Endometriosis: Leuprolide in a 3-monthly versus a monthly depot formulation for the treatment of symptomatic endometriosis: a pilot study

An open-label randomized pilot study was conducted to evaluatethe efficacy and acceptability of 6 months treatment with leuprolidein a 3-monthly versus a monthly i.m. depot injection for therelief of chronic pelvic pain in women with endometriosis. Atotal of 30 women aged 18-38 years were allocated to the 3-monthlydepot arm (n = 15) or to the monthly depot arm (n = 15) afterlaparoscopic diagnosis of pelvic endometriosis. Mean (SD) deepdys-pareunia scores according to a 0–3 point verbal ratingscale decreased from 1.8 (0.9) at baseline to 1.3 (0.7) at theend of treatment in the 3-monthly depot group and from 2.1 (1.2)to 1–3 (0.7) in the monthly depot group. Correspondingvalues in non-menstrual pain scores fell from 2.1 (0.6) to 1.1(03), and from 2.1 (0.8) to 1.2 (0.4) respectively, withoutstatistically significant differences between the groups. Serumluteinizing hormone (LH) and 17-oestradiol concentrations weresignificantly suppressed at 12 and 24 weeks compared with baselinevalues, without differences between the groups. The monthlydepot caused a slightly more marked inhibition of serum folliclestimulating hormone (FSH) levels with respect to the 3-monthlypreparation. Mean (SD) endometriosis scores at baseline andat 6-month follow-up laparoscopy were respectively 32.8 (25.1)and 12.2 (9.3) in the 3-monthly depot group and 29.0 (22.7)and 13.1 (15.3) in the monthly depot group (paired Mest, P 0.05). Mean percentage decrease in lumbar spine bone mineraldensity was 5.2% in the former and 4.9% in the latter subjects.In the 3-monthly depot group, 13 women graded the tolerabilityof their treatment schedule as ‘good’ compared withseven in the monthly depot group (² = 5.40, P = 0.02).     

The effect of intravenously administered salbutamol on serum potassium in asthmatic and nonasthmatic atopic subjects

The role of adrenergic mechanism in the pathogenesis of allergic disease is controversial. Recent experimental and clinical reports have suggested that -adrenergic blockade impairs and stimulation enhances extrarenal potassium uptake in humans. This led us to study the effect of the intravenous administration of salbutamol, a specific -2-adrenergic agonist, on serum potassium in 9 healthy subjects and in 23 patients with allergic asthma and/or rhinitis. Serum potassium fell significantly and reached a peak decline at the end of venous infusion in all the normal subjects. Seventeen atopic subjects showed a lower or absent serum K⁺ decrement: there was no difference between asthmatic and rhinitic patients. There was no relation among the salbutamol-induced serum potassium decrement, serum glucose increment, blood pressure and heart-rate changes, and nonspecific bronchial reactivity. These findings suggest that -2-adrenergic hyporesponsiveness is present only in some allergic patients.     

HER-2/neu and bcl-2 in ovarian carcinoma: clinicopathologic, immunohistochemical, and molecular study in patients with shorter and longer survival.

The bcl-2 protein is a membrane protein involved in prolonging cell survival by inhibiting apoptosis. The HER-2 oncogene, which is located on chromosome 17 and encodes for a tyrosine-kinase growth factor receptor, is amplified and HER-2/neu is overexpressed in 25% to 30% of breast carcinomas. The authors analyzed the bcl-2 expression and the bcl-2 gene and HER-2/neu overexpression and amplification in FIGO stage IIIC, serous, G3, ovarian carcinomas obtained from living patients who had no evident disease 5 years after primary treatment compared with ovarian carcinomas obtained from patients, matched for stage, grade of differentiation, and treatment, who had died of progression of disease no later than 2 years after primary treatment. bcl-2 overexpression was statistically correlated with progression of disease during first-line chemotherapy (P=0.021). The HER-2/neu status was found not to correlate with progression of disease during first-line chemotherapy. Both bcl-2 and HER-2/neu expression were not statistically associated with the clinical outcome of ovarian cancer patients. Gene amplification of the HER-2/neu chromosome 17 was found in all the HER-2/neu, 3+ score, positive-staining ovarian carcinomas. None of the analyzed samples revealed a translocation t(14;18)(q32;q21) in the bcl-2 gene. The knowledge of additional prognostic or even predictive factors, such as bcl-2 expression, in patients with advanced ovarian carcinoma before the primary chemotherapeutic treatment may help in the management of patients who require a more tailored treatment. In addition, the gene amplification of the HER-2/neu suggests that HER-2 is a potential target for treatment in ovarian cancer.     

Correlation of epidermal growth factor receptor expression with tumor microdensity vessels and with vascular endothelial growth factor expression in ovarian carcinoma

We analyzed in advanced ovarian serous G3 carcinoma the correlation between epidermal growth factor receptor (EGFR) overexpression and tumor angiogenesis and their relation with clinical outcome. Microvessel density (MVD) and vascular endothelial growth factor (VEGF) were statistically correlated with disease-free interval and death from disease both in univariate and multivariate analyses while EGFR expression was not correlated with clinical outcome. MVD was significantly associated with progression of disease during chemotherapy while VEGF and EGFR expression were not correlated with responsiveness to chemotherapy (Fisher's exact test). VEGF expression was correlated with MVD (Fisher's exact test). EGFR showed a trend to correlation with MVD. Further studies focusing on the use of angiogenesis inhibitors in addition to EGFR inhibitors on ovarian carcinoma cells may produce therapeutic strategies in the selection of tailored therapies in ovarian cancer patients.     

Identification of sixty-two novel and twelve known FBN1 mutations in eighty-one unrelated probands with Marfan syndrome and other fibrillinopathies

Marfan Syndrome (MFS) is an autosomal dominant disorder of the connective tissue due to mutations of Fibrillin-1 gene (FBN1) in more than 90% of cases and Transforming Growth Factor-Beta-Receptor2 gene (TGFB2R) in a minority of cases. Genotyping is relevant for diagnosis and genotype-phenotype correlations. We describe the FBN1 genotypes and related phenotypes of 81 patients who were referred to our attention for MFS or Marfan-like phenotypes. Patients underwent multidisciplinary pertinent evaluation in the adult or paediatric setting, according to their age. The diagnosis relied on Ghent criteria. To optimise DHPLC analysis of the FBN1 gene, all coding regions of the gene were directly sequenced in 19 cases and 10 controls: heterozygous amplicons were used as true positives. DHPLC sensitivity was 100%. Then, DHPLC was used to screen 62 other cases. We identified 74 FBN1 mutations in 81 patients: 64 were novel and 17 known. Of the 81 mutations, 41 were missense (50.6%), 27, either nonsense or frameshift mutations and predicted a premature termination codon (PTC) (33%), 11 affected splice sites (13.6%), and two predicted in-frame deletions (2.5%). Most mutations (67.9%) occurred in cbEGF-like modules. Genotype was clinically relevant for early diagnosis and conclusion of the diagnostic work-up in patients with incomplete or atypical phenotypes.     

Metastatic Psammomatous Somatostatinoma of the Pancreas Causing Severe Ketoacidotic Diabetes Cured by Surgery

A case of somatostatin-producing pancreatic tumor associated with severe insulindependent diabetes mellitus and ketoacidotic coma is reported. The tumor, a 10-cm expansile mass arising from the pancreatic tail of a 70-yr-old woman, was first detected by ultrasonography, performed because of abdominal pain, and subsequently confirmed by computed tomography and fine-needle tumor aspiration. Pathologic investigation showed a predominatly solid-trabecular structure with scattered microacini and psammomatous bodies. A large proportion of tumor cells expressed somatostatin and/or calcitonin. Following resection of the primary tumor and three peripancreatic lymph nodes with metastases, the patient recovered rapidly from her diabetic syndrome and remained in substantially good health during a subsequent 8-yr follow-up period, without evidence of tumor recurrence.     

Interleukin-6 gene alleles affect the risk of Alzheimer's disease and levels of the cytokine in blood and brain

Two different polymorphic regions of the interleukin-6 (IL-6) gene were investigated in patients with Alzheimer's disease (AD) and non-demented controls. The -174 C allele in the promoter region of IL-6 gene was over-represented in AD patients compared to controls and significantly increased the risk of AD. Moreover, the -174 CC genotype was associated with a high risk of the disease in women. The D allele of a variable number of tandem repeat (VNTR) was in strong linkage disequilibrium with the -174 C allele and slightly increased AD risk. On the other hand, the frequency of the VNTR C allele was decreased in patients with AD and was negatively associated with the risk of developing AD. Both the -174 CC and VNTR DD genotypes were also associated with increased IL-6 levels in the blood and brain from AD. These findings suggest that IL-6 may play a multifaceted role in AD by affecting the turnover of the cytokine.     

Involvement of chromosomes 12 and 14 in the cutaneous stage of mycosis fungoides: Cytogenetic evidence for a multistep pathogenesis of the disease

Cytogenetic studies were performed on the cells of bone marrow, peripheral blood, and skin tumor biopsies from a patient with mycosis fungoides at an early stage. Chromosome abnormalities were detected in 100% of the cells harvested from the cutaneous specimen, whereas the cells of the bone marrow and blood were karyotypically normal. Three related clones, showing increasing cytogenetic complexity, were found. Chromosome #12 was abnormal in all metaphases, and an abnormal 14q chromosome was present in a minority of cells belonging to the most complex emerging subclone. These data, along with the finding of important signs of chromosome imbalance, suggest a polyphasic evolution of this chronic T lymphoproliferative disease.     

Immunohistochemical localization of nNOS in the skin and nerve fibers of the earthworm Lumbricus terrestris L. (Annelida Oligochaeta)

The epidermis of the earthworm Lumbricus terrestris is a multifunctional tissue. It is composed of supporting, mucous, neuroendocrine-like, sensory and basal cells. NO is considered to be a molecule that regulates numerous functional activities (also in non-neuronal cells) in vertebrates. In the earthworm epidermis, we found neuronal NO synthase immunopositivity in orthochromatic and metachromatic mucous cells, neuroendocrine-like cells and in epidermal and subepidermal nerve fibers and striated muscle fibers. It is suggested that NO has a multitude of biological actions, affecting functional activities of the epidermis such as tissue homeostasis, control of secretion, proliferation, respiration, defense, water-salt balance, as well as regulation of tonus in vascular and striated muscles.