm developed in a mandibular cyst and recurred 5 years after initial enucleation. This is the first report of a central (intraosseous) sweat gland adenoma of the mandible. The differential diagnosis and possible histogenesis are discussed.

Differential expression of metallopanstimulin/S27 ribosomal protein in melanocytic lesions of the skin.

We have previously shown that human metallopanstimulin (MPS-1) is a ubiquitous 9.4-kDa multifunctional ribosomal S27/nuclear "zinc finger" protein which is expressed at high levels in a wide variety of cultured proliferating cells and tumor tissues, including melanoma. In the present study, we have examined the expression of the MPS-1 protein in various types of human benign and malignant melanocytic lesions of the skin. The expression of the MPS-1 protein was studied by immunohistochemistry using specific anti-MPS-1 antibodies. We found that in benign nevi, the staining is weak and in a gradient; most often, only type A melanocytes stain positive. The B and particularly the C types are negative. Remarkably, congenital nevi show a similar gradient staining of regular benign nevi, but in addition one example showed intensely positive dermal nodules adjacent to areas of negative melanocytes. In melanomas, the staining patterns for MPS-1 are more complex. While some melanomas stain evenly and intensely positive, others have remarkably variable expression of MPS-1. The scattered melanocytes migrating to the upper layers of the epidermis are usually intensely positive. In summary, benign lesions stain in an orderly pattern with staining gradients that correlate with the cellular differentiation of the nevi. Malignant melanomas have an erratic, often intense staining that also correlates with the disorderly growth of these neoplasms. These differential results indicate that the MPS-1 antigen is a useful marker for melanocytic lesions at the immunohistochemical level.

[Cutaneous adenolipoma]. / L'adénolipome cutané.

INTRODUCTION: Adenolipoma of the skin is an unusual microscopic variant of the solitary lipoma, superposable to the adenolipoma of the breast, characterized by the presence of normal eccrine sweat glands inside the fat proliferation. OBSERVATIONS: Two new cases are reported. DISCUSSION: Adenolipoma of the skin is a benign lesion whose clinical features are similar to those of solitary lipoma. Probably, it is only a histological curiosity in which the eccrine glands are entrapped and carried by the adipose proliferation.

Alopecia: histologic diagnosis by transverse sections.

Histologic evaluation for alopecia can be difficult and in part can be attributed to confusing categorization and limited information derived from examination of traditionally prepared biopsy specimens. The transverse section technique has many advantages, and with experience is the preferable method for evaluating specimens for alopecia. Using this technique, numerous follicles can easily be seen in one tissue profile allowing evaluation of follicular density, follicular unit morphology, and follicular growth dynamics, ie, anagen-telogen ratio. Specimens are categorized as scarring or nonscarring alopecia, and further diagnostic criteria discussed herein assist the pathologist in making specific diagnoses of nonscarring and scarring alopecias. Scarring alopecia may be primary or secondary, and primary scarring alopecias are further classified as lymphocyte-associated and neutrophil-associated. Although the clinical impression is very important in diagnosing alopecia, transversely sectioned biopsy specimens can greatly aid the diagnosis and management of patients with alopecia.

Cutaneous granular cell angiosarcoma.

The majority of cutaneous angiosarcomas display typical architectural features of irregular anastomosing vascular channels in the dermis and subcutis. Nuclei are usually hyperchromatic and pleomorphic but the volume of cytoplasm of the neoplastic cells is often small. Diagnosis can be made readily on an adequate biopsy. We recently experienced difficulty diagnosing an angiosarcoma composed predominantly of cells with abundant granular cytoplasm. We were able to compare the present case with sections obtained from the only other reported example. The architectural expression of an anastomosing vascular pattern in areas of tumor, combined with the positive staining for Factor VIII-related antigen (FVIIIRAg) and Ulex europaeus agglutinin-1 (UEA1) enabled us to make a diagnosis of angiosarcoma. The tumor failed to stain for the other endothelial markers (CD31 and CD34) which were positive in the original case. A marker for lysosomes (CD68) stained the granules in both cases. The granular cell variant of cutaneous angiosarcoma is very rare. Diagnosis is possible by recognizing the typical anastomosing neoplastic vascular channels at the periphery of the lesion, and by use of a combination of lectin (UEA1) and immunohistochemical (FVIIIRAg, CD34 and CD31) endothelial markers.

Epithelioid cell histiocytoma. A report of 10 cases including a new cellular variant.

Epithelioid cell histiocytoma is a recently recognized lesion that is considered to be a variant of cutaneous fibrous histiocytoma (dermatofibroma). Ten cases are presented, including their light microscopic, immunohistochemical, and ultrastructural features. Eight of the cases are similar to those previously reported, presenting as elevated nodules arising on the extremities and composed of epithelioid histiocytes with overlying epidermal effacement. Two of the cases were composed of cells with the same morphologic and immunohistochemical characteristics as typical epithelioid cell histiocytoma, including factor XIIIa positivity, but these arose in the reticular dermis and exhibited prominent cellularity.

Clear cell basal cell carcinoma: an unusual degenerative variant.

Clear cell basal cell carcinoma (BCC) is an unusual variant of BCC which is characterized by a variable component of large clear cells. Twenty cases are presented which are further subdivided into pure, mixed, or metatypical categories. Although initially thought to represent sebaceous or tricholemmal differentiation, electron microscopic studies demonstrated that the clear cell changes are a degenerative phenomenon, probably involving lysosomes.

Nerve sheath myxoma (neurothekeoma) of the skin: light microscopic and immunohistochemical reappraisal of the cellular variant.

Nerve sheath myxoma (NSM) is a rare cutaneous neoplasm, the histogenesis of which is controversial. Fifteen cases of NSM were studied by routine light microscopy and with a broad panel of immunohistochemical stains. NSM were classified into three groups based on cellularity, mucin content and growth pattern. 1) The hypocellular (myxoid) type (5/15 cases) showed frequent encapsulation or sharp circumscription. Immunohistochemically this type was strongly positive for S-100 protein and collagen type IV and variably positive for epithelial membrane antigen. 2) The cellular type (4/15 cases) had scant mucin and ill-defined nodular or infiltrating growth. Immunostaining showed positive reaction for neuron specific enolase (2/4), Leu-7 (1/4) and smooth muscle specific actin (2/4), and was negative with the other antibodies. 3) The "mixed type" (6/15 cases) had variable cellularity and mucin content with poor demarcation and variable immunolabeling. We conclude that: 1) there are major light microscopic and immunohistochemical differences between the classical hypocellular (myxoid) and the cellular forms of NSM (neurothekeoma); 2) while the immunohistochemical results support the presence of nerve sheath differentiation in the classical forms of NSM, and to some extent in the mixed forms, there is an absence of convincing evidence of neural differentiation in the cellular variant by either light microscopy or immunohistochemistry; 3) the variable immunophenotypes suggest that differentiation other than neural may take place in CNT.

Adenolipoma of the skin: a report of nine cases.

BACKGROUND: We have identified nine cases of a variant of superficial lipoma that are characterized by the presence of eccrine sweat glands. OBJECTIVE: The purpose of this study was to elucidate the clinical and histopathologic features of this distinctive lesion. METHODS: Nine cases of lipoma that contain eccrine glands were retrieved from our pathology files from 1989 through 1992. Their clinical and histopathologic features were studied and compared with those of conventional lipoma. RESULTS: The clinical features of these lesions did not deviate appreciably from those of the usual lipomas. However, their microscopic appearances differed by the presence of displaced and distorted eccrine glands. One lesion had the added features of a myxolipoma. CONCLUSION: Adenolipoma of the skin is a distinct lesion that can occur in the dermis or subcutaneous tissue.

Plexiform and other unusual variants of palisaded encapsulated neuroma.

Palisaded, encapsulated neuroma (PEN) has been described as a predominantly solitary, nodular tumor; plexiform or multinodular growth patterns have not been reported in detail. We reviewed 55 PEN in order to evaluate: 1) the predominant growth patterns; 2) features that may indicate previous trauma; and 3) association with acne-like changes. Sixteen cases (29%) had growth patterns other than the solitary, nodular type. These patterns were: a) plexiform (7/16), b) multinodular (5/16), and c) fungating (4/16). Other unusual features included evidence of trauma, i.e., fibrosis, myxoid change, chronic inflammation (5/16), partially incomplete capsule (6/16), and association with acne-like features (13/16). These results suggest that: 1) plexiform or multinodular growth patterns occur relatively often in PEN; 2) some changes indicate a possible histogenetic relation to traumatic neuroma, probably via secondary traumatization; 3) a high frequency of association with acne-like changes which could imply, but does not prove, an acne-induced histogenesis; and 4) the differential diagnosis of cutaneous plexiform lesions should include PEN.

Angiomatosis with luminal cryoprotein deposition.

BACKGROUND: Angioendotheliomatosis has recently been separated into two types. Malignant angioendotheliomatosis is a lymphoma in which the neoplastic cells accumulate in vascular lumens. Reactive angioendotheliomatosis is a proliferation of capillaries that is less well characterized. OBJECTIVE: Our purpose was to describe the clinical and histopathologic features of three cases of reactive angiomatosis in patients with cryoproteinemia. METHODS: Clinical and histologic data were correlated. Immunoperoxidase staining and electron microscopy were used in the histologic evaluation. RESULTS: All three cases showed tufts of capillaries with luminal deposits of cryoproteins. Immunohistochemical studies showed that the cellularity of the tufts was primarily caused by a proliferation of pericytes. CONCLUSION: Cryoproteinemia can cause angiomatosis that simulates a vascular neoplasm.

Comparative light-microscopic and immunohistochemical study of traumatic and palisaded encapsulated neuromas of the skin.

The primary hyperplastic nature of palisaded encapsulated neuromas (PENs) has been recently challenged by suggesting a traumatic origin. We studied eight cases of traumatic neuroma (TN) and 12 cases of PEN by routine light-microscopic, histochemical, and immunohistochemical methods to assess evidence of previous tissue injury. Sections from the formalin-fixed, paraffin-embedded tissue were stained with hematoxylin-eosin, trichrome, elastic, reticulin, Giemsa, colloidal iron (with and without hyaluronidase), and Bielschowsky silver stains. Antibodies were applied to collagen types I, III, and IV, MAC 387, factor XIIIa, alpha 1-antitrypsin (A1AT), epithelial membrane antigen (EMA), Leu-7, and myelin basic protein using ABC techniques. We found that (a) in TN the individual fascicles were usually surrounded by perineurial cells, whereas in PEN the perineurial cells were observed mainly in the capsular areas and only rarely within the fascicles as evidenced by EMA antibodies; (b) histochemically TN contained considerably larger amounts of collagen (types I and III), acidic mucin, and myelin products than did PEN; and (c) neither PEN nor TN contained increased inflammatory cells or cells positive for factor XIIIa, MAC 387, or A1AT. We conclude that (a) there are substantial structural and histochemical differences between TN and PEN, (b) the changes suggest that the classic form of PEN has a different histogenesis than TN, and (c) on histologic grounds, chronic minor trauma could not be excluded as an etiologic factor for PEN.