RELAPSING HEPATITIS A AS AN INDICATION FOR LIVER TRANSPLANTATION
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s Submitted for the 68th Annual Scientific Meeting of the American College of Gastroenterology October 10-15, 2003, Baltimore, Maryland: CLINICAL VIGNETTES: PDF OnlyLassa virus
Lassa fever
Recombinant virus
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P1180 Aims: In the initial days after transplantation hyperglycemia has been related to increasedβcell death and reducedβcell mass, suggesting that transitory hyperglycemia could have a positive effect on transplanted islets. The aim of this study is to identify the insulin treatment that can reduce βcell death after syngeneic islet transplantation. And to test whether insulin treatment to recipient before and after transplantation can save the number of transplanted islet. Methods: Male Lewis rats aged 8-10weeks were used as donors and recipients of transplantation. Islets were isolated by collagenase digestion and histopaque separation method and hand-picked under a dissecting microscope. Islets were cultured for 5days and transplanted into the renal subcapsular space of streptozotocin induced diabetic rats. Three groups of recipient were studied. Group1 (n=6): no insulin treatment; Group2 (n=6): insulin treatment from day 7 before transplantation to transplantation day; Group3(n=6): insulin treatment from day 7 before transplantation to day 7 after transplantation. In each group, 250 islets and 500 islets were transplanted. Blood glucose were measured 28 day after transplantation. Nephrectomy was performed on day 28 and graft was examined in histology (hematoxylin and eosin stain) and immunohistochemistory (insulin stain). Results: In each group, recipient rats transplanted 500 islets maintained normoglycemia throughout the initial 14days. Islet grafts were nice looking and well vascularized. Histologically, these grafts contained abundantβcell. On the other hand, in group3 recipient rats transplanted 250 islets maintained normoglycemia and grafts contained enoughβcell, but failed in that of group1 and group2. Conclusions: Insulin-induced normoglycemia in the initial 7days after islet transplantation could maintain the islets graft in good condition. As a result, we could reduce transplanted islets (250 islets) to maintain normoglycemia.
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The envelope (E) glycoprotein of JEV is the major antigen to elicit neutralizing antibody (NAb) against JEV infection. In order to develop a rapid and safe neutralization assay system for evaluation of the JEV vaccine strains, we constructed JEV-pseudotyped viruses with JEV env genes (Nakayama-NIH, Beijing-1). The titers of JEV-pseudotyped viruses with NK and BJ strains were 4.0×104 IFU/ml and 1.3×105 IFU/ml in Vero cell cultures, respectively. We have analyzed the neutralization activity of immunized mouse sera with JEV-NK and JEV-BJ pseudotyped viruses. The neutralizing antibody titers of NK and BJ (50% reduction of virus) were about 1:10,000 at each immunized sera. Compared with conventional plaque reduction neutralization test (PRNT), the method using JEV-pseudotyped virus has desirable advantages such as more rapid, easier, and non-biohazardous. This neutralization assay system might be useful to evaluate NAb activity against JEV vaccine strains or vaccine candidates.
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1Liver Transplant Program, Mayo ClinicRochesterMN *Address reprint requests to Timucin Taner, M.D., Ph.D., Liver Transplant Program, Mayo Clinic, 1216 2nd Street SW, Rochester, MN, 55902. E‐mail: [email protected]
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We read with interest the recent article entitled "Concomitant diagnosis of sexually transmitted infections and human monkeypox in patients attending a sexual health clinic in Milan, Italy" by Rizzo et al.1 in the "Journal of Medical Virology". The recent global outbreaks of human monkeypox virus (mpxv) infections have raised international concerns regarding modes of transmission particularly in developed countries.1, 2 Cases of cutaneous coinfections with herpes simplex, varicella zoster, and human immunodeficiency viruses have been reported.3-10 Our aim is to highlight a novel clinicopathologic observation of concomitant mpxv skin infections with herpes simplex virus and cytomegalovirus in two men. Similar to Rizzo et al. study, this brief communication points to sex as a potential human-to-human mode of transmission of the current outbreak. Multiple viruses may be detected from the lesions of patients with mpox, and therefore a broad workup should be performed in these patients. The first patient was a previously healthy 30-year-old Asian man who presented with a skin rash that started on the penile shaft spreading over the trunk, arms, and face for 10 days. Initially, the skin lesions were asymptomatic then they became itchy, and painful, and were associated with fever, arthralgia, headache, and myalgia. The rash began 2 weeks after having sexual contact. The patient disclosed bisexual sexual behavior of having multiple sexual encounters with multiple different partners. He denied a history of recent travel, contact with animals, insect or rodent bites, drug intake, or similar previous lesions before the current presentation. He sought a private clinic, and was prescribed non-steroid anti-inflammatory drugs and antibiotics for 5 days without improvement. Physical examination revealed several vesicles, pustules, eroded papules, and eschars with erythematous bases scattered over the genitalia, upper trunk, arms, and face (Figure 1A). The palms and soles were free. The patient did not have penile discharge, intraoral or eye lesions, lymphadenopathy, or organomegaly. Clinical differential diagnoses included viral exanthems, syphilis, and drug eruption. Serologic tests were negative for human immunodeficiency virus, cytomegalovirus, and treponema. A repeat serology confirmed the negative status for human immunodeficiency virus. His immune status screen for lymphocytes was normal. Serology revealed positive IgG and IgM for herpes simplex virus type 2. A throat swab test and a sample from the biopsied skin pustule were submitted for virus polymerase chain reaction, which detected mpxv DNA. The patient was treated with intravenous acyclovir, followed for 3 weeks and the rash started to heal. Skin punch biopsy showed a pustular vesicle (Figure 1B). The vesicle revealed acantholytic keratinocytes, some with eosinophilic intracytoplasmic inclusions and others with smudged nuclear inclusions. Typical viral cytopathic changes of herpes infection were partly obscured. Immunohistochemistry demonstrated positive herpes simplex virus inclusions (Figure 1C). The second patient was a 34-year-old heterosexual African man with a history of human immunodeficiency virus infection. He was not on antiretroviral therapy. He denied a history of recent travel. He developed a fever and multiple painful small boils that became indurated crusted lesions on the genitalia, limbs, face, and trunk, which developed 2 weeks after having sexual contact (Figure 2A). He did not have penile discharge, oral or ocular lesions, lymphadenopathy, or organomegaly. His palms and soles were free of skin lesions. Clinical differential diagnoses included viral infections and syphilis. His immune status screen showed a CD4 count of 11.0 cells/µL and a CD4:CD8 ratio of 0.09. Serology revealed positive IgG and IgM for cytomegalovirus, negative for herpes simplex virus and syphilis. He had a blood sample for a polymerase chain reaction that detected CMV DNA. Throat swab and biopsied skin lesion DNA polymerase chain reaction tests were positive for mpxv. The patient succumbed to death due to CMV-related pneumonia, sepsis, and multiple organ failure despite treatment with intravenous ganciclovir. Skin biopsy showed an epidermal pustular vesicle with acantholytic keratinocytes with eosinophilic intracytoplasmic inclusions. Herpes simplex virus immunomarker was negative. The deep dermis also demonstrated vasculitic and dermal inflammatory changes with subtle features suspicious for cytomegalovirus cytopathic changes (Figure 2B). This was confirmed by positive nuclear immunostaining (Figure 2C). Monkeypox is a zoonotic skin infection that starts on the face spreads over the trunk and extremities, involves the palms and soles, and is associated with lymphadenopathy.2 Histologically, the skin lesions show a spongiotic intraepidermal blister with mixed inflammatory infiltrates and eosinophilic intracytoplasmic inclusions in the keratinocytes.11 Occasional multinucleated cells, nuclei with central ground-glass inclusion-like appearance, and follicular involvement may be seen in some cases. Differential diagnoses might include herpes and varicella viruses and other pox viruses.11 Cases of atypical varicella zoster virus skin infections in patients with mpxv infection or from endemic areas have been reported.3, 4 In addition, coinfections between mpox, herpes simplex virus, varicella zoster virus, syphilis, and gonorrhea particularly among HIV-infected homosexual men have been also reported.5-10 This raises a speculated transmission relationship between these viruses, particularly to the current outbreaks.12 The recent outbreaks occurring outside the usual endemic regions of mpxv, most cases were unlinked to recent travel from endemic countries, and the occurrence of multiple clusters may point to a yet undetected chain of possible human-to-human transmission.1, 2, 12 A significant proportion of the reported cases was detected in homosexual men, some from facilities for sexually transmitted diseases.1, 2, 12, 13 The current unusual clinical presentations suggest that mpxv is spreading sexually in certain social groups depending on the routes of virus inoculation.1, 2, 12, 13 Similarly, our cases showed clinical presentations of mpox with simultaneous herpes simplex virus and cytomegalovirus skin coinfections. The patients disclosed sexual contact with multiple partners and developed the rash after sexual intercourse. The rash started on the penis and then spread to the trunks, face, and arms. The skin lesions histologically mimicked herpesvirus skin vesicles in which the characteristic eosinophilic intracytoplasmic inclusions of orthopoxvirus were partly obscured by herpes smudgy nuclear inclusions in the first patient, and by cytomegalovirus vasculitic inflammatory changes in the second patient. Similar to previous reports, our observations point to mpxv infections being sexually transmitted and possibly modified by other virus coinfections, which may mutually be concealed by the superimposed mpxv skin lesions. Serology for acute HSV and CMV is poor.14, 15 IgM is an indicator of recent infection only in subjects who lack detectable IgG.14 Even though IgM detection is a sensitive marker of primary viral infection, but its specificity is poor because IgM may be also produced during viral reactivation and persists following primary infection in some individuals.15 Our patients showed positive serologic tests for both IgM and IgG. This suggests herpes simplex virus and cytomegalovirus reactivation. The fact that they developed the new skin lesions 2 weeks after sexual exposure determines that these individuals were acutely rather than chronically infected with the reactivated viruses. The initial viral cutaneous lesions may serve as entry routes for mpxv during sexual intercourse setting the conditions for simultaneous infections. Because of the possibility of multiple viral skin infections, it is always useful to carry out diagnostic laboratory and instrumental tests to arrive at the correct diagnosis. Noninvasive diagnostics in dermatology has recently made use of new instrumental techniques for the diagnosis of viral skin infections. Using line-field confocal optical coherence tomography, Cortonesi et al.16 have demonstrated patterns corresponding to orthopoxvirus histopathologic features, which was confirmed to be cowpox virus in a child. This tool can guide to a viral infection and a correct diagnosis. In conclusion, our clinicopathologic observations highlight mpxv cutaneous infection with simultaneous herpes simplex virus and cytomegalovirus coinfections in the same skin lesions. In this era of multiple coexisting ongoing and newly emerging viral pandemics, unusual cutaneous manifestations with atypical modes of transmission warrant high vigilance by clinicians and pathologists to consider emerging viral zoonotic outbreaks with modified modes of transmission and consider multiple viral coinfections, particularly in certain vulnerable social groups. Badr AbdullGaffar carried out conceptualization, histologic data collection, and data analysis and wrote and edited the manuscript. Suad Abdulrahman carried out clinical data collection and analysis, and reviewed, and approved the final manuscript draft. The authors declare no conflict of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Monkeypox
Concomitant
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Infectious bursal disease
Newcastle Disease
Recombinant virus
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Recombinant virus
Poxviridae
Duck embryo vaccine
Attenuated vaccine
Orthopoxvirus
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