15 research outputs found
Comparison of Results of Retrocalcaneal Decompression for Retrocalcaneal Bursitis and Insertional Achilles Tendinosis with Calcific Spur
Telomere shortening and senescence checkpoint deactivation during multistep human hepatocarcinogenesis
Frequency and Effects of Intratendinous and Peritendinous Calcifications after Open Achilles Tendon Repair
Sporadic endolymphatic sac tumor : its clinical, radiological, and histological features, management, and follow-up
BACKGROUND:
Sporadic endolymphatic sac tumor (ELST) is rare. We described the clinical, radiological, and histological features, treatment, and follow-up of ELST.
METHOD:
This was a retrospective analysis of 7 cases of sporadic ELST that were managed between 1993 and 2010.
RESULTS:
Twenty-five to 75 years was the age range of the patients. Subjective hearing loss and tinnitus were the most common presenting features. Five patients had total deafness and 2 had severe sensorineural hearing loss. The most common radiological feature was temporal bone destruction with tumor extension to cerebellopontine angle and posterior cranial fossa. Cholesterol or hemosiderin cysts around the tumor could be a characteristic feature. Major skull base procedures were performed in all 7 cases, and complete tumor excision was achieved in 6 of them. One patient needed a second surgery after she was referred to us after an incomplete first surgery. Recurrences were detected in 2 patients during follow-up; 1 of them received irradiation without minimal change to the tumor size and the second refused any treatment for the recurrence. Both of them are alive with disease.
CONCLUSION:
Early detection and radical surgical excision at first attempt give best results. Radiotherapy could be considered only in unresectable recurrences. \ua9 2012 Wiley Periodicals, Inc. Head Neck, 2012
Telomere shortening and loss of p21-expression characterize multistep hepatocarcinogenesis in humans
Telomere shortening and inactivation of cell cycle checkpoints characterize carcinogenesis. Whether these molecular features coincide at specific stages of human hepatocarcinogenesis is unknown. The preneoplasia-carcinoma sequence of human HCC is not well defined. Small cell changes (SCC) and large cell changes (LCC) are potential precursor lesions. We analyzed hepatocellular telomere length, the prevalence of DNA damage, and the expression of p21 and p16 in biopsy specimens of patients with chronic liver disease (n = 27) that showed different precursor lesions and/or HCC: liver cirrhosis (n = 25), LCC (n = 26), SCC (n = 13), and HCC (n = 13). The study shows a decrease in telomere length in nondysplastic cirrhotic liver compared with normal liver and a further significant shortening of telomeres in LCC, SCC, and HCC. HCC had the shortest telomeres, followed by SCC and LCC. Hepatocytes showed an increased p21 labeling index (p21-LI) at the cirrhosis stage, which remained elevated in most LCC. In contrast, most SCC and HCC showed a strongly reduced p21-LI. Similarly, p16 was strongly expressed in LCC but reduced in SCC and not detectable in HCC. \u3b3H2AX-DNA-damage-foci were not detected in LCC but were present in SCC and more frequently in HCC. These data indicate that LCC and SCC represent clonal expansions of hepatocytes with shortened telomeres. Conclusion: The inactivation of cell cycle checkpoints coincides with further telomere shortening and an accumulation of DNA damage in SCC and HCC, suggesting that SCC represent more advanced precursor lesions compared with LCC
Bilateral testicular masses and adrenal insufficiency: is congenital adrenal hyperplasia the only possible diagnosis? First two cases of TARTS described in Addison-only X-linked adrenoleukodystrophy and a brief review of literature
Background: Testicular adrenal rest tumors (TARTs) are benign masses deemed to originate from pluripotent testicular steroidogenic cells that grow under chronic ACTH stimulation. These lesions, occasionally misdiagnosed as Leydig cell tumors (LCTs), are typically described in patients with congenital adrenal hyperplasia (CAH). X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder of beta-oxidation with accumulation of very long chain fatty acids (VLCFAs) in various tissues, and a rare cause of primary adrenal insufficiency (PAI). TARTs have never been associated with X-ALD. Case 1 description: A 19-year old male, who had previously undergone bilateral enucleation of presumed LCTs, was referred to our unit. Follow-up scans showed persistent bilateral lesions compatible with TARTs. Biochemical exams revealed PAI but excluded CAH. A serum VLCFAs panel was consistent with X-ALD, with gene testing confirming the diagnosis. Histological revision of the previously resected testicular lesions was compatible with TARTs. Start of glucocorticoid replacement therapy was associated with a reduction of testicular masses. Case 2 description: A 26-year old X-ALD male was diagnosed with bilateral testicular lesions compatible with TARTs. These lesions increased after ACTH elevation following switch to modified-release hydrocortisone. Clinical and sonographic findings allowed for a “watchful-waiting" approach, avoiding unnecessary surgery. Conclusion: These are the first cases reported of TARTs in patients with X-ALD-associated PAI. Testicular lesions in patients with an early onset of ACTH elevation, regardless of the cause, should always be thoughtfully investigated, as they may reveal themselves as TARTs. We suggest that all patients affected from chronic ACTH elevation of a young age of onset should undergo testicular ultrasound in order to evaluate the presence of these lesions. GRT in these patients might also help preserving fertility
Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis
Hepatocellular nodules in cirrhosis include regenerative (large regenerative, LRN) and dysplastic (low and high grade, LGDN and HGDN) nodules, early and grade 1 HCC (eHCC-G1), and overt HCC. The differential diagnosis may be particularly difficult when lesions such as HGDN and eHCC-G1 are involved. We investigated the diagnostic yield of a panel of 3 putative markers of hepatocellular malignancy such as HSP70, glypican 3 (GPC3), and glutamine synthetase (GS). We selected 52 surgically removed nonmalignant nodules (15 LRNs, 15 LGDNs, 22 HGDNs) and 53 HCCs (10 early, 22 grade 1, and 21 grade 2-3) and immunostained them for HSP70, GPC3, and GS. The sensitivity and specificity of the individual markers for the detection of eHCC-G1 were 59% and 86% for GS, 69% and 91% for GPC3, and 78% and 95% for HSP70. We identified 2 main phenotypes: (1) all negative, seen in 100% LRN and LGDN, 73% HGDN and 3% eHCC-G1; (2) all positive, a feature detected in less than half the eHCC-G1. Using a 3-marker panel, when at least 2 of them, regardless which, were positive, the sensitivity and specificity for the detection of eHCC-G1 were respectively 72% and 100%; the most sensitive combination was HSP70+/GPC3+ (59%) when a 2-marker panel was used. Conclusion: The adopted panel of 3 markers is very helpful in distinguishing eHCC-G1 from dysplastic nodules arising in cirrhosis. Copyrigh
Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis
Trapped in class? Material manifestations of poverty and prosperity in Alice Munro’s “Royal Beatings” and “The Beggar Maid”
Direct Modulation of Microtubule Stability Contributes to Anthracene General Anesthesia
Recently,
we identified 1-aminoanthracene as a fluorescent general
anesthetic. To investigate the mechanism of action, a photoactive
analogue, 1-azidoanthracene, was synthesized. Administration of 1-azidoanthracene
to albino stage 40–47 tadpoles was found to immobilize animals
upon near-UV irradiation of the forebrain region. The immobilization
was often reversible, but it was characterized by a longer duration
consistent with covalent attachment of the ligand to functionally
important targets. IEF/SDS-PAGE examination of irradiated tadpole
brain homogenate revealed labeled protein, identified by mass spectrometry
as β-tubulin. In vitro assays with aminoanthracene-cross-linked
tubulin indicated inhibition of microtubule polymerization, similar
to colchicine. Tandem mass spectrometry confirmed anthracene binding
near the colchicine site. Stage 40–47 tadpoles were also incubated
1 h with microtubule stabilizing agents, epothilone D or discodermolide,
followed by dosing with 1-aminoanthracene. The effective concentration
of 1-aminoanthracene required to immobilize the tadpoles was significantly
increased in the presence of either microtubule stabilizing agent.
Epothilone D similarly mitigated the effects of a clinical neurosteroid
general anesthetic, allopregnanolone, believed to occupy the colchicine
site in tubulin. We conclude that neuronal microtubules are “on-pathway”
targets for anthracene general anesthetics and may also represent
functional targets for some neurosteroid general anesthetics