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Biomedical subjects

J Carballido

Publications and source records attributed to J Carballido.

At least 19 recordsLinked to original sources

Long-term follow-up of a randomized prospective trial comparing a standard 81 mg dose of intravesical bacille Calmette-Guérin with a reduced dose of 27 mg in superficial bladder cancer.

OBJECTIVES: To determine the efficacy of a three-fold reduced dose (RD, 27 mg) of intravesical bacille Calmette-Guérin (BCG) against the standard dose (81 mg) in patients with superficial bladder cancer, assessing recurrence, progression and differences in toxicity. PATIENTS AND METHODS: Five hundred patients with superficial bladder cancer (Ta, T1, Tis) were enrolled and randomly assigned to be treated after transurethral resection of all visible lesions with intravesical BCG Connaught strain (weekly x six and thereafter fortnightly x six) either with the standard or RD instillation. RESULTS: All but one of the 500 patients were evaluable for efficacy and toxicity (252 in the standard arm and 247 in the RD arm). The median follow-up was 69 months (maximum 104); 71 (28%) patients in the standard arm and 76 (31%) in the RD arm developed recurrences; the median time to recurrence has not yet been attained, but at 5 years the mean (sd) percentage of recurrence-free patients was 70.5 (3.12) and 70.4 (3.1) for the standard and RD arms, respectively. In patients presenting with multifocal tumours, the standard dose was more effective against recurrences than the RD (P=0.0151). In those with G3 and high-risk tumours overall, the superiority of the standard dose was marginal (P=0.060 and P=0.082). Twenty-nine (11.5%) tumours in the standard arm and 33 (13.3%) in the RD arm progressed to invasive disease; the median time to progression has not yet been attained, but the percentage of progression-free patients at 5 years was 88.8 (2.23) and 86.9 (2.31) for the standard and RD arms, respectively. The standard dose was more effective than the RD against progression only in patients with multifocal disease (P=0.048). Twelve (4.8%) cystectomies were performed in the standard and 15 (6.1%) in the RD arm. Currently, 106 (21.2%) patients have died, but only 38 (7.6%) from bladder cancer, i.e. 20 (7.9%) in the standard and 18 (7.5%) in RD arm. Overall the disease-specific death rate was lower for those patients who completed the scheduled treatment. The cause-specific survival at 5 years did not differ between the arms (P=0.76) but there was a trend toward better cause-specific survival for patients with multifocal tumours in the standard arm. Toxicity differed between the arms, significantly more patients having no toxicity in the RD arm, and fewer having delayed instillations or withdrawing. However, severe systemic toxicity occurred even in patients treated with the RD, in a similar proportion to those receiving the standard dose. CONCLUSION: Overall, the RD gave similar results for recurrence and progression but with significantly less toxicity. However, patients with multifocal tumours fared better with the standard dose and there was a trend towards better recurrence rates in patients with high-risk tumours. We recommend continuing to use the standard dose for high-risk tumours, while we consider the reduced dose safe and effective for intermediate-risk lesions and for maintenance schedules.

Adjuvants, Immunologic↗

Repair of posterior coronary lacerations.

Posterior lacerations of the coronary arteries that occur during arteriotomy should be repaired if significant. We describe a modification of the standard technique to repair posterior coronary artery lacerations. This technique avoids distortion and narrowing of the coronary artery.

Coronary Vessels↗

Influence of sociodemographic and health status variables on the American Urological Association symptom scores in patients with lower urinary tract symptoms.

OBJECTIVES: To evaluate the relationship between sociodemographic and health status variables and the American Urological Association Symptom Score (AUA-7) because low associations between clinical measures of lower urinary tract symptoms and scores on the AUA-7 suggest that symptoms may be influenced by other variables. METHODS: Sociodemographic, clinical, and health status variables were recorded for 666 patients with benign prostatic hyperplasia (BPH). BPH symptoms were measured with the AUA-7. Bivariate and multivariate analyses were used to determine correlations between sociodemographic and health status variables and AUA-7 scores. RESULTS: BPH-related variables (clinical rating of severity, number of BPH treatments, and being scheduled for surgery) were included in the final regression model, which explained 25% of the overall variability in scores. An additional 7% of the total variability was explained by other non-BPH-related variables (educational level, presence of depression/anxiety, and pain/discomfort). CONCLUSIONS: The AUA-7 is a robust questionnaire that is little influenced by sociodemographic variables and general health status. The educational level, mood, and presence of pain/discomfort of patients should be taken into account when interpreting scores, as a combination of these characteristics could mean a difference of up to 6 points on the AUA-7.

Age Factors↗

Guidelines on renal cell cancer.

OBJECTIVES: On behalf of the European Association of Urology (EAU), Guidelines for Diagnosis, Therapy and Follow-Up of Renal Cell Carcinoma Patients were established. Criteria for recommendations were evidence based and included aspects of cost-effectiveness and clinical feasibility. METHOD: A systematic literature research using Medline Services was conducted. References were weighted by a panel of experts on renal cell carcinoma (RCC). RESULTS: RCC is characterised by a constant rise in incidence over the last 50 years, with a predominance of men over women and an incidence peak in the 6th and 7th decade. There is no risk factor established and the current TNM system (UICC, 1997) is endorsed for staging purposes. Clinical signs and symptoms of RCC are becoming less frequent, incidental discovery constitutes already a majority of cases. Diagnosis is established by ultrasound and abdominal CT, extension assessment in routine cases is done by chest X-ray. Additional examinations may be required in select cases. The therapy of choice in organ-confined RCC is surgery. Radical tumour nephrectomy is considered as a standard. Efficacy and side-effects of organ-sparing surgery, lymphadenectomy and inclusion/omission of ipsilateral adrenalectomy in selected cases is a matter of ongoing clinical research. In metastatic cases, tumour nephrectomy should only be considered in the context of modern systemic immunotherapy. A follow-up at regular intervals is recommended because certain cases of recurrences may be candidates for surgery and/or immunomodulating therapy. CONCLUSION: A rise in incidence, improved diagnostic procedures, and evolving multimodality therapeutic concepts justify the need for rational guidelines on this most challenging urologic malignancy.

Carcinoma, Renal Cell↗

Effect of mode of administration on I-PSS scores in a large BPH patient population.

OBJECTIVES: The International Prostate Symptoms Score (I-PSS) was designed to be self-administered to patients with benign prostatic hyperplasia. This study tested for a possible mode of administration effect on the I-PSS and assessed the reliability of the I-PSS over time when modes of administration varied. METHODS: Benign prostatic hyperplasia patients over 50 years of age were recruited at 52 Spanish centres. The I-PSS was administered on two occasions 1 month apart. Patients were sequentially classified into groups A-D according to the mode of administration (S = self-administered, I = interview administered) at the two visits (A = S-S, B = S-I, C = I-S, and D = I-I). The intraclass correlation coefficient was used to assess test-retest reliability, and multiple regression analysis was used to test the effects of the mode of administration and the visit number on I-PSS scores. RESULTS: 926 patients (mean age 66 years) were evaluated. The mean I-PSSs symptoms score at visit 1 in groups A-D were, respectively, 13.19, 13.57, 12.06, and 12.29. Multiple regression analysis between-group scores were 0.93 points higher when the I-PSS was self-administered and 1.98 points lower at the second visit. The intraclass correlation coefficients were: group A = 0.77, group B = 0.70, group C = 0.67, and group D = 0.76. CONCLUSIONS: Interview administration of the I-PSS results in slightly lower scores. The reliability is higher when the same mode of administration is used at two recurrent visits.

Age Factors↗

The association between CD2+ peripheral blood lymphocyte subsets and the relapse of bladder cancer in prophylactically BCG-treated patients.

We investigated the potential existence of differences in the distribution of T-lymphocyte subsets and in the proliferative response of these CD2+ cells to polyclonal mitogens in patients with transitional cell bladder carcinoma (SBTCC) treated with prophylactic intracavitary instillations of bacillus Calmette-Guerin (BCG) according to their clinical response to this treatment. Before BCG treatment, different subset distribution (CD8+ and CD3+ CD56+), activation antigen expression (CD3+ HLA- DR+) and proliferative response to mitogenic signals were found in CD2+ cells from SBTCC patients prophylactically treated with BCG who remained free of disease or those who had recurrence of tumour. Otherwise, the prophylactic intracavitary BCG instillations in SBTCC patients are associated with a transitory variation of T-lymphocyte subset distribution (CD4 and CD8) and activation antigens expression (CD25).

Adjuvants, Immunologic↗

Immunological changes in peripheral blood mononuclear cells of patients with metastatic renal cell carcinoma after low doses of subcutaneous immunotherapy with IFN-alpha-2b and IL-2.

To elucidate the immunologic changes induced by low doses of subcutaneous interferon (IFN)-alpha-2b plus interleukin-2 (IL-2) in patients with metastatic renal cell cancer, we have studied a group of eight patients undergoing two cycles of immunotherapy after radical nephrectomy. Natural killer (NK) cytotoxic activity, proliferative response to T-lymphocyte mitogens, and phenotypic profile of T and NK cells were determined in peripheral blood mononuclear cells (PBMCs) before and after each cycle. No significant differences were found in either of the studies realized between untreated patients and their counterpart healthy controls. However, after the first cycle, there was a significant increase in NK-cytotoxic activity and in the number of CD16+/CD56+ cells that parallelled a significant decrease in the percentage of CD3+ and CD4+ lymphocytes with no changes in the proliferative response to T-cell mitogenic signals. Individual analysis of each patient on the basis of their clinical response to treatment showed that after the first cycle of immunotherapy there were no significant differences in the immunological profiles analyzed between patients with complete or partial responses and those who did not respond to treatment, whereas, at the end of the second cycle, patients who achieved complete or partial clinical responses had higher NK-cytotoxic activity that those who remained in disease progression. We conclude that subcutaneous immunotherapy with IFN-alpha-2b and IL-2 induces a systemic immunomodulatory effect on PBMCs, manifested preferentially in a systemic NK activation and expansion that is related to the clinical outcome.

Aged↗

Intraluminal milrinone for dilation of the radial artery graft.

There is renewed interest in the use of the radial artery as a conduit for coronary artery bypass surgery. The radial artery is, however, a very muscular artery, prone to vasospasm. Milrinone, a potent vasodilator, has demonstrated vasodilatory properties superior to those of papaverine. In this report, we describe our technique of radial artery harvesting and the adjunctive use of intraluminal milrinone as a vasodilator in the preparation of this conduit for coronary artery bypass grafting. We have used these techniques in 25 patients who have undergone coronary artery bypass grafting using the radial artery. No hand ischemic complications have been observed in this group. Intraluminal milrinone appears to dilate and relax the radial artery, rendering this large conduit spasm free and very easy to use. We recommend the skeletonization technique for radial artery harvesting and the use of intraluminal milrinone as a radial artery vasodilator in routine myocardial revascularization.

Adult↗

Surgical treatment of aortic dissections: initial experience with the adventitial inversion technique.

BACKGROUND: The adventitial inversion technique obliterates the false lumen and converts a dissected aorta into a conduit with tough adventitia on the inside and outside. Dacron grafts can be anastomosed to the aorta with fine sutures, which hold without tears. METHODS: From August 1995 to March 1997, we treated 6 patients with acute dissecting aneurysms. Three aneurysms were type I (A) involving the entire aorta, two type II (A) involving the ascending aorta, and one type III (B) involving the thoracoabdominal aorta. Circulatory arrest was used in 3 patients, 1 with type I aneurysm (A), 1 type II (A), and 1 type III (B). RESULTS: All Dacron-aorta anastomoses held sutures well and did not bleed intraoperatively or postoperatively. One patient (type II [A]) died of intraoperative low cardiac output. In patients with type I (A) aneurysms, the false lumen was obliterated, but 1 patient required resection of a 6-cm abdominal aortic aneurysm. CONCLUSIONS: The adventitial inversion technique is a safe technique for the treatment of acute dissecting aneurysms, which facilitates operation and solves the problem of intraoperative or postoperative bleeding due to tissue friability.

Acute Disease↗

Validation of a harmonized Spanish version of the IPSS: evidence of equivalence with the original American scale. International Prostate Symptom Score.

OBJECTIVES: To validate the use in Spain of a linguistically harmonized Spanish version of the International Prostate Symptom Score (IPSS Sp), and to compare it with the original American scale (IPSS Am). METHODS: Validity and reliability were studied in 59 patients with benign prostatic hyperplasia (BPH) (age >50 years) and 68 control subjects without BPH (age 18 to 49 years). Construct validity was assessed by correlating IPSS Sp scores with the EuroQol-5D (EQ-5D), the Psychological General Well-Being Index (PGWBI), and item 8 (quality of life) of the IPSS. Discriminatory power was assessed by calculating the area under the receiver operating characteristic (ROC) curve. Reliability was evaluated using the test-retest method, and internal consistency was assessed using Cronbach's alpha. Sensitivity to change was expressed as the effect size in preintervention versus postintervention scores in 26 additional patients with BPH (age >50 years) who underwent transurethral resection of the prostate. RESULTS: Correlations of the IPSS Sp were -0.07 to 0.36 with EQ dimensions; -0.29 with the EQ visual analogue scale score; 0.14 to 0.41 with PGWBI dimensions; and 0.72 with item 8 of the IPSS. ROC area was 0.95 +/- 0.02 (standard error). Using a cutoff point of 7, sensitivity was 83% and specificity was 98%. Test-retest reliability was 0.92 and Cronbach's alpha was 0.79. Mean preoperative and postoperative IPSS Sp scores were 25.56 and 8.48, respectively (P < 0.001 ). Overall effect size was 2.52. These results are similar to those of the original American scale. CONCLUSIONS: This Spanish translation of the IPSS is valid, reliable, and sensitive to clinical change and has demonstrated equivalent psychometric properties to the original American instrument. Scores obtained with the two instruments can therefore be reliably compared and aggregated when statistically appropriate.

Aged↗

Determinants and mechanisms of human immune responses to bee venom phospholipase A2.

The elicitation of an immune response to protein antigens depends on the specific recognition of antigenic determinants (epitopes) by T and B lymphocytes. Bee venom phospholipase A2 (PLA) represents the major antigen/allergen of honey bee venom. It displays three dominant immunogenic peptide and one glycopeptide T cell recognition sites. These epitopes are equally recognized by both allergic and nonallergic individuals. A mixture of the three epitope containing peptides was successfully used in specific immunotherapy of bee venom-allergic patients. Both peptide and whole bee venom immunotherapy induced a state of specific anergy in T cells. The production of specific IgE and IgG4 antibodies directly correlated with the secreted interleukin-4:gamma-interferon (IL-4:IFNgamma) ratio, which itself depended on the concentration of available antigen and the strength of the T cell-activating signal. This signal comprises accumulated molecular interactions delivered by engagement of the antigenic peptide/MHC class II complex with the T cell receptor (TcR). Indeed the thermodynamic laws of chemical equilibrium reactions reveal that the antigen concentration, together with the equilibration constant Ki and the related Gibbs standard free energy DeltaG degrees of the MHC-II/Ag/TcR complex reaction, may govern the secreted IL-4:IFNgamma ratio, and in consequence, differential IgE and IgG4 antibody formation. Ki includes epitope and MHC-II haplotype variability and therefore represents a measure of immunological individuality. A major B cell epitope was determined by using point-mutated PLA. Specific antigen recognition by B cells can trigger distinct cytokine profiles in T cells and contribute to the differential regulation of specific IgE and IgG4 antibodies. Our results indicate that distinct cytokine profiles inducing allergic and nonallergic responses can be attributed to thresholds of T cell activation generated by the specific binding properties of individual MHC-II molecules to immunogenic T cell epitopes and their presentation to TcR.

Allergens↗

Dendritic cell ontogeny: a human dendritic cell lineage of myeloid origin.

Dendritic cells (DC) have been thought to represent a family of closely related cells with similar functions and developmental pathways. The best-characterized precursors are the epidermal Langerhans cells, which migrate to lymphoid organs and become activated DC in response to inflammatory stimuli. Here, we demonstrate that a large subset of DC in the T cell-dependent areas of human lymphoid organs are nonactivated cells and belong to a separate lineage that can be identified by high levels of the interleukin 3 receptor alpha chain (IL-3Ralphahi). The CD34+IL-3Ralphahi DC progenitors are of myeloid origin and are distinct from those that give rise to Langerhans cells in vitro. The IL-3Ralphahi DC furthermore appear to migrate to lymphoid organs independently of inflammatory stimuli or foreign antigens. Thus, DC are heterogeneous with regard to function and ontogeny.

Cell Lineage↗

Prophylactic intracavitary treatment with interferon alpha increases interferon gamma production by peripheral blood mononuclear cells in patients with superficial transitional cell carcinoma of the bladder.

The immunomodulatory effect of prophylactic intravesical instillations of interferon alpha 2b (IFN-alpha-2b) on interferon gamma (IFN-gamma) and interleukin 4 (IL-4) production by peripheral blood mononuclear cells (PBMCs) from patients with superficial transitional cell carcinoma (STCC) of the bladder has been analysed. There were no significant differences in the production of IFN-gamma and IL-4 by PBMCs from untreated patients and healthy control subjects after 24 h of phytohaemagglutinin (PHA) stimulation. However, between 3 and 6 months after finishing the prophylactic intracavitary treatment with IFN-alpha-2b, PHA-stimulated PBMCs from patients with STCC of the bladder showed a significantly enhanced production of IFN-gamma and a significantly decreased production of IL-4. Both IFN-gamma and IL-4 returned to pretreatment levels 1 year after ending the treatment. In conclusion, prophylactic intravesical instillations of IFN-alpha-2b in patients with STCC of the bladder have an immunoregulatory effect on the production of IFN-gamma and IL-4 by PBMCs.

Adjuvants, Immunologic↗

SLAM and its role in T cell activation and Th cell responses.

Following the initial events of T cell activation, triggered by binding of specific peptide-MHC complex to the TCR for antigen and engagement of costimulatory molecules, a number of activation molecules are expressed on the cell surface. Many of these molecules regulate T cell function, T-T cell interactions and the interaction of T cells with other cells. One such molecule is SLAM, a multifunctional 70 kDa glycoprotein member of the Ig superfamily with multiple isoforms. SLAM is rapidly induced on naive T cells and B cells following activation. Engagement of SLAM by a specific antibody (mAb A12) results in IL-2-independent T cell expansion and induction/up-regulation of IFN-gamma by activated T cells, including Th2 cells. SLAM was found to be a high-affinity self-ligand mediating molecular and cellular homophilic interactions. In this review we discuss SLAM as a receptor involved in T cell expansion and in directing immune responses to a Th0-Th1 pathway.

Antigens, CD↗

T lymphocytes infiltrating the bladder wall of patients with carcinoma of urinary bladder are in vivo activated.

OBJECTIVES: This paper studies the phenotypical characteristics of the lymphocytes present in mononuclear cell (MNC) preparations from peripheral blood (PBMNC), lymph nodes (LNMNC), tumor bladder (TBMNC), and tumor-free bladder (TFBMNC) from patients with infiltrated transitional cell carcinoma (TCC) of the bladder and PBMNC of healthy controls. METHODS: Eight patients diagnosed with TCC of the bladder, according to UICC criteria, and 10 healthy controls were studied. For immunofluorescence staining, T lymphocytes were incubated with combinations of fluorescein (FITC, green)- and phycoerytrin (PE, red)-labelled monoclonal antibodies. RESULTS: The percentage of NK cells in the LNMNC and TFBMNC was significantly decreased in comparison to that found in the PBMNC from these patients (p < 0.05). A significant enhancement of the expression of class II molecules of the major histocompatibility complex (MHC) by CD3+ T lymphocytes from TBMNC and TFBMNC specimens from bladder walls was found with respect to those quantified in CD3+ T lymphocytes from PBMNC (p < 0.05). In addition, the percentage of CD3+CD25+ T lymphocytes was significantly higher in PBMNC in TCC patients than in healthy controls (p < 0.05). CONCLUSIONS: Our data clearly demonstrate that the presence of infiltrative TCC of the bladder is associated to an infiltration of in vivo activated T lymphocytes of the urinary bladder wall. This in vivo T lymphocyte activation has been considered an expression of the immune response against the tumor cells.

Aged↗

Use of intracavitary interferon-alpha-2b in the prophylactic treatment of patients with superficial bladder cancer.

BACKGROUND: The evolution of superficial transitional cell carcinoma (TCC) of the bladder poses a clinical management problem due to its tendency to recur after initial transurethral resection (TUR). Natural Killer (NK) cells are a distinct subset of lymphocytes that possess the ability to lyse tumor cells without prior sensitization in a nonmajor histocompatibility-restricted fashion. These cytotoxic cells constitute a relevant barrier against the local growth and systemic dissemination of neoplastic diseases. METHODS: The immunomodulatory effect, after TUR of the tumor, of the prophylactic treatment with intravesical instillations of interferon-alpha-2b (IFN-alpha-2b) upon the NK activity of peripheral blood mononuclear cells (PBMNC) in 17 patients with superficial TCC of the bladder was analyzed using a 4-hour 51sodium chromate (51Cr)-release cytotoxicity assay against both NK-sensitive, or K562, and NK-resistant, or JY, tumor target cells. RESULTS: There were no significant modifications of the NK activity of PBMNC during the 3 months of IFN-alpha-2b intracavitary treatment (P > 0.05). However, with respect to their levels before treatment, NK activity in PBMNC at 3 months posttreatment was enhanced significantly in the 14 patients who showed no sign of tumor recurrence in the 12 months of follow-up (P < 0.01). Six months after finishing the intracavitary IFN-alpha-2b instillations, the PBMNC NK activity in these patients had returned to the levels found before initiating the therapy (P > 0.05). This temporary enhancement of the PBMNC NK activity was not found in three patients with evidence of tumor recurrence at some time during the 12 months after treatment. In similar experimental conditions, significant enhancement of the NK activity in PBMNC was not observed in nine patients with superficial bladder TCC who were treated with intracavitary instillations of mitomycin C (MMC) after the TUR of the tumor and who were free of recurrence of the disease at 1 year of follow up. CONCLUSION: The prophylactic intracavitary treatment of superficial bladder TCC with IFN-alpha-2b may induce an immunomodulatory effect in the NK activity of PBMNC that appears to be associated with the clinical evolution of the disease.

Administration, Intravesical↗