Synthesis of novel C4-benzazole naphthalimide derivatives with potent anti-tumor properties against murine melanoma.

Novel C4-benzazole naphthalimide derivatives were synthesized and tested in vitro and in vivo as anti-cancer drugs. Among these synthetic molecules, compounds 9 and 10 exhibited cytotoxicity against murine B16F10 melanoma cells. In addition, the above-mentioned compounds significantly suppressed lung tumor metastasis with no visible sign of toxicity.

Relapsing Polychondritis Presenting with Meningoencephalitis and Dementia: Correlation with Neuroimaging and Clinical Features.

PURPOSE: Relapsing polychondritis (RP) is a rare systemic autoimmune disease affecting cartilaginous and non-cartilaginous structures. Neurological involvement is rarer but results in profound disability. Early identification and treatment of underlying RP may promote neurological recovery. CASE REPORT: We illustrated a 53-year-old man diagnosed with dementia. Neuroimaging and cerebrospinal fluid studies disclosed meningoencephalitis. "Prominent ear sign" was evident on diffusion-weight magnetic resonance imaging. After glucocortisone administration, the improvement of clinical manifestations was closely correlated subsequent neuroimaging findings. CONCLUSION: The importance of better understanding of this disease in terms of the prevention of further tissue damage in patients with RP cannot be overemphasized.

Juvenile idiopathic arthritis presenting with prolonged fever.

BACKGROUND/PURPOSE: Systemic-onset juvenile idiopathic arthritis (s-JIA) is a systemic disease often accompanied by a fever. We examined 16 patients with s-JIA and reported the clinical manifestations, laboratory data, treatments and outcomes. METHODS: From 1984 to 2007, 16 children (aged 1-16 years), who were diagnosed as having s-JIA, were admitted to the Mackay Memorial Hospital in Taiwan. We retrospectively reviewed their medical charts. RESULTS: There were nine boys and seven girls, with mean age of onset of 7.4±5.5 years. Fever (100%), typical rash (63%), and arthritis (75%) were the three most common symptoms. Lymphadenopathy (50%), hepatosplenomegaly (63%), pleural pulmonary manifestations (13%) and myalgia (25%) were also noted. One patient had Epstein-Barr virus-associated hemophagocytic syndrome complications. Neutrophilic leukocytosis was a common feature. Other laboratory data showed elevated C-reactive protein levels (25.1±50.3 mg/dL), and erythrocyte sedimentation rates (69±28 mm/hr) and abnormal liver enzymes. Marked hyperferritinemia (> 2,000 ng/mL) was noted in 57% (4/7) of the patients. The mean time from onset of symptoms to diagnosis was 9.2 weeks. Non-steroidal anti-inflammatory drugs, steroids, disease-modifying anti-rheumatic drugs and anti-tumor necrosis factor agents were used for treatment. Due to prolonged fever, 2.0±1.6 (maximum=5) different kinds of antibiotics were used before a diagnosis was made. Most cases had satisfactory therapeutic outcomes except one boy, who had permanent joint contracture. CONCLUSION: The clinical manifestations of s-JIA in Taiwan were often accompanied by a prolonged fever. This results in clinicians often suspecting bacterial infections and prescribing several kinds of antibiotics. In the case of prolonged fever, s-JIA should always be placed on the list of differential diagnoses.

Insulinoma causing hypoglycemia in a patient with type 2 diabetes.

Insulinoma in a patient with pre-existing diabetes is extremely rare. A 74-year-old woman with type 2 diabetes mellitus who had been treated with a sulfonylurea for 6 years began experiencing frequent episodes of hypoglycemia. Endogenous hyperinsulinism was found 9 months after the sulfonylurea was discontinued, and transabdominal ultrasonography and magnetic resonance imaging identified a pancreatic tumor. Pathology examination of the resected tumor demonstrated an insulinoma. Postoperatively, the patient had no further episodes of hypoglycemia. Thereafter, she required insulin to control her hyperglycemia. Although hypoglycemic agents are the commonest cause of hypoglycemia in type 2 diabetes, insulinomas may occur in these patients. This possibility should be considered if the hypoglycemia persists despite dose adjustment or cessation of the drugs.

Influence of HLA-DRB1 genes and the shared epitope on genetic susceptibility to rheumatoid arthritis in Taiwanese.

OBJECTIVE: To investigate the association of predisposing and protective HLA-DRB1 alleles with rheumatoid arthritis (RA) and its clinical markers in a Taiwanese population. METHODS: A total of 273 patients with RA and 480 healthy controls, all of Taiwanese origin, were genotyped for HLA-DRB1 alleles by polymerase chain reaction and sequence-based typing assays. The associations between RA and HLA-DRB1 alleles and genotypes were investigated by chi-squared test. RESULTS: The DRB1*0405 and *1001 phenotypes showed the most significant associations with RA (OR 4.04, 95% CI 2.84-5.77, pc = 3.2 10(-14); OR 5.25, 95% CI 2.10-13.06, pc = 3.0 10(-3), respectively). Individuals carrying single or double doses of the shared epitope (SE/non-SE or SE/SE) had higher risks of RA. The compound heterozygote of DRB1*0405/*1001 showed the largest increase in RA risk (OR 15.8, 95% CI 2.48-100.7, pc = 0.004). Single or double doses of SE alleles were significantly associated with a higher bone erosion rate. Rheumatoid factor positivity and bone erosion were more frequent in patients with at least one copy of DRB1*0405. CONCLUSION: Our results show that SE-encoding HLA-DRB1*0405 and *1001 are associated with RA in a Taiwanese population; this is the first time DRB1*1001 has been described in persons of Asian ethnicity. Heterozygotes of DRB1*0405 and *1001 predicted the strongest susceptibility to RA, suggesting that this genotype enhances susceptibility to RA in Taiwanese.

A randomized controlled trial of cetirizine plus pseudoephedrine versus loratadine plus pseudoephedrine for perennial allergic rhinitis.

The purpose of this study was to compare the safety and efficacy of cetirizine plus pseudoephedrine (C+P) with loratadine plus pseudoephedrine (L+P) in the treatment of perennial allergic rhinitis. This was a double blind, randomized, parallel trial with an active control. Subjects aged 12 to 70 years with perennial allergic rhinitis for at least 2 years were enrolled and randomized to receive either of the active study medications plus a placebo resembling the other, twice daily for 4 weeks. Nasal total symptom scale (NTSS) including sneezing, rhinorrhea, nasal itching and nasal stuffiness is evaluated by subjects daily and at baseline, 2 weeks, and 4 weeks by the investigator as efficacy measurement. A total of 51 eligible patients were enrolled and 45 patients completed the treatment course. Both groups had significant reductions in NTSS after 4 weeks of treatment as assessed by the subjects, but there was no significant difference between the two groups (mean +/- SD) reduction of 4.25 +/- 2.45 with C+P vs. 3.52 +/- 2.41 with L+P, p = 0.215. As assessed by the investigator, sneezing was significantly better at 2 weeks (-1.13 vs. -0.52, p = 0.028) and nasal congestion at 4 weeks (-1.71 vs. -1.19, p = 0.031) in subjects treated with C+P compared to those treated with L+P. There were 37 treatment-related adverse events (5 in 4 subjects in the C+P group and 32 in 16 subjects in the L+P group). It was concluded that both cetirizine plus pseudoephedrine and loratadine plus pseudoephedrine are efficacious for perennial allergic rhinitis in Taiwanese subjects. Relief of sneezing and nasal congestion may be marginally better with the cetirizine preparation, which also seemed to be slightly better tolerated, although the incidence of side effects did not differ significantly.

Outcome of pregnancy in patients with systemic lupus erythematosus.

OBJECTIVE: To study the maternal and fetal outcomes in women with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Over a period of 10 years, 24 pregnancies in 17 females with SLE in a single center were enrolled. Fetal and maternal outcomes were studied retrospectively. RESULTS: The mean patient age was 27.7 years. Twenty-one of the 24 pregnancies occurred in the period of disease remission at the time of conception. Proteinuria presented in 12 pregnancies; however, no patient developed acute renal failure or deterioration of renal function. There were three cases of preeclampsia in this study. Two patients had their disease flare up and delivered stillborns. One woman with secondary antiphospholipid syndrome (APS) had a fetal loss. There was no maternal mortality. The mean gestation age was 34.3 weeks (range, 17-41 weeks), and the mean birth weight was 2,179 g. The mean APGAR scores were 8 and 9 at 1 and 5 minutes, respectively. One baby with congenital atrioventricular block was born to a mother with positive anti-SSA antibody. There were five cases (20.8%) of intrauterine growth retardation and 10 preterm deliveries (41.6%) in this study. CONCLUSION: Pregnancy is relatively safe in women with SLE in remission but should be considered as a high-risk pregnancy. APS is associated with poor pregnancy outcome. The patient needs to cooperate with obstetricians and physicians for optimal disease control and detailed monitoring throughout the gestation.