Polymorphisms in the glutathione S-transferase class mu and theta genes interact and increase susceptibility to lung cancer in minority populations (Texas, United States)

The genes coding for separate isoforms of both the human glutathioneS-transferase class mu and class theta enzymes (GSTM1and GSTT1) arepolymorphic with a variable ethnic distribution. These enzymes detoxifyreactive epoxides, including carcinogens produced by tobacco smoke. Becauseof this, the null polymorphism in the GSTM1 gene (coding for the glutathioneS-transferase class mu enzyme) has been studied widely as a possible sourceof inherited susceptibility to smoking-related lung cancer. The more recentlydescribed null polymorphism in the GSTT1 gene also could contribute to anincreased risk of smoking-related lung cancer. As the incidence of lungcancer is known to differ by ethnicity, we have conducted a case-controlstudy in the United States of 108 African-Americans (Blacks) and 60Mexican-Americans (Hispanics) with lung cancer and 132 African-American(Black) and 146 Mexican-American (Hispanic) controls to investigate theassociation of the GSTT1 and GSTM1 polymorphi sms with lung cancer inminority populations. In the unadjusted data, there was a borderlinesignificant association of the GSTM1 null polymorphism with lung cancer inMexican-Americans (odds ratio [OR] = 1.8, 95 percent confidence interval [CI]= 1.0-3.3 ) that was not observed in African-Americans. The GSTT1 nullpolymorphism also had a higher prevalence in cases than controls in bothracial/ethnic groups, but this increase was not statistically significant.When the data were analyzed using logistic regression controlling for age,gender, race, and smoking, no significant association of either trait withlung cancer was observed, with ORs for both traits of approximately 1.3.However, when the prevalence of individuals who were null for bothpolymorphisms was compared by case status, a significant interaction wasobserved. Logistic regression models showed the OR for the association oflung cancer and the presence of both null polymorphisms compared with one(either GSTT1 or GSTM1) or no null genotype to be 2.9 (P < 0.04). Theseresults suggest that there may be carcinogenic intermediates in cigarettesmoke that are substrates for both the GSTT1 and GSTM1 enzymes, and that lungcancer risk is increased more than additively for individuals who have bothGSTT1 and GSTM1 null polymorphisms.     

Prosopo-Thoracopagus Conjoined Twins and Other Cephalopagus-Thoracopagus Intermediates: Case Report and Review of the Literature

Prosopo-thoracopagus twins are united from the face down to the umbilicus, none with union in the brain but all with visceral anomalies intermediate between those of cephalopagus and thoracopagus. In a review of over 1200 cases of conjoined twins reported during the past 100 years, there were 14 that illustrate the continuum between cephalopagus and thoracopagus, including three that were united only from the cervical region to the umbilicus. Classic cephalopagus twins are joined from the top of the head to the umbilicus, sharing a single foregut as well as two relatively normal hearts, the “posterior” one often diminished. Typical thoracopagus, however, are conjoined only from the upper thorax to the umbilicus, each twin with a normal foregut but both sharing a single complex multiventricular heart. The intermediate cases shared either a single very abnormal heart or two hearts united by double aortic arches, and all except one had a single foregut. It is these cases intermediate between cephalopagus and thoracopagus which are the subject of this report. Received September 11, 1996; accepted December 16, 1996     

Lung volume measurements in infants with and without chronic lung disease

Infants born prematurely who develop chronic lung disease (CLD) have airways obstruction and hence may have low lung volume. The aim of this study was to test that hypothesis and ascertain whether the nature of the comparison control group influenced the results. Sixteen infants who were oxygen dependent for more than 28 days (CLD) and eight infants without CLD had measurements of functional residual capacity (FRC) at 14 and 28 days. The 16 CLD infants consisted of eight less than 27 weeks gestational age (group A) and eight greater than 26 weeks gestational age (group B). The eight infants without CLD (group C) were each matched for gestational age and gender to infants in group B. Group A compared to group C had lower FRCs both at 14 days (median 18 ml/kg vs 27 ml/kg, P<0.01) and 28 days (median 20 ml/kg vs 26 ml/kg, P<0.05), but group A differed from group C with respect to both gestational age (P<0.01) and birth weight (P<0.01). The FRC results of group B were lower than those of their matched controls (group C) only at 28 days (median 22 vs 26 ml/kg, P<0.05). Overall, the FRC results at 14 and 28 days correlated significantly with the duration of oxygen and ventilator dependence and weakly with gestational age. Conclusion These results support the hypothesis that FRC results are lower in infants with CLD compared to those without CLD when measured in the neonatal period and emphasize the importance of an appropriate control group. Measurement of lung volume may facilitate assessment of the response to therapies for CLD. Received: 5 May 1997 / Accepted in revised form: 29 September 1997     

Risk factors for respiratory syncytial virus associated apnoea

Respiratory syncytial virus (RSV) infections are characterized by upper or lower respiratory tract symptoms including bronchiolitis and pneumonia. Apnoea may be the first sign of disease in children with RSV infection. The aims of this study were the identification of independent risk factors for RSV associated apnoea and the prediction of the risk for mechanical ventilation in children with RSV associated apnoea. Medical records of children younger than 12 months of age admitted with RSV infection between 1992 and 1995 to the Sophia Children's Hospital, were reviewed. Demographic parameters, clinical features and laboratory parameters (SaO₂, pCO₂ and pH) were obtained upon admission and during hospitalization. Children with and without apnoea were compared using univariate and multivariate logistic and linear regression analysis. One hundred and eighty-five patients with RSV infection were admitted of whom 38 (21%) presented with apnoea. Patients with apnoea were significantly younger, had a significantly lower temperature, higher pCO₂ and lower pH and had on chest radiographs also more signs of atelectasis. The number of patients admitted to the ICU because of mechanical ventilation and oxygen administration was significantly higher in children with RSV associated apnoea. Apnoea at admission was a strong predictor for recurrent apnoea. The relative risk for mechanical ventilation increased with the number of episodes of apnoea: 2.4 (95% CI 0.8 – 6.6) in children with one episode of apnoea (at admission) versus 6.5 (95% CI 3.3 – 12.9) in children with recurrent episodes of apnoea. Conclusions Age below 2 months is the strongest independent risk factor for RSV associated apnoea. Apnoea at admission increases the risk for recurrent apnoea. The risk for mechanical ventilation significantly increases in children who suffer from recurrent apnoea. Received: 12 May 1997 / Accepted in revised form: 22 August 1997     

Metastasis to the iris in squamous cell lung cancer

A 72-year-old Japanese woman, suffering from squamous cell lung cancer with brain metastasis, underwent 2 courses of combination chemotherapy, consisting of cisplatin and vindesine. Although both the primary tumor and the brain metastasis regressed markedly, she developed left ocular pain with blurred vision. An abnormal mass was found in the left iris, and cytologic examination of the aqueous aspirate revealed a few malignant cells, which, when examined by electron microscopy, were considered to be derived from squamous cell carcinoma of the lung.     

Potentiation of Paclitaxel Cytotoxicity by Inostamycin in Human Small Cell Lung Carcinoma, Ms-1 Cells

In the present study, we found that inostamycin increased the ability of paclitaxel to induce apoptosis in Ms-1 cells. A considerably higher concentration of paclitaxel was required for the induction of apoptosis in Ms-1 cells than in other cell lines tested. Treatment of Ms-1 cells with inostamycin, an inhibitor of phosphatidylinositol (PI) synthesis, reduced the dosage of paclitaxel required to induce cell death by apoptosis. This effect of inostamycin is specific to Ms-1 cells, and inostamycin did not increase the cytotoxicity of other antitumor drugs such as adriamycin, vinblastine, methotrexate, cisplatin, etoposide, or camptothecin in Ms-1 cells. Addition of inostamycin to paclitaxel-treated cells caused a significant increase in the sub G1 peak, representing apoptosis, which was accompanied by a decrease in the G2/M peak seen in paclitaxel-treated Ms-1 cells, without affecting paclitaxel-inhibited tubulin depolymerization. Moreover, paclitaxel did not enhance inostamycin-inhibited PI synthesis. The expression levels of Bcl-2, Bax, and Bcl-X_L were not changed following the co-treatment with inostamycin plus paclitaxel, whereas the activated form of caspase-3 was markedly increased. Thus, inostamycin is a chemosensitizer of paclitaxel in small cell lung carcinoma Ms-1 cells.     

双途径化疗治疗晚期肺癌并胸腔积液33例报道

目的观察双途径化疗对晚期非小细胞肺癌合并胸腔积液的疗效.方法采用胸腔穿刺、CVP管植入灌注顺铂＋地塞米松与长春瑞宾（NVB）＋顺铂（DDP）联合静脉化疗相结合的方法治疗33例肺癌.结果治疗胸腔积液的有效率为93.94%,肺部病灶治疗有效率为48.48%.结论双途径给药为临床上值得推广的方法.     

吉西他滨治疗高龄晚期非小细胞肺癌

目的:观察吉西他滨治疗高龄晚期非小细胞肺癌的疗效,并与同期单纯支持治疗的患者比较,以探讨高龄晚期非小细胞肺癌的治疗方案。方法:吉西他滨组21例,采用吉西他滨单药化疗,剂量为1250mg/m2,静脉滴注,第1、8天用药,每21天为1周期,共4周期。对照组23例不用任何化疗,单纯支持对症治疗。结果:吉西他滨组总有效率为28.6%,其中PR6例,SD12例,PD3例。对照组无CR和PR者。吉西他滨组中位缓解期6.3个月。吉西他滨组和对照组中位肿瘤进展时间分别为5.8和2.6个月,中位生存时间分别为12.8和4.6个月(P<0.01);1年生存率分别为46.6%和9.2%(P<0.01)。吉西他滨组KPS、体重增加和临床症状改善情况均显著高于对照组(P<0.01)。毒副反应方面吉西他滨组12例(57.1%)出现Ⅰ、Ⅱ级血小板减少,7例(33.3%)出现Ⅰ、Ⅱ级白细胞下降,未见Ⅲ、Ⅳ级毒性反应。少数患者血红蛋白下降Ⅰ度,恶心呕吐Ⅰ/Ⅱ度。结论:吉西他滨单药治疗高龄晚期非小细胞肺癌是安全有效的。     

长春瑞滨治疗27例高龄晚期非小细胞肺癌

目的:探讨单药长春瑞滨治疗70岁以上高龄晚期非小细胞肺癌患者的疗效及毒副反应。方法:2002年9月至2004年9月采用长春瑞滨治疗70岁以上高龄晚期非小细胞肺癌(NSCLC)27例,长春瑞滨25~30mg/m2 60ml生理盐水稀释,静注第1、8天,21天为1个周期,一般3~4周期,共进行了92周期。观察近期疗效、远期疗效、不良反应、中位缓解期和中位生存期。结果:PR9例,NC10例,PD8例,总有效率33.3%。中位缓解期4.1个月,中位生存期10.3个月。白细胞减少发生率为55.4%(51/92),Ⅲ/Ⅳ度为18.5%(17/92),血小板减少率为8.7%(8/92),静脉炎发生率为6.5%(6/92)。结论:长春瑞滨在治疗高龄晚期NSCLC患者中,有较好的近期疗效,毒副反应可耐受,临床应用安全,可以作为高龄晚期非小细胞肺癌的治疗方案选择之一。