Objective  To study the rate of change in prostate specific antigen (PSA velocity) in patients with prostate cancer initially managed by ‘watchful waiting’. Patients and methods  Serial PSA levels were determined in 141 patients with prostate cancer confirmed by biopsy, who were initially managed expectantly and enrolled between May 1990 and December 1995. Sixty‐seven patients eventually underwent surgery (mean age 59 years) because they chose it (the decision for surgery was not based on PSA velocity). A cohort of 74 patients remained on ‘watchful waiting’ (mean age 69 years). Linear regression and logarithmic transformations were used to segregate those patients who showed a rapid rise, defined as a>50% rise in PSA per year (or a doubling time of <2 years) and designated ‘rapid risers’. Results  An initial analysis based on a minimum of two PSA values showed that 31% were rapid risers. Only 15% of patients with more than three serial PSA determinations over ≥6 months showed a rapid rise in PSA level. There was no advantage of log‐linear analysis over linear regression models. Conclusion  Three serial PSA determinations over ≥6 months in patients with clinically localized prostate cancer identifies a subset (15%) of patients with a rapidly rising PSA level. Shorter PSA surveillance with fewer PSA values may falsely identify patients with rapid rises in PSA level. However, further follow‐up is required to determine if a rapid rise in PSA level identifies a subset of patients with an aggressive biological phenotype who are either still curable or who have already progressed to incurability through metastatic disease.

This study showed that short-term (40-80 min) nitrous oxide anaesthesia did not affect cobalamin levels but reduced serum folate levels in this elderly population. Although this reduction was clinically irrelevant, some patients with pre-existing asymptomatic folate deficiency developed nitrous oxide-induced folate deficiency.

Nam J‐H, Kim J‐H, Huh J, Koh C‐W, Na J‐H, Kim B‐H, Kim Y‐M, Kim Y‐T, Mok J‐E. Correlation of lesion grade in cervical neoplasia with cell proliferation and apoptosis. Int J Gynecol Cancer 1998; 8: 279–286. In order to understand better the mechanisms underlying the development of cervical neoplasia, we examined the indices of cellular proliferation and apoptosis in cervical neoplasia. Archival cervical tissue samples from normal cervix, low‐grade squamous intra‐epithelial lesions (LSIL), high‐grade squamous intra‐epithelial lesions (HSIL), and squamous cell carcinomas were evaluated for the expression of nuclear antigen Ki‐67 and chromatin cleavage, a hallmark of apoptosis. Five‐micrometer sections from each case were immunohistochemically stained using MIB‐1 mouse monoclonal antibody, and Ki‐67 index was defined as the number of positively labeled cells per 100 cells. Apoptosis was determined by in situ end‐labelling of DNA strand breaks induced by terminal deoxynucleotidyl transferase (TdT) and was expressed as apoptotic index (AI = [sum of apoptotic bodies/total epithelial nuclei] × 100). To compensate for the effect of proliferative fraction on AI, corrected apoptotic index (CAI = [AI/Ki‐67 index] × 100) was calculated. Both the Ki‐67 index and AI significantly increased (P < 0.001, both) as the grade of cervical neoplasia increased. Corrected AI also significantly increased (P < 0.001) with lesion grade. These data suggest that the progression of neoplasia in the uterine cervix is accompanied by increased cellular deletion as well as cellular proliferation. The significant correlation of corrected AI with lesion grade suggests that apoptosis may have an independent role in the development of preinvasive and invasive cervical lesion.

MQO is a distributed multiple query processing

Abstract. The transforming growth factor receptor III (TGFßRIII) is the most abundant and essential TGF-ß binding protein that functions as a co-receptor with other receptors in TGF-ß signaling. In earlier studies, expression of TGFßRIII was reported to be decreased in a variety of human cancers. Functional assessment of TGFßRIII was performed in many previously studied cancers but not in hepatocellular carcinoma. Therefore, in this study, we investigated the expression and genetic alterations of TGFßRIII in hepatocellular carcinoma (HCC) by quantitative real-time PCR (qRT-PCR) and singlestrand conformation polymorphism (SSCP) analysis. The qRT-PCR showed down-regulation of TGFßRIII in the tumor samples. To investigate whether genetic alterations mediated decreased expression of TGFßRIII, we performed mutation analysis of 67 human HCC tissues by SSCP and direct sequencing. We found five previously reported and one novel single nucleotide polymorphisms in exons 2, 3, 5, 13 and 14, but no mutations were detected. These polymorphisms were not associated with amino acid changes except for a base change found in exon 2 (TCC→TTC, S15F). The loss of heterozygosity (LOH) analysis performed on 10 tumors and corresponding normal pairs, showed a low rate of LOH (2/10). The results of this study suggest that TGFßRIII is transcriptionally down-regulated in hepatocellular carcinoma. In addition, genetic alterations did not appear to be associated with the reduced expression level of TGFßRIII. To clarify the role of TGFßRIII in hepatocellular tumor development and progression, functional analysis is needed in future studies.