Radiolabelled antimicrobial peptides for imaging of infections: a review

Risk factors suggestive of relatively late exposure to EBV have been consistently associated with Hodgkin's disease (HD) in younger adults. In addition, evidence of EBV infection has been found in the Reed-Sternberg cells themselves in about one-third to one-half of all HD cases. However, no study yet published has correlated these childhood social environment risk factors with the presence of EBV in Hodgkin's tumor cells. We examined whether EBV-positive HD occurs in those patients whose childhood environment would predispose them to relatively late exposure to EBV. The study population consisted of 102 cases of mixed cellularity (MC; n = 25) or nodular sclerosing (n = 77) HD. Samples that tested positive for either EBV-encoded RNA or latent membrane protein or both were considered EBV-positive. Of the 102 cases, 83 completed a questionnaire regarding childhood social environment. The association with EBV-positivity was estimated by the odds ratio (OR) with 95% confidence intervals (CI). Twenty-two percent of the cases were EBV-positive. These cases were more likely to be MC (OR, 6.2; CI, 2.3-16.3) and male (OR, 3.4; CI, 1.3-9.0). History of infectious mononucleosis (IM) was not predictive of EBV-positivity, with only 3 of 14 such patients being EBV-positive (P = 0.82). Contrary to our hypothesis, no association between EBV and childhood environment risk factors was identified. The association of EBV with MC histology and male gender agrees with previous reports. The most intriguing finding was the dissociation between IM history and EBV-positivity, in that almost all of the cases with a history of IM were EBV-negative.     

Epstein-Barr virus and Hodgkin's disease: further evidence for the three disease hypothesis

The epidemiology of Hodgkin's disease suggests that it is a heterogeneous condition comprising more than one disease entity. The Epstein-Barr virus (EBV) is present in the Reed-Sternberg cells of a proportion of cases and is likely to play a role in the pathogenesis of these cases. In this study we show that EBV association rates vary with age at diagnosis. We suggest that Hodgkin's disease can be divided into three disease entities on the basis of EBV association and age, thereby providing biological support for the multiple aetiology hypothesis proposed by MacMahon (Cancer Res 1966; 26: 1189-1290).     

Roles of COX-1 and COX-2 in gastrointestinal pathophysiology

We studied 40 cases of Hodgkin's disease (HD) from Costa Rica for evidence of Epstein-Barr virus (EBV) in the Reed-Sternberg and Hodgkin (RS-H) cells. We also compared the epidemiologic features of these patients with previous reports of HD in industrialized and developing nations. Because Costa Ricans enjoy a relatively higher standard of living than the residents of other developing Central American nations yet live in the same general geographic region and are genetically similar, we believed that this comparison might shed additional light on the hypothesis that the prevalence of EBV in HD and the epidemiologic factors of HD are influenced by socioeconomic factors. In 16 (40%) of 40 cases, immunohistochemical studies demonstrated that the RS-H cells were positive for EBV latent membrane protein (LMP), including 1 case of lymphocytic depletion analyzed, 12 (86%) of 14 cases of mixed cellularity, and 3 (15%) of 20 cases of nodular sclerosis. All five cases of lymphocytic predominance were negative. In the 16 EBV LMP-positive cases, polymerase chain reaction studies revealed that the virus was type A in 12 cases and type B in 4 cases. Nodular sclerosis was the most common type of HD, accounting for 20 cases (50%), followed by mixed cellularity, with 14 cases (35%). The relatively low prevalence of EBV in the RS-H cells of HD and the high incidence of nodular sclerosis in Costa Rica are similar to industrialized nations and are unlike HD in neighboring Central American countries. These findings further support the hypothesis that the prevalence of EBV in HD and the epidemiologic features of HD are most closely linked with socioeconomic conditions, and geographic location or ethnic heritage are of relatively less importance.     

Determination of HLA-A*02 antigen status in Hodgkin's disease and analysis of an HLA-A*02-restricted epitope of the Epstein-Barr virus LMP-2 protein

There is good evidence for an association between Epstein-Barr virus (EBV) and Hodgkin's disease (HD). In approximately one-third of cases, the EBV genome is detectable in Reed-Sternberg (RS) cells and there is expression of the viral nuclear antigen EBNA-1 and the latent membrane protein LMP-1. Expression of LMP-2 has been demonstrated at the mRNA level, and it is presumed that the protein is expressed alongside LMP-1. The LMP-2 protein is known to contain an epitope presented to cytotoxic T-cells which is restricted through the HLA class I antigen A*0201 in healthy seropositive individuals. Since most HLA-A*02-positive Caucasians are HLA-A*0201-positive, it was hypothesized that HLA-A*02-positive individuals would be under-represented among Caucasians with EBV-associated HD. HLA-A*02 status was determined, using flow cytometry and/or the polymerase chain reaction, for 276 individuals including 176 cases of HD. There was no significant difference between the frequency of HLA-A*02 positivity in HD cases and controls, and between EBV-associated and non-associated cases of HD. The A*02 alleles of 14 cases of EBV-associated HD were further subtyped using nested PCR; all except one case were found to be A*0201-positive. We therefore investigated whether there was any evidence for mutation of the epitope representing amino acids 426-434 of LMP-2a which is restricted through HLA-A*0201. In 10/11 cases the nucleotide sequence encoding this epitope was identical to the published sequence; in the remaining case there was a mutation which would not be expected to alter the conformation of the epitope. Overall, our data suggest that other mechanisms of immune escape must be operative in EBV-associated HD.     

Hodgkin's disease, work, and the environment. A review

Hodgkin's disease (HD), a lymphoma with an annual incidence in the United States of approximately 7500 cases, primarily affects the lymph nodes, spleen, and liver. The point of this article is to critically review the literature regarding the purported relationships between HD, certain occupations, and exposure to chemical agents. Attention will also be focused on recent advances in molecular genetics in the etiology of this ailment. A MEDLINE search was conducted to assess case-control and mortality evaluations that investigated links between HD and certain occupations and exposure to designated hazards. A review of citations in the Silver Platter Occupational and Environmental Medicine CD-ROM database was also conducted to ensure that all pertinent reports were obtained. Of the industries evaluated, woodworking showed the most consistent link between an increased risk of HD (relative risk, 1.8 to 7.2), but not all studies conducted showed positive associations. Although certain chemicals (ie, chlorophenols, pesticides) were reported as risks, no chemical was consistently and unambiguously linked with HD. Recent investigative work, however, points to a major etiological role for the Epstein-Barr virus (EBV), genetic fragments of which have been noted in Reed-Sternberg cells, the classic malignant cells of HD. The occupation most consistently associated with HD appears to be woodworking, although no specific chemical has been consistently linked with this lymphoma. The most persuasive evidence regarding the cause of HD arises from recent studies, including epidemiological, clinical, and genetic studies, that point to a major role by the EBV.     

Lack of involvement of known oncogenic DNA viruses in Epstein-Barr virus-negative Hodgkin's disease

Epstein-Barr virus (EBV) is associated with around one-third of cases, but young adult cases are rarely EBV associated. In this study, known oncogenic DNA viruses, including human adenoviruses, papovaviruses and the human herpesviruses-6 (HHV-6) and -8 (HHV-8) were not detected in Hodgkin's disease lesions. These results suggest that an as yet unidentified infectious agent is involved in the pathogenesis of non-EBV-associated Hodgkin's disease.     

Changing pattern of respiratory tuberculosis in the UK in adult patients from the Indian subcontinent

BACKGROUND: Clinical observations over a 12 year period have suggested a changing pattern of adult respiratory tuberculosis in patients from the Indian subcontinent in two districts of the United Kingdom with a high incidence of tuberculosis. METHODS: Details of all patients for the period 1981-92 residing in the Newham and Blackburn districts aged 15 and over whose ethnic origin was from the Indian subcontinent (n = 1308) were analysed by stepwise logistic regression to determine the relationship between sputum smear positivity, sputum culture positivity, and isolated mediastinal lymphadenopathy, year of notification, age, sex, ethnic group (Indian or Pakistani), and whether the patient had visited the Indian subcontinent within the last three years. RESULTS: The proportion of cases who were smear positive rose over the 12 years of the study, as did the proportion of culture positive cases. The proportion with isolated mediastinal lymphadenopathy fell. These changes took place in both districts. They were not explained by demographic changes in age, sex, or ethnic group, nor was there evidence that smear and culture positivity increased in those who had recently visited India or Pakistan. CONCLUSIONS: The pattern of tuberculosis in adult patients originating from the Indian subcontinent has altered over time towards that seen in the white population in the UK.     

Psychiatric disorder in a birth cohort of young adults: Prevalence, comorbidity, clinical significance, and new case incidence from ages 11–21.

Mental health data were gathered at ages 11, 13, 15, 18, and 21 in an epidemiological sample using standardized diagnostic assessments. Prevalence of Diagnostic and Statistical Manual of Mental Disorders-III-Revised (DSM-III-R) mental disorders increased longitudinally from late childhood (18%) through mid- (22%) to late-adolescence (41%) and young adulthood (40%). Nearly half of age-21 cases had comorbid diagnoses; and comorbidity was associated with severity of impairment. The incidence of cases with adult onset was only 10.6%: 73.8% of adults diagnosed at age 21 had a developmental history of mental disorder. Relative to new cases, those with developmental histories were more severely impaired and more likely to have comorbid diagnoses. The high prevalence rate and significant impairment associated with a diagnosis of mental disorder suggests that treatment resources need to target the young adult sector of the population. The low new-case incidence in young adulthood, however, suggests that primary prevention and etiological research efforts need to target children and adolescents. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Do children with repaired low anorectal malformations have normal bowel function?

To determine the association of Epstein-Barr virus (EBV) with primary cutaneous amyloidosis (PCA), a retrospective study was conducted on skin tissue from 27 Chinese patients with lichen amyloidosus and macular amyloidosis. In situ hybridization with oligonucleotide probes was used to detect the expression of EBV-encoded RNAs (EBERs). Eleven of 27 cases (40.7%) were found to contain the EBV genome. No EBV genome was detected in the skin of the control groups, including three cases of secondary cutaneous amyloidosis, two cases of primary systemic amyloidosis, and four cases of lichen simplex chronicus. Our study showed no correlation between the presence of EBV in PCA patients and the patients' age, sex, clinical type or severity of the skin lesions. Although our results suggest that EBV may be associated with some cases of PCA, the true aetiological role of EBV in PCA remains unknown.     

Interactions between presynaptic calcium channels and proteins implicated in synaptic vesicle trafficking and exocytosis

We report the clinicopathologic characteristics of pulmonary lymphomatoid granulomatosis (LYG) in 11 patients (identified from a series of 330 consecutive patients who underwent autopsy between 1984 and 1995 at the University of Texas Medical Branch at Galveston, Texas) with a diagnosis of acquired immunodeficiency syndrome (AIDS). We used immunohistochemical stains, RNA in situ hybridization (ISH), and gene rearrangement studies to identify the immunophenotype and the presence or absence of Epstein-Barr virus (EBV) infection. All of the patients were men ranging in age from 27 to 65 years (mean age, 38.6 yr). Autopsy lungs of 21 age-matched controls were examined for EBV using ISH; these included 9 patients with AIDS who did not have pulmonary lesions and 12 HIV-negative individuals who died accidentally (mean age, 38.6 yr). All of the 11 pulmonary lesions showed the gross and microscopic characteristics of LYG, with zonal necrosis and prominent angioinvasion. The tumor nodules consisted of a mixture of atypical large lymphocytes, with vesicular nuclei and prominent nucleoli and with a background of small and intermediate-size lymphocytes, histiocytes, and plasma cells. The large lymphocytes were CD20 positive, consistent with a B-cell phenotype. Ten of the 11 cases demonstrated EBV1-encoded RNA and CD20 positivity in the large, atypical lymphocytes by double labeling. One patient showed EBV positivity in CD20-negative, CD45RO-positive large cells, but these cells were CD3 negative and showed a monoclonal heavy chain gene rearrangement by polymerase chain reaction, indicating that these were of B-cell origin. Aberrant CD43 coexpression was identified in four cases. EBV latent membrane protein was demonstrated in 9 of 11 cases by immunohistochemical stains. The lungs of all of the 21 control patients were negative for EBV by ISH. We conclude that, in our series, AIDS-associated LYG is a B-cell neoplasm and that it has a strong association with EBV infection.     

Characteristics of pancreatic injury in children: a comparison with such injury in adults

A retrospective study of eight pediatric patients (under 15 years of age) who had pancreatic injuries was undertaken. Comparisons were made with 59 adult patients who sustained pancreatic injuries over the same 15-year period. All the pediatric injuries and 96.6% of the adult resulted from blunt abdominal trauma. Bicycle accidents (children, 75.0%; adults, 0%; P < .001) and automobile accidents (children, 0%; adults, 61.0%; P < .01) were the most common causes of pancreatic injury in the two groups. There was no significant difference in the incidence of abdominal pain or peritoneal irritation between the groups. However, abdominal pain in the adults was poorly localized. Isolated pancreatic injuries were noted in 62.5% of the pediatric patients and in 15.3% of the adult patients (P < .05). Associated intraabdominal injuries were present in 25.0% of the children and in 69.5% of the adults (P < .05). The duodenum was injured in two (25.0%) pediatric patients and in 10 (16.9%) adult patients. Whereas the duodenal injuries in pediatric patients were intramural hematomas without perforation in both cases, all but one of these injuries in adults were perforations or transections (P < .05). There was a significant difference in the type of pancreatic injury between the two groups (P < .05). Surgery was performed in 12.5% of the pediatric cases and in 78.0% of the adult cases (P < .01). There were no deaths among the pediatric patients, but 8.5% of the adults died in the hospital. The difference with respect to clinical course might be related to the differences in cause of injury.     

The impact of long-term hemodialysis on pituitary-adrenocortical function

The activity of the hypothalamic-pituitary-adrenal axis in hemodialyzed (HD) patients has been investigated, with conflicting results. Different results are reported concerning both basal ACTH and cortisol concentration and the responses to different stimulating agents, in chronic hemodialyzed patients. The present study was performed in order to asses whether the length of the hemodialytic treatment may affect the pituitary and adrenocortical response to stimulation with ovine CRH (oCRH) and with exogenous ACTH in a group of patients on chronic HD for more than 10 years. Ten uremic patients (aged 38-71, 6 males and 4 females) on chronic hemodialysis for at least 10 years and 7 healthy subjects matched for age and sex were studied. The patients were tested on the day preceding dialysis session. Each subject received on different non-consecutive days oCRH (100 micrograms i.v. in bolus) and ACTH (Synacthen 0.25 mg i.v. in bolus), and blood samples were obtained at appropriate intervals. Basal ACTH and cortisol levels of HD patients were in the upper limit of normal range (ACTH 39.21 +/- 11.11 pg/mL in HD patients vs. 26.88 +/- 14.12 pg/mL in controls; cortisol 19.96 +/- 5.07 in HD patients vs. 12.66 +/- 4.44 in controls); however, the means were not significantly different compared with controls. Following oCRH administration a net increase of ACTH and cortisol was observed in every patient tested (ACTH peak 83.81 +/- 28.49 in HD vs. 78.73 +/- 22.87 pg/mL in controls; cortisol peak 30.73 +/- 19.31 in HD vs. 20.05 +/- 3.19 micrograms/dL in controls).(ABSTRACT TRUNCATED AT 250 WORDS)     

Absence of Epstein-Barr virus (EBV) in a gastrointestinal stromal cell tumour (GIST) in an adult human immunodeficiency virus-seropositive patient with past EBV infection

Gastrointestinal stromal cell tumours (GIST) of the small intestine are rare malignancies. Recently, an association of Epstein-Barr virus (EBV) with malignant stromal cell tumour in young people with AIDS and past EBV infection has been described. We describe a 33-year-old heterosexual male with asymptomatic human immunodeficiency virus (HIV) infection who had had an EBV infection in the past and who presented with an EBV-negative GIST. The association between EBV and malignant stromal cell tumours in young people with AIDS could not be reconfirmed in our adult patient. The relationship between EBV and malignant stromal cell tumours in AIDS patients and the possible pathogenetic role of EBV remains to be established, at least in adults.     

Laparoscopic approach excision of mesenteric cysts

The authors reports a case of a young woman suffering from mesenteric cyst. The incidence of these lesions is 1 to 100,000 admissions in adult patients and 1 to 20,000 admissions in pediatric age. These cysts, with retroperitoneal and omental cysts, have a similar etiopathogenesis as lymphatic ectopic tissue. In the majority of cases these cysts are asymptomatic and often the diagnosis is intraoperative. In this case the cyst was removed successfully with laparoscopic approach. This mini-invasive method allows a complete and radical excision of the cyst and reduces postoperative hospital stay and morbidity.     

Depression and the risk of coronary heart disease in the Normative Aging Study

BACKGROUND: Epstein-Barr virus (EBV) infection is common after liver transplantation in children and is associated with the risk of posttransplant lymphoproliferative disorders (PTLD). METHODS: This retrospective study examined the frequency of gastrointestinal (GI) symptoms and the risk of PTLD in pediatric liver recipients who developed symptomatic EBV infection. We reviewed 172 children who received orthotopic liver transplants between March 1988 to December 1994. Twenty-two cases were retransplants. The mean age at transplantation was 3.7 years (range, 0.1-17 years). The immunosuppressive regimens consisted of induction therapy with Minnesota antilymphocyte globulin/antithymocyte globulin/OKT3 in most cases and maintenance therapy with prednisone and either cyclosporine or tacrolimus (FK506). RESULTS: After 1 year of minimum follow-up, 54 of 172 patients had symptomatic EBV infections (confirmed by serology, histology, or whole blood polymerase chain reaction. At the time of infection, 38.5% (21/54) had either diarrhea or GI bleeding or both. PTLD developed in 11 patients (6.4%). The incidence of PTLD was 42.9% (9/21) when GI bleeding or diarrhea was associated with EBV infections, compared with 6.1% (2/33) when EBV infection was not associated with GI symptoms. Seven of 10 (70%) patients with GI bleeding and 2 of 11 (18.2%) with diarrhea developed PTLD. Of seven patients examined by endoscopy for GI bleeding, two had biopsy-proven PTLD of the GI tract, whereas one of two patients examined by endoscopy for diarrhea had biopsy-proven PTLD. DISCUSSION: In summary, a high incidence of PTLD was found in patients who developed GI bleeding or diarrhea associated with EBV infection after pediatric liver transplantation. In these patients, endoscopy and biopsy may lead to early diagnosis of PTLD.     

A comparative study of the outcome of renal transplantation in peritoneal dialysis and hemodialysis patients

Fifty-four cases of renal transplantation performed in peritoneal dialysis (PD) patients were compared with 48 cases in hemodialysis (HD) patients. Three immunosuppressive treatments were used: prednisolone, azathioprine and cyclosporine. Methylprednisolone was used to treat rejection, and polyclonal Atgem or monoclonal OKT3 antibodies were used if there was no response. There was no difference in sex, age, donor source, immunosuppressive regime, duration of dialysis before transplantation, or duration of follow-up between the two groups. Following transplantation, there was no significant difference in patient mortality and survival or graft survival between the groups. The incidences of infections were also similar in the two groups. PD is commonly used in developing countries as an alternative to hemodialysis for the treatment of chronic renal failure. This study has shown that renal transplantation can be successfully performed in patients treated by this method.