Central Nervous System Involvement in Mantle Cell Lymphoma Presenting Magnetic Resonance Imaging Features of Mild Encephalitis/Encephalopathy with a Reversible Splenial Lesion

Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) has not been described in lymphoma patients. A 65-year-old man with refractory mantle cell lymphoma (MCL) presented typical MRI features of MERS. The patient''s cerebrospinal fluid contained an increased number of reactive T-cells; a small number of MCL cells were detected by immunoglobulin heavy chain-polymerase chain reaction (IGH-PCR). His symptoms and the splenial lesion resolved in response to ibrutinib treatment, although the patient eventually died of progressive MCL with overt leptomeningeal disease. We suggest that central nervous system involvement in MCL can present clinicoradiological features of MERS and that ibrutinib could be a choice of treatment.     

Frequent infection with a viral pathogen,parvovirus B19, in rheumatic diseases of childhood

OBJECTIVE: To find further evidence of the association of parvovirus B19 infection with juvenile rheumatic diseases, and to get new insights into the immunopathogenesis of these diseases. METHODS: Paired serum and synovial fluid samples from 74 children with rheumatic disease were analyzed with respect to their content of viral DNA and antibodies directed against the B19 viral proteins VP1, VP2, and NS1. Control sera from 124 children with noninflammatory bone diseases or growth retardation were also analyzed. The sequence of the viral DNA, amplified by polymerase chain reaction (PCR), was determined. IgG-complexed virus was isolated from sera and synovial fluid by adsorption to protein A beads. The amount of free virus versus immunocomplexed virus particles was determined by quantification of the viral genomes by quantitative PCR. RESULTS: Twenty-six of the 74 patients (35%) had detectable amounts of parvovirus B19 DNA in the serum (n = 22 [30%]) and/or the synovial fluid (n = 16 [22%]), whereas only 9 of the 124 control sera (7%) were positive for the viral DNA (P < 0.0001). Forty-six patients (62%) had serum IgG against the structural proteins, indicating past infection with B19. NS1-specific antibodies were detected in sera from 29 patients (39%) and 27 controls (22%) (P < 0.001). In addition, 3 patients (4%) showed VP2-specific IgM. In 15 patients, viral DNA could be repeatedly detected in followup samples of serum and synovial fluid. Sequencing revealed low-degree nucleotide variations that are in the range of genotype 1 of parvovirus B19. Immunocomplexed virus was present in varying amounts, both in the sera and in the synovial fluid samples. CONCLUSION: Parvovirus B19 is frequently found in serum or synovial fluid of children with rheumatism. The rate of persistent B19 infection in these patients is significantly higher than in age-matched controls.     

Severe encephalitis associated with disseminated echovirus 22 infection

Severe encephalitis associated with disseminated echovirus 22 infection occurred in a previously healthy 5-month-old boy. Echovirus 22 was diagnosed by a seroconversion both in serum and cerebrospinal fluid and by isolation of the virus from several stool samples. The child damaged severely and at the age of 8 1/2 months infantile spasms developed.     

Virological and serological studies of neurological complications of acute hemorrhagic conjunctivitis in Thailand.

An extensive outbreak of acute hemorrhagic conjunctivitis (AHC) occurred from September to December 1974 in Thailand. At least 29 patients with polio-like motor paralysis that complicated AHC were hospitalized in Bangkok. Paired or triplicate samples of serum from 16 patients were tested for neutralizing antibody to enterovirus type 70 (EV70). A significant rise in titer of antibody was found for two patients, and the other 14 had neutralizing antibody titers ranging from 1:8 to 1:512 without an increasf larger than or equal to 1:16, a level which is considered to be diagnostically significant. Neutralizing antibody to EV70 was detected in 19S fractions of nine sera examined, but neutralizing antibody to three types of poliovirus was confined to 7S fractions. EV70 was isolated from one of seven stool specimens collected on day 37 after the onset of AHC and none of 10 samples of cerebrospinal fluid. These results and additional clinical and epidemiologic findings gave further support to the hypothesis that EV70 infection can cause polio-like motor paralysis as a complication of AHC.     

Rotavirus antigenemia in patients with acute gastroenteritis

Although rotavirus infections are generally considered to be confined to the intestine, recent reports suggest that extraintestinal disease occurs. We studied whether rotavirus infection was associated with antigenemia during a major outbreak of gastroenteritis in the Kingston metropolitan area, during July-August 2003. Rotavirus antigen was identified in 30 of 70 acute-phase serum samples (including from 2 deceased individuals) but in only 1 of 53 control samples. Serum antigen levels were inversely associated with time since symptom onset and were directly associated with antigen levels in stool (P = .02). Serum antigen levels were significantly elevated during primary infections (acute-phase serum immunoglobulin G [IgG] titers, <25), compared with those in subsequent infections (acute-phase serum IgG titers, > or = 25) (P = .02). Antigenemia was common in this outbreak and might provide a mechanism to help explain rare but well-documented reports of findings of extraintestinal rotavirus. In situations in which stool samples are not readily available (i.e., patients with severe dehydration or those recently recovered or deceased), serum testing by enzyme immunoassay offers a new and practical diagnostic tool.     

Frequent infection with a viral pathogen,parvovirus B19, in rheumatic diseases of childhood

Objective

To find further evidence of the association of parvovirus B19 infection with juvenile rheumatic diseases, and to get new insights into the immunopathogenesis of these diseases.

Methods

Paired serum and synovial fluid samples from 74 children with rheumatic disease were analyzed with respect to their content of viral DNA and antibodies directed against the B19 viral proteins VP1, VP2, and NS1. Control sera from 124 children with noninflammatory bone diseases or growth retardation were also analyzed. The sequence of the viral DNA, amplified by polymerase chain reaction (PCR), was determined. IgG‐complexed virus was isolated from sera and synovial fluid by adsorption to protein A beads. The amount of free virus versus immunocomplexed virus particles was determined by quantification of the viral genomes by quantitative PCR.

Results

Twenty‐six of the 74 patients (35%) had detectable amounts of parvovirus B19 DNA in the serum (n = 22 [30%]) and/or the synovial fluid (n = 16 [22%]), whereas only 9 of the 124 control sera (7%) were positive for the viral DNA (P < 0.0001). Forty‐six patients (62%) had serum IgG against the structural proteins, indicating past infection with B19. NS1‐specific antibodies were detected in sera from 29 patients (39%) and 27 controls (22%) (P < 0.001). In addition, 3 patients (4%) showed VP2‐specific IgM. In 15 patients, viral DNA could be repeatedly detected in followup samples of serum and synovial fluid. Sequencing revealed low‐degree nucleotide variations that are in the range of genotype 1 of parvovirus B19. Immunocomplexed virus was present in varying amounts, both in the sera and in the synovial fluid samples.

Conclusion

Parvovirus B19 is frequently found in serum or synovial fluid of children with rheumatism. The rate of persistent B19 infection in these patients is significantly higher than in age‐matched controls.

     

The presence of parvovirus B19 VP and NS1 genes in the synovium is not correlated with rheumatoid arthritis

OBJECTIVE: To amplify both NS1 and VP genes of Parvovirus B19 DNA in synovial membrane (SM) and serum obtained from patients with rheumatoid arthritis (RA) and to analyze whether the presence of viral DNA is correlated with synovitis. METHODS: DNA obtained from 30 SM and 24 serum samples from RA patients was analyzed using single round-polymerase chain reaction (PCR) and nested PCR for both VP and NS1 genes of parvovirus B19. Twenty-four SM and serum samples from sex and age matched subjects with osteoarthritis (OA) or joint trauma served as controls. RESULTS: The first round PCR was negative for NS1 in RA samples. After nested PCR, NS1 was detected in the SM of 6/30 patients and of 10/24 controls and in the serum of 4/24 patients and controls. Nested PCR for the VP gene detected viral DNA in the SM of 7/30 patients with RA and of 7/24 of the controls and in the serum of 5/24 patients and of 2/24 controls. Altogether parvovirus DNA was found in the SM of 11/30 (36.6%) patients and of 12/24 (50%) controls and in the serum of 8/24 (33.3%) patients with RA and of 5/24 (20.8%) controls. CONCLUSION: Our results suggest that the amplification by nested PCR of both NS1 and VP genes is necessary to define the presence of viral DNA in tissue samples and confirm that the presence of parvovirus B19 DNA is similar in RA and control SM, suggesting that simple detection of viral DNA is not sufficient to confirm a link between the virus and RA.     

应用特异单克隆抗体测定猪囊尾蚴病人血清和脑脊液中的循环抗原

我们应用特异的抗猪囊尾蚴抗原的单克隆抗体(CCy1),建立了单克隆抗体抑制性ELISA方法以测定囊尾蚴病患者的循环抗原(CAg)。测定灵敏度为ng水平。83例囊尾蚴病患者血清的CAg阳性率为71.1％。其范围为0.16-128μg/ml。对41例囊尾蚴病患者,同时测定了血清和脑脊液中的CAg。单项或两项阳性的总阳性率为90.2％。114例正常人血清、107例其它寄生虫病患者(包括30例包虫病患者)的血清及10例非寄生虫病患者的脑脊液的CAg量均为零。有23例囊尾蚴病患者治疗半年到1年后,有21例抗原浓度为零。另2例分别为0.64μg/ml和1.6μg/ml。表明测定CAg不仅可以确定活动性囊尾蚴感染,而且可考核疗效。     

Detection and characterization of human rotavirus among children with diarrhoea in Botswana

This study reports the detection, for the first time, of human rotavirus in stools of children and the molecular characterization of isolated circulating strains in Botswana. We collected 249 stool samples between 1999 and 2001 from children with diarrhoea in three health districts of Botswana and examined them for the presence of rotavirus antigens and particles. Group A rotavirus antigen was detected in 43 of 249 (17%) of the samples tested by enzyme-linked immunosorbent assay. Of the 43 children shedding rotaviruses, 37 (86%) were infants < or =2 years of age. The presence of rotavirus particles was also confirmed by direct electron microscopy. The characteristic 11 segments of the double-stranded RNA mobility pattern of rotavirus were demonstrated by polyacrylamide electrophoresis in 20 of 43 (47%) of the rotavirus-positive samples. The predominant electrophoretic pattern detected was the long (L) electrophoretype 14 of 20 (70%) followed by the short (S) electrophoretype five of 20 (25%). One strain had a mixed (L/S) pattern. Of the 26 samples subjected to subgrouping by enzyme immuno assay, eight were typed as subgroup-II specific and seven were subgroup I. The predominant VP7 genotypes detected were G1 (59%). Two mixed strains of G1 + G3 (5%) and G1 + G2 (5%) were also detected. VP4 genotypes in circulation were: P[4] (5%), P[6] (33%) and P[8] (33%). Mixed P-types P[4 + 6] (5%) and P[6 + 8] (18%) were also detected. Rotavirus strains G1 P[8] and GI P[6 + 8] were the most common cause of diarrhoea in our study area.     

Diagnosis of human schistosomiasis by detection of circulating cathodic antigen with a monoclonal antibody.

Monoclonal antibody (MAb) 5H11 reacted with repeating epitopes on Schistosoma mansoni circulating cathodic antigen (CCA) and detected CCA in sera of Egyptian S. mansoni-infected patients. MAb 5H11 was both capture and biotinylated detection antibody in a sandwich ELISA of trichloroacetic acid-pretreated serum samples. Sera of patients with 7-500 eggs/g of stool were positive by MAb 5H11-CCA sandwich ELISA. Stool egg counts and CCA serum levels correlated (r = .52), and CCA levels decreased by 4 weeks after praziquantel treatment in patients with pretreatment egg counts of greater than or equal to 50/g of stool (P less than .05). Sera of Schistosoma haematobium-infected patients, uninfected individuals, and most patients with other helminths were negative in this assay. The MAb 5H11-CCA sandwich ELISA appears sensitive and specific for immunodetection of active schistosomiasis mansoni and useful for monitoring its chemotherapy.     

烟台地区病毒性脑炎病毒分离与病原学分析

目的了解烟台地区病毒性脑炎病原谱及其基因特征。方法采集烟台地区病毒性脑炎患者脑脊液46份及粪便标本10份,通过细胞培养分离病毒,RT-PCR扩增肠道病毒VP1区并测序,进行基因序列分析。结果从46例病毒性脑炎患者脑脊液标本中分离到11株病毒,分离率为23.91%,10份粪便标本中分离病毒5株。16株病毒经鉴定7株为肠道病毒,其中EV71型4株。EV71与其他地区流行株VP1区序列差异较小。结论烟台市病毒性脑炎以肠道病毒为主,有EV71型流行,与其他地区流行株相比,EV71型VP1区基因变异较小。     

Antigens, antibodies and immune complexes in cerebrospinal fluid of patients with cerebral gnathostomiasis

Methods for the detection of antigens, antibodies and immune complexes in the cerebrospinal fluid (CSF) of patients with neurological manifestations suggestive of cerebral gnathostomiasis were developed, in the hope that they may be useful in confirming the diagnosis of Gnathostoma spinigerum infection. Gnathostoma antigens were determined by a sandwich enzyme linked immunosorbent assay (ELISA) using antibodies from rabbits immunized with the excretory/secretory (ES) antigens obtained from the in vitro supernatant fluid in which the third-stage G. spinigerum larvae were maintained. With a biotin streptavidin procedure, the presence of G. spinigerum antigens as low as 2 ng in one ml of CSF could be detected. An indirect ELISA was used for the quantitation of IgG antibodies in the paired serum and CSF of these patients. A complement consumption method was used for the detection of immune complexes in the concentrated CSF specimens. Of the 11 patients with clinical signs and symptoms suggestive of having G. spinigerum infection involving the central nervous system, only one patient had antigens detected in the CSF and in this one patient no antibody could be demonstrated. One other patient had immune complexes in her CSF. All remaining patients had IgG antibodies demonstrable in the CSF specimens. These data suggest that the detection of IgG antibodies in CSF is more reliable than the other two methods in confirming the diagnosis of cerebral gnathostomiasis.     

Analysis of a predominant immunoglobulin population in the cerebrospinal fluid of a multiple sclerosis patient by means of an anti-idiotypic hybridoma antibody.

We have produced hybridoma antibodies directed against immunoglobulins present in the cerebrospinal fluid of a patient with multiple sclerosis (MS). One hybridoma antibody recognized an idiotypic determinant of an immunoglobulin population [an idiotype (Id)] which constituted approximately 1% of the immunoglobulin present in the cerebrospinal fluid. The Id focused in the pH range 8.0-8.4. It was present at roughly 10- to 15-fold higher relative (compared to total immunoglobulin) concentration in cerebrospinal fluid than in serum of the homologous MS patient. The Id could not be detected in three cerebrospinal fluid samples and 28 serum samples of heterologous MS patients or in the serum of 43 optic neuritis patients. The Id persisted in the homologous MS patient at increased concentration over the entire (6 years) observation period. The Id could be shown to react with a Theiler murine encephalomyelitis virus strain WW which was isolated from mice after inoculation with periplaque white matter from brain in a histologically confirmed case of MS.     

Virology of the Hepatitis A Epidemic in Italy

We studied the virologic aspects of a hepatitis A epidemic that occurred among hemophilia patients in Italy between 1989 and 1992. Twelve lots of factor VIII concentrate manufactured by the solvent-detergent chromatographic technique and suspected of contamination by the hepatitis A virus (HAV) were analyzed by a two-step, nested polymerase chain reaction (PCR) procedure. PCR was applied to 1-ml samples of factor VIII concentrate and 100-μl serial serum samples available from 2 patients. Particular care was taken to rule out the possibility of false-positive results during analysis. Results demonstrated PCR amplification of the 3'-region of the VP3 gene in 5 of the 12 implicated lots of factor VIII and in the serial serum samples of both patients. PCR amplification also revealed that the gene sequences detected in patients' sera were identical to the sequences detected in the product they had received. In all, 3 VP3 sequences (found to be 96–99% identical) were amplified. Further characterization of the HAV found in the factor VIII concentrate and the patients' sera was attempted by PCR amplification of the VP1/2A region. Successful amplification of this region was achieved in the serum of only 1 patient and in the concentrate he received. This fourth amplified sequence was identical in both serum and factor VIII concentrate. Attempts to transmit hepatitis A from the contaminated lots to 3 chimpanzees resulted in no signs of infection after 10 months of observation. Based on the Italian experience, persons with severe hemophilia who receive large-pool concentrate are at potential risk for HAV infection and should be vaccinated against HAV or use an alternative to solvent-detergent-prepared concentrate. Since June 1992, no cases of HAV have been reported in Italian hemophiliacs, most of whom have been vaccinated.     

Treatment of human late stage gambiense trypanosomiasis with alpha-difluoromethylornithine (eflornithine): efficacy and tolerance in 14 cases in C?te d'Ivoire

alpha-Difluoromethylornithine (DFMO; eflornithine), an inhibitor of polyamine biosynthesis, was used to treat 14 patients with late stage gambiense sleeping sickness, 12 cases having been previously treated with and considered refractory to melarsoprol. alpha-Difluoromethylornithine was administered intravenously at a dose of 400 mg/kg/day for 14 days followed by oral treatment, 300 mg/kg/day, for 21-28 days. In all patients treatment was associated with rapid disappearance of trypanosomes from body fluids (in several cases within 24 hr) and decreased cerebrospinal fluid white blood cell counts. In all but one patient, who died of a pulmonary infection during treatment, alpha-difluoromethylornithine produced a dramatic reversal of clinical signs and symptoms of the disease. Determination of drug concentrations in serum and cerebrospinal fluid of 5 patients demonstrated that alpha-difluoromethylornithine diffuses into the central nervous system with cerebrospinal fluid levels representing up to 51% of corresponding serum concentrations. Diarrhea, abdominal pain, and anemia were the most frequent side effects associated with therapy, but were reversible and did not necessitate discontinuation of treatment. Four patients have been followed for more than 2 years post-treatment without evidence of relapse.     

Cryptococcosis in the acquired immunodeficiency syndrome

The clinical course and response to therapy of 27 patients with cryptococcosis and the acquired immunodeficiency syndrome were reviewed. Cryptococcosis was the initial manifestation of the syndrome in 7 patients, and the initial opportunistic infection in an additional 7. Meningitis was the commonest clinical feature (18 patients). Blood cultures and serum cryptococcal antigen were frequently positive. In patients with meningitis, leukocyte count, protein level, and glucose level in cerebrospinal fluid were frequently normal; cerebrospinal fluid India ink test (82%), culture (100%), and cryptococcal antigen (100%) were usually positive. Only 10 of 24 patients had no evidence of clinical activity of cryptococcal infection after completion of therapy; 6 of these 10 had relapses shown by clinical findings or at autopsy. Standard courses of amphotericin B alone or combined with flucytosine were ineffective. Cryptococcosis in patients with the syndrome is a debilitating disease that does not respond to conventional therapy; earlier diagnosis or long-term suppressive therapy may improve the prognosis.     

Antiphospholipid antibodies in pediatric and adult patients with rheumatic disease are associated with parvovirus B19 infection

OBJECTIVE: To show a possible association between parvovirus B19 infection and the presence of antiphospholipid antibodies (aPL) in patients with rheumatic diseases. METHODS: Serum samples obtained from 88 children with various forms of juvenile rheumatic disease and from 40 adults with systemic lupus erythematosus, the antiphospholipid syndrome, or other rheumatic disease, who had previously been tested and shown to be positive for IgG aPL, were analyzed for the presence of B19 DNA, for antibodies against the B19 viral proteins VP1, VP2, and NS1, and for IgG aPL (anticardiolipin, anti-beta(2)-glycoprotein I, and antiphosphatidylserine). As controls, serum samples obtained from 135 children with noninflammatory bone diseases or growth retardation were also analyzed. RESULTS: Twenty-four (27%) of the 88 children with rheumatic diseases had detectable amounts of IgG aPL. Fourteen (58%) of these 24 IgG aPL-positive patients showed IgG against VP1/VP2 and viral genomes, indicating the presence of acute (2 patients) or persistent (12 patients) infection. Past parvovirus B19 infection was identified in 7 (29%) of 24 IgG aPL-positive children, as indicated by VP1/VP2-specific IgG in the absence of viral DNA. Three (12%) of 24 IgG aPL-positive children had not been infected with B19. Sixty-nine (51%) of 135 control children displayed VP1/VP2-specific IgG. Three (2%) of these 135 children were IgG aPL positive (2 children had past parvovirus B19 infection, and 1 was negative for parvovirus B19). Analysis of the parvovirus B19 status of 40 adult IgG aPL-positive patients showed that 33 (83%) were anti-IgG VP1/VP2-positive, and viral DNA was detected in 11 patients (28%). Ten of these 11 viremic patients were in the subgroup of 28 IgG aPL-positive SLE patients. CONCLUSION: Antiphospholipid antibodies are preferentially found in serum of children with juvenile idiopathic arthritis who have been previously infected with parvovirus B19 and have established, persistent infection. Adult patients with IgG aPL positivity have a high incidence of persistent parvovirus B19 infection. We conclude that parvovirus B19 might be directly involved in the elicitation of autoimmune reactions partly mediated by aPL.     

Detection and characterization of human rotavirus in hospitalized patients in the cities of Ponta Grossa,Londrina and Assai - Pr,Brazil

Acute diarrheal disease is still one of the major public health problems worldwide. Rotaviruses (RV) are the most important viral etiologic agents and children under five years of age are the target population.ObjectiveTo investigate the rate of RV infection in hospitalized patients due to acute diarrhea in the cities of Ponta Grossa, Londrina and Assai - Paraná.MethodsLatex agglutination (LA); immunochromatography (ICG); polyacrylamide gel electrophoresis (PAGE) and negative staining electron microscopy (ME) tests were used to detect the virus. For the genotyping, RT-PCR and RT-PCR-ELISA were used, respectively, for NSP4 and VP4/VP7.ResultOut of 124 samples there were 69 positive stool samples for RV, for at least one of the used tests, 67 of them being RV group A (RV-A). Overall, most of the RV positive stool samples came from children under thirteen years of age. However, 12 positive cases occurred in patients aged 13 years or above, including an 81-year old patient.ConclusionThe data showed similar electropherotypes and genotypes G, P and NSP4 of the inland wild circulating strains of RV.     

Local anti-P32 humoral response in tuberculous meningitis

We report five cases of severe pulmonary tuberculosis admitted to hospital with a suspicion of meningeal involvement. The diagnosis of tuberculous meningitis was confirmed by standard bacteriological techniques in two of the five patients. Specific IgG class antibodies directed against the recently purified BCG antigen P32 were detected by a dot immunoblotting technique in the serum and in the cerebrospinal fluid of each patient; however, a higher anti-P32 immunoglobulins/total immunoglobulins ratio was observed in the cerebrospinal fluid of patients with tuberculous meningitis than in their serum while the reverse situation was observed in the other patients.