Reduction of GH response to the GABA-B agonist baclofen in patients with major depression

In order to establish whether alterations in the GABAergic control of GH secretion occur in male patients with major depression, the GH response to the GABAergic-B agonist baclofen (10 mg at 0830h) or to placebo was tested in 9 depressed men and in 10 age- and weight-matched male normal controls.

The basal concentrations of GH were significantly lower in the depressed patients (0.87± 0.69 ng/ml) than in the normal controls (1.57±0.33 ng/ml) (p=0.011) and were not modified by the administration of placebo. The administration of baclofen induced a striking, significant increase in GH concentrations in the normal controls (mean peak at 90 MIN=6.4±1.5 ng/ml). In contrast, a slight, nonsignificant GH increase occurred in the depressed patients after baclofen (mean peak at 90 MIN=1.57±1.45 ng/ml). The GH response was significantly lower in the depressed than in the control subjects (p<0.001). These data indicate the presence of reduced GABAergic control of GH secretion in male depressed patients.     

A Case of Hypopigmented Mycosis Fungoides in a Young Caucasian Boy

Abstract: Hypopigmented mycosis fungoides is a variant of mycosis fungoides characterized by the presence of hypopigmented patches as the sole manifestation of the disease. It has been described aimost always in young black or dark-skinned patients. The only white patient described was a 64-year-oid woman who not oniy had hypopigmented lesions, but also nodular lesions with lymphadenopathy. We describe hypopigmented lesions arising in a white boy 12 years of age, born in northern Italy, without any foreign ancestors. The microscopic alterations, with epidermotropism, the immunoiogic markers, the negativity of T-cell receptor gene rearrangement, and the good response to PUVA therapy correspond to the main findings in black patients with this disease. Long-term follow-up of these patients is important to obtain better knowledge of the natural history of the disorder, Hypopigmented mycosis fungoides must now be included in the differential diagnosis of hypopigmented macular lesions not only in black or dark-skinned patients but also in white patients.     

Functional enuresis: pharmacological versus behavioral treatment

Treatment of childhood enuresis requires a careful anamnesis, physical examination, urinalysis, and urine culture to determine if a subject is affected with functional or organic enuresis. Functional enuresis (FE) was present in the majority of our patients (168/204). These 168 subjects, aged from 6 to 11 years, were randomly divided into three therapy groups (pharmacological therapy, behavioral therapy, and behavioral therapy with the aid of a personal computer). Our study shows that behavioral therapy gave better results in FE than did pharmacological therapy. We point out the usefulness of combining bladder retention training and behavioral therapy to improve the general maturity and autonomous behavior of the child, and the resultant positive effects on his personality.     

A comprehensive in vitro characterization of pancreatic ductal carcinoma cell line biological behavior and its correlation with the structural and genetic profile

There are a large number of stable pancreatic ductal carcinoma cell lines (PDCL) that are used by researchers worldwide. Detailed data about their differentiation status and genetic alterations are present in the literature, but a systematic correlation with cell biological behavior is often lacking. PDCL (n=12) were clustered by source of tumor cell (ascites, primary tumor, metastasis), and the data of functional cell biology were correlated with the reported structural and genetic profiles. Major histocompatibility complex expression, chemosensitivity and aneuploidia appeared to be related to the source of PDCL, and proliferative capacity appeared to be related to the grade of differentiation. No correlation between genetic/structural features of PDCL and biological behavior was found. All the cell lines appeared generally insensitive to in vitro treatment with 5-fluorouracil and showed variable degrees of susceptibility to gemcitabine, raltitrexed and oxaliplatin. All the PDCL showed resistance to Fas-mediated apoptosis but were significantly sensitive to the pro-apoptotic effect of inflammatory cytokines [interleukin (IL)-1, tumor necrosis factor (TNF) and interferon ]. PDCL were characterized for the secretion of several factors relevant to the tumor-immune cross talk. Vascular endothelial growth factor, CCL2, CCL5 and transforming growth factor were the factors most frequently released; less frequent was the secretion of CXCL8, CCL22, IL-6 and sporadically CXCL12, IL-10 and hepatocyte growth factor. The cytokines IL-1 and TNF were always undetectable. In conclusion, a clear correlation between structural/genetic features and function could not be detected, suggesting the weakness of a morphological classification for the in vitro studies of pancreatic cancer.     

Papillary carcinoma of the thyroid: hepatocyte growth factor (HGF) stimulates tumor cells to release chemokines active in recruiting dendritic cells

Tissue distribution of dendritic cells was investigated in eight cases of papillary carcinoma of the thyroid using immunohistochemistry. Most dendritic cells had an immature phenotype (CD1a++, CD11c+, CD40+, CD86-, HLA-DR-) and were located at the invasion edge of the tumor. This pattern of distribution was profoundly different from that of CD68+ macrophages, which were evenly distributed throughout the tumor. The ability of tumor cells to release chemotactic factors active on dendritic cells was investigated in primary cultures of the same cases of papillary carcinoma, and was compared to that of the corresponding normal thyroid cells obtained from the tumor-free contralateral lobe. Chemotactic activity of culture supernatants was tested against dendritic cells in a chemotaxis chamber. It was found that papillary carcinoma cells were active in releasing chemotactic activity, that hepatocyte growth factor (HGF; 100 ng/ml) or interleukin (IL)-1beta (10(3) U/ml) induced a fourfold increase in the amount of chemotactic activity released, and that normal thyroid cells obtained from the same patients were as effective as tumor cells. Characterization of chemokines at RNA level revealed that unstimulated cells contain large amounts of IL-8 and monocyte chemotactic protein (MCP)-1 RNAs, and that stimulation with HGF or IL-1beta induced RNAs for regulated upon activation normal T expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-3alpha, interferon-gamma-inducible protein 10 (IP-10), and, to a lesser extent, MIP-1alpha and MIP-1beta. The possibility that HGF/Met interaction has a biological role in vivo was investigated in serial sections of six tumors immunostained for CD1a+, Met protein, and HGF. It was found that all six tumors were intensely and diffusely positive for Met protein, that HGF staining was present in tumor cells of the advancing edge, and that HGF+/Met+ tumor cell nests were infiltrated by CD1a+ dendritic cells. The foregoing observations are consistent with the possibility that HGF stimulation of Met+ tumor cells is one of the molecular mechanisms involved in the recruitment of dendritic cells.     

Long-term ST database: A reference for the development and evaluation of automated ischaemia detectors and for the study of the dynamics of myocardial ischaemia

The long-term ST database is the result of a multinational research effort. The goal was to develop a challenging and realistic research resource for development and evaluation of automated systems to detect transient ST segment changes in electrocardiograms and for supporting basic research into the mechanisms and dynamics of transient myocardial ischaemia. Twenty-four hour ambulatory ECG records were selected from routine clinical practice settings in the USA and Europe, between 1994 and 2000, on the basic of occurrence of ischaemic and non-ischaemic ST segment changes. Human expert annotators used newly developed annotation protocols and a specially developed interactive graphic editor tool (Semia) that supported paperless editing of annotations and facilitated international co-operation via the Internet. The database contains 86 two- and three-channel 24h annotated ambulatory records from 80 patients and is stored on DVD-ROMs. The database annotation files contain ST segment annotations of transient ischaemic (1155) and heart-rate related ST episodes and annotations of non-ischaemic ST segment events related to postural changes and conduction abnormalities. The database is intended to complement the European Society of Cardiology ST-T database and the MIT-BIH and AHA arrhythmia databases. It provides a comprehensive representation of ‘real-world’ data, with numerous examples of transient ischaemic and non-ischaemic ST segment changes, arrhythmias, conduction abnormalities, axis shifts, noise and artifacts.     

Rapid identification of mycobacteria to the species level by polymerase chain reaction and restriction enzyme analysis.

A method for the rapid identification of mycobacteria to the species level was developed on the basis of evaluation by the polymerase chain reaction (PCR) of the gene encoding for the 65-kDa protein. The method involves restriction enzyme analysis of PCR products obtained with primers common to all mycobacteria. Using two restriction enzymes, BstEII and HaeIII, medically relevant and other frequent laboratory isolates were differentiated to the species or subspecies level by PCR-restriction enzyme pattern analysis. PCR-restriction enzyme pattern analysis was performed on isolates (n = 330) from solid and fluid culture media, including BACTEC, or from frozen and lyophilized stocks. The procedure does not involve hybridization steps or the use of radioactivity and can be completed within 1 working day.     

Immunomagnetic cell selection performed for HLA haploidentical transplants with the CliniMACS device: effect of additional platelet removal on CD34+ cell recovery

Immunomagnetic CD34+ cell selection (ICS) is a widely employed technology in autotransplant and allotransplant settings. When an haploidentical transplant is performed, a high dose of purified CD34+ cells together with efficient T and B cell depletion are required to minimize the risks of graft versus host disease (GVHD) and Epstein-Barr virus (EBV)-related lymphoma. To ameliorate the performances of the CliniMACS (Miltenyi Biotec) ICS device, we compared 73 ICS performed following the manufacturer's recommended platelet depletion versus 48 performed after adjunctive centrifugations to increase platelet depletion of the leukapheresis (LKF) product. A total of 121 ICS (from single or fractioned LKF products) were carried out on 93 LKF collected from 47 related healthy donors. A statistical significance in terms of CD34+ cell recovery (81.8% vs. 71.2%) was found in favor of the modified ICS procedure (p=0.0049) with a comparable stem cell purity and viability. The modification of the standard manufacturer's technique for increasing platelet depletion can further improve the recovery of stem cells with no influence on T and B cell depletion. These results demonstrate the negative influence exerted on CD34+ cell recovery by LKF platelet contamination.