Gynaecomastia: is one cause enough?

Gynaecomastia can be detected in between one-third and two-thirds of men. A wide variety of causes of gynaecomastia, some physiological, some very serious, have been identified. We present a case in which the cause of the gynaecomastia seemed obvious after history taking and physical examination but we finally ended up with a more complex combination of diagnoses. This case stresses the importance of combining history taking and physical examination with additional laboratory testing for the assessment of gynaecomastia.

Acute renal failure caused by Klebsiella pneumoniae pyelonephritis.

We report a 34-year-old male patient without prior medical history who presented with acute renal failure due to acute bacterial pyelonephritis. Both blood and urine cultures grew Klebsiella pneumoniae. Although a kidney biopsy revealed extensive necrosis and no viable glomeruli, renal function recovered to near normal after intermittent hemodialysis and antibiotic therapy. We believe that it is important to include this entity in the differential diagnosis of acute renal failure since proper diagnosis and treatment is essential for recovery of renal function. Furthermore, we would like to draw attention to Klebsiella pneumoniae as an important potential pathogen in such cases, in addition to Escherichia coli.

Effects of interferon alfa and gamma on human uveal melanoma cells in vitro.

BACKGROUND: Uveal melanoma is a tumour with a high incidence of metastasis and a high mortality rate. Additional therapies to obtain a better local control or an effective treatment of metastases are necessary. Interferons may be applied. METHODS: The effects of human interferon alfa and gamma on proliferation and expression of immunologically important molecules of human uveal melanoma cells in vitro were studied. A propidium iodide assay was used to determine proliferation and immunostaining with monoclonal antibodies was applied to detect changes in antigen expression on two primary uveal melanoma cell lines, Mel 202 and 92-1. RESULTS: Interferon alfa inhibited proliferation of cell line 92-1 at a concentration of 50 IU/ml, but had no effect on cell line Mel 202, while interferon gamma inhibited growth of both cell lines. Only interferon gamma had a visible effect on cell morphology. With respect to the immunomodulatory effects, interferon alfa increased monomorphic HLA class I expression, but did not affect HLA class II expression. Interferon gamma induced not only HLA class I but also class II expression. The effects on HLA expression were locus-specific with the strongest effects observed for HLA-B and DR products. Small differences were observed with respect to the susceptibility of two different melanoma cell lines to antiproliferative effects and to modulation of antigen expression. CONCLUSION: The effects of interferon alfa and gamma on human uveal melanoma cells in vitro suggest a potential role of these cytokines in the treatment of patients with uveal melanoma. In particular, the immunomodulatory effects of these cytokines in vitro imply that treatment of patients with these cytokines might stimulate a beneficial antimelanoma immune response in vivo.

Cytokine-mediated modulation of integrin, ICAM-1 and CD44 expression on human uveal melanoma cells in vitro.

Adhesion molecules are likely to play a role in the process of tumour progression. We investigated the expression of integrins, ICAM-1, and CD44 and the influence of interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), and tumour necrosis factor-alpha (TNF-alpha) on expression of these molecules on four uveal melanoma cell lines. The in vitro integrin expression was quite variable. The alpha V and beta 1 subunits were expressed on all cell lines, and none of the cell lines showed any alpha 3, beta 2, or beta 4 expression. Other integrin subunits showed a more variable pattern. ICAM-1 and CD44 were strongly expressed on all cell lines. IFN-alpha, IFN-gamma, and TNF-alpha upregulated alpha 1, alpha 2, and alpha 3 expression, and did not alter alpha 4, alpha 5, alpha 6, beta 2, alpha v beta 3, and beta 4 expression. The effects on alpha V and alpha V beta 5 were variable. ICAM-1 was upregulated by IFN-gamma and TNF-alpha, but not by IFN-alpha. Cytokine treatment hardly changed CD44 expression. In one case a comparison was made between expression on cultured cells and on tissue sections of the tumour of origin. Differences in expression were observed for the integrin subunits alpha 2, alpha 3, and alpha 5. This study shows that integrins and ICAM-1 expression on uveal melanoma cells in vitro are susceptible to cytokine treatment, but that the effects on integrin expression are cytokine and cell line dependent. Furthermore, some differences in integrin expression between cells in vivo and in vitro exist.

Transforming growth factor ß2 levels in aqueous humor during corneal transplantation and cataract surgery.

Transforming growth factor-ß (TGF-ß) is a molecule with an extremely wide range of biological activities. In aqueous humor (AH) TGF-ß is one of the factors involved in immunosuppression, and contributes to the immunological privilege of the anterior chamber of the eye. It may well be that ocular diseases, like corneal inflammation, disturb this immunological privilege by altering the cytokine equilibrium in AH. We compared the amounts of active, total, and the ratio active/total TGF-ß in AH of patients with severe corneal disease leading to corneal transplantation with those values in patients with cataract. IL-6 levels in AH were determined too since raised levels may indicate intraocular inflammation. The aqueous humor samples were collected from patients with cataract undergoing cataract surgery and patients with corneal disease undergoing corneal transplantation. TGF-ß(2) levels and IL-6 levels in AH were measured with a capture ELISA. TGF-ß(2) in AH was mainly present as a latent complex. Eyes with corneal disease prior to corneal transplantation did not differ from eyes with cataract in the level of active, total, or the ratio active/total TGF-ß(2) in AH. None of the eyes showed significant IL-6 levels. In both corneal disease and cataract the amounts of IL-6 and TGF-ß(2) in AH thus suggest the presence of a normal immunological balance. This may have a positive influence on corneal graft survival. However, we observed raised levels of active TGF-ß(2) in age-group 61-80 years, which might be related to the onset of cataract development.