Prevention of anterior glottic stenosis after transoral microresection of glottic lesions involving the anterior commissure with mitomycin C

OBJECTIVE: To evaluate the effectiveness of topical mitomycin C (MMC) in preventing anterior glottic stenosis (AGS) after transoral microresection of glottic lesions involving the anterior commissure (AC). STUDY DESIGN: Prospective clinical study. METHODS: Sixteen patients with benign or malignant glottic lesions involving the AC were studied. The lesions were removed by transoral microsurgery using a CO2 laser or cold microinstruments. In all patients, the anterior glottis was treated topically with 0.4 mg/mL MMC for 5 minutes at the end of surgery. The postoperative vocal folds and voice quality of patients were evaluated using video strobolaryngoscopy and voice recordings. RESULTS: Four patients had local recurrences after surgery and were treated with repeat microsurgery. Postoperatively, five patients (31%) developed acceptable small webs in the anterior glottis; one resolved with web lysis and a second with topical MMC. Postoperative vocal quality was affected mainly by the extent of vocal fold resection and the subsequent wide glottal gaps and extensive scarring, rather than by MMC use per se. Significant local side effects or atrophy of the vocal folds owing to MMC were not found. CONCLUSION: Topical MMC may be useful for preventing AGS and subsequent dysphonia after transoral microresection of glottic lesions involving the AC.     

Radiation therapy with UFT and low dose weekly cisplatin for nasopharyngeal carcinoma

OBJECTIVE: We conducted this study to determine the effectiveness and toxicity of chemoradiation therapy using UFT and low-dose cisplatin in 37 patients with nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Between March 1999 and December 2001, 37 patients with newly diagnosed and histologically proven nasopharyngeal carcinoma treated in Department of Radiation Oncology, Asan Medical Center were enrolled in this protocol. Cisplatin was administered weekly, starting on day 1 of radiation therapy, as an intravenous infusion at 20 mg/m2 of body-surface area. Oral UFT was administered daily, at a dose of 300 mg in three divided doses. Radiation therapy was given in doses of 1.8-2.0 Gy, 5 days per week, with 4-15 MV photons. The dose of elective nodal area was 60 Gy, and primary tumors and enlarged lymph nodes were boosted with intracavitary brachytherapy or 3D conformal therapy. RESULTS: All patients received the planned doses of radiation. Cisplatin was administered for a median of 6 cycles, and 81% of patients received UFT for more than 5 weeks. The complete response rate was 95% for all patients, and the overall response rate was 100%. No patient experienced hematologic toxicity of grade 3 or higher. Five patients experienced grade 3 non-hematologic toxicity but recovered with conservative management. There was no treatment-related hospitalization or death. CONCLUSION: These findings suggest that UFT and low-dose cisplatin is a safe and effective regimen of concurrent chemoradiation therapy for patients with nasopharyngeal carcinoma.     

VDUP1 is required for the development of natural killer cells

Vitamin D3 upregulated protein 1 (VDUP1) is a stress-response gene that is upregulated by 1,25(OH)2D3 in tumor cells. The in vivo roles of VDUP1 were investigated by producing mice lacking VDUP1 (VDUP1-/- mice). VDUP1-/- mice showed minimal changes in the development of T and B cells, but there was a profound reduction in the numbers of natural killer (NK) cells. As well, these mice showed decreased NK activity. In the VDUP1-/- mice, the expression of CD122 was reduced, demonstrating that VDUP1 is required for CD122 expression and NK maturation. In addition, severe lymphoid hyperplasia in the small intestine was observed in VDUP1-/- mice. Taken together, these results suggest that VDUP1 is a critical factor for the development and function of NK cells in vivo.     

High-resolution whole-organ mapping with SNPs and its significance to early events of carcinogenesis

We attempted to identify deleted segments in two model tumor suppressor gene loci on chromosomes 13q14 and 17p13 that were associated with clonal expansion of in situ bladder preneoplasia using single nucleotide polymorphisms (SNPs)-based whole-organ histologic and genetic mapping. For mapping with SNPs, the sequence-based maps spanning approximately 27 and 5 Mb centered around RB1 and p53, respectively, were assembled. The integrated gene and SNP maps of the regions were used to select 661 and 960 SNPs, which were genotyped by pyrosequencing. Genotyping of SNPs was performed on DNA samples corresponding to histologic maps of the entire bladder mucosa in human cystectomy specimens with invasive urothelial carcinoma. By using this approach, we have identified deleted regions associated with clonal expansion of intraurothelial neoplasia; which ranged from 0.001 to 4.3 Mb (average 0.67 Mb) and formed clusters of discontinuous deleted segments. The high resolution of such maps is a prerequisite for future positional targeting of genes involved in early phases of bladder neoplasia. This approach also permits analysis of the overall genomic landscape of the involved region and discloses that a unique composition of noncoding DNA characterized by a high concentration of repetitive sequences may predispose to deletions.     

Voltage-gated calcium channels play crucial roles in the glutamate-induced phase shifts of the rat suprachiasmatic circadian clock

The resetting of the circadian clock based on photic cues delivered by the glutamatergic retinohypothalamic tract is an important process helping mammals to function adaptively to the daily light-dark cycle. To see if the photic resetting relies on voltage-gated Ca(2+) channels (VGCCs), we examined the effects of VGCC blockers on the glutamate-induced phase shifts of circadian firing activity rhythms of suprachiasmatic nucleus (SCN) neurons in hypothalamic slices. First, we found that a cocktail of amiloride, nimodipine and omega-conotoxin MVIIC (T-, L- and NPQ-type VGCC antagonists, respectively) completely blocked both phase delays and advances, which were, respectively, induced by glutamate application in early and late night. Next, we discovered that: (i) amiloride and another T-type VGCC antagonist, mibefradil, completely obstructed the delays without affecting the advances; (ii) nimodipine completely blocked the advances while having less impact on delays; and (iii) omega-conotoxin MVIIC blocked largely, if not entirely, both delays and advances. Subsequent whole-cell recordings revealed that T-type Ca(2+) currents in neurons in the ventrolateral, not dorsomedial, region of the SCN were larger during early than late night, whereas L-type Ca(2+) currents did not differ from early to late night in both regions. These results indicate that VGCCs play important roles in glutamate-induced phase shifts, T-type being more important for phase delays and L-type being so for phase advances. Moreover, the results point to the possibility that a nocturnal modulation of T-type Ca(2+) current in retinorecipient neurons is related to the differential involvement of T-type VGCC in phase delays and advances.     

Cerebellar and cerebral atrophy in trichothiodystrophy

Trichothiodystrophy is a rare neuroectodermal disorder of autosomal recessive inheritance that is characterized by brittle hair, nail dysplasia, ichthyosis, mental retardation, and gonadal failure. We describe a female patient whose cranial MRI revealed almost total lack of myelination in the supratentorial white matter, which is similar to the previously described cases. In addition, there was progressive cerebellar and cerebral atrophy, which has not been well documented in association with trichothiodystrophy.     

A short cervix in women with preterm labor and intact membranes: a risk factor for microbial invasion of the amniotic cavity

OBJECTIVE: The purpose of this study was to determine whether there was a relationship between sonographic cervical length and the presence of culture-proven microbial invasion of the amniotic cavity in women with preterm labor and intact membranes. STUDY DESIGN: Ultrasonography and amniocentesis were performed in 401 patients admitted with preterm labor (22-35 weeks) and cervical dilatation of < or = 3 cm, as assessed by digital examination. Cervical length was determined by transvaginal ultrasound at admission. Outcome variables were the presence of microbial invasion of the amniotic cavity (defined as a positive amniotic fluid culture) and the occurrence of preterm delivery before 35 weeks. Contingency tables, chi2 test, receiver-operator characteristic (ROC) curves, and logistic regression were used for statistical analysis. RESULTS: The prevalence of microbial invasion of the amniotic cavity was 7% (28/401). Spontaneous preterm delivery (< or = 35 weeks) occurred in 21.4% (82/384) of patients. ROC curve analysis showed a significant relationship between the frequency of microbial invasion of the amniotic cavity and the length of the uterine cervix (area under the curve: 0.77; P < .005). Patients with a cervical length < 15 mm had a higher rate of a positive amniotic fluid culture than patients with a cervical length > or = 15 mm (26.3% [15/57] vs. 3.8% [13/344], respectively; P < .05). Moreover, patients with a short cervix (defined as < 15 mm) were more likely to deliver spontaneously before 35 weeks, 32 weeks, within 7 days, and within 48 hours of admission ( P < .05 for all comparisons). Forty percent of patients (161/401) had a cervical length > or = 30 mm. These patients had a very low risk of microbial invasion of the amniotic cavity (1.9% [3/161]), spontaneous delivery < or = 35 weeks (4.5% [7/154]), < or = 32 weeks (2.6% [2/76]), within 7 days (1.9% [3/154]), and within 48 hours (0% [0/154]) of admission. CONCLUSION: Endovaginal ultrasonographic examination of the uterine cervix in women with preterm labor identifies patients at increased risk for intrauterine infection.     

5-(3,5-Di-tert-butyl-4-hydroxybenzylidene) thiazolidine-2,4-dione modulates peroxisome proliferators-activated receptor gamma in 3T3-L1 adipocytes: roles as a PPARgamma ligand

Based on the binding between peroxisome proliferators-activated receptor gamma (PPARgamma) and steroid receptor co-activator-1 (SRC-1), an enzyme-linked immunosorbent assay (ELISA) was used to screen new PPARgamma ligands from various benzylidinethiazole derivatives, which have anti-inflammatory activity. Among those derivatives, 5-(3,5-di-tert-butyl-4-hydroxybenzylidene) thiazolidine-2,4-dione (BTZD) increased the binding between PPARgamma and SRC-1. BTZD was found to induce adipogenesis and PPARgamma trans-activation in 3T3-L1 pre-adipocyte, and increased the binding between PPARgamma and SRC-1 in in vitro binding assay and complex consisting of PPARgamma and SRC-1 in the co-immunoprecipitaion. Chromatin immunoprecipitation (ChIP) analysis revealed that BTZD induced the binding of PPARgamma-SRC-1 complex to PPAR response element (PPRE) in the same pattern of other PPARgamma ligand. From these studies, we have identified and studied the function of a new PPARgamma ligand, BTZD. We suggest that BTZD can be used as a modulator of PPARgamma. This study applying ELISA and ChIP assay can offer new methods to screen PPARgamma ligand and understand the effects of PPARgamma ligands on inflammation.     

Timing of lamivudine administration according to Child class in patients with decompensated cirrhosis

BACKGROUND: Few clinical trials have investigated the use of lamivudine (LAM) in patients with decompensated cirrhosis related to chronic hepatitis B. The aim of the present study was to evaluate the efficacy of extended LAM treatment and to determine the timing of LAM administration in patients with decompensated cirrhosis. METHODS: A total of 17 patients were treated with LAM 100 mg/day. The mean duration of follow up was 28 +/- 8.4 months (range: 14-42 months). All patients were evaluated for evidence of clinical, biochemical and serologic replication of hepatitis B virus (HBV) infection. There were 12 patients with Child class B and five with Child class C. RESULTS: Ten of 17 patients (58.2%) responded to LAM treatment. Of the breakthrough patients, six (86%) had YMDD motif variants. Clinical improvement was observed in nine out of 10 responders (90%), six of the seven breakthrough patients (86%) and five of six patients with YMDD variant DNA. Mean time to achieve a 2-point reduction in Child-Pugh-Turcotte score was 14 months in patients with Child class C, compared with 5.9 months in those with Child class B (P < 0.001). Mean time required to gain a 0.5 g/dL increment in albumin was 14 months in Child class C and 5.8 months in Child class B. Hepatitis B e antigen (HBeAg) seroconversion was achieved in five of 13 HBeAg-positive patients at the last follow up and during the follow-up period. CONCLUSION: Long-term administration of LAM for patients with decompensated cirrhosis is effective. Earlier LAM administration in Child class B patients led to improved clinical outcomes.     

Mirtazapine treatment for pathological laughing and crying after stroke

Selective serotonin reuptake inhibitors (SSRIs) have been recognized as the treatment of choice for pathological laughing and crying (PLC), which is a common, distressing condition that follows stroke. There have been few reports about other treatment options for PLC. Here, the authors report rapid responses to mirtazapine in two patients with poststroke PLC who failed to respond to SSRIs or bupropion. In the first case, a 63-year-old woman with severe long-standing crying spells that had persisted for 3 months responded well to low-dose mirtazapine within a few days; she could not tolerate citalopram or sertraline. In the second case, both the laughing and crying spells of a 64-year-old woman were improved within a few days of mirtazapine administration, after they had not responded to bupropion. This is one of the first reports to suggest that mirtazapine may be an alternative to SSRIs for treating poststroke PLC.