Sequencing of the alpha-synuclein gene in a large series of cases of familial Parkinson's disease fails to reveal any further mutations. The European Consortium on Genetic Susceptibility in Parkinson's Disease (GSPD)

A mutation in exon 4 of the human alpha-synuclein gene was reported recently in four families with autosomal dominant Parkinson's disease (PD). In order to examine whether mutations in this exon or elsewhere in the gene are common in familial PD, all seven exons of the alpha- synuclein gene were amplified by PCR from index cases of 30 European and American Caucasian kindreds affected with autosomal dominant PD. Each product was sequenced directly and examined for mutations in the open reading frame. No mutations were found in any of the samples examined. We conclude that the A53T change described in the alpha- synuclein gene is a rare cause of PD or may even be a rare variant. Mutations in the regulatory or intronic regions of the gene were not excluded by this study.      

Utility of human bone marrow obtained incidental to orthopedic surgery for hematopoietic clonal assays

We describe the establishment of a convenient method of acquiring human bone marrow cells for use in microcapillary clonal assays. Femoral epiphyseal and diaphyseal bone fragments and femoral canal reamings were collected incidental to total hip replacement surgery and cultured for human granulocyte-macrophage colony-forming units, erythroid burst-forming units and erythroid colony-forming units. This readily available source of normal human marrow provides an abundant quantity of hematopoietic progenitors of documented normalcy.     

Monocytoid B-cell lymphoma with bone marrow and peripheral blood involvement at presentation

A case of malignant lymphoma showing in a lymph node the characteristic morphologic features of the so-called monocytoid B-cell lymphoma (MBCL) is described. This case differs from the reported cases in the literature because atypical cells were observed in the bone marrow biopsy and marrow and peripheral blood smears that were obtained from the patient, a 61-year-old man, during the staging procedures. Lymphocyte surface marker studies on peripheral blood by flow cytometry and DNA analysis revealed a monoclonal population of lambda-positive lymphocytes. The immunophenotype of MBCL cells was studied both in paraffin-embedded lymph node sections by immunoperoxidase method and in peripheral blood by flow cytometric analysis; the cells expressed the SIg with lambda light chain restriction and the HLA-DR antigen; they also had positive results for B-cell-associated antigens, including LN1, LN2, CD 20, CD 22, CD 19, CD 9 but not CD 21, CD 24, and CD 10, T-cell-associated antigens and monocytic markers. In addition, they had negative results for CD 25, CD 38, PCA-1. This report emphasizes that in MBCL, peripheral and marrow involvement may occur at presentation analogous to other low-grade B-cell lymphomas. The immunophenotypic characteristics of MBCL cells, though not pathognomonic, are considered to be helpful in differentiating them from circulating cells of other B-cell lymphomas.     

Anti-Müllerian hormone concentrations in maternal serum during pregnancy

BACKGROUND: In females, anti-Müllerian hormone (AMH) is expressed only by the ovary. AMH is secreted by the granulosa cells of ovarian follicles and appears to regulate early follicle development. AMH is detected in serum from women of reproductive age and its levels vary slightly with the menstrual cycle, reaching the peak value in the late follicular phase. This study investigated serum AMH levels throughout gestation and after delivery in healthy pregnant women. METHODS: This cross-sectional study recruited pregnant women and healthy non-pregnant women, 84 in total. AMH, FSH and E2 were measured in the follicular phase, in the three trimesters of pregnancy and in early puerperium. RESULTS: Estradiol and FSH levels followed the expected patterns during gestation. During the follicular phase of the menstrual cycle AMH levels were 1.9 +/- 0.5 ng/ml. In the three trimesters of pregnancy and in early puerperium AMH levels were: 2.1 +/- 0.56, 2.4 +/- 0.64, 1.95 +/- 0.6 and 2.05 +/- 0.55 ng/ml respectively. No significant modifications were found in AMH levels during pregnancy and in the early puerperium. CONCLUSIONS: This study has obtained information on AMH and on the possible relationship with FSH. We hypothesize that the profile of the new marker of ovarian activity AMH may indicate that initial non-cyclic ovarian follicular activity during pregnancy is not abolished. Moreover FSH, does not seem to play a direct role on AMH synthesis and secretion.     

Transdermal administration of estradiol and norethisterone: effect on the uterus and uterine arteries

OBJECTIVE: To evaluate the short- and long-term effect on the uterus, endometrium, and vascular reactivity of uterine arteries of sequential transdermal estradiol (50 microg/day) and norethisterone (0.25 mg/day in the last 14 days of each cycle). DESIGN: An intravaginal ultrasound evaluation was performed in 48 postmenopausal women before and at the 3rd and 12th month of treatment, during the last 3 days of both estradiol alone and estradiol plus norethisterone. An endometrial biopsy was also performed before and at the end of treatment. In 11 participants, intravaginal ultrasound and endometrial biopsy were repeated after 48 months of treatment. RESULTS: Uterine volume (33.7 +/- 3.3 cm3 to 56.8 +/- 3.7 cm3; p = 0.001) and endometrial thickness (3.07 +/- 0.48 mm to 5.74 +/- 0.41 mm; p = 0.001) increased within 3 months, with no further increases. Thickness was similar in the estradiol and estradiol-norethisterone phase. Endometrial hyperplasia was found in one participant at 12 months of treatment. A significant decrease (p = 0.002) in the pulsatility index of uterine arteries was observed only during the estradiol phase. After 48 months of treatment, the pulsatility index of uterine arteries was lower than at baseline (2.78 +/- 0.24 vs. 2.23 +/- 0.33; p = 0.044) even when evaluated in the combined phase. CONCLUSIONS: The transdermal administration of sequential estradiol and norethisterone reduces uterine artery resistance and induces a self-limiting growth of the uterus and endometrium.     

The pathology spectrum of AIDS-related non-Hodgkin's lymphoma

Patients with acquired immunodeficiency syndrome (AIDS) are at increased risk of developing non Hodgkin's lymphomas (NHL). Current estimates indicate that 5-10% of HIV-infected individuals develop AIDS-related NHL (AIDS-NHL). AIDS-NHL share several clinical features, including frequent extranodal presentation, aggressive clinical course and poor outcome. However, AIDS-NHL are a heterogeneous group of malignancies. They traditionally included systemic and primary brain lymphomas, but nowadays their updated clinicopathologic spectrum also comprises two novel entities, namely primary effusion lymphoma and plasmablastic lymphoma of the oral cavity. In the last few years, several studies have shown that the pathologic heterogeneity of AIDS-NHL correlates with the heterogeneity of the molecular lesions associated with these lymphomas. However, despite their pathologic and molecular heterogeneity, AIDS-NHL have a common B-cell origin, although the precise stage of B-cell differentiation reflected by the different tumor types has not been clarified yet.     

Enzyme- and immunohistochemical study of a case of histiocytic necrotizing lymphadenitis

Summary A combined morphological, immunohistological, and enzyme histochemical analysis was performed on frozen and fixed lymph node tissue in a case of histiocytic necrotizing lymphadenitis (HNL) using conventional histology, a panel of monoclonal and polyclonal antibodies, and a series of common haematological enzyme reactions. Histology showed multiple paracortical necrotizing foci which, in a prominently necrobiotic background devoid of granulocytes, contained large numbers of foamy histiocytes and macrophages intermingled with cells resembling degenerating plasmacytoid T-cells. Most of the histiocytes were alpha₁-antichymotrypsin positive and foamy cells were also distinctly Leu-M1 positive. Strong granular acid phosphatase (AP) positivity was present in the cytoplasm of the macrophages and histiocytes. The cells with plasmacytoid features showed weaker and homogeneously diffuse AP staining. Alpha-naphthyl acetate esterase (ANAE) activity was much less striking than AP in the necrotizing foci and most of the ANAE negative cells corresponded to those with plasmacytoid features. No cells with B-cell lineage markers were present within the necrotizing foci; most of the occasional T-cells (Leu-1⁺, Leu-4⁺) present in the foci were Leu-2a⁺ (OKT8⁺) whereas OKT10⁺ lymphoid cells were abundant and appeared to correspond with the cells with plasmacytoid features. Our combined data confirm that the special type of necrosis found in HNL develops within foci of plasmacytoid T-cells undergoing regressive changes and apparently exhibiting distinct immunohistological and enzyme histochemical features.This study was supported in part by Grant n. 84.00525.44 from Consiglio Nazionale delle Ricerche Progetto Finalizzato Oncologia, Roma and by the Associazione Italiana per la Ricerca sul Cancro, Milano     

Kava-Kava administration reduces anxiety in perimenopausal women

OBJECTIVE: Disturbances of mood, such as anxiety and depression, increase in the perimenopausal period. Hormone replacement therapy or neuroactive drugs represent useful treatments for these disturbances but may be contraindicated or not accepted. Herein it was investigated the efficacy of Kava-Kava, an extract of Piper Methysticum, on mood of perimenopausal women. DESIGN: A 3-months randomized prospective open study investigating in perimenopausal women modifications induced by calcium supplementation (control; n=34), calcium plus Kava-Kava at the dose of 100 mg/day (n=15) or calcium plus Kava-Kava at the dose 200 mg/day (n=19). Anxiety was evaluated by the State Trait Anxiety Inventory (STAI); depression by the Zung's scale (SDS), and climacteric symptoms by the Greene's scale. Evaluations were performed at baseline and after 1 and 3 months. RESULTS: In the control group during the 3 months, anxiety, depression and climacteric symptoms tended to decline, but not significantly. During Kava-Kava anxiety declined (P<0.001) at 1 (-3.8+/-1.03) and 3 (-5.03+/-1.2) months, depression declined at 3 months (-5.03+/-1.4; P<0.002) and climacteric score declined (P<0.0006) at 1 (-2.87+/-1.5) and 3 (-5.38+/-1.3) months. Only the decline of anxiety induced by Kava-Kava was significantly greater than that spontaneously occurring in controls (P<0.009). CONCLUSIONS: The present data indicate that, in perimenopausal women, administration of Kava-Kava induces an improvement of mood, particularly of anxiety.     

An intrauterine progesterone contraceptive system (52 mg) used in pre- and peri-menopausal patients with endometrial hyperplasia

An intrauterine progesterone contraceptive system (IPCS) (52 mg) was inserted in 25 women with cystic endometrial hyperplasia. Among these women, 11 complained of heavy climacteric symptoms and also received an oestrogen replacement therapy consisting of conjugated oestrogens (0.625 mg/day) administered cyclically for 3 out of 4 wk. Prior to the therapy and after 6 mth of treatment, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), oestrone (E1) and oestradiol (E2) plasma levels were measured and endometrial histology was evaluated. In the women receiving IPCS treatment alone, there were no significant changes in FSH, LH, PRL, E1 and E2 plasma levels. However, there were remarkable changes found in their endometrial histology. In the remaining women receiving both treatments there was a sharp decrease in FSH and LH plasma levels and an increase in E1 and E2 plasma levels, while the prolactin levels remained unchanged. With the exception of two of these women, the endometrial histology changed remarkably. The endometrial morphology of the two exceptions remained unchanged. All climacteric symptoms disappeared after the administration of both IPCS and the oestrogen replacement therapy. The remarkable changes which did occur in the endometrial histology resulted in a less active glandular epithelium and stromal decidual formation, thus proving a useful effect of treatment.