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INTRODUCTION AND OBJECTIVE:Studies have shown that patients treated with conventional radiation can have higher risk of gastrointestinal and genitourinary side effects. There are limited data showi...

A 46-year-old, right-handed, African American man presented to the emergency department after 1 week of persistent hiccups and 3 days of nausea and vomiting. His family member also noted that he had been experiencing right-hand tremor and gait imbalance for the last 3 months. Over the 6 months prior to presentation, the patient's coworkers had noticed that he was completing his work more slowly, that he was forgetting how to perform simple tasks, and that several times he had come to work at the wrong hours. The patient had a history of HIV diagnosed 10 years earlier and reported good adherence to an antiretroviral regimen consisting of tenofovir, emtricitabine, and atazanavir boosted by ritonavir, without any changes for several years. His viral load was undetectable when tested 8 months prior to presentation.

Purpose To perform a histological analysis of free epithelial flaps that were intentionally created with an Epi-K epikeratome (Moria S.A.) during epi-LASIK in eyes with virgin corneas and eyes with previous corneal surgery or keratoconus. Setting Vissum–Instituto Oftalmologico de Alicante, Alicante, Spain. Methods This prospective and consecutive case series comprised 18 free flaps obtained from 18 patients. Twelve patients had virgin corneas, and 6 had altered corneas from previous surgery, trauma, or keratoconus. The flaps were fixed in 4% buffered formaldehyde (pH 7) for posterior histopathological analysis. Serial cuts of each flap were performed, and the sheets were stained with hematoxylin–eosin and periodic acid-Schiff. The main outcome measure was the histopathology of the corneal flaps. Results All flaps from virgin corneas consisted entirely of epithelium without residual stromal tissue or Bowman's layer. Histopathological analysis of the flaps after epi-LASIK in patients with previously altered corneas showed varying levels of stroma in all cases. Conclusion Epi-LASIK with the Epi-K epikeratome effectively cleaved the epithelium from Bowman's layer in healthy corneas; however, when the integrity of Bowman's layer is compromised, epi-LASIK should be avoided as stromal invasion will likely occur.

Peritonitis occurring after liver transplantation (PLT) has been poorly characterized to date. The aims of this study were to define the incidence, risk factors, microbiology profiles, and outcome of nonlocalized PLT. This was a retrospective study of 950 cadaveric liver transplantation (LT) procedures in 837 patients, followed for a mean of 1,086 days (range, 104-2,483 days) after LT. PLT was defined as the presence of at least one positive ascitic fluid culture after LT. There were 108 PLT episodes in 91 patients occurring at a median of 14 days (range, 1-102 days) after LT. Significant risk factors associated with the development of PLT by multivariate analysis included pre-LT model for end-stage liver disease score, duration of LT surgery, Roux-en-Y biliary anastomosis, and renal replacement therapy after LT. Biliary complications, intra-abdominal bleeding, and bowel leak/perforation were associated with 34.3%, 26.9%, and 18.5% of episodes, respectively. Multiple organisms, gram-positive cocci, fungus, and multidrug-resistant bacteria were isolated in 61.1%, 92.6%, 25.9%, and 76.9% of ascitic fluid cultures, respectively. The 28 fungal PLT episodes were associated with bowel leak/perforation and polymicrobial peritonitis. Patients who developed PLT after their first LT had a significantly greater risk of graft loss or mortality compared to unaffected patients. Parameters significantly associated with these adverse outcomes by multivariate analysis were recipient age at LT and bowel leak or perforation after LT. In conclusion, PLT is a serious infectious complication of LT, associated with significant intra-abdominal pathology and reduced recipient and graft survival.

Background. Invasive fungal infection has a major impact on the morbidity and mortality of liver transplant recipients. Human herpesvirus (HHV)-6 infection after transplantation is associated with an immunosuppressive state and the development of cytomegalovirus disease. Because cytomegalovirus infection is a risk factor for invasive fungal infection after transplantation, we have examined whether HHV-6 and fungal infection are associated after transplantation. Methods. Pretransplantation sera from 247 consecutive liver transplant recipients were analyzed for IgG to HHV-6. Thirty-three (13%) HHV-6-seronegative recipients were identified. Six of 33 (18%) seronegative recipients experienced fungal infection as compared with 15 of 214 (7%) seropositive recipients (P=0.034). Results. In a univariate analysis of risk factors for fungal infection, pretransplantation seronegativity to HHV-6 (P=0.034), intraoperative cryoprecipitate requirements greater than the 75th percentile (P=0.035), reoperation (P=0.005), biliary stricturing postoperatively (P=0.046), and gastrointestinal or vascular complications postoperatively (P=0.030) were identified as significant risk factors. Moreover, in pairwise multivariate analysis, pretransplantation HHV-6 seronegativity remained a significant variable even in the presence of each of the other variables. Conclusions. These results suggest that HHV-6 seronegativity before transplantation is a valuable clinical marker that identifies patients at risk for developing fungal infection after transplantation.

In a cohort of 43 liver transplant recipients who did not receive antiviral prophylaxis, qualitative and quantitative polymerase chain reactions (PCRs) from peripheral blood were prospectively compared to determine their value in the diagnosis of established cytomegalovirus (CMV) disease and for the early detection of CMV replication as a marker for preemptive antiviral therapy. Using a cutoff of 7000 copies of CMV DNA per sample, the specificity and positive predictive values of qualitative PCR for the diagnosis of established CMV disease increased from 33% to 89% and from 54% to 82%, respectively, without reducing the 100% sensitivity and negative predictive value. By contrast, quantification of viral load provided no additional advantage to qualitative PCR for the early diagnosis of CMV infection before development of disease.

Objective: To determine the effects of an immune-enhancing experimental diet (XD = supplemental arginine, trace elements, and increased omega-3 fatty acids) versus standard diet (SD), on immune cell function and clinical outcome of critically injured patients Design: Prospective randomized clinical trial of patients admitted to the surgical intensive care unit after trauma (Injury Severity Score > 13). Materials and Methods: Patients received early enteral nutrition with either XD or SD for a minimum of 5 days. Measurements: Mortality, intensive care unit, ventilator, and hospital days, as well as incidence of adult respiratory distress syndrome (ARDS) and infectious complications were recorded. Nutritional parameters were also studied. Peripheral blood leukocytes were isolated from normal volunteers and from patients on days 1, 6, and 10 of feeding. Main Results: Demographics and injury severity were similar in both groups. Both SD (n = 21) and XD (n = 22) groups revealed depressed monocyte function (tumor necrosis factor, prostaglandin E 2 , and procoagulant activity) on day 1 compared with a reference group (p < 0.05). However, monocytes from XD patients began to normalize their response (tumor necrosis factor, prostaglandin E 2 , and procoagulant activity) by day 6. Although ARDS occurred more frequently in the XD group (45 vs. 19%), the majority of ARDS in both groups occurred very early, with only three patients in the XD (13.6%) and one patient in the SD (4.7%) groups developing ARDS after study entry. XD patients remained on the ventilator longer (16.4 vs. 9.7 days) and in the hospital longer (32.9 vs. 22 days) compared with the SD group, but overall mortality was nearly identical (4.5 vs. 5%). Conclusion: The exact role and timing for diets with immune-enhancing effects has yet to be defined.

Cytomegalovirus (CMV) strains resistant to ganciclovir have been associated with specific mutations in the UL97 and UL54 genes. The UL97 gene of a CMV strain isolated from a renal transplant recipient before and after 438 days of ganciclovir treatment was amplified by polymerase chain reaction and sequenced. A novel mutation resulting in deletion of codons 595 to 603 was identified in the viral DNA from specimens obtained after, but not before, prolonged ganciclovir therapy. Clinical and virological resolution of CMV disease occurred after switching to foscarnet therapy. Although many ganciclovir resistance mutations have been mapped to the UL97 codon range 591-607, this one is unusual in that it involves deletion of half these codons. Because UL97 seems to be necessary for effective CMV replication, this deletion suggests that much of codons 591-607 can be removed without destroying the biological function of UL97, and that this codon range can be altered in various ways to affect ganciclovir susceptibility. Rapid, flexible genotypic assays directed at this part of UL97 may facilitate the early recognition of ganciclovir resistance.

Endotoxin (lipopolysaccharide) stimulation of macrophages (M phi) induces the generation of toxic reactive oxygen intermediates (ROI); however, recent studies implicate intracellular redox changes in signal transduction pathways for cytokines. To test whether oxidant stress modulates M phi activation, rabbit alveolar M phi were exposed to the following: diamide (oxidizes intracellular glutathione); glucose oxidase (generates hydrogen peroxide); or xanthine oxidase (generates superoxide), before lipopolysaccharide. Supernatants were assayed for tumor necrosis factor (TNF) and cell lysates were assayed for procoagulant activity (PCA). TNF mRNA was analyzed by Northern blot. M phi exposure to diamide and glucose oxidase augmented TNF production, PCA expression, and TNF mRNA accumulation; however, xanthine oxidase exposure inhibited TNF production while augmenting PCA expression. M phi signal transduction can be enhanced by increasing cellular oxidant stress. The differential response of TNF versus PCA suggests the existence of distinct redox-sensitive signal transduction pathways. These data define a mechanism by which oxidants generated during inflammation may modulate M phi function.