Heterogeneity of human colon carcinoma

Summary In order to better understand colon cancer, a model system reflecting the heterogenous nature of this disease was developed and used in the development of new cytotoxic and non-cytotoxic therapeutic approaches. A large bank of colon carcinoma cell lines was established from primary human colon carcinomas and grouped based on their tumorigenicity in athymic mice, their growth rates in soft agarose and in tissue culture, and their secreted levels of carcinoembryonic antigen. These cell lines were later characterized based on cell surface proteins and antigens detected with antisera raised against a differentiated colon carcinoma cell line. Although these biochemical markers correlated with the biological classification of these cell lines, there was still extensive heterogeneity within each group in all properties examined. This colon carcinoma cell system was used to study natural vs. selected resistance to the anticancer drug mitomycin C (MMC). The differing IC₅₀ values in vitro were reflected in the inhibition by MMC of xenograft growth in athymic mice. A new, more readily bioactivatable analogue of MMC was tried and shown to be more active in vitro and in vivo, suggesting that rapid efflux of the drug before activation may be important in examining causes of resistance to MMC. Another approach to the treatment of colon cancer is the use of non-cytotoxic agents such as growth factors and differentiation agents to restore normal growth to the malignant cells. We have isolated and characterized two types of polypeptides from colon carcinoma cells and conditioned medium from these cells. The first, transforming growth factors (TGF's) confer a transformed phenotype on non-transformed fibroblasts while the second, tumor inhibitory factors (TIF's), inhibits the anchorage independent growth of transformed cells. The fact that extracts of colon carcinoma cells contain both activities suggests that the heterogeneity of the cell lines could be due to different levels of TGF's and TIF's produced. The effectiveness of differentiation agents to restore normal growth control using a transformed mouse embryo cell line was examined. Treatment of these cells with differentiation agents restored normal growth control to these cells. An increased synthesis of TGF's resulted from these treatments. Therefore, differentiation agents may be useful in non-cytotoxic treatment. The use of this model system for human colon carcinoma will hopefully lead to more effective drugs for the treatment of colon cancer in man.Supported by NIH Grant 34432 and ACS Grant PDT-109.     

Fetal intracranial teratoma: US diagnosis of three cases and a review of the literature

We describe three cases of fetal intracranial teratoma diagnosed by ultrasound and review the literature. Sonographic features include cranial enlargement, gross distortion of normal cerebral architecture by a hyperechoic, multicystic mass, and polyhydramnios. Despite early diagnosis, the cesarean section rate is high and the overall prognosis is dismal.     

Routine use of antimicrobials by pregnant Indian women does not improve birth outcome: a randomized controlled trial

Low birth-weight is a leading health problem in developing countries. In a randomized controlled trial, the effect of antimicrobials in pregnant women on improving birth-weight and duration of gestation was evaluated. Two hundred twenty-four pregnant women in their second trimester were randomized to receive metronidazole (200 mg 3 times daily for 7 days) and cephalexin (500 mg twice daily for 5 days) orally by one group. The mean (+/-SD) birth-weights were 2,545 g (+/-374) and 2584 g (+/-358, p=0.51), the low birth-weight rates (<2.5 kg) were 40% and 36% (p = 0.28), and the prematurity rates were 8% and 11% (p = 0.6) in the treated group and the control group respectively. Due to small sample size, it is cautiously concluded that routine antimicrobials for genital and urinary tract infections of pregnant women do not improve birth-weight or duration of gestation. Rather an unexpected observation was the proportion requiring caesarian section or forceps, which was five-fold higher in the treated group (p = 0.001), and given no plausible explanations, this finding needs confirmation. Stunted mothers (<25th centile or 146.4 cm) had two-fold higher risk for low birth-weight (p = 0.04) and assisted delivery (p = 0.1). Low maternal body mass index (<25th centile or 18) had six-fold higher risk for stillbirth or abortion (p = 0.007), and high body mass index (>75th centile or 21.2) had three-fold higher risk for assisted delivery (p = 0.003).     

Primary total knee arthroplasty using the P.F.C Sigma®‐rotating platform cruciate retaining endoprosthesis — A 6 year follow up

BackgroundMobile-bearing Total Knee Replacement allows unconstrained axial rotation. Increased articular conformity minimizes polyethylene contact stresses, thereby reducing linear wear and fatigue failure.MethodsWe prospectively reviewed a consecutive series of 161 patients with mobile bearing total knee replacements using the PFC Sigma Cruciate Retaining Rotating Platform System. (DePuy, Leeds, United Kingdom) with midterm follow up (minimum 6 and maximum 9 years, mean 7.2 years). One hundred forty‐seven patients from February 2001 to March 2004 were followed up till date. Primary osteoarthritis 96%; was the main indication followed by rheumatoid arthritis 3% and one case of psoriatic arthritis. Fifty‐seven percent were females with mean age of 69.5 years (Range 51–90 years). Oxford and American Knee Society scores were measured.ResultsMean Oxford score improved from 43 (Range 29–55) pre operatively to 21(Range 13–44) at last follow up and mean Knee Society score from 53 (Range 43–70) to 80 (Range 58–90). Range of movement improved from 91° (Range 70–110) to 113° (Range 75–130) at last follow up. One patient had dislocation of bearing needing manipulation. One patient had superficial infection treated with antibiotics. No patients had deep infection. There was one case reported of deep vein thrombosis and one of non-fatal pulmonary embolism.ConclusionThe midterm results in our series with PFC Sigma mobile bearing knee replacement are excellent with good outcome scores. Cohort will be followed for long term results.Level of Evidence IV     

Trends in socioeconomic and nutritional status of children younger than 6 years in India

The main aims of this study are to find out the trends in the (a) prevalence of undernutrition and severe anemia and (b) degree of association of undernutrition and severe anemia in children younger than 6 years in India with some socioeconomic variables. Using the Reproductive and Child Health Survey data, z score of weight for age and hemoglobin status were analyzed to understand the state and agewise variation and their association with the sociodemographic variables through logistic regression. The prevalence of malnutrition according to both the criteria was first seen to increase, attain a maximum value at some age between 12 and 48 months, and then decrease. Statewise distribution showed a close link between the stage of development and the prevalence of malnutrition-prevalence rate being less for developed states. The rates were also less for the Northeastern states of India. The regression analysis clearly points out that children with illiterate mothers, of lower age groups, or from low standard of living households are more prone to become malnourished. The economic growth alone is not sufficient for substantially reducing malnutrition. It is necessary to improve the rate of literacy, especially of women, to reduce the prevalence of malnutrition and anemia among children. It is not only economic development but also overall human development that is needed in India.