Global hemostatic assay of different target procoagulant activities of factor VIII and factor IX

BACKGROUND: Korean National Health Insurance reimburses factor VIII (FVIII) and factor IX (FIX) clotting factor concentrate (CFC) infusions to discrepant activity levels, allowing elevation of FVIII activity to 60 IU/dL and FIX to 40 IU/dL. We aimed to assess hemostatic response to these target levels using global hemostatic assays. METHODS: We enrolled 34 normal healthy men, 34 patients with hemophilia A, and 36 with hemophilia B, with residual factor activity of 3 IU/dL or less and without inhibitors. Patients with hemophilia A and B received injected CFCs according to reimbursement guidelines. Fifteen minutes after injection, we assessed hemostatic response with global hemostatic assays: thrombin generation assay (TGA), thromboelastography (TEG), and clot waveform analysis (CWA). RESULTS: Normal healthy men and patients with hemophilia A and B were 36.7, 37.2, and 35.1 years old, respectively. FVIII and recombinant FIX concentrate doses were 28.8 IU/kg and 43.6 IU/kg. Post-infusion FVIII activity rose from 0.5 IU/dL to 69.4 IU/dL, while FIX activity rose from 1.4 IU/dL to 46.8 IU/dL. Post-infusion peak thrombin concentrations in hemophilia A and B were 116.6 nM/L and 76.4 nM/L (P < 0.001). Post-infusion endogenous thrombin potential (ETP) in hemophilia A and B was 1349.8 nM/min and 915.6 nM (P < 0.001). TEG index of hemophilia A and B was 0.11 and −0.51 (P=0.006). CONCLUSION: Current reimbursed doses for FIX concentrates are insufficient to achieve hemostatic responses comparable to those after reimbursed doses for FVIII concentrates in terms of peak thrombin concentration, ETP, and TEG index.

Cicatricial Fibromatosis Diagnosis after Suspected Local Recurrence at the Bronchial Stump Following Lobectomy for Lung Cancer

A mass excision surrounding the bronchial stump was performed to exclude malignancy in a 42-year-old man who had undergone a right lower lobectomy for lung cancer. The mass was identified as a cicatricial fibroma. Cicatricial fibromatosis, which is desmoid fibromatosis that arises in a surgical scar, is a well-known clinical condition. It consists of histologically benign neoplasms. Their occurrence after thoracic surgery is extremely rare. Biopsy or excision of suspicious lesions is very important for diagnosis. R0 resection remains the principal outcome for intra-thoracic desmoid fibromatosis. We report that a cicatricial fibromatosis in the subcarinal space was removed after suspicion of local recurrence at the bronchial stump follwing lobectomy for lung cancer.

Measurement of FVIII:C Level by Clot Waveform Analysis / 임상소아혈액종양

BACKGROUND: By using ACL 9000 coagulation analyzer (Instrumentation Laboratory Co., Lexington, Massachusetts, USA), we tried to investigate the possibility that activated partial thromboplastin time (aPTT) clot waveform analysis (CWA) may provide additional information on patients with hemophilia A. METHODS: Plasma samples were obtained from 35 patients with hemophilia A. The factor VIII levels of those patients were measured by a conventional one-stage factor VIII:C clotting assay and a factor VIII antigen assay. The data were applied to a Microsoft excel program calculating the index of the second derivative, and the time at point b (Min2), the point in time that clotting is initiated was also calculated. RESULTS: The corresponding aPTT clotting times were prolonged in all 9 patients with severe hemophilia A. The CWA could further discriminate between different levels of FVIII:C in the patients (n=20), with a FVIII:C level <4 IU/dL by conventional assay. The correlation between FVIII:C and the recalculated aPTT using Min2 was very high in patients with FVIII:C < or =4 IU/dL (r=0.952). Among the 9 patients who showed a lot of discrepancy from the FVIII:C level, there was 8 patients with mild hemophilia and 1 patient with moderate hemophilia (FVIII:C level 4.5%). CONCLUSION: Our study suggested that CWA and Min2 values might have greater discriminatory power in assessing low clotting factor activity. Further study is needed, including more patients with hemophilia A using CWA, correlation according to the severity group, a lower limit of detection for VIII:C, and a multiple one-stage assay.

Measurement of FVIII:C Level by Clot Waveform Analysis / 임상소아혈액종양

BACKGROUND: By using ACL 9000 coagulation analyzer (Instrumentation Laboratory Co., Lexington, Massachusetts, USA), we tried to investigate the possibility that activated partial thromboplastin time (aPTT) clot waveform analysis (CWA) may provide additional information on patients with hemophilia A.METHODS: Plasma samples were obtained from 35 patients with hemophilia A. The factor VIII levels of those patients were measured by a conventional one-stage factor VIII:C clotting assay and a factor VIII antigen assay. The data were applied to a Microsoft excel program calculating the index of the second derivative, and the time at point b (Min2), the point in time that clotting is initiated was also calculated.RESULTS: The corresponding aPTT clotting times were prolonged in all 9 patients with severe hemophilia A. The CWA could further discriminate between different levels of FVIII:C in the patients (n=20), with a FVIII:C level <4 IU/dL by conventional assay. The correlation between FVIII:C and the recalculated aPTT using Min2 was very high in patients with FVIII:C < or =4 IU/dL (r=0.952). Among the 9 patients who showed a lot of discrepancy from the FVIII:C level, there was 8 patients with mild hemophilia and 1 patient with moderate hemophilia (FVIII:C level 4.5%).CONCLUSION: Our study suggested that CWA and Min2 values might have greater discriminatory power in assessing low clotting factor activity. Further study is needed, including more patients with hemophilia A using CWA, correlation according to the severity group, a lower limit of detection for VIII:C, and a multiple one-stage assay.

Ameliorative Effect of Palmiwon on Polychlorinated Biphenyl (PCB, Aroclor 1254)-Induced Spermiotoxicity in the Rat / 대한남성과학회지

PURPOSE: Polychlorinated biphenyls (PCBs, Aroclor 1254), synthetic chlorinated organic compounds, are known to decrease thyroid function, sperm count, and fertility, and increase the risk of testicular cancer; they may have serious effects on male reproduction. The aim of this study was to investigate the possible protective role of palmiwon on PCB-induced spermiotoxicity in rats. MATERIALS AND METHODS: 90-day-old male Sprague Dawley rats were randomly divided into three groups, each consisting of ten animals. The control group (Group I) received corn oil, the second group of rats (Group II) was administered 2 mg/kg body weight/day of Aroclor 1254+corn oil intraperitoneally for 30 days. The third group of rats (Group III) was treated with 2 mg/kg body weight/day of Aroclor 1254+corn oil intraperitoneally plus palmiwon (300 mg/day) orally for 30 days. Twenty-four hours after the last treatment, the animals were killed by decapitation. Their serum testosterone levels was measured before and after the experimental medication was taken, and the number and motility of sperm, which had been collected from the cauda epididymal region, were evaluated. RESULTS: The results of this experiment show that treatment with palmiwon significantly improved sperm motility and number in rats that had been exposed to PCBs. There was no marked difference in body weight, testis weight, or epididymis weight among the groups. Nor were there any significant pathological differences in the testes among the groups. CONCLUSIONS: Palmiwon has the potential for treating PCB-induced spermiotoxicity. More experiments with larger samples and a longer period of treatment are needed.

Neutralizing Antibody Induction and Cytotoxic T Lymphocyte Response to Nakayama-NIH and Beijing-1 as Japanese Encephalitis Virus Vaccine Strains

The Japanese encephalitis virus (JEV), a member of the Flaviviridae family and Flavivirus genus, is transmitted by mosquitoes. JEV, of which some 35,000 cases are recorded every year, is a positive RNA virus. Two types of JEV vaccines have been developed to prevent the onset of encephalitis in humans, namely formalin-inactivated and liveattenuated vaccines. JEV inactivated vaccines are usually made using the Nakayama-NIH or Beijing-1 strains of the JEV virus. In this study, the immunological response to the Nakayama-NIH and Beijing-1 strains was analyzed as part of the effort to compile basic data which could lead to the selection of a suitable vaccine strain. To this end, the virus titer of Beijing-1 was found to be two-fold higher than that of Nakayama-NIH by plaque assay. Moreover, Beijing-1-induced neutralizing antibodies showed a higher level of titers when confronted by Korean JEV isolates than Nakayama-NIH-induced neutralizing antibodies (1:320 vs. 1:160, respectively). However, as a minimum ratio of 1:10 neutralizing antibody titers are required to protect against JEV infection, both strains in effect exhibited a sufficient level of neutralizing antibody titers. What's more, Beijing-1 was found to induce a somewhat higher cytotoxic T lymphocyte (CTL) response than Nakayama-NIH. Taken together, this can be taken to mean that Beijing-1 may in fact be a more effective vaccine candidate strain when it comes to inducing a high level of protective immunity against JEV infection.

A case of multiple primary malignancy involving the endometrial cancer / 부인종양

The incidence of multiple primary malignancy is extremely rare although the prevalence rate is increasing recently. There are several reasons of increment of multiple primary malignancy. First, the advances in the treatment and the diagnostic modality of malignancy have led to increased survival rate. So many of the patients who survived the first cancer could live long enough to develop additional primary cancers. Second, the long term effects of chemotherapy and radiation therapy have been proved oncogenic. Third, increasing age, environmental carcinogen, some kinds of viral infection, and genetic predisposition have potentials for multiple carcinogenesis. Most of multiple primary cancer is double primary, however triple primary cancer is rare. We experienced a case of triple primary cancer involving endometrium, colon, and stomach. We report this case with a review of literatures.

Tonsillar Lymphangiomatous Polyp: Report of Two Cases

Tonsillar lymphangiomatous polyp is an uncommon hamartomatous lesion that generally arises from the tonsillar surface, and it has rarely been reported in the medical literature. Because of the uncommon clinical and pathological features of these polyps, pathologists and clinicians may experience difficulty in correctly classifying them. We report herein two cases of lymphangiomatous polyp of the tonsil in a 49 year-old man and a 30 year-old man who both presented with a tonsillar mass of the palatine tonsil. Microscopically, there were protruding polypoid lesions that had a core of fibroadipose tissue with dilated multiple lymphatics and aggregated lymphoid tissue. Both patients have been stable since resection.

Prevalence of Occupational Asthma and Exposure Level of Pharmaceutical Dust of Workers in a Pharmaceutical Company / 대한산업의학회지

OBJECTIVES: After the investigation of one worker with occupational asthma, we surveyed the prevalence of occupational asthma and the exposure level of pharmaceutical dust of 32 workers in a pharmaceutical company. METHODS: Thirty-two of the 90 employees participated in the survey which consisted of questionnaire, blood sampling, spirometry and skin prick tests with 8 common allergens as well as 9 antibiotics and 2 enzymes. Various indices of the working environment were also measured. Subjects who had a symptom suggestive of work-related asthma or positive skin prick test were further investigated by PC20 methacholine. Nine subjects who had a PC20 result of 16 mg/ml or less (n=7) or had work-related symptoms and positive skin prick test (n=2) were referred to undergo a specific bronchial provocation test to pharmaceutical dust in an academic allergic disease center. RESULTS: Eleven of 32 workers (34.4%) had a work-related symptom suggestive of occupational asthma. Ten (31.2%) showed positive skin prick test. 8 (25.0%) had a PC20 result of 16 mg/ml or less (indicative of significant bronchial hyperresponsiveness), and 5 (15.6%) had a positive result on the specific bronchial provocation test. Exposure levels of stuffing, input of raw materials and screening process were relatively high. CONCLUSIONS: This survey showed that pharmaceutical workers have an increased risk of occupational asthma. Although pharmaceutical factories maintain a relatively good working environment, careful control of respiratory tract exposures, especially during stuffing, input of raw materials and screening process, is important to prevent occupational asthma. Pharmaceutical workers need to undergo regular skin prick and methacholine bronchial provocation tests, as well as asthmatic symptom survey, to ensure the early detection and prevention of occupational asthma.

Hyperprolactinemia After Severe Head Trauma

Patients of head injury may manifest neurohypophyseal dysfunction during the early post-traumatic period. A case of hyperprolactinemia and low prolactin response to thyrotrophin-releasing hormone in a woman 7 months after severe head injury is presented and literatures are also reviewed.

A Case of Rupture of Right Common Iliac Artery and Vein during Lumbar Discectomy: A case report / 대한구급학회지

Intraabdominal vascular complications associated with lumbar disc surgery are rare but have potentially fatal consequences. Clinical manifestations of such injuries may be extremely variable and confused with anesthetic complications, myocardial infarction, or pulmonary embolism. So, the presence of vascular injury may not be recognized immediately. Recently, we experienced a case of extensive retroperitoneal hemorrhage during lumbar disc surgery. The patient was a 35 year-old healthy female. During operation, unexplained profound hypotension and tachycardia developed, but abnormal bleeding was not seen in the operative wound. Emergency CT of the abdomen was performed, and huge retroperitoneal hematoma was confirmed by the CT scan. Immediate abdominal exploration revealed the injury to right common iliac artery and vein. The patient underwent primary repair of lacerated artery and vein. Postoperative recovery was uneventful. We think awareness of the likelihood of vascular complications related to disc surgery is quite important for early diagnosis and management of these life-threatening complications.