Age-related changes in male gonadal function. Implications for therapy.

In contrast with women, who experience a complete and abrupt cessation of ovarian function during the menopause, aging men largely maintain their testicular androgen production. Nevertheless, most cross-sectional studies indicate that there is a partial decrease in testosterone levels with aging, although this has not been confirmed by other studies. The disparity among studies stems from differences in study design, patient numbers, assay techniques and inclusion criteria. Proposed mechanisms for an age-associated decline in testosterone production include: (i) defects in the hypothalamic-pituitary-testicular axis; (ii) an increase in sex hormone binding globulin levels; (iii) environmental factors; (iv) medication use; and (v) chronic illness. The potential beneficial effects of testosterone replacement therapy in hypogonadal men include increased bone density, increased muscle strength, an improved feeling of well-being and an improved metabolic profile. These benefits need to be weighted against the potential risks of androgen therapy, such as erythrocytosis, sleep apnoea, and the stimulation of benign prostatic hypertrophy or an occult prostate malignancy. Consequently, androgen replacement should be used with caution in elderly men with hypogonadism until the results of well-controlled prospective studies are available.

Laparoscopic removal of a right adrenal pheochromocytoma in a pregnant woman.

Pheochromocytomas are a rare cause of hypertension in pregnancy. Laparoscopic adrenalectomy has been used effectively and safely in nonpregnant patients with pheochromocytoma, with the resultant benefits to the patients of less postoperative pain, shorter hospital stay, and quicker return to normal activities than is associated with open techniques. This represents the first report of a laparoscopic adrenalectomy for pheochromocytoma in a pregnant woman. Issues that are unique to laparoscopic surgery in pregnant patients are discussed.

Herpes simplex virus ICP0 and ICP4 immediate early proteins strongly enhance expression of a retrovirus harboured by a leptomeningeal cell line from a patient with multiple sclerosis.

A leptomeningeal cell line (LM7) harbouring an unknown retrovirus was recently isolated from the cerebrospinal fluid of a patient with multiple sclerosis. However, spontaneous expression of the LM7 retrovirus in this primary culture is quite low. We present results showing that in vitro infection of LM7 cells with herpes simplex virus type 1 (HSV-1), but not that of control cells, results in (i) potent stimulation of the specific reverse transcriptase (RT) activity detected in the culture supernatant and (ii) co-expression of both typical HSV-1 virions and abundant retrovirus-like particles. Transfection of LM7 cells with plasmids expressing HSV-1 immediate early (IE) ICP0 and ICP4 proteins produced a similar enhancement of RT activity in culture supernatants with retrovirus-like particles being identifiable by electron microscopy. These effects were not observed with a plasmid expressing ICP27 or with the parental plasmid in LM7 cells, nor with any of these four plasmids in control cells. These results show that HSV IE trans-activating proteins strongly enhance the expression of the latent retrovirus present in LM7 cells. The possible role in vivo of herpesviruses as 'triggering' cofactors in the retrovirus hypothesis for multiple sclerosis aetiology is also discussed.

In vitro transmission and antigenicity of a retrovirus isolated from a multiple sclerosis patient.

We have recently isolated an apparently novel retrovirus (LM7) from a patient with multiple sclerosis (MS). We present here results showing that (1) LM7 retrovirus can be transmitted in vitro to a normal human leptomeningeal cell culture and that (2) specific antibody against this retroviral strain can be detected in MS cases. Our results suggest that, if this virus is an endogenous retrovirus, it is different from human endogenous elements already described.

Molecular identification of a novel retrovirus repeatedly isolated from patients with multiple sclerosis. The Collaborative Research Group on Multiple Sclerosis.

The partial molecular characterization of multiple sclerosis (MS)-associated retrovirus (MSRV), a novel retrovirus previously called LM7, is reported. MSRV has been isolated repeatedly from leptomeningeal, choroid plexus and from Epstein-Barr virus-immortalized B cells of MS patients. A strategy based on reverse transcriptase PCR with RNA-purified extracellular virions yielded an initial pol fragment from which other regions of the retroviral genome were subsequently obtained by sequence extension. MSRV-specific PCR primers amplified a pol region from RNA present at the peak of reverse transcriptase activity, coinciding with extracellular viral particles in sucrose density gradients. The same sequence was detected in noncellular RNA from MS patient plasma and in cerebrospinal fluid from untreated MS patients. MSRV is related to, but distinct from, the endogenous retroviral sequence ERV9. Whether MSRV represents an exogenous retrovirus with closely related endogenous elements or a replication-competent, virion-producing, endogenous provirus is as yet unknown. Further molecular epidemiological studies are required to determine precisely the apparent association of virions containing MSRV RNA with MS.