High-dose Valganciclovir Treatment for Resistant Cytomegalovirus Colitis due to UL97 and UL54 Mutations.

We report the first case of a ganciclovir-resistant cytomegalovirus (CMV) involving the gastrointestinal tract that was successfully treated with high-dose valganciclovir. A kidney transplant recipient developed drug-resistant CMV colitis which was initially treated with valganciclovir, but his CMV was found to have major resistance to ganciclovir and cidofovir due to UL97 and UL54 mutations. The patient was switched to intravenous foscarnet 40 mg/kg given every twelve hours. However, foscarnet had to be discontinued after 4 days of treatment due to acute kidney injury. Patient was restarted on valganciclovir at a higher target dose of 1800 mg twice a day based on the creatinine clearance. CMV became undetectable 2 weeks after valganciclovir treatment was completed. High-dose valganciclovir along with immune suppression reduction may be a treatment option for CMV colitis with ganciclovir resistance due to dual UL97 and UL54 gene mutations.

Cytomegalovirus colitis in a patient undergoing postoperative adjuvant chemotherapy for lung adenocarcinoma with uracil-tegafur.

When we examine a patient with symptoms of acute enteritis in the course of chemotherapy with oral fluoropyrimidines such as uracil-tegafur (often referred to as UFT), we usually suspect 5-fluorouracil-induced enterocolitis. In case of persistent clinical symptoms despite discontinuation of chemotherapy, cytomegalovirus colitis should be considered in the differential diagnosis of chemotherapy-induced enterocolitis. We herein report the case of a patient who underwent surgery for lung adenocarcinoma followed by postoperative adjuvant chemotherapy with uracil-tegafur and was diagnosed as having cytomegalovirus colitis during the therapy. In the course of chemotherapy, cytomegalovirus colitis occasionally occurs even though the patient does not experience severe myelosuppression; thus, it is necessary that we recognize its potential occurrence.

Enhanced transduction of colonic cell lines in vitro and the inflamed colon in mice by viral vectors, derived from adeno-associated virus serotype 2, using virus-microbead conjugates bearing lectin.

BACKGROUND: Virus-mediated delivery of therapeutic transgenes to the inflamed colon holds a great potential to serve as an effective therapeutic strategy for inflammatory bowel disease, since local, long-term expression of the encoded therapeutic proteins in the colorectal system is potentially achievable. Viral vectors, derived from adeno-associated virus (AAV), should be very useful for such therapeutic strategies, particularly because they can establish long-term expression of transgenes. However, few studies have been carried out to investigate the ability of AAV-based vectors to transduce the inflamed colon. RESULTS: AAV, derived from adeno-associated virus serotype 2 (AAV2), showed a limited ability to transduce colonic cell lines in vitro when used in free form. No appreciable enhancement of the transduction efficiency was seen when AAV2 particles were attached stably to the surfaces of microbeads and delivered to target cells in the form of AAV2-microbead conjugates. However, the transduction efficiency of these colonic cell lines was enhanced substantially when a lectin, concanavalin A (Con A), was co-attached to the microbead surfaces, to which AAV2 particles had been conjugated. This considerable infectivity enhancement of AAV2-microbead conjugates by the co-attachment of Con A may be derived from the fact that Con A binds to alpha-D-mannosyl moieties that are commonly and abundantly present in cell-surface carbohydrate chains, allowing the conjugates to associate stably with target cells. Intracolonical administration of free AAV2 or AAV2-microbead conjugates without Con A into a mouse colitis model by enema showed very poor transduction of the colonic tissue. In contrast, the delivery of AAV2 in the form of AAV2-microbead conjugates bearing Con A resulted in efficient transduction of the inflamed colon. CONCLUSION: AAV2-microbead conjugates bearing Con A can serve as efficient gene transfer agents both for poorly permissive colonic cell lines in vitro and for the inflamed colon in a mouse colitis model. This efficient transduction system for the inflamed colon should be useful for the development of gene therapy strategies for inflammatory bowel disease.

[Cytomegalovirus colitis simulating neoplasm in a patient with HIV infection]. / Colitis por citomegalovirus que simula una neoplasia en paciente con infección por HIV.

AIM: Cytomegalovirus colitis occurs in at least 5-10% of patients with AIDS. The most usual form of clinical presentation is that of a chronic picture of diarrhea, fever and abdominal pain in a patient with AIDS with a CD4 lymphocyte count lower than 100/mm3, although it can be the diagnostic index for AIDS up to in 25% of the cases. METHODS: Cytomegalovirus colitis in a patient with AIDS was diagnosed by endoscopy and colonic biopsy. The clinical was diagnosed by endoscopy and colonic biopsy. The clinical picture consisted of abdominal pain, without the findings of fever and diarrhea described in almost 80% and 100% respectively of the cases published in the literature. The barium enema carried out showed a stenotic appearance, like serviette ring, in the ascending colon, which suggested neoplasia of the colon. RESULTS: Induction therapy with ganciclovir was effective. However, the patient was readmitted one year later for chorioretinitis due to cytomegalovirus, without any evidence of gastro-intestinal involvement. CONCLUSIONS: Although unusual, cytomegalovirus colitis can be present with an abdominal clinical picture without diarrhea. Radiological and/or endoscopic pseudotumoral forms which this entity can adopt are often described. Endoscopy with digestive biopsy in essential for diagnosis. Therapy with ganciclovir can be effective although the reappearance of findings from cytomegalovirus can occur at another area, or as a gastrointestinal recurrence.