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Biomedical subjects

M Battaglia

Publications and source records attributed to M Battaglia.

At least 19 recordsLinked to original sources

Negative immunomagnetic purging of peripheral blood stem cell harvests from breast carcinoma patients reduces tumor cell contamination while not affecting hematopoietic recovery.

BACKGROUND: Because tumor contamination of hematopoietic stem cell grafts may influence the outcome in breast carcinoma (BC) patients undergoing high dose chemotherapy (HDC), several ex vivo procedures for the purging of autologous harvests have been investigated. The authors studied the presence of epithelial tumor cells and the growth of hematopoietic progenitors in peripheral blood stem cell (PBSC) collections from patients with metastatic breast carcinoma before and after a purging procedure performed by a negative immunomagnetic BC cell separation. METHODS: Eighteen patients entered the study. Tumor contamination was assessed by conventional immunocytochemistry (ICC) and by a liquid culture assay developed in the study laboratory. Committed and more primitive hematopoietic progenitors were quantitated before and after the negative selection. Ten patients received HDC with purged PBSC support. RESULTS: Before purging, 4 of 18 PBSC collections were found to be contaminated by liquid culture; among these samples, only 1 was positive by ICC. Three of the four positive collections, including the ICC positive sample, became negative after immunomagnetic selection whereas BC cells still were present after the procedure in one harvest. A high recovery of both primitive and mature hematopoietic progenitors was found after the purging procedure. Patients receiving purged PBSC after myeloablation had a prompt and complete hematopoietic reconstitution, and no graft failure was observed at a median follow-up of 1 year. CONCLUSIONS: The preliminary results of the current study suggest that negative selection of BC cells is able to purge PBSC effectively while having no apparent affect on hematopoietic progenitor recovery in vitro and in vivo.

Adult↗

Shuttle-box avoidance learning in mice: improvement by glucose combined with stimulant drugs.

Glucose was tested alone or in combination with two stimulant drugs, amphetamine and nicotine, in mice of the CD-1 strain subjected to five daily shuttle-box training sessions. Pretraining intraperitoneal administration of glucose (50 or 100 mg/kg) had no effect, while amphetamine and nicotine, given alone, significantly improved avoidance acquisition at a dose of 0.5 mg/kg, but not 0.025 mg/kg. Significant improvement of avoidance learning was also produced by a combination of glucose with the lower dose of amphetamine or nicotine. This enhancing action, produced by a combination of glucose and stimulant drugs, at doses ineffective by themselves, might be due to a concomitant cholinergic and dopaminergic activation, induced by glucose and stimulant drugs, respectively.

Animals↗

An open trial of paroxetine in the treatment of children and adolescents diagnosed with dysthymia.

This open-label study examined the potential efficacy of paroxetine in the treatment of children and adolescents diagnosed with dysthymia over a period of 3 months. Seven subjects were evaluated by the Hamilton Depression Rating Scale (HAM-D), by the Clinical Global Impression Severity of Illness Scale (CGI-S), and the Clinical Global Impression Improvement Scale (CGI-I). Seventy-one percent of patients had a satisfactory response, suggesting the efficacy of paroxetine in children with dysthymia.

Adolescent↗

[Significance of ultrasonography in the diagnosis of appendicitis].

AIM: The authors aim to evaluate the sensitivity and specificity of abdominal ultrasonography in 183 in-patients (113 females--70 males), aged between 3 and 78 years old, in the General Surgery department of Pugliese Hospital in Catanzaro, for abdominal pain and possible acute appendicitis, using a retrospective study. All patients underwent ultrasonography at the Division of Radiology in the same hospital. METHODS: The technique used was graded-compression US (useful to eliminate gas artifacts and to reduce the distance from the appendix) using a linear transducer between 3.5 and 7.5 MHz. The method lasted an average of 15 minutes and was performed by specially trained radiologists. The transducer was held between the forefinger and thumb and pushed into the abdomen using both palms, as if palpating the abdomen. When compression is applied slowly and gently, the pain is surprisingly well tolerated by the patient. The radiologist records whether the inflamed appendix is visualised ultrasonographically and with what degree of certainty, and whether perforations or the formation of abscesses and other pathological processes can be seen. In this case, clinical diagnosis was confirmed by radiological imaging and eventually by surgical evidence. RESULTS: Of the 183 patients examined, 135 showed positive US findings, 11 refused surgery and pain was resolved by pharmacological treatment, and 9 presented other pathologies (3 gastric ulcers, 4 acute cholecystitis and 2 extrauterine pregnancies). Therefore, 115 patients were effectively positive. Of the 183 patients, 48 were negative but of these, only 39 were effectively negative because 3 were false negatives and 6 revealed other pathologies when examined using other methods of diagnosis. Even if the diagnosis of appendicitis was confirmed by clinical examination in most cases, US is of value both to confirm the clinical diagnosis and to rule out any complications. In this particular case it was also useful for the surgeon as a means of locating the position of the appendix. Even if this method is partly conditioned by the patient's clinical conditions, the results were excellent. CONCLUSIONS: The authors conclude that US of the appendix is a valuable aid in the diagnosis of appendicitis, especially in the case of acute or subacute forms in which other radiological imaging might worsen the pathology and lead to the onset of further complications. US offers undeniable advantages using a non-invasive, low cost technique with a specificity of around 80% and sensitivity between 85 and 93%. It also provides a means of identifying other sources of low abdominal pain. However, we still regard clinical examination as being essential for diagnosis.

Adolescent↗

Coexistence of two functioning T-cell repertoires in healthy ex-thalassemics bearing a persistent mixed chimerism years after bone marrow transplantation.

Bone marrow transplantation (BMT) from an HLA-identical donor is an established therapy to cure homozygous beta-thalassemia. Approximately 10% of thalassemic patients developed a persistent mixed chimerism (PMC) after BMT characterized by stable coexistence of host and donor cells in all hematopoietic compartments. Interestingly, in the erythrocytic lineage, close to normal levels of hemoglobin can be observed in the absence of complete donor engraftment. In the lymphocytic lineage, the striking feature is the coexistence of immune cells. This implies a state of tolerance or anergy, raising the issue of immunocompetence of the host. To understand the state of the T cells in PMC, repertoire analysis and functional studies were performed on cells from 3 ex-thalassemics. Repertoire analysis showed a profound skewing. This was due to an expansion of some T cells and not to a collapse of the repertoire, because phytohemagglutinin stimulation showed the presence of a complex repertoire. The immunocompetence of the chimeric immune systems was further established by showing responses to alloantigens and recall antigens in vitro. Both host and donor lymphocytes were observed in the cultures. These data suggest that the expanded T cells play a role in specific tolerance while allowing a normal immune status in these patients.

Adolescent↗

Magma intrusion beneath long valley caldera confirmed by temporal changes in gravity

Precise relative gravity measurements conducted in Long Valley (California) in 1982 and 1998 reveal a decrease in gravity of as much as -107 +/- 6 microgals (1 microgal = 10(-8) meters per square second) centered on the uplifting resurgent dome. A positive residual gravity change of up to 64 +/- 15 microgals was found after correcting for the effects of uplift and water table fluctuations. Assuming a point source of intrusion, the density of the intruding material is 2.7 x 10(3) to 4.1 x 10(3) kilograms per cubic meter at 95 percent confidence. The gravity results require intrusion of silicate magma and exclude in situ thermal expansion or pressurization of the hydrothermal system as the cause of uplift and seismicity.

Journal Article↗

A psychometric-genetic study of schizotypal disorder.

This study aimed to clarify the structure and the etiological constituents of schizotypal disorder (SPD) by directly interviewing pairs of twins. A latent class analysis was applied to each individual's outcome for specified SPD items, such that each subject's phenotype could be redefined in terms of individual probabilities of class membership. Intraclass correlations were then calculated for each twin pair, and a standard univariate twin model applied. The best latent class analysis solution encompassed a model with four latent classes (three latent classes of SPD subjects, one of non-SPD). The intraclass correlations revealed a moderate to high heritability for two out of three SPD classes and for the modal class (a class composed of subjects that possessed a conditional probability of belonging to any of the SPD classes). Model fittings revealed considerable variation in the extent to which the different classes of SPD were influenced by additive genetic constituents or non-genetic factors. Although these data confirm the importance of genetic contributors in determining liability to SPD and the schizophrenia spectrum, they indicate that there is a relationship between psychometric multidimensionality and etiological heterogeneity in SPD.

Adult↗

First-cycle REM density in never-depressed subjects with borderline personality disorder.

BACKGROUND: There is much interest in the identification of polysomnographic markers of liability to the mood disorders that may predate the onset of illness in high-risk subjects, and/or remain altered after remission. One such putative marker is rapid eye movement (REM) density during the first REM period. METHODS: Never-depressed subjects with borderline personality disorder (BPD) as a group at high risk for the mood disorders were compared by continuous 48-hour ambulatory electroencephalographic monitoring to age- and gender-matched controls. RESULTS: Subjects with BPD had significantly higher REM density during the first REM period. One man with BPD who later committed suicide had REM density values exceeding the mean value of his group by 2 SD. CONCLUSIONS: These data extend the view that REM density in the first REM period can be a marker of liability to the mood disorders, as it is present in a group of young subjects at heightened risk for depression.

Adult↗

Attenuation by nimodipine of amitriptyline-induced avoidance impairment in mice.

The effects of the dihydropyridine calcium channel blocker nimodipine on avoidance impairment induced by the tricyclic antidepressant amitriptyline were assessed during shuttle-box training and in previously trained mice of the DBA/2 strain. Nimodipine (0, 0.5, 1, 2.5, or 5 mg/kg) had no effect alone, but attenuated the avoidance impairment induced by 5 mg/kg amitriptyline on avoidance acquisition, as well as on a previously learned avoidance response. The avoidance improving action of the calcium channel blocker was less evident in mice receiving a larger dose (7.5 mg/kg) of the antidepressant drug. The effect of nimodipine did not appear to be specifically related to the avoidance impairment induced by amitriptyline, because the calcium antagonist also attenuated the avoidance impairing action of the neuroleptic chlorpromazine. The avoidance impairment induced by amitriptyline and chlorpromazine, and the related ameliorating action of nimodipine, seem imputable to drug effects on the performance of the avoidance response, rather than to interferences with learning processes. The results suggest that, in the case of concomitant administration, nimodipine could alleviate adverse side effects of tricyclic antidepressant, i.e., psychomotor disturbances.

Amitriptyline↗

Effects of serotonin transporter promoter genotype on platelet serotonin transporter functionality in depressed children and adolescents.

OBJECTIVE: To investigate possible associations between serotonin transporter (5-HTT) promoter genotypic variants (l/l, l/s, and s/s) and differential regulation of platelet 5-HTT functionality parameters in a group of drug-naive depressed children and adolescents and healthy controls. METHOD: Children and adolescents with major depression (n = 18) defined by DSM-III-R criteria and normal controls (n = 21) were assessed both for platelet serotonin functionality and for genotypic variants on 5-HTT promoter region. Four parameters were considered: (1) serotonin uptake rate (Vmax); (2) serotonin dissociation constant (K(m)); (3) paroxetine binding and density of site (Bmax); and (4) paroxetine dissociation constant (Kd). RESULTS: Depressed children had lower Vmax and K(m). Control subjects with l/l genotype had significantly higher Vmax than control subjects with l/s and s/s genotype. Control subjects with l/l genotype also had significantly higher Vmax than their depressed homologs. In contrast, Vmax was not significantly different between depressed and nondepressed subjects who carried the other 2 genotypes. The 5-HTT promoter genotype, diagnoses, or their interaction had no effect on the other serotonin parameters. CONCLUSIONS: While showing a significant decrease of Vmax and K(m) in a group of drug-naive depressed children and adolescents, these data suggest that l/l genotype has a substantial effect on the decrease of Vmax during a depressive episode.

Adolescent↗

Bicalutamide monotherapy versus flutamide plus goserelin in prostate cancer patients: results of an Italian Prostate Cancer Project study.

PURPOSE: To compare the efficacy of bicalutamide monotherapy to maximal androgen blockade (MAB) in the treatment of advanced prostatic cancer. PATIENTS AND METHODS: Previously untreated patients with histologically proven stage C or D disease (American Urological Association Staging System) were randomly allocated to receive either bicalutamide or MAB. After disease progression, patients treated with bicalutamide were assigned to castration. The primary end point for this trial was overall survival. Secondary end points included response to treatment, disease progression, treatment safety, quality-of-life (QOL), and sexual function. RESULTS: A total of 108 patients received bicalutamide and 112 received MAB. There was no difference in the percentage of patients whose prostate-specific antigen returned to normal levels. At the time of the present analysis (median follow-up time, 38 months; range, 1 to 60 months), 129 patients progressed and 89 died. There was no difference in the duration of either progression-free survival or overall survival. However, a survival trend favored bicalutamide in stage C disease but MAB in stage D disease. Overall and subgroup trends were confirmed by multivariate analysis. Serious adverse events and treatment discontinuations were more common in patients receiving MAB (P =.08 and P =.04, respectively). Fewer patients in the bicalutamide group complained of loss of libido (P =. 01) and of erectile dysfunction (P =.002). Significant trends favored bicalutamide-treated patients also with respect to their QOL, namely relative to social functioning, vitality, emotional well-being, and physical capacity. CONCLUSION: Bicalutamide monotherapy yielded comparable results relative to standard treatment with MAB, induced fewer side effects, and produced a better QOL.

Adult↗

The Iowa Personality Disorder Screen: development and preliminary validation of a brief screening interview.

The length and expense of comprehensive personality disorder interviews makes them unwieldy for routine use. A brief but sensitive screen could eliminate administration of longer instruments in many instances. We describe the development of the Iowa Personality Disorder Screen (IPDS)--a mini-structured interview which can be completed in less than 5 minutes. Retrospective analyses using 1,203 SIDP-R interviews suggested that the IPDS items should provide good sensitivity and specificity. We present results from a prospective validation study, using a mixed group of 52 nonpsychotic inpatients and outpatients who were diagnosed using the SIDP-IV. Blind administration of the IPDS yielded excellent sensitivity (92%) and good specificity (79%), using a subset of five screening items. Addition of two more items leads to an estimated sensitivity of 79% and specificity of 86%. The IPDS shows promise as a quick personality disorder screen for use in research settings or standard clinical interviews.

Adult↗

[Role of ultrasonography in the control of patients receiving perioperative total parenteral nutrition].

BACKGROUND: On the basis of personal experience and literature, this study has been carried out in order to clarify the impact of ultrasonography on the diagnosis and prevention of hepatobiliary complications Total Parenteral Nutrition (TPN)-related. METHODS: Between April 1995-April 1997 in the Department of General Surgery-University of Catanzaro, 18 adult patients submitted to major thoracic or abdominal surgery, underwent to TPN for perioperative time (range: 9-55 days). In these patients ultrasonography was performed at pre-established days in pre- and postoperative time in order to diagnose precociously the possibility of hepatobiliary complications. RESULTS: Ultrasonography showed: 3 cases of hepatic steatosis, 5 cases of steatosis and gallbladder biliary sludge, 2 cases of gallbladder biliary sludge alone, 1 case of gallbladder biliary sludge with microlithiasis, 1 case of acute acalculous cholecystitis. The other 6 patients presented only little laboratory tests alterations, but normal ultrasonographic findings. CONCLUSIONS: Therefore it is underlined the importance of systematic ultrasonographic follow-up of patients on TPN as a non invasive method in the early diagnosis of hepatobiliary complications TPN-related. The good compliance of the patients to this instrumental investigation and the not excessive increase of their management's costs are also underlined.

Adult↗

Shuttle-box avoidance learning in mice: improvement by combined glucose and tacrine.

Glucose and the acetylcholinesterase inhibitor tacrine were tested, alone and in combination, in mice of the CD-1 strain subjected to five daily shuttle-box training sessions. Pretraining intraperitoneal administration of glucose alone (50-400 mg/kg) had no significant effect, while tacrine alone (0.5-3 mg/kg) improved avoidance acquisition at the dose of 2 mg/kg only. Significant avoidance learning improvements were instead produced by 50 or 100 mg/kg glucose combined with 0.5 or 1 mg/kg tacrine. The effects on shuttle-box avoidance acquisition produced by glucose combined with a cholinomimetic agent support the hypothesis that cholinergic mechanisms may be involved in the action of glucose on learning and memory. However, the main finding of the present study is related to the enhancement by glucose of the learning improving action of a drug clinically used as cognitive enhancer.

Animals↗

Epithelial tumour cell detection and the unsolved problems of nested RT-PCR: a new sensitive one step method without false positive results.

Sensitive detection of circulating epithelial cancer cells might have important therapeutic and prognostic implications in patients with breast cancer (BC) receiving high-dose chemotherapy and PBSC support. We have compared the specificity and sensitivity of the recently developed 'one tube' reverse transcriptase PCR (RT-PCR) assay with the more widely used nested RT-PCR method for detection of cytokeratin 19 (CK19)-positive cells. The analysis of 30 control samples provides evidence that one tube RT-PCR is highly specific in contrast to the nested method which showed 23% false positive results. The sensitivity of both techniques to detect tumour contamination was 10(-6). PBSC harvests from 45 BC patients were tested with both RT-PCR methods and the results were compared with immunocytochemistry (ICC). The five samples found positive by ICC were also positive by one tube RT-PCR; in addition, 11 more samples were positive by one tube RT-PCR analysis. The greater number of PBSC found positive by one tube RT-PCR might be due to the larger number of cells analysed. We conclude that one tube RT-PCR is sensitive and reveals no false positive results. This method is less time consuming than the nested one, technically simpler and should be considered for tumour cell detection.

Biomarkers, Tumor↗

Anticipation of age at onset in panic disorder.

OBJECTIVE: Anticipation (i.e., the decrease in age at onset or the increase in severity of a disorder in successive generations) has recently been reappraised as a key to understanding the genetics of some familial illnesses. The purpose of this study was to search for possible anticipation in panic disorder. METHOD: Thirty-eight unilineal, multigenerational families with multiple directly interviewed members who had panic disorder were compared across two successive generations for 1) age at the first panic attack, 2) age at the onset of panic disorder, and 3) the highest degree of agoraphobia ever experienced, as a tentative index of severity of illness. Intergenerational pairwise comparisons were implemented according to four different sampling schemes: random pairs, random transmitting pairs, all possible pairs, and all possible transmitting pairs. RESULTS: Life table analyses showed a significant decrease in the time before the first episode of panic and onset of panic disorder from the older to the younger generation. Evidence for anticipation was found for both indexes of onset in all four sampling schemes. No evidence of a generational effect on the index of severity of agoraphobia was found. Corrections for possible biases suggested that these results are not likely to be simple artifacts. CONCLUSIONS: Anticipation is supported in this specific set of families and, if it is confirmed by other studies, a role for trinucleotide repeat sequences may be considered to account for the familial aggregation of panic disorder.

Adolescent↗