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Biomedical subjects

P Costa

Publications and source records attributed to P Costa.

At least 37 records · Page 2Linked to original sources
PubMed2002

A shared care approach to the management of erectile dysfunction in the community.

Erectile dysfunction (ED) affects men of all ages and results in considerable distress and impact on quality of life for those who suffer from it. As ED is associated with a wide variety of under-lying conditions and cardiovascular co-morbidities, there is a requirement for diversity of treatment options and several factors must be considered to customise and optimise therapy. In the ideal holistic approach to management of the ED patient, both primary care and specialist physicians have an important role to play. This article reports on a sequential approach for the diagnosis and treatment of ED, with an emphasis on 'shared care'. The deliberations are based on a pan-European inter-disciplinary group that met at the Lygon Arms, UK on 22 February 2002.

Erectile Dysfunction↗
PubMed2001

Human prostatic cell line PNT1A, a useful tool for studying androgen receptor transcriptional activity and its differential subnuclear localization in the presence of androgens and antiandrogens.

The human immortalized prostatic cell line PNT1A has been proved to be a good model for analysis of cellular processes such as the prostatic epithelium proliferation in response to androgens and growth factors. Here we used this cell line for studying the transcriptional activity and trafficking of the androgen receptor (AR) by analyzing several actions of antiandrogens. Transient transfection experiments with PNT1A cells were performed with wild type human AR and an androgen-responsive gene reporter. We demonstrated that the transcription of reporter gene could be triggered by natural androgens (testosterone and dihydrotestosterone) in PNT1A cells as well as in the prostatic carcinoma cell line DU-145. With competitive experiments in the two cell lines, we observed no difference between the antagonistic capacity of cyproterone acetate (CPA) and hydroxyflutamide at 10(-7) M. At this concentration, bicalutamide antagonist activity was lower. In parallel, we compared the subcellular localization of the modified green fluorescent protein (EGFP)-AR in COS-7, PNT1A and DU-145 cell lines under fluorescence microscopy: we found different distributions between nucleus and cytoplasm, depending on the cell line and the culture medium. Androgen induced cluster formation within the nucleus of the PNT1A and DU-145 cells. However, the cytonuclear trafficking of androgen bound EGFP-AR in the same living cell and nuclear foci were easier to examine in the PNT1A cells. The antiandrogen capacity of bicalutamide was manifested by a slower androgen-dependent nuclear transfer of EGFP-AR and a homogeneous nuclear localization. A delayed advent of nuclear clusters was observed in presence of CPA. We conclude that the PNT1A cell line is a better model than the DU-145 cell line to analyze the trafficking of AR and the association of AR on the nuclear matrix, as well as to observe the action of antiandrogens on these critical steps in prostate cells.

Active Transport, Cell Nucleus↗
PubMed2001

An alternative method to the evaluation of similarity factor in dissolution testing.

This paper addresses an alternative method to the evaluation of similarity factor f(2) as a criterion for assessment of similarity between two in-vitro dissolution profiles as proposed in the SUPAC-IR Guidance (1995). Diltiazem hydrochloride Sustained-Release (SR) tablets were tested and the following independent-model dissolution parameters were used: t10% dissolution time, t25% dissolution time, t50% dissolution time, mean dissolution time (MDT), dissolution efficiency (DE) at t(120), and at t(360). To compare the dissolution profiles, several release models were tested such as Higuchi, zero order, first order, Baker-Lonsdale, Hixson-Crowell, Weibull and Korsmeyer-Peppas. The similarities between two in-vitro dissolution profiles were assessed by pair-wise independent-model procedures such as difference factor (f1), similarity factor (f2) and Rescigno index (xi1 and xi2). The in vitro release kinetics of diltiazem hydrochloride sustained release tablets were evaluated using USP apparatus 2.

Analysis of Variance↗
PubMed2001

Differential disappearance of inhibitory natural killer cell receptors during HAART and possible impairment of HIV-1-specific CD8 cytotoxic T lymphocytes.

BACKGROUND: Highly active antiretroviral therapy (HAART) is associated with a decrease in viral replication to undetectable levels and with an increase in CD4 T lymphocytes. Residual HIV-1 replication occurs together with incomplete recovery of cytotoxic CD8 T lymphocyte (CTL) numbers and function. We sought to determine whether expression of HLA class I-specific inhibitory natural killer receptors (iNKR) on the CTL of patients who had been treated successfully with HAART for 24 months could be involved, at least in part, in residual CTL functional inhibition. METHODS: Two-colour cytofluorometry was used to analyse the expression of six different iNKR including p58.1, p58.2, p70, p140, CD94/NKG2A and LIR1/ILT2 on the CD3, CD8 lymphocytes of eight patients with successful long-term suppression of viral replication before and after 3, 6 and 24 months of HAART. Healthy subjects were analysed as controls. HIV-1-specific cytotoxic activity was determined after 24 months of HAART in the presence and absence of iNKR-masking. RESULTS: No significant reduction of iNKR expression on CD8 T cells was observed by 6 months. Expression of p70 and p140 was inversely correlated with the increasing CD4 numbers. After 24 months CD8 T-lymphocytes expressing p58.1, p58.2, p70, p140 and CD94/NKG2A returned to levels indistinguishable from those of the healthy controls. A significantly increased proportion of CD8 CTL still expressed LIR1/ILT2, a receptor with broad HLA-class I specificity. Functional analysis of freshly separated cells revealed that the disruption of the interaction between LIR1/ILT2 and HLA-class I could partly restore HIV-1-specific lysis. CONCLUSIONS: A decrease in CD3CD8iNKR cells is observed beyond 6 months of HAART. In some patients functional impairment due to LIR1/ILT2 expression may persist even after 24 months of successful HAART.

Adult↗
PubMed2001

Identification, molecular cloning and functional characterization of NKp46 and NKp30 natural cytotoxicity receptors in Macaca fascicularis NK cells.

Natural killer (NK) cell recognition and function in humans is regulated by multiple cell surface receptors. The "on" signal leading to NK cell triggering is primarily mediated by natural cytotoxicity receptors (NCR). Analysis of NK cells in primate animal models is of particular relevance because NK cells may play an essential role in host defenses against infections. We analyzed Macaca fascicularis PBMC and in vitro-derived NK cell populations and clones by cytofluorometry, using a wide panel of mAb, and by cytolytic activity assays. In addition, RT-PCR strategy and transient transfections were used to isolate M. fascicularis NCR. NCR-specific mAb reactivity (anti-NKp46 and anti-NKp30) was present on M. fascicularis PBMC and on NK cell cultures. Macaque NCR were functional in both redirected killing and in mAb-mediated masking assays. Cloning of macNKp46 and macNKp30 NCR homologous genes showed a high sequence similarity (86 % and 88 %, respectively) with their human counterparts. Attempts at identifying NKp44 surface reactivity and at cloning the macaque homologue were unsuccessful. NKp46 and NKp30 NCRs, but not NKp44, are highly conserved in M. fascicularis NK cells. This suggests the possibility of a staged appearance of the NCR during phylogenesis and provides a useful tool for the study of natural immunity correlates of protection in primate SIV/SHIV infection models.

Amino Acid Sequence↗
PubMed2001

Modeling and comparison of dissolution profiles.

Over recent years, drug release/dissolution from solid pharmaceutical dosage forms has been the subject of intense and profitable scientific developments. Whenever a new solid dosage form is developed or produced, it is necessary to ensure that drug dissolution occurs in an appropriate manner. The pharmaceutical industry and the registration authorities do focus, nowadays, on drug dissolution studies. The quantitative analysis of the values obtained in dissolution/release tests is easier when mathematical formulas that express the dissolution results as a function of some of the dosage forms characteristics are used. In some cases, these mathematic models are derived from the theoretical analysis of the occurring process. In most of the cases the theoretical concept does not exist and some empirical equations have proved to be more appropriate. Drug dissolution from solid dosage forms has been described by kinetic models in which the dissolved amount of drug (Q) is a function of the test time, t or Q=f(t). Some analytical definitions of the Q(t) function are commonly used, such as zero order, first order, Hixson-Crowell, Weibull, Higuchi, Baker-Lonsdale, Korsmeyer-Peppas and Hopfenberg models. Other release parameters, such as dissolution time (tx%), assay time (tx min), dissolution efficacy (ED), difference factor (f1), similarity factor (f2) and Rescigno index (xi1 and xi2) can be used to characterize drug dissolution/release profiles.

Chemistry, Pharmaceutical↗
PubMed2001

Divisability of diltiazem matrix sustained-release tablets.

The objective of this work was to study the possibility of a solid sustained-release dosage form, like a tablet, be divided without changing its release characteristics. Diltiazem hydrochloride Sustained-Release (SR) tablets with a standard groove on one face, were tested and the following dissolution parameters were evaluated: t10%, t25%, and t50% dissolution time, and dissolution efficiency at t120, and at t360. To analyze the release mechanism, several release models were tested such as Higuchi, zero order, first order, Baker-Lonsdale, Hixson-Crowell, Weibull, and Korsmeyer-Peppas. The similarities between two in vitro dissolution profiles were assessed by the difference factor (f1), the similarity factor (f2) and the Rescigno index (xi(i)). The in vitro release kinetics of diltiazem hydrochloride tablets were evaluated using USP apparatus 4. Using a one-way ANOVA (a = 0.05), statistically significant differences were found for t10%, t25%, and t50% dissolution times with a constant and with a variable pH dissolution fluid. The variation coefficient for the divisibility assay (Portuguese Pharmacopoeia VI) was lower than the limit value of 10%. The diltiazem release rate from this pharmaceutical system was not constant, and diminished with the square root of time (Higuchi model) showing that the phenomenon controlling drug release was the diffusion occurring inside the swelled polymeric matrix. Diltiazem release rate was a function of the area in direct contact with the dissolution fluid and not of the pharmaceutical matrix volume. The results obtained permit us to conclude that the division, in this case, affects the drug release characteristics.

Analysis of Variance↗
PubMed2001

The National Birth Defects Prevention Study.

The National Birth Defects Prevention Study was designed to identify infants with major birth defects and evaluate genetic and environmental factors associated with the occurrence of birth defects. The ongoing case-control study covers an annual birth population of 482,000 and includes cases identified from birth defect surveillance registries in eight states. Infants used as controls are randomly selected from birth certificates or birth hospital records. Mothers of case and control infants are interviewed and parents are asked to collect buccal cells from themselves and their infants for DNA testing. Information gathered from the interviews and the DNA specimens will be used to study independent genetic and environmental factors and gene-environment interactions for a broad range of birth defects. As of December 2000, 7,470 cases and 3,821 controls had been ascertained in the eight states. Interviews had been completed with 70% of the eligible case and control mothers, buccal cell collection had begun in all of the study sites, and researchers were developing analysis plans for the compiled data. This study is the largest and broadest collaborative effort ever conducted among the nation's leading birth defect researchers. The unprecedented statistical power that will result from this study will enable scientists to study the epidemiology of some rare birth defects for the first time. The compiled interview data and banked DNA of approximately 35 categories of birth defects will facilitate future research as new hypotheses and improved technologies emerge.

Case-Control Studies↗
PubMed2001

Quality of life in spinal cord injury patients with urinary difficulties. Development and validation of qualiveen.

BACKGROUND: Quality of life (QoL) may be severely affected in patients with spinal cord injury (SCI) and resulting urinary difficulties (UD). There is, however, a need for instruments capable of measuring QoL in these patients. The aim of this study was to develop and validate a questionnaire suitable for use in SCI patients with urinary disorders. METHODS: Following patient interviews, a questionnaire was developed in French that was subjected to item reduction and cross-sectional validation. The resulting Qualiveen (Qualiveen is a pending registration trade mark of Coloplast A/S, DK-3050 Humlebaek, Denmark) questionnaire underwent multi-trait and principal component analysis and the test-retest reliability of the questionnaire was examined in stable patients. RESULTS: Patient interviews identified 257 concepts relevant to SCI patients with urinary disorders. Item reduction led to a 30-item questionnaire, which was psychometrically validated in 281 SCI patients with UD. The median age of patients was 41 years, 78% were male and the majority were paraplegic (55%). The construct and clinical validity of the Qualiveen was confirmed, as well as its reliability in patients whose condition was stable over a 15-day period. Patients confirmed that it was easy to understand, complete and comprehensive. CONCLUSIONS: The Qualiveen is a reliable and psychometrically validated instrument that may be used to measure the QoL of SCI patients with UD.

Adult↗
PubMed2001

The use of an artificial urinary sphincter in women with type III incontinence and a negative Marshall test.

PURPOSE: We evaluate the efficacy of the AMS 800 artificial urinary sphincter in women with type III incontinence. MATERIALS AND METHODS: We enrolled 207 women with genuine stress incontinence due to intrinsic sphincter deficiency. Primary inclusion criterion was a negative Marshall test. A modified surgical procedure was used to implant the AMS 800 through an abdominal approach, with placement of the cuff around the bladder neck between the periurethral fascia and vagina. Followup data were available for 206 women, including 179 with nonneurogenic and 27 with neurogenic bladders (mean followup 3.9 years). RESULTS: There were 12 (5.9%) explantations due to the prosthesis either through an erosion, extrusion or both that were necessary. The only significant risk factor for explantation was perioperative injury. This injury resulted in 8 explantations in 49 patients compared with 4 in 155 who did not have such injuries (p = 0.0016). Of the 190 patients with working devices continence was achieved in 88.7% (49 of 168) and 81.8% (18 of 22) of those with nonneurogenic and neurogenic bladders, respectively. Social continence (slight leakage but no pad use) was reported by 7.7% (13 of 168) and 9.1% (2 of 22) of patients in the nonneurogenic and neurogenic groups, respectively. The remaining patients reported leakage and pad use. CONCLUSIONS: The AMS 800 can be used successfully to treat women with genuine stress incontinence due to intrinsic sphincter deficiency. The modified surgical approach resulted in fewer perioperative injuries and, consequently, a low explantation rate. Women with genuine stress incontinence, a low urethral closure pressure and negative Marshall test indicating severe intrinsic sphincter deficiency are potential candidates for artificial urinary sphincter implantation.

Adult↗
PubMed2001

Surgical treatment of primary and metastatic sternal tumours.

BACKGROUND: Primary and metastatic malignancies of the sternum are uncommon. Surgery that is the best treatment for the majority of primary sternal tumors, and arguably for metastatic lesions, has improved permitting us to perform wide resection and simultaneous reconstruction safely. METHODS: From January 1988 to December 1998 we treated 13 patients, 4 with primary chondrosarcoma and 9 with sternal metastasis, 5 breast cancer, 3 kidney cancer and 1 thyroid cancer. In 3 patients total sternectomy was performed and in 10 a partial sternectomy associated with resection of the anterior segment of the ribs in 7 cases and resection of the clavicle in 5 patients. Bone reconstruction was done in the majority of cases (5) with Marlex mesh with methylmethacrylate and in 3 cases rib grafts were used to strengthen a Vicryl mesh. The major pectoralis muscle was the most frequently used soft tissue, 9 of 12. RESULTS: Our postoperative mortality was 15%, 2 cases. The median overall survival was 48 months. All the primary tumours were alive after a mean follow-up of 34 months (range 4-84 months). While survival of the sternal metastasis was 24 months. CONCLUSIONS: Surgical resection and reconstruction of sternal lesions represent a basic step in the treatment of the primary tumors with encouraging survival results while in the metastatic lesions surgery can be a part of a multimodality approach with unsatisfactory results.

Aged↗
PubMed2000

Multiple HLA-class I-specific inhibitory NK receptor expression and IL-4/IL-5 production by CD8+ T-cell clones in HIV-1 infection.

Several mechanisms may contribute to the decline in HIV-1 specific CD8+ cytotoxic T-lymphocyte (CTL) activity that is observed in infected patients, including loss of CD4+ cell help, antigenic shift, impaired clonogenicity and functional impairment due to expression of inhibitory NK receptors (iNKRs). In addition to a decrease in HIV-1-specific cytolytic activity, an increased proportion of CD8+ T-cells producing IL-4 and IL-5 has been recently observed in advanced HIV-1 infection. Remarkably, an impaired HIV-1-specific CTL activity was primarily detected among the TC0/Tc2 CD8+ CTLs. A series of CD3+CD8+ T-cell clones expressing inhibitory NK receptors (iNKRs) isolated from HIV-1 infected patients was analyzed in order to determine their cytokine production pattern and to assess the extent of iNKR expression at the single cell level. Our data indicate that iNKR+CD3+CD8+ clones isolated from infected patients frequently express multiple iNKR and may produce IL-4 and IL-5 to a relevant extent.

Antigens, CD↗
PubMed2000

Pharmacokinetics of enoxacin and its oxometabolite after multiple oral dosing and penetration into prostatic tissue.

The objective of this study was to determine the concentrations of enoxacin and its oxo-metabolite in human prostatic tissue after multiple oral doses (400 mg bd) in 13 patients. On the first day of treatment, elimination half-lives were 6.8 h for enoxacin and 7.1 h for its metabolite; they were increased on day 4 (10.3 and 13.2 h, respectively). The ratios of drug concentration in prostatic tissue and plasma averaged 2.2 for enoxacin and 1.4 for its metabolite. In conclusion, concentrations of enoxacin achieved within the prostatic tissue were higher than plasma concentrations suggesting that there was an active transport mechanism.

Administration, Oral↗
PubMed2000

Compression wood-responsive proteins in developing xylem of maritime pine (Pinus pinaster ait.).

When a conifer shoot is displaced from its vertical position, compression wood (CW) is formed on the under side and can eventually return the shoot to its original position. Changes in cell wall structure and chemistry associated with CW are likely to result from differential gene/protein expression. Two-dimensional polyacrylamide gel electrophoresis of differentiating xylem proteins was combined with the physical characterization of wooden samples to identify and characterize CW-responsive proteins. Differentiating xylem was harvested from a 22-year-old crooked maritime pine (Pinus pinaster Ait.) tree. Protein extracted from different samples were revealed by high-resolution silver stained two-dimensional polyacrylamide gel electrophoresis and analyzed with a computer-assisted system for single spot quantification. Growth strain (GS) measurements allowed xylem samples to be classified quantitatively from normal wood to CW. Regression of lignin and cellulose content on GS showed that an increase in the percentage of lignin and a decrease of the percentage of cellulose corresponded to increasing GS values, i.e. CW. Of the 137 studied spots, 19% were significantly associated with GS effect. Up-regulated proteins included 1-aminocyclopropane-1-carboxylate oxidase (an ethylene forming enzyme), a putative transcription factor, two lignification genes (caffeic O-methyltransferase and caffeoyl CoA-O-methyltransferase), members of the S-adenosyl-L-methionine-synthase gene family, and enzymes involved in nitrogen and carbon assimilation (glutamine synthetase and fructokinase). A clustered correlation analysis was performed to study simultaneously protein expression along a gradient of gravistimulated stressed xylem tissue. Proteins were found to form "expression clusters" that could identify: (a) Gene product under similar control mechanisms, (b) partner proteins, or (c) functional groups corresponding to specialized pathways. The possibility of obtaining regulatory correlations and anticorrelations between proteins provide us with a new category of homology (regulatory homology) in tracing functional relationships.

Cellulose↗
PubMed2000

Carotid surgery without angiography is possible and safe.

BACKGROUND: To evaluate the possibility to perform carotid surgery without angiography. METHODS: From January 1994 to June 1998, 514 patients with carotid obstructive disease were operated upon, 225 of them (43.8%) without previous angiography; 55 out of 68 (80.8%) during the last six months. Eighty-one (36.0%) had lateralizing symptoms, 50 aspecific ones (22.2%) and 94 were asymptomatic (41.8%). All patients were investigated by color-coded duplex sonography (CDS) of the arteries at the neck and by transcranial Doppler (TCD) and computed tomography (CT). One hundred eighty-eight patients were operated upon under local anaesthesia and 37 under general anesthesia; 204 had a carotid endartereotomy (90.7%) with patch angioplasty in 154 (75.5%), and 21 required a bypass graft (9.3%). In 26 patients (11.5%) an indwelling shunt was needed. RESULTS: Findings at surgery were consistent with CDS for plaque composition, ulcerations and degree of stenosis. There were no early deaths. Neurologic or ocular deficits occurred in 2 cases (0.9%). No strokes were observed in follow-up from 6 to 34 months. CONCLUSIONS: Carotid endarterectomy can be done without angiography in selected cases provided CDS plus TCD are of high quality. Under such conditions it can be considered a safer way to deal with carotid obstructive disease.

Aged↗
PubMed2000

[Simultaneous radio-chemotherapy for infiltrating bladder carcinoma. What is new since 1997?].

Concomitant radiotherapy-chemotherapy is increasingly used in urology in the treatment of invasive bladder tumours. In 1997, the outcome of 552 patients was reported in the international literature. Two years later, another 617 patients had been treated according to various modalities. The initial complete response rate ranged from 56 to 87% (median: 70%). 5-year overall survival rates were between 55 and 68% for T2 tumours. The metastasis rate was between 22 and 35% for the overall treated population. Concomitant radiotherapy-chemotherapy using a platinum salt represents a possible therapeutic modality in some patients, but it cannot be considered to be equivalent to total cystectomy, which remains the reference treatment in operable patients with an operable tumour, achieving a 63 to 80% 5-year survival for pT2 tumours.

Clinical Trials as Topic↗