Sexual morbidity following radiotherapy for germ cell tumours of the testis.

An anonymous questionnaire study was designed to assess sexual function after orchidectomy and radiotherapy for testicular cancer. Questionnaires were sent to: (1) 237 patients treated with orchidectomy and abdominal radiotherapy in Edinburgh from 1974 to 1988; (2) 32 patients under "surveillance" following orchidectomy alone; (3) 402 "normal" age-matched controls. All were asked questions concerning sexual function over the preceding 6 months. All the patients were also asked the same questions with reference to the first 6 months after completion of treatment. Completed questionnaires were returned from 137 (62%) radiotherapy patients, 18 (56%) surveillance patients and 121 (35%) controls. There was a significant difference between the radiotherapy patients and the controls in almost all the parameters looked at including erection, ejaculation and libido with the treated group performing less well. In addition, almost 24% of the radiotherapy patients felt disabled or disfigured by the treatment, most commonly because of the presence of only one testicle. A deterioration in sexual function was observed with increasing age. In the radiotherapy group of patients there was no difference in response between the two time periods or in any of the treatment variables. The clinical significance of these observations are unclear but together with the increasing information on other toxicities emerging following this therapy the role of radiation for early stage seminoma is being brought into question. This study also confirms the morbidity of orchidectomy. We suggest that testicular implants should be offered more widely.     

Methodological aspects of phase-I studies of novel anticancer agents (review)

In the last 5 years we have performed 14 phase I studies in our department. Eight of these trials involved evaluation of both the clinical and the pharmacokinetic behaviour of novel anti-cancer agents. The remainder investigated various aspects of drug delivery, targetting or resistance modification with existing anti-cancer drugs. In total these studies have involved over 200 patients. In this review article we have drawn upon our experience to suggest guidelines for future studies.     

Prevalence and natural history of periodontal disease in Scotland – The mediaeval period (900–1600 A. D.)

The periodontal status of a Scottish medieval population was studied. No individual over the age of 11 years had an entirely healthy periodontium. While gingivitis was widespread in the younger age groups, it was essentially a "contained" gingivitis which appeared to progress towards a periodontitis at a fairly constant but slow rate. The pattern of prevalence and distribution of gingivitis and periodontitis was similar to many modern epidemiological studies on natural dentitions but did not support the view that the prevalence of periodontitis in historic material was high. A small proportion of individuals appeared to be either susceptible or resistant to periodontal disease. It was concluded that the study of historic material provides valuable information with regard to the natural history of human periodontal disease.     

Experimental cryptorchidism in the adult mouse. III. Qualitative and quantitative electron microscopic morphology of Leydig cells.

The morphology of Leydig cells of control and 28-day-old cryptorchid mice was studied by electron microscopy and stereologic techniques. Leydig cell profiles of control mice were larger in section when compared to cryptorchid mice, but no differences were observed in the distribution of organelles in Leydig cells in the two groups. Quantitatively, the absolute volumes of smooth endoplasmic reticulum (SER), rough endoplasmic reticulum (RER), mitochondria, lysosomes, multivesicular bodies, peroxisomes, cytoplasmic matrix, nucleus, lipid droplets, membrane whorls, ribosomal aggregates, and annulate lamellae per Leydig cell were reduced significantly after 28 days of cryptorchidism. However, the absolute volumes of these organelles per testis were not significantly different between control and cryptorchid mice, due to the increase in Leydig cell number per testis in the cryptorchid testis, compared to the controls, except that the absolute volume of Golgi per Leydig cell was not significantly different between control and cryptorchid rats, but the absolute volume of Leydig cell Golgi was significantly lower in control rats. Based on these results, we conclude that, morphologically, a 28-day cryptorchid mouse Leydig cell clearly approximates a "half unit" of a control Leydig cell.     

Non-invasive detection of fecal protein kinase C betaII and zeta messenger RNA: putative biomarkers for colon cancer

We have developed a non-invasive method utilizing feces, containing sloughed colonocytes, as a sensitive technique for detecting diagnostic colonic biomarkers. In this study, we used the rat colon carcinogenesis model to determine if changes in fecal protein kinase C (PKC) expression have predictive value in monitoring the neoplastic process. Weanling rats were injected with saline or azoxymethane (AOM) and 36 weeks later fecal samples and mucosa were collected, poly A+ RNA isolated, and quantitative RT-PCR performed using primers to PKC betaII and zeta. Fecal PKC betaII and zeta mRNA levels were altered by the presence of a tumor, with tumor-bearing animals having a 3-fold higher (P < 0.05) PKC betaII expression as compared with animals without tumors. In addition, AOM-injection increased mucosal PKC betaII mRNA expression compared with saline controls. No effect of tumor incidence on mucosal PKC betaII expression was observed. In contrast, fecal PKC zeta expression was 2.5-fold lower (P < 0.05) in animals injected with azoxymethane versus saline. Since tumor incidence exerts a reciprocal effect on fecal PKC betaII and zeta mRNA expression, data were also expressed as the ratio between PKC betaII and zeta. The isozyme ratio was strongly related to tumor incidence, i.e. ratio for animals with tumors was 2.18 +/- 1.25, animals without tumors was 0.50 +/- 0.16, P = 0.025. We demonstrate that the expression of fecal PKC betaII and zeta may serve as a noninvasive marker for development of colon tumors. A sensitive technique for the detection of colon cancer is of importance since early diagnosis can substantially reduce mortality.