Development of monolithic matrix type transdermal patches containing cinnarizine: Physical characterization and permeation studies

To overcome the problems associated with bioavailability and systemic side effects of the drug by oral administration, monolithic matrix type transdermal patches containing cinnarizine (CNZ) were developed. For this purpose, films based on hydroxypropyl methylcellulose and polyvinylpyrrolidone as matrix-forming polymers were designed. Physical characteristics of transdermal films and drug-excipient compatibility were investigated. Factors affecting in vitro drug release and ex vivo skin penetration and permeation of the drug were studied. It was confirmed that films displayed sufficient flexibility and mechanical strength for application onto the skin for a long time period. Ex vivo penetration experiments gave satisfactory results for transdermal drug delivery through rat skin. The parameters determining good skin penetration were also evaluated. The highest drug permeation rate was obtained with incorporation of Transcutol® (0.102 mg/cm2/h) into the base CNZ formulation, followed by propylene glycol (0.063 mg/cm2/h), menthol (0.045 mg/cm2/h), and glycerin (0.021 mg/cm2/h) as penetration enhancers (p < 0.05). As a result, the developed transdermal patches of CNZ may introduce an alternative treatment for various conditions and diseases such as idiopathic urticarial vasculitis, Ménière's disease, motion sickness, nausea, and vertigo. Thus, the risk of systemic side effects caused by the drug can be reduced or eliminated

Estudo da eficácia de encapsulação da Cinarizina em cubossomos não-iônicos: caracterização estrutural e citotóxica / Study of the encapsulation efficacy of Cinnarizine in non-ionic cubosomes: structural and cytotoxic characterization

Os cubossomos são partículas nanoestruturadas em forma de bicamada lipídica, bicontínuas e altamente curvadas, as quais devem ser estabilizadas por um polímero não-iônico, neste caso o Pluronic® F-127. Podem ser compostos por alguns tipos de lipídios específicos que possuem a capacidade de se auto associar em estruturas cúbicas quando estão em excesso de água, como o fitantriol (PHY) e a monoleína (GMO). Devido a sua estrutura única, cubossomos possuem um grande potencial para serem considerados como sistemas drug delivery. Os sistemas drug delivery são amplamente utilizados na pesquisa farmacêutica e em contextos clínicos para aumentar a eficácia de compostos utilizados para diagnóstico e de fármacos. No caso da cinarizina (CNZ), fármaco já aprovado para o tratamento de náuseas, vômitos e vertigens causadas pela doença de Ménière, existem inúmeros efeitos colaterais associados a sua baixa solubilidade. Desta forma, a encapsulação em cubossomos se torna uma abordagem promissora para resolver os problemas de atividade farmacológica relacionados ao fármaco. Neste trabalho, realizamos uma caracterização biofísica da interação da CNZ em cubossomos (contendo PHY ou myverol, MYV, sendo este composto por 80% de GMO). As técnicas biofísicas utilizadas foram: espalhamento de raios-X em baixos ângulos (SAXS), espalhamento dinâmico de luz (DLS), microscopia eletrônica de transmissão (TEM), crio microscopia eletrônica de transmissão (Crio-TEM), análise de rastreamento de nanopartículas (NTA) e potencial zeta. A cromatografia líquida de alta eficiência (HPLC) foi realizada para verificar a porcentagem de eficiência de encapsulação (%EE) da CNZ nos cubossomos, enquanto que a citotoxicidade foi avaliada em eritrócitos através da análise da atividade hemolítica. Inicialmente, a influência de diferentes solventes (acetona, clorofórmio, etanol e octano) nas propriedades estruturais de cubossomos de PHY foi investigada, a fim de se minimizar os efeitos do solvente utilizados para a encapsulação da CNZ. Para amostras com acetona, descobriu-se que apenas altas concentrações tiveram influência na estrutura cristalográfica das nanopartículas, sendo o resultado foi totalmente reversível após 24h. O etanol fez com que o parâmetro de rede aumentasse de 10-15%. O clorofórmio e o octano tiveram efeitos diferentes sobre cubossomos de PHY em comparação com a acetona e o etanol; ambos induziram uma transição cúbico-hexagonal-micelar. Posteriormente, constatamos que as nanopartículas de PHY e MYV apresentaram diferentes estruturas cristalográficas, sendo elas Pn3m e Im3m, respectivamente. Devido a problemas com a baixa solubilidade de CNZ em PHY os estudos para esse lipídio foram suspensos. Nos testes para cubossomos de MYV ao incorporar a CNZ foi observado uma alteração da estrutura cúbica de Im3m para Pn3m e os valores dos parâmetros de rede se alteraram de acordo com a estrutura cristalina encontrada, porém os valores não apresentaram diferenças significativas de tamanho quando se trata da mesma estrutura, sugerindo que a CNZ não interferiu no parâmetro de rede. Os tamanhos das nanopartículas apresentaram uma população monodispersa com ~200 nm. DLS mostrou uma interferência da CNZ no tamanho dos cubossomos, variando de forma diretamente proporcional a concentração de CNZ na amostra, enquanto as técnicas de NTA e microscopia apresentaram nanopartículas de tamanhos bastante variados, mas independente da interferência da CNZ. A encapsulação de CNZ também foi dosada por HLPC em cubossomos de MYV, obtendo um limite superior de 0,6 mg/mL. A atividade citotóxica dos cubossomos foi testada em eritrócitos, revelando uma taxa de hemólise bastante inferior em cubossomos com CNZ em relação a cubossomos puros. Acreditamos que os cubossomos podem sim ser utilizados como sistemas carreadores de CNZ

Cubosomes are nanostructured particles in the form of a lipid bilayer, bicontinuous and highly curved, which must be stabilized by a non-ionic polymer, in this case Pluronic® F-127. They can be composed of some types of specific lipids that have the ability to self-associate in cubic structures when they are in excess of water, such as phytantriol (PHY) and monolein (GMO). Due to their unique structure, cubosomes have a great potential to be considered as drug delivery systems. Drug delivery systems are widely used in pharmaceutical research and clinical settings to increase the efficacy of compounds used for diagnostics and drugs. In the case of cinnarizine (CNZ), a drug already approved for the treatment of nausea, vomiting and vertigo caused by Ménière's disease, there are numerous side effects associated with its low solubility. Thus, cubosomal encapsulation becomes a promising approach to solve drug-related problems of pharmacological activity. In this work, we performed a biophysical characterization of the CNZ interaction in cubosomes (containing PHY or myverol, MYV, which is composed of 80% GMO). The biophysical techniques used were: low angle X-ray scattering (SAXS), dynamic light scattering (DLS), transmission electron microscopy (TEM), cryo transmission electron microscopy (Crio-TEM), nanoparticle tracking analysis (NTA) and zeta potential. High performance liquid chromatography (HPLC) was performed to verify the percentage of encapsulation efficiency (%EE) of CNZ in cubosomes, while cytotoxicity was evaluated in erythrocytes by analyzing the hemolytic activity. Initially, the influence of different solvents (acetone, chloroform, ethanol and octane) on the structural properties of PHY cubosomes was investigated in order to minimize the effects of the solvent used for the encapsulation of CNZ. For samples with acetone, it was found that only high concentrations had an influence on the crystallographic structure of the nanoparticles, with the result being fully reversible after 24h. Ethanol caused the network parameter to increase by 10-15%. Chloroform and octane had different effects on PHY cubosomes compared to acetone and ethanol; both induced a cubic-hexagonal-micellar transition. Later, we found that PHY and MYV nanoparticles presented different crystallographic structures, being Pn3m and Im3m, respectively. Due to problems with the low solubility of CNZ in PHY, studies for this lipid were suspended. In the tests for MYV cubosomes when incorporating CNZ, a change in the cubic structure from Im3m to Pn3m was observed and t he lattice parameters changed according to the crystal structure found, but the differences observed were not significant when it comes to the same structure, suggesting that the CNZ did not interfere with the network parameter. The nanoparticle sizes showed a monodisperse population with ~200 nm. DLS showed an interference of CNZ in the size of the cubosomes, varying directly proportionally to the concentration of CNZ in the sample, while NTA and microscopy techniques showed nanoparticles of widely varying sizes, but independent of CNZ interference. CNZ encapsulation was also dosed by HLPC in MYV cubosomes, obtaining an upper limit of 0.6 mg/ml. The cytotoxic activity of cubosomes was tested in erythrocytes, revealing a much lower rate of hemolysis in cubosomes with CNZ compared to pure cubosomes. We believe that cubosomes can indeed be used as CNZ carrier systems

Potenciais interações entre medicamentos alopáticos e fitoterápicos/ plantas medicinais no Município de Rondonópolis ­ MT / Potential interactions between allopathic and phytotherapy mediciation/medicinal plants in the Municipality of Rondonópolis

Introdução: no Brasil, a utilização de fitoterápicos e plantas medicinais é uma prática amplamente difundida, todavia, o consumo destes compostos em associação com medicamentos alopáticos caracteriza um risco à saúde devido às potenciais interações medicamentosas e seus efeitos. Objetivo: analisar as potenciais interações envolvendo fitoterápicos e plantas medicinais com medicamentos alopáticos na população de Rondonópolis, MT. Metodologia: trata-se de um estudo transversal de base populacional com 370 participantes. Os dados foram coletados em visitas domiciliares com um instrumento estruturado e padronizado. Para identificar as potenciais interações foi utilizada a base de dados Medscape® e a literatura nacional e internacional. Resultados: 131 (35,40%) indivíduos informaram consumir plantas medicinais e ou fitoterápicos concomitante a medicamentos alopáticos. A interação entre fitoterápicos e medicamentos alopáticos mais frequente foi entre Passiflora incarnata e cinarizina, para plantas medicinais foi entre hortelã e sinvastatina. As consequências mais prevalentes decorrentes das interações foram a intensificação da depressão do Sistema Nervoso Central, o aumento da anticoagulação e o risco de hipoglicemia. Conclusão: os dados analisados no presente estudo possibilitaram identificar potenciais interações existentes entre medicamentos alopáticos e plantas medicinais/fitoterápicos na população de Rondonópolis-MT e apontam para a necessidade de se estimular o uso racional da fitoterapia no âmbito da saúde pública.

Introduction: in Brazil, the use of phytotherapy medication and medicinal plants is a widespread practice. However, the consumption of these compounds in association with allopathic medicinal products is a health risk due to potential drug interactions and their effects. Objective: to analyze the potential interactions involving phythotherapy medication and medicinal plants with allopathic drugs in the population of Rondonópolis, state of MT. Methodology: this is a cross-sectional population-based study with 370 participants. Data were collected in home visits with a structured and standardized instrument. Medscape® database and national and international literature were used to identify potential interactions. Results: 131 (35, 40%) individuals reported consuming medicinal plants and/or phytotherapy medication concomitantly with allopathic drugs. The most frequent interaction between phytotherapeutic and allopathic drugs was between Passiflora incarnata and cinnarizine, and in medicinal plants, it was between peppermint and simvastatin. The most prevalent consequences of the interactions were intensification of central nervous system depression, increased anticoagulation and risk of hypoglycemia. Conclusion: data analyzed in the present study enabled the identification of potential interactions between allopathic medicines and herbal plants/phytotherapeutic medication in the population of Rondonópolis (MT), and demonstrated the need to stimulate the rational use of phytotherapy in public health.

Optimization of self-nanoemulsifying formulations for weakly basic lipophilic drugs: role of acidification and experimental design

ABSTRACT Formulators face great challenges in adopting systematic approaches for designing self-nanoemulsifying formulations (SNEFs) for different drug categories. In this study, we aimed to build-up an advanced SNEF development framework for weakly basic lipophilic drugs, such as cinnarizine (CN). First, the influence of formulation acidification on CN solubility was investigated. Second, formulation self-emulsification in media with different pH was assessed. Experimentally designed phase diagrams were also utilized for advanced optimization of CN-SNEF. Finally, the optimized formulation was examined using cross polarizing light microscopy for the presence of liquid crystals. CN solubility was significantly enhanced upon external and internal acidification. Among the various fatty acids, oleic acid-based formulations showed superior self-emulsification in all the tested media. Surprisingly, formulation turbidity and droplet size significantly decreased upon equilibration with CN. The design was validated using oleic acid/Imwitor308/Cremophor El (25/25/50), which showed excellent self-nanoemulsification, 43-nm droplet size (for CN-equilibrated formulations), and 88 mg/g CN solubility. In contrast to CN-free formulations, CN-loaded SNEF presented lamellar liquid crystals upon 50% aqueous dilution. These findings confirmed that CN-SNEF efficiency was greatly enhanced upon drug incorporation. The adopted strategy offers fast and accurate development of SNEFs and could be extrapolated for other weakly basic lipophilic drugs.

Angiomyofibroblastoma of the vulva

Angiomyofibroblastoma (AMFB) is an uncommon benign mesenchymal tumor. AMFB occurs almost in the vulvo-vaginal area of women. The gross features of AMFB are well-circumscribed so it clinically is often thought as Bartholin gland cyst or aggressive angiomyxoma. Usually, most tumors grow slowly, and patients do not feel pain. It also has low tendency for local recurrence. The histologic findings of the tumors are abundant thin-walled blood vessels with hypocellular and hypercellular areas. Almost all tumor cells have immunoreactivity for both desmin and vimentin. It also has estrogen and/or progesterone receptors, but staining for cytokeratin is negative. Here is a case of AMFB of the vulva occurring in a 40-year-old woman, involving the right labia majora. The patient described that her vulva mass grew in about few months. The maximum dimension of the tumor was measured as 2 cm, and we resected the tumor one month after as her second visit.

Liver retransplantation for adult recipients

Living donor liver graft can be used for the first or second liver transplantation. The timing of retransplantation also should be stratified as 2 types according to the reoperation timing. Combination of these two classifications results in 6 types of living donor liver transplantation (LDLT)-associated retransplantation. However, late retransplantation to LDLT might have not been performed in most LDLT programs, thus other 4 types of LDLT-associated retransplantation can be taken into account. The most typical type of LDLT-associated retransplantation might be early living donor-to-deceased donor retransplantation. For early living donor-to-living donor retransplantation, its eligibility criteria might be similar to those of early living donor-to-deceased donor retransplantation. For early deceased donor-to-living donor retransplantation, its indications are exactly the same to those for aforementioned living donor-to-living donor retransplantation. Late deceased donor retransplantation after initial LDLT has the same indication for ordinary late deceased donor retransplantation.

Clinical utility of tumor marker cutoff ratio and a combination scoring system of preoperative carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 72-4 levels in gastric cancer / 대한외과학회지

PURPOSE: The present study is to investigate the clinical utility of tumor marker cutoff ratio (TMR) and develop a TMR combination scoring system based on preoperative tumor marker (TM) levels to prognosis prediction in gastric cancer. METHODS: We include 1,142 patients for whom two or more TMs were measured and who underwent radical gastrectomy between 1990 and 2003. RESULTS: Five-year risk of recurrence (5 YRR) for carcinoembryonic antigen (CEA) TMRs were 18.3%, 29.8%, 61.4% for TMR or = 2.0 respectively. 5 YRR for carbohydrate antigen 19-9 (CA 19-9) TMR were 19.7%, 35.6%, 58.4% for TMR or = 3.0, respectively. 5 YRR for carbohydrate antigen 72-4 (CA 72-4) TMR were 15.2% and 33.6% for TMR or = 1.0, respectively. We defined high TMR (TMR > or = 2.0 for CEA, TMR > or = 3.0 for CA19-9), low TMR (1.0 < or = TMR < 2 for CEA, 1.0 < or = TMR < 3.0 for CA 19-9 and 1.0 < or = TMR for CA72-4) and negative TMR (TMR < 1.0 for all TMs). A TMR combination scoring system was devised with negative scored as zero points, low as 1 and high as 2 for each TMR. TMR scores were divided into four categories (score 0, 1, 2, 3 and above) based on the calculated TMR score and 5 YRR were found to be 12.8%, 23.9%, 45.5%, and 68.3%, respectively (P < 0.05). Multivariate analysis showed that our scoring system was a significant independent prognostic factor. CONCLUSION: Preoperative TMRs such as CEA, CA 19-9, and CA 72-4 show a correlation with prognosis and the TMR combination scoring system could be a useful tool for the prediction of prognosis in gastric cancer.

Comparison of the Outcomes between Axillary and Femoral Artery Cannulation for Acute Type A Aortic Dissection

BACKGROUND: At present, many surgeons prefer axillary artery cannulation because it facilitates antegrade cerebral perfusion and may diminish the risk of cerebral embolization. However, axillary artery cannulation has not been established as a routine procedure because there is controversy about its clinical advantage. MATERIALS AND METHODS: We examined 111 patients diagnosed with acute type A aortic dissection between January 2000 and December 2009. The right axillary artery was cannulated in 58 patients (group A) and the femoral artery was cannulated in 53 (group F). The postoperative outcomes were retrospectively reviewed and compared between the two groups. RESULTS: There were 46 male and 65 female patients with a mean age of 58.9+/-13.1 years (range, 26 to 84 years). The extent of aortic replacement in both groups did not differ. There were 8 early deaths (7.2%) and 2 late deaths (1.8%). The mean follow-up duration was 46.0+/-32.6 months (range, 1 month to 10 years). Transient neurologic dysfunction was observed in 11 patients (19.0%) in group A and 14 patients (26.4%) in group F. A total of 11 patients (9.9%) suffered from a permanent neurologic dysfunction. Early and delayed stroke were observed in 6 patients (10.3%) and 2 patients (3.4%), respectively, in group A as well as 2 patients (3.8%) and 1 patient (1.9%), respectively, in group F. There were no statistical differences in the cannulation-related complications between both groups (3 in group A vs. 0 in group F). CONCLUSION: There were no differences in postoperative neurologic outcomes and cannulation-related complications according to the cannulation sites. The cannulation site in an aortic dissection should be carefully chosen on a case-by-case basis. It is important to also pay attention to the possibility of intraoperative malperfusion syndrome occurring and the subsequent need to change the cannulation site.

Effect of sociodemographic variables on complete denture satisfaction

PURPOSE: The objective of this study was to evaluate the effect of sociodemographic factors on quality of satisfaction towards denture treatment. MATERIALS AND METHODS: One hundred subjects (filling inclusion criteria) who were wearing a denture for at least two months were enrolled and divided into five groups on the basis of sociodemographic variables (age, gender, literacy level, socio-economic and marital status). Questionnaires consisting of 38 questions (positive and negative attitude towards denture satisfaction) related to patients' perception of clinical outcome in different domains such as mastication, appearance, speech, comfort, health, denture care and social status were scored by the subjects. Questions reflecting positive attitude were scored as 2, 1, or 0 (yes, uncertain and no, respectively) and reversely for the negative questions. Statistical analysis was done by using Statistical Package for Social Sciences (alpha = .05). RESULTS: Level of denture satisfaction was higher in age subgroup belonging to 45 - 65 years of age in relation to comfort, health and denture care. Female and male showed significant priority for denture treatment because of esthetic and function respectively. Level of satisfaction was statistically significant with literacy level. Upper high income group showed significantly higher level of satisfaction only in case of social status. Married group showed significantly higher satisfaction level only with comfort. CONCLUSION: Patients' sociodemographic variables were influential factors on denture satisfaction.

Effect of sociodemographic variables on complete denture satisfaction

PURPOSE: The objective of this study was to evaluate the effect of sociodemographic factors on quality of satisfaction towards denture treatment. MATERIALS AND METHODS: One hundred subjects (filling inclusion criteria) who were wearing a denture for at least two months were enrolled and divided into five groups on the basis of sociodemographic variables (age, gender, literacy level, socio-economic and marital status). Questionnaires consisting of 38 questions (positive and negative attitude towards denture satisfaction) related to patients' perception of clinical outcome in different domains such as mastication, appearance, speech, comfort, health, denture care and social status were scored by the subjects. Questions reflecting positive attitude were scored as 2, 1, or 0 (yes, uncertain and no, respectively) and reversely for the negative questions. Statistical analysis was done by using Statistical Package for Social Sciences (alpha = .05). RESULTS: Level of denture satisfaction was higher in age subgroup belonging to 45 - 65 years of age in relation to comfort, health and denture care. Female and male showed significant priority for denture treatment because of esthetic and function respectively. Level of satisfaction was statistically significant with literacy level. Upper high income group showed significantly higher level of satisfaction only in case of social status. Married group showed significantly higher satisfaction level only with comfort. CONCLUSION: Patients' sociodemographic variables were influential factors on denture satisfaction.

Heterotopic Ossification Following Cervical Total Disc Replacement: Iatrogenic or Constitutional?

OBJECTIVE: To elucidate etiological factors of heterotopic ossification (HO) by evaluating retrospectively if HO is a unique finding following cervical total disc replacement (CTDR) or a finding observable following an anterior cervical interbody fusion (ACIF). METHODS: The authors had selected 87 patients who underwent anterior cervical surgery (TDR or ACIF), and could be followed up more than 24 months. A cervical TDR was performed using a Bryan disc or a ProDisc-C and an ACIF using a stand-alone cage or fibular allograft with a plate and screws system. The presence of HO was determined by observing plain radiography at the last follow up. The relation between HO occurrence and specific preoperative radio-logical findings (osteophyte and calcification of posterior longitudinal ligament (PLL)) at the index level was investigated. RESULTS: Cervical TDR was performed in 40 patients (43 levels) and ACIF in 47 patients (54 levels). At the final radiographs, HO was demonstrated at 27 levels (TDR-Bryan; 8/18, TDR-Prodisc-C; 12/25, ACIF-cage alone; 7/29, and ACIF-plate screw; 0/25). Mean ROM at the last follow-up of each TDR subgroup were 7.8+/-4.7degrees in Bryan, 3.89+/-1.77degrees in Prodisc-C, and it did not correlated with the incidence of HO. Fusion status of ACIF groups was observed as 2 case of grade 1, 6 of grade 2, and 21 of grade 3 in cage alone subgroup, and no case of grade 1, 4 of grade 2, and 21 of grade 3 in plate screw subgroup. Fusion status in ACIF-cage alone subgroup was significantly related to the HO incidence. The preoperative osteophyte at the operated level observed in 27 levels, and HO was demonstrated in 12 levels (TDR-Bryan; 3/5, TDR-Prodisc-C; 2/3, ACIF-cage alone; 7/11, and ACIF-plate screw; 0/8). Preoperative PLL calcification at the operated level was observed 22 levels, and HO was defined at 14 levels (TDR-Bryan; 5/5, TDR-Prodisc-C; 4/5, ACIF-cage alone; 5/7, and ACIF-plate screw; 0/5). The evidence of preoperative osteophyte and PLL calcification showed statistically significant relations to the occurrence of HO. CONCLUSION: HO was observed in both TDR and ACIF groups. HO was more frequently occurred in TDR group regardless of prosthesis type. In ACIF group, only cage alone subgroup showed HO, with relation to fusion status. Preoperative calcification of longitudinal ligaments and osteophyte were strongly related to the occurrence of HO.

Development of Quantitative Real-Time PCR Primers for the Detection of Aggregatibacter actinomycetemcomitans

The purpose of this study was to develop species-specific real-time quantitative PCR (RT-qPCR) primers for use in the detection of Aggregatibacter actinomycetemcomitans. These primers were designed based on the nucleotide sequences of the RNA polymerase beta-subunit gene (rpoB). We assessed the specificity of the primers against nine strains of A. actinomycetemcomitans, eight strains (three species) of the Haemophilus genus, and 40 strains of 40 other oral bacterial species. Primer sensitivity was determined by testing serial dilutions of the purified genomic DNAs of A. actinomycetemcomitans ATCC 33384T. Our data reveal that we had obtained species-specific amplicons for all of the tested A. actinomycetemcomitans strains, and that none of these amplicons occurred in any of the other species. Our PCR protocol proved able to detect as little as 2 fg of A. actinomycetemcomitans chromosomal DNA. Our findings suggest that these qRT-PCR primers are suitable for application in epidemiological studies.

Moderate drinking and motivational enhancement therapy

Alcohol consumption rates of Korean men and women are 85.8% and 65.4%, respectively. In regard to the amount of drinking, the highest frequency in men, among 37.2%, was over 10 glasses and in women was 1-2 glasses (1 glass, 12-14 g of alcohol) per day. Moderate drinking was defined as 2 glasses per day for men and 1 glass per day for women. Drinking beyond the moderate level could be risky or problematic. Alcohol related problems such as liver disease, cancer, cerebrovascular disease, accidents, crimes, injuries, and social and family problems in Korea create a great socioeconomic burden and threaten public health. Evidence-based treatments for problematic drinking, such as brief intervention, behavior change counseling, and motivational enhancement interviewing or therapy, have been suggested. An especially effective method would be motivation enhancement treatment (MET) due to since it is a client-centered approach and enhances self-efficacy based decisional balance. The major techniques of MET are feedback, responsibility, advice about changing, menu of change options, empathic counseling, self efficacy. The success factors for MET are sit squarely, open posture, lean toward patient, eye contact, relax posture. However, scientific accumulation of research results on the benefit of counseling for problematic drinking in Korea is still insufficient to provide the evidence for above treatment techniques.

Angiotensin-Converting Enzyme Inhibitors and Angioedema

PURPOSE: To investigate the incidence and clinical characteristics of angioedema associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) in an outpatient allergy department. METHODS: A retrospective review of medical records of new patients seen in an allergy clinic. Demographic and clinical data of patients with ACEI-induced angioedema were analyzed. RESULTS: Nine (0.37%) out of 2,421 new patients attending the allergy clinic developed ACEI-associated angioedema. Enalapril was the drug most frequently incriminated. The onset of the angioedema was as early as after the first dose or as late as 2 years after beginning treatment. Six patients experienced life-threatening angioedema involving the tongue, oropharynx, or larynx, and two patients required transfer to the intensive care unit. One patient required a tracheostomy. CONCLUSIONS: Angiotensin-converting enzyme inhibitor treatment is often responsible for angioedema, especially involving the upper airways. Due to the high proportion of the population exposed to ACEIs and to the severity of this adverse effect, it is important that physicians consider ACEIs as possible inducers when evaluating patients with acute or recurrent angioedema.

A Case of Postrenal Acute Renal Failure due to Hemorrhagic Cystitis / 대한신장학회지

Hemorrhagic cystitis (HC), a serious form of cystitis, is characterized by diffuse bladder mucosal inflammation with hemorrhage. The known causes of HC are radiation, chemotherapy, drug, and infection. But, most cases happen without definite etiology. Radiation induced HC can be developed at any time from 6 months to 10 years after pelvic irradiation therapy, and can appear as late as 2 decades. The complications of HC are anemia, chronic cystitis, and acute renal failure (ARF). However, HC- induced severe postrenal ARF is rare. We experienced a case of a postrenal ARF caused by hematoma in HC. A 55-year-old woman had past history of pelvic irradiation therapy for carcinoma of the cervix 13 years ago. She was initially treated by bladder catheterization and bladder irrigation with normal saline. HC and renal function were improved. However, HC was recurred shortly after stopping irrigation and serum creatinine was elevated again. Thus, we treated this patient successfully with both percutaneous nephrostomy and antegrade double J stent catheterization.

Risk Factors Associated with Frequent Hospital Readmissions for Exacerbation of COPD / 결핵및호흡기질환

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of disability and mortality worldwide. The aim of this study was to evaluate the risk factors associated with recurrent hospital admissions for exacerbation of COPD in Korea. METHODS: A retrospective study of 77 consecutive patients hospitalized for exacerbation of COPD at Pusan National University Hospital during the time period January 2005 to May 2008 was performed. The information was collected from the hospitalization period: clinical information, spirometric measures, and laboratory variables. In addition, socioeconomic characteristics, co-morbidity, anxiety, and depression were reviewed. Frequent readmission was defined as 2 or more hospitalizations in the year following discharge. RESULTS: During the 1-year period after discharge, 42 patients (54.6%) reported one hospital admission and 35 patients (45.4%) reported 2 or more hospital readmissions. Among the 35 frequent readmission patients, 4 had more than 10 readmissions. Univariate analysis showed that a body mass index (BMI) 36 months, forced expiratory volume in 1 second (FEV1) 40 mm Hg, and arterial oxygen saturation (SaO2) 40 mm Hg at discharge were independently associated with frequent readmissions for exacerbation of COPD. CONCLUSION: Frequent readmissions for exacerbation of COPD were associated with low BMI and hypercapnia at discharge.

Observation on therapeutic effect of He's Santong needling methods on cold erythema multiforme / 中国针灸

<p><b>OBJECTIVE</b>To search for an effective therapy for cold erythema multiforme in ham.</p><p><b>METHODS</b>One hundred and eighty cases with cold erythema multiforme in ham were randomly divided into a Santong group (n=90) and a western medicine group (n=90). The Santong group was treated by He's Santong needling methods and Huantiao (GB 30), Fengshi (GB 31), Zusanli (ST 36), etc. were selected. The western medicine group was treated by oral administration of Cinnarizine, Cyproheptadine and Vitamin E. Two weeks later, their therapeutic effects were observed.</p><p><b>RESULTS</b>The cured rate was 68.9% and the recurrence rate was 11.3% in the Santong group, and 33.3% and 53.3% in the western medicine group, with significant differences in the cured rate and the recurrence rate between the two groups (both P<0.01).</p><p><b>CONCLUSION</b>He's Santong needling methods can increase the cured rate and reduce the recurrence rate of cold erythema multiforme in ham.</p>

The Diagnostic Accuracy of Fine Needle Aspiration Cytology and the Diagnostic Usefulness of Galectin-3 Immunostaining for the Follicular Variant of Papillary Thyroid Carcinoma / 대한세포병리학회지

The cytologic diagnosis of the follicular variant of papillary thyroid carcinoma (FVPTC) has become one of the common causes of false negative diagnoses when performing fine needle aspiration cytology (FNAC) of the thyroid gland. We retrospectively reviewed all the aspirates for which a diagnosis of FVPTC had been made based on the surgically excised specimens, regardless of the cytologic diagnosis. 145 FNACs was performed in 135 patients. The cytologic diagnoses were categorized as 2 unsatisfactory specimens (1.4%), 16 benign (11.0%), 49 atypical (33.8%) and 78 malignant lesions (53.8%). The tumor cells consistently showed significant nuclear overlapping, irregular nuclei and fine chromatin in all cases; however, nuclear grooves and inclusions were scarce. Galectin-3 immunostaining was performed on the cell blocks of 65 cases and this was positive for 45 cases (69.2%). The results of our study demonstrate that the determination of minimal cytologic criteria is needed to raise the sensitivity of detecting FVPTC by FNAC, and galectin-3 immunostaining is useful to make decisions on the surgical treatment of cytologically atypical thyroid nodules.

N-Methyl-D-Aspartate (NMDA)-induced Apoptosis in Rabbit Retina

PURPOSE: To evaluate the involvement of apoptosis in N-methyl-D-aspartate (NMDA)-induced excitotoxicity in the rabbit retina. METHODS: After intravitreal injection of 680 and 2,000 nmoles of NMDA in rabbit eyes, the eyes were enucleated at 2, 16, and 60 hours and 1 and 2 weeks. The apoptotic cell death was determined with TdT-mediated biotin-dUTP nick end labeling (TUNEL) stain, and immunohistochemical stains of Bcl-2, Bax, and caspase-3 were performed. RESULTS: TUNEL showed increased labeling scattered in the ganglion cell layer and inner nuclear layer from 16 to 60 hours. The number of TUNEL-positive nuclei decreased at 60 hours, and none was observed at 2 hours, 1 week, and 2 weeks. More TUNEL-positive nuclei were seen with injection of 2,000 nmoles compared to 680 nmoles. Bcl-2, Bax, and caspase-3 were seen histologically as early as 2 hours in the ganglion cell layer and inner nuclear layer; there was no stained nuclei with the TUNEL stain. At 2 hours after intravitreal NMDA injection, Bcl-2, Bax, and caspase-3 were also stained in Muller cells. CONCLUSIONS: This study showed that apoptosis is involved in NMDA-induced excitotoxicity in the rabbit retina. Bcl-2, Bax, and caspase-3 may play important roles in modulating the apoptosis in NMDA-induced excitotoxicity, and Muller cells are involved in the apoptotic pathway.