Soluble HLA-G in heart transplantation: their relationship to rejection episodes and immunosuppressive therapy.

The aims of this study were to quantify the level of soluble HLA-G in heart transplant patients, to determine the relationship between the sHLA-G levels and the appearance of acute rejection episodes, and to identify the influence of immunosuppressive therapy on sHLA-G levels. Analysis of sHLA-G, measured by enzyme-linked immunosorbent assay in the transplant patients, revealed the existence of two similarly sized groups of patients. One group displayed a significant increase (p < 0.001) in sHLA-G during the first month after transplantation while the other group maintained low levels of the molecule (0-30 ng/ml) throughout the study. The latter group displayed a high incidence of recurrent severe rejection. A significant increase (p < 0.01) in sHLA-G 2 hours after administration of immunosuppressive treatment (mycophenolate mofetil, cyclosporine A/FK506, corticoids) was found. These results suggest that sHLA-G participates in the induction of certain levels of immunological tolerance in these recipients.

Antithrombin III prevents early pulmonary dysfunction after lung transplantation in the dog.

BACKGROUND: Ischemia-reperfusion injury with the resulting inflammatory response is a devastating complication of lung transplantation; much of the tissue damage could be diminished by control of the inflammatory response. Recent studies have show that antithrombin III (AT III) has an anti-inflammatory effect in addition to its established role in the regulation of blood coagulation. Thus, we hypothesized that the administration of AT III might help to prevent ischemia-reperfusion injury after lung transplantation. METHODS AND RESULTS: The study was performed in a dog model of orthotopic lung transplantation. Dogs were randomly assigned to receive either vehicle (controls) or AT III. We observed that in control dogs, during the 180-minute period after lung transplantation, the arterial O(2) partial pressure decreased and both the alveolar-arterial O(2) difference and the pulmonary vascular resistance increased. By contrast, these parameters remained unchanged in the group of dogs receiving AT III. Dogs with transplants receiving AT III did not show an increase in cell adhesion molecules, and histological examination revealed almost an absence of inflammatory response. The administration of AT III produced a marked increase in serum prostacyclin (PGI(2)) levels, whereas in control dogs, the PGI(2) levels did not change. The beneficial effect of AT III was not observed when dogs received indomethacin to prevent the stimulation of PGI(2) release by AT III. CONCLUSIONS: Our results demonstrate that AT III prevents ischemia-reperfusion injury in a dog model of lung transplantation and that this effect is conditioned by an increase in PGI(2) production.

Intracoronary ultrasound assessment of directional coronary atherectomy: immediate and follow-up findings.

OBJECTIVES: This study was conducted to assess the relations among intracoronary ultrasound, angiographic and histologic data obtained from patients with coronary artery disease successfully treated by directional coronary atherectomy. In addition, it was designed to elucidate whether some aspects of intravascular ultrasound or pathologic findings could predict a propensity to restenosis. BACKGROUND: Intracoronary ultrasound is a useful technique in guiding and assessing atherectomy. However, there is little information about the characterization of the different types of coronary plaques and the changes observed in them after resection. Furthermore, the follow-up ultrasound appearance of previously treated lesions remains undepicted. METHODS: Fifty-two patients (54 +/- 10 years old) were studied. All were successfully treated by atherectomy with the aid of intracoronary ultrasound guidance. Qualitative and quantitative ultrasound and angiographic variables were derived before and after resection. Quantitative histologic morphometric information was also obtained from the specimens. In 22 patients, a follow-up echoangiographic reevaluation was performed 6 +/- 4 months later. RESULTS: Echogenic plaques had a higher collagen and calcium content, whereas echolucent plaques had an increased level of fibrin, nuclei and lipids. Ultrasound plaque reduction after atherectomy was greater in echolucent (76 +/- 21%) than in echogenic plaques (60 +/- 18%; p < 0.05). That reduction correlated with the weight of the resected material (r = 0.62; p < 0.01). At follow-up study, 13 of 22 patients had angiographic and ultrasound evidence of restenosis. Most recurrent lesions had a stenotic three-layer appearance. The incidence of restenosis of primary lesions treated with atherectomy was higher in echolucent (100%) than in echogenic (33%) plaques. Similarly, a higher proportion of nuclear content in the resected material was observed in patients who developed restenosis (2.1 +/- 0.7%) than in patients who had late success after atherectomy (1.2 +/- 0.6%). CONCLUSIONS: Our findings suggest that echolucent plaques are easier to resect than are echogenic plaques but frequently develop restenosis. In contrast, the resection of echogenic plaques, although often incomplete, is associated with better long-term results.

Results of heart transplantation in recipients with active infection.

Although active infection in the recipient is generally considered to be an absolute contraindication for heart transplantation, seven of our first 104 transplant patients (6.7%) had active severe infection within the week before transplantation. Because of unstable clinical condition of these recipients, heart transplantation was performed when an adequate donor was offered, in spite of infection. Patients were managed with cyclosporine as the only immunosuppressive therapy during the first week after transplantation. Mortality rate and incidence of acute rejection were not different for these seven patients than for the remaining 97 patients.

Preliminary experience with deflazacort, a new synthetic steroid with fewer undesirable side effects, in heart transplant patients.

Prednisone is widely used by most heart transplant units, despite its frequent side effects. Deflazacort, a new oral synthetic steroid with fewer side effects, has not been studied in heart transplant patients. Our initial experience with 26 heart transplant patients in whom prednisone was replaced by deflazacort at 11 +/- 11 months after transplantation is reported. After the switch to deflazacort, a significant decreased was noted in glycemia, total cholesterol, and LDL-cholesterol (p < 0.001). No difference was noted in severity or frequency of rejection and infection between patients being treated with deflazacort and another 26 patients who continued to be treated with prednisone over a comparable period of time after transplantation.

Visceral Kaposi's sarcoma without mucocutaneous involvement in a heart transplant recipient.

Kaposi's sarcoma has been occasionally reported in heart transplant recipients, but its occurrence without mucocutaneous involvement is extremely rare. In these uncommon cases, the tumor can be indistinguishable from opportunistic infections, making diagnosis difficult. The case of a patient in whom visceral Kaposi's sarcoma was diagnosed by necropsy 6 months after heart transplantation is reported.

Repetitive nontreated episodes of grade 1B or 2 acute rejection impair long-term cardiac graft function.

BACKGROUND: Episodes of grade 1B or 2 acute heart rejection are usually not treated, and most of them resolve spontaneously. METHODS: With the aim to assess long-term outcome in patients with repetitive nontreated episodes of low-grade (1B, 2) acute rejection, we have studied 141 heart transplant recipients in whom the evolutive pattern of acute rejection during the first 6 months after transplantation could be determined. RESULTS: Forty-four patients (31%) had only grade 0 or 1A acute rejection episodes (pattern A); 23 patients (16%) had three or more episodes of grade 1B or 2 acute rejection without 3A or more advanced rejection (pattern B); 48 patients (34%) had one or two episodes of grade 3A, 3B, or 4 acute rejection only during the first 6 months after transplantation (pattern C); and 26 patients (19%) had three or more episodes of grade 3A, 3B, or 4 acute rejection (pattern D). Overall mortality was 11%, 26%, 19%, and 46% for patients with patterns A, B, C, and D, respectively. No difference was found among patterns with regard to incidence of graft atherosclerosis. Left ventricular ejection fraction at 1 year after transplantation was significantly lower (p < 0.05) for patients with pattern B (50% +/- 5% versus 59% +/- 7%, 59% +/- 11%, and 56% +/- 6% for patterns A, C, and D, respectively); cardiac index also was lower for patients with pattern B than for those with pattern A (3.6 +/- 0.6 versus 4.1 +/- 0.6 L/min/m2, p < 0.05). CONCLUSIONS: Although mortality was higher for patients with more severe episodes of acute rejection, only repetitive nontreated episodes of grade 1B or 2 rejection significantly impaired long-term graft function.

Influence on survival after heart transplantation of contraindications seen in transplant recipients.

Fifty-seven patients underwent heart transplantation at our hospital between April 1986 and April 1991. In an attempt to assess the result of and the influence of contraindications seen in transplant recipients before transplantation on the outcome after transplantation, we have analyzed six of these "relative" contraindications: (1) age over 55 years (21% of patients); (2) pulmonary hypertension (pulmonary vascular resistance of more than 5 Wood units, and/or transpulmonary gradient of more than 12 mm Hg; 26% of patients); (3) renal failure (serum creatinine level of more than 2 mg/dl, and/or creatinine clearance of less than 35 ml/min; 11% of patients); (4) active infection (9% of patients); (5) diabetes mellitus (7% of patients); and (6) critical/unstable clinical condition before transplantation (25% of patients). An overall "risk score," obtained by adding one point for each contraindication, was also analyzed. Risk score was 0 (the "ideal" recipient) in 38% of patients, 1 in 25% of patients; 2 in 23% of patients; and 3 or more in 14% of patients. Actuarial survival was significantly lower for patients over 55 years of age (45% versus 68% at 18 months; p less than 0.05), for patients with elevated pulmonary vascular resistance (38% versus 72%; p less than 0.01), and for patients with kidney failure (16% versus 70%; p less than 0.01). On the contrary, survival at 18 months was not significantly different for patients with or without diabetes mellitus (50% versus 63%; not significant [NS]), active infection (60% versus 63%; NS), or critical/unstable condition (45% versus 69%; p less than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized study comparing deflazacort and prednisone in heart transplant patients.

Prednisone is widely used by most heart transplantation units despite its frequent side effects. Deflazacort, an oral synthetic steroid with fewer side effects, has been successfully used in patients after heart transplantation, but a prospective study comparing deflazacort and prednisone in transplant patients is lacking. We have carried out, in the last year, a prospective trial of deflazacort versus prednisone involving 35 consecutive heart transplant patients. Two of these patients died perioperatively (surgical mortality, 5.7%), and another two were excluded from the protocol because of diabetes mellitus in one patient and active infection before transplantation in the other patient. Thus 31 patients were enrolled in the 3-month study. All of them were treated with antithymocyte globulin, 10 mg/kg/day for 3 days after transplantation, azathioprine, and cyclosporine; patients were randomly assigned groups: 15 patients to receive deflazacort therapy, 1.5 mg/kg/day, and 16 patients to receive prednisone therapy, 1 mg/kg/day, starting the first day after transplantation. Steroids were rapidly tapered, reaching the maintenance dose at 2 to 3 weeks after transplantation (prednisone, 0.15 mg/kg/day; deflazacort, 0.25 mg/kg/day). Both groups were similar in terms of age, gender, ABO identity, serum cyclosporine levels, azathioprine dosage, and pretransplantation serum glucose and lipids levels. Seven endomyocardial biopsies were performed on each patient, at 1, 2, 3, 5, 7, 10, and 13 weeks after transplantation. Incidence of acute rejection was similar between prednisone and deflazacort groups; 33% of patients receiving prednisone therapy and 42% of patients receiving deflazacort therapy had one episode of 3A or higher rejection (not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Renal involvement in chronic graft-versus-host disease: a report of two cases.

We report details of renal involvement during the course of chronic graft-versus-host disease (cGVHD) in two patients undergoing bone marrow transplantation as treatment for acute leukemia. In both cases, the clinical picture was primarily characterized by proteinuria without hypertension or renal failure. Electron microscopy of renal biopsy specimens revealed a similar pattern in the two cases with extensive coalescence of foot processes and intramembraneous deposition of electron-dense material. Our data suggest that the kidney may be a target organ in chronic GVHD.

Interferon therapy in hemodialysis patients with chronic hepatitis C virus infection induces a high rate of long-term sustained virological and biochemical response.

AIM: The aim of the present study was to analyze the efficacy and tolerance of interferon (IFN) therapy in hemodialysis (HD) patients with chronic hepatitis C virus (HCV) infection. Specifically, we assessed whether the "normalization" of serum ALT levels was associated with the disappearance of the HCV-RNA. METHODS: Thirteen hemodialysis patients with chronic hepatitis C were treated for one year with 3 MU of alpha-IFN. The primary end point was a sustained virological response defined as the absence of HCV-RNA in the last follow-up; the secondary end points were normalization of the serum ALT levels and histological improvement. ALT was considered "normal" below 27 IU/l. RESULTS: Ten patients completed the treatment, which was discontinued in the other 3 (23%). By the end of the treatment a virological response was observed in 8 of the 10 patients (80%) who completed the one-year IFN therapy. Biochemical response was associated with a virological response in 8 of the 9 patients in whom ALT levels became normal. Three patients had a biochemical and virological relapse in the follow-up. Two of them received a further year of IFN therapy, which resulted in a sustained biochemical and virological response. In all patients who underwent a liver biopsy (n = 5), the inflammation score improved. After a median follow-up of 5 years (range 2 - 7), a sustained response was observed in 6 (46%) of the 13 patients enrolled. Two patients with a sustained response received a kidney transplant and after more than 6 years still maintain a biochemical and virological response. Side effects included flu-like syndrome (n = 8), hemoglobin decrease (n = 8), thrombocytopenia (n = 3), depression (n = 1) and seizures (n = 1). CONCLUSION: IFN treatment over a one-year period produces a high rate of long-term virological response in HD patients, associated to a biochemical response in all cases.

Immunoscintigraphy of lung cancer using 111In-labelled antiCEA F023C5-F(ab')2 fragments.

Forty-one patients with known lung carcinoma or suspicion of bearing this disease were studied with 111In-antiCEA F023C5-F(ab')2. Five patients with positive results were further studied to assess in vivo specificity using 111In-4C4-F(ab')2 (MoAb antihepatitis). Immunoscintigraphic results have been compared to immunohistochemistry in 16 patients. Tumour visualization with non-specific MoAb was present in all five patients although the maximum tumour/background (T/B) ratio obtained was 1.51. Therefore a 'specificity criterion' has been applied to examinations performed with MoAb antiCEA. There was considered to be a positive result when the T/B ratio was greater than 1.60. Results obtained in this way for thoracic lesions were 25/34 true positive (TP) (73%) and 6/7 true negative (TN) (86%). When studies were analysed visually only, the results were 32/34 TP (94%) and 3/7 TN (43%). In addition, immunoscintigraphic results are more concordant with immunohistochemical results when the specificity criterion is applied. In metastatic lesions results were 9/13 TP (69%) with only 1/3 TP (33%) for liver metastasis (anatomic site of lowest detection ability). SPECT imaging did not improve results over planar images, although it clearly contributed to a better anatomic location of lesions. The constant presence of non-specific uptake in thoracic lesions makes it necessary to establish a T/B ratio limit in order to obtain adequate specificity with the immunoscintigraphic technique.

[Short- and long-term course of heart transplantation recipients with severe dysfunction of the graft associated with acute rejection]. / Evolución a corto y largo plazo de los pacientes sometidos a trasplante cardíaco con disfunción severa del injerto asociada a rechazo agudo.

INTRODUCTION AND OBJECTIVES: Acute rejection is still a common cause of death after heart transplantation, in spite of cyclosporine. The aim of our study was to assess the incidence of severe graft dysfunction associated with acute rejection and the short and long-term outcome of these patients. METHODS: Ten of our 100 first heart transplant patients have developed rejection-induced severe cardiac dysfunction (left ventricular ejection fraction determined by echocardiography < 35% associated with 3A, 3B or 4 acute rejection). Clinical outcome, complications and evolution of left ventricular function were studied. RESULTS: Five patients were given intravenous methylprednisolone 500 to 1000 mg/day for 3 days. The other 5 patients had severe heart failure and received antilymphocyte antibodies. Three patients treated with methylprednisolone alone and one patient treated with antilymphocyte antibodies died within the first week after therapy. Left ventricular ejection fraction increased from 26 +/- 4% to 51 +/- 6% at 1 month after therapy in the 6 survivor patients. Four of the 6 survivor patients also died before 1 year after rejection (3 due to infection). Thus, long-term, overall mortality was 80%. CONCLUSIONS: Although favorable short-term results can be achieved in patients with rejection-induced severe cardiac dysfunction with immunosuppressive therapy (mainly antilymphocyte antibodies), long-term prognosis seems poor, due to the increased rate of life-threatening infections.

Isolated laryngeal leishmaniasis in an immunocompetent patient: successful treatment with surgery.

The localization of Leishmania spp. in the larynx is rare but it has recently been described in patients infected by human immunodeficiency virus (HIV). The normal treatment given is antimonials. We describe a case of isolated leishmaniasis in the larynx which was cured by surgery. Our patient was a 47-year-old man who had suffered visceral leishmaniasis in his childhood with no immunosuppression.

[Acute renal failure in a patient with myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria phenotype]. / Fracaso renal agudo en pacientes con síndrome mielodisplásico y fenotipo de hemoglobinuria paroxística nocturna.

Hemoglobin and myoglobin heme pigments and iron have acute and chronic nephrotoxic effects, which are often associated with massive hemolysis and rhabdomyolysis. We report a patient with a myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria phenotype who developed an acute renal failure after a severe haemolytic crisis. There was not evidence of renal vascular pathology, urinary tract obstruction or prerenal factors. Renal biopsy showed features of acute tubular necrosis, with extended iron deposits in tubule cell cytoplasm and tubulo-interstitial fibrosis and atrophy. The patient was oliguric requiring hemodialisys during three weeks, recovering renal function on the fourth week after admission. This case underlines the nephrotoxic role of heme pigment and iron, and possible pathophysiologic mechanisms involved in acute and chronic toxicity of both agents are reviewed.

[Transient diabetes insipidus following removal of a medullary thyroid carcinoma (author's transl)]. / Diabetes insípida transitoria tras la extirpación de carcinoma medular de tiroides.

Medullary thyroid carcinoma (MTC) is a known apudoma producing calcitonin, prostaglandins and serotonin. It can present itself as a familial or sporadic form or as part of a multiple endocrine adenomatosis. We present here the case of a patient admitted with a four-year history of diarrhea, enlargement of the thyroid and palpable lymph nodes in the right side of the neck. There was no uptake of 131I in the right lobe of the thyroid and the serum calcitonin levels were very high. With the diagnosis of MTC a total thyroidectomy mas performed developping within hours of the surgical procedure a picture of diabetes insipidus with 31 liters of urine output in the first 48 hours. It responded to vasopressin and disappeared spontaneously in two weeks. We have considered the different mechanisms that could explain the development of diabetes insipidus, and after failing to find one, we especulate at prostaglandins could play an important role in the synthesis and/or release of ADH. The sudden depletion of prostaglandins after removal of the neoplasm that produced them could account for the diabetes insipidus in our patient. We have not found any similar case described in the literature. We call attention to the need for a close postoperative observation of patients operated for MTC for the possible onset of diabetes insipidus.

[Study of 13 cases of anisakiasis in the province of Cordoba]. / Estudio de 13 casos de anisakiasis en la provincia de Córdoba.

Anisakiasis, or anisakidosis, is a parasitic zoonosis due to the infestation by nematodes of the Anisakidae family, mainly by Anisakis simplex. Notwithstanding its world wide distribution, in our country its appearance is quite recent (1991) with only 19 cases previously reported. We refer 13 cases diagnosed in different hospitals in the province of Córdoba, Spain, from September 1994 to July 1998 which represents the biggest series described in Spain so far. All the patients had a clinical onset as acute abdomen, so that they required early surgery in which a narrowing and inflammatory intestinal segment was observed and subsequently resected. Pathology revealed in such segments an intense eosinophilic infiltrate in the mucosa. Only in one of the cases parasitic fragments were detected in the intestinal mucosa and in the 12 remaining cases the diagnosis was immunological by IgE specific for Anisakis simplex determination and antigens detection of the nematode with monoclonal antibodies. As interesting epidemiologic antecedent we shall mention the fact that all patients referred a usual raw fish consumption (mainly anchovy with vinegar) which is host of third-stage larval of the parasite.

Actinomycotic ulcer of the oral mucosa: an unusual presentation of oral actinomycosis.

Although the oral mucosa is often the site of entry of actinomyces into the deeper tissues, actinomycosis in the oral mucosa is extremely rare. Actinomycotic lesions are usually described as either single or multiple abscesses or indurated masses with hard fibrous walls and soft central loculations. Actinomyces israelii is the principal cause of human actinomycosis. We present a rare case of actinomycosis caused by Actinomyces odontolyticus; it presented primarily as a long-standing ulcer of the oral mucosa mimicking a squamous cell carcinoma.

Endoscopic polypectomy in the treatment of colonic adenomas containing adenocarcinoma.

Fifty-seven adenomas containing adenocarcinoma were removed endoscopically from the colons of 56 patients (36 males and 20 females) with a mean age of 64.5 years. The 13 polyps containing carcinoma in situ were satisfactorily treated by endoscopic resection. In 29 cases, the carcinoma had invaded the head, neck or stalk of the polyp. The outcome was good in every case, including one involving invasion of the resection margin. Follow-up or intraoperative studies disclosed the presence of residual lesion in only 4 patients out of 15 with submucosal invasion. All four had invaded resection margins and incomplete endoscopic excision. Endoscopic polypectomy is a suitable therapeutic option for most colonic adenomas containing a carcinoma provided a complete resection is achieved with wide resection margins, particularly in those cases in which the submucosa is not reached.