A clinical trial of adjunctive oestrogen treatment in women with schizophrenia

Summary A double-blind, 28-day, placebo-controlled study was conducted with three groups of women of child-bearing age (N = 12 in each group) who received standardised antipsychotic medication plus a) 50 μg transdermal estradiol or b) 100 μg transdermal estradiol or c) transdermal placebo. Preliminary analyses show that women receiving 100 μg of estradiol made greater improvements in the symptoms of schizophrenia than either the 50 μg estradiol or placebo groups. The addition of 100 μg adjunctive transdermal oestrogen significantly enhanced treatment responsivity of acute, severe psychotic symptoms in women with schizophrenia. The positive impact of oestrogen treatment on psychotic symptoms via a multiplicity of possible actions (see accompanying articles in this issue) may prove clinically useful in the overall treatment of women with schizophrenia. Accepted June 2002, Published online September 16, 2002 Correspondence: Prof. Jayashri Kulkarni, Alfred Psychiatry Research Centre, Alfred Hospital, Commercial Road, Prahran. Vic. 3181, Australia; e-mail: jayashri.kulkarni@med.monash.edu.au     

What is an Oligodendroglioma?

With this issue, we begin a new series of articles entitled “Controversies in neuropathology.” These will represent brief position papers on controversial topics in our specialty. They are not intended to be review articles, rather will represent “position papers” on topical issues, with a relatively circumscribed and selective bibliography. Authors of these papers are encouraged to present and defend their own views on the subject in question. Most of these papers will be by invitation, but authors who would like to submit an article for this series are encouraged to contact the Brain Pathology editorial office. HVV     

Relationship between serum follicle stimulating hormone in the male and standard sperm parameters, and the results of intracytoplasmic sperm injection

Serum follicle stimulating hormone (FSH) is routinely measured when evaluating the infertile male for intracytoplasmic sperm injection (ICSI). However, among the sperm parameters, only its relationship with sperm concentration is well documented. Few investigations concern the relationship between FSH and sperm motility and morphology, and the results of ICSI. A retrospective study of 316 couples who underwent ICSI was carried out to determine the relationships between serum FSH concentrations in the male and (i) standard sperm parameters_(concentration, motility and morphology) and (ii) fertilization, cleavage, pregnancy and implantation rates after ICSI. There was an inverse correlation with sperm concentration and total motility but no relationship was found with progressive motility and sperm morphology. Neither was any relationship found between serum FSH and fertilization, cleavage, pregnancy and implantation rates, and the results of ICSI. These findings suggest the need to review the routine measurement of serum FSH in the infertile male when ICSI is the planned treatment procedure.      

Human Th1 cells preferentially induce interleukin (IL)-1β while Th2 cells induce IL-1 receptor antagonist production upon cell/cell contact with monocytes

The role of human T cells in the induction and regulation, upon cell/cell contact, of inflammatory responses by monocytic cells was investigated. The production of interleukin (IL)-1β and IL-1 receptor antagonist (IL-1Ra) by the monocytic THP-1 cell line was measured upon contact with either Th1 or Th2 cell clones. CD4⁺ T cell clones specific for purified protein derivative of Mycobacterium tuberculosis, predominantly Th1 [high interferon (IFN)-γ and low IL-4 producers], or tetanus toxoid, predominantly Th2 (low IFN-γ and high IL-4 producers), were generated. Cell membranes from antigen-stimulated, but not from resting T cell clones induced dose-dependent cytokine production by THP-1 cells. Th1 clones induced higher levels of IL-1β production (484–806 pg/ml) than did Th2 clones (21–114 pg/ml). In contrast, Th1 clones induced lower levels of IL-1Ra (0.9–7.8 ng/ml) than did Th2 clones (7.0–49.6 ng/ml). Similar results were obtained when T cell clones were activated by cross-linked CD3 and CD28. IL-1β production by THP-1 cells correlated with IFN-γ production by T cell clones but was unaffected by IFN-γ neutralization. IL-1Ra production by THP-1 cells correlated with IL-4 production by T cells and was partially inhibited by IL-4 neutralization. These data indicate that activated Th1 and Th2 cells express different molecules on the cell surface able to induce distinct pro-inflammatory (IL-1β) or anti-inflammatory (IL-1Ra) responses in monocytes. This differential induction of molecules with opposite effects on inflammation stresses the functional heterogeneity in CD4⁺ T cells.     

The Development of the Pathologic Changes of Alzheimer''s Disease and Senile Dementia in Patients with Down''s Syndrome

Senile plaques, neurofibrillary change and granulovacuolar degeneration characterize Alzheimer's disease (presenile dementia) and senile dementia and are also seen in the aged human brain. The development of these lesions was studied in 13 patients with Down's syndrome, ages 12 to 65, with the purpose of defining similarities and dissimilarities, if any, between their morphologies in these four conditions. Evaluation by light and, when applied, electron microscopy established apparent identities. The findings suggest that Down's syndrome, with its partially characterized genotypic and phenotypic abnormalities, is an appropriate model for the study of the pathogenesis of these lesions.     

Appearance of cellular and humoral immunity in guinea pigs after infection with Coxiella burnetii administered in small-particle aerosols.

The development of humoral and cell-mediated immune responses was studied in guinea pigs infected with Coxiella burnetti administered in small-particle aerosols. Direct macrophage migration inhibition was observed in cultured peritoneal exudate cells as early as 3 days after exposure. Maximum inhibition of macrophages cultured with phase I or II antigen occurred 14 to 21 days postexposure and persisted through 35 days. This inhibitory action was no longer detectable at 42 days. Serum antibody to the phase II antigen of C. burnetii was detected at 14 days, and serum antibody to phase I antigen was detected at 21 days, 18 days after the cell-mediated immune response.     

Oestrogen, progesterone, and androgen receptors in ovarian neoplasia: correlation between immunohistochemical and biochemical receptor analyses

AIM: To investigate the correlation between immunohistochemical and biochemical steroid receptor analyses by measurement of oestrogen, progesterone, and androgen receptor status in ovarian neoplasia. METHODS: Tissue samples were obtained from 27 ovarian neoplasms, including two borderline tumours. Immunohistochemical staining of the tissue slides was scored semiquantitatively, incorporating the intensity and percentage of positive staining (histo-score). Tumours with a histo-score of 10 or more were considered steroid receptor positive. The epithelial and stromal fractions of the tumours were analysed separately. To study the uniformity of receptor expression throughout a tumour, up to four samples were analysed. RESULTS: Immunohistochemical histo-scores of the oestrogen receptor in the epithelial fractions were significantly correlated with the biochemical oestrogen receptor values (r = 0.408). Androgen receptor status in the epithelial fraction was correlated with that in the stromal fraction (r = 0.741), while androgen receptor histo-scores in the epithelial fraction correlated with the biochemical assay values (r = 0.463). On biochemical analysis, 17 of the 27 ovarian tumours were oestrogen receptor positive and seven were progesterone receptor positive. On immunohistochemical analysis, eight tumours were oestrogen receptor positive and two were progesterone receptor positive. Biochemical analysis showed that 14 of the 26 tumours were slightly androgen receptor positive (10-50 fmol/mg protein), while all the others were negative. On immunohistochemical analysis, seven of the 26 tumours were androgen receptor positive. When two or more specimens from one tumour were analysed, marked differences in steroid status were found, especially in progesterone receptor and androgen receptor expression. Some parts of a tumour were steroid receptor positive, while other parts were negative owing to heterogeneity of expression. CONCLUSIONS: Immunohistochemical and biochemical analysis of steroid receptors in ovarian tumours correlated weakly or not at all. Heterogeneity of expression within a tumour and the presence of progesterone and androgen receptors in the stromal fraction partly accounted for this observation. Biochemical and immunohistochemical androgen receptor status was much lower than in previous reports.     

Differentiation of C3b receptors on human lymphocytes, phagocytes, erythrocytes and renal glomerulus cells by monoclonal antibodies.

C3b receptor protein was purified form human erythrocytes by 2 M KBr solubilization and affinity chromatography on C3-coated sepharose. This material served as antigen for raising monoclonal antibodies. To investigate the distribution and antigenetic relationship between the receptors for C3b on human erythrocytes, lymphoid and phagocytic cells, as well as kidney cells three monoclonal antibodies were selected which inhibited the binding of EAC14 degrees 23b to complement receptor-bearing cells. This could be shown for human erythrocytes by inhibiting the immune adherence reaction, for tonsil lymphocytes, Raji cells, and guinea-pig spleen cells by inhibition of rosette formation of these cells with EAC14 degrees 23b, and for human renal glomeruli by blocking of the the adherence of EAC14 degrees 23b to kidney sections. In contrast, these monoclonal antibodies were not capable of inhibiting rosette formation of human granulocytes and monocytes with EAC14 degrees 23b. The antibodies only interfered with the rosette formation, of EAC14 degrees 23bi and EAC14 degrees 23d with Raji cells and tonsil lymphocytes-if at all-at high concentrations, whereas the rosette formation of Raji cells and tonsil lymphocytes with EAC14 degrees 23b was influenced by supernatants of the selected clones up to a dilution of 1:10(3) to 1:10(5).