Multiple thrombosis associated with Cytomegalovirus enterocolitis in an immunocompetent patient: a case report.

BACKGROUND: Cytomegalovirus (CMV) is reported to have thrombogenic characteristics that activate factor X in vitro and stimulate the production of factor VIII and von Willebrand factor (vWF). Thrombosis associated with CMV infection is prevalent among immunocompromised patients and predominantly presents as a solitary large thrombus in the deep vein, pulmonary artery, splanchnic arteriovenous ducts, or other similar sites. Multiple thrombi, however, are rarely observed in such cases. Here, we report about an immunocompetent man with multiple microthrombi associated with CMV infection. CASE PRESENTATION: A 72-year-old Japanese man who complained of abdominal pain was hospitalized with multiple colonic stenosis. He was later diagnosed with CMV enterocolitis and treated with ganciclover from Day 27 post-admission. During hospitalization, the patient developed thrombi in his fingers. He was initially treated with anticoagulant therapy (rivaroxaban); however, the therapy was discontinued owing to a prolonged activated thromboplastin time and an elevated international normalized ratio of prothrombin time. Instead, vitamin K and fresh-frozen plasma were administered. Nevertheless, his coagulation profile remained abnormal. Eventually, he developed colonic perforation and had to undergo emergency surgery. An intraoperative specimen showed several microthrombi in the middle and small arteriovenous ducts of his small and large intestines. The patient's coagulopathy improved preoperatively, and his overall condition improved postoperatively. Since the activation of ADAMTS13 was reduced remarkably, the thrombotic tendency was determined to be a thrombotic microangiopathy-like condition owing to increased vWF. We could not attribute the coagulopathy to any other cause except CMV infection; therefore, we concluded that this was a case of multiple thrombosis associated with CMV. CONCLUSIONS: We present an extremely rare case of a patient with multiple thrombotic microangiopathy-like microthrombosis caused by CMV infection. Our findings suggest that CMV infection may be considered as a differential diagnosis for immunocompetent individuals who present with thrombosis of unspecified cause.

Acute superior mesenteric vein thrombosis in the setting of cytomegalovirus mononucleosis: a case report and review of the literature.

Cytomegalovirus is a viral genus of the overarching family Herpesviridae, and is of particular importance because of its relevance to human disease. This association is predominantly due to human cytomegalovirus, a well-studied pathogen. In addition to the mononucleosis syndrome that can occur during acute cytomegalovirus viraemia, this virion has been recurrently implicated as a provoking factor for thromboembolic disease in the published scientific literature. As physicians increasingly forgo extensive laboratory investigation in the setting of clinical hypercoagulability, it has also become evident that in some circumstances whether or not a particular investigation alters clinical management is not necessarily the only important question. Viraemia as a provoking factor for thrombosis stands as such an example. The aim of this Grand Round is to further explore the role of cytomegalovirus as it pertains to thromboembolic disease, especially in the present era of viral-associated thromboembolism.

Acute cytomegalovirus infection associated with pulmonary embolism treated successfully with rivaroxaban: case report.

Severe life-threatening thromboembolism may be caused exclusively by the presence of an acute CMV infection or due to the association of this agent and other thrombogenic factors. We report a case of an immunocompetent young female patient who presented a pulmonary embolism associated with acute CMV infection. The patient did not have any other apparent cause of thrombosis. She was successfully treated with rivaroxaban for 6 months without further episodes. To the best of our knowledge, this is the first report of a pulmonary embolism associated with CMV treated with a direct oral anticoagulant. The current case report calls attention to the importance of signs and symptoms of thromboembolism among patients with CMV. Direct oral anticoagulants can potentially bring the same benefits to treat pulmonary embolism associated with CMV as those observed in patients not infected.

Use of Novel Oral Anticoagulant to Treat Pulmonary Thromboembolism in Patient with Ulcerative Colitis Superinfected Cytomegalovirus Colitis.

Crohn's disease and ulcerative colitis are the two major types of inflammatory bowel disease, and affect mainly the gastrointestinal tract but also have extraintestinal sequelae, such as arterial and venous thromboembolism. Thromboembolic complications, particularly pulmonary thromboembolism, can be life threatening and require prompt management with anticoagulants. Conventional vitamin K antagonists have been used for the treatment of thromboembolic complications, but the development of novel oral anticoagulants has shifted the paradigm. We report a case of a 42-year-old female with ulcerative colitis who experienced an acute flare-up due to cytomegalovirus superinfection with pulmonary thromboembolism. She was treated with oral mesalamine, intravenous steroid and ganciclovir and low-molecular-weight heparin, followed by rivaroxaban, a novel oral anticoagulant. Her symptoms resolved after treatment, and no recurrence was noted during a 6-month post-treatment follow-up.

Hypomagnesemia and increased risk of new-onset diabetes mellitus after transplantation in pediatric renal transplant recipients.

BACKGROUND: New-onset diabetes after transplantation (NODAT) is a significant co-morbidity following kidney transplantation. Lower post-transplant serum magnesium levels have been found to be an independent risk factor for NODAT in adult kidney transplant recipients. METHODS: We undertook a retrospective analysis of risk factors for NODAT in pediatric renal transplant recipients at our institution with the aim of determining if hypomagnesemia confers a significant risk of developing NODAT in this patient population. RESULTS: A total of 173 children with a median age at transplantation of 7.0 (range 1.3-17.5) years were included. Hypomagnesemia was found to be a significant independent risk factor for NODAT (p = 0.01). High trough tacrolimus levels were also independently associated with NODAT (p < 0.001). There was no significant association between NODAT and body mass index at the time of transplantation, monthly cumulative steroid dose or post-transplant cytomegalovirus viremia (p = 0.9, 0.6 and 0.7, respectively). CONCLUSIONS: This study identifies hypomagnesemia as a significant independent risk factor for the development of NODAT in pediatric renal transplant recipients. Given the clear association between hypomagnesemia and NODAT in both adults and children following renal transplantation, further studies are merited to clarify the etiology of this association and to examine the effect of magnesium supplementation on NODAT.

Hearing configuration in children with cCMV infection and proposal of a flow chart for hearing evaluation.

OBJECTIVE: This study had three main goals: (1) to determine the hearing configuration in hearing-impaired children born with a congenital CMV (cCMV) infection, (2) to see whether auditory neuropathy spectrum disorder (ANSD) was present, and (3) to propose a flow chart for the follow-up of hearing in children with cCMV. DESIGN: Hearing configuration and the presence of ANSD in cCMV infected children was analysed. Selection criteria were: hearing-impaired children with a regular audiometric follow-up for at least 36 months, no other major risk factors for hearing loss, a normal middle-ear status, and an appropriate behavioral response to the given pure-tone stimuli. STUDY SAMPLE: Out of a cohort of 206 cCMV infected children, 18 hearing-impaired children were selected. RESULTS: Audiograms of all children showed a flat configuration of SNHL: the slope between octave bands was never greater than 10 decibels. None of the 18 children were found to have ANSD. CONCLUSIONS: Hearing impairment in cCMV infants affected all frequencies equally and ANSD does not appear to be a feature of cCMV infection. A flow chart for hearing follow-up in children with cCMV infection was suggested in order to provide guidance, improve uniformity in follow-up, and to make results easier to compare.

Infección sistémica por citomegalovirus: influencia del tratamiento con foscarnet en los niveles plasmáticos de calcio y magnesio / Systemic cytomegalovirus infection: Changes in serum calcium and magnesium levels with foscarnet treatment

La infección por citomegalovirus es frecuente en pacientes trasplantados cardiacos. Foscarnet se utiliza, con evidencia limitada, como tratamiento de segunda línea tras el fracaso de ganciclovir en estos pacientes. Presentamos un caso de alteraciones electrolíticas por foscarnet administrado para el tratamiento de infección por citomegalovirus en un paciente pediátrico trasplantado cardiaco. La infección se resolvió tras 6 semanas de tratamiento, apareciendo niveles de calcio iónico bajos durante la infusión del fármaco e hipomagnesemia mantenida tratada con suplementos, que revirtieron al retirar el fármaco

Cytomegalovirus infection is common in cardiac transplant patients. Foscarnet is used, with limited evidence, as second-line treatment after ganciclovir failure in these patients. We describe the case of a paediatric cardiac transplant patient who developed electrolyte disturbances during foscarnet treatment for cytomegalovirus infection. The infection resolved after 6 weeks of treatment. Low ionized calcium and magnesium levels were observed during the drug infusion, which were treated with supplements. The serum levels reverted to normal after drug withdrawal

Consistent associations between measures of psychological stress and CMV antibody levels in a large occupational sample.

Cytomegalovirus (CMV) is a herpes virus that has been implicated in biological aging and impaired health. Evidence, largely accrued from small-scale studies involving select populations, suggests that stress may promote non-clinical reactivation of this virus. However, absent is evidence from larger studies, which allow better statistical adjustment for confounding and mediating factors, in more representative samples. The present study involved a large occupational cohort (N=887, mean age=44, 88% male). Questionnaires assessed psychological (i.e., depression, anxiety, vital exhaustion, SF-12 mental health), demographic, socioeconomic (SES), and lifestyle variables. Plasma samples were analyzed for both the presence and level of CMV-specific IgG antibodies (CMV-IgG), used as markers for infection status and viral reactivation, respectively. Also assessed were potential biological mediators of stress-induced reactivation, such as inflammation (C-reactive protein) and HPA function (awakening and diurnal cortisol). Predictors of CMV infection and CMV-IgG among the infected individuals were analyzed using logistic and linear regression analyses, respectively. Confirming prior reports, lower SES (education and job status) was positively associated with infection status. Among those infected (N=329), higher CMV-IgG were associated with increased anxiety (ß=.14, p<.05), depression (ß=.11, p=.06), vital exhaustion (ß=.14, p<.05), and decreased SF-12 mental health (ß=-.14, p<.05), adjusting for a range of potential confounders. Exploratory analyses showed that these associations were generally stronger in low SES individuals. We found no evidence that elevated inflammation or HPA-function mediated any of the associations. In the largest study to date, we established associations between CMV-IgG levels and multiple indicators of psychological stress. These results demonstrate the robustness of prior findings, and extend these to a general working population. We propose that stress-induced CMV replication warrants further research as a psychobiological mechanism linking stress, aging and health.

[POSITIVE EFFECTS OF MODERN IMMUNOCORRECTION ACCORDING TO THE ANALYSIS OF CYTOKINES AND SLPI IN PATIENTS WITH PYELONEPHRITIS].

The peculiarities of cytokines as compounds of immunogenesis are shown in the patients having acute (A) and chronic (Ch) pyelonephritis (PN). The combination of antibacterial therapy with Nukleinat and Galavit promotes the positive changes of cytokin-producing ability of immunocompetent cells and decrease in the level of proinflammation cytokines in blood and urine, secretory leucocyte protease inhibitor (SLPI) in urine. In children with PN and adult patients with diagnostically elevated titres of antibodies (IgG) to Herpes simplex virus, Cytomegalovirus are shown the positive effects of Kanephron® H and Proteflazidum, accordingly. Clinico-immunological effects of immunomodulators testify to the expediency of this usage in complex therapy with the aim to modulate the cytokine link of immunity for improvement of the effective treatment in APN and the protection against aggravation of kidney functioning in ChPN.

Acute cytomegalovirus hepatitis in an immunocompetent host.

A 52-year-old woman presented with a 1-week history of recurrent fevers and joint pains accompanied by abdominal and low back discomfort. She has a history of hypoparathyroidism and is on calcium supplements. Physical examination revealed fever and tachycardia. The rest of the examination was normal. Laboratory tests showed newly increased transaminase activity. Serum bilirubin and prothrombin time were normal. She was admitted for evaluation of acute hepatitis. Serology for hepatitis A, B, C and HIV were negative. Her serum acetaminophen and alcohol were undetected. Abdominal imaging was normal. Cultures were sterile. Additional tests for uncommon viral hepatitis included herpes simplex virus, cytomegalovirus and Epstein-Barr virus. Liver biopsy revealed non-specific inflammation. Subsequently, cytomegalovirus serology showed an IgM positive and negative IgG titre. Cytomegalovirus DNA qualitative PCR was also positive. No antiviral medication was given. She continued to have intermittent daily fever but reported no associated symptoms. She was discharged 9 days after admission in stable condition per her request with the advice to follow-up in the clinic in 1 week. Her serum hepatic profile returned to normal and she reported no more episodes of fever. Repeated titres of cytomegalovirus serology showed seroconversion.

Herpesvirus infections and allergic sensitization in children of families with anthroposophic and non-anthroposophic lifestyle - the ALADDIN birth cohort.

BACKGROUND: Growing up in families with an anthroposophic lifestyle has been associated with reduced risk of allergic disease in children. The aim of this report was to assess whether children with this lifestyle are infected earlier with Epstein-Barr virus (EBV), which has been associated with reduced risk of allergic disease, and three other herpesviruses potentially involved in allergy development, namely Human herpesvirus 6 (HHV6), Human herpesvirus 7 (HHV7) and cytomegalovirus (CMV). METHODS: Within the ALADDIN (Assessment of Lifestyle and Allergic Disease During Infancy), birth cohort study 157 children were categorized according to lifestyle into anthroposophic and non-anthroposophic. IgG-levels for EBV, HHV6, HHV7 and CMV were determined in plasma samples collected at ages 12 and 24 months and from parents. IgE levels against seven common allergens were analyzed at 24 months. RESULTS: No significant differences in seroprevalence of EBV, HHV7 or CMV were detected at any age between the two lifestyle groups. The seroprevalence of HHV6 was significantly lower in the anthroposophic group at 24 months of age (74.6% vs. 87.5%, p-value 0.048). Further, no significant associations between allergic sensitization and seropositivity to any of the viruses were detected; however, an interaction effect of lifestyle could not be ruled out. CONCLUSIONS: Our results indicate that there is no strong influence of exposure to the anthroposophic lifestyle on the time for infection with EBV, HHV6, HHV7 or CMV. These infections can therefore not be assumed to be important factors in the allergy-protective effect of this lifestyle.

[Multi-organ failure in a patient with fungaemia due to Saprochaete capitata]. / Fallo multiorgánico en paciente con fungemia por Saprochaete capitata.

BACKGROUND: The significant increase in systemic fungal infections is mainly due to the increase in immunocompromised patients. The high morbimortality of these infections, along with the high hospitalization costs they generate, makes them a problem of great importance in our hospital practice. Saprochaete capitata is a rare fungus that causes invasive infections, usually in immunocompromised patients, and for which there is still no consensus on the treatment regimen to be used. CASE REPORT: We present a case of disseminated infection by this fungus in a heavily immunosuppressed patient, who died as a result of multiple organ failure despite the life support measures taken and the wide spectrum antibiotics. CONCLUSIONS: It is vital to begin the antibiotic treatment as soon as possible, as well as the monitoring and follow-up cultures to test for fungi in neutropenic patients.

Presumed cytomegalovirus-associated retrobulbar optic neuritis in a patient after allogeneic stem cell transplantation.

A case of cytomegalovirus (CMV)-associated bilateral retrobulbar optic neuritis (ON) following haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is reported. Abrupt onset of bilateral decreased vision occurred in a 33-year-old man 7 months after haplo-HSCT. His cerebrospinal fluid (CSF) demonstrated pleocytosis with an absence of leukemic cells. CMV DNA was detected in his blood and CSF sample. Neither encephalopathy nor retinopathy was found in this patient. He was diagnosed with bilateral retrobulbar ON. Although he was given enough antiviral treatment against CMV and immunosuppression with high-dose methylprednisolone, the patient's vision showed no improvement, and he has almost total bilateral blindness. This is the first report, to our knowledge, of CMV-associated bilateral retrobulbar ON in allogeneic stem cell transplantation.

Caprylic acid in the effective treatment of intractable medical problems of frequent urination, incontinence, chronic upper respiratory infection, root canalled tooth infection, ALS, etc., caused by asbestos & mixed infections of Candida albicans, Helicobacter pylori & cytomegalovirus with or without other microorganisms & mercury.

There are many causes of frequent urination. Whenever water or fluids are consumed, the patient has to urinate within 10 or 20 min. Often urinary bladder examinations & blood tests show no significant abnormalities, & treatment by anti-bacterial or anti-viral agents does not improve the symptoms significantly. In intractable frequent urination with difficulty holding urine, as well as other intractable medical problems such as frequent coughing, white pus in gingiva, infection of the apex of a root canalled tooth, slow-healing wounds, & ALS, the authors often found coexisting mixed infections of Candida albicans (C.A.), Helicobacter pylori (H.P.), & Cytomegalovirus (CMV) with or without additional bacterial (Chlamydia trachomatis, etc.) or viral infections & increased Asbestos, with or without Hg deposits. We often found various degrees of mixed infections with C.A., H.P., & CMV in the external sphincters of the urethra & in the Trigone of the urinary bladder which consists of (1) a horizontal, band-like area between the 2 ureter openings & (2) the funnel shaped part of the Trigone at the lower half of the urinary bladder. In the coexistence of significant amounts of C.A., H.P. & CMV, the infection cannot be reduced by otherwise effective medicines for H.P. & CMV. However, one optimal dose of Diflucan, or Caprylic acid taken orally or externally applied, rapidly reduced the symptoms significantly. We found the best treatment is to give a combination of an optimal dose of Caprylic acid orally in the form of "CaprilyCare" or "Caprylic Acid," with a capsule of Omega-3 Fish Oil as an anti-viral agent, Amoxicillin, Substance Z & a Cilantro tablet. We found that an optimal dose of Caprylic acid increases normal cell telomere (NCT) to a desirable 750 ng BDORT units while Diflucan increases NCT by only 25 ng BDORT units, & with Omega-3 fish oil, leads to a mutual cancellation of both drugs. Thus, Caprylic acid is superior to & less expensive than Diflucan, & has potential application for anti-cancer, anti-aging, anti-Alzheimer's disease, anti-Autism, anti-infection, & general circulatory improvement.

Thalamic pain syndrome due to cytomegalovirus vasculitis in an HIV-positive child.

Dejerine-Roussy syndrome, also known as the thalamic pain syndrome is a condition in which the body becomes hypersensitive to pain as a result of damage to the thalamus, a part of the brain that affects sensation. Association of this syndrome with HIV is rare with few case reports described in adults. We report a 10 year old male child who was HIV positive and had developed this syndrome due to cytomegalovirus vasculitis.

Esophageal ulcer in Brazilian patients with HIV: prevalence and comparative analysis among diagnostic methods.

Esophageal ulcer (EU) represents an important comorbidity in AIDS. We evaluated the prevalence of EU, the accuracy of the endoscopic and histologic methods used to investigate viral EU in HIV-positive Brazilian patients and the numerical relevance of tissue sampling. A total of 399 HIV-positive patients underwent upper gastrointestinal (UGI) endoscopy. HIV-positive patients with EU determined by UGI endoscopy followed by biopsies were analyzed by the hematoxylin-eosin (HE) and immunohistochemical (IH) methods. EU was detected in 41 patients (mean age, 39.2 years; 23 males), with a prevalence of 10.27%. The median CD4 count was 49 cells/mm(3) (range, 1-361 cells/mm(3)) and the viral load was 58,869 copies per milliliter (range, 50-77,3290 copies per milliliter). UGI endoscopy detected 29 of 41 EU suggestive of cytomegalovirus (CMV) infection and 7 of 41 indicating herpes simplex virus (HSV) infection. HE histology confirmed 4 of 29 ulcers induced by CMV, 2 of 7 induced by HSV, and 1 of 7 induced by HSV plus CMV. IH for CMV and HSV confirmed the HE findings and detected one additional CMV-induced case. UGI endoscopy showed 100% sensitivity and 15% specificity for the diagnosis of EU due to CMV or HSV compared to HE and IH. HE proved to be an adequate method for etiologic evaluation, with 87% sensitivity and 100% specificity compared to IH. The number of samples did not influence the etiologic evaluation. The data support the importance of IH as a complementary method for HE in the diagnosis of EU of viral etiology.

Current state of clinical diagnosis and treatment of infantile cytomegaloviral hepatitis.

Cytomegaloviral hepatitis is an infantile liver disease commonly encountered in China, which could be differentiated into 4 patterns with different clinical conditions. Along with the progress of laboratory diagnostic techniques, multiple diagnostic approaches are available for this disease, but accurate diagnosis can only be made when individual patients' realities are taken into consideration. Clinical treatments are various, and the Western medicine used is mainly anti-viral agents such as Ganciclovir, and so far no unified therapeutic program has been formed. More and more ways of regarding Chinese medicine treatment of cytomegaloviral hepatitis have been published increasingly in recent years, though further research to seek preferable treatment programs is still expected.

Macrocyclic lathyrane diterpenes as antitumor promoters.

Human cytomegalovirus (CMV) preferentially infects tumor tissues and the accumulated CMV immediate-early (IE) antigen may lead to tumor promotion and progression. The development of strategies to inhibit human CMV IE antigen expression and/or function is an important goal to prevent and treat certain forms of cancers associated with human CMV. The aim of this study was to search for antitumor promoters from plant sources. The effect of six macrocyclic lathyrane-type diterpenoids, latilagascenes A-E (1-5) and jolkinol B (6), isolated from the methanol extract of Euphorbia lagascae, on the expression of IE antigen in lung cancer cells (A549) infected by CMV was studied. All the compounds, except latilagascene D (4), decreased IE antigen expression of CMV.

Therapeutic effect of a traditional Chinese medicine, ren-shen-yang-rong-tang (Japanese name: Ninjin'yoeito) on nitric oxide-mediated lung injury in a mouse infected with murine cytomegalovirus.

The therapeutic effect of a traditional Chinese medicine ren-shen-yang-rong-tang (Japanese name: Ninjin'yoeito, NYT) on murine cytomegalovirus (MCMV)-associated pneumonitis was examined. In MCMV-pneumonitis, IFN-gamma-induced nitric oxide (NO) mediates its pathogenesis. When mice, which had been infected with 0.2LD(50) of MCMV at 28 days previously, were intraperitoneally injected with anti-CD3 monoclonal antibody (mAb), MCMV-pneumonitis was induced in the lung, where high amounts of IFN-gamma-producing cells thereafter accumulated, accompanied by an elevation in the NO level in the serum and abundant expression of inducible NO synthase (iNOS) mRNA, thus resulting in all mice eventually dying. When the mice were orally treated with NYT (1000 mg/kg/day) once on the day of mAb injection and once the day after, the expression level of iNOS-mRNA was suppressed and NO level in the serum decreased. The survival rate improved from 0% to 57.1%. The pathological findings of the lungs in the NYT-treated mice were comparable to those of the uninfected controls. In contrast, NYT itself did not affect either the ratio of IFN-gamma-producing cells or MCMV titer. As a result, NYT had a therapeutic effect on MCMV-pneumonitis by decreasing the degree of inflammation mediated by the IFN-gamma-induced NO. It is also interesting to note that only two oral administrations of NYT had a therapeutic effect on viral disease.