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Background: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure (HF) with clinical phenotypes that vary across regions and genotypes. We sought to characterize the clinical characteristics of ATTR-CM in Asia., Methods: Data from a nationwide cohort of patients with ATTR-CM from six major tertiary centres in South Korea were analysed between 2010 and 2021. All patients underwent clinical evaluation, biochemical laboratory tests, echocardiography, and transthyretin (TTR) genotyping at the time of diagnosis. The study population comprised 105 Asian ATTR-CM patients (mean age: 69 years; male: 65.7%, wild-type ATTR-CM: 41.9%)., Results: Among our cohort, 18% of the patients had a mean left ventricular (LV) wall thickness < 12 mm. The diagnosis of ATTR-CM increased notably during the study period (8 [7.6%] during 2010-2013 vs. 22 [21.0%] during 2014-2017 vs. 75 [71.4%] during 2018-2021). Although the duration between symptom onset and diagnosis did not differ, the proportion of patients with HF presenting mild symptoms increased during the study period (25% NYHA class I/II between 2010-2013 to 77% between 2018-2021). In contrast to other international registry data, male predominance was less prominent in wild-type ATTR-CM (68.2%). The distribution of TTR variants was also different from Western countries and from Japan. Asp38Ala was the most common mutation., Conclusion: A nationwide cohort of ATTR-CM exhibited less male predominance, a proportion of patients without increased LV wall thickness, and distinct characteristics of genetic mutations, compared to cohorts in other parts of the world. Our results highlight the ethnic variation in ATTR-CM and may contribute to improving the screening process for ATTR-CM in the Asian population., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry., Methods: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY)., Results: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY)., Conclusion: There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications., Trial Registration: ClinicalTrials.gov Identifier: NCT01389843., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: Although the primary vaccine coverage rate for coronavirus disease 2019 (COVID-19) in South Korea has exceeded 80%, the coronavirus continues to spread, with reports of a rapid decline in vaccine effectiveness. South Korea is administering booster shots despite concerns about the effectiveness of the existing vaccine., Methods: Neutralizing antibody inhibition scores were evaluated in two cohorts after the booster dose. For the first cohort, neutralizing activity against the wild-type, delta, and omicron variants after the booster dose was evaluated. For the second cohort, we assessed the difference in neutralizing activity between the omicron infected and uninfected groups after booster vaccination. We also compared the effectiveness and adverse events (AEs) between homologous and heterologous booster doses for BNT162b2 or ChAdOx1 vaccines., Results: A total of 105 healthcare workers (HCWs) that were additionally vaccinated with BNT162b2 at Soonchunhyang University Bucheon Hospital were enrolled in this study. Significantly higher surrogate virus neutralization test (sVNT) inhibition (%) was observed for the wild-type and delta variants compared to sVNT (%) for the omicron after the booster dose (97%, 98% vs. 75%; P < 0.001). No significant difference in the neutralizing antibody inhibition score was found between variants in the BNT/BNT/BNT group (n = 48) and the ChA/ChA/BNT group (n = 57). Total AEs were not significantly different between the ChA/ChA/BNT group (85.96%) and the BNT/BNT group (95.83%; P = 0.11). In the second cohort with 58 HCWs, markedly higher sVNT inhibition to omicron was observed in the omicron-infected group (95.13%) compared to the uninfected group (mean of 48.44%; P < 0.001) after four months of the booster dose. In 41 HCWs (39.0%) infected with the omicron variant, no difference in immunogenicity, AEs, or effectiveness between homogeneous and heterogeneous boosters was observed., Conclusion: Booster vaccination with BNT162b2 was significantly less effective for the neutralizing antibody responses to omicron variant compared to the wild-type or delta variant in healthy population. Humoral immunogenicity was sustained significantly high after 4 months of booster vaccine in the infected population after booster vaccination. Further studies are needed to understand the characteristics of immunogenicity in these populations., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Background: The purpose of study was to investigate the incidence rate of suicide in elderly patients with osteoporotic fractures in a nested case-control model and to analyze the change in the risk of suicide death over time after each osteoporotic fracture., Methods: We used the National Health Insurance Service-Senior cohort of South Korea. Suicide cases and controls were matched based on sex and age at the index date. Controls were randomly selected at a 1:5 ratio from the set of individuals who were at risk of becoming a case at the time when suicide cases were selected. Conditional logistic regression analysis was performed to evaluate the association between each type of osteoporotic fracture and the risk of suicide death., Results: Three thousand seventy suicide cases and 15,350 controls were identified. Patients with hip fracture showed an increased risk of suicide death within 1 year of fracture (adjusted odds ratio [aOR] = 2.64; 95% confidence interval [CI], 1.57-4.46; P < 0.001) compared to controls. However, the increased risk of suicide death in patients with hip fracture lasted up to 2 years (aOR = 1.59; 95% CI, 1.04-2.41; P = 0.031). Spine fracture increased the risk of suicide deaths for all observation periods. There was no evidence that humerus fracture increased the risk of suicide death during the observational period. Radius fracture increased only the risk of suicide death within 2 years of fracture (aOR = 1.43; 95% CI, 0.74-2.77; P = 0.282)., Conclusion: There were noticeable differences in both degree and duration of increased suicide risks depending on the type of osteoporotic fracture. Mental stress and suicide risk in elderly patients after osteoporotic fracture should be assessed differently depending on the types of fracture., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Backgrounds: The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has spread worldwide. Cardiac injury after SARS-CoV-2 infection is a major concern. The present study investigated impact of the biomarkers indicating cardiac injury in coronavirus disease 2019 (COVID-19) on patients' outcomes., Methods: This study enrolled patients who were confirmed to have COVID-19 and admitted at a tertiary university referral hospital between February 19, 2020 and March 15, 2020. Cardiac injury was defined as an abnormality in one of the following result markers: 1) myocardial damage marker (creatine kinase-MB or troponin-I), 2) heart failure marker (N-terminal-pro B-type natriuretic peptide), and 3) electrical abnormality marker (electrocardiography). The relationship between each cardiac injury marker and mortality was evaluated. Survival analysis of mortality according to the scoring by numbers of cardiac injury markers was also performed., Results: A total of 38 patients with COVID-19 were enrolled. Twenty-two patients (57.9%) had at least one of cardiac injury markers. The patients with cardiac injuries were older (69.6 ± 14.9 vs. 58.6 ± 13.9 years old, P = 0.026), and were more male (59.1% vs. 18.8%, P = 0.013). They showed lower initial oxygen saturation (92.8 vs. 97.1%, P = 0.002) and a trend toward higher mortality (27.3 vs. 6.3%, P = 0.099). The increased number of cardiac injury markers was significantly related to a higher incidence of in-hospital mortality which was also evidenced by Kaplan-Meier survival analysis ( P = 0.008)., Conclusion: The increased number of cardiac injury markers is related to in-hospital mortality in patients with COVID-19., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Although various basal-bolus insulin therapy (BBIT) protocols have been used in the clinical environment, safer and more effective BBIT protocols are required for glucose control in hospitalized patients with type 2 diabetes (T2D). Modeling approaches could provide an evaluation environment for developing the optimal BBIT protocol prior to clinical trials at low cost and without risk of danger. In this study, an in-silico model was proposed to evaluate subcutaneous BBIT protocols in hospitalized patients with T2D. The proposed model was validated by comparing the BBIT protocol and sliding-scale insulin therapy (SSIT) protocol. The model was utilized for in-silico trials to compare the protocols of adjusting basal-insulin dose (BBIT1) versus adjusting total-daily-insulin dose (BBIT2). The model was also used to evaluate two different initial total-daily-insulin doses for various levels of renal function. The BBIT outcomes were superior to those of SSIT, which is consistent with earlier studies. BBIT2 also outperformed BBIT1, producing a decreased daily mean glucose level and longer time-in-target-range. Moreover, with a standard dose, the overall daily mean glucose levels reached the target range faster than with a reduced-dose for all degrees of renal function. The in-silico studies demonstrated several significant findings, including that the adjustment of total-daily-insulin dose is more effective than changes to basal-insulin dose alone. This research represents a first step toward the eventual development of an advanced model for evaluating various BBIT protocols.

Breast cancer is the second leading cancer for Korean women and its incidence rate has been increasing annually. If early diagnosis were implemented with epidemiologic data, the women could easily assess breast cancer risk using internet. National Cancer Institute in the United States has released a Web-based Breast Cancer Risk Assessment Tool based on Gail model. However, it is inapplicable directly to Korean women since breast cancer risk is dependent on race. Also, it shows low accuracy (58%-59%). In this study, breast cancer discrimination models for Korean women are developed using only epidemiological case-control data (n = 4,574). The models are configured by different classification techniques: support vector machine, artificial neural network, and Bayesian network. A 1,000-time repeated random sub-sampling validation is performed for diverse parameter conditions, respectively. The performance is evaluated and compared as an area under the receiver operating characteristic curve (AUC). According to age group and classification techniques, AUC, accuracy, sensitivity, specificity, and calculation time of all models were calculated and compared. Although the support vector machine took the longest calculation time, the highest classification performance has been achieved in the case of women older than 50 yr (AUC = 64%). The proposed model is dependent on demographic characteristics, reproductive factors, and lifestyle habits without using any clinical or genetic test. It is expected that the model could be implemented as a web-based discrimination tool for breast cancer. This tool can encourage potential breast cancer prone women to go the hospital for diagnostic tests.

The purpose of this study was to elucidate the origin and cellular composition of retrocorneal membranes (RCMs) associated with chemical burns using immunohistochemical staining for primitive cell markers. Six cases of RCMs were collected during penetrating keratoplasty. We examined RCMs with hematoxylin and eosin (H&E), periodic acid-Schiff (PAS) staining and immunohistochemical analysis using monoclonal antibodies against hematopoietic stem cells (CD34, CD133, c-kit), mesenchymal stem cells (beta-1-integrin, TGF-β, vimentin, hSTRO-1), fibroblasts (FGF-β, α-smooth muscle actin), and corneal endothelial cells (type IV collagen, CD133, VEGF, VEGFR1). Histologic analysis of RCMs revealed an organized assembly of spindle-shaped cells, pigment-laden cells, and thin collagenous matrix structures. RCMs were positive for markers of mesenchymal stem cells including beta-1-integrin, TGF-β, vimentin, and hSTRO-1. Fibroblast markers were also positive, including FGF-β and α-smooth muscle actin (SMA). In contrast, immunohistochemical staining was negative for hematopoietic stem cell markers including CD34, CD133 and c-kit as well as corneal endothelial cell markers such as type IV collagen, CD133 except VEGF and VEGFR1. Pigment-laden cells did not stain with any antibodies. The results of this study suggest that RCMs consist of a thin collagen matrix and fibroblast-like cells and may be a possible neogenetic structure produced from a lineage of bone marrow-derived mesenchymal stem cells.

Heart failure (HF) complicating acute myocardial infarction (AMI) is common and is associated with poor clinical outcome. Limited data exist regarding the incidence and in-hospital mortality of AMI with HF (AMI-HF). We retrospectively analyzed 1,427 consecutive patients with AMI in the five major university hospitals in Korea at two time points, 1998 (n = 608) and 2008 (n = 819). Two hundred twenty eight patients (37.5%) in 1998 and 324 patients (39.5%) in 2008 of AMI patients complicated with HF (P = 0.429). AMI-HF patients in 2008 were older, had more hypertension, previous AMI, and lower systolic blood pressure than those in 1998. Regarding treatments, AMI-HF patients in 2008 received more revascularization procedures, more evidence based medical treatment and adjuvant therapy, such as mechanical ventilators, intra-aortic balloon pulsation compared to those in 1998. However, overall in-hospital mortality rates (6.4% vs 11.1%, P = 0.071) of AMI-HF patients were unchanged and still high even after propensity score matching analysis, irrespective of types of AMI and revascularization methods. In conclusion, more evidence-based medical and advanced procedural managements were applied for patients with AMI-HF in 2008 than in 1998. However the incidence and in-hospital mortality of AMI-HF patients were not significantly changed between the two time points.

The incretin effect, which is a unique stimulus of insulin secretion in response to oral ingestion of nutrients, is calculated by the difference in insulin secretory responses from an oral glucose tolerance test (OGTT) and a corresponding isoglycemic intravenous glucose infusion (IIGI) study. The OGTT model of this study, which is individualized by fitting the glucose profiles during an OGTT, was developed to predict the glucose profile during an IIGI study in the same subject. Also, the model predicts the insulin and incretin profiles during both studies. The incretin effect, estimated by simulation, was compared with that measured by physiologic studies from eight human subjects with normal glucose tolerance, and the result exhibited a good correlation (r > 0.8); the incretin effect from the simulation was 56.5% ± 10.6% while the one from the measured data was 52.5% ± 19.6%. In conclusion, the parameters of the OGTT model have been successfully estimated to predict the profiles of both OGTTs and IIGI studies. Therefore, with glucose data from the OGTT alone, this model could control and predict the physiologic responses, including insulin secretion during OGTTs and IIGI studies, which could eventually eliminate the need for complex and cumbersome IIGI studies in incretin research.

The purpose of this study was to evaluate the relation between ocular discomfort and ocular Demodex infestation, and therapeutic effects of tea tree oil (TTO) in Demodex blepharitis patients. Three hundred and thirty-five patients with ocular discomfort were evaluated for ocular Demodex infestation and subjective symptoms with ocular surface discomfort index (OSDI) score. Among them, Demodex-infested patients were randomized to receive either eyelid scrubbing with TTO (TTO group,106 patients) or without TTO (Control group, 54 patients) for 1 month. Demodex were found in 84% of patients with ocular discomfort. The number of Demodex was significantly correlated with age (P = 0.04) and OSDI score (P = 0.024). After eyelid scrub treatment, Demodex count was reduced from 4.0 ± 2.5 to 3.2 ± 2.3 in the TTO group (P = 0.004) and from 4.3 ± 2.7 to 4.2 ± 2.5 in the control group (P = 0.27). Also, OSDI score was reduced from 34.5 ± 10.7 to 24.1 ± 11.9 in the TTO group (P = 0.001) and from 35.3 ± 11.6 to 27.5 ± 12.8 in the control group (P = 0.04). In conclusion, Demodex number showed a significant positive correlation with age and subjective ocular discomfort. The tea tree oil eyelid scrub treatment is effective for eliminating ocular Demodex and improving subjective ocular symptoms.

The purpose of this study was to investigate clinical and immunological responses to Demodex on the ocular surface. Thirteen eyes in 10 patients with Demodex blepharitis and chronic ocular surface disorders were included in this study and treated by lid scrubbing with tea tree oil for the eradication of Demodex. We evaluated ocular surface manifestations and Demodex counts, and analyzed IL-1β, IL-5, IL-7, IL-12, IL-13, IL-17, granulocyte colony-stimulating factor, and macrophage inflammatory protein-1β in tear samples before and after the treatment. All patients exhibited ocular surface manifestations including corneal nodular opacity, peripheral corneal vascularization, refractory corneal erosion and infiltration, or chronic conjunctival inflammatory signs before treatment. After treatment, Demodex was nearly eradicated, tear concentrations of IL-1β and IL-17 were significantly reduced and substantial clinical improvement was observed in all patients. In conclusion, we believe that Demodex plays an aggravating role in inflammatory ocular surface disorders.

Human adipose tissue-derived mesenchymal stem cell (hATMSC) have emerged as a potentially powerful tool for bone repair, but an appropriate evaluation system has not been established. The purpose of this study was to establish a preclinical assessment system to evaluate the efficacy and safety of cell therapies in a nude rat bone defect model. Segmental defects (5 mm) were created in the femoral diaphyses and transplanted with cell media (control), hydroxyapatite/tricalcium phosphate scaffolds (HA/TCP, Group I), hATMSCs (Group II), or three cell-loading density of hATMSC-loaded HA/TCP (Group III-V). Healing response was evaluated by serial radiography, micro-computed tomography and histology at 16 weeks. To address safety-concerns, we conducted a GLP-compliant toxicity study. Scanning electron microscopy studies showed that hATMSCs filled the pores/surfaces of scaffolds in a cell-loading density-dependent manner. We detected significant increases in bone formation in the hATMSC-loaded HA/TCP groups compared with other groups. The amount of new bone formation increased with increases in loaded cell number. In a toxicity study, no significant hATMSC-related changes were found in body weights, clinical signs, hematological/biochemical values, organ weights, or histopathological findings. In conclusion, hATMSCs loaded on HA/TCP enhance the repair of bone defects and was found to be safe under our preclinical efficacy/safety hybrid assessment system.

We report our experience with corneal epithelium, grown in vivo, transplantation in three patients with persistent epithelial defect (PED). The three patients had ocular surface disease unresponsive to standard treatments and were therefore chosen for transplantation. They underwent transplantation of epithelial sheets, grown in vivo, to the most affected eye. In vivo cultivation was carried out in the cornea of a living related donor. After epithelialization was completed, the epithelium grown on an amniotic membrane was harvested gently; it was then transplanted into the patient's eye after debridement of fibrovascular tissue. The cultivated epithelium was completely epithelialized by 2 weeks; it was well-differentiated with well-formed hemidesmosome. On immunohistochemical staining, p63, connexin 43, and Integrin beta4 were expressed in the cells on the epithelial sheet. The PED was covered completely and maintained for 4 weeks in all cases. However, corneal erosion recurred after 5 weeks in two cases. This novel technique demonstrates the corneal epithelial cells can be expanded in vivo successfully on denuded amniotic membrane of a healthy cornea and harvested safely. A corneal epithelial sheet, grown in vivo, can be transplanted to treat eye with a severe ocular surface disease, such as total limbal deficiency.

Polyarteritis nodosa (PAN) is a systemic vasculitis characterized by multi-organ involvement with protean manifestations. We evaluated the clinical features of PAN in Korea. Twenty-seven patients were diagnosed as PAN at Seoul National University Hospital between January 1990 and July 2003. The male-to-female ratio was 1.7:1 and mean age at onset (+/-SD) was 47.4+/-20 yr. Their presenting features at diagnosis were similar to those reported previously, i.e., myalgia, muscle weakness or leg tenderness (70%), fever (52%), weight loss >4 kg (44%), skin rash (44%), peripheral edema (33%), abdominal pain (33%), and arthralgia/arthritis (30%). However, the prevalence of testicular pain or tenderness was higher (24%) than reported previously and only three (11.5%) had HBsAg positivity without liver enzyme elevation. Nine patients (33%) had a five-factor score (FFS) of 2. Fourteen patients (52%) responded to treatment, 2 patients relapsed and 4 died within 1 yr of diagnosis. During a median follow-up of 55.5 months, three of the four PAN-related deaths had an initial FFS of 2. The clinical features of PAN were not significantly different from those reported previously. However, testicular pain or tenderness was more frequent and patients with a high FFS tended to have a poorer prognosis.

The purpose of this study is to characterize and compare the ultrastructural changes occurring during the in vivo cultivation of corneal epithelium on amniotic membrane (AM) at several different time points. Corneal burn patients (n=7) with a corneal epithelial defect and severe limbal damage were selected. Initially, AM transplantation with limbal autograft was performed at the acute stage of corneal burn to reconstruct the damaged ocular surface. One to six (mean interval; 3.3+/-1.2) months later, the central part of AM containing an in vivo expanded corneal epithelium was excised and retransplanted in adjacent lesions. The excised epithelium with AM was examined by electron microscopy and immunohistochemical study. By electron microscopy, one and two months after expansion, cultivated epithelium on AM showed an undifferentiated epithelium and an incomplete basement membrane (BM). But, after three months, the cultivated epithelium began to differentiate into a multilayered epithelium with a continuous BM with increased hemidesmosomes. These findings were further confirmed by immunohistochemical study, that cytokeratin K3 was expressed in the cultivated corneal epithelium and newly formed BM was partially positive of collagen IV at three months. At least 3 months may be needed for the proliferation and differentiation of in vivo cultivated corneal epithelium on AM.

To evaluate the efficacy of amniotic membrane in the management of painful bullous keratopathy secondary to the intractable glaucoma and in preventing exposure of drainage devices, we inserted Ahmed valve with amniotic membrane patch graft over the implant itself, and debrided corneal epithelium with amniotic membrane graft over the exposed stroma as a single operation. During the follow-up periods, we monitored vision, intraocular pressure (IOP), presence of ocular pain, and postoperative complications associated with the implants. The mean follow up period was 8.4+/-3.2 months. IOP was well controlled after the intervention. The preoperative mean IOP was measured as 43.9+/-9.0 mmHg and lowered to 16.1+/-1.8 mmHg at the last visit and no complications associated with the implants were noted. Even though the improvement in vision was not prominent, the ocular surface stabilized rapidly and ocular pain associated with bullous keratopathy disappeared soon after surgery. Conclusively the use of amniotic membrane in conjunction with Ahmed valve implantation is an effective way to relieve ocular pain and lessen the chances of complications associated with the implant in patients with intractable glaucoma and bullous keratopathy.

To determine if the involuntary contractions of eyelids may have any effects on the development of corneal astigmatism, we performed this prospective study which includes 19 patients with either essential blepharospasm or hemifacial spasm. In hemifacial spasm, the degree of corneal astigmatism was evaluated between two eyes. Then the topographic changes were checked using vector analysis technique before and after passively opening the eyelids. They were also measured before and at 1 and 6 months after the injection of Botulinum toxin. Resultantly, 20 eyes had the with-the-rule (group1) and 9 eyes against-the-rule (group2) astigmatism. In hemifacial spasm, significantly more astigmatism was found at spastic eyes. The corneal topographic changes after passively opening the eyelids showed 10 eyes with the astigmatic shift to the with-the-rule, while the remaining 19 to the against the- rule. At 1 month after injection of Botulinum toxin, group 1 showed reduced average corneal astigmatism, whereas group 2 showed increased astigmatism. The astigmatic change vector showed significantly more against-the-rule. In the contrary, 6 months after treatment, corneal astigmatism again increased in group 1 and decreased in group 2. So they took on the appearance of pretreatment astigmatic status eventually. Conclusively eyelids may play an important role in corneal curvature.

We describe a case of a 54-yr-old AL amyloidosis patient who developed femoral compressive neuropathy due to iliopsoas pseudohypertrophy. The patient, who presented with end stage renal disease, was referred to our clinic because of lower extremity weakness and polyarthritis. Finally, he was diagnosed as having kappa-AL amyloidosis, complicated by femoral compressive neuropathy, hypertrophic amyloid myopathy, amyloid arthropathy, carpal tunnel syndrome, and end stage renal disease. Femoral compressive neuropathy has never been reported in association with amyloid induced iliopsoas hypertrophic myopathy. This report expands the clinical spectrum of AL amyloidosis.

We evaluated DNA protection effect of heat shock protein (HSP) against cytotoxic effects of exogenous nitric oxide (NO) and reactive oxygen intermediate (ROI). Cultured human corneal fibroblasts were divided into 4 groups. Control (Group I) was not exposed to a sub-lethal heat treatment. Other 3 groups were exposed to 43 degrees C for 1 hr, then incubated at 37 degrees C during different duration (1, 6, 24 hr, Group II, III, IV, respectively). Expression pattern of HSP 70 was analyzed by Western blot. Cell viability was measured by MTT assay and the relationship between HSP 70 expression and DNA damage was examined by terminal deoxyribonucleotidyl transferase mediated dUTP-digoxigenin nick and labeling (TUNEL) stain and single cell gel electrophoresis. Expression pattern of HSP 70 was dependent on recovery times. Cell viability following heat treatment was significantly increased and the TUNEL positive cell number was decreased at 6 hr. In single cell gel electrophoresis, tail moments were increased in a dose-dependent manner by SNAP and X/XO. Following heat treatment, tail moments showed decreased significantly at 6 hr. These results suggest that induction of HSP 70 by sub-lethal heat treatment is closely related with cytoprotective effects against oxidative stresses in human corneal fibroblasts., (Copyright The Korean Academy of Medical Sciences)

We report two cases of band keratopathy who were treated with thick amniotic membrane that contained a basement membrane structure as a graft, after ethylenediaminetetraacetic acid chelation with trephination and blunt superficial lamellar keratectomy in the anterior stroma. In each case, basement membrane was destroyed and calcium plaque invaded into anterior stroma beneath Bowman's membrane. The calcified lesions were removed surgically, resulting in a smooth ocular surface, and the fine structures of band keratopathy were confirmed by pathologic findings. After that, amniotic membrane transplantation was performed to replace the excised epithelium and stroma. Wound healing was completed within 10 days. Stable ocular surface was restored without pain or inflammation. During the mean follow-up period of 13.5 months, no recurrence of band keratopathy was observed. This combined treatment is a safe and effective method for the removal of deep-situated calcium plaque and allowing the recovery of a stable ocular surface., (Copyright The Korean Academy of Medical Sciences)

The purposes of this study were to assess the expression patterns of heat shock proteins (Hsps), after eyeball heating or cooling, and to elucidate their relationships with corneal wound healing and intraocular complications after excimer laser treatment. Experimental mice were grouped into three according to local pretreatment type: heating, cooling, and control groups. The preconditioning was to apply saline eyedrops onto the cornea prior to photoablation. Following photoablation, we evaluated corneal wound healing, corneal opacity and lens opacity. Hsp expression patterns were elucidated with Western blot and immunohistochemical staining. The heating and cooling groups recovered more rapidly, and showed less corneal and lens opacity than the control group. In the heating and cooling groups, there were more expressions of Hsps in the cornea and lens than in the control group. These results were confirmed in the Hsp 70.1 knockout mouse model. Our study showed that Hsps were induced by the heating or cooling preconditioning, and appeared to be a major factor in protecting the cornea against serious thermal damage. Induced Hsps also seemed to play an important role in rapid wound healing, and decreased corneal and lens opacity after excimer laser ablation.

The role of nitric oxide (NO) in the ocular surface remains unknown. We investigated the conditions leading to an increase of NO generation in tear and the main sources of NO in ocular surface tissue. We evaluated the dual action (cell survival or cell death) of NO depending on its amount. We measured the concentration of nitrite plus nitrate in the tears of ocular surface diseases and examined the main source of nitric oxide synthase (NOS). When cultured human corneal fibroblast were treated with NO producing donor with or without serum, the viabilities of cells was studied. We found that the main sources of NO in ocular surface tissue were corneal epithelium, fibroblast, endothelium, and inflammatory cells. Three forms of NOS (eNOS, bNOS, and iNOS) were expressed in experimentally induced inflammation. In the fibroblast culture system, the NO donor (SNAP, S-nitroso-N-acetyl-D, L-penicillamine) prevented the death of corneal fibroblast cells caused by serum deprivation in a dose dependent manner up to 500 micrometer SNAP, but a higher dose decreased cell viability. This study suggested that NO might act as a double-edged sword in ocular surface diseases depending on the degree of inflammation related with NO concentration.

We present an epidemiologic study of cleft lip and palate in the Republic of Korea from January 1, 1993 through December 31, 1993. In 1993, the number of total live births was 715,817. And from 1993 through 1995, a total of 1,293 new patients with cleft lip and palate who were born in 1993 were identified. The incidence of cleft lip and palate was 1.81 per 1000, that is, 1 per 554 live births. The cleft lip: cleft lip and palate: cleft palate alone ratio was 1.13:1:1.19. The male: female ratio was 2.1:1 in the cleft lip group, and 2.5:1 in the cleft lip and palate group. We could detect a male predominance in both groups. In contrast, the ratio was 0.95:1 in the cleft palate group. The left: right: bilateral ratio was 1.9:1:0.23 in cleft lip group, and the ratio was 2.2:1:1.1 in the cleft lip and palate group. This is the first nation-wide study to provide detailed data on the incidence of cleft lip and palate in the live births in the Republic of Korea.