Enhanced intra-articular therapy for rheumatoid arthritis using click-crosslinked hyaluronic acid hydrogels loaded with toll-like receptor antagonizing peptides.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that results in the deterioration of joint cartilage and bone. Toll-like receptor 4 (TLR4) has been pinpointed as a key factor in RA-related inflammation. While Toll-like receptor antagonizing peptide 2 (TAP2) holds potential as an anti-inflammatory agent, its in vivo degradation rate hinders its efficacy. We engineered depots of TAP2 encapsulated in click-crosslinked hyaluronic acid (TAP2+Cx-HA) for intra-articular administration, aiming to enhance the effectiveness of TAP2 as an anti-inflammatory agent within the joint cavity. Our data demonstrated that FI-TAP2+Cx-HA achieves a longer retention time in the joint cavity compared to FI-TAP2 alone. Mechanistically, we found that TAP2 interacts with TLR4 on the cell membranes of inflammatory cells, thereby inhibiting the nuclear translocation of NF-κB and maintaining it in an inactive cytoplasmic state. In a rat model of RA, the TAP2+Cx-HA formulation effectively downregulated the inflammatory cytokines TNF-α and IL-6, while upregulating the anti-inflammatory cytokine IL-10 and the therapeutic protein 14-3-3ζ. This led to a more rapid restoration of cartilage thickness, increased deposition of glycosaminoglycans, and new bone tissue formation in the regenerated cartilage, in comparison to a single TAP2 treatment after a six-week period. Our results suggest that TAP2+Cx-HA could serve as a potent intra-articular treatment for RA, offering both symptomatic relief and promoting cartilage regeneration. This innovative delivery system holds significant promise for improving the management of RA and other inflammatory joint conditions. STATEMENT OF SIGNIFICANCE: In this study, we developed a therapy by creating toll-like receptor 4 (TLR4)-antagonizing peptide (TAP2)-loaded click-crosslinked hyaluronic acid (TAP2+Cx-HA) depots for direct intra-articular injection. Our study demonstrates that FI-TAP2+Cx-HA exhibits a more than threefold longer lifetime in the joint cavity compared to FI-TAP2 alone. Furthermore, we found that TAP2 binds to TLR4 and masks the nuclear localization signals of NF-κB, leading to its sequestration in an inactive state in the cytoplasm. In a rat model of RA, TAP2+Cx-HA effectively suppresses inflammatory molecules, specifically TNF-α and IL-6, while upregulating the anti-inflammatory cytokine IL-10 and the therapeutic protein 14-3-3ζ. This resulted in faster regeneration of cartilage thickness, increased glycosaminoglycan deposits in the regenerated cartilage, and a twofold increase in new bone tissue formation compared to a single TAP2 treatment.

Development and In Vivo Assessment of an Injectable Cross-Linked Cartilage Acellular Matrix-PEG Hydrogel Scaffold Derived from Porcine Cartilage for Tissue Engineering.

The cartilage acellular matrix (CAM) derived from porcine cartilage, which does not induce significant inflammation and provides an environment conducive for cell growth and differentiation, is a promising biomaterial candidate for scaffold fabrication. However, the CAM has a short period in vivo, and the in vivo maintenance is not controlled. Therefore, this study is aimed at developing an injectable hydrogel scaffold using a CAM. The CAM is cross-linked with a biocompatible polyethylene glycol (PEG) cross-linker to replace typically used glutaraldehyde (GA) cross-linker. The cross-linking degree of cross-linked CAM by PEG cross-linker (Cx-CAM-PEG) according to the ratios of the CAM and PEG cross-linker is confirmed by contact angle and heat capacities measured by differential scanning calorimetry. The injectable Cx-CAM-PEG suspension exhibits controllable rheological properties and injectability. Additionally, injectable Cx-CAM-PEG suspensions with no free aldehyde group are formed in the in vivo hydrogel scaffold almost simultaneously with injection. In vivo maintenance of Cx-CAM-PEG is realized by the cross-linking ratio. The in vivo formed Cx-CAM-PEG hydrogel scaffold exhibits certain host-cell infiltration and negligible inflammation within and near the transplanted Cx-CAM-PEG hydrogel scaffold. These results suggest that injectable Cx-CAM-PEG suspensions, which are safe and biocompatible in vivo, represent potential candidates for (pre-)clinical scaffolds.

Preparation and evaluation of injectable microsphere formulation for longer sustained release of donepezil.

In this study, donepezil-loaded PLGA and PLA microspheres (Dp-PLGA-M/Dp-PLA-M) and Dp-PLA-M wrapped in a polyethylene glycol-b-polycaprolactone (PC) hydrogel (Dp-PLA-M/PC) were prepared to reduce the dosing frequency of injections to treat Alzheimer's disease patients. Dp-PLGA-M and Dp-PLA-M with a uniform particle size distribution were repeatably fabricated in nearly quantitative yield and with high encapsulated Dp yields using an ultrasonic atomizer. The injectability and in vitro and in vivo Dp release, biodegradation, and inflammatory response elicited by the Dp-PLGA-M, Dp-PLA-M, and Dp-PLA-M/PC formulations were then compared. All injectable formulations showed good injectability with ease of injection, even flow, and no clogging using a syringe needle under 21-G. The injections required a force of <1 N. According to the biodegradation rate of micro-CT, GPC and NMR analyses, the biodegradation of Dp-PLA-M was slower than that of Dp-PLGA-M, and the biodegradation rate of Dp-PLA-M/PC was also slower. In the Dp release experiment, Dp-PLA-M sustained Dp for longer compared with Dp-PLGA-M. Dp-PLA-M/PC exhibited a longer sustained release pattern of two months. In vivo bioavailability of Dp-PLA-M/PC was almost 1.4 times higher than that of Dp-PLA-M and 1.9 times higher than that of Dp-PLGA-M. The variations in the Dp release patterns of Dp-PLGA-M and Dp-PLA-M were explained by differences in the degradation rates of PLGA and PLA. The sustained release of Dp by Dp-PLA-M/PC was attributed to the fact that the PC hydrogel served as a wrapping matrix for Dp-PLA-M, which could slow down the biodegradation of PLA-M, thus delaying the release of Dp from Dp-PLA-M. Dp-PLGA-M induced a higher inflammatory response compared to Dp-PLA-M/PC, suggesting that the rapid degradation of PLGA triggered a strong inflammatory response. In conclusion, Dp-PLA-M/PC is a promising injectable Dp formulation that could be used to reduce the dosing frequency of Dp injections.

Electrostatically optimized adapalene-loaded emulsion for the treatment of acne vulgaris.

Adapalene (AD) is an FDA-approved drug that shows good therapeutic efficacy for the treatment of acne vulgaris. However, due to its negative charge, AD cannot efficiently penetrate across the also negatively-charged skin membrane. This study is the first to assess the treatment of acne vulgaris using electrostatically optimized AD emulsions prepared using anionic AD with methoxy polyethylene glycol-b-poly(ε-caprolactone) (MC) as an anionic emulsifier coupled with a newly synthesized MC with different contents of an amine pendant-group (MC-[NH2]x) as a cationic emulsifier. The AD emulsion prepared using MC-[NH2]x with high cationic charge potential was significantly stable in the short-term studies compared with anionic MC or no emulsifier. Furthermore, the AD emulsion prepared with the cationic MC-[NH2]x emulsifier provided a two or three times stronger therapeutic effect against acne vulgaris than the AD emulsion prepared with the anionic MC emulsifier or no emulsifier in an animal study. Additionally, the AD emulsion with high cationic charge potential exerted a remarkable inhibition of macrophage expression, as confirmed by histological analysis. Therefore, the electrostatic interaction between the negatively-charged skin membrane and the AD emulsion prepared with the cationic MC-[NH2]x emulsifier provides a promising therapeutic strategy for acne vulgaris.

Comparison of Three Cardiovascular Risk Scores among HIV-Infected Patients in Korea: The Korea HIV/AIDS Cohort Study / 감염과화학요법

Background@#We investigated cardiovascular disease (CVD), risk factors for CVD, and applicability of the three known CVD risk equations in the Korean human immunodeficiency virus/ Acquired Immune Deficiency Syndrome (HIV/AIDS) cohort. @*Materials and Methods@#The study parcitipants were HIV-infected patients in a Korean HIV/ AIDS cohort enrolled from 19 hospitals between 2006 and 2017. Data collected at entry to the cohort were analyzed. The 5-year CVD risk in each participant was calculated using three CVD risk equations: reduced CVD prediction model of HIV-specific data collection on adverse effects of anti-HIV drugs (R-DAD), Framingham general CVD risk score (FRS), and Korean Coronary Heart Disease Risk Score (KRS). @*Results@#CVD events were observed in 11 of 586 HIV-infected patients during a 5-year (median) follow-up period. The incidence of CVD was 4.11 per 1,000 person-years. Older age (64 vs. 41 years, P = 0.005) and diabetes mellitus (45.5% vs. 6.4%, P <0.001) were more frequent in patients with CVD. Using R-DAD, FRS, and KRS, 1.9%, 2.4%, and 0.7% of patients, respectively, were considered to have a very high risk (≥10%) of 5-year CVD. The discriminatory capacities of the three prediction models were good, with c-statistic values of 0.829 (P <0.001) for R-DAD, 0.824 (P <0.001) for FRS, and 0.850 (P = 0.001) for KRS. @*Conclusion@#The FRS, R-DAD, and KRS performed well in the Korean HIV/AIDS cohort. A larger cohort and a longer period of follow-up may be necessary to demonstrate the risk factors and develop an independent CVD risk prediction model specific to Korean patients with HIV.

Endogenous Stem Cell-Based In Situ Tissue Regeneration Using Electrostatically Interactive Hydrogel with a Newly Discovered Substance P Analog and VEGF-Mimicking Peptide.

The use of chemoattractants to promote endogenous stem cell-based in situ tissue regeneration has recently garnered much attention. This study is the first to assess the endogenous stem cell migration using a newly discovered substance P (SP) analog (SP1) by molecular dynamics simulations as an efficient chemoattractant. Further, a novel strategy based on electrostatic interaction using cationic chitosan (Ch) and anionic hyaluronic acid (HA) to prepare an SP1-loaded injectable C/H formulation without SP1 loss is developed. The formulation quickly forms an SP1-loaded C/H hydrogel in situ through in vivo injection. The newly discovered SP1 is found to possess human mesenchymal stromal cells (hMSCs) migration-inducing ability that is approximately two to three times higher than that of the existing SP. The designed VEGF-mimicking peptide (VP) chemically reacts with the hydrogel (C/H-VP) to sustain the release of VP, thus inducing vasculogenic differentiation of the hMSCs that migrate toward the C/H-VP hydrogel. Similarly, in animal experiments, SP1 attracts a large number of hMSCs toward the C/H-VP hydrogel, after which VP induces vasculogenic differentiation. Collectively, these findings indicate that SP1-loaded C/H-VP hydrogels are a promising strategy to facilitate endogenous stem cell-based in situ tissue regeneration.

Preparation of a cross-linked cartilage acellular matrix-poly (caprolactone-ran-lactide-ran-glycolide) film and testing its feasibility as an anti-adhesive film.

To protect unwanted tissue adhesions occurring after surgeries, we aimed to fabricate an anti-adhesive film using cartilage acellular matrix (CAM) with anti-vascular inhibition activity. Additionally, to fabricate anti-adhesive films with tunable swelling, mechanical, and biodegradation properties, a biodegradable polyester (PEP) with N-hydroxysuccinimide (NHS) in the chain end position was synthesized as a cross-linker. CAM/PEP (CP) films were prepared with various CAM: PEP ratios in the wide size with repeatable reproducibility, and then, cross-linked CP (Cx-CP) were obtained by the interpenetrating cross-linking reaction between the amine group on CAM and the NHS group on PEP cross-linkers under thermal treatment. The biodegradation, wettability, swelling, and mechanical properties of the prepared anti-adhesive Cx-CP films were controlled by varying the CAM:PEP ratio. The degradation half-life, contact angle, elastic moduli and toughness of Cx-CP films increased according to the increasing PEP content. Additionally, Cx-CP films significantly inhibits the attachment and proliferation of HUVECs. Cx-CP film prepared by varying the CAM:PEP ratio can be tailored to meet individual requirements for in vivo injured tissues. In animal experiments, anti-adhesive Cx-CP films implanted between the peritoneal wall and the cecum significantly suppressed tissue adhesion between them. Additionally, good adhesion effect observed at anti-adhesive film maintained for proper time period at injured tissues. Taken together, in this work, we successfully achieved strategy for the development of anti-adhesive barrier with tunable swelling, mechanical, and biodegradation properties.

An injectable click-crosslinked hyaluronic acid hydrogel modified with a BMP-2 mimetic peptide as a bone tissue engineering scaffold.

An injectable, click-crosslinking (Cx) hyaluronic acid (HA) hydrogel scaffold modified with a bone morphogenetic protein-2 (BMP-2) mimetic peptide (BP) was prepared for bone tissue engineering applications. The injectable click-crosslinking HA formulation was prepared from HA-tetrazine (HA-Tet) and HA-cyclooctene (HA-TCO). The Cx-HA hydrogel scaffold was prepared simply by mixing HA-Tet and HA-TCO. The Cx-HA hydrogel scaffold was stable for a longer period than HA both in vitro and in vivo, which was verified via in-vivo fluorescence imaging in real time. BP acted as an osteogenic differentiation factor for human dental pulp stem cells (hDPSCs). After its formation in vivo, the Cx-HA scaffold provided a fine environment for the hDPSCs, and the biocompatibility of the hydrogel scaffold with tissue was good. Like traditional BMP-2, BP induced the osteogenic differentiation of hDPSCs in vitro. The physical properties and injectability of the chemically loaded BP for the Cx-HA hydrogel (Cx-HA-BP) were nearly identical to those of the physically loaded BP hydrogels and the Cx-HA-BP formulation quickly formed a hydrogel scaffold in vivo. The chemically loaded hydrogel scaffold retained the BP for over a month. The Cx-HA-BP hydrogel was better at inducing the osteogenic differentiation of loaded hDPSCs, because it prolonged the availability of BP. In summary, we successfully developed an injectable, click-crosslinking Cx-HA hydrogel scaffold to prolong the availability of BP for efficient bone tissue engineering.

Injectable In Situ-Forming Hydrogels for Protein and Peptide Delivery.

Injectable in situ-forming hydrogels have been used clinically in diverse biomedical applications. These hydrogels have distinct advantages such as easy management and minimal invasiveness. The hydrogels are aqueous formulations, and a simple injection at the target site replaces a traditional surgical procedure. Here, we review injectable in situ-forming hydrogels that are formulated by physical and chemical methods to deliver proteins and peptides. Prospects for using in situ-forming hydrogels for several specific applications are also discussed.

Substance P-loaded electrospun small intestinal submucosa/poly(ε-caprolactone)-ran-poly(l-lactide) sheet to facilitate wound healing through MSC recruitment.

In this work, we prepared an electrospun small intestinal submucosa/poly(ε-caprolactone)-ran-poly(l-lactide) (SIS/PCLA) sheet onto which substance P (SP) was loaded, and this was employed as a cell-free scaffold for wound healing through the mobilization of human mesenchymal stem cells (hMSCs). SP release from the SP-loaded scaffold was 42% at 12 h and 51% at 24 h due to an initial burst of SP, but after 1 day, it exhibited a linear release profile and was released at a sustained rate for 21 days. The SP-loaded SIS/PCLA sheet exhibited higher in vitro and in vivo hMSC migration than did the PCLA and SIS/PCLA sheets. Large hMSCs injected into the tail vein of mice models migrated towards the wound to a greater extent in the presence of the SP-loaded SIS/PCLA sheet than with the PCLA and SIS/PCLA sheets, as confirmed by the CD44 and CD29 markers of recruited hMSCs. In animal wound models, significantly higher wound contraction (∼97%) in the group treated with the SP-loaded SIS/PCLA sheet was observed compared with the PCLA (∼74%) and SIS/PCLA (∼84%) groups at 3 weeks. In addition, SP-loaded SIS/PCLA-treated animals showed significant epidermal regeneration and collagen density (56%) in the mature granulation tissue at 3 weeks compared to the PCLA and SIS/PCLA groups. The wound area after SP-loaded SIS/PCLA sheet treatment also showed high blood vessel formation at the early stage, resulting in enhanced wound healing. Furthermore, the SP-loaded SIS/PCLA group exhibited a lower macrophage count (2.9%) than did the PCLA (7.7%) and SIS/PCLA (3.4%) groups. It was thus confirmed that the use of SP-loaded SIS/PCLA sheet as a cell-free scaffold could effectively enhance wound healing through MSC recruitment.

An Injectable Click-Crosslinked Hydrogel that Prolongs Dexamethasone Release from Dexamethasone-Loaded Microspheres.

Our purpose was to test whether a preparation of injectable formulations of dexamethasone (Dex)-loaded microspheres (Dex-Ms) mixed with click-crosslinked hyaluronic acid (Cx-HA) (or Pluronic (PH) for comparison) prolongs therapeutic levels of released Dex. Dex-Ms were prepared using a monoaxial-nozzle ultrasonic atomizer with an 85% yield of the Dex-Ms preparation, encapsulation efficiency of 80%, and average particle size of 57 µm. Cx-HA was prepared via a click reaction between transcyclooctene (TCO)-modified HA (TCO-HA) and tetrazine (TET)-modified HA (TET-HA). The injectable formulations (Dex-Ms/PH and Dex-Ms/Cx-HA) were fabricated as suspensions and became a Dex-Ms-loaded hydrogel drug depot after injection into the subcutaneous tissue of Sprague Dawley rats. Dex-Ms alone also formed a drug depot after injection. The Cx-HA hydrogel persisted in vivo for 28 days, but the PH hydrogel disappeared within six days, as evidenced by in vivo near-infrared fluorescence imaging. The in vitro and in vivo cumulative release of Dex by Dex-Ms/Cx-HA was much slower in the early days, followed by sustained release for 28 days, compared with Dex-Ms alone and Dex-Ms/PH. The reason was that the Cx-HA hydrogel acted as an external gel matrix for Dex-Ms, resulting in the retarded release of Dex from Dex-Ms. Therefore, we achieved significantly extended duration of a Dex release from an in vivo Dex-Ms-loaded hydrogel drug depot formed by Dex-Ms wrapped in an injectable click-crosslinked HA hydrogel in a minimally invasive manner. In conclusion, the Dex-Ms/Cx-HA drug depot described in this work showed excellent performance on extended in vivo delivery of Dex.

An injectable cationic hydrogel electrostatically interacted with BMP2 to enhance in vivo osteogenic differentiation of human turbinate mesenchymal stem cells.

We have designed and characterized an injectable, electrostatically bonded, in situ-forming hydrogel system consisting of a cationic polyelectrolyte [(methoxy)polyethylene glycol-b-(poly(ε-caprolactone)-ran-poly(L-lactic acid)] (MP) copolymer derivatized with an amine group (MP-NH2) and anionic BMP2. To the best of our knowledge, there have been hardly any studies that have investigated electrostatically bonded, in situ-forming hydrogel systems consisting of MP-NH2 and BMP2, with respect to how they promote in vivo osteogenic differentiation of human turbinate mesenchymal stem cells (hTMSCs). Injectable formulations almost immediately formed an electrostatically loaded hydrogel depot containing BMP2, upon injection into mice. The hydrogel features and stability of BMP2 inside the hydrogel were significantly affected by the electrostatic attraction between BMP2 and MP-NH2. Additionally, the time BMP2 spent inside the hydrogel depot was prolonged in vivo, as evidenced by in vivo near-infrared fluorescence imaging. Biocompatibility was demonstrated by the fact that hTMSCs survived in vivo, even after 8 weeks and even though relatively few macrophages were in the hydrogel depot. The osteogenic capacity of the electrostatically loaded hydrogel implants containing BMP2 was higher than that of a hydrogel that was simply loaded with BMP2, as evidenced by Alizarin Red S, von Kossa, and hematoxylin and eosin staining as well as osteonectin, osteopontin, osteocalcin, and type 1α collagen mRNA expression. The results confirmed that our injectable, in situ-forming hydrogel system, electrostatically loaded with BMP2, can enhance in vivo osteogenic differentiation of hTMSCs.

Electrostatically Interactive Injectable Hydrogels for Drug Delivery.

BACKGROUND: Several injectable hydrogels have been developed extensively for a broad range of biomedical applications. Injectable hydrogels forming in situ through the change in external stimuli have the distinct properties of easy management and minimal invasiveness, and thus provide the advantage of bypassing surgical procedures for administration resulting in better patient compliance. METHODS: The injectable in situ-forming hydrogels can be formed irreversibly or reversibly under physiological stimuli. Among several external stimuli that induce formation of hydrogels in situ, in this review, we focused on the electrostatic interactions as the most simple and interesting stimulus. RESULTS: Currently, numerous polyelectrolytes have been reported as potential electrostatically interactive in situ-forming hydrogels. In this review, a comprehensive overview of the rapidly developing electrostatically interactive in situ-forming hydrogels, which are produced by various anionic and cationic polyelectrolytes such as chitosan, celluloses, and alginates, has been outlined and summarized. Further, their biomedical applications have also been discussed. CONCLUSION: The review concludes with perspectives on the future of electrostatically interactive in situ-forming hydrogels.

Sudden Deaths of Neonates Receiving Intravenous Infusion of Lipid Emulsion Contaminated with Citrobacter freundii

At an intensive care unit, four neonates died consecutively within 80 minutes. Citrobacter freundii was isolated from blood samples of the 4 patients. It was also cultured from the leftover SMOFlipid that had been infused intravenously into the patients. In this in vitro study, we evaluated the bacterial growth kinetics and change in size of fat globules in SMOFlipid contaminated with C. freundii. Following the growth of bacteria, pH of SMOFlipid decreased to < 6, and the number of fat globules larger than 5 µm increased. Pulmonary fat embolism is proposed as a possible cause of the sudden deaths as well as fulminant sepsis.

Identification of distinctive clinical significance in hospitalized patients with endoscopic duodenal mucosal lesions

BACKGROUND/AIMS: Duodenitis is not infrequent finding in patient undergoing endoscopy. However, hospitalized patients have a higher incidence of secondary duodenal mucosal lesions that might be related with inflammatory bowel disease (IBD), cytomegalovirus (CMV) infection, tuberculosis, immunologic disorders, or other rare infections. We aimed to identify clinicopathologic features of duodenal mucosal lesions in hospitalized patients. METHODS: All hospitalized patients having duodenal mucosal lesions were identified by endoscopic registration data and pathologic data query from 2011 to 2014. The diagnostic index was designed to be sensitive; however, a detailed review of medical record and endoscopic findings was undertaken to improve specificity. Secondary duodenal lesion was defined as having specific reason to explain the duodenal lesion. RESULTS: Among 6,334 hospitalized patients have undergone upper endoscopy, endoscopic duodenal mucosal lesions was detected in 475 patients. Secondary duodenal lesions was 21 patients (4.4%) and the most frequent secondary cause was IBD (n = 7). The mean age of secondary group was significantly lower than that in primary group (42.3 ± 18.9 years vs. 58.5 ± 16.8 years, p = 0.00), and nonsteroidal anti-inflammatory drugs were less frequently used in secondary group, but there was no differences of gender or presence of Helicobacter pylori. The involvement of distal part of duodenum including postbulbitis or panduodenitis was more frequently detected in secondary group than in primary group. By multivariate regression analysis, younger age of 29 years and the disease extent were significant predictors for the secondary mucosal lesions. CONCLUSIONS: Secondary duodenal mucosal lesions with different pathophysiology, such as IBD or CMV infection, are rare. Disease extent and age seems the most distinctive feature of secondary duodenal mucosal lesions.

Incidentally Discovered Aldosterone and Cortisol Cosecreting Adrenal Cortical Adenoma / 이화의대지

A substantial proportion of adrenal incidentalomas demonstrates subtle hormonal hypersecretion; however, adenomas that cosecrete aldosterone and cortisol are rare. We here report a case of an adrenal mass that was incidentally detected on a computed tomography scan in a 57-year-old man. The patient had a 10-year history of diabetes mellitus and a 5-year history of hypertension. Evaluation revealed hyperaldosteronemia with an elevated plasma aldosterone-to-renin ratio, hypokalemia, unsuppressed cortisol after dexamethasone administration, and elevated urinary free cortisol concentration. The appearance of the right adrenalectomy specimen indicated adrenal adenoma. Postoperatively, the blood glucose and blood pressure control improved and the urinary cortisol and aldosterone-to-renin ratio normalized. A complete endocrine evaluation in patients with incidentally discovered adrenal masses should be performed, even if the patient has a long-standing history of hypertension and diabetes, to avoid any postoperative adrenal crises.

Primary Malignant Melanoma of the Esophagus Treated by Early Diagnosis and Surgical Resection

Primary malignant melanoma of the esophagus is an extremely rare disease and accounts for approximately 0.1~0.2% of all esophageal malignancies. It is also a very aggressive disease with 5 year survival rates ranging from 2.2% to 37.5%. A 51-year-old woman with no previous medical history visited the hospital complaining of mild epigastric discomfort and belching. Endoscopy revealed a dark pigmented, polypoid lesion which was later diagnosed as primary malignant melanoma of the esophagus. Here we report a case of primary malignant melanoma of the esophagus that was diagnosed in a very early phase and successfully resected with an Ivor-Lewis procedure.

Spontaneous Renal Rupture Following Urinary Tract Infection and Its Recovery through Conservative Treatment / 이화의대지

Spontaneous renal rupture with subcapsular renal hematoma is a rare disease entity. Hereby, we report a 60-year-old female who presented with abrupt right flank pain and was diagnosed as spontaneous renal rupture with subcapsular hematoma related to urinary tract infection and review related literatures.

The effect of colpoperineoplasty on female sexual function / 대한산부인과학회지

OBJECTIVE: To evaluate female sexual function after colpoperineoplasty. METHODS: Women who visited regional clinic for colpoperineoplasty from June. 2004-Aug. 2004. filled in FSFI (The Female Sexual Function Index) questionnarie before and 4 months after surgery. Six weeks after surgery, they start pelvic muscle training with HMT 2000 (Korea, electric stimulator). RESULTS: Frequency of coitus, sexual desire, arousal, lubrication and orgasm was increased after colpoperineoplasty. Percentage of patients who had coitus more than once a week increased from 18% to 63%. In sexual desire, about 18% felt sexual arousal more than or about half the time before surgery, but increased to 45% after surgery. In sexual arousal, percentage of who felt sexually aroused during more than half of sexual activity increased from 34% before surgery to 69% after surgery. In Lubrication, percentage of who became lubricated during more than half of sexual activity increased from 44% before surgery to 82% after surgery. Who reached orgasm more than half of sexual activity increased from 29% before surgery to 70%. CONCLUSION: Colpoperineoplasty increased female sexual activity.

Conservative management of cervical pregnancy with H2O2 irrigation of cervical canal / 대한산부인과학회지

Prevent vaginal bleeding before and after conservative management of cervical pregnancy is the important part of the treatment. We can choose two methode for the conservative management of cervical pregnancy. One is curettage and bleeding control, and the other is using fetocidal agent. Most frequently used fetocidal agent is methotrexate. But additional treatment would be needed after single dose of MTX, and for multiple dosage of MTX, one should be hospitalized about 7 to 10 days. We have used H2O2 intracervical irrigation through enema syringe for conservative management of cervical pregnancy, which is very useful and has no risk of consequent bleeding. So we report it with brief review of literatures.