Primary classic Hodgkin lymphoma of the ileum and Epstein-Barr virus mucocutaneous ulcer of the colon: two entities compared.

Primary classic Hodgkin lymphoma of the gastrointestinal tract represents a rare occurrence. A full patient's work-up is essential in order to exclude a secondary intestinal involvement. Histologically Epstein-Barr virus mucocutaneous ulcer closely resembles Hodgkin lymphoma. The differential diagnosis between these two entities is relevant, since both the therapeutic approach and the clinical behavior are different. Herein, we describe a case of primary classic Hodgkin lymphoma arising in the ileum and a case of Epstein-Barr virus mucocutaneous ulcer of the colon, focusing on the main clinicopathological differences.

In Silico and in Vitro Screening for P-Glycoprotein Interaction with Tenofovir, Darunavir, and Dapivirine: An Antiretroviral Drug Combination for Topical Prevention of Colorectal HIV Transmission.

The aim of the study was to use in silico and in vitro techniques to evaluate whether a triple formulation of antiretroviral drugs (tenofovir, darunavir, and dapivirine) interacted with P-glycoprotein (P-gp) or exhibited any other permeability-altering drug-drug interactions in the colorectal mucosa. Potential drug interactions with P-gp were screened initially using molecular docking, followed by molecular dynamics simulations to analyze the identified drug-transporter interaction more mechanistically. The transport of tenofovir, darunavir, and dapivirine was investigated in the Caco-2 cell models and colorectal tissue, and their apparent permeability coefficient (Papp), efflux ratio (ER), and the effect of transporter inhibitors were evaluated. In silico, dapivirine and darunavir showed strong affinity for P-gp with similar free energy of binding; dapivirine exhibiting a ΔGPB value -38.24 kcal/mol, darunavir a ΔGPB value -36.84 kcal/mol. The rank order of permeability of the compounds in vitro was tenofovir < darunavir < dapivirine. The Papp for tenofovir in Caco-2 cell monolayers was 0.10 ± 0.02 × 10-6 cm/s, ER = 1. For dapivirine, Papp was 32.2 ± 3.7 × 10-6 cm/s, but the ER = 1.3 was lower than anticipated based on the in silico findings. Neither tenofovir nor dapivirine transport was influenced by P-gp inhibitors. The absorptive permeability of darunavir (Papp = 6.4 ± 0.9 × 10-6 cm/s) was concentration dependent with ER = 6.3, which was reduced by verapamil to 1.2. Administration of the drugs in combination did not alter their permeability compared to administration as single agents. In conclusion, in silico modeling, cell culture, and tissue-based assays showed that tenofovir does not interact with P-gp and is poorly permeable, consistent with a paracellular transport mechanism. In silico modeling predicted that darunavir and dapivirine were P-gp substrates, but only darunavir showed P-gp-dependent permeability in the biological models, illustrating that in silico modeling requires experimental validation. When administered in combination, the disposition of the proposed triple-therapy antiretroviral drugs in the colorectal mucosa will depend on their distinctly different permeability, but was not interdependent.

Post-kidney transplant large bowel lymphoproliferative disorder.

Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation. The gastrointestinal (GI) tract is a common site involved, but non-specific signs and symptoms often delay the diagnosis. We report a case of EBV-associated GI-PTLD in a 68-year-old kidney transplant patient who received the kidney ten months earlier. He presented with chronic diarrhea and developed massive pneumo-peritoneum secondary to multiple colonic perforations.

Opportunistic cytomegalovirus infection causing colonic perforation in a patient with systemic lupus erythematosus.

We present the case of a 58-year-old woman with a long-standing history of systemic lupus erythematosus (SLE) who developed a cytomegalovirus (CMV) infection with colonic perforation and subsequent purulent peritonitis whilst using combined immunosuppressive therapy. The pathogenesis and the clinical presentation of this unique case is discussed in detail. Opportunistic infection should always be kept in mind in SLE patients presenting with fever. Viral serology should be routinely performed in these patients, especially when immunosuppressive therapy is given, to avoid delay in instituting adequate management and therapy.

Cytomegalovirus: a cause of colonic stricture in a premature infant.

A 27-week-old infant developed symptoms of bowel obstruction when full enteral feeds were started. Laparotomy revealed strictures in the ascending and proximal transverse colon. Right hemicolectomy was performed. Histological examination of the resected large bowel demonstrated the presence of Cytomegalovirus inclusion bodies. Cytomegalovirus infections of the gut are extremely rare in neonates. This case report alerts neonatologists and microbiologists to consider Cytomegalovirus infection as a possible cause of bowel obstruction and necrotising enterocolitis like symptoms.

Evaluation of anatomic changes in young children with natural rotavirus infection: is intussusception biologically plausible?

BACKGROUND: Several studies have shown an association between vaccination with the rotavirus vaccine and the development of intussusception. We evaluated the plausibility of a causal association between natural rotavirus infection and intussusception. METHODS: We performed ultrasound measurements, in infants with confirmed rotavirus infection and in healthy control subjects, of the ileum wall thickness and mesenteric lymph nodes, at enrollment and 1 month later. RESULTS: Thirteen pairs of patients with rotavirus infection and control subjects were enrolled. The mean distal ileum wall thickness at the first examination was 3.0 mm in patients with rotavirus infection and 2.0 mm in control subjects (P = .037). The maximum lymph node size in patients with rotavirus infection was 11.6 mm at the first examination and 7.4 mm at the second examination (P = .017). Nodal aggregates and free fluid were also observed more commonly among patients with rotavirus infection (54% vs. 9%; P = .033 for both). CONCLUSION: Rotavirus infection was associated with increased distal ileum wall thickness and lymphadenopathy during the illness period. These changes suggest a plausible mechanism by which rotavirus infection could cause intussusception.

Severe recurrent cytomegalovirus disease revealed by a colocutaneous fistula in a kidney transplant recipient.

Intestinal disorders are classical complications of cytomegalovirus (CMV) infection in kidney transplant recipients (Helderman JH, Goral S. Gastrointestinal complications of transplant immunosuppression. J Am Soc Nephrol 2002: 13: 277-287). Severe ulcerative colitis that is sometimes lethal has been reported (Foucar E, Mukai K, Foucar K, Sutherland DE, Van Buren CT. Colon ulceration in lethal cytomegalovirus infection. Am J Clin Pathol 1981: 76: 788-801 and Frankel AH, Barker F, Williams G, Benjamin IS, Lechler R, Rees AJ. Neutropenic enterocolitis in a renal transplant patient. Transplantation 1991: 52: 913-914). The immunosuppressive drugs currently used, and notably mycophenolate mofetil (Cellcept), cause significant changes in the incidence, duration, and viral load of CMV infections with severe atypical forms of CMV disease (De Maar EF, Verschuuren EA, Homan vd Heide JJ, et al. Effects of changing immunosuppressive regimen on the incidence, duration and viral load of cytomegalovirus infection in renal transplantation: a single center report. Transpl Infect Dis 2002: 4: 17-24 and Perez Valentin MA, Cofan F, Sole M, et al. Atypical cytomegalovirus in renal transplantation: a new form of presentation. Nefrologia 2002: 22: 381-385). This report describes a patient who suffered from several episodes of colitis due to an unusual and late-appearing CMV infection.