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P Costa

Publications and source records attributed to P Costa.

At least 91 records · Page 5Linked to original sources

Age-Specific Anti-Hepatitis A Virus Seroepidemiology in Italian Travelers: Indications for Anti-Hepatitis A Vaccination.

Background: Hepatitis A virus (HAV) circulation in the environment is decreasing in most industrialized Western countries. This decrease has lead to low seroprevalence rates in adults. As a consequence, many nonimmune unprotected travelers from areas of low prevalence are considered at risk of acquiring HAV infection when traveling to high HAV endemic areas in developing countries. The recent HAV inactivated vaccine has proved safe and effective, and its use in different geographic areas should be guided by local age-specific HAV seroprevalence rates. The aim of this paper is to describe the age-specific sero-epidemiology of HAV infection in travelers from a highly industrialized region in Northern Italy (Lombardy). Methods: Seven hundred and forty-four consecutive travelers aged from 20 to 59 years, subdivided in 10-year age groups, gave blood samples in the collaborative Health Centers in the Lombardy region and sera were tested for HAV IgG antibodies. A questionnaire was given to travelers that investigated alimentary habits and a history of previous travel. Results: Anti-HAV seroprevalence was 18.0%, 58.0%, 75.8%, and 89.5% in the 20-29, 30-39, 40-49, and 50-59 age groups, respectively. Age was the single most important determinant of anti-HAV seroprevalence. The influence of previous travels, eating shellfish, or ingestion of self-cultivated vegetables was ruled out by multivariate analysis. Conclusions: In the Lombardy region (Northern Italy), age specific anti-HAV seroprevalence rates are much higher than those reported in other Western European countries. The cost-benefit analysis suggested that travelers born after 1960 do not need serologic screening before vaccination. Whenever possible, however, HAV serologic screening is advisable for travelers born before 1960. However, the severity of the disease in older subjects, and the proved safety of HAV vaccination in immune subjects, may advise d'emblée HAV vaccination without prior screening, when serologic investigation is unfeasible because of lack of time or the unavailability of testing facilities.

Journal Article↗

Chorionic villus sampling and transverse digital deficiencies: evidence for anatomic and gestational-age specificity of the digital deficiencies in two studies.

Several but not all studies indicate that chorionic villus sampling (CVS) is associated with an increased risk for transverse limb deficiencies, including digital deficiencies. It has been suggested that variations in results regarding the transverse digital deficiencies (TDDs) may be due to the use of different classification criteria. We present the combined analysis of two case-control studies, the U.S. Multistate CVS (US) study and the Italian Multicentric Birth Defects (IP-IMC) study, using two different definitions of TDDs. We compared the frequency of CVS exposure in control infants with that among those infants with any number of affected digits (any TDD), and those with all five digits of at least one limb affected (extensive TDDs). The estimated relative risk (RR) for any TDD following CVS was 10.6 (IPIMC) and 6.6 (US). For the extensive TDDs, the RR was 30.5 (IPIMC) and 10.7 (US). In both studies, extensive TDDs were less than 25% of all TDDs. Compared to all TDDs, extensive TDDs were more likely to occur after CVS performed earlier in the first trimester (before 10-11 weeks' gestation). These findings suggest a relationship between the timing of CVS and the severity of TDDs; indicate that using a restrictive definition of TDDs (all five digits affected) may limit the ability to evaluate the association between CVS and TDDs in populations in whom CVS is usually performed at or after 10 weeks' gestation; and highlight the necessity to consider gestational age in any evaluation of the relative risk for limb deficiencies associated with CVS.

Adult↗

Acetylcholine as a mitogen: muscarinic receptor-mediated proliferation of rat astrocytes and human astrocytoma cells.

The mitogenic effect of muscarinic receptor agonists in glial cells has been characterized in rat cortical astrocytes and human 132 1N1 astrocytoma cells. The muscarinic receptor agonist carbachol caused a dose- and time-dependent increase in proliferation, as measured by [3H]thymidine incorporation. The mitogenic effect was mimicked by several muscarinic, but not nicotinic receptor agonists, and was blocked by muscarinic receptor antagonists. Reverse transcription-polymerase chain reaction (RT-PCR) experiments indicated the presence of m2, m3 and to a lesser degree, m5 muscarinic receptor mRNA in both astrocytes and astrocytoma cells. Proliferation experiments with subtype-specific muscarinic receptor antagonists suggest that carbachol-induced proliferation is due to activation of muscarinic M3 receptors. The phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) also stimulated glial cell proliferation. Down-regulation of protein kinase C, or the protein kinase C antagonist 1,5-(isoquinolynsulfanyl)-2-methylpiperazine dihydrochloride (H7) blocked proliferation induced by either TPA or carbachol. Of other neurotransmitters tested, histamine caused glial cell proliferation, norepinephrine and gamma-aminobutyric acid were ineffective, while serotonin and glutamate inhibited basal or serum-stimulated proliferation.

Acetylcholine↗

Dissection of lymphocyte function-associated antigen 1-dependent adhesion and signal transduction in human natural killer cells shown by the use of cholera or pertussis toxin.

The effect of the guanosine triphosphate-binding protein (G-protein) inhibitors cholera toxin (Ctx) and pertussis toxin (Ptx) has been analyzed on lymphocyte function-associated antigen 1 (LFA-1)-dependent adhesion and signal transduction in human natural killer (NK) cells. Ctx, but not Ptx, inhibited the LFA-1-dependent adhesion of NK cells to tumor target cells which constitutively express the intercellular cell adhesion molecule-1 (ICAM-1) and to NIH/3T3 mouse fibroblasts stably transfected with human ICAM-1. This effect was detectable only by the use of the entire Ctx but not of the Ctx B subunit. In addition, Ctx could inhibit both NK cell binding and spreading to purified ICAM-1 protein. NK cell treatment with Ctx modified neither the surface expression of LFA-1 nor its Mg2+ binding site. These findings, together with the absence of any detectable effect of Ctx on the constitutive phosphorylation of LFA-1 alpha, suggests that this toxin modifies the avidity of LFA-1 for ICAM-1 by acting on LFA-1-cytoskeletal protein association. Unlike Ctx, Ptx did not affect NK cell adhesion. The effects of Ctx and Ptx are unlikely to depend on intracellular levels of cyclic adenosine 3',5'-monophosphate (cAMP), since a strong increase of cAMP was induced by both toxins. Moreover, this was confirmed by the observation that the LFA-1-dependent adhesion was not inhibited by the adenylate cyclase activator forskolin (FSK), the phosphodiesterase inhibitor isobutyl-1-methylxanthine (IBMX), or both, which increase intracellular cAMP levels. Unlike the differential effect on cell adhesion, both the intracellular calcium [Ca2+]i increase and phosphoinositide breakdown mediated via LFA-1 were consistently inhibited in a dose-dependent manner by both Ctx and Ptx. Also in this case, the inhibitory effect did not depend on an increase of intracellular cAMP as indicated by NK cell treatment with FSK, IBMX, or both. Further evidence of the involvement of G-proteins in LFA-1-mediated signal transduction was the inhibitory effect of the GDP analog guanosine-5'-O-2-thiodiphosphate (GDP beta S) on LFA-1-mediated calcium mobilization. Taken together, our data provide evidence that the LFA-1-mediated NK cell adhesion and signal transduction are partially independent phenomena which may be regulated by different G-proteins.

Adenylate Cyclase Toxin↗

Expression of human NKRP1A by CD34+ immature thymocytes: NKRP1A-mediated regulation of proliferation and cytolytic activity.

In this study, we show that NKRP1A is expressed and functions on a subset of immature human thymocytes. We took advantage of the monoclonal antibody (mAb) 191B8 that was obtained by immunizing mice with cultured human thymocytes characterized by an immature surface phenotype [CD2- CD3- CD4- CD8- stem cell factor receptor (SCFR)+] and expressing cytoplasmic CD3 epsilon chain. The 191B8 antibody homogeneously reacted with the immunizing population but not with most unfractionated thymocytes. It stained a minor population of resting immature thymocytes co-expressing CD34, SCFR, or both. Following culture of the CD34+ or CD34- fractions of CD2- CD3- CD4- CD8- purified immature thymocytes with recombinant interleukin-2 (rIL-2), the 191B8-defined antigen was expressed on virtually all cells even when 191B8+ cells were removed from the starting population. On the other hand, no 191B8+ cells were detected in fresh or cultured thymocytes expressing a more mature phenotype. Biochemical analysis of 191B8 mAb-reactive molecules revealed, under non-reducing conditions, two bands displaying apparent molecular masses of 80 and 44 kDa and a single band of 44 kDa under reducing conditions. Digestion with proteases indicated that the 80-kDa form represented a homodimeric form of two 44-kDa molecules, while deglycosylation with N-glycanase suggested the existence of four N-glycosylation sites. Transfection of COS7 or NIH3T3 cells with hNKRP1A cDNA showed that the 191B8 mAb recognized NKRP1A as shown by both immunofluorescence analysis and immunoprecipitation experiments. Functional studies showed that the 191B8/NKRP1A molecule mediated strong inhibition of the cytolytic activity of cultured CD2- CD3- immature thymocytes against a panel of tumor target cells. More importantly, 191B8 mAb induced proliferation of CD2- CD3- fresh thymocytes which was not increased by rIL-2. Thus, we propose that NKRP1A molecules, which are expressed in highly immature thymocytes, may play a regulatory role in their growth and function.

Antigens, CD34↗

Effect of intravenous alfuzosin on urethral pressure in patients with neurogenic bladder dysfunction. DORALI Study Group.

In order to assess the ability of a single intravenous (i.v.) injection of alfuzosin, a selective alpha-1 blocker, in reducing high urethral tone in patients with symptomatic neurogenic bladder dysfunction (NBD), 163 patients (mean maximal urethral pressure [MUP] 108 +/- 46 cm H2O) were enrolled in a double-blind, placebo-controlled, parallel-group trial and were randomly allocated to receive 0.5 mg (n = 45), 1 mg (n = 41), 2 mg (n = 39) alfuzosin or placebo (n = 38). The decrease in MUP was dose-dependent and statistically significant (P < or = 0.05) for 1 and 2 mg alfuzosin (respectively, 43 +/- 28 cm H2O and 46 +/- 27 cm H2O decreases vs. baseline) in comparison with placebo (23 +/- 30 cm H2O). The 2 mg dose level was the most effective leading to a > or = 30 or 50% decrease in MUP in, respectively, 69 and 44% of patients. The safety of all three alfuzosin dose levels was satisfactory and comparable to placebo. I.v. alfuzosin induces, in a dose-related manner, a clinically significant decrease in urethral pressure in patients with NBD and high urethral tone, and may be safely used as a pharmacological test as part of an urodynamic investigation.

Adolescent↗

Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses.

OBJECTIVE: The concentration-time profiles of specific metabolites of moxisylyte, an alpha-adrenoceptor blocking agent, in the plasma and urine from 18 healthy volunteers were investigated after intracavernous (IC) administrations at three dose levels (10, 20 and 30 mg). RESULTS: Four metabolites, unconjugated desacetyl-moxisylyte (DAM), DAM glucuronide, and DAM and monodesmethylated DAM (MDAM) sulphates were found in plasma and urine. For all metabolites, t1/2 elimination was independent of the administered dose (1.19 h for unconjugated DAM; 1.51 h for DAM glucuronide; 1.51 h for DAM sulphate; and 2.17 h for MDAM sulphate). Cmax and AUC increased in direct proportion to dose, except for the inactive DAM glucuronide. Any the differences detected were small and equivalence of the three doses can be accepted. CONCLUSION: The pharmacokinetics of moxisylyte in humans following intracavernous administration were linear in the dose range 10 to 30 mg.

Adrenergic alpha-Antagonists↗

Pharmacokinetics of moxisylyte in healthy volunteers after intravenous infusion and intracavernous administration with and without a penile tourniquet.

The concentration-time profiles of metabolites of moxisylyte (or thymoxamine), an alpha-blocking agent, were investigated in 18 healthy volunteers after intravenous (i.v.) and intracavernous (i.c.) administrations with and without a tourniquet. Four metabolites, unconjugated desacetylmoxisylyte (DAM), DAM glucuronide, and DAM and monodesmethylated DAM (MDAM) sulfates, were found in plasma and urine. For all metabolites, tmax was significantly increased after i.c. administrations and Cmax was significantly decreased. Maximum plasma level of unconjugated DAM was lower after i.c. administration with (1.81-fold) and without (1.26-fold) a tourniquet than after i.v. administration (43.6 +/- 19.6 ng/ml). The elimination half-life of each metabolite showed no change between the three treatments. The difference of 19 min between the mean residence times of unconjugated DAM after i.c. administration with and without a tourniquet may be compared with the difference between the mean duration of the intumescence, that is, 19 min (73 and 54 min with and without a tourniquet, respectively). Total percentages of metabolites recovered in urine were 66.2 +/- 20.9, 61.4 +/- 12.2, and 58.7 +/- 9.1% after i.v. and i.c. administrations with and without a tourniquet, respectively. In conclusion, tourniquet placed before i.c. administration increased the mean residence time of unconjugated DAM of approximately 25% and seemed to increase the efficacy of the drug in healthy volunteers.

Adult↗

[Hot flashes and hormonal treatment of prostate cancer].

Androgen suppression in the context of the treatment of prostatic cancer is responsible for hot flashes in 75% of patients, which alter the quality of life to varying degrees depending on the patient. They constitute a source of major discomfort in 30 to 40% of patients. The pathophysiology of this effect is now known and involves: sex steroids, central opiates and intrahypothalamic catecholamines. The incidence of hot flashes appears to vary according to the type of hormonal treatment administered. The various treatments available are not equally effective. Non-hormonal treatments are of little value. Hormonal treatments: oestrogens and steroidal antiandrogens are the most effective. Progestogens also appear to be just as effective or even more effective than these other agents, with negligible adverse effects at the doses used in this indication.

Androgen Antagonists↗

A technical report reviewing the use of the 11-mm Gamma nail: interoperative femur fracture incidence.

Two years after the first large series on the Gamma nail, the authors analyze 119 surgical procedures for proximal femur fractures performed using the 11 mm Gamma nail. The study was performed by 24 surgeons (from six orthopedics departments) at different levels of learning, as in the previous study. The small-sized nail allows an easier surgical procedure and a manual introduction of the nail even in small femurs, as suggested by the previous experience. A careful operative technique and a 2 mm overreaming, which was almost always adopted, explains the decrease in interoperative and postoperative complications (evaluated in 88 cases), compared to the last case report published in 1991. No interoperative shaft fractures occurred in 119 nailings.

Adult↗

Amino acid substitutions can influence the natural killer (NK)-mediated recognition of HLA-C molecules. Role of serine-77 and lysine-80 in the target cell protection from lysis mediated by "group 2" or "group 1" NK clones.

Natural killer (NK) cells have been shown to express a clonally distributed ability to recognize HLA class I alleles. The previously defined NK clones belonging to "group 1" recognize HLA-C*0401 (Cw4) and other HLA-C alleles sharing Asn at position 77 and Lys at position 80. Conversely, the "group 2" NK clones recognize HLA-Cw*0302 (Cw3) and other HLA-C alleles characterized by Ser at position 77 and Asn at position 80. We assessed directly the involvement of these two residues in the capacity of NK cell clones to discriminate between the two groups of HLA-C alleles. To this end, Cw3 and Cw4 alleles were subjected to site-directed mutagenesis. Substitution of the amino acids typical of the Cw3 allele (Ser-77 and Asn-80) with those present in Cw4 (Asn-77 and Lys-80) resulted in a Cw3 mutant that was no longer recognized by group 2 NK cell clones, but that was recognized by group 1 clones. Analysis of Cw3 or Cw4 molecules containing single amino acid substitutions indicates roles for Lys-80 in recognition mediated by group 1 clones and for Ser-77 in recognition mediated by group 2 clones. These results demonstrate that NK-mediated specific recognition of HLA-C allotypes is affected by single natural amino acid substitutions at positions 77 and 80 of the heavy chain.

Amino Acid Sequence↗

[Medical treatment of disorders of the bladder sphincter].

A lot of drugs can increase or decrease bladder activity or urethral sphincter activity. Some of them are used for treatment of incontinence or chronic retention. In case of severe pollakiuria or urge incontinence secondary to bladder instability, numerous medications can be used: anticholinergic agents, musculotropic relaxants, calcium antagonists, prostaglandin inhibitors, beta-adrenergic agonists, tricyclic antidepressants. Anticholinergic agents are regularly used on first choice. When stress incontinence is present, alpha agonists administered with estrogen and perineal reeducation represent the first stage before surgery. For medical treatment of retention, if there is not outlet obstruction, one can increase detrusor activity with betanechol chloride. In case of outlet obstruction, alpha-blockers or 5 alpha-reductase inhibitors can be used, if there is benign prostatic hyperplasia. Pygeum africanum can be used, but to date there is no clinical study proving its efficacy.

Humans↗

Association of radiographic features of osteoarthritis of the knee with knee pain: data from the Baltimore Longitudinal Study of Aging.

OBJECTIVE: To examine the association between self-reported knee pain and radiographic features of osteoarthritis (OA) of the knee. METHODS: A sample of participants in the Baltimore Longitudinal Study of Aging (452 Caucasian males and 223 Caucasian females) completed questionnaires and underwent a standing radiograph of both knees at the same biennial visit between 1984 and 1989. Radiographs were interpreted using both the Kellgren-Lawrence and individual features scales. Odds ratios were calculated for the association of radiographic features with knee pain after adjustment for age, sex, and body mass index. RESULTS: Overall, 156 (23%) persons reported ever having knee pain, and 104 (15%) reported current knee pain (within the previous year). Both ever knee pain and current knee pain were significantly associated with the presence of definite knee OA (Kellgren-Lawrence grade > or = 2) and with the presence of all individual features. There was a direct relationship between all measures of severity of radiographic OA and knee pain. CONCLUSION: These data demonstrate that radiographic features of knee OA are significantly associated with knee pain. The data also support the continued use of the Kellgren-Lawrence grading scale for defining knee OA in population studies.

Adult↗

Increased risk for transverse digital deficiency after chorionic villus sampling: results of the United States Multistate Case-Control Study, 1988-1992.

Although numerous infants have been reported with transverse limb deficiencies after their mothers had undergone chorionic villus sampling (CVS), it has been unclear whether the procedure caused these defects. We report the results of the first multistate case-control study to assess and quantify the risk for specific limb deficiencies associated with CVS. Case subjects were 131 infants with nonsyndromic limb deficiency ascertained from 7 population-based birth defect surveillance programs, and born from 1988-1992 to mothers 34 years of age or older. Control subjects were 131 infants with other birth defects. We ascertained exposure to CVS from medical records and maternal and physician questionnaires. We assessed rates and timing of exposure to CVS, and estimated relative and absolute risks for anatomic subtypes of limb deficiency. The odds ratio for all types of limb deficiency after CVS from 8-12 weeks' gestation was 1.7 (95% confidence interval, 0.4-6.3). For specific anatomic subtypes, the strongest association was for transverse digital deficiency (odds ratio = 6.4; 95% confidence interval, 1.1-38.6). The risk for transverse digital deficiency increased with earlier gestational exposure (P < 0.01 for trend). We estimated that the absolute risk for transverse digital deficiency in infants after CVS was 1 per 2,900 births (0.03%). Exposure to CVS was associated with a sixfold increase in risk for transverse digital deficiency. The causality of this association is supported by its strength, specificity, biologic plausibility, and consistency with the results of previous studies. Although some centers already inform patients about risk for limb deficiency, this study quantifies the magnitude of risk associated with CVS from 8-12 weeks' gestation.

Case-Control Studies↗

Identification of m3, m4 and m5 subtypes of muscarinic receptor mRNA in human blood mononuclear cells.

In this study we made use of the Reverse transcription-polymerase chain reaction to analyze the expression of mRNA for the five subtypes of muscarinic acetylcholine receptors in human blood mononuclear cells. mRNA for m3, m4 and m5 subtypes was detected, while mRNA for m1 and m2 muscarinic receptors was not found. Similar results were obtained for three different healthy human subjects studied. Interestingly, the m5 subtype was expressed at higher levels in blood mononuclear cells than in cerebral cortex. To our knowledge this is the first time that m5 muscarinic receptor mRNA has been found outside of the central nervous system.

Adult↗

An expansible splint for treatment of nostril stenosis.

Stenosis of the nostrils is an uncommon deformity frequently caused by a circumferential scar retraction after trauma, infection, or iatrogenic procedures. To avoid recurrence of postoperative stenosis, it is necessary to maintain the corrected contour of the nostril during the period of wound contraction. For this purpose, we describe a new acrylic nostril conformer that is expansible. The splint fits the patient's nostril exactly and by its expansion can even achieve an overcorrection, improving a poor surgical result.

Adult↗

Percentage area density of epithelial and mesenchymal components in benign prostatic hyperplasia: comparison of results between single biopsy, multiple biopsies and multiple tissue specimens.

OBJECTIVE: To determine whether histological analysis of six multiple random biopsies of the gland or analysis of only one biopsy provides a good estimate of the different components of the hyperplastic gland compared with the results obtained from tissue specimens (reference values). MATERIALS AND METHODS: The various components of prostate tissue obtained from 30 men undergoing suprapubic adenomectomy were investigated. The histological analysis was performed on multiple tissue specimens reflecting adenoma (reference values) and on one and six biopsies performed at random on the enucleated material of the hyperplastic gland. Immunohisto chemistry using anti-actin as a label of smooth muscle and specific histological staining coupled with computer-assisted quantitative morphometric analysis was used to ascertain the histological composition of the prostate. RESULTS: The mean ( +/- SD) area densities obtained from tissue specimens were 34.1 +/- 5%, 32.4 +/- 6.9%, 17.6 +/- 4.5% and 15.9 +/- 5.5% of smooth muscular and fibrous tissue, and epithelium and glandular lumen, respectively. The mean ratio of stromal to epithelial hyperplasia averaged 4.05 +/- 1.73. Both one and six biopsies gave a good estimate of fibrous tissue and glandular epithelium, but the percentage of smooth muscles was overestimated and the percentage of glandular lumen was underestimated. There was a significant relation between the prostate area densities of glandular epithelium (r = -0.41, P < 0.05), the percentage area density of prostate smooth muscle (r = 0.43, P < 0.05), and the weight of enucleated adenoma. No correlation was found with prostate-specific antigen (PSA). CONCLUSION: It seems feasible to propose medical treatment of benign prostatic hyperplasia (BPH) based on the histological composition of the prostate gland. One biopsy, reflecting in good proportions the nature of the adenoma, would be used to provide insight into the pathogenesis and therapy of BPH.

Aged↗