The problem of urolithiasis is not a simple one for many kinds of stones are known which probably require different conditions for their nucleation and growth. Calculi are found in the kidneys, ureters, bladder and urethra and for those not resulting from any anatomical abnormality, there is no proven reason why growth should occur in say the upper urinary tract as opposed to the lower. Nevertheless, the results of many epidemiological studies (see, for example, references in review articles such as Andersen, 1969) have shown the existence of well-defined zones in the world in which either upper or lower urinary tract stones predominate. Bladder stones in children and adults are a problem in certain areas of technically developing countries like India and Thailand, while kidney stones in adults constitute most of the calculi from industrialised countries. Some possibly indirect connection between these 2 broad categories is, however, likely, for in certain countries of intermediate economic development, both varieties are found, usually but not always in different areas, and the distribution of upper and lower urinary tract stones in them is again dependent on the extent and duration of "industrialisation" present. There is also evidence that bladder stones were a problem in parts of Great Britain, Northern Ireland and Northern Europe prior to this century but they died out about 50 to 60 years ago and have been succeeded by kidney stones. Conditions which have led or are leading to the disappearance of one kind probably then favour the formation of the other.Stones also differ widely in composition. Many compounds can crystallise in them and frequently several are present in one calculus, but the importance of each constituent, as judged by its frequency of occurrence in collections of stones, varies considerably. In a geographical and historical investigation of the composition of urinary calculi, we have studied representative collections of stones from different countries and found that a few constituents, not always the same, predominate in each but that there is an overall similarity in the total amount of some of the constituents in collections comparable with respect to the variables already mentioned, namely the patient's age, the site of the stone in the urinary tract and the extent of economic development in the geographical area concerned (Sutor, 1972).We have now extended this work using a computer to group together comparable collections of stones and then to derive data on the patients and the calculi in each subdivision. This we hope will lead to a better understanding of the different types of urolithiasis as revealed by our study of stone composition, and demonstrate their distribution past and present on a geographical basis. Material and MethodsCollections of urinary calculi from the following countries, cities and institutions are included in this study: Czechoslovakia (99 stones), Eire (69) England (656 stones from 10 cities), India (176 stones from 2 centres), Kuwait (67) Northern Ireland (...
Summary In a collection of 856 urinary calculi from Great Britain and Northern Ireland, the most abundant and frequently occurring crystalline constituents are the mono‐ and di‐hydrates of calcium oxalate and hydroxy‐ and carbonate‐apatite. On the basis of composition, most stones can be assigned to a few well‐defined groups. The most common composition type, accounting for 34% of the collection, is that composed of calcium oxalate+calcium phosphate. The oxalate can be either or both of the hydrates, often both are present, but the calcium phosphate is generally hydroxyapatite. Stones consisting of pure calcium oxalate make up 27% of the total, while those comprised of struvite+calcium phosphate contribute 17%. In the latter variety the calcium phosphate is almost invariably carbonate‐apatite. The other group considered consists of the pure calcium phosphate calculi which account for 7% of the collection. The incidence of stones in relation to their site in the urinary tract and the patient's age and sex has been investigated, together with the effect of the stone site, patient's age and sex on the distribution of calculi in the main composition groups and the effect of composition, site, age and sex on the stone weight. Most of these variables have a significant effect on one another. The incidence of stones is also related to daily occupation, professional workers being 10 times more likely to develop urolithiasis than labourers. We thank the Medical Research Council and Nuffield Foundation who financed most of this work and Mr D. Sturt who kindly agreed to the participation of the Computer Centre in this project. We are greatly indebted to Mr N. W. Please for advice and many helpful discussions on the statistics and for carrying out the analysis of variance. Finally, we are grateful to the many surgeons and physicians who provided the stones and the data.
MSR1 repeats act as molecular switches that modulate gene expression. It is likely that CNV of MSR1 will affect risk of development of various forms of cancer, including that of breast and prostate. The MSR1 cluster at KLK14 represents the strongest risk factor identified to date in non-familial breast cancer and a significant risk factor for prostate cancer. Analysis of MSR1 genotype will allow development of precise stratification of disease risk and provide a novel target for therapeutic agents.
Summary The combination of 5-fluorouracil (5-FU) and interferon-alpha (IFN-a) has reported activity in the treatment of advanced colorectal carcinoma. Laboratory studies of IFN-n suggest that this agent may offer theoretical advantages over IFN-a in combination with 5-FU. A total of 27 patients with advanced or recurrent colorectal carcinoma were treated in a non-randomized open phase 11 study with a combination of 5-fluorouracil (750 mg m-1 daily for 5 days as a continuous intravenous (i.v.) infusion followed, from day 15, by i.v. bolus 750 mg m-2 every 7 days) and recombinant interferon-f [r-hlFN-P-1 a; 9 MIU (total dose) by subcutaneous injection from day 1 on every Monday, Wednesday and Friday throughout the treatment period]. Toxicity was less than that seen with this schedule of 5-FU in combination with IFN-a. Among 21 evaluable patients, four objective responses were seen. Recombinant human interferon-beta-1 a in combination with 5-FU is an acceptable regimen in terms of toxicity. However, the study did not demonstrate a superior response rate when compared with previous reports of treatment with 5-FU alone or in combination with IFN-a.Keywords: interferon-beta; 5-fluorouracil; chemotherapy; colorectal carcinoma Five year survival from carcinoma of the colon and rectum is less than 40%. Although 5-fluorouracil has been the mainstay of palliative systemic therapy for advanced colorectal carcinoma for over 30 years, it is not curative in patients with metastatic disease. This agent gives objective responses in less than 25% of patients when used as a single agent, and there has been much interest in the potential for modulating its effects. Several studies indicate that 5-FU and IFN-a act in synergy to inhibit the growth of tumour cell lines in vitro (Wadler and Schwartz, 1990), and in some clinical studies this combination results in response rates (35-62%) higher than that predicted for 5-FU alone (Pazdur et al, 1990; Wadler and Wiernick, 1990;Wadler et al, 1991). However, this activity has not been confirmed in other trials (Corfu-A Study Group, 1995;Hill et al, 1995) Although IFN-,B has only 30% homology with interferon-a (de Grado et al, 1982), it binds with greater affinity to certain subclasses of interferon receptors (Ruzicka et al, 1987). In laboratory studies, r-hIFN-P-la exhibits greater antiproliferative activity than IFN-a against some tumour cell lines (Borden et al, 1982) and, against colorectal carcinoma cell lines, it demonstrates both direct antiproliferative activity and synergy in combination with 5-FU (Wong et al, 1989;Kase et al, 1993 (Lillis et al, 1987;Triozzi et al, 1987). This is similar to the single-agent activity of IFN-a, which has been reported to produce three responses among 66 patients (Kemeny and Younes, 1992). There is, therefore, a significant rationale for the testing of IFN-P in combination with 5-FU in this patient group.A phase II study examining the combination of r-hIFN-p-1a and 5-FU was designed modelled on the 5-FU/IFN-a regimen of Wadler et al (1990). In phase ...
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