[Ischemic hepatitis in an 81 year old patient with congenitally corrected transposition of the great arteries]. / Hepatitis isquémica en paciente de 81 años con transposición congénita corregida de grandes vasos.

The congenitally corrected transposition of the great arteries is a rare form of congenital heart disease, with survival beyond the 6th decade of life being rare. Even more unusual is its presentation alone, without any other form of congenital heart disease. Ischemic hepatitis is a rare entity characterized by an elevation of transaminasas and a centrilobular necrosis due to a reduction in hepatic blood flow, generally of reversible evolution. The authors present a case of ischemic hepatitis in an 81-year-old patient with congenitally corrected transposition of the great arteries. The fatal evolution of the episode and the longevity of the patient are both notable. We comment on the clinical and diagnostic aspects of both entities.

Hepatitis isquémica en paciente de 81 años con transposición congénita corregida de grandes vasos / Ischemic hepatitis in an 81 year old patient with congenitally corrected transposition of the great arteries

La transposición corregida de grandes vasos es una malformación congénita cardiaca extraordinariamente inusual, con muy escasa supervivencia por encima de la sexta década. Todavía más rara es su presencia sin otras anomalías cardiacas asociadas.La hepatitis isquémica es una entidad poco frecuente caracterizada por una elevación de transaminasas y necrosis centrolobulillar debida a una reducción del flujo hepático, generalmente de evolución reversible. Se presenta un caso de hepatitis isquémica de curso fulminante en un paciente de 81 años con transposición corregida de grandes vasos. Destacan tanto la tórpida evolución de la hepatitis, como la longevidad del paciente. Comentamos los aspectos clínicos y diagnósticos de ambas entidades

Small bowel intussuspeption is an unusual pathology in the adult. Most commonly, it is secondary to intestinal wall organic disorders. ;;A complete small bowel obstruction is the most frequent clinical presentation, which requires emergency surgery in many cases. The preoperative diagnosis is infrequent. ;;The best treatment is surgical resection

Antiviral susceptibility of Herpes simplex viruses and its clinical correlates: a single center's experience.

The in vitro susceptibility to acyclovir of 204 herpes simplex virus isolates from 165 immunocompromised patients treated at our hospital was determined by the cytopathic effect reduction assay. Approximately 95% of herpes simplex virus 1 and 73% of herpes simplex virus 2 isolates were inhibited by acyclovir at concentrations of <2 microgram/mL. From 8 patients (5%), an isolate with low susceptibility to acyclovir (50% inhibitory dose, >3 microgram/mL) was recovered. Medical records of 83 patients were reviewed. Lesions resolved in most of the patients, independent of treatment. Treatment failures were not always associated with isolation of an in vitro-resistant virus. On the contrary, when a virus with low susceptibility to acyclovir was isolated, resolution of the lesion was the rule. In 9 of 10 patients with subsequent recurrent episodes of disease, the susceptibility of the viruses isolated was similar to that of the first episode. Routine susceptibility testing in our geographic area is not encouraged because of the low incidence of acyclovir-resistant herpes simplex viruses.

Utilidad clínica del estudio de la sensibilidad al aciclovir de los virus herpes simple / Clinical utility of susceptibility testing of herpes simplex virus to acyclovir

Se ha estudiado la sensibilidad in vitro al aciclovir de 96 cepas de virus herpes simple, aisladas de 80 pacientes inmunodeprimidos atendidos en nuestro hospital, mediante la técnica de reducción del efecto citopático. El 98 por ciento (61/62) de las cepas de virus herpes simple tipo 1 y el 91 por ciento (31/34) de las de virus herpes simple tipo 2 eran sensibles a una concentración de aciclovir inferior a 3 mg/l. En un 5 por ciento de los pacientes estudiados se aislaron cepas de virus herpes simple resistentes al aciclovir (DI50 >3 mg/l). El 98 por ciento de las lesiones causadas por virus herpes simple sensibles in vitro al aciclovir (DI50 <3 mg/l) se resolvieron independientemente del tratamiento. En dos casos la técnica de reducción del efecto citopático no pudo predecir el fallo del tratamiento y la persistencia de las lesiones no se asoció con el aislamiento de una cepa resistente in vitro. En cuatro casos el aislamiento de una cepa resistente al aciclovir no fue indicativo de fallo terapéutico. En conclusión, creemos que no es necesario determinar la sensibilidad in vitro de los virus herpes simple al aciclovir de forma sistemática, y que este estudio debe reservarse para aquellos casos en que persistan las lesiones y se hayan descartado otras circunstancias como posible causa de la falta de respuesta clínica. (AU)

[In vitro susceptibility to ganciclovir and foscarnet of cytomegaloviruses]. / Sensibilidad in vitro de citomegalovirus al ganciclovir y al foscarnet.

Ganciclovir is the drug of choice for the treatment of acute cytomegalovirus infections. This antiviral agent is a nucleoside analog of guanine whose activity is dependent upon its intracellular phosphorylation to the triphosphate derivative. Foscarnet is used to treat immunosuppressed patients such as organ transplant recipients and AIDS patients with cytomegalovirus who do not tolerate or develop resistance to ganciclovir. Foscarnet is a pyrophosphate analog that directly inhibits viral DNA polymerase. Resistant isolates have been recovered from immunocompromised patients treated with both anticytomegalovirus compounds. The aims of this study were to prepare a plaque reduction assay to study the in vitro susceptibility of cytomegalovirus to ganciclovir and foscarnet, and to apply it to the knowledge of in vitro susceptibility values of cytomegalovirus isolated from clinical samples. Eighty isolates from patients who had never been treated with ganciclovir or foscarnet were tested for antiviral susceptibility. The plaque reduction assay took 6-8 weeks. The results are expressed as ID(50) (inhibitory dose 50), and the ID(50) values of ganciclovir were between 2.14 and 13.49 microM. The ID(50) for ganciclovir was higher that 12 microM in only two cases (2%). The molecular study of the DNA of these did not show any mutation in the UL97 gene. The ID(50) values of foscarnet were between 46.65 and 460.22 microM. In 78 cases (98%) foscarnet ID(50) was lower than 400 microM. These results were comparable with those obtained by other authors. To summarize, the frequency of cytomegalovirus strains resistant in vitro to ganciclovir and foscarnet in previously untreated patients was low and when it was present it did not involve therapeutic failure since the patients progressed favorably.

Sensibilidad in vitro de citomegalovirus al ganciclovir y al foscarnet / In vitro susceptibility to ganciclovir and foscarnet of cytomegaloviruses

El antivírico de elección en el tratamiento de las infecciones graves causadas por citomegalovirus es el ganciclovir, un análogo del nucleósido de guanina que precisa ser fosforilado a la forma ganciclovir trifosfato para actuar como antivírico. En los casos en que por alguna razón el ganciclovir no sea el tratamiento de elección, la alternativa terapéutica es el foscarnet, que se engloba en el grupo de los análogos del pirofosfato. En pacientes con sida y otras inmunodeficiencias se ha descrito enfermedad por citomegalovirus resistente al tratamiento con ganciclovir o foscarnet. Los objetivos de este trabajo han sido la puesta a punto de la técnica de reducción del número de placas para el estudio de la sensibilidad in vitro al ganciclovir y al foscarnet, y su aplicación para el conocimiento de los valores de sensibilidad in vitro de los citomegalovirus aislados de muestras clínicas. Se estudiaron 80 cepas de citomegalovirus obtenidas de pacientes que no habían recibido tratamiento previo. La realización de la técnica requirió entre seis y ocho semanas. Los resultados se han expresado como DI50 (dosis inhibitoria 50) y los valores para el ganciclovir se han situado entre 2,14 y 13,49 µM. En 78 cepas (98 por ciento) la DI50 del ganciclovir fue inferior a 12 µM. Para el foscarnet los valores de DI50 se han situado entre 46,65 y 460,22 µM. En 78 cepas (98 por ciento) la DI50 del foscarnet fue inferior a 400 µM. En dos cepas la DI50 del ganciclovir fue superior a 12 µM, y en ellas el estudio molecular de su DNA no mostró ninguna mutación del gen UL97. En otras dos cepas la DI50 del foscarnet fue superior a 400 µM. En resumen, la frecuencia de cepas de citomegalovirus resistentes in vitro al ganciclovir y al foscarnet en pacientes no tratados previamente ha sido baja, y cuando ha existido no ha sido indicativa de fallo terapéutico puesto que los pacientes de que se aislaron evolucionaron favorablemente (AU)

[Clinical utility of susceptibility testing of herpes simplex virus to acyclovir]. / Utilidad clínica del estudio de la sensibilidad al aciclovir de los virus herpes simple.

In vitro susceptibility to acyclovir of 96 strains of herpes simplex virus isolated from 80 immunocompromised patients attended in our hospital was studied by the cytopathic effect reduction assay. Ninety-eight percent (61/62) of herpes simplex virus 1 strains and 91% (31/34) of herpes simplex virus 2 strains were inhibited by acyclovir concentrations lower than 3 mg/l. In 5% of the patients herpes simplex strains resistant to acyclovir (ID(50) >3 mg/l) were isolated. Ninety-eight percent of the lesions caused by herpes simplex viruses susceptible to acyclovir (ID(50) <3 mg/l) resolved independently of treatment. In two cases, the cytopathic effect reduction assay was not able to predict treatment failure and persistance of the lesions was not always associated with isolation of a resistant strain in vitro. In four cases, isolation of a strain resistant to acyclovir was not indicative of treatment failure. In conclusion, we believe there is no need to routinely test susceptibility of herpes simplex viruses to acyclovir and that susceptibility testing should be indicated only in patients in whom lesions persist and other causes have been ruled out.

Community respiratory virus infections in patients with hematologic malignancies.

BACKGROUND AND OBJECTIVE: The main difficulty of PCR-based clonality studies for B-cell lymphoproliferative disorders (B-LPD) is discrimination between monoclonal and polyclonal PCR products, especially when there is a high background of polyclonal B cells in the tumor sample. Actually, PCR-based methods for clonality assessment require additional analysis of the PCR products in order to discern between monoclonal and polyclonal samples. Heteroduplex analysis represents an attractive approach since it is easy to perform and avoids the use of radioactive substrates or expensive equipment. DESIGN AND METHODS: We studied the sensitivity and specificity of heteroduplex PCR analysis for monoclonal detection in samples from 90 B-cell non Hodgkin's lymphoma (B-NHL) patients and in 28 individuals without neoplastic B-cell disorders (negative controls). Furthermore, in 42 B-NHL and in the same 28 negative controls, we compared heteroduplex analysis vs the classical PCR technique. We also compared ethidium bromide (EtBr) vs. silver nitrate (AgNO(3)) staining as well as agarose vs. polyacrylamide gel electrophoresis (PAGE). RESULTS: Using two pair consensus primers sited at VH (FR3 and FR2) and at JH, 91% of B-NHL samples displayed monoclonal products after heteroduplex PCR analysis using PAGE and AgNO(3) staining. Moreover, no polyclonal sample showed a monoclonal PCR product. By contrast, false positive results were obtained when using agarose (5/28) and PAGE without heteroduplex analysis: 2/28 and 8/28 with EtBr and AgNO(3) staining, respectively. In addition, false negative results only appeared with EtBr staining: 13/42 in agarose, 4/42 in PAGE without heteroduplex analysis and 7/42 in PAGE after heteroduplex analysis. INTERPRETATION AND CONCLUSIONS: We conclude that AgNO(3) stained PAGE after heteroduplex analysis is the most suitable strategy for detecting monoclonal rearrangements in B-NHL samples because it does not produce false-positive results and the risk of false-negative results is very low.

Conventional respiratory viruses recovered from immunocompromised patients: clinical considerations.

Lower respiratory tract infection is the most common complication in the immunocompromised patient. From January 1991 to December 1995, 785 consecutive patients with suspected respiratory tract infections were studied. One hundred ninety-nine viruses were isolated from 182 (23%) of 785 bronchoalveolar lavage fluid specimens. Cytomegalovirus was isolated from 131 patients, herpes simplex virus was recovered from 31, and conventional respiratory viruses (CRVs) were recovered from 36. There were 9 influenza A viruses, 2 influenza B viruses, 7 parainfluenza viruses, 5 respiratory syncytial viruses, 5 adenoviruses, 6 enteroviruses, and 3 rhinoviruses. We identified 22 patients from whom a CRV was the only microorganism recovered; 13 patients developed pneumonia, 10 had acute respiratory failure, 5 required support with mechanical ventilation, and 5 (23%) died. In conclusion, CRVs are frequent causes of respiratory illnesses and are associated with high rates of morbidity and mortality among immunocompromised patients.

Cytomegalovirus pp65 antigenemia-guided pre-emptive treatment with ganciclovir after allogeneic stem transplantation: a single-center experience.

The optimal prophylactic strategy for cytomegalovirus (CMV) disease after allogeneic hematopoietic stem cell transplantation has not yet been established. The aim of this study was to analyze our single-center experience with a uniform protocol of CMV antigenemia-guided pre-emptive treatment with ganciclovir (GCV) after allografting. Fifty-two consecutive adult patients, 48 of them transplanted from HLA-identical matched related donors were included. T cell-depleted marrow or peripheral blood were used in 21 cases. After engraftment, weekly blood samples were tested for CMV pp65 antigenemia and viremia (conventional cultures) until day +100. GCV was started if CMV antigenemia and/or CMV viremia were detected. CMV infection (CMV-I) was found in 19 patients (37%). Seven patients suffered from CMV disease (CMV-D), three colitis and four pneumonias. There was one death directly related to CMV-D and three further cases died from refractory GVHD with CMV-D. Only one patient developed CMV pneumonia without any previous positive antigenemia and/or viremia. Multivariate analysis identified grades II-IV acute GVHD (P = 0.02) and peripheral blood stem cell transplantation (P = 0.03) to be risk factors for developing CMV-I. In conclusion, this monitoring protocol allowed early treatment of CMV-I without progression to CMV-D. Pre-emptive therapy had the additional advantage of avoiding GCV administration in most of our allograft recipients.