Primary angiitis of the central nervous system in a patient with transient episodes of headache and aphasia: A case report.

Primary angiitis of the central nervous system (PACNS) refers to a rare form of vasculitis of unknown cause, with a challenging diagnostic work-up. We report the case of a 57-year-old patient who presented with transient episodes of headache and global aphasia. Cerebrospinal fluid (CSF) examination revealed lymphocytic pleocytosis with moderate elevated protein and normal glucose. CSF and serum tests for infections and autoimmune/paraneoplastic antibodies were negative, except CSF polymerase chain reaction testing that detected Epstein-Barr virus (EBV). Magnetic resonance imaging of the brain with intravenous gadolinium showed meningeal enhancement and pachymeningitis. Due to continuous relapsing episodes of aphasia, a leptomeningeal and brain tissue biopsy was performed and revealed lesions of granulomatous necrotising vasculitis of medium-sized leptomeningeal and intracranial vessels, as well as negative in situ hybridism for EBV. A diagnosis of primary granulomatous necrotising angiitis of the central nervous system was made, and the patient was treated with intravenous methylprednisolone and oral cyclophosphamide, showing excellent response to treatment. Diversity in clinical and laboratory features makes it difficult for PACNS to be distinguished by other systemic vasculitides. Laboratory tests and neuroimaging can provide guidance in evaluation of the patients and exclude other possible causes, but tissue biopsy remains the gold standard for a definite diagnosis.

Association between preoperative neurocognitive status and IDH1 mutation status in high-grade gliomas.

Background: High-grade glioma (HGG) patients present with variable impairment in neurocognitive function (NCF). Based on that, isocitrate dehydrogenase 1 (IDH1) wild-type HGGs are more aggressive than IDH1 mutant-type ones, we hypothesized that patients with IDH1 wild-type HGG would exhibit more severe NCF deficits than their IDH1 mutant counterparts. Methods: NCF was assessed by Mini Mental Status Exam (MMSE), Trail Making Test (TMT), Digit Span (DS), and Controlled Word Association Test (COWAT) tests in 147 HGG patients preoperatively. Results: Analyses between IDH1 groups revealed a significant difference on MMSE concentration component (p ≤ .01), DS (p ≤ .01), TMTB (p ≤ .01), and COWAT (p ≤ .01) scores, with the IDH1 wild group performing worse than the IDH1 mutant one. Age and tumor volume were inversely correlated with MMSE concentration component (r = -4.78, p < .01), and with MMSE concentration (r = -.401, p < .01), TMTB (r = -.328, p < .01), and COWAT phonemic scores (r = -.599, p < .01), respectively, but only for the IDH1 wild-type group. Analyses between age-matched subsamples of IDH1 groups revealed no age effect on NCF. Tumor grade showed nonsignificance on NCF (p > .05) between the 2 IDH1 mutation subgroups of grade IV tumor patients. On the contrary, grade III group showed a significant difference in TMTB (p < .01) and DS backwards (p < .01) between IDH1 subgroups, with the mutant one outperforming the IDH1 wild one. Conclusions: Our findings indicate that IDH1 wild-type HGG patients present greater NCF impairment, in executive functions particularly, compared to IDH1 mutant ones, suggesting that tumor growth kinetics may play a more profound role than other tumor and demographic parameters in clinical NCF of HGG patients.

Wireless Direct Microampere Current in Wound Healing: Clinical and Immunohistological Data from Two Single Case Reports.

Chronic pressure ulcers are hard-to-heal wounds that decrease the patient's quality of life. Wireless Micro Current Stimulation (WMCS) is an innovative, non-invasive, similar to electrode-based electrostimulation (ES) technology, that generates and transfers ions that are negatively-charged to the injured tissue, using accessible air gases as a transfer medium. WMCS is capable of generating similar tissue potentials, as electrode-based ES, for injured tissue. Here, through immunohistochemistry, we intended to characterize the induced tissue healing biological mechanisms that occur during WMCS therapy. Two single cases of bedridden due to serious stroke white men with chronic non-healing pressure ulcers have been treated with WMCS technology. WMCS suppresses inflammatory responses by decreasing the aggregation of granulocytes, followed by stimulating myofibroblastic activity and a new formation of collagen fibers, as depicted by immunohistochemistry. As a result, WMCS provides a special adjunct or stand-alone therapy choice for chronic and non-healing injuries, similar to electrode-based ES, but with added (i.e., contactless) benefits towards its establishment as a routine clinical wound healing regime.

Wireless electrical stimulation: an innovative powerful tool for the treatment of a complicated chronic ulcer.

High-voltage electrical stimulation has been long proposed as a method of accelerating the wound healing process. Its beneficial effect has been successfully evaluated in the treatment of a number of chronic ulcers and burns. We present here the implementation of a new wireless electrical stimulation technique for the treatment of a complicated chronic ulcer of the lower limb. The device is transferring charges to the wound, without any contact with it, creating a microcurrent that is able to generate the current of injury. The results suggest that this easy-to-use method is an effective therapeutic option for chronic ulcers.

G1 cell cycle regulators in congenital melanocytic nevi. Comparison with acquired nevi and melanomas.

BACKGROUND: Congenital nevi are one of the known risk factors for the development of melanoma. However, the magnitude of the risk for both large and small congenital nevi is controversial. METHODS: In order to elucidate the behavior of congenital nevocytes and to define any possible similarities or differences with common nevi and melanomas, we investigated the expression of Ki-67, Rb, p16, cyclin D1, p53 and p21/Waf-1 in 41 congenital nevi, 16 melanomas and 20 acquired common nevi by immunohistochemistry. RESULTS: Congenital nevi highly expressed p16 (81.82 +/- 9.98) but showed limited, if any, reactivity for Ki-67 (1.34% +/- 0.89), Rb (0.76% +/- 0.94), cyclin D1 (0.21% +/- 0.29), p53 (0.54% +/- 0.93) and p21 (0.0609% +/- 0.32). No statistically significant difference was found between giant and nongiant congenital nevi and between congenital and common nevi for any of the markers. The expression of p16 was significantly higher in congenital nevi than in melanomas (p < 0.0001). On the contrary, the expression of Ki-67, p53, p21, Rb and cyclin D1 was significantly higher in melanomas (p < 0.0001). CONCLUSION: Our data regarding the immunohistochemical expression of Rb, p16, p53, cyclin D1 and Ki-67 in congenital nevi indicate that either the alteration of their expression is not an initiating event in melanoma formation or, alternatively, congenital melanocytic nevi may not be the first step in malignant transformation.

Intravascular B-cell lymphoma with leukemic presentation: case report and literature review.

Intravascular lymphoma is an extremely rare, disseminated, and aggressive extranodal CD20+ non-Hodgkin's lymphoma characterized by the presence of lymphoma cells only in the lumina of small vessels. We report a 72-year-old woman with a diagnosis of intravascular lymphoma presented with splenomegaly and leukemic appearance in the peripheral blood smear. Her clinical course was rapidly deteriorated before the initiation of specific chemotherapy and finally died due to multiorgan insufficiency. Bone marrow biopsy revealed a characteristic infiltration of CD5, CD10 B-cell lymphoma. To our knowledge, this is the first reported case of a CD5, CD10 intravascular B-cell lymphoma with leukemic presentation in peripheral blood with multiple cytogenetic aberrations.

Cell cycle and apoptosis regulators in Spitz nevi: comparison with melanomas and common nevi.

BACKGROUND: Deregulated cell cycle control is one of the hallmarks of tumor development. The expression of different cell cycle regulators has been used in various neoplasms as an adjunct to diagnosis. OBJECTIVE: We sough to determine the expression of cell cycle and apoptosis regulators in Spitz nevi and to appraise its value as a diagnostic adjunct in the differential diagnosis from melanomas and common nevi. METHODS: Ki-67, p-27, p-16, p-53, p-21, Rb, cyclin D1, cyclin A, cyclin B1, bcl-2, and bax expression was assessed by immunohistochemistry in 10 Spitz nevi and was compared with 16 melanomas and 20 common nevi immunohistochemical expression. RESULTS: P-27 (60% +/- 20.13), p-16 (62.00% +/- 10.85), and bcl-2 (46.00% +/- 42.47) were highly expressed in Spitz nevi, whereas Ki-67 (2.80% +/- 2.55), Rb (3.75% +/- 4.55), p-53 (2.30% +/- 0.10), cyclin A (0.70% +/- 1.56), B1 (0.20% +/- 0.34), and bax (2.65% +/- 6.37) demonstrated a limited expression. Cyclin D1 (8.60% +/- 7.30) and p-21 (6.40% +/- 5.37) showed a moderate expression. The expression of bax (P = .001), Ki-67 (P < .0001), Rb (P < .0001), p-16 (P < .0001), cyclin A (P < .0001), and cyclin B1 (P < .0001) was significantly higher in melanomas in comparison with Spitz nevi, whereas p-27 expression was significantly higher in Spitz nevi (P < .0001). A trend for significant difference in favor of melanomas was also observed for p-53 (P = .002). On the other hand, no difference was detected for bcl-2 (P = .275), p-21 (P = .055), or cyclin D1 (P = .077). Spitz nevi demonstrated a trend for a higher expression for p-21 (P = .008) and cyclin D1 (P = .006), whereas they exhibited lower p-16 (P = .004) in comparison with common nevi. LIMITATIONS: The number of Spitz nevi was relatively small. CONCLUSION: Spitz nevi differ from melanomas in their immunohistochemical pattern of expression of cell cycle and apoptosis regulators and more closely resemble common benign nevi.

Histological and immunohistochemical study of granuloma annulare and subcutaneous granuloma annulare in children.

BACKGROUND: The aim of this study was to investigate the histological and immunohistochemical features of granuloma annulare (GA) in comparison to deep granuloma annulare (DGA) and granulomatous dermatoses (GDs). METHODS: Our material comprised 13 GA, 8 DGA and 1 atypical granuloma annulare (AGA) in a child with primary immunodeficiency, 10 cases of nonspecific GDs and 1 case of sarcoidosis with cutaneous involvement. The immunohistochemical streptavidin-biotin-Horseradish peroxidase (HRP) analysis was performed on paraffin sections for the detection of CD68/KP-1, CD68/anti-human CD68 clone PGM1 (PGM1), lysozyme, S-100 protein, CD1a, CD3, CD20/L-26, CD4 and CD8. RESULTS: All 13 GA were characterized by typical palisading and interstitial granulomas. In 6 cases, the lesion extended to the subcutaneous fat, while a considerable perivascular lymphocytic infiltrate without any signs of vasculitis was observed in 10 cases. The DGA were located to the deep dermis and subcutaneous fat, showing palisading granulomas with central necrobiosis. Immunohistochemistry revealed a broad intense expression of CD68/PGM1 in the histiocytic population in all cases, a constant but fainter detection of CD68/KP-1 and a variable one of lysozyme. T-cell markers (CD3, CD4 and CD8) were mainly detected in the perivascular lymphocytic infiltrate of GA and DGA, with CD4+ T lymphocytes predominating over CD8+ in GA and DGA, while CD8+ T lymphocytes was the predominant population in AGA. CONCLUSIONS: CD68/PGM1 is a sensitive and reliable histiocytic marker in confirming the histiocytic nature of equivocal GA and DGA, but the histiocytic immunoprofile is of no particular usefulness in differentiating GA from other GD.

Changes in liver histology accompanying massive weight loss after gastroplasty for morbid obesity.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is common in morbid obesity. Our goal was to evaluate the alterations in liver histology and biochemistry before and after weight loss in 51 morbidly obese patients following Mason's vertical banded gastroplasty. METHODS: Two biopsies were performed (on entry and after an average of 18 months), while 16 of these subjects had a third biopsy 17 months after the second. RESULTS: On entry, steatosis and steatohepatitis (mostly grade 3) were present in 98.0% and fibrosis (mostly stage 2) in 94.1% of the subjects. After an excess weight loss of 66%, steatosis and steatohepatitis improved significantly (P<0.001). Although a significant overall decrease in fibrosis occurred (P=0.002), 21 patients (41.1%) did not change and only 6 patients (11.7%) increased in fibrosis. None developed cirrhosis. The decrease in steatohepatitis was significantly correlated (P=0.011) with the reduction of BMI. Fasting serum glucose, lipids, lipoproteins, transaminases, gamma-glutamyl transpeptidase, alkaline phosphatase and fibrinogen were also significantly improved at the time of the second biopsy. The third biopsy performed in 16 of the subjects showed further significant improvement in liver histology. CONCLUSION: NASH improved significantly with massive weight loss in non-diabetic, non-alcoholic, morbidly obese subjects, while fibrosis improved in nearly half of the patients.

Intralesional 5-fluorouracil in the treatment of keloids: an open clinical and histopathologic study.

BACKGROUND: The treatment of keloids remains unsatisfactory. Intralesional 5-fluorouracil (FU) has not been much investigated as a monotherapy in the treatment of keloids. OBJECTIVE: We sought to evaluate the use of intralesional injections of 5-FU in the treatment of keloids. METHODS: A total of 20 patients (11 male and 9 female) were treated once weekly with intralesional injections of 5-FU (50 mg/mL). Patients received an average of 7 treatments. Average injection volumes were 0.2 to 0.4 mL/cm2. All patients had full blood cell count, liver function tests, and renal function tests before and after treatment was commenced. A total of 10 patients had biopsy specimens taken before starting treatment as a baseline and after 6 sessions. Routine hematoxylin-eosin and immunohistochemical analysis detecting Ki-67 and transforming growth factor-beta were performed on paraffin sections. All patients were followed up for 12 months, or until recurrence was noted. RESULTS: Of 20 patients, 17 (85%) showed more than 50% improvement. Only one did not respond favorably. Small and previously untreated lesions improved the most. Pain (20 of 20), hyperpigmentation (20 of 20), and tissue sloughing (6 of 20) were the main adverse effects. Histopathologic and immunohistochemical evaluation were consistent with the clinical observations. Ki-67 proliferative index was significantly reduced (P = .0001) after treatment. Transforming growth factor-beta was reduced less significantly. Recurrence was noted in 47% (9 of 19) of patients who responded to treatment within 1 year. A correlation was found ( P = .028) between the duration of the lesions and recurrence. CONCLUSION: Our study demonstrates that intralesional 5-FU may be effective in the treatment of keloids, but recurrence is common and further investigation is required.

Aspergillus endocarditis in a native valve after amphotericin B treatment.

Systemic infection with Aspergillus fumigatus is an opportunistic disease that affects mainly immunocompromised hosts and is associated with a high mortality rate. We report a case of A. fumigatus endocarditis after an episode of thrombotic thrombocytopenic purpura. Diagnosis was established after sudden rupture of posterior papillary muscle of the normal native mitral valve. Soon after mitral valve replacement, Aspergillus endocarditis recurred, associated with multiple peripheral emboli, which necessitated a second operation.

Tumor to tumor metastasis: report of two cases and review of the literature.

Tumor-to-tumor metastases are uncommon. The most frequent donor tumor is lung cancer, while renal cell carcinoma (RCC) is by far the most common recipient. In this report, a carcinoma of the uterine cervix metastasizing to an RCC and a urothelial carcinoma of the urinary bladder metastasizing to a solitary fibrous tumor of the pleura are described. No similar cases have been found in the accessible literature. These cases are discussed and the findings are correlated with the data of the literature.