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We compared the efficacy of ganciclovir versus that of cytomegalovirus (CMV) immunoglobulin for the prevention of CMV disease in 31 CMV-seropositive heart transplant recipients who had received early immunoprophylaxis with OKT3 monoclonal antibodies. The incidence of CMV disease and visceral involvement was much higher in the CMV immunoglobulin group than in the ganciclovir group (40 versus 6%, respectively; P = 0.03). No adverse effects were found in the CMV immunoglobulin group, but 19% of the patients in the ganciclovir group developed mild leukopenia or a mild increase in their serum creatinine levels.

Donors age 50 years was an exclusion criteria in past decades. The increase of patients in the waiting list has determined the acceptance of older donors (over 65 years old). We analyze our results in liver transplantation using donors over 65 years.From 1986 to may 1994, we performed 381 OLT. In five cases (1.3%) the OLT was performed using donors over 65 years of age (66, 67, 68, 70 and 71). The selection criteria for donors and recipients were similar to the other transplanted patients. Immunosuppression included cyclosporine or FK-506, prednisone and azathioprine.There were no primary graft failures and preservation damage, biochemical and clinical evolution were not different to the procedures using younger donors. Three grafts presented non-corticoresistant acute rejection. After a follow-up of 11.6 mo (range 4-37 mo) only one graft was lost (Kaposi's sarcoma in the liver). Four grafts and four patients are in excellent biochemical and clinical condition.Donor age should not be an exclusion criteria. Grafts from older donors (over 65 years old) may be considered safe and will permit to increase the number of OLT.

Hepatitis C virus (HCV) infection was studied in 60 liver transplant recipients. Antibodies to HCV were tested by both a second-generation ELISA test and a four-recombinant immunoblot assay (4-RIBA) just before the transplant and every three months thereafter. HCV RNA detection was performed by polymerase chain reaction (PCR) at least three times after the transplant in all the patients. Thirty-nine patients tested negative by ELISA before LT (group A), 14 patients tested positive by both serological tests (group B), and seven tested positive only by ELISA (group C). Posttransplant hepatitis was diagnosed in 11/14 in group B in comparison with 3/39 in group A (P

A case of epididymo-orchitis due to Nocardia asteroides in a liver transplant recipient is reported. Nocardiosis is an extremely rare cause of epididymo-orchitis. Four other cases published in the English language medical literature are reviewed. All patients were immunocompromised, and other organs were affected simultaneously. Clinically the infection presented as a painful enlargement of the testicle with few inflammatory signs. Mortality was high (3/5), and in the two survivors long-term sulfonamide therapy was combined with orchiectomy. Nocardiosis should be considered in the diagnosis of epididymo-orchitis in the immunocompromised host.

The efficacy of ganciclovir, given prophylactically, to prevent cytomegalovirus-related disease was evaluated in liver transplant recipients, mostly seropositive, under treatment with OKT3 monoclonal antibodies. The incidence of cytomegalovirus disease and visceral involvement was reduced, respectively, from 52 and 36% in the control group to 12 and 8% in the ganciclovir-treated patients. Leukopenia was a frequent (32%) side effect of ganciclovir administration.

We have performed 284 OLT and from 1990 we accept donors older than 50 years. We analyzed 100 consecutive OLT from 1990 in relation to donor age and we divided them in three groups: A) 10 liver transplants with donors16 years old; B) 76 liver transplants with donors between 16 and 49 years old, and C) 14 liver transplants with donors49 years old. The follow-up was more than 6 months. The liver preservation was carried out with Belzer solution and the immunosuppression was performed with cyclosporine A, corticoids and azathioprine. The C group donors were more stable haemodynamically (less dopamine dosage-p0.001- and less hours with arterial hypotension-p0.05-) and they died less of craneoencephalic traumatism than A group donors (p0.01). The C group donors didn't have more frequence of liver esteatosis or greater graft harvest lesions (p = n.s.). The cold ischaemia time was greater in C group vs A (p0.05) and its pretransplant clinical status was more serious than in A and B groups (p0.05). There were no significant differences between groups in relation to recipient status, frequence of hepatic artery or portal vein thrombosis, frequence of acute rejection, chronic rejection or biochemical graft evolution at first month. There were more primary graft non functions in B vs A (p0.05) and retransplants in B vs A and C (p0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Liver transplantation is a valid treatment in chronic viral B and C hepatitis. But disease recurrence is very frequent in HBV hepatitis after the procedure, and its prevention and treatment are unresolved problems. Hepatitis C recurrence in the graft seems also to be common, and further studies of its pathobiology are needed.

Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality in liver transplant recipients. The aim of this study was to determine the incidence, clinical characteristics, risk factors and response to treatment of CMV infection in liver transplant recipients.Fifty-nine adult patients who underwent a liver transplant in our hospital were prospectively studied. Cell cultures were used to document CMV infection and disease. Ganciclovir treatment was only given to patients with documented CMV disease.Active infection was shown in 47 of 59 patients (80%), and symptomatic infection (disease) in 17 (29%). The most frequent clinical presentation was hepatitis (9 cases) followed by flu-like syndrome (6 cases) and pneumonitis (4 cases). The average time from transplant to the diagnosis of CMV disease was 36 days. The seronegative recipients of seropositive donors developed symptomatic infection more frequently (66%) than other patients (p0.05). As well as the CMV serologic status before transplantation, the use of anti-OKT3 antibodies was the only risk factor related to CMV disease (p0.01). The treatment with ganciclovir was successful in 17 of 19 symptomatic episodes.Active and symptomatic CMV infection in recipients of liver transplantation were very frequent in our study. The transplant from seropositive to seronegative and the use of anti-OKT3 antibodies increased the incidence of CMV disease. Ganciclovir appeared as a safe and, apparently, highly efficient drug.

We have evaluated the microbiologic output and clinical significance of the detection of cytomegalovirus in 111 bronchoalveolar lavage specimens from immunosuppressed patients with pneumonitis. The samples were simultaneously processed by conventional tube culture and the rapid shell-vial centrifugation culture assay. Cytomegalovirus was recovered from 30 specimens (27%). The rapid shell-vial procedure was more sensitive than the tube culture, but in two cases cytomegalovirus was isolated only in tube cultures. Cytomegalovirus was considered clinically significant in only 3 from 13 HIV positive patients. All culture positive, HIV negative patients received treatment with ganciclovir. However, ganciclovir was never used on culture negative, HIV negative patients and cytomegalovirus related morbi-mortality was not found in these patients. A prospective study is needed to conclude if a cytomegalovirus negative culture also has a treatment exclusion value in HIV positive patients.

The incidence and characteristics of major bacterial infections were studied prospectively in 50 consecutive adult patients who underwent liver transplantation (LT). All patients received the same protocol of immunosuppression, bowel decontamination, antibiotics prophylaxis, and follow-up. Thirty-two patients (64%) had at least one episode of major bacterial infection. One death was directly related to a bacterial infection, accounting for 13% of postoperative mortality. The most critical period for infection was the first 2 months after surgery, when 69% of the infections occurred. The most frequent clinical presentations were bacteremia, pneumonia and abdominal abscesses. Eighty percent of the bacteremias had an identifiable source, the most frequent being intravascular catheters. Gram-positive microorganisms (69%) predominated over gram-negative rods (26%) and anaerobes (5%). The use of selective bowel decontamination (SBD) with norfloxacin may explain this predominance. Major bacterial infections are an important source of morbidity and mortality after LT. Efforts to prevent these infections and to determine their source and specific treatment, will improve the management and the outcome of these patients in the future.

We describe a severe case of meningoencephalitis and polyradiculoneuritis that occurred following rubella in an otherwise healthy 19-year-old man. The diagnosis was made serologically. To our knowledge this is the first reported case of extensive neurological involvement in an adult with rubella.

The effects and the persistence of a single injection of ivermectin (Ivomec®) to steers, at the recommended dose rate of 200 μg kg −1 body weight, were studied in spring field experiments (Spanish conditions). Elimination of ivermectin by cattle (faecal route) was rapid (12 days), with a peak in day 5. The persistence of ivermectin in dropped dung was low under field conditions (< 6 days). The drug itself did not increase attraction of beetles to dung. The attraction of beetles to dung from treated animals increased after day 5 until day 17, beyond the time when ivermectin was available. The hypothesis made was that ivermectin modified the gut flora of treated cattle after the peak of elimination. Watering of pats did not influence results

In the context of solid organ transplantation, screening of recipients and organ donors is crucial, and should be performed with great rigour to minimize the reactivation or the risk of transmission of certain infectious processes. This review aims to update understanding of the possible pathologies involved, as well as of emerging infections that, as a result of globalization, are gaining increasing prominence on a daily basis.

A study was made of 10,438 individuals belonging to 19 species from the families Scarabaeidae and Geotrupidae to analize their daily flight activity throughout the year. Based on the results of the study, two groups of species were defined : one with primarily crepuscular or nocturnal activity and another with diurnal activity. The crepuscular species concentrate their activity within a very narrow range of light (110-0 lux), whereas the nocturnal species fly from dusk until shortly after midnight. In spring the diurnal species fly in the afternoon, but in sunmer each species adjusts its flight pattern according to the time of day when the levels of temperature and humidity are optimum for that species. Variations in the maximum flight activity may also occur. Analysis is then made of the influence of both endogenous and exogenous factors as regulatory agents of the daily flight activity., 10.438 individus appartenant à 19 espèces de Scarabaeidae et Geotrupidae ont été étudiés. L'auteur a effectué l'analyse de l'activité journalière de ces insectes pendant une année. Deux groupes d'espèces se distinguent sur la base de cette étude : l'un ayant une activité de vol crépusculaire ou nocturne, l'autre ayant une activité diurne. L'auteur montre que l’activité des espèces crépusculaires se centre sur une courte période de faible intensité lumineuse (110-0 lux), alors que les espèces nocturnes se manifestent dès la tombée de la nuit, jusque vers minuit. Au printemps, les espèces diurnes volent l'après-midi ; en été, chaque espèce a sa période d'activité de vol en accord avec les niveaux de température et d'humidité correspondant au préférendum de l 'espèce. Les facteurs exogènes et endogènes intervenant sur l'activité de vol sont également analysés., Mena J., Galante Eduardo, Lumbreras C.-J. Daily flight activity of Scarabaeidae and Geotrupidae (Col.) and analysis of the factors determining this activity. In: Ecologia mediterranea, tome 15 n°1-2, 1989. pp. 69-80.

To evaluate the clinic characteristics and therapeutic aspects of endocarditis by Streptococcus pneumoniae sensitive and resistant to penicillin.Twelve cases of pneumococcal endocarditis evaluated in 4 Spanish hospitals over the last 10 years were studied, analyzing their clinical characteristics and the existence of resistance to penicillin. The features were compared with a series of 98 cases found in a review of the literature.All the patients were males, most being alcoholics. The course of the disease was acute (2 weeks) in all the cases and evolved with great aggressivity: cardiac failure (9 patients), myocardial abscess (7 patients), multiple arterial embolisms (5 patients), septic arthritis (4 patients). Three patients had simultaneous pneumococcal meningitis but only one had pneumonia. The valve most affected was the aortic (9 cases). Three cases were due to strains of Streptococcus pneumoniae with moderate resistance to penicillin (CMI 0.5-1 micrograms/ml). Global mortality was 42%. All the patients receiving inadequate antibiotic treatment died. Vancomycin and cefotaxime appear to be effective in the treatment of cases produced by strains of pneumococcus with intermediate sensitivity to penicillin. There were no apparent differences in mortality between the cases of endocarditis by pneumococcus sensitive or moderately resistant to penicillin.Pneumococcal endocarditis continues to condition a high mortality similar to that produced in previously made series. The classic relation with meningitis and pneumonia is infrequent today. The appearance of strains resistant to penicillin may increase the incidence of this infection and further worsen prognosis.

Recent development of an assay based on the hybridization of the amplification product obtained by polymerase chain reaction (PCR) of the RNA of hepatitis C virus (HCV) with specific probes for each viral genotype ("reverse-hybridization"), has permitted to have a rapid, simple and reproductible technique to identify the different genotypes of HCV. The identification of HCV genotypes seems to be important given their different pathogenic capacity and response to interferon therapy.We prospectively studied 221 patients with HCV infection defined by the detection of viral RNA in serum by "nested-PCR". HCV genotype was determined by "reverse-hybridization" using specific oligonucleotide-probes for each genotype corresponding to the 5, UTR.HCV 1b genotype was predominant in 221 patients studied (180/221, 81%), followed by 1a (10%) and by 3 and 4 (4% respectively). Two patients presented mixed infection (1a/1b). No case of infection by genotypes 2 and 5 was found. The predominance of 1b genotype was more evident in adults than in children (83 vs 62%) (p0.05).HCV 1b is the predominant genotype among our patients with hepatic disease induced by HCV. The reverse-hybridization assay is a simple and rapid technique that permit the identification of the most important genotypes of hepatitis C virus.

Seventy three adults underwent orthotopic liver transplantations between February 1987 and November 1989 and were followed (54 retrospectively and 19 in a prospective study) with the aim of establishing the incidence of deep mycoses (3 disseminated candidiasis due to C. albicans, 1 invasive aspergillosis due to A. fumigatus and 1 invasive pulmonary aspergillosis due to A. niger and A. fumigatus). 4/5 of these infections occurred in the first month after transplantation. All the patients were associated with the following clinical risk factors: previous use of wide spectrum antibiotics (5/5); more than 1 abdominal laparotomy (4/5), due to primary failure of the graft (3/4) and thrombosis of the hepatic artery (1/4). Two of the three patients [corrected] with invasive candidiasis had previous episodes of documented fungemia. 24 patients of the group who didn't show MIP had some risk factor which in all of them was the previous use of high dose steroids and/or of wide spectrum antibiotics, in addition to the used in surgical prophylaxis. In our series, the one risk factor associated with MIP was more than one previous laparotomy (p less than 0.001). Other significant associated infections were 3 bacterial sepsis (2 due to Enterococcus faecalis and 1 due to Staphylococcus epidermidis) and one viral (Cytomegalovirus viremia). The mortality rate was 100%, however the cause of death was multifactorial.

The aim of this study was to analyze the effect of using different antibiotics on the risk of acquiring a bacterial or fungal superinfection in hospital-acquired infections. A systematic review of the literature using the PubMed (Medline) database from January 1990 to December 2003 was performed. We selected only those studies with at least 25 patients in each arm in which the clinical efficacy of several antibiotics (third generation cephalosporins, fluorquinolones, piperacillin-tazobactam and carbapenems) were evaluated for the treatment of severe infections, and which specifically reported the rate of superinfection. The microorganisms most frequently implicated in the development of superinfection were: Candida spp. (42.3%), Enterococcus spp. (18.8%), enterobacteria (13.8%), Staphylococcus spp. (9.5%), Pseudomonas aeruginosa (6.6%), and Clostridium difficile (4.1%). The antibiotic most frequently related to superinfection was ciprofloxacin (38.1%), followed by cefotaxime (23.3%), imipenem (12%), meropenem (10.2%), and cefepime (6.1%). The lowest percentage of superinfection was observed with the use of piperacillin-tazobactam (5.4%).

The polymerase chain reaction (PCR) and viral culture techniques were prospectively compared for the detection of cytomegalovirus (CMV) in blood samples from 24 liver transplant recipients. Nine patients had one or more episodes of viremia, seven of which were clinically symptomatic infections. All samples in which CMV was isolated by culture were positive by the PCR. However, the PCR result was also positive for one or more samples from 11 patients who never developed CMV-related symptoms. Although the PCR is a very sensitive technique for CMV detection in blood samples from liver transplant recipients, it is not useful as a marker of symptomatic CMV disease.

Amphotericin B is the medication of choice in systemic or invasive fungal infections, but its use often is limited by nephrotoxicity. Lipid formulations of amphotericin B have reduced this risk, but it is not known if these medications also prevent the deterioration of kidney function in patients with previous kidney failure or at risk of kidney failure, such as newborns and patients treated with cyclosporine A.A retrospective analysis was made of epidemiological, clinical and analytic data collected from the clinical histories of patients with previous renal failure or at high risk of nephrotoxicity who were treated with liposomal amphotericin B at our hospital between January 1991 and January 1997.An analysis was made of 23 patients (15 men and 8 women, mean age 38 years) who met established criteria. All had severe immunosuppression. Twelve patients had been treated previously with conventional amphotericin B, but treatment was interrupted for kidney failure. The other 11 patients in the group received cyclosporine A (9 cases) or were at risk of nephrotoxicity because of their underlying disease or situation (2 cases). No deterioration of kidney function due to liposomal amphotericin B was observed in any patient. In 5 of the 12 patients who had deterioration of kidney function as a result of previous use of conventional amphotericin B and lived more than one week after changing treatment, it was observed that kidney function recovered and baseline creatinine levels were reached.Our findings suggest that liposomal amphotericin B can be used safely in immunocompromised patients with fungal infection who have failure or high risk of kidney failure.

Presented in part at the 35th American Society of Clinical Oncology meeting. Atlanta (GA); 1999. Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; BACKGROUND Granulocyte colony-stimulating factors (G-CSFs) have been shown to help prevent febrile neutropenia in certain subgroups of cancer patients undergoing chemotherapy, but their role in treating febrile neutropenia is controversial. The purpose of our study was to evaluate-in a prospective multicenter randomized clinical trial-the efficacy of adding G-CSF to broad-spectrum antibiotic treatment of patients with solid tumors and high-risk febrile neutropenia. METHODS A total of 210 patients with solid tumors treated with conventional-dose chemotherapy who presented with fever and grade IV neutropenia were considered to be eligible for the trial. They met at least one of the following high-risk criteria: profound neutropenia (absolute neutrophil count

Human autologous liver transplantation is possible due to an adequate suppression of the body's immune response. This also causes a higher hepatitis infection rate, making hepatitis prevention very important.We describe our experience with hepatitis B virus vaccination in 140 adult liver transplant recipients, transplanted from 1986 to 1994 with more than one year of follow-up. Excluded were those who had hepatitis B surface antigens or antibodies to those antigens before the transplant. The vaccination schedule was 0-1-2 months with a double dose of recombinant vaccine.The total response rate (surface antigen antibodies10 U) was 40% (56/140); the rate was 47.7% in men and 26% in women. At the end of the study, only 17.1% (24/140) of the patients had antibodies10 U. The response rate was higher in patients with antibodies to hepatitis B core antigen (66.6%) than in those lacking antibodies (31.7%), and more long lasting (42.4% vs 11.2%). The response rate in 116 patients with booster doses was 12.9%. Six correctly vaccinated patients (4.28%) acquired new hepatitis B virus infections after the operation.The total response rate in these patients is much lower than in the general population, and there is a rapid decline of titers, probably due to immunosuppression. The role of booster doses in these patients should be clarified.

We review 27 episodes of nosocomial fungemia due to Candida parapsilosis over a 6 year period, compared to a control group of 27 episodes of nosocomial fungemia due to Candida albicans. During the study period, C. parapsilosis accounts for 23% of all yeast isolated from blood-cultures. Fungemia due to C. parapsilosis was more frequently seen in males (23/4). More than half of the cases (15/27) presented in the postoperative period. In 89% of cases the patients were under total parenteral nutrition and 81% had received broad-spectrum antibiotics. In 41% of cases, the source of the fungemia was unknown, and in another 41% of cases was related to an iv line infection. Direct attributable mortality to C. parapsilosis infection was 11%. When compared to the control group, nosocomial fungemia due to C. parapsilosis occurs in patient with more prolonged courses of total parenteral nutrition, and also was related with less frequent development of septic shock and lower attributable mortality.

We evaluated the pathogenic role of Corynebacterium urealyticum in the development of encrusted pyelitis (EP) and encrusted cystitis (EC), and their clinical consequences in renal transplant recipients. During a 4-year period, we studied seven renal transplant recipients with EP and two with EC. The records of 320 other renal transplant patients studied during the same period were used as a control group. C urealyticum (> or = 10(5) CFU/ml) was isolated from 4 patients with EP (urine 3, blood 1) and from 1 patient with EC (urine). Alkaline urines with struvite crystals, microscopic hematuria, and sterile conventional urine cultures were present in all our cases. All the patients with EP developed obstructive uropathy with deterioration of the renal function and pyelonephritis (4 patients) or renal abscesses (3 patients). Chronic urinary discomfort and macroscopic hematuria were present in the 2 patients with EC. Long-term vesical and ureteral catheterization were considered the most important risk factors for the development of EC and EP, respectively. Vancomycin was successfully used in 5 cases, but all the patients required a derivative procedure or a surgical resection of the incrustations to improve. We conclude that EP and EC should be investigated in renal transplant patients who develop pyelonephritis, obstructive uropathy, or chronic urinary symptoms. EP and EC could lead to the loss of their grafts. C urealyticum appears to have a pathogenic role in these entities.

The aim of the study was to determine whether the detection of Clostridium difficile toxin in stools may be more profitable than conventional stool cultures for the etiologic study of nosocomial diarrhea and to analyze what risk factors favor the development of nosocomial diarrhea by C. difficile.The presence of enteropathogens and A and B toxins of C. difficile were investigated (by monoclonal antibody enzymoimmunoassay) in stools of patients with nosocomial diarrhea. A series of patients simultaneously admitted without diarrhea were selected as the control group.During a 6 month period 92 patients with nosocomial diarrhea and 82 controls without diarrhea were studied. The C. difficile toxin was detected in 8 of these 174 patients (4.6%). Eight point seven percent of the nosocomial diarrheas were related with C. difficile while only 1% were due to an enteropathogen (Salmonella enteritidis). C. difficile toxin was not detected in any patient who did not have diarrhea. In comparison with the patients with diarrhea due to other causes, the patients with diarrhea by C. difficile had more frequently received antibiotics over the previous 7 days (57 vs 88%) and had been hospitalized for a longer time (or = 7 days) (58 vs 88%) (p0.05).In the author's institution infection by Clostridium difficile is the most frequent cause of nosocomial infectious diarrhea, especially in patients admitted for a prolonged time or who receive antibiotics. The routine investigation of enteropathogens in the cases of nosocomial diarrhea does not seem justified while the detection of the A and B toxins of C. difficile may be more profitable.

A case of severe graft versus host disease in a liver transplant recipient is presented. Due to HLA similarity between donor and recipient, the demonstration of cellular chimerism had to be made by PCR-HLA-B sequencing. In addition, we review the literature on this entity emphasizing its poor outcome, the difficulty of the differential diagnosis, and the need for the development of new prophylactic and therapeutic strategies in its management.

A prospective, randomized, multicenter study addressed the safety and efficacy of fluconazole therapy in 143 liver transplant patients. Seventy-six patients received daily oral fluconazole (100 mg), and 67 received nystatin (4 X 10(6) U) during the first 28 days after transplantation. Candida colonization occurred in 25% and 53% of patients in the fluconazole and nystatin groups, respectively (P = .04), and 13% and 34% of patients in the respective groups had Candida infections (P = .022). Of these patients, 10.5% in the fluconazole group and 25.3% in the nystatin group had superficial candidal infections (P = .024). Invasive candidiasis developed in 2 patients in the fluconazole group (2.6%) and 6 in the nystatin group (9.0%) (P = .12). There was no increased hepatotoxicity, cyclosporine interaction, or emergence of clinically relevant resistant Candida strains attributable to fluconazole. Thus, oral fluconazole (100 mg) is safe and reduces Candida colonization and infection after liver transplantation.