Biomedical subjects

P Costa

Publications and source records attributed to P Costa.

At least 73 records · Page 4Linked to original sources

PubMed1998

[The solitary pulmonary nodule. A retrospective study of 119 cases].

The authors review 119 cases of solitary pulmonary nodule submitted to surgery, analysing their aetiology and correlating them with their clinical and radiological aspects as well as with the patient's age, sex and smoking habits. An analysis of some pre-surgical diagnostic methods was also made. In half of the nodules (54%) the diagnosis made was of malignancy. Some of these (8%) were pulmonary metastases. There was no sex preference in the distribution of malignant or benign lesions. The average diameter of malignant nodules was 2.8 +/- 10.9 cm and benign nodules 2.1 +/- 10.9 cm. The large majority of malignant lesions was found in both upper lobes, whilst benign lesions did not have a preferential location. Adenocarcinomas were the most common primary lung tumours found, (59%), followed by squamous (27%) and neuroendocrine tumours (12.5%). Most benign nodules were benign neoplasias (43%--hamartomatous tumours) or of infectious aetiology (mostly granulomatous chronic disease--39%). The evaluation of the imagiological criteria of benignity or malignancy resulted in a sensitivity of 67% and specificity of 76%. In this study, negative respiratory cytology and bronchofibroscopic biopsies were not particularly helpful in excluding malignancy. This study confirms results published by other authors, in concluding that larger nodules have a greater probability of malignancy, that these are more frequent in males with smoking habits, and that they predominate in the upper lobes.

Adult↗

PubMed1998

Sacral reflex latency correlated by age and sex.

This prospective study was undertaken on 190 subjects who had no prior central or peripheral nerve supply pathology and where the value of the sacral reflex latency was compared by age and sex in order to determine precise norms. There were 90 men whose age averaged 56.9 +/- 13 years and 100 women with an average age of 54 +/- 13.1. The reflex was obtained by stimulating the dorsal nerve of the penis and the clitoris and taking a reading in the intermediate part of the external anal sphincter muscle. An averaging technique was used (over 30 stimulation occurrences). The average intensity of the stimulation was 15 mA. The value of the stimulus reaction latency taken at the positive peak was analyzed statistically. The average value was 37.6 +/- 5.36 ms in male subjects and 46.6 +/- 8.08 in female subjects. In men, values varied from 36.6 +/- 4.26 ms at under 35 years of age and reached 42 +/- 3.52 ms at over 75 years. In women, values varied from 37.33 +/- 7.69 ms at under 35 years to 55.6 +/- 4.39 ms at over 75 years of age. In a previous article we discussed ageing features in nerves and muscles. These features are largely responsible for the occurrence of static pelvic problems. The purpose of this study is to compare the sacral reflex latency by sex and age in normal subjects.

Adult↗

PubMed1998

[Treatment of stress urinary incontinence in women: rehabilitation or surgery?].

Considerable progress has been made in the treatment of female urinary incontinence over the last 20 years, affecting both surgical treatment, by the introduction, apart from reference techniques, of so-called "minimal" techniques, which allow an extension of the indications to elderly patients, and medical treatment, but also due to the introduction of increasingly better defined retraining techniques. A better understanding of the pathophysiology of incontinence and the growth of urodynamic techniques allow a better analysis of the mechanisms responsible for incontinence, which is often multifactorial. The prevalence of female urinary incontinence also gives this disease a considerable economic significance. Surgery is therefore no longer currently the only treatment that can be proposed to the patient. The respective indications for retraining and surgery need to be discussed, bearing in mind that, schematically, the 2-year results of surgery achieve 80 to 85% of cure with a more marked erosion over time when the initial repair was less solid, and retraining cures approximately 30% of women and improves another 30%.

Aged↗

PubMed1997

Close phenotypic and functional similarities between human and murine alphabeta T cells expressing invariant TCR alpha-chains.

Several studies have demonstrated the existence of a murine NK1.1+ alphabeta T cell subset expressing V alpha14+ TCR alpha-chains with highly conserved invariant junctional sequences and able to secrete Th2 cytokines when exposed to CD1+ stimulator cells. In humans, alphabeta T cells carrying invariant V alpha24+ TCR alpha-chains highly homologous to those expressed by murine NK1.1 cells have been recently described. Here we show that these cells (referred to as V alpha24inv T cells) and murine NK1.1+ alphabeta T cells resemble each other in several ways. First, like their murine counterparts, T cells expressing high levels of V alpha24inv TCRs can be either CD4- CD8- double negative (DN) or CD4+, but they never express heterodimeric CD8 molecules. Second, most V alpha24inv T cells are brightly stained by NKRP1-specific mAb but not by mAb directed against other type II transmembrane proteins of the NK complex. Third, DN and particularly CD4+ V alpha24inv T cells are greatly enriched for IL-4 producers. The concomitant expression of highly conserved TCRs of a particular set of NK markers and of Th2 cytokines in human and murine alphabeta T cells suggests a coordinate acquisition of these phenotypic and functional properties. Furthermore, the relatively high frequency of human V alpha24inv T cells, which are presently shown to represent on average 1/500 PBL, and the high interindividual variations of the size of this cell subset under physiologic conditions go for a major role played by alphabeta T cells carrying invariant TCR in a large array of immune responses.

Animals↗

PubMed1997

Ciliary neurotrophic factor corrects obesity and diabetes associated with leptin deficiency and resistance.

Receptor subunits for the neurocytokine ciliary neurotrophic factor (CNTF) share sequence similarity with the receptor for leptin, an adipocyte-derived cytokine involved in body weight homeostasis. We report here that CNTF and leptin activate a similar pattern of STAT factors in neuronal cells, and that mRNAs for CNTF receptor subunits, similarly to the mRNA of leptin receptor, are localized in mouse hypothalamic nuclei involved in the regulation of energy balance. Systemic administration of CNTF or leptin led to rapid induction of the tis-11 primary response gene in the arcuate nucleus, suggesting that both cytokines can signal to hypothalamic satiety centers. Consistent with this idea, CNTF treatment of ob/ob mice, which lack functional leptin, was found to reduce the adiposity, hyperphagia, and hyperinsulinemia associated with leptin deficiency. Unlike leptin, CNTF also reduced obesity-related phenotypes in db/db mice, which lack functional leptin receptor, and in mice with diet-induced obesity, which are partially resistant to the actions of leptin. The identification of a cytokine-mediated anti-obesity mechanism that acts independently of the leptin system may help to develop strategies for the treatment of obesity associated with leptin resistance.

Animals↗

PubMed1997

NKRP1A molecule is involved in transendothelial migration of CD4+ human T lymphocytes.

Among human CD4+ T lymphocytes, 5-20% express the C-type lectin molecule NKRP1A. Interestingly, CD4+ NKRP1A+ T lymphocytes express high levels of beta 1 and beta 2 integrins, thus representing a T lymphocyte subset that can possibly adhere and migrate through vascular endothelium. Indeed, resting CD4+ NKRP1A+ lymphocytes, differently from the CD4+ NKRP1A- subset, migrated across endothelial cell monolayers in a Transwell chamber system. This transendothelial migration was strongly reduced after pre-treatment with an anti-NKRP1A monoclonal antibody (mAb). In addition, the NKRP1A negative Jurkatt CD4+ T-cell line that had been stably transfected with NKRP1A cDNA, migrated more rapidly and efficiently than untransfected Jurkatt cells. Finally, mAb-mediated cross-linking of NKRP1A molecule in CD4+ T lymphocytes induced the upregulation of the LFA1 Mg2+ binding site as well as beta 1 and beta 2 integrin chains. Altogether, these findings indicate that NKRP1A molecule is involved in transendothelial migration of resting CD4+ T lymphocytes.

Antigens, Surface↗

PubMed1997

Association of a polymorphism in intron 13 of the monoamine oxidase B gene with Parkinson disease.

Monoamine oxidase B (MAO-B) is an enzyme that has relevance for Parkinson disease (PD) because of its roles in catabolizing dopamine and potentially activating exogenous neurotoxicants. A polymorphism of the gene encoding MAO-B has been identified as a single base change (A or G) in intron 13 of the X chromosome. The A allele was previously associated with an approximately twofold risk of PD. The present study compared A and G allele frequencies between newly diagnosed idiopathic PD cases and a control group free of neurodegenerative diseases. All study subjects were Caucasian. Cases were 37 men and 25 women, age 37-80 years; controls were 50 men and 29 women, age 45-82 years. MAO-B genotype was determined by the allele-specific polymerase chain reaction on DNA extracted from peripheral lymphocytes. In complete contrast to previous studies, elevated risks were detected with the G allele. The age-adjusted odds ratio for the G allele in males was 1.87 ((95% confidence interval) 0.78-4.47). Among females the age-adjusted odds ratios were 5.00 ((95% confidence interval) 1.13-22.1) for the GA genotype and 5.60 ((95% confidence interval) 1.01-30.9) for the GG genotype. These findings, although of limited statistical precision, suggest that the G allele of this MAO-B polymorphism may relate to PD risk.

Adult↗

PubMed1997

Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I. A model for stunted growth in children with chronic inflammation.

Stunted growth is a major complication of chronic inflammation and recurrent infections in children. Systemic juvenile rheumatoid arthritis is a chronic inflammatory disorder characterized by markedly elevated circulating levels of IL-6 and stunted growth. In this study we found that NSE/hIL-6 transgenic mouse lines expressing high levels of circulating IL-6 since early after birth presented a reduced growth rate that led to mice 50-70% the size of nontransgenic littermates. Administration of a monoclonal antibody to the murine IL-6 receptor partially reverted the growth defect. In NSE/hIL-6 transgenic mice, circulating IGF-I levels were significantly lower than those of nontransgenic littermates; on the contrary, the distribution of growth hormone pituitary cells, as well as circulating growth hormone levels, were normal. Treatment of nontransgenic mice of the same strain with IL-6 resulted in a significant decrease in IGF-I levels. Moreover, in patients with systemic juvenile rheumatoid arthritis, circulating IL-6 levels were negatively correlated with IGF-I levels. Our findings suggest that IL-6-mediated decrease in IGF-I production represents a major mechanism by which chronic inflammation affects growth.

Adolescent↗

PubMed1997

Phenotypic and functional analysis of CD4+ NKRP1A+ human T lymphocytes. Direct evidence that the NKRP1A molecule is involved in transendothelial migration.

In this report, we show that among human CD4+ T lymphocytes 5-20% express the C-type lectin molecule NKRP1A. This lymphocyte subset displays a slightly more limited T cell receptor V beta repertoire than the CD4+ NKRP1A- counterpart. CD4+ NKRP1A+ T lymphocytes are characterized by a high expression of beta 1 and beta 2 integrins, thus representing a T lymphocyte subset that can possibly adhere and migrate through vascular endothelium. Indeed, resting CD4+ NKRP1A+ lymphocytes, differently from the CD4+ NKRP1A- subset, migrated across endothelial cell monolayers in a Transwell chamber system. Pretreatment of CD4+ NKRP1A+ T lymphocytes with an anti-NKRP1A monoclonal antibody (mAb) strongly reduced transendothelial migration, suggesting the involvement of the NKRP1A molecule in the transmigration process. Furthermore, cells of the NKRP1A- Jurkat CD4+ T cell line stably transfected with NKRP1A cDNA migrated more rapidly and efficiently than either untransfected or mock-transfected Jurkat cells. Finally, mAb-mediated cross-linking of NKRP1A molecules in CD4+ T lymphocytes induced the up-regulation of the lymphocyte function-associated antigen 1 Mg(2+)-binding site as well as beta 1 and beta 2 integrin chains. Altogether, these findings suggest that the NKRP1A molecule is involved in transendothelial migration of resting CD4+ T lymphocytes.

Antigens, Surface↗

PubMed1997

[Electrophysiologic studies in the descending perineum in women].

Seventy five female patients (mean age: 55 +/- 13 years) were included into the study. Electromyography of the perineum with study of the intramuscular activity of the external anal sphincter was done and measures of the sacral reflex latency were obtained by stimulation of the cavernous nerve of the clitoris, recording in the external anal sphincter muscle. Neurogenic syndromes of pudendal nerve either isolated or associated with muscular disorders have been shown to be correlated with descending perineum. In our study, we investigated whether a history of obstetrical or surgical interventions is related to the occurrence of this syndrome. We did not find any significant relationship.

Adult↗

PubMed1997

Induction of interleukin-6 (IL-6) autoantibodies through vaccination with an engineered IL-6 receptor antagonist.

Neutralization of cytokine activity by monoclonal antibodies or receptor antagonists is beneficial in the treatment of immune and neoplastic diseases, but the necessity for continuous parenteral delivery of these anticytokine agents poses considerable practical limitations. A viable alternative is to induce a neutralizing antibody response. Using transgenic mice with high circulating levels of human interleukin-6 (hIL-6), we show that injection of the hIL-6 receptor antagonist Sant1 (an IL-6 variant with seven amino-acid substitutions) induces a strong anti-hIL-6 antibody response. The elicited antibodies bind circulating hIL-6 with very high affinity, totally masking it, and neutralize hIL-6 bioactivity both in vitro and in vivo.

Aluminum Hydroxide↗

PubMed1997

p40 molecule regulates NK cell activation mediated by NK receptors for HLA class I antigens and TCR-mediated triggering of T lymphocytes.

p40 was previously described as a regulatory molecule capable of inhibiting both the natural and the CD16-mediated cytotoxicity of NK cells. In this study, we analyze the effect of p40 molecule engagement on the NK cell triggering induced by activating HLA class I-specific NK receptors (NKR) or on TCR alpha beta-mediated T cell activation. CD3-CD16+ NK cell clones expressing activating NKR (either CD94 or p50) were analyzed in a redirected killing assay using P815 target cells and appropriate mAb. A strong target cell lysis was detected in the presence of anti-NKR or anti-CD16 mAb alone. Addition of anti-p40 mAb resulted in a strong inhibition of both anti-NKR or anti-CD16 mAb-induced cytolysis. mAb specific for either CD45 or lymphocyte function associated antigen-1 did not exert any inhibitory effect in the same experimental system. Free intracellular calcium ([Ca2+]i) increase induced by mAb cross-linking of activating CD94 or p50 was inhibited by simultaneous engagement of p40 molecules, but not of other NK surface molecules including CD44 and CD56. In addition, cross-linking of p40 molecules strongly inhibited the CD94-induced tumor necrosis factor-alpha and IFN-gamma production. Analysis of TCR alpha beta or gamma delta T cell clones revealed that the engagement of p40 molecules, using specific mAb, induced some degree of inhibition only on anti-V beta (but not anti-V delta or anti-CD3) mAb-induced cytotoxicity. On the other hand, the p40 molecule engagement prevented T cell proliferation induced by either anti-V beta 8 or anti-V delta 2 mAb. A similar inhibitory effect was found on the IL-2-induced NK cell proliferation. Taken together, our present findings suggest that p40 may play a role in the regulation of NK and T lymphocyte activation and proliferation.

Calcium↗

PubMed1997

Early-onset benign occipital seizure susceptibility syndrome.

PURPOSE: Childhood epilepsy with occipital paroxysms (CEOP) is characterised by ictal visual hallucinations and occipital epileptiform activity on interictal EEG. A variant has been described with nonvisual symptoms including tonic head and eye deviation, vomiting, and episodes of partial status epilepticus. We fully documented the electroclinical features of such patients to determine whether classification separate from CEOP is justified. METHODS: This was a multicentre study with participating investigators submitting details of patients with idiopathic occipital seizures characterised by ictal head or eye deviation and vomiting. RESULTS: One hundred thirteen patients were recruited. Seizures began in early childhood (mean, 4.6 years) and occurred infrequently (mean total seizures, 3); 30% of patients had only a single seizure. Two thirds of seizures were nocturnal. Ictal eye deviation occurred in 79%, vomiting in 70%, and head deviation in 35%. Seizures were predominantly complex partial in type. Partial status epilepticus occurred in 44% of patients. Seventy-four percent of patients had occipital interictal EEG epileptiform activity, predominantly right sided, with fixation-off sensitivity. Extraoccipital EEG abnormalities occurred in 35% of patients. Prognosis was excellent: the mean duration of active seizures was 1 year. CONCLUSIONS: Although the two groups shared identical EEG features, the distinct clinical symptoms probably justify separate classification. Early-onset benign occipital seizure syndrome (EBOSS) is suggested as an appropriate name for the variant group.

Adolescent↗

PubMed1997

[Neuroendocrine tumor of the bladder apropos of a case. Review of the literature].

Neuroendocrine bladder tumours are exceptional, and the positive diagnosis is only established when they are already large and advanced. We report an original case in view of its small dimensions. We discuss the differential diagnosis (mainly bladder metastases from lung cancer) and pathological specificities, particularly the value of epithelial immunolabelling allowing exclusion of lymphoma. Because of the similarities with bronchial neuroendocrine tumours, the potential value of serum NSE assay should be emphasized. Combined surgery-cisplatin-based adjuvant chemotherapy is recommended.

Aged↗

PubMed1997

[Concomitant radiochemotherapy in invasive bladder tumors].

The treatment of muscle-invasive bladder tumors currently consists of radical cystectomy with lymph node dissection. A combined radio-chemotherapy treatment could allow to preserve a functional bladder without greater risk of relapse. We present a review of 38 available publications found in the international literature concerning this combination treatment. Only 9 publications with appropriate analysis were considered, including 552 evaluable patients, 44% of whom were suitable for radical cystectomy. Cisplatin is the most often used drug. The protocols are variable and generally well tolerated. The median follow-up time is 36 months. The immediate complete response rates vary between 48 and 92% and the overall survival rate is between 42 and 82%. The survival with bladder preservation is between 38 and 75%, while the disease-free survival with bladder preservation is between 33 and 53%. 11% of the initially complete responders had a superficial recurrence and 30% had distant metastases. There is no proven advantage of neoadjuvant polychemotherapy, there is no consensus for the therapeutical protocol, the follow-up protocol remains to be defined, and the function of the preserved bladder has to be studied. Only a prospective randomized trial could precise the role of this experimental technique compared to surgery despite the major evident difficulties (ethical and practical) to conduct such a trial.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Assessing the impact of urinary incontinence in a female population.

Urinary incontinence (UI) is a symptom. Patients seeking medical attention do so because of this symptom. As individuals' views of bothersomeness vary significantly, the objective degree of symptom severity is less important than the patient's overall outlook. Assessing well-being can be done by symptom evaluation, and general or condition-specific health-related quality of life questionnaire (HRQOL). Several studies using HRQOL questionnaires documented the negative effects of UI on the patient's well-being, especially on daily activities and psychological distress. Generalised HRQOL instruments can be used but they may lack sensitivity to the characteristics of incontinence and its impact. Recently condition-specific UI questionnaires have been developed for a better assessment of specific issues and a greater sensitivity to changes after treatments. They reveal a substantial impact on everyday life, but a poor correlation was observed between the objective and subjective measurements. More useful short-form versions have recently been developed that meet many of the needs of therapists.

Female↗

PubMed1997

Transrectal ultrasonography in prostatic cancer: interexaminer variability of interpretation.

OBJECTIVE: To compare the variability of transrectal ultrasonographic (TRUS) interpretation for the decision of performing biopsies and the lesions to biopsy. METHODS: We extracted at random from our videotape database 16 records of patients who had undergone biopsies, added 2 normal glands and duplicated 2 of these 18 records. Based on the records, 5 well-trained physicians had to describe the images on the tape, and to decide whether or not to biopsy the prostate. A kappa test was computed between each couple of readers, and for the whole group. The kappa test denotes the agreement between examiners. A value of kappa < 0.20 is considered poor to slight agreement, 0.2-0.40 is considered fair agreement. RESULTS: The agreement between the 5 readers was poor for the biopsy decision (kappa < 0.2) and the difficulty to read the records (kappa = 0.05). The results with the global kappa were similar with a highest value < 0.3. Most of the abnormalities were described in the peripheral zone. The global kappa for the seminal vesicles interpretation is poor, but better for the capsular penetration. CONCLUSION: TRUS has a poor informative value between different practitioners. This poor agreement between different practitioners must lead to more objective ultrasonographic methods.

Biopsy, Needle↗

PubMed1997

[Cervical factor in sterility: treatment with intravaginal estriol].

BACKGROUND: The aim of our study was to evaluate the efficacy and tolerability of vaginal estriol in treating the isolated cervical factor. METHODS: Three different groups of patients were selected at random on the basis of the administered therapy (estriol, ethinyl-estradiol, bromhexine associated with gonadotropins). The patients (thirty in all) came to the Autonomous Sterility Department of the Niguarda Ca' Granda Hospital in Milan during the November 1994-January 1996 period. The following parameters were evaluated: cervical score according to Insler, cervical pH; in vivo penetration test (PCT) at third and sixth cycle of treatment; evaluation of the hormonal profile during the ovulatory period of estriol, estradiol, LH and progesterone at the third and sixth cycles of treatment; any possible pregnancy. RESULTS: On the whole, 23 patients out of 30 (76.6%) had a positive in vivo penetration test. Particularly, a more favourable result was observed in the group to which vaginal estriol was administered as it presented, at treatment end, a positive PCT in 90% of cases. Moreover, always in the latter group, a greater percentage of pregnancies (40%) was observed. CONCLUSIONS: The obtained results have demonstrated that the drug we have studied can be recommended as a valid therapy for the treatment of the isolated cervical factor of sterility.

Administration, Topical↗