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Biomedical subjects

P Costa

Publications and source records attributed to P Costa.

At least 55 records · Page 3Linked to original sources
PubMed1999

Efficient and regulated erythropoietin production by naked DNA injection and muscle electroporation.

We show that an electric treatment in the form of high-frequency, low-voltage electric pulses can increase more than 100-fold the production and secretion of a recombinant protein from mouse skeletal muscle. Therapeutical erythopoietin (EPO) levels were achieved in mice with a single injection of as little as 1 microgram of plasmid DNA, and the increase in hematocrit after EPO production was stable and long-lasting. Pharmacological regulation through a tetracycline-inducible promoter allowed regulation of serum EPO and hematocrit levels. Tissue damage after stimulation was transient. The method described thus provides a potentially safe and low-cost treatment for serum protein deficiencies.

5' Untranslated Regions↗
PubMed1999

IL-12-mediated NKRP1A up-regulation and consequent enhancement of endothelial transmigration of V delta 2+ TCR gamma delta+ T lymphocytes from healthy donors and multiple sclerosis patients.

Gamma delta T lymphocytes are thought to play a role in the pathogenesis of multiple sclerosis (MS) contributing to demyelinization and fibrosis in the central nervous system. In this study, we show that, in MS patients with active disease, the percentage of circulating V delta 2+ gamma delta T cells coexpressing NKRP1A is significantly increased compared with healthy donors. V delta 2+ and V delta 1+ T cells were sorted from MS patients and healthy volunteers and cloned. At variance with V delta 1+ clones, all V delta 2+ clones expressed NKRP1A, which was strongly up-regulated upon culture with IL-12; this effect was neutralized by specific anti-IL-12 Abs. No up-regulation of NKRP1A by IL-12 was noted on V delta 1+ clones. RNase protection assay showed that IL-12R beta 2 subunit transcript was significantly less represented in V delta 1+ than V delta 2+ clones. This finding may explain the different effect exerted by IL-12 on these clones. In transendothelial migration assays, V delta 2+ NKRP1A+ clones migrated more effectively than V delta 1+ clones, and this migratory potential was enhanced following culture with IL-12. Migration was strongly inhibited by the F(ab')2 of an anti-NKRP1A Ab, suggesting that this lectin is involved in the migration process. We also show that, in freshly isolated PBMC from MS patients, the migrated population was enriched for V delta 2+ NKRP1A+ cells. We conclude that the expression of NKRP1A on V delta 2+ cells is associated with increased ability to migrate across the vascular endothelium and that this phenomenon may be regulated by IL-12 present in the microenvironment.

Adjuvants, Immunologic↗
PubMed1999

The relationship of anxiety and depression with self-reported knee pain in the community: data from the Baltimore Longitudinal Study of Aging.

OBJECTIVE: To investigate the relationship between anxiety and depression and reporting of knee pain in the community. METHODS: Subjects (n = 374) were community volunteers aged 40 years and above who are participants in the Baltimore Longitudinal Study of Aging, a prospective multidisciplinary research study of normative aging. Knee pain was defined by the First National Health and Nutrition Examination Survey question "have you ever had pain in or around your knee on most days for at least one month?"; anxiety and depression were measured by the relevant subscales of the Arthritis Impact Measurement Scales questionnaire. All subjects had standing anteroposterior radiographs, read for Kellgren and Lawrence (K + L) grade. RESULTS: After adjustment for age, women reporting "ever" knee pain had significantly higher anxiety scores than those reporting "never" pain (3.06 +/- 0.26 versus 2.35 +/- 0.17; P = 0.025). Pain reporting was related neither to anxiety scores in men, nor to depression in either sex. Analysis stratified by radiographic severity, adjusted for age and gender, showed that differences in anxiety were confined to those reporting knee pain in the absence of radiographic change (i.e., K + L grade 0). CONCLUSIONS: In the community, women reporting knee pain in the absence of radiographic osteoarthritis have higher anxiety scores than those without pain. Depression was not significantly related to knee pain in this population. Psychosocial factors may explain some of the discrepancy between reported knee pain and structural change as seen on x-ray.

Aged↗
PubMed1999

Randomized comparison of transurethral electroresection and holmium: YAG laser vaporization for symptomatic benign prostatic hyperplasia.

OBJECTIVE: To evaluate the safety and efficacy of holmium:YAG laser vaporization v transurethral electroresection (TURP) for benign prostatic hyperplasia. PATIENTS AND METHODS: Thirty-six patients were randomized. Two laser procedures (60 to 80 W) were performed for one TURP. Symptom Score, peak flow rate, potency, and ejaculation status were measured at baseline and at 1, 3, 6, and 12 months. RESULTS: The mean operative time was 75 minutes for laser and 56 minutes for TURP (P = 0.0407). With a mean laser energy delivered of 103.6 kJ, hemostasis was satisfactory during vaporization. The mean catheterization time was 1.7 and 2.1 days in the laser and TURP group, respectively. For the laser and TURP groups, the mean AUA Score improved from 20 preoperatively to 7 and from 24.1 to 5, respectively, at 12 months. The mean peak flow increased from 8.4 to 19.5 mL/sec and from 7.6 to 16.8 ml/sec, respectively, at 12 months. These results are not statistically different. No significant initial dysuria occurred. No significant difference between the groups appeared in potency or ejaculatory status during the follow-up. One patient in the laser group (Day 5) and two in the TURP group (2nd and 6th month) had to undergo a second procedure to relieve obstruction. CONCLUSION: Although taking slightly longer to accomplish, holmium:YAG laser vaporization of BPH provides early results very similar to those of TURP with a shorter catheterization time and no initial dysuria or pain.

Aged↗
PubMed1999

Systolic blood pressure within an intermediate range may reduce memory loss in an elderly hypertensive cohort.

The objective of this study was to determine if maintenance of systolic blood pressure (BP) within a high range or low range among treated hypertensive patients increases the risk of memory decline. Biennial neuropsychological evaluations were performed on 158 hypertensive subjects. Decline/year was measured on the Cued Selective Reminding test (total free recall and delayed recall) in three systolic BP groups (low-i.e., mean systolic BP during the follow-up period < 135 mm Hg; intermediate-i.e., 135 mm Hg < or = mean systolic BP < or = 150 mm Hg; high-i.e., mean systolic BP > 150 mm Hg). In total free recall, the three systolic BP groups had significantly different declines per year (P = .02), with patients in the high subgroup showing the greatest decline. In delayed recall, the three systolic BP groups also showed significantly different declines per year (P = .04), with patients in the low subgroup having the greatest decline. Chronically elevated systolic BP > 150 mm Hg is associated with accelerated memory decline compared to older treated hypertensive patients with systolic BP in an intermediate range. Chronically maintained systolic BP within a low normal range < 135 mm Hg in older treated hypertensive subjects may be associated with accelerated memory decline, specifically in a test of delayed memory recall, compared to patients with systolic BP in an intermediate range. Optimal regulation of systolic BP may be a potential modifiable risk factor to prevent or minimize memory loss in older hypertensive patients.

Aged↗
PubMed1999

[Autonomic nervous system and prostatic physiology. Specific features of the alpha-adrenergic system].

A better understanding of the rich autonomic innervation of the prostate allows more effective treatment of voiding disorders secondary to benign prostatic hyperplasia. The glandular contingent possesses mainly cholinergic innervation (M2 muscarinic receptors). Smooth muscle cells are richly supplied with alpha and beta catecholaminergic receptors, involved in muscle contraction and muscle relaxation, respectively, but they may also be involved in growth. These alpha receptors, divided into 2 families (alpha 1 and alpha 2), belong to the family of G protein-coupled seven membrane-spanning helix receptors. The genes, followed by the recombinant proteins of 3 subtypes of alpha 1 receptors have been described: alpha 1-a, -b, -d. In the prostate, these receptors are predominantly located in the stroma, mainly in the centroprostatic region. The mRNA present mainly code for the alpha 1a subtype. The use of specific agonists and antagonists shows that these receptors control smooth muscle contraction according to a mechanism initially considered to be of the alpha 1a type. However, their low affinity for prazosin and the development of new alpha 1 blocking agents is in favour of the involvement of a different functional subtype: alpha 1L. This difference could be explained by a different conformation of the receptor or by different coupling mechanisms. The subtype involved in prostatic smooth muscle contraction has yet to be characterized.

Autonomic Nervous System↗
PubMed1999

[Loco-regional block in ophthalmic surgery: single drug or drug combination with hyaluronidase? Randomized prospective study].

UNLABELLED: The aim of this study is the comparison between the use of bupivacaine alone and a mixture of bupivacaine, mepivacaine and hyaluronidase in both retrobulbar and peribulbar blockades for eye surgery. Three hundred ninety-nine consecutive adult patients scheduled for cataract surgery with regional anaesthesia were included in this prospective, randomized and partially blind study. Peribulbar blockade was performed on 199 patients (group P). Ninety-nine of them received a mixture of local anaesthetics and hyaluronidase (sub-group M), while 100 received bupivacaine alone (sub-group B). Retrobulbar blockade was performed on 200 patients (group R): 100 of them received the mixture with hyaluronidase (sub-group M), while 100 received bupivacaine (sub-group B). The interval between anaesthesia and motor blockade (onset time), the presence of residual ocular movements, the need of further anaesthesia, the quality of anaesthesia, the ocular tone, the length of anaesthesia and possible complications were registered. RESULTS: Retrobulbar blockade has the only advantage of a shorter onset time, while peribulbar blockade shows a longer anaesthetic effect. Mixture with hyaluronidase (the sub-group M) has a shorter onset time, a lesser need of further anaesthesia, fewer residual ocular movements and a better quality of anaesthesia. CONCLUSIONS: Local anaesthetics mixture with hyaluronidase associated with peribulbar blockade presents the advantages of rapidity, duration and better quality without the risks of retrobulbar blockade side effects.

Adult↗
PubMed1999

Rupture of Dacron aorto-femoral graft. Case report.

A 74-year-old patient was admitted to our department in a serious general condition due to massive bleeding. He had been treated 10 years previously in another hospital with an aorto-bifemoral bypass for obstructive disease using a knitted-Dacron graft. A large pulsating mass was present in the right iliac fossa as well as enormous pulsating enlargement of the scrotum. Echo color-Doppler investigation detected dilation up to 5 cm in diameter of the right branch of the graft and a large perigraft hematoma communicating with a similar mass in the scrotum. The patient was submitted to emergency surgery and a large rupture of the graft was found. The dilated segment was resected and replaced by a new 8 mm Dacron graft. Postoperative course was uneventful.

Aged↗
PubMed1998

Water-deficit-responsive proteins in maritime pine.

Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) was used to identify drought-responsive proteins during progressive water deprivation of two-year old maritime pine seedlings. Stress was applied by withholding water during vegetative growth. Needles were sampled before, during and after the stress. Out of about 1000 spots that were quantified by computer analysis, 38 responded during stress. Some proteins were accumulated while others were suppressed. One to three internal microsequences were obtained for 11 proteins, 10 of which were identified on the basis of sequence homologies. These proteins are quite diverse and are involved in photosynthesis, cell elongation, antioxidant metabolism and lignification.

Amino Acid Sequence↗
PubMed1998

Reversed-phase high-performance liquid chromatographic determination of enoxacin and 4-oxo-enoxacin in human plasma and prostatic tissue. Application to a pharmacokinetic study.

A simple high-performance liquid chromatographic method has been developed for the simultaneous determination of enoxacin and 4-oxo-enoxacin in plasma and prostatic tissue. The work-up procedure involves a liquid-liquid extraction step followed by isocratic chromatography on a reversed-phase analytical column, with ultraviolet absorbance detection (lambda = 340 nm). Using a mobile phase of 20.9% (v/v) acetonitrile buffer (pH 2.1), adequate retention time and separation among the analytes has been obtained using tetrabutylammonium hydroxide included in the eluent. Retention times are 5.2 min for enoxacin, 6.8 min for pefloxacin and 12 min for 4-oxo-enoxacin. For plasma and prostatic tissue, the precision of the assay was below 9%. The percent recovery from the nominal values for accuracy ranged from 94 to 108%. The limits of quantitation were 20 ng/ml for plasma and 50 ng/g for tissue (precision < 18%). The detection limits were 10 ng/ml and 25 ng/g, respectively. The calibration curves were linear from 20 to 1000 ng/ml for plasma and from 50 to 2500 ng/g for tissue. In plasma, the extraction recoveries averaged 52% for enoxacin and 63% for 4-oxo-enoxacin. In prostatic tissue, they were 57 and 76% for the two analytes, respectively. This method has been employed for the determination of enoxacin and 4-oxo-enoxacin in plasma and prostatic tissue samples from patients following repeated oral administration of enoxacin (400 mg twice a day for four days).

Adenoma↗
PubMed1998

Interleukin 6 is required for the development of collagen-induced arthritis.

Interleukin-6 (IL-6) is overproduced in the joints of patients with rheumatoid arthritis (RA) and, based on its multiple stimulatory effects on cells of the immune system and on vascular endothelia, osteoclasts, and synovial fibroblasts, is believed to participate in the development and clinical manifestations of this disease. In this study we have analysed the effect of ablating cytokine production in two mouse models of arthritis: collagen-induced arthritis (CIA) in DBA/1J mice and the inflammatory polyarthritis of tumor necrosis factor alpha (TNF-alpha) transgenic mice. IL-6 was ablated by intercrossing an IL-6 null mutation into both arthritis-susceptible genetic backgrounds and disease development was monitored by measuring clinical, histological, and biochemical parameters. Two opposite responses were observed; while arthritis in TNF-alpha transgenic mice was not affected by inactivation of the IL-6 gene, DBA/1J, IL-6(-/-) mice were completely protected from CIA, accompanied by a reduced antibody response to type II collagen and the absence of inflammatory cells and tissue damage in knee joints. These results are discussed in the light of the present knowledge of cytokine networks in chronic inflammatory disorders and suggest that IL-6 receptor antagonists might be beneficial for the treatment of RA.

Animals↗
PubMed1998

Neurohormonal stimulation of histamine release from neuroendocrine cells of the human adenomatous prostate.

BACKGROUND: Neuroendocrine cells (NE) constitute a population of highly specialized cells in prostatic glands; histamine has never been described in these cells. This article shows the presence and the regulation of release of histamine in NE. METHODS: In 21 prostatic adenomas, NE were identified by specific antisera against neuroendocrine markers (chromogranin-A, synaptophysin), histamine, and histidine decarboxylase (HDC); a rate HDC-cDNA probe was used to detect this enzyme by in situ hybridization. RESULTS: Immunoreactive cells for chromogranin-A, histamine, and HDC were found among luminal epithelial glandular cells. Similar cells were also labeled with the HDC-cDNA probe. Glandular cells, isolated from prostatic adenomas, were shown to contain histamine (7-40 pmol/mg cellular protein). L(-) norepinephrine causes a time-dependent (t1/2 = 22 min) histamine release; the alpha 1-receptor antagonists WB-4101 and YM-617 specifically inhibited this release, in agreement with a mediation by alpha 1-adrenoreceptor subtype. CONCLUSIONS: There is some evidence for the presence in prostatic adenomas of histamine-forming cells of neuroendocrine type; histamine release from these cells is under the control of alpha 1-adrenoreceptor subtype.

Adrenergic alpha-Agonists↗
PubMed1998

IL-12-induced up-regulation of NKRP1A expression in human NK cells and consequent NKRP1A-mediated down-regulation of NK cell activation.

IL-12, in contrast to IL-2, strongly up-regulated the expression of the NKRP1A lectin molecule on human NK cells. This effect appeared to be specific for NKRP1A as the expression of other functional NK cell surface molecules such as CD16 and different killer inhibitory receptors (KIR) including CD158a and CD158b, p70 and p140 were not affected by culture in IL-12. In addition, we found that polyclonal or clonal NK cell populations derived in the presence of IL-2 displayed an increased expression of NKRP1A after culture in IL-12. The IL-12-induced NKRP1A expression was time and dose dependent, reaching a maximum by 7 days of culture in the presence of 2 ng/ml IL-12 and it was inhibited by the addition of anti-IL-12 monoclonal antibody. The IL-12-dependent NKRP1A up-regulation was abrogated by the incubation of NK cells with actinomycin D, thus suggesting that IL-12 induces de novo transcription of NKRP1A mRNA. Functional analysis revealed that the engagement of the NKRP1A molecule in IL-12- but not in IL-2-cultured NK cells leads to a strong inhibition of the cytolytic activity induced by cross-linking of CD16 or p46, a recently described NK cell-specific triggering surface molecule. Our findings suggest that IL-12 up-regulates the expression of NKRP1A which, in turn, can regulate NK cell activation induced via different triggering pathways. This would imply that NKRP1A-mediated functions may be regulatd by the cytokine microenvironment that NK cells may encounter at inflammatory sites.

Antigens, Surface↗
PubMed1998

Double-blind multicenter study comparing alprostadil alpha-cyclodextrin with moxisylyte chlorhydrate in patients with chronic erectile dysfunction.

PURPOSE: We compared the efficacy and safety of alprostadil alpha-cyclodextrin and moxisylyte chlorhydrate to induce erections adequate for sexual intercourse in a prospective, randomized, parallel double-blind study in patients with erectile dysfunction. MATERIALS AND METHODS: A total of 156 men with erectile dysfunction due to organic, nonorganic and mixed origin was randomized into 2 parallel treatment groups receiving titrations of an individual optimum dose of alprostadil alpha-cyclodextrin or moxisylyte chlorhydrate. Erectile response was measured by the buckling test. A positive test was associated with axial erection rigidity that did not buckle/deform to 1.0 kg. load. The buckling test was repeated every 10 minutes for up to 60 minutes. RESULTS: A total of 56 patients (75%) in the alprostadil alpha-cyclodextrin group and 32 patients (40%) in the moxisylyte chlorhydrate group responded with at least 1 positive buckling test during the office period. Investigators assessed erections after alprostadil alpha-cyclodextrin to be adequate for sexual intercourse in 61 patients (81%) compared to 37 patients (46%) after moxisylyte chlorhydrate. All efficacy parameters in office reached statistical significance of p < 0.001 in favor of alprostadil alpha-cyclodextrin. During self-injection therapy at home 58 patients (85%) reported at least 1 rigid erection after alprostadil alpha-cyclodextrin compared to 37 patients (61%) after moxisylyte chlorhydrate. Patient and partner opinion of treatment achieved statistically significantly better scores in the alprostadil alpha-cyclodextrin group compared to the moxisylyte chlorhydrate group. CONCLUSIONS: Alprostadil alpha-cyclodextrin is significantly more effective than moxisylyte chlorhydrate in producing full penile rigidity in office and at home. Injection related side effects occur with the same frequency but moxisylyte results in more systemic side effects and alprostadil results in more painful and prolonged erections. Patients and partners are significantly more satisfied with alprostadil alpha-cyclodextrin.

Adrenergic alpha-Antagonists↗
PubMed1998

Artificial urinary sphincter AMS 800 for urinary incontinence after radical prostatectomy: the French experience.

Post-radical prostatectomy urinary incontinence (PRP-UI) has a major negative impact on the patient's quality of life with the incidence accounting for over 30% on a patient questionnaire basis. In 1995 the French Urological Association started a prospective survey to investigate the efficacy and safety of the AMS 800 artificial urinary sphincter (AUS) in PRP-UI, and preliminary results are presented for the 103 men enrolled in the study in whom bulbar urethral cuff placement was used exclusively. Surgical revision was necessary in 22 patients (21%). Infection and erosion accounted for 12 non-mechanical revisions leading to complete removal of 6 AUS and to eventual replacement of 6 devices with new ones. Mechanical malfunction accounted for revision in l0 patients (9.7%). Fifty-nine patients (61.45%) reported no leakage for the 96 working devices. Twenty-seven patients (28%) wore no pads, 3 patients used 1 pad and 4 patients used 2 pads/day, and all these patients reported improvement, with only 3 patients (3%) having had more than 2 pads/day. Currently, no non-prosthetic procedure reliably affords such good objective results. Insertion of the AMS 800 AUS no doubt represents an attractive treatment modality available for male urinary incontinence following radical prostatectomy.

France↗
PubMed1998

Cryptococcal meningitis and intracranial tuberculoma in a patient with Waldenstrom's macroglobulinemia treated with fludarabine.

We report a patient with Waldenstrom's Macroglobulinemia who presented with cryptococcal meningitis followed by an intracranial tuberculoma during the 18 months period after termination of cytotoxic therapy with Fludarabine. Opportunistic infections due to intracellular organisms are extremely rare in the course of this malignancy and we review the predisposing factors of these infectious entities.

Antineoplastic Agents↗
PubMed1998

[Re-evaluation of the diagnosis in congenital hypothyroidism].

Newborn screening for congenital hypothyroidism (CH) has become routine in Italy. It provided new information regarding the epidemiology, diagnosis and treatment of CH infants and allowed to identify transient disorders of thyroid function in infancy. In fact, when the permanence of hypothyroidism has not been established in the newborn period, a confirmation of the diagnosis at 2-3 years of life should be performed. In this study results regarding the diagnosis reevaluation performed in 23 out of 184 CH children followed at the follow-up center for CH of the University of Rome "La Sapienza", are reported. Eleven of 23 reevaluated children had transient hypothyroidism (TH) and permanent CH was confirmed in the others. Four of the 11 TH children had law gestational age at birth, 1 had high antithyroid peroxidase titre due to maternal autoimmune thyroiditis and 2 were resident in iodine deficient areas. Our results show the importance of diagnosis reevaluation to identify transient disorders of thyroid function in infancy and confirm the role of neonatal, maternal and environmental factors in the etiopathogenesis of TH.

Biomarkers↗