Effective strategies for the management of pyoderma gangrenosum: a comprehensive review.

Pyoderma gangrenosum (PG) is an inflammatory disease characterized by painful skin ulcerations with undermined and erythematous borders. The etiology of PG is not well understood, but it is generally considered to be an aberrant immune response characterized by a dermal neutrophilc infiltrate. Given the existence of only a few PG clinical trials, treatment options are largely based upon anecdotal data and small case studies. In addition to classic immunosuppressive medications, PG has been reported to respond well to the anti-TNF agents, infliximab, etanercept, adalimumab. Newer biologics such as ustekinumab (anti-IL-23), ixekizumab (anti-IL-17) and brodalumab (anti-IL-17R) are promising given the effect of IL-17 on neutrophil migration. However, the effectiveness of these newer agents remains to be rigorously evaluated. Multi-drug regimens have not been well described in the literature but are an excellent alternative for patients with refractory disease. Herein, we provide a comprehensive review of the pathophysiology of PG and of the different treatments available for managing PG patients, including the theoretical benefit of initiating multidrug regimens. We also provide one possible treatment algorithm for patients with refractory disease and give examples of refractory PG cases successfully treated with multidrug regimens.

Metastatic melanoma - a review of current and future treatment options.

Despite advances in treatment and surveillance, melanoma continues to claim approximately 9,000 lives in the US annually (SEER 2013). The National Comprehensive Cancer Network currently recommends ipilumumab, vemurafenib, dabrafenib, and high-dose IL-2 as first line agents for Stage IV melanoma. Little data exists to guide management of cutaneous and subcutaneous metastases despite the fact that they are relatively common. Existing options include intralesional Bacillus Calmette-Guérin, isolated limb perfusion/infusion, interferon-α, topical imiquimod, cryotherapy, radiation therapy, interferon therapy, and intratumoral interleukin-2 injections. Newly emerging treatments include the anti-programmed cell death 1 receptor agents (nivolumab and pembrolizumab), anti-programmed death-ligand 1 agents, and oncolytic vaccines (talimogene laherparepevec). Available treatments for select sites include adoptive T cell therapies and dendritic cell vaccines. In addition to reviewing the above agents and their mechanisms of action, this review will also focus on combination therapy as these strategies have shown promising results in clinical trials for metastatic melanoma treatment.

Blastic Plasmacytoid Dendritic Cell Neoplasm: Progress in Cell Origin, Molecular Biology, Diagnostic Criteria and Therapeutic Approaches.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy characterized by recurrent skin nodules, an aggressive clinical course with rapid involvement of hematological organs, and a poor prognosis with poor overall survival. BPDCN is derived from plasmacytoid dendritic cells (pDCs) and its pathogenesis is unclear. The tumor cells show aberrant expression of CD4, CD56, interleukin-3 receptor alpha chain (CD123), blood dendritic cell antigen 2 (BDCA 2/CD303), blood dendritic cell antigen 4 (BDCA4) and transcription factor (E protein) E2-2 (TCF4). The best treatment drugs are based on experience by adopting those used for either leukemia or lymphoma. Relapse with drug resistance generally occurs quickly. Stem cell transplantation after the first complete remission is recommended and tagraxofusp is the first targeted therapy. In this review, we summarize the differentiation of BPDCN from its cell origin, its connection with normal pDCs, clinical characteristics, genetic mutations and advances in treatment of BPDCN. This review provides insights into the mechanisms of and new therapeutic approaches for BPDCN.

[A Study On The Fine Structure Of Clonorchis Sinensis, A Liver Fluke: II. The Alimentary Tract And The Excretory System]

A morphological study on the ultrastructures of the alimentary tract and the excretory system of Clonorchis sinensis was conducted. The liver flukes were collected from rabbit liver six months after the experimental infection The worms were washed with 0.85% saline solution and immediately moved to cold 2.5% glutaraldehyde in 0.1 M phosphate buffer pH 7.4. The materials were dissected and fixed for two hours. The blocks were post-fixed in 1% osmium tetroxide. The blocks were embedded in Epon 812. Ultra thin sections were cut with Sovall MT-2 ultramicrotome and stained with uranyl acetate and lead citrate. Sections were then observed with Hitachi HS-7S electron microscope. The following results were obtained in a series of observations. The walls of oral cavity and esophagus comprised tegumental syncytium, basement membrane, loose connective tissue, muscular layer and parenchymal cells. The apical surface and the base of the syncytium were covered with a protoplasmic membrane for each forming numerous invaginations. Granular endoplasmic reticulum was developed in the epithelium of the oesophagus. The gastrodermis of Clonorchis sinensis comprised two types of cells in general. The first cell type was numerous one forming a single continuous layer of epithelial cells. Each of the cells had outfolded cytoplasm into the caecal lumen and lamellae along the cell surface. Among the above epithelial cells, no considerable differences in structure reflecting their functional states were identified. The second cell type was less differentiated in nature and lay within the gastrodermis above the basement membrane but not in contact with the caecal lumen, being overlapped by neighboring gastrodermal cells of the type described above. At this portion the gastrodermis seemed to be a pseudostratified epithelium. There were well-developed lamellae along the surface of epithelia of all canals or duct concerning evacuation. The excretory pore was 7.5 micrometer in diameter and dorso-terminally opended. The epithelium of the excretory pore, a syncytial layer, contained many microtubules unlike the other part of tegumental layer of this worm. The epithelium thickness of the excretory pore was very irregular(1.3-5.5 micrometer).

A Morphological Study On Spermatogenesis In The Liver Fluke, Clonorchis Sinensis.

Spermatogenesis in liver flukes, C. sinensis, was investigated by using light and electron microscopes. The epithelium of the testis was composed of a basement membrane, numerous lamellae protuded from the membrance and large number of spermatogonia supported by the lamellae. The lumen of the testis was filled with numerous 8, 16 and 32-cell groups representing primary spermatocytes, secondary spermatocytes and spermatids respectively. None of cell groups with over 32 or under 8 cells was noticed. The process of spermatogenesis is presumably as follows; A cell group of 8 spermatogonia, attached together by a cytophore, is separated from the testis epithelium during the growth period, thus becoming primary spermatocytes. The primary spermatocytes divide to form a cell group of 16 secondary spermatocytes giving rise to a cell group of 32 spermatids through meiotic germ cell division. The spermatids begin to undergo a spermiogenesis. The newly formed sperms remain attached together in the lumen for a while before migrating through the vasa efferentia.

The Effect of High dose Corticosteroid Therapy on the Optic Nerve Head Blood Flow in Experimental Traumatic Optic Neuropathy

The objective of this study was to establish the effect of high dose steroid therapy in traumatic optic neuropathy with Heidelberg Retina Flowmeter(HRF) to detect the changes of optic nerve head bleed flow. HRF permits the noninvasive assessment of the blood velocity, volume and flow(flux) in a sample volume of the nerve head. Such measurements were performed in two groups of experimental traumatic optic neuropathy rabbits. We experimentally damaged the optic nerves of ten white rabbits with a Hartman mosquito. The first group(n=5) was intravenously infected with 0.25mg/kg dexamethasone every six hours for a 48 hour period. The second group(n-5) was used as controls. Both groups were tested before operation, 1 week, 1 month, and 2 months later Experimental optic nerve damage created a significant decrease in optic nerve head blood flow 50.51%(p=0.001), with blood volume decreased by 46.02%(p=0.001) and blood velocity reduced by 43.12%(p=0.002) compared to the baseline value. After 2 months of high dose corticosteroid therapy, optic nerve head blood flow was increased by 76.90% (p=0.012), blood volume 77.53%(p=0.012)and blood velocity 47.21%(p=0.012) as compared to control group. The high dose corticosteroid therapy improved the optic nerve head blood flow as demonstrated in traumatic optic neuropathy. HRF may be used to assess the therapeutic responses in traumatic optic neuropathy under variable conditions.

A study on the fine structure of Clonorchis sinensis, a liver fluke II. The alimentary tract and the excretory system

A morphological study on the ultrastructures of the alimentary tract and the excretory system of Clonorchis sinensis was conducted. The liver flukes were collected from rabbit liver six months after the experimental infection The worms were washed with 0.85 percent saline solution and immediately moved to cold 2.5 percent glutaraldehyde in 0.1 M phosphate buffer pH 7.4. The materials were dissected and fixed for two hours. The blocks were post-fixed in 1 percent osmium tetroxide. The blocks were embedded in Epon 812. Ultra thin sections were cut with Sovall MT-2 ultramicrotome and stained with uranyl acetate and lead citrate. Sections were then observed with Hitachi HS-7S electron microscope. The following results were obtained in a series of observations. The walls of oral cavity and esophagus comprised tegumental syncytium, basement membrane, loose connective tissue, muscular layer and parenchymal cells. The apical surface and the base of the syncytium were covered with a protoplasmic membrane for each forming numerous invaginations. Granular endoplasmic reticulum was developed in the epithelium of the oesophagus. The gastrodermis of Clonorchis sinensis comprised two types of cells in general. The first cell type was numerous one forming a single continuous layer of epithelial cells. Each of the cells had outfolded cytoplasm into the caecal lumen and lamellae along the cell surface. Among the above epithelial cells, no considerable differences in structure reflecting their functional states were identified. The second cell type was less differentiated in nature and lay within the gastrodermis above the basement membrane but not in contact with the caecal lumen, being overlapped by neighboring gastrodermal cells of the type described above. At this portion the gastrodermis seemed to be a pseudostratified epithelium. There were well-developed lamellae along the surface of epithelia of all canals or duct concerning evacuation. The excretory pore was 7.5 micrometer in diameter and dorso-terminally opended. The epithelium of the excretory pore, a syncytial layer, contained many microtubules unlike the other part of tegumental layer of this worm. The epithelium thickness of the excretory pore was very irregular(1.3-5.5 micrometer).

A morphological study on spermatogenesis in the liver fluke, Clonorchis sinensis

Spermatogenesis in liver flukes, C. sinensis, was investigated by using light and electron microscopes. The epithelium of the testis was composed of a basement membrane, numerous lamellae protuded from the membrance and large number of spermatogonia supported by the lamellae. The lumen of the testis was filled with numerous 8, 16 and 32-cell groups representing primary spermatocytes, secondary spermatocytes and spermatids respectively. None of cell groups with over 32 or under 8 cells was noticed. The process of spermatogenesis is presumably as follows; A cell group of 8 spermatogonia, attached together by a cytophore, is separated from the testis epithelium during the growth period, thus becoming primary spermatocytes. The primary spermatocytes divide to form a cell group of 16 secondary spermatocytes giving rise to a cell group of 32 spermatids through meiotic germ cell division. The spermatids begin to undergo a spermiogenesis. The newly formed sperms remain attached together in the lumen for a while before migrating through the vasa efferentia.

Central Vagal Involvement in Ovarian Innervation of the Rat / 체질인류학회지

The mammalian ovary has been known as receiving its innervation by sympathetic and sensory neurons of the peripheral nervous system from the brain. Recently, there were several functional reports that the vagus nerves were also regulating the ovarian function, but the vagus nerve had not been identified by clear morphological evidence. A viral transneuronal tracing technique has been used to demonstrate the morphological evidence for the central vagal involvement in ovarian innervation in brain areas. Bartha strain of pseudorabies virus injection was made into the ovary of Sprague Dawley rats. In experimental group, the vagus nerve of the same injection side was removed right after ovarian injection. At five days after initial injection, all the rats were sacrificed and brains were processed for immunohistochemistry. Several central nuclei including hypothalamic paraventricular nucleus showed strong bilateral positive labelings after unilateral injection in control rats, but the positive labelings were disappeared or decreased in several hypothalamic nuclei and nuclei of the vagus nerve. In conclusion, these results provide the morphological evidence that vagus nerve has neural connection to ovary and by which the central nervous system may maintains the state of ovulation and reproduction as a possible parasympathetic routes in mammals.

A Case of Pulmonary and Retroperitoneal Lymphangioleiomyomatosis / 결핵

Lymphangioleiomyomatosis, a rare disease in women of childbearing age, is the result of benign nodular hypertrophy of the smooth muscle of the lypmhatics and other tissues of the abdomen and thorax. We report a 36-years-old woman with pulmonary and retroperitoneal lymphangioleiomyomatosis who responded with hormone treatment. She developed vaginal pruritis and a pelvic ultraound was done given her significant past medical history. Ultrasound examination demonstrated a large mass in the right side of her pelvis. Therefore she was admitted to St. Michael's Hospital in Toronto for laparoscopy. Result of cytology was to be consistent with the diagnosis of retroperitoneal lymphangioleiomyomatosis. High resolution CT sacn of the thorax demonstrated multiple small cystic lesions, without associated nodularity compatible with a diagnosis of pulmonary lymphangioleiomyomatosis. She has been taking Provera tablets l00mg po tid since Dec. 15, 1993. We have given her a prescription for Depo provera 500mg IM monthly since she came back to Korea, and made arrangements for regular follow up monthly. We performed chest X-ray, CT of chest(high resolution), abdomen and pelvis, pulmonary function tests and arterial blood gas analysis. Chest X-ray and CT findings showed no significant change since July. 20, 1993.