Focal hepatic masses and fatty infiltration detected by enhanced dynamic CT

A prospective evaluation of 185 consecutive patients with abdominal pain or suspected hepatic malignancy was performed to compare the diagnostic accuracy of contrast material-enhanced incremental dynamic computed tomography (IDCT) scans with plain CT scans for detection of hepatic masses and fatty infiltration of the liver. After a series of nondynamic plain CT scans, patients were examined at 7.5 scans/min during intravenous injection of 50 g of iodinated contrast material. Enhanced IDCT study was found to be an accurate, reproducible technique for liver evaluation. Of 155 neoplasms measured in 59 patients, liver-to-lesion differences of less than 10 HU were seen in only two tumors in IDCT scans as compared with 31 in plain CT scans. These differences were not significantly affected by lesion size for neoplasms greater than 6 mm in diameter. A confident diagnosis of fatty infiltration (23 patients) could be made when the spleen-minus-liver difference was 25 HU on enhanced IDCT scans and 10 HU on plain CT scans. In eight patients with liver metastases, there was little variation in the attenuation values of normal-appearing liver between serial examination studies (8 HU average).     

Patient satisfaction with the management of infertility

The objective of this study was to assess patient satisfaction with the investigation and initial management of infertility. A postal questionnaire survey was carried out of 1366 women attending outpatient clinics for the investigation and initial management of infertility at 12 hospitals throughout Scotland. The response rate to the questionnaire was 59% (806/1366). Overall, 87% of responders were satisfied or very satisfied with their care but a number of deficiencies were identified. Thirty-nine per cent had never been asked to bring their partner to the clinic and 86% felt they had not been given enough help with the emotional aspects of infertility. Forty- seven per cent felt they were not given a clear plan for the future and 23% of those who had been given drug treatments reported receiving little or no information about the treatment or possible side-effects. Overall, only a third had been given any written information and 78% expressed a wish for more written information. Women ranked 'the information and explanation given' and the 'attitude of the doctor at the clinic' highly in comparison to other aspects of their care, including 'help with the emotional aspects of infertility'. In general women were satisfied with their care but improvements may be made by giving more explanation and written information and by adopting a more couple-centred approach. Where resources allow, clinics should take steps to address the emotional aspects of infertility.      

Cleavage, aggregation and toxicity of the expanded androgen receptor in spinal and bulbar muscular atrophy

Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by the expansion of a polyglutamine repeat within the androgen receptor (AR). We have studied the mutant AR in an in vitro system, and find both aggregation and proteolytic processing of the AR protein to occur in a polyglutamine repeat length-dependent manner. In addition, we find the aberrant metabolism of expanded repeat AR to be coupled to cellular toxicity, indicating a likely molecular basis for the toxic gain of AR function that produces neuronal degeneration in SBMA.      

The OX-40 receptor provides a potent co-stimulatory signal capable of inducing encephalitogenicity in myelin-specific CD4+ T cells

The OX-40 receptor, a member of the nerve growth factor/tumor necrosis factor receptor gene family, is expressed preferentially on autoreactive CD4+ T cells isolated from the site of inflammation in rats with clinical signs of experimental autoimmune encephalomyelitis (EAE). To examine whether the OX-40 receptor has biologic relevance to T cell function, we evaluated the ability of a rat OX-40 receptor- specific antibody to co-stimulate a myelin basic protein (MBP)-reactive CD4+ T cell line. The anti-OX-40 antibody provided a potent co- stimulatory signal to CD4+ T cells when added in conjunction with a submitogenic dose of anti-CD3, but the anti-OX-40 antibody alone did not produce a mitogenic response. The magnitude and dose-response of anti-OX-40 co-stimulation was virtually identical to the signal delivered to T cells when cultured with anti-CD28 in conjunction with anti-CD3. MBP-specific T cells stimulated with both anti-CD3 and anti- OX-40 antibodies expressed increased mRNA and protein for IL-2 when compared to anti-CD3 alone. MBP-specific T cells stimulated with both anti-CD3 and anti-OX-40 antibodies were also able to induce EAE when transferred into naive Lewis rats. In contrast, cells stimulated with anti-CD3 alone were not encephalitogenic. These data suggest that the function of the OX-40 receptor on activated T cells is to provide an alternative pathway for T cell co-stimulation that may be similar in potency to the CD28-mediated signal.      

Apoptosis and expression of apoptotic regulators in the human testis following short- and long-term anti-androgen treatment

Apoptosis and its augmentation by androgen withdrawal is an important event in the testis. In other tissues apoptosis is regulated by genes belonging to the bcl-2 family. However, little is known about these pathways in the human testes. Human testes were obtained from patients with prostate cancer, undergoing orchidectomy for permanent androgen ablative treatment. The patients were either untreated or had previously received short- or long-term anti-androgen therapy by cyproterone acetate or GnRH agonist (goserelin). In comparison with untreated patients, testicular testosterone concentrations were reduced by 83% in patients treated with cyproterone acetate and by 99% in patients treated with goserelin. Apoptotic cells were identified in tissue sections by in-situ end labelling of fragmented DNA. The expression of Bcl-2, Bcl-xl, Bax, p53 and poly(ADP) ribose polymerase (PARP) was demonstrated in tissue extracts by Western blotting. Apoptotic germ cells were present in the spermatogenic epithelium of untreated patients and patients who received short-term anti-androgen treatment. There were few or no apoptotic cells in the seminiferous tubules following long-term anti-androgen treatment. Following short- term treatment, the concentrations of the apoptosis-related proteins examined did not change. However, in the long-term treated testes, Bcl- xl and PARP expression declined, Bax and p53 protein concentrations were unchanged, and Bcl-2 was up-regulated. In conclusion, apoptosis occurs in spermatogenic cells of the human testis and may contribute to the regulation of germ cell populations. The apoptosis-related gene products which have been described in other tissues are present in the human testis and are modulated by androgenic stimuli.      

Preimplantation development of mouse and human embryos biopsied at cleavage stages using a modified displacement technique

A modified embryo biopsy method was tested on four- and eight-cell stage mouse embryos and used on human embryos to obtain blastomeres for preimplantation genetic diagnosis. The biopsy method tested combines zona drilling and fluid displacement to force one or two cells through an opening in the zona pellucida of the cleavage-stage embryo. Rates of cell division and the percentage of mouse embryos forming blastocysts following biopsy at the eight-cell stage were not significantly different from those observed in unoperated control embryos. The percentage blastocyst formation was not significantly different in embryos biopsied at the four-cell stage and in control embryos, although cell division was significantly retarded following biopsy. 96% of the mouse blastomeres isolated at the eight-cell stage were recovered intact and 96% of those placed in culture underwent cell division. Survival and division of cells isolated at the four-cell stage were 92 and 84% respectively. Most of the cultured blastomeres cleaved several times and formed small trophoblast vesicles. Chromosomes were observed in 59% of blastomeres incubated in the presence of colcemid. In the initial use of this biopsy technique for human preimplantation genetic diagnosis, blastocyst formation was observed in 9 of 13 human embryos biopsied at the 7- to 10-cell stage. These findings support the use of this biopsy method as an alternative to aspiration techniques.