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Biomedical subjects

R Hinojosa

Publications and source records attributed to R Hinojosa.

At least 19 recordsLinked to original sources

Is an emergency heart transplantation justified?

INTRODUCTION: Emergency heart transplantation remains an important controversy due to the shortage of donors and the previously demonstrated results inferior to other patients. These recipients display a worse clinical status and their donors are more often considered suboptimal. Nevertheless, it is the only therapeutic option for patients with advanced cardiomyopathy and acute decompensation with no response to other therapies. We compared results among the emergency indication with those of elective transplants. METHODS: We analyzed the 213 patients who underwent cardiac transplantation in our center up to December 2004 to compare emergency with elective heart transplantations for preoperative and surgical variables as well as outcomes. RESULTS: A higher percentage of emergency patients were New York Heart Association class IV, displayed renal dysfunction, and were women. Regarding donors, a higher percentage were over 40 years of age. No differences were observed in the early and first-year mortality or morbidity rates, although we noted a greater 5-year mortality rate among emergency cases. CONCLUSIONS: In our center emergency heart transplantation was associated with only slightly worse results compared with elective transplantations. Both donors and recipients should be carefully selected to improve results.

Adult↗

Is it possible to reduce the number of endomyocardial biopsies with new immunosuppressive drugs?

INTRODUCTION: Using previous immunosuppressive regimens the considerable number of rejections of heart transplantations required routine surveillance myocardial biopsies, particularly during the early months. More effective immunosuppressive regimens would probably allow routine biopsies to be reduced. Our objectives were to assess the incidence of and the time to rejection with a new immunosuppressive protocol, considering the possibility of reducing the number of routine biopsies. MATERIALS AND METHODS: We undertook a retrospective study of patients who had undergone heart transplantation from January 2002 to August 2005 and who received induction therapy with Daclizumab (two doses) and maintenance therapy with tacrolimus + mycophenolate + low doses of steroids. RESULTS: Among 42 patients, 13 (31%) showed myocardial rejection in the first 3 months. All episodes were grade 3A and none had hemodynamic consequences. After 3 months, three patients (7.1%) experienced 3A rejection and 1 (2.4%), grade 4 acute rejection after ceasing medical treatment. Each episode of rejection was predictable, either owing to reduction in immunosuppression therapy or to a previous history of rejection. CONCLUSIONS: The majority of rejection episodes occur in the first 3 months posttransplantation. After that time, the incidence of rejection is less and clinically predictable. Therefore, surveillance biopsies should be limited to the first 3 months, and performed later either in symptomatic patients (with a history of previous rejection) or in those whose immunosuppressive therapy needs to be reduced.

Biopsy↗

Combination therapy with sildenafil and bosentan reverts severe pulmonary hypertension and allows heart transplantation: case report.

INTRODUCTION: Severe pulmonary hypertension with no response to vasodilators on an acute hemodynamic study is a contraindication to cardiac transplantation. The development of oral pulmonary vasodilators improves the prognosis in these patients. We present the case of a patient whose admission to the waiting list for cardiac transplantation was possible after 6 months of combination therapy with Sildenafil and Bosentan. CASE REPORT: The patient was a 50-year-old man with severe dilated alcohol-induced cardiomyopathy. A pretransplantation study, including a right hemodynamic analysis, revealed irreversible pulmonary hypertension, with 59 mm Hg mean pulmonary artery pressure and 6.4 Wood IU pulmonary vascular resistance, with no response to acute vasodilators with nitric oxide or prostacyclin. Initially, heart transplantation was not possible and the patient started treatment with oral Sildenafil. After 6 months there was no improvement in echocardiographic or hemodynamic parameters, and combination therapy with Bosentan was started. With the combination therapy, the patient progressively improved clinically and hemodynamically, the pressures becoming normal at the sixth month, at which time he was included on the waiting list for a heart transplantation. Eight months later he received a graft with a good posttransplantation course, no right ventricular failure in the acute phase, and absence of pulmonary hypertension on echocardiogrphic and invasive studies. CONCLUSION: Combinations of an oral pulmonary vasodilator with diverse action mechanisms may represent an alternative for patients with irreversible pulmonary hypertension who do not respond to monotherapy.

Antihypertensive Agents↗

Sirolimus experience in heart transplantation.

INTRODUCTION: Sirolimus is a potent, nonnephrotoxic immunosuppressant with antiproliferative activity in nonimmune cells. Recent data support the conversion in late renal failure secondary to calcineurin inhibitors (CNIs), with limited experience in de novo regimens in patients with predictive factors of postoperative renal impairment. OBJECTIVE: We evaluated our experience of sirolimus-based immunosuppression administered to 25 heart transplant recipients. METHODS: A retrospective analysis of 25 heart transplant recipients who received sirolimus included 17 conversions due to late CNI-related chronic renal dysfunction, six patients with a de novo regimen, and two patients who developed posttransplant pulmonary neoplasms. The conversion from CNI to sirolimus was started with 2 mg, with an average time after transplantation of 78 +/- 43 months and a mean baseline serum creatinine level of 2.1 +/- 0.45 mg/dL. The mean clinical follow-up was 17 +/- 9 months postconversion, and included echocardiography and laboratory studies. In the de novo group successive endomyocardial biopsies were performed during the first semester. RESULTS: Serum creatinine fell from 2.1 +/- 0.45 mg/dL to 1.8 +/- 0.51 mg/dL (P = .012). Mean sirolimus levels were 15 +/- 9 ng/mL (doses 2.2 +/- 0.4 mg). This improvement continued until 3 months (creatinine 1.5 +/- 0.35 P < .01)/sirolimus levels 11.7 +/- 5 ng/mL [1.9 +/- 0.7 mg]), with maintenance at 6 months (1.58 +/- 0.3 mg/dL/14 +/- 4 ng/mL [1.85 +/- 0.7 mg]) and 1-year postconversion (1.53 +/- 0.39 mg/dL; P = .019/10.7 +/- 2.5 ng/mL [1.5 +/- 0.7 mg]). De novo, after a mean follow-up of 13 months (range 3 to 35), sirolimus appeared to increase the incidence of a moderate histological grade of rejection without hemodynamic compromise. Side effects were common (63%), including peripheral edema, skin eruptions, and pericardial effusion. Only one patient discontinued treatment, due to intestinal intolerance. Four patients died during follow-up: two because of lung neoplasms and two because of progressive graft vessel disease. CONCLUSION: Sirolimus improved late CNI-related chronic renal dysfunction. Kidney function was preserved using a de novo CNI-free immunosuppressive regimen for recent cardiac transplant recipients.

Adult↗

Sirolimus improves renal function in cardiac transplantation.

In kidney and liver transplantation, sirolimus therapy has been shown to be comparable to cyclosporine in a head-to-head comparison, but it results in better preservation of renal reserve. In heart transplantation, information about the use of sirolimus is limited. We present the results of the progressive conversion from cyclosporine to sirolimus in a series of 8 heart transplant patients in whom renal dysfunction developed. The baseline creatinine level was 2.4 +/- 0.5 mg/dL, and plasma levels of cyclosporine were within the therapeutic range. After the introduction of sirolimus, the creatinine level fell within the first month to 1.76 +/- 0.2 mg/dL, or mean decrease of 0.6 +/- 0.25 mg/dL (P < .05). After 3 +/- 2.2 months the improvement continued (1.69 +/- 0.2 mg/dL). In 1 patient sirolimus was withdrawn during the first 24 hours, because of gastric intolerance. No patient developed an opportunist infection, allograft rejection, or important hematologic disorder. We conclude that sirolimus appears to be effective in heart transplant patients to improve renal function.

Antibodies, Monoclonal↗

Use of oral sildenafil in patients with irreversible pulmonary hypertension not eligible for heart transplantation.

Heart transplantation is contraindicated in patients with acute irreversible pulmonary hypertension (PH), but new drugs are opening up therapeutic possibilities. Sildenafil citrate is a nonselective pulmonary vasodilator that is being used in our hospital to treat several patients with PH and which has allowed the inclusion of 1 patient on the waiting list for heart transplantation. A 20-year-old man with Becker muscular dystrophy was diagnosed at the age of 19 years with dilated cardiomyopathy with severe pulmonary artery systolic pressure (PH = 60 mm Hg). A pretransplantation study, including a right hemodynamic analysis with an acute vasodilator test using intravenous epoprostenol, revealed the irreversible character of the PH. Inasmuch as the administration of dobutamine did not achieve an adequate reduction of PH, oral sildenafil was started (25 mg every 12 hours) as salvage therapy. An echocardiogram obtained 2 months after starting sildenafil therapy showed normal right cavities, previously dilated, as well as minimal protosystolic tricuspid regurgitation without PH. A new right hemodynamic study performed after 4 months showed a reduction in pulmonary vascular resistance, from 8 U to 3.5 U Woods. As a result, the patient has now been included on the waiting list for heart transplantation. The promising example of this patient confirms the necessity to carry out controlled trials to establish definitively the indications for the use of sildenafil in patients with irreversible PH.

Administration, Oral↗

Comparative study of muromonab-CD3 (OKT3) versus daclizumab (Zenapax) in cardiac transplantation at our center.

Recent studies support the addition of new immunosuppressive drugs as cytolytic induction therapy in cardiac transplantation. We carried out a comparative study comprising 52 patients who had undergone cardiac transplantation at our center. Thirty patients received muromonab-CD3 (OKT3, Janssen-Cilag, The Netherlands) as the induction therapy, whereas 22 patients received Daclizumab (Zenapax, Hoffman-La Roche, Nutley, NJ, USA) instead. All patients received cyclosporine or tacrolimus, mycophenolate, and steroids. Over an average follow-up period of 23.21 +/- 18 months, we analyzed retrospectively the incidence of grade > or = 3A biopsy-confirmed acute rejection episodes, the presence of infectious processes at 1 and 6 months, the occurrence of significant secondary effects, and the necessity to modify the immunosuppressive therapy during the follow-up. The results suggest that daclizumab is linked to a decreased incidence of grade > or = 3A biopsy-confirmed acute rejection and to a reduced necessity to modify the immunosuppressive therapy during the medium-term follow-up.

Antibodies, Monoclonal↗

Myocardial preservation using Celsior: clinical results in high-risk cardiac transplantation.

Graft failure during the first few days posttransplantation remains one of the main unresolved complications. The objective of this study was to evaluate the influence of Celsior preservation solution on the incidence of early graft failure in high-risk cardiac transplant recipients. A retrospective study was carried out evaluating the cardiac transplants in 179 heart recipients. The patients were divided into 2 groups: (1) Celsior preservation solution (n = 37), and (2) Control solution (n = 142). To evaluate the efficacy of the Celsior solution, a subgroup of transplants from older donors or with ischemia times greater than 4 hours was compared with the other cases. The incidence of early graft failure was lower among the Celsior subgroups with longer ischemia times or of older donors compared with the control groups. We conclude that preservation with Celsior solution in cardiac transplantation is safe and effective. It even has advantages to reduce early graft failure compared with conventional solutions, a benefit that may be more evident in subgroups at high risk for myocardial dysfunction.

Disaccharides↗

Aminoglycoside ototoxicity: a human temporal bone study.

OBJECTIVE: Hearing loss after aminoglycoside administration has been thought to result primarily from hair cell injury. The purpose of the study was to determine the potential for direct injury of spiral ganglion cells and hair cells in cases of documented human aminoglycoside ototoxicity. STUDY DESIGN: Retrospective case review. METHODS: The clinical course of two individuals with aminoglycoside ototoxicity are documented, including the details of administration of tobramycin and other ototoxic medication and serial audiograms. The temporal bones were processed, and the cochlear elements quantified. RESULTS: Histopathological study of the temporal bones from the individuals in the study demonstrated reduction of both ganglion cell and hair cell populations. Spiral ganglion cell loss was not necessarily subadjacent to areas of hair cell loss in cases of aminoglycoside ototoxicity. Instead, spiral ganglion cell reduction may be present in segments of the cochlea with normal-appearing hair cells. CONCLUSIONS: The study suggests that aminoglycoside antibiotics can injure spiral ganglion cells directly, as well as hair cells. Thus, the characteristic hearing loss of ototoxicity can result from degeneration of either cochlear element.

Adult↗

Antonio Scarpa and the discovery of the membranous inner ear.

OBJECTIVE: To give a historical perspective of Antonio Scarpa's contributions to otology, specifically the discovery of the inner ear organs as the foundation for the experimental work that followed. BACKGROUND/METHOD: Scarpa's original descriptions of the human inner ear were translated from the Latin text, and his illustrations were analyzed and compared with current knowledge. CONCLUSIONS: Antonio Scarpa's anatomic and clinical studies place him among the great scientists of the eighteenth century. His discoveries about the inner ear established the limit of what could be learned without advanced histologic techniques and provided the foundation for the work that eventually led to the modern understanding of ear physiology.

Anatomy↗

Aplasia of the cochlear nerve: a temporal bone study.

OBJECTIVE: The purpose of this study was to evaluate the temporal bone findings in individuals with cochlear nerve aplasia. STUDY DESIGN: Retrospective case review. METHODS: Two individuals with unilateral profound deafness caused by aplasia of the cochlear nerve were identified. The temporal bones were processed, and the cochlear elements were quantified. RESULTS: Histopathologic study of the temporal bones from these individuals demonstrate that a fully formed cochlea and normal-appearing organ of Corti can occur in the absence of the spiral ganglion and cochlear nerve. Cochlear nerve aplasia can occur in both a narrow or a normal-sized internal auditory canal. CONCLUSION: These findings suggest that the development of the cochlea and organ of Corti are not dependent on the presence of the cochlear nerve and spiral ganglion. The entity of cochlear nerve aplasia in the presence of a normally formed cochlea must be considered when evaluating individuals as candidates for cochlear implantation.

Adult↗

Temporal bone histopathology in connexin 26-related hearing loss.

OBJECTIVE: Mutations in GJB2, a gene that encodes a gap junction protein, Connexin 26 (Cx26), are responsible for approximately one third of sporadic severe-to-profound or profound congenital deafness and half of severe-to-profound or profound autosomal recessive nonsyndromic hearing loss (ARNSHL). Mouse mutants homozygous for knockouts of this gene are nonviable, precluding histopathologic studies of the associated inner ear pathology in this animal model. Therefore, we studied archival temporal bone sections to identify temporal bone donors with Cx26-related deafness. STUDY DESIGN: Temporal bone donors with a history of congenital severe-to-profound or profound deafness were identified in the registry of the Temporal Bone Library at the University of Iowa. Histological findings were interpreted in a blinded fashion. DNA extracted from two celloidin-embedded mid-modiolar sections from each temporal bone was screened for the 35delG Cx26 mutation. The entire coding region of Cx26 was screened for other deafness-causing mutations if the 35delG mutation was detected. RESULTS: Of five temporal bone donors with congenital severe-to-profound deafness, one donor was found to have Cx26-related deafness. This individual was a Cx26 compound heterozygote, carrying the 35delG mutation and a noncomplementary Cx26 missense mutation on the opposing allele. Microscopic evaluation of this temporal bone showed no neural degeneration, a good population of spiral ganglion cells, near-total degeneration of hair cells in the organ of Corti, a detached and rolled-up tectorial membrane, agenesis of the stria vascularis, and a large cyst in the scala media in the region of the stria vascularis. CONCLUSION: This study is the first to report the temporal bone histopathology associated with Cx26-related deafness. Preservation of neurons in the spiral ganglion suggests that long-term successful habilitation with cochlear implants may be possible in persons with severe-to-profound or profound Cx26-related deafness.

Adult↗