This study evaluated the immune response elicited by two formulations of an AS03(A)-adjuvanted H5N1 A/Indonesia/05/2005 prepandemic influenza vaccine, developed using manufacturing processes with or without thiomersal. In addition, it also evaluated compliance to the Centre for Biologics Evaluation and Research and Committee for Medicinal Products for Human Use (CHMP) immunogenicity guidance criteria for pandemic influenza vaccines in adults.
This phase III, observer-blind, randomized study (NCT00812981) enrolled 320 subjects aged 18-60 years into two groups to receive, 21 days apart, two doses of the formulation manufactured using either the thiomersal-containing process (Group TC) or the thiomersal-free process (Group TF). Blood samples collected before vaccination, 21 days after the second vaccine dose, and 6 months following the first vaccine dose (Days 0, 42, and 180) were analysed using a hemagglutination inhibition (HI) assay. Safety assessments were made for the entire study period.
Twenty-one days after the second dose of vaccine, both groups met the CHMP criteria for vaccine-homologous HI response (seroprotection rates/seroconversion rates ≥ 98.7%, seroconversion factor ≥ 121.9) and also for a heterologous HI response against the A/Vietnam/1194/2004 strain (seroprotection rates/seroconversion rates ≥ 81.3%, seroconversion factor ≥ 10.8). Six months after the first dose of vaccine, a marked persistence of the vaccine-homologous HI response was observed that still met one or more CHMP criteria. Pain at the injection site (Group TF 95%, Group TC 91.8%) and myalgia (Group TF 68.8%, Group TC 63.5%) were the most frequently recorded solicited symptoms. Overall, both formulations had a clinically acceptable safety profile.
Administration of two doses of the AS03(A)-adjuvanted H5N1 prepandemic influenza vaccine was found to be highly immunogenic in adults with a clinically acceptable safety profile. The ability to confer cross-clade protective immunity makes it a suitable option for mitigation of the morbidity and mortality of outbreaks and pandemics due to H5N1 and drifted strains.
This study was performed to evaluate the role of non-contrast 3D time-of-flight (TOF) magnetic resonance angiography (MRA) to detect and quantify intracranial steno-occlusive disease.
Between April 2004 and January 2006, 45 patients with both 1.5T TOF MRA and digital subtraction angiography (DSA) performed within a 30-day interval were included. We evaluated the following intracranial arterial segments: petrous internal carotid artery (ICA), cavernous ICA, supraclinoid ICA, M1 of middle cerebral artery, A1 of anterior cerebral artery, P1 of posterior cerebral artery, basilar artery, and distal vertebral artery. In total, 675 arterial segments were evaluated and categorized as negative, moderate-1 (3049% stenosis), moderate-2 (5069%), severe (7099% stenosis, including gap sign on MRA), and occlusion.
The sensitivity and specificity of TOF MRA for > 29% stenosis and > 49% stenosis were 94%, 96% and 95%, 96%, respectively; while sensitivity and specificity for occlusion lesions were both 100%. However, 44 segments (37% of diseased segments) were overestimated by MRA, including 20 false-positive stenoses (which occurred in 10 [22%] patients) and 24 overestimated stenosis degree. The gap sign as severe stenosis only showed about 21% sensitivity and 41% specificity. Seven lesions were underestimated by MRA: three arterial segments were out of the field of MRA examination, and four were moderate-1stenosis on DSA.
TOF MRA has high sensitivity and specificity in detecting all categories of stenosis degree and occlusion. However, it tends to overestimate lesions. Therefore, MRA can be considered as a screening study. Confirmation with other studies is recommended in doubtful cases.
The neutral lipids existing in the intercellular spaces of the stratum corneum (SC) provide a permeability barrier to prevent water loss. Nile red is the most sensitive lipid stain for tissue sections. However, due to the extremely flattened morphology of corneocytes and the resolution limits of the light microscope, Nile red staining is seldom used as a fluorescent probe for the lipid-rich SC. In this study, we modified the traditional method for visualization of intracellular lipid by adding 4% potassium hydroxide after Nile red staining. This modified method not only allowed visualization of lipids existing in the intercellular membrane regions and the lateral junctions of the adjoining corneocytes, but also clearly demonstrated small lipid droplets within pathological corneocytes. These features were not observed with the traditional staining method. Thus, this modified Nile red staining method greatly improved the resolution of the SC lipids under light microscopy and should be useful for studying lipid depositions in both normal and pathological SC.
Survivin, an inhibitor of apoptosis, is expressed in fetal tissues but undetectable in normal adult tissues. It is also expressed in most common human cancers. This study evaluated the expression of survivin in breast cancers.
A monoclonal anti-survivin antibody B1 was generated. Immunohistochemical staining was performed in 226 paraffin sections of primary breast cancers and correlated with the patients' clinicopathological characteristics.
Survivin was expressed in the cytoplasm of tumor cells in 59.3% of breast cancers. Expression of survivin was associated with high histologic grade (p = 0.027), high mitotic count (p = 0.014), positive p53 immunostaining (p = 0.012), neu overexpression (p = 0.018), and with bcl-2 (p = 0.001) and bak (p < 0.001) expression. No correlation was found between survivin expression and age, tumor size, estrogen receptor, progesterone receptor or Bax expression. Survivin expression was not significantly associated with overall or disease-free survival.
Survivin expression is correlated with high histologic grade, high mitotic count, p53 overexpression, and bcl-2 expression in breast cancer. It does not have significance as a marker in predicting overall or disease-free survival.
Elevation of C-reactive protein (CRP) level is associated with increased risk of cardiovascular events. The 1059 G>C polymorphism in exon 2 of the CRP gene has been shown to affect plasma concentration of CRP. We want to elucidate the effect of this polymorphism on the development of coronary artery disease (CAD) among the Chinese population in Taiwan.
We scrutinized 536 patients undergoing coronary angiography (365 patients with CAD and 171 controls with patent coronaries) and evaluated the association of CRP gene 1059 G>C polymorphism with CAD. Genotyping of the polymorphism was performed by polymerase chain reaction and MaeIII restriction enzyme digestion.
The CC genotype was associated with lower plasma CRP concentration (GG, 6.5+/-5.8; GC, 3.3+/-4.4; CC, 2.3+/-3.1 mg/L; p=0.02). Subjects with CAD or myocardial infarction (MI) had significantly higher plasma CRP concentration than that in controls (CAD vs. controls, 8.9+/-18.9 vs. 3.3+/-7.2 mg/L; p<0.001), while patients with MI showed higher CRP when compared to those with chronic stable angina (13.5+/-22.9 vs. 5.2+/-14.1 mg/L; p<0.001). However, this polymorphism was not associated with CAD in our population.
Our data suggest that human CRP gene 1059 G>C polymorphism is associated with plasma CRP concentration among Chinese in Taiwan receiving coronary angiography.
Mammography is the radiographic imaging of the breast and includes screen-film mammography and xeromammography. From September 1987 to March 1990, 108 patients with breast carcinoma received mammographic examinations at Chang Gung Memorial Hospital. The spectrum of mammographic appearance included mass abnormalities (50.9%), calcifications (10.2%), a combination of mass abnormalities and calcifications (25%), asymmetrical increased density (4.6%), and parenchymal distortion (1.9%). The remaining 7.4% of the lesions lacked any radiologic sign of malignancy and primarily appeared as dense breast on the mammogram. In this series, mammography had a sensitivity of 86.1%, a specificity of 77.3% and a positive predictive value of 67.4%. Recognition of these mammographic appearances is beneficial in detecting breast carcinoma and in establishing a correct diagnosis. In addition, knowing the abilities, as well as limitations, of mammography will optimize the efficacy of this examining modality.
Resistance to chemotherapy is a major cause of treatment failure in human cancer. Accumulating evidence has indicated that the acquisition of resistance to chemotherapeutic drugs involves the activation of the PI3K/Akt pathway. Modulating Akt activity in response to chemotherapy has been observed often in chemoresistant cancers. The potential molecular mechanisms by which chemotherapeutic agents activate the PI3K/Akt pathway are emerging. Activation of this pathway evades the cytotoxic effects of chemotherapeutic agents via regulation of essential cellular functions such as protein synthesis, antiapoptosis, survival and proliferation in cancer. How chemotherapeutic agents induce Akt activation and how activated Akt confers chemoresistance through regulation of signaling networks are discussed in this review. Combining PI3K/Akt inhibitors with standard chemotherapy has been successful in increasing the efficacy of chemotherapeutic agents both in vivo and in vitro. Several small molecules have been developed to specifically target PI3K/Akt and other components of this pathway, which in combination with chemotherapy may be a valid approach to overcome therapeutic resistance. We propose several feedback and feedforward regulatory mechanisms of signaling networks for maintenance of the Akt activity for cell survival. These regulatory mechanisms may limit the efficacy of PI3K/Akt-targeted therapy; therefore, disruption of these mechanisms may be an effective strategy for development of novel anti-cancer therapies.
We report a girl with partial DiGeorge anomaly associated with a distal chromosome 10p deletion. The initial manifestation was hypocalcemia convulsion at the age of 14 days. The patient was small for her gestational age and showed symptoms of poor feeding and inspiratory stridor. Facial dysmorphisms included a cupped ear, hypertelorism downslanted and short palpebral fissures frontal bossing, anteverted nostrils, a flat nasal bridge, and micrognathia. Developmental delay was also noted. Hypoplasia of the thymus was detected by ultrasound examination, but results of immunologic studies were all normal at 6 weeks of age. The echocardiogram, brain ultrasound, electroencephalogram, and magnetic resonance images of the brain were normal, but brainstem auditory evoked potentials showed bilateral sensorineural hearing loss. Chromosomal analysis showed 16, XX, del(10)(p12.3); the parents had normal karyotypes. After treatment with vitamin D, calcium gluconate, and magnesium sulfate, the patient's serum calcium and magnesium levels were within normal limits. She was discharged and received regular follow-up at our clinic for physical therapy and to ensure adequate supply of divalent cations. Complex partial seizure was noted at the age of 1 year and was controlled with carbamazepine. To our knowledge, this is the first Taiwanese reported to have partial DiGeorge anomaly associated with 10p deletion. We recommend that standard karyotyping should be performed in children suspected to have this anomaly.
Partial trisomy 3q syndrome is often the result of an unbalanced translocation or inversion. The duplicated segments are mostly from 3q25 to 3qter. We describe a karyotype of 46,XY,der(10)t(3;10)(q25.3;q26.1) in a 1-day-old male infant who presented with multiple congenital anomalies including synophrys, a long philtrum, thin lips with down-turned angles of the mouth, micrognathia, a high-arched and cleft palate, clenched hands, genital hypoplasia, cryptorchidism, a large ventricular septal defect, a subependymal cyst, and corpus callosum hypoplasia. The patient had cardiopulmonary distress resulting from multiple congenital anomalies. He died of heart failure at the age of 18 days. The chromosome aberration resulted from a maternal balanced translocation. The dup(3q) syndrome superficially resembles but can be distinguished from Brachmann-de Lange syndrome. Craniofacial features, cleft palate and urinary tract anomaly are more frequent in dup(3q) syndrome. Oligodactyly and phocomelia are more characteristic of Brachmann-de Lange syndrome.
Distal 10q trisomy is a well defined but rare syndrome, and almost always the result of an unbalanced translocation. Clinical evaluation and cytogenetic molecular analyses were performed in a 6-year-old boy with developmental delay and facial dysmorphism including marked blepharophimosis. His karyotype showed an unbalanced translocation between chromosomes 9 and 10, resulting in trisomy of the distal part of the long arm of chromosome 10q26. A balanced translocation of the segment between chromosomes 9 and 10 with breakpoints at 10q26.1 and 9pter or p24.3 was found in his father, who had normal phenotype. Unlike most cases of partial 10q trisomy which have concurrent partial monosomy of one other translocated chromosome, fluorescence in situ hybridization studies revealed this case to be a pure 10q26 trisomy. The translocated 10q segments in most cases of 10q trisomy originate from the father. Imprinting effect may exist in this chromosomal syndrome; distal 10q trisomy from paternal reciprocal translocations is more compatible with life.
The "eradication of malaria" in Taiwan was announced by WHO in 1965. From 1966 to 1989, 919 malaria cases were detected in Taiwan. Of these cases, 803 were classified as imported malaria. During 1977 to 1989, our hospital collected 11 cases of imported malaria, 6 of Plasmodium falciparum (PF), including 1 suspicious case, 2 of Plasmodium vivax (PV), 1 of mixed infection (PF plus PV), and 2 unclassified. Most of the patients presented clinically with fever and chills. Hepatosplenomegaly was the most common abnormal finding during the physical examination. Jaundice and anemia occurred in the more severe cases. No cases had lymphadenopathy which is helpful in making a differential diagnosis. Six cases had thrombocytopenia which may be considered as an indirect sign in the diagnosis. The MCV levels were within normal limits in all of the cases. This may indirectly imply a potential protective effect against malaria infection in cases of congenital hemoglobinopathy such as thalassemia or G6PD deficiency. Initially, 10 cases were given "standard treatment", which consisted of chloroquine 450 mg qd for 2 days then 300 mg qd for 2 days and primaquine 15 mg qd for 2 weeks. Four cases of chloroquine resistance were encountered, all in cases with PF infection. Two cases were grade I delayed type resistance and were successfully treated with Fansidar, tetracycline and quinine. Two cases were grade II resistance and presented clinically as cerebral malaria. Intravenous quinine was given plus Fansidar and tetracycline. The cases were resolved without sequele or recurrence. None of the cases, except for 2, received chemoprophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)
Solitary cerebellar metastatic tumors are rarely reported in the literature. We reviewed 240 posterior fossa tumors treated in the past eight years. There were 11 cases of solitary metastases in the cerebellum. The primary tumor was lung cancer in five cases and breast carcinoma in two cases; the remaining three cases had colon cancer, nasopharyngeal carcinoma (NPC) and Ewing's sarcoma, respectively. All patients underwent craniectomy and gross total excision of the tumor. Seven patients survived less than one year, two cases died in the second year, and one case of NPC survived for more than two years. The only survival is a case of Ewing's sarcoma who underwent surgery 14 months ago. The symptoms and signs of all patients improved satisfactorily after surgery. Four patients received postoperative irradiation to the posterior fossa and two cases of lung cancer had a thoracotomy for the primary lung lesion; however, the survival period was not prolonged. We suggest that a cancer patient or a patient in the fifth to seventh decades of life presenting headache, gait disturbance and vomiting should promptly undergo a computed tomography (CT) scan of the head. In selected cases, surgical intervention for solitary metastatic tumors in the tiny posterior fossa may be the best initial treatment. Adjuvant therapies should then be added according to the type of tumor.
The most common diagnostic finding of autoimmune thyroid disease (AITD) is the presence of antithyroid antibodies. While autoimmune thyroiditis (AT) is a common AITD, aspiration cytology is one of the important diagnostic tools of AT.
We evaluated 116 AT patients with ultrasound-guided aspiration cytology and then analyzed the correlation between thyroid hormone status and thyroid autoantibodies. This was a retrospective analysis with prospective collection of data with a mean follow-up period of 68.8 ± 37.8 months. The patients were classified as either euthyroid, hypothyroid, or hyperthyroid (HT). Of the 116 patients, 22 were hypothyroid, 37 were euthyroid, and 57 were HT.
During the follow-up period, 95.5% of the hypothyroid group remained hypothyroid and only one patient improved to euthyroid. In the euthyroid group, 16.2% progressed to hypothyroid and 83.8% remained euthyroid. In the HT group, 8.7% progressed to hypothyroid, 70.2% progressed to euthyroid, and 21.1% remained HT. Most patients with a high titer of thyroglobulin antibody (TgAb) will progress to hypothyroid, and patients with a high titer of thyroid stimulating hormone (TSH) receptor antibody (TRAb) will remain HT. Strong correlations between thyroid functional status and positive number of thyroid autoantibodies were seen in this study. Patients with all the three antibodies positive had a high prevalence of hyperthyroidism.
In our study, most patients were HT; this may be because of the early diagnosis and treatment of AT in our clinic. Although antithyroperoxidase antibody (TPOAb) is a hallmark antibody of HT, it cannot predict the initial presentation and clinical outcome.
Partial trisomy of chromosome 11q is a rare but rather distinct clinical syndrome. Cases of distal trisomy of chromosome 11(q23.1-qter) in 2 sisters are described. The features included microbrachycephaly, long philtrum, retracted lower lip, short neck, heart defects, marked leukocytosis, and psychomotor retardation. These patients died at the age of 3 months and 6 months, respectively. Chromosome analyses showed a distal trisomy 11q resulting from maternal t(11;13)(q23.1;q34). Fluorescence in situ hybridization using the painting probes for chromosomes 11 and 13, along with a unique sequence for mixed lineage leukemia (MLL) gene confirmed this condition. The phenotypes of both sisters are most likely to be related to partial trisomy of 11q and a triplicated gene dosage of MLL.
Patients with partial trisomy 3p seldom present major dysmorphic features, and holoprosencephaly occurs in only 10% of the cases with partial trisomy 3p. It has been suggested that multiple genetic hits or environmental exposures are required for the clinical expression of holoprosencephaly. At 16 weeks of gestation, prenatal sonography identified a fetus with holoprosencephaly, orofacial clefts, pyelectasis, and a unilateral duplex renal system. Amniocentesis revealed the karyotype of 46,XX,der(11)t(3;11)(p21;q23)pat with partial trisomy 3p (3p21-->pter) and partial monosomy 11q (11q23-->qter). The pregnancy was subsequently terminated. Postnatally, the proband showed hypotelorism, a depressed nasal bridge, orofacial clefts and holoprosencephaly-premaxillary agenesis. The present case provides evidence that partial trisomy 3p/monosomy 11q can be a genetic cause of holoprosencephaly and del(11)(q23-->qter) is associated with a duplex renal system.
Cervical cancer remains a health problem among women worldwide. Delineation of genetic changes is critical to understanding the molecular basis of tumor progression, as well as for identifying genetic markers for early identification of patients at high risk for a poor outcome.
To provide comparative genomic hybridization data for cervical squamous cell carcinoma in Taiwan, and to gain further insight into genetic markers associated with lymph node metastasis of this disease, we performed comparative genomic hybridization analysis of 30 consecutive cases of cervical squamous cell carcinoma (24 stage IB and 6 stage IIB).
The results disclosed that higher staged tumors or those with lymph node metastasis had more chromosomal imbalances. The commonly recurrent chromosomal imbalances were gains of 3q (46.7%), 1q (36.7%) and 8q (20.0%) and losses of 11q (36.7%), 3p (33.3%), 6q (23.3%), and 2q (20.0%). The frequencies of these chromosomal imbalances in stage IB and IIB tumors did not differ significantly. However, when compared with tumors without lymph node metastasis, the loss of 11q14-q22 (5/9 vs. 3/21, p = 0.019) and gains of 3q11-q22 and 3q26-qter (6/9 vs. 5/21, p = 0.026) were significantly more prevalent in tumors with lymph node metastasis.
The results suggest that certain tumor-associated genes residing on 3q and 11q warrant further investigation to elucidate their role in the progression of this disease.
A rare form of congenital adrenal hyperplasia (CAH), 11 beta-hydroxylase deficiency, may be misdiagnosed as 21-hydroxylase deficiency, the most common form of CAH, because of similar clinical presentations at times and elevated level of 17-hydroxyprogesterone in both conditions. We report a case of 11 beta-hydroxylase deficiency that was originally misdiagnosed as 21-hydroxylase deficiency. Hypertension and hypokalemia complicated with seizures and arrhythmia developed in this 9-year-old girl after abrupt withdrawal of oral dexamethasone but maintenance of fludrocortisone. Suspicion of 11 beta-hydroxylase deficiency led to DNA mutation analysis, which revealed a novel point mutation (CTG 461 CCG) in the CYP11B1 gene converting leucine to proline. Her condition stabilized rapidly after withdrawal of fludrocortisone and administration of hydrocortisone. Regular measurement of blood pressure should be performed in all patients with CAH and test of serum 11-deoxycortisol or deoxycorticosterone level should be performed in those patients with elevated blood pressure to avoid misdiagnosis of 11 beta-hydroxylase deficiency.
It has been speculated that novelty seeking (NS) behavior is related to the dopaminergic system. Fifty-two subjects completed the Tridimensional Personality Questionnaire and underwent single photon emission computed tomography with (123)I-iodobenzamide. A marginally positive correlation was noted between NS and striatal dopamine D(2)/D(3) receptor availability (r = 0.25, p =0.07). A positive association was noted between the NS scores and left striatal D(2)/D(3) receptor availability (r= 0.29, p =0.04). The results suggest that a relationship might exist between NS score and dopaminergic activity.
Mixed epithelial and stromal tumor of the kidney is a newly categorized lesion, with few reported cases. We report a rare case of a 45-year-old woman with a palpable abdominal mass and elevated serum level of serum cancer antigen 125, who was not receiving hormones or contraceptive agents. Abdominal magnetic resonance imaging revealed a large multilocular cystic tumor that arose in the left central kidney. Nephrectomy was performed under the initial impression of cystic renal cell carcinoma; however, a diagnosis of mixed epithelial and stromal tumor was confirmed according to pathological and immunohistochemical findings. Serum level of cancer antigen 125 returned to normal after 1 month postoperatively and no recurrence was found in the following 18 months.
A 37-year-old female presented with a 2-month history of abdominal distention. Omentum masses with massive ascites were found and ovarian cancer with peritoneal carcinomatosis was suspected. Her serum CA-125 level was over 500 U/ml before therapy. Tuberculous peritonitis was diagnosed via peritoneal biopsy. The serum CA-125 level returned to normal after antituberculous therapy. Elevated serum CA-125 does not always indicate ovarian malignancy. This tumor marker may be used to monitor the disease activity in non-neoplastic ascitic states.
Serotypes, biotypes, and antibiotic susceptibility of 126 Haemophilus influenzae isolates were determined. Five of the 126 isolates were from blood and were encapsulated type b strains; those taken from other sites were not typable. There were 13% biotype I, 36% biotype II, 38% biotype III, 5% biotype IV, 4% biotype V, and 4% biotype VI isolates. Antibiotic susceptibility tests using the standard disk diffusion method showed the following resistance: ampicillin 51%, cefamandole 10%, cefuroxime 3%, chloramphenicol 28%, tetracycline 37% and sulfamethoxazole-trimethoprim 49%. None of the five type b isolates were resistant to cefotaxime, a third generation cephalosporin. The second generation cephalosporins, cefamandole and cefuroxime, showed a superior activity against H. influenzae isolates, compared to other antibiotics. Multiple drug resistance was found in 64 (51%) isolates. Four of the five type b isolates were resistant to multiple drugs. The multiple-resistance pattern most frequently observed was to ampicillin, chloramphenicol, tetracycline and sulfamethoxazole-trimethoprim. Most clinical isolates did not contain plasmids; therefore, the antibiotic resistance of these H. influenzae strains was probably chromosome-mediated.
Polymerase chain reaction with restriction enzyme analysis (PRA) was first tested on 15 reference strains and 50 subcultured clinical isolates of mycobacteria according to the reference algorithm by Telenti et al . Next, we evaluated the application of this method to 108 isolates from liquid media (BACTEC 12B). Of them, 15 M. tuberculosis complex and 81 mycobacteria other than tuberculosis (MOTT) had comparable results with both PRA and the BACTEC 460 TB systems. However, seven M. tuberculosis complex and three potentially pathogenic MOTT were identified by PRA rather than the BACTEC TB system. PRA seems to be an efficient method for the identification of mycobacteria to the species level and a good aid to detect potentially pathogenic mycobacteria, especially in mixed mycobacterial cultures.
Postintubation tracheal injury is a rare but potentially fatal complication. Here we present a case of a 13-year-old boy who was transferred to our pediatric intensive care unit with presentation of severe subcutaneous emphysema after emergent intubation. Computed tomography and fiberoptic bronchoscopy revealed a pouch-like lesion at the middle to lower part of trachea which was in favor of tracheal injury during emergent intubation. The symptoms of the air leak subsided gradually under conservative management. Early surgical repair is traditionally considered to be the treatment of choice for tracheal injury, but conservative management now is considered to be a better alternative.
A five-year-old boy with psychomotor retardation, microcephaly, bilateral cataracts, hearing impairment and hypospadia with microphallus was found to have multiple cell lines from peripheral blood: 46,XY/46,XY, -13,+r(13)/46, Xy, -13, +dic r(13) in the ratio of 35%/61%/4% by trypsin-Giemsa, and C-bandings. Using fluorescence in situ hybridization (FISH) with biotin-labeled alpha-satellite probe (D21Z1/D13Z1) and fluorescence staining (FITC), we confirmed that the ring originated from chromosome 13. To elucidate changes in the chromosome ends in the ring originated from chromosome 13. To elucidate changes in the chromosome ends in the ring formation, we used human telomere-specific probes for FISH study; it showed an absence of telomeres on the ring chromosome, although Ag-NOR staining was positive. These findings yielded different breaking points on the ends of both the short and long arms of chromosome 13 from those reported in the literature.
Pericardial effusion is a common sequel to cardiac surgery. Urgent pericardiocentesis is required in the case of cardiac tamponade. In adult patients, most pericardiocentesis is accomplished using transthoracic echocardiographic imaging. However, transthoracic echocardiographic imaging may interfere with the procedure field in children. We report the case of a 13-month-old boy who developed cardiac tamponade resulting in heart failure after surgical repair of tetralogy of Fallot. Urgent pericardiocentesis was safely performed at the bedside under transesophageal echocardiographic guidance. Transesophageal echocardiographic monitoring during pericardiocentesis in children has the advantages of better imaging of pericardial effusion without procedure-field interference.
The response of peripheral T-cell lymphoma to 13-cis retinoic acid (13-cis-RA) has been well established, especially in Ki-1+ anaplastic large cell lymphoma (ALCL) confined to the skin. Here, we report the use of 13-cis-RA in combination with interferon alpha in a patient with refractory ALCL. The patient, an 18-year-old man, suffered from retroperitoneal, hepatic, and splenic ALCL. Reactive hemophagocytic syndrome also developed. Active Epstein-Barr virus infection was demonstrated by serologic tests and in situ hybridization of Epstein-Barr virus early RNA-1. Although high-dose intravenous immunoglobulin (IgG), etoposide, and steroids were administered, only chemotherapy (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone) successfully controlled the progress of hemophagocytosis. However, the retroperitoneal mass and splenic tumor did not show a satisfactory response to three cycles of chemotherapy. Hence, interferon 4.5 MU/m2 every other day with 13-cis-RA 1 mg/kg/day was instituted. Abdominal computed tomogram after 58 days of treatment revealed that the tumor had significantly reduced in size. Bone marrow biopsy demonstrated alleviation of hemophagocytosis as well. However, lymphoma cells had begun to infiltrate the bone marrow. Our findings suggest that 13-cis-RA and interferon alpha may be partially effective in treating ALCL.
Point mutations of the K-ras gene have been reported in a wide variety of human tumors. By using polymerase chain reaction followed by direct DNA sequencing, we screened for point mutations at codons 12 and 13 of the K-ras gene in specimens obtained from fresh frozen tumors in 38 patients with non-small cell lung cancers. Point mutations were detected in two of 38 (5.3%) resected non-small cell lung cancers. Both of them were G to T transversions. One patient was found to have a K-ras codon 13 point mutation (GGC to TGC, gly to cys), while the other had a codon 12 point mutation (GGT to GTT, gly to val). Based on the limited numbers in this study, we found that the frequency of K-ras point mutations in codons 12 and 13 among Asian patients with lung adenocarcinomas was lower than that detected among Caucasian patients.
In order to provide better quality of care at Taipei Veterans General Hospital, 13,911 emergency patients coming into the medical emergency room were studied using the computer to key in all demographic data including registration time, time to be seen, desposition time, impression, triage category, discipline as well as daily dynamic status in the observation room from August through December 1989. The study showed that 8.6% were triage category 1 (life-threatening cases) and 22.08% were triage 4 (pseudo-emergency patients). Of the average 101 studied patients seen per day, 20 (20.27%) should have been theoretically admitted, but only 14.7% were admitted, and 18 (18.08%) were sent to the observation room. In general, the daily dynamic status of the patients in the observation room were: (1) Out of 45 overnight patients, 12 (27%) were waiting for admission; and (2) 9 (20.14%) were waiting for a transfer to other convalescent hospitals. We conclude that less than one-tenth of the emergency patients were really emergencies in such a large and busy emergency department, and there was enormous patients stasis in the observation room causing overcrowding of the emergency department, which is the main issue we have to resolve if the quality assurance of the emergency department is to be improved.
During the 13-year period from 1978 to 1991, 202 patients with differentiated thyroid carcinoma were treated with radioactive iodine-131 (I-131) post-operatively. The therapeutic response and survival rates were studied. Of these patients, 172 (85%) patients were shown to be totally disease-free; others showed a partial response or persistence of disease. A total of 134 patients (66%) achieved total thyroid ablation with only one therapeutic dose of I-131, ranging from 100-200 mCi. Patients over the age of 40 years at the time of diagnosis had a lower survival rate than those under 40 years old (98.6% vs 68.9%; p < 0.001). However, patients over the age of 50 years and follicular patients had a lower recurrence rate than patients under the age of 50 years and those with papillary carcinoma. Eight of the 32 patients (25%) with lung metastases were detected by a therapeutic I-131 whole body scan (WBS), in which the diagnostic I-131 WBS was negative. In six of the 16 patients (37.5%) with bony metastases, the I-131 WBS showed more obvious positive results than the Tc-99m methylene diphosphonate (MDP) bone scanning. Most of the remaining patients exhibited the same findings for the two methods. Therefore, I-131 WBS is superior to Tc-99m MDP bone scanning in the detection of bony metastases from thyroid carcinoma. The mortality rate of patients with bony metastases was four times that of patients with lung metastases (40% vs 10%). Patients with follicular carcinoma had higher rates of distant metastases than those with papillary carcinoma (13% vs 4%).(ABSTRACT TRUNCATED AT 250 WORDS)
Seventeen patients who received radioiodine (131I) therapy for Graves' hyperthyroidism had serial blood samples taken before therapy and after therapy for a period of at least 1 year. At 1 year post-therapy, six patients were hypothyroid. Seven patients were euthyroid, and four patients were hyperthyroid. Prior to isotope administration, 14 patients had detectable serum thyrotropin-binding inhibiting immunoglobulin (TBII) and 16 patients had detectable serum thyroperoxidase antibody (TPOAb). Three to 6 months after therapy, 11 of 14 TBII-positive patients demonstrated a marked increase (> 10%) in serum TBII activity. Four patients out of 11 developed hypothyroidism and six of the 11 developed euthyroidism. A decrease in TBII was observed in three patients who developed hyperthyroidism. In the three patients with undetectable TBII prior to therapy, two had high titers of TPOAb. Seven patients demonstrated a marked increase in TPOAb 3 to 6 months after therapy. Of these, four developed hypothyroidism and three developed euthyroidism, whereas three of the four patients who had a marked decrease in TPOAb developed hyperthyroidism. This study demonstrated that an increase in serum TBII and TPOAb activity 3 to 6 months after 131I therapy, may be useful in predicting which patients may develop euthyroidism or hypothyroidism after 1 year of 131I therapy.
It is difficult, but important, to diagnose extra-adrenal pheochromocytomas before surgery. Failure to recognize the existence and nature of an extra-adrenal pheochromocytoma can cause life-threatening problems even in a minor surgical operation. We present two rare cases of extra-adrenal pheochromocytomas which were detected by 131I-MIBG scintigraphy. One of them was intrapericardial, and the other was a vesical pheochromocytoma. We used a combined 99mTc-MDP bone scan and 131I-MIBG scintigraphy to locate the pheochromocytomas. Both cases of extra-adrenal pheochromocytoma were correctly diagnosed preoperatively and successfully resected in the subsequent operations.
18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a relatively new modality in the follow-up of patients with differentiated thyroid cancer (DTC) who have undergone total thyroidectomy and postoperative radioiodine therapy. The aim of this study was to assess the diagnostic value of FDG-PET, comparing it with 131I whole-body scan (WBS) and 201Tl WBS.
Fifteen selected patients with local invasive and/or aggressive DTC were included in this study. The follow-up period ranged from 1 to 12 years, with a mean +/- standard error of 6 +/- 3 years. FDG-PET was performed when patients were still receiving thyroxin therapy.
In the cervical region, residual cancer in two patients was demonstrated by FDG-PET, but could not be detected using 131I WBS or 201Tl WBS. Pathology of the surgical specimen showed dedifferentiation of thyroid cancer in one of these patients. Metastatic cervical lymph nodes were detected using FDG-PET in three patients, but in only one patient using 131I WBS and in another one patient using 201Tl WBS. Mediastinal metastases were detected using FDG-PET in three patients, 131I WBS in two patients, and 201Tl WBS in one patient. Diffuse lung metastasis was detected only by 131I WBS in two patients. The use of FDG-PET in conjunction with computerized tomography provided useful diagnostic information about small nodular lesions of the lung which could not be localized by 131I WBS or 201Tl WBS in three patients. In skeletal metastases, 131I WBS detected more metastatic lesions than FDG-PET or 201Tl WBS, especially when the lesions were located in the pelvis.
In the follow-up evaluation of patients with post-therapy DTC, FDG-PET was useful for detecting dedifferentiated lesions and was superior to 131I WBS in detecting residual cervical or mediastinal lesions and suspected small metastatic foci in the lung. FDG-PET was inferior to 131I WBS in detecting diffuse lung metastases and distant bone metastases.
Gain or loss of a fragment in human chromosomes has been associated with abnormal phenotypes in numerous genetic disorders. However, it is also possible that lack or excess of a particular chromosomal segment is a neutral polymorphism among populations and thus does not cause obvious abnormal phenotype. In this study, conventional GTG-banded karyotyping and molecular cytogenetic analyses (including fluorescence in situ hybridization, spectral karyotyping and comparative genomic hybridization) were applied to study the genotype-phenotype correlation in a Taiwanese family, in which a concomitant segregation of del(13)(q31q31) interstitial deletion and t(13;18)(q32;p11.2) reciprocal translocation in a 2-year-old girl (the proband) was noticed. Two family members (the father and grandmother of the proband) who carried the del(13)(q31q31) but not the translocation t(13;18) both revealed a normal phenotype at adulthood. The finding, which appears novel, that interstitial deletion 13q31 could be associated with a normal phenotype, is therefore valuable in genetic counseling.
There are limited data on the pattern of cancer distribution among adolescents in Taiwan. This study evaluated the characteristics of these rare cancers in a medical center.
Analyses of the characteristics of malignant neoplasms for patients aged 14 to 17 years at diagnosis were performed for all cases recorded in the tumor registry of Chang Gung Memorial Hospital (CGMH) at Linkou for the period 1995 to 2001. All eligible tumors were categorized in 1 of 12 diagnostic groups according to the scheme of the International Classification of Childhood Cancer (ICCC). Relative frequencies, age, and gender variations and the characteristics of tumor types were analyzed.
Cancer was diagnosed in 320 adolescents during the study period. The male/female ratio was 1.17. Leukemia was the leading diagnostic group. The frequency of carcinomas increased with age and was highest among 17-year-olds. In this age group, non-rhabdomyosarcoma soft tissue sarcoma/primitive neuroectodermal tumor (non-RMS STS/PNET), thyroid carcinoma (CA) and ovarian germ cell tumor (GCT) were the 3 most common solid tumors; the embryonal malignancies were rare. Tumors with the greatest male predominance were intracranial GCT (91%), nasopharyngeal CA (87.5%), osteosarcoma (84.6%), and colorectal CA (75%). Tumors with the greatest female predominance were thyroid CA (78.3%), gonadal GCT (75%), and non-RMS/PNET (56.5%). Hepatocellular CA comprised 9.4% of all carcinomas.
The relative frequency and the distribution of histology subtypes among adolescents were between those of childhood and adult cancers. There were marked variations in tumor occurrence between genders and among different ages.
Data on the in vitro activities of orally administered cephalosporins, particularly third-generation cephalosporins, against recent pathogens responsible for community-respiratory tract infection are lacking.
A susceptibility surveillance of 267 isolates of Streptococcus pneumoniae, 205 of Streptococcus pyogenes, 204 of Haemophilus influenzae, and 147 of Moraxella catarrhalis to 14 oral antimicrobial agents using the agar dilution method was carried out from March 2002 to October 2002 in Taiwan.
High rates of non-susceptibility to penicillin (60%), cefaclor (67%), cefuroxime (62%), cefpodoxime (64%), clarithromycin (91%), and trimethoprim-sulfamethoxazole (98%) for S. pneumoniae isolates and high rates of non-susceptibility to ampicillin (70%), clarithromycin (34%), and trimethoprim-sulfamethoxazole (63%) for H. influenzae isolates were found. The rank order of oral cephalosporin activity based on the minimum concentrations at which 90% of the isolates were inhibited (MIC90s) for S. pneumoniae was cefpodoxime > cefuroxime > cefixime > cefaclor, cephradine > cephalexin and for H. influenzae and M. catarrhalis was cefixime > cefpodoxime > cefuroxime > cefaclor > cephalexin, cephradine. Among the 75 S. pneumoniae isolates resistant to penicillin (MICs ranged 2 to 4 mg/L), 4% were intermediate to amoxicillin and > 90% were resistant to cefaclor, cefuroxime, and cefpodoxime. For S. pyogenes isolates, all were susceptible to penicillin, 21% were not susceptible to clarithromycin and 4% were not susceptible to clindamycin. Thirty four percent of H. influenzae isolates were not susceptible to clarithromycin. The MIC90 of clarithromycin against M. catarrhalis isolates was 0.5 mg/L.
Cefpodoxime, cefixime, and cefuroxime are promising agents against these bacterial pathogens, except for penicillin-non-susceptible S. pneumoniae isolates.
The authors describe the rare occurrence of nasopharyngeal carcinoma (NPC) in 14 aboriginals of Taiwan (ABT), a minor ethnic group now accounting for less than 2% of the total population in Taiwan. The observation is epidemiologically unusual, representing a low-risk ethnic group in an NPC prevalent area. With regard to patient characteristics, symptomatology and pathology, we have not found any appreciable differences in reports from other geographic areas. Serological profiles of antiEBV-VCA (Epstein-Barr virus, viral capsid antigen) antibody in 7/9 patients available for review of IgA and 5/7 patients available for review of IgG were found significantly elevated, ranging respectively from 1:40-640/1:160-1280. Interestingly, 12 of the 14 patients were found to be exclusively from the Paiwan tribe residing in Pintung, a district in southern Taiwan. Since the exact prevalence of NPC in this minority remains unknown, it is not clear whether the apparent preponderance is real or merely causal due in part to geographic bias. To a lesser extent, however, our observations indicate that NPC is not an uncommon malignancy in Paiwan aboriginals of southern Taiwan.
A total of 6,160 gravidas with gestational ages from 14 to 25 weeks were collected to quantify maternal serum alpha-fetoprotein (MSAFP) using an enzyme immunoassay kit. A level over 2.5 MoM (multiples of the median) was defined as high and a level below 0.4 MoM as low. Ninety-eight women (1.59%) had an initially high MSAFP and 88 (1.42%) a low MSAFP. In the low MSAFP group, 80% returned for a further checkup. Among them, 46% had an over-estimation of gestational age based on their last menstrual period (LMP), 28% had a normal MSAFP and 9% still had a low MSAFP level on a repeat test. Pathologic conditions in other pregnancies included a hydatidiform mole, miscarriage and pseudocyesis. One nonresponder had an ectopic pregnancy. After delivery, no major fetal abnormalities, including trisomy syndromes, were noted in pregnancies carried to term. In the high MSAFP group, 84% returned for check-up. Among them, 15% had an under-estimation of gestational age based on LMP, 16% had twin pregnancies, 46% had a normal MSAFP and 12% still had a high MSAFP on a repeat test. Pathologic conditions in the other pregnancies included one anencephaly, one hydrocephaly and 6 miscarriages. Wrong dating by LMP and false positivity were the most frequent causes of abnormal levels of MSAFP. Two gravidas had artificial abortions because of undue anxiety. MSAFP screening in Taiwan for open neural tube defects does not seem appropriate and using 0.4 MoM as a fixed low cut-off point is inadequate for trisomy syndrome screening. Maternal anxiety should be seriously considered and proper genetic counseling implemented in a screening procedure.
Although gram-positive organisms are the most common causes of nosocomial bloodstream infections, gram-negative bacteremia carries higher risks of severe sepsis, septic shock, and death among critically ill patients in intensive care units (ICUs). We performed a prospective epidemiologic analysis of nosocomial gram-negative bacteremia episodes among ICU patients and sought to identify risk factors for mortality among these patients. All episodes of nosocomial gram-negative bacteremia documented in five ICU wards of our hospital during a 2-year period were included. There were 147 episodes (124 patients) of gram-negative bacteremia documented during the study period. The overall mortality rate was 36.1%, and 77.4% of all deaths were directly related to the bloodstream infection. Gram-negative bacteremia was associated with prolonged ICU stay (45.7 d vs 6.1 d for all ICU patients). The most common isolate was Acinetobacter baumannii, followed by Burkholderia cepacia and Enterobacter cloacae. The most frequent source of infection was the lower respiratory tract (32.0%). Of the agents tested, ciprofloxacin, imipenem, and ceftazidime were the most active against the clinical isolates. Multivariate logistic regression analysis identified the presence of septic shock (odds ratio, OR = 17.66, p < 0.001) and rapidly fatal and ultimately fatal underlying conditions (OR = 3.47, p = 0.032) as being independent risk factors for mortality. Early appropriate antibiotic treatment did not result in significant improvement in survival. These findings suggest that prevention of lower respiratory tract colonization and nosocomial pneumonia are crucial for reducing the incidence of nosocomial gram-negative bacteremia in the ICU. Serious underlying illnesses and septic shock were the most important risk factors for death in these patients.
Taiwan is a hyperendemic area of liver diseases. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the two major etiologies of liver diseases in Taiwan. This study investigated the seroprevalence of HBV and HCV in Taiwan.
Since 1996, a series of outreach community-based screening programs for liver diseases have been available to the general population aged > or = 18 years. Blood samples were obtained from the subjects and sent for hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) tests.
The prevalence of HBsAg(+) was 17.3% (27,210/157,720), while the prevalence of anti-HCV(+) was 4.4% (6904/157,720). Geographic variation in HBV and HCV seroprevalence was found, with the highest anti-HCV positive rate in Miaoli County, Chiayi County, Chiayi City, and Yunlin County, and the highest HBsAg positive rate in Keelung City and Yilan City. The HBsAg positive rate progressively decreased after the age of 50 years, while the anti-HCV positive rate progressively increased after the age of 20 years. The estimated total number of HBsAg carriers in the general population > 20 years old is 3,067,307, while the estimated number of anti-HCV positive patients is 423,283.
This study estimated a 17.3% seroprevalence of HBV and a 4.4% seroprevalence of HCV in Taiwan. Significant geographic variations in the seroprevalence of HBV and HCV were found. These data suggest the importance of modifying programs for the prevention and treatment of chronic viral hepatitis in Taiwan to reflect its varying prevalence and epidemiology.
Deletion (14)(q11.2q13.1) is a rare cytogenetic abnormality associated with severe neurological deficit, microcephaly and psychomotor retardation. We report a case of de novo interstitial deletion of chromosome (14)(q11.2q13.1) in an 8-month-old girl, who presented with marked microcephaly, a nearly closed anterior fontanelle, dysmorphic facies, severe neurological deficits, and delayed developmental milestones. Three-dimensional computed tomography of the brain showed premature closure of the coronal suture and magnetic resonance imaging of the brain showed frontal atrophy and hypoplastic corpus callosum.
The diagnostic value and indications for fiberoptic bronchoscopy in the preoperative assessment of patients with esophageal cancer have not been fully studied. We evaluated the role of fiberoptic bronchoscopic examination in the stage work-up of patients with esophageal cancer and correlated the results with survival time analysis.
The medical records of 153 patients with an initial diagnosis of esophageal cancer were reviewed. Clinical data, bronchoscopic findings, treatment courses, and survival time of these patients were analyzed.
On initial bronchoscopic examinations, distortion/compression of the normal structure and protrusion at the posterior wall of the trachea or bronchus were the most common bronchoscopic findings (35.9%). We stratified patients into 3 subgroups according to bronchoscopic findings of direct invasion, external compression, and negative findings. The symptoms of dyspnea, hoarseness, aspiration and fever were more frequent in patients with direct airway invasion compared with patients with external compression and negative bronchoscopic findings (p < 0.02). Washing and brushing cytology examinations were all negative in patients with external compression of the airway. There was a significant difference of survival time among these 3 groups of patients (direct invasion: 5.6 +/- 0.6 months; external compression: 12.3 +/- 0.9 months; negative findings: 13.3 +/- 1.1 months, p < 0.01). Direct airway invasion and original cancer stage were the most important variables for survival in the multivariate analysis, and the hazard ratio for prognosis was 2.5 (95% confidence interval [CI], 1.1-4.6) and 4.2 (95% CI, 1.5-9.3), respectively. Twelve patients (80%) with tracheoesophageal (TE) fistulae died within 3 months after diagnosis due to aspiration pneumonia and septic shock.
The role of bronchoscopic examination in patients with esophageal cancer for preoperative evaluation resides in its ability to predict airway invasion and its impact on survival. Advanced cancer stage (stage IV) and direct airway invasion (especially TE fistula) were significantly associated with poor prognosis. These results suggest that patients suffering from dyspnea, hoarseness, aspiration and fever, implicating a high probability of airway invasion, are more likely to benefit from bronchoscopic examination and proper management in order to prevent aspiration or complications.
To evaluate the epidemiology, clinical features, and microbiological features (including antibiotic susceptibility) of infective endocarditis (IE) at Kitasato University Hospital, Japan.
We retrospectively analyzed 153 patients (155 episodes) with definite IE according to the Duke criteria, who presented over a 17-year period. The minimum inhibitory concentrations of antibiotics for cultured causative microorganisms were also examined.
Viridans group streptococci were the most common pathogens (36.8%, 57 episodes), followed by Staphylococcus aureus [21.3%, 33 episodes, including 10 episodes due to methicillin-resistant S. aureus (MRSA)]. Thirty-nine of the 40 strains of viridans streptococci were fully susceptible to penicillin. Comparison of IE due to methicillin-sensitive S. aureus (MSSA) and MRSA showed that the latter had a higher mortality rate (34.8%, 8/23 vs. 70.0%, 7/10). Compared with MSSA, IE caused by MRSA was significantly more likely to be related to nosocomial infection (10/10, p < 0.001), hemodialysis (4/10, 40.0%, p = 0.005), and surgery or intravascular catheter insertion (8/10, 80.0%, p = 0.007). There was a significantly higher mortality rate in non-operated (15/43, 34.9%) than in operated (2/21, 9.5%) (p < 0.001) elderly patients. In 92/155 episodes (59.4%), antibiotics were given before blood cultures were obtained. Culture-negative IE occurred in 20.7% (19/92) of patients on antibiotics versus 6.3% (4/63) of those not on antibiotics (p = 0.02). Of 155 episodes of IE, 34 (21.9%) were fatal and staphylococcal had significantly higher mortality than streptococcal IE [(19/40, 47.5%) vs. (7/72, 9.7%); p < 0.001].
The most frequently isolated pathogens were viridans group streptococci, which differed from other recent studies. In the present study, no penicillin-resistant strains were detected and there was a higher mortality rate for IE caused by MRSA than MSSA. IE should be considered in MRSA patients with the following risk factors: nosocomial infection, hemodialysis, and surgery or intravascular catheter insertion.
Site-dependent profiles of chromosome imbalances (CIs) have been reported in gastrointestinal stromal tumors (GISTs). However, the role of specific CIs in association with metastasis is not clear.
Thirteen resected liver metastatic GISTs, including seven from the stomach and six from the small intestine, were analyzed using comparative genomic hybridization (CGH). The CIs associated with metastatic risk were assessed by comparing them with those identified in our previous study of 25 primary GISTs, including 14 from the stomach and 11 from the small intestine.
Synchronous detection of liver metastasis was found more often in patients with intestinal than gastric GIST (5/6 vs. 2/7, p = 0.048). When compared with the primary tumors, the CI profile of liver metastases was similar in the intestinal group, but became more complex in the gastric group. Deletions of chromosomes 1p and 15q were very common (> 80%) in primary and metastatic tumors of the intestinal group, and exhibited a trend towards increase in the metastatic tumors of the gastric group. Both groups had a doubling in the frequency of 22q deletion in the liver metastases, which was not significantly different. Other CIs, including 9p deletion, increased significantly in the liver metastases of the gastric group, but not in the intestinal group.
Our results, together with clinical findings, indicated a CGH profile associated with the intrinsic aggressiveness of the GISTs. Deletion of 1p and 15q play a critical role in the acquisition of aggressiveness during early GIST development.