Tumor cell-enhanced sensitivity of vascular endothelial cells to photodynamic therapy

Effective antitumor photodynamic therapy (PDT) may be related to damage of vasculature within the tumor. The purpose of this study was to determine if tumor cells secrete factors that stimulate proliferation of human umbilical vein endothelial cells (HUVEC) and result in enhanced sensitivity of HUVEC to aluminum-sulfonated phthalocyanine (AISPc)-PDT. Three human tumor cell lines—pharyngeal squamous carcinoma, colonic carcinoma, and mammary carcinoma—were used in this study. Co-culture of HUVEC and either squamous carcinoma or colonic carcinoma, but not mammary carcinoma, significantly increased HUVEC proliferation and AlSPc-PDT mediated cell damage. In addition, supernatant from squamous carcinoma and colonic carcinoma cultures also stimulated HUVEC proliferation and sensitivity to AISPc-PDT. Both supernatant and cell lysate from squamous carcinoma cells contained angiogenic factors consistent with basic and acidic fibroblast growth factors, as evidenced by Western blot analysis and BALB/c 3T3 fibroblast cell proliferation assays. Collectively, these results suggest that selected tumor cell lines produce angiogenic factors that induce HUVEC proliferation and subsequently enhance sensitivity to AISPc-PDT. © 1994 Wiley-Liss, Inc.     

Carcinoma ex pleomorphic adenoma of the upper lip

Carcinoma ex pleomorphic adenoma (CXPA) is a rare salivary gland malignancy most often reported within the parotid gland. Of the salivary gland tumours that occur within the minor salivary glands at least 50% are reported to be malignant. This proves to be inaccurate when describing salivary gland tumours within the upper lip which are usually benign. A Medline search of the English language literature yields only one case report of a CXPA located within the upper lip. The authors present a second case report of CXPA within the upper lip and a review of its pathologic features and management.     

Survivin: a novel neuroendocrine marker for pheochromocytoma

OBJECTIVE: To study survivin expression in human adrenal medulla and in benign and malignant pheochromocytoma tissue as a tool to predict tumor metastatic potential and prognosis. DESIGN: Blinded study to assess the role of the anti-survivin antibody in chromaffin cells. METHODS: We performed immunohistochemistry with a purified rabbit-polyclonal anti-survivin antibody on 39 formalin-fixed and paraffin-embedded pheochromocytoma/paraganglioma specimens, and on 10 normal adrenal medulla samples from patients unaffected by a chromaffin cell tumor. Fourteen samples were from 14 patients with benign pheochromocytoma (<8 year follow-up, mean 5.2 years), 18 specimens were from 12 patients with malignant pheochromocytoma (<13 year follow-up, mean 6.3 years), 5 samples were from 2 patients with malignant paraganglioma (<6 year follow-up, mean 4 years), and 2 specimens from 2 patients with benign paraganglioma (<7 year follow-up, mean 5.5 years). Malignancy was defined by metastases in non-chromaffin tissues. Staining intensity with the anti-survivin antibody was scored from 0 (none) to 3+ (heavy). Tissues from human kidney, breast, and melanoma served as controls. RESULTS: All pheochromocytoma/paraganglioma specimens stained either 2+ or 3+. By analysis of variance (ANOVA), there was no statistically significant difference between the staining intensity of benign and malignant samples. All normal adrenal medulla specimens stained positively with anti-survivin but to a lesser degree than the chromaffin cell tumors (P<0.01). CONCLUSIONS: Based on these findings, we conclude that (i) survivin may represent a novel neuroendocrine marker for chromaffin cell tumors, and (ii) survivin does not appear to reliably distinguish benign from malignant pheochromocytomas/paragangliomas and thus does not identify patients at risk of recurrent disease.     

The R345W mutation in EFEMP1 is pathogenic and causes AMD-like deposits in mice

Age-related macular degeneration (AMD) is the most common cause of vision loss in developed countries. A defining characteristic of this disorder is the accumulation of material between Bruch's membrane and the retinal pigment epithelium (RPE), first as microscopic basal deposits and later as clinically evident drusen. The pathogenesis of these deposits remains to be defined. Biochemical and genetic studies have suggested that inflammation and complement activation may play roles in AMD. Several lines of evidence also suggest that alterations to the extracellular matrix (ECM) of the RPE and choroid contribute to the development of AMD. The inherited macular degeneration Doyne honeycomb retinal dystrophy/Malattia Leventinese is thought to be caused by an R345W mutation in the EFEMP1 gene (also called fibulin-3). The pathogenicity of this mutation has been questioned because all individuals identified to date with the R345W mutation have shared a common haplotype. We investigated the pathogenicity of this mutation in families with early-onset macular degeneration and by generating Efemp1-R345W knockin mice. Genetic studies show that one of the identified families with the R345W mutation has a novel haplotype. The mutant Efemp1-R345W mice develop deposits of material between Bruch's membrane and the RPE, which resemble basal deposits in patients with AMD. These basal deposits contain Efemp1 and Timp3, an Efemp1 interacting protein. Evidence of complement activation was detected in the RPE and Bruch's membrane of the mutant mice. These results confirm that the R345W mutation in EFEMP1 is pathogenic. Further, they suggest that alterations in the ECM may stimulate complement activation, demonstrating a potential connection between these two etiologic factors in macular degeneration.     

Alternative medicine in atrial fibrillation treatment—Yoga,acupuncture, biofeedback and more

The last decade has seen a significant improvement in the management of atrial fibrillation (AF) with the development of newer medications and improvement in catheter ablation techniques. Recurrence of AF remains a significant problem in these patients and medications offer limited supportive role. Complementary and alternative treatment strategies therefore remain a viable option for these AF patients. Several studies have shown improvement in AF symptoms with yoga therapy, acupuncture and biofeedback. There are also several herbal medicine and supplements such as omega-3 fatty acids, antioxidant vitamins, barberry, motherwort, cinchona, Shensongyangxin, hawthorn, Kella and Wenxin Keli that have been evaluated as potential therapeutic options in AF. These studies are however limited by small sample sizes with mixed results. Besides the pharmacological action, metabolism, interactions with other medications and the adverse effects of the herbal medications and supplements remain poorly understood. In spite of the above limitations, complementary therapies remain a promising option in the management of AF and further studies are necessary to validate their safety and efficacy.     

Postprocedural neuropathy after atrial fibrillation ablation

Purpose

Access-related neuropathy after atrial fibrillation (AF) ablation is underappreciated. We intend to describe the incidence, management, and prognosis of postprocedural neuropathy after AF ablation.

Methods

We performed a retrospective analysis of all consecutive patients with postprocedural neuropathy who underwent AF ablation in three high-volume tertiary care hospitals between January 2007 and April 2011.

Results

Of the 3,128 patients who underwent AF ablation during the study period, 25 (0.8 %) patients had postprocedural neuropathy and were included in the current study. Mean age was 58.5?±?11.5 years with 18 (72 %) being males and 14 (56 %) having paroxysmal AF. Ulnar nerve, lateral femoral cutaneous nerve manifesting as meralgia paresthetica, and femoral nerve were involved in 5 (20 %), 13 (54 %), and 7 (26 %) of the patients, respectively. Majority of neuropathies were associated with periprocedural hematomas (19, 76 %), and a quarter (19/72, 26 %) of all hematomas were associated with neuropathy. Initial treatment included warm and cold compresses followed by nonsteroidal anti-inflammatory and narcotic pain medications. In addition to the above regimen, in some patients (11, 44 %), oral gabapentin was used and it was associated with a shorter time to symptom resolution (9.4 vs. 14.1 days, p?=?0.007). All patients were symptom free within 90 days of the procedure.

Conclusion

Postprocedural neuropathy after AF ablation is rare and is frequently associated with a periprocedural hematoma. Patients typically become symptom free within 90 days of the procedure, and gabapentin may have a role in earlier symptom resolution.