The adverse effect of treatment prolongation in cervical cancer by high-dose-rate intracavitary brachytherapy.

BACKGROUND AND PURPOSE: The potential risk of prolongation of treatment time in cervical cancer has been reported for many low-dose rate (LDR) studies, with an estimated loss of local control ranging from 0.3 to 1.6% per day of treatment prolongation. Since the treatment schedule for fractionated high-dose rate intracavitary brachytherapy (HDRICB) is not directly comparable with that for low-dose rate studies, this report aims to evaluate the adverse effect of treatment prolongation specifically for cervical cancer treated with HDRICB. MATERIAL AND METHODS: From September 1992 to December 1997, 257 patients diagnosed with uterine cervical cancer (35 Ib, 26 IIa, 122 IIb, 10 IIIa, 57 IIIb, 7 IVa), who underwent external radiotherapy combined with between two and four courses of HDRICB and a minimum of 3 years of follow-up (median 57 months), were analyzed. Treatment consisted of irradiation of the whole pelvis with 44-45 Gy consisting of 22-25 fractions by 5 weeks, with the dose boosted to 54-58 Gy (with central shielding) for patients diagnosed as FIGO stage IIb-IVa bilateral parametrial disease. HDRICB was performed using an Ir-192 remote afterloading technique at 1-week intervals. The standard prescribed dose for each course of HDRICB was 7.2 Gy to point A for three insertions (before July 1995), or 6.0 Gy to point A for four insertions (after July 1995). Total prescribed point A doses (external beam radiotherapy+HDRICB) ranged from 58 to 71.6 Gy (median, 65.6 Gy) for stage IB-IIA, while analogous dosage for larger lesions (stage IIb-IVa) ranged from 59 to 75.6 Gy (median, 65.6 Gy). Kaplan-Meier and multivariate analyses were used to test the effect of treatment time on pelvic control rate (PCR) and cause-specific survival (CSS) at 5 years. RESULTS: Median treatment time was 63 days. For all stages of disease, the 5-year CSS and PCR were significantly different comparing treatment times of less than and greater than or equal to 63 days [83% and 65% (P=0.004], 93% and 83% (P=0.02), respectively]. These associations were also significant for stage Ib/IIa [97% and 79% (P=0.01), and 100% and 87% (P=0.02), respectively), but not for stage IIb [75% and 72% (P=0.79), and 93% and 87% (P=0.83), respectively] or stage III [66% and 49% (P=0.2), and 83% and 72% (P=0.21), respectively]. Multivariate analysis identified three prognostic factors for CSS, stage (P<0.001), tumor response to external RT (P=0.001), and overall treatment time (OTT; P=0.006). Prognostic factors for pelvic failure were stage (P<0.001), tumor response to external RT (P=0.001), and OTT (P=0.03). Prolongation of treatment time resulted in a daily decrease in pelvic control rate of 0.67% overall, and 0.43% for stage Ib-IIa, 0.57% for stage IIb, and 0.73% for stage III patients. CONCLUSION: Analysis of the data from the current study demonstrates that the adverse effect of treatment prolongation was observed later in the treatment course for the high-dose rate (HDR) series compared to the LDR analog, however, treatment-time prolongation still negatively influenced the cause-specific survival and pelvic control rate for both dosage groups.     

Three-dimensional ultrasound diagnosis of Larsen syndrome with further characterization of neurological sequelae.

Larsen syndrome consists of skeletal dysplasia with multiple joint dislocations and a characteristic facies. The basis of this abnormality is a generalized mesenchymal disorder involving connective tissues. We describe our findings in a woman who was referred at 28 weeks' gestation due to multiple fetal anomalies suspected initially at an 18-week ultrasound examination. On three-dimensional (3D) ultrasound we found the fetus had bilateral genu recurvatum. Further 3D examination at 36 weeks confirmed the lower limb anomaly and revealed facial anomalies that led to the diagnosis of Larsen syndrome. An elective Cesarean section was performed at 38 weeks' gestation to minimize neurological sequelae. Magnetic resonance imaging was performed postnatally and showed pachygyria, colpocephaly and agenesis of the corpus callosum. In this case, 3D ultrasound facilitated the prenatal diagnosis of Larsen syndrome. A careful prenatal investigation for other associated anomalies such as those of the cardiovascular or neurological systems is warranted with this diagnosis. These associated lesions are likely to have a greater impact on prognosis than the classic symptoms of Larsen syndrome and a collaborative approach is necessary to optimize delivery and postnatal management of an affected fetus.     

Transgenic mice that express different forms of the influenza virus hemagglutinin as a neo-self-antigen

We have generated transgenic mouse lineages that express the influenza virus hemagglutinin in different physical forms. One kind expresses the full-length hemagglutinin molecule as a cell surface glycoprotein and can be recognized by hemagglutinin-specific B and T cells. The other expresses a truncated polypeptide corresponding to the N-terminal third of the hemagglutinin molecule. This polypeptide encodes known hemagglutinin-specific T-cell determinants; however, it contains no native B-cell epitopes, since these depend on the conformation of the fully folded protein. In each case, the hemagglutinin transgenic mice display ubiquitous expression of transgenic messenger RNA and induce T-cell tolerance to the transgene-encoded T-cell determinant site 1. Thus, the hemagglutinin is a neo-self-antigen in both kinds of hemagglutinin transgenic mice and should provide a useful system for understanding the factors and mechanisms that govern tolerance and autoimmunity to self-antigens.     

A dideazatetrahydrofolate analogue lacking a chiral center at C-6, N-[4-[2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl]benzoyl]-L-glutamic acid, is an inhibitor of thymidylate synthase.

N-[4-[2-(2-Amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl]benzoyl]-L-glutamic acid (15), prepared in five steps from 2-pivaloyl-7-deazaguanine, has been found to be an antitumor agent with its primary site of action at thymidylate synthase rather than purine synthesis. This compound appears to be a promising candidate for clinical evaluation.     

Effect of a two-solution fluoride mouthrinse on remineralization of enamel lesions in vitro.

A previous study showed that a two-solution fluoride (F) rinse deposited significantly more loosely-bound F on the tooth surface than did a sodium fluoride (NaF) rinse with the same F concentration (12 mmol/L). In the present study, this experimental rinse was evaluated for its ability to cause remineralization of enamel lesions in an in vitro pH-cycling model. Caries-like lesions were formed in the enamel of extracted human molars by means of a pH 4 demineralizing solution. Fifty-one approximately 120-microns-thick sections containing lesions were randomly divided into (1) control, (2) NaF rinse, and (3) two-solution F rinse groups. With the cut surfaces protected, the control samples were immersed in a pH 7 remineralizing solution for 12 days, and twice daily the sections were also exposed to a pH 4 demineralizing solution for 30 min. Samples in the NaF group received an additional one-minute rinse with a NaF (12 mmol/L) solution twice daily. Samples in the two-solution rinse group received the rinse treatment with a 12 mmol/L F solution prepared by combination of a Na2SiF6 and phosphate-containing solution with a calcium solution just before use. The mineral contents of the lesions were assessed by quantitative microradiography. The results showed that (1) no significant de- or remineralization was detected in the controls; (2) a 46% decrease in mineral loss (delta Z) of the lesion was produced by the NaF rinses; and (3) a 94% decrease in delta Z and a 20-microns-thick, mineral-dense surface-coating were produced by the two-solution F rinse treatment.     

Sustained-release theophylline-uniphyllin in nocturnal asthmatics

For a period of six months, we collected 12 cases of nocturnal asthmatics (7 males, 5 females); their ages ranged from 20 to 66 (the average age is 49). We found that administration of Uniphyllin (10 mg/kg) once a day at 6 PM could maintain the blood level of theophylline within therapeutic range at least 12 to 24 hrs. The peak expiratory flow rate of the 6 cases we collected, were significantly improved. The result of pharmokinetic parameters: 1) The average of a single dose (12 cases) is AUC (ug. hr/ml) 275.1 +/- 62. k; Kel (hr-1) 0.068 +/- 0.019; Ka (hr-1) 0.33 +/- 0.07); Tmax (hr) 6.3 +/- 1.4; T 1/2 (hr) 11.2 +/- 4.4; Clearance/F (ml/kg/hr) 37.9 +/- 9.0.2). The average of steady state (12 cases) is Css (mg/L) 5. 7 +/- 2.6; Cmax-Cmin (mg/L) 10.09 +/- 1.46.3). The average of relative bioavailability (3 cases) is 82%, 83%, 102%. However, the extent of absorption data is available for only 3 subjects. There are too few subjects to draw any meaningful conclusions about this relative bioavailability. Four cases show slight symptoms, including 1 case of dizziness, 2 cases of nausea, and 1 case gaseousness. It is suggested that the drug be administered at about 6-8 PM to coincide peak levels in the early morning in nocturnal asthmatics.     

口服耐受的机制及其在自身免疫病治疗中的应用

口服耐受是指口服蛋白引起的一种免疫低反应状态。自Ｗｅｌ１ｓｌ９１１年首先报道这种现象以来，口服耐受引起了广泛关注，大量研究者发现给动物饲服蛋白质或绵羊红细胞后，再次消化道外免疫时，动物对这些抗原不再具有良好的反应性，而对其它抗原的反应正常［１］。免疫...