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Biomedical subjects

M J Levin

Publications and source records attributed to M J Levin.

At least 55 records · Page 3Linked to original sources
PubMed1998

Atypical herpes simplex virus encephalitis diagnosed by PCR amplification of viral DNA from CSF.

OBJECTIVE: To determine the frequency of mild/atypical herpes simplex virus encephalitis (HSVE) among patients with CSF specimens submitted to a university diagnostic virology laboratory for HSV PCR. BACKGROUND: HSVE is the most commonly recognized cause of acute sporadic encephalitis in the United States. Recognized clinical features are based on autopsy- or brain biopsy-confirmed cases. This is likely to produce ascertainment bias for features associated with severe disease and under-recognition of mild or atypical cases. Amplification of HSV DNA by PCR from CSF provides a sensitive and specific method for diagnosis of HSVE. METHODS: Results of all HSV CSF PCR tests sent to a university diagnostic virology laboratory (January 1, 1993, to December 31, 1996) were reviewed. Clinical information was prospectively collected and retrospectively reviewed. Patients with positive HSV CSF PCR tests were classified as having meningitis, encephalitis, or neonatal infection. Encephalitis was considered typical or atypical based on published criteria. RESULTS: A total of 7.6% of 1,224 CSF specimens were positive for HSV DNA. CSF HSV DNA-positive patients had meningitis (52%), encephalitis (26%), neonatal infection (17%), or nonclassifiable disease (5%). A total of 17% of HSVE patients had mild or atypical disease characterized by the absence of focal findings and slow progression in the absence of antiviral therapy. Atypical HSVE was associated with HSV-2 infection (two of the four patients), immunosuppression by steroid therapy or coexisting HIV infection (three of the four patients), or disease predominantly involving the nondominant temporal lobe (two of the four patients). CONCLUSIONS: Approximately one-fifth of HSVE patients have mild or atypical disease. CSF PCR for HSV DNA should be performed in patients with febrile encephalopathy even in the absence of focal features, initial CSF pleocytosis, or abnormal CT. Mild or atypical HSVE may be associated with infection with either HSV-1 or HSV-2. Mild or atypical HSVE was frequently associated with immunocompromise or asymmetric HSV infection affecting predominantly the nondominant temporal lobe.

DNA, Viral↗
PubMed1997

Antibodies to ribosomal P proteins of Trypanosoma cruzi in Chagas disease possess functional autoreactivity with heart tissue and differ from anti-P autoantibodies in lupus.

Anti-P antibodies present in sera from patients with chronic Chagas heart disease (cChHD) recognize peptide R13, EEEDDDMGFGLFD, which encompasses the C-terminal region of the Trypanosoma cruzi ribosomal P1 and P2 proteins. This peptide shares homology with the C-terminal region (peptide H13 EESDDDMGFGLFD) of the human ribosomal P proteins, which is in turn the target of anti-P autoantibodies in systemic lupus erythematosus (SLE), and with the acidic epitope, AESDE, of the second extracellular loop of the beta1-adrenergic receptor. Anti-P antibodies from chagasic patients showed a marked preference for recombinant parasite ribosomal P proteins and peptides, whereas anti-P autoantibodies from SLE reacted with human and parasite ribosomal P proteins and peptides to the same extent. A semi-quantitative estimation of the binding of cChHD anti-P antibodies to R13 and H13 using biosensor technology indicated that the average affinity constant was about 5 times higher for R13 than for H13. Competitive enzyme immunoassays demonstrated that cChHD anti-P antibodies bind to the acidic portions of peptide H13, as well as to peptide H26R, encompassing the second extracellular loop of the beta1 adrenoreceptor. Anti-P antibodies isolated from cChHD patients exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats, which resembles closely that of anti-beta1 receptor antibodies isolated from the same patient. In contrast, SLE anti-P autoantibodies have no functional effect. Our results suggest that the adrenergic-stimulating activity of anti-P antibodies may be implicated in the induction of functional myocardial impairments observed in cChHD.

Amino Acid Sequence↗
PubMed1997

Oral famciclovir for suppression of recurrent genital herpes simplex virus infection in women. A multicenter, double-blind, placebo-controlled trial. Collaborative Famciclovir Genital Herpes Research Group.

OBJECTIVE: To evaluate the efficacy and safety of oral famciclovir in the suppression of genital herpes. METHODS: In this randomized, double-blind, placebo-controlled trial that was performed at 11 university and 9 private ambulatory care referral centers, 375 women who were 18 years of age or older and had a history of 6 or more episodes of genital herpes during 12 of the last 24 months in the absence of suppressive therapy were treated for 4 months with oral famciclovir, 125 mg once daily or twice daily, 250 mg once daily or twice daily, 500 mg once daily, or placebo. The primary outcome measures included the time to first clinically and virologically confirmed recurrences, and safety as measured by clinical laboratory tests and adverse experiences. RESULTS: The median time to first recurrence was 82 days in the placebo group, 114 days in those receiving famciclovir, 125 mg once daily, and more than 120 days in the other treatment groups. When compared with placebo recipients, the time to the first clinical recurrence was significantly prolonged in subjects who received famciclovir, 125 mg twice daily (hazard ratio, 1.8; 95% confidence interval, 1.0-3.0; P = .03), and in those who received famciclovir, 250 mg twice daily (hazard ratio, 3.6; 95% confidence interval, 1.9-6.9; P < .001). Treatment was well tolerated, and there was no evidence of emergence of resistance during or after suppressive famciclovir therapy. CONCLUSIONS: Oral famciclovir, 250 mg, given twice daily for 4 months is an effective, well-tolerated treatment for the suppression of genital herpes in women with frequent recurrences, but single daily doses produced less complete suppression of genital herpes.

2-Aminopurine↗
PubMed1997

Assessment of pain in herpes zoster: lessons learned from antiviral trials.

Pain typically accompanies acute herpes zoster and, in a proportion of patients, it persists well beyond rash healing. Pain must therefore be analyzed in trials of antiviral agents in herpes zoster, but different methods have been used to analyze pain in recent published trials. These reports are reviewed and their methodological strengths and weaknesses examined. Based on this review, recommendations for the design and analysis of future trials of antiviral agents in herpes zoster are proposed. The principal recommendation is that antiviral efficacy should be evaluated both by distinguishing post-herpetic neuralgia from acute pain and by considering pain as a continuum. The primary endpoint should address both the prevalence and duration of post-herpetic neuralgia and should be examined in those patients who have post-herpetic neuralgia. Adopting the proposed recommendations in design and analysis of future trials should facilitate comparison across trials of the efficacy of antiviral agents in the treatment of herpes zoster.

Antiviral Agents↗
PubMed1997

Characterization of an interspersed repetitive DNA element in the genome of Trypanosoma cruzi.

We report the molecular characterization of a middle repetitive DNA sequence, named C6, isolated from the Trypanosoma cruzi genome. C6 appears to be a composite repeated element since 3 subregions may be defined within it on the basis of sequence similarities with other T. cruzi genomic sequences. Sequences homologous to C6 are interspersed in the genome and can be mapped out on most chromosomal bands of different T. cruzi. strains. The copy number of the C6 element is about 1000 per haploid genome. Given the species specificity and different genomic distribution of C6 homologous sequences among the T. cruzi strains the C6 element could be a useful probe for diagnosis and typing of parasites. C6 is a polymorphic marker with potential as a tool for physical mapping of the T. cruzi genome.

Animals↗
PubMed1997

A simple Trypanosoma cruzi enzyme-linked immunoassay for control of human infection in nonendemic areas.

An enzyme linked immunosorbent assay (ELISA) was developed for detecting IgM and IgG antibodies against Trypanosoma cruzi in blood bank donors from endemic or nonendemic areas. A crude extract of trypomastigotes from cultures was used as antigen. A total of 494 serum samples from patients with acute, congenital, or chronic form of Chagas' disease, and from healthy French individuals were studied. The sensitivity of the ELISA was determined with 89 serum samples from chagasic patients and was evaluated to 98.8%. The specificity was determined with 405 serum samples from French blood transfusion centers donors and evaluated to 98.3%. Two hundred and eighty-five serum samples from blood donors from Argentina and Brazil were also tested. Furthermore, in order to assess the absence of cross-reactivity with other protozoan infections, we studied 86 serum samples including (i) 32 individuals with cutaneous leishmaniasis living in a T. cruzi endemic region of Bolivia, and (ii) 54 patients from nonendemic area for Chagas' disease, 19 of them with kala-azar and 35 others with malaria.

Animals↗
PubMed1997

Immunization with recombinant Trypanosoma cruzi ribosomal P2beta protein induces changes in the electrocardiogram of immunized mice.

Molecular expression cloning techniques revealed that patients with severe chronic Chagas heart disease showed a strong humoral response against the cloned C-terminal portion of the Trypanosoma cruzi ribosomal P2beta protein, previously named JL5. The main linear epitope of this polypeptide was mapped to the 13 C-terminal amino acid sequence EEEDDDMGFGLFD (named R13), which is almost identical to the mammalian ribosomal P consensus sequence EESDDDMGFGLFD (named H13). Enzyme-linked immunosorbent assay measurements demonstrated that sera from patients with chronic Chagas heart disease presented a very specific anti-P humoral response with high anti-R13, but low H13 antibody levels. We attempted to develop an animal model that would reproduce, at least partially, two features of the human infection: (1) the serological pattern of the anti-P response, and (2) specific cardiac symptoms. To this effect, mice were immunized with T. cruzi P2beta recombinant protein. Immunization reproduced the typical anti-P antibody profile defined for chronic infections, but did not induce cardiac inflammatory lesions. However, it altered significantly the electrocardiograms of immunized mice. It is suggested that this assay represents a functional test for assessing the biological activity of antibodies against T. cruzi ribosomal P protein on cardiac muscle.

Animals↗
PubMed1996

Structural and functional analysis of the B cell epitopes recognized by anti-receptor autoantibodies in patients with Chagas' disease.

IgG fractions of patients were screened for autoantibodies against the beta1- and beta2-adrenoceptors and the M2 acetylcholine receptor by enzyme immunoassays and surface plasmon resonance (SPR) using peptides corresponding to the second extracellular loop of these receptors. A high prevalence of anti-M2 acetylcholine receptor and, in decreasing order, of anti-beta1- and anti-beta2-adrenoceptor autoantibodies was shown. The enzyme immunoassays and the SPR studies on the anti-beta1 adrenoceptor and the M2 acetylcholine receptor autoantibodies were dependent on the ionic strength of the interaction buffer, suggesting the importance of electrostatic interactions in Ab recognition. IgG fractions showed chronotropic effects on neonatal rat cardiomyocytes in vitro. The positive chronotropic effect was enhanced in the presence of 1 microM of atropine, demonstrating a muscarinic stimulation by the IgG fractions in the presence of a beta-adrenergic stimulation, which was blocked by the use of 1 microM of the beta1-selective antagonist bisoprolol. The beta2-selective antagonist ICI 118,551 only partially inhibited the positive chronotropic effect induced by the IgG fractions, confirming the minor functional importance of autoantibodies against the beta2-adrenoceptor. Affinity-purified Abs confirmed that Abs against the beta1-adrenoceptors and the M2 muscarinic receptors exist together with an Ab population recognizing a cross-reactive epitope on both receptors. This epitope could be identified as a polyanionic stretch present in the second extracellular loop of both the beta1-adrenoceptor and the M2 acetylcholine receptor. This stretch corresponds to the previously determined cross-reactive epitope between the P0 ribosomal protein of Trypanosoma cruzi and the beta1-adrenoceptor.

Adrenergic beta-Antagonists↗
PubMed1996

Improved detection of varicella zoster infection with a spin amplification shell vial technique and blind passage.

BACKGROUND: Among the methods available for the diagnosis of varicella zoster virus (VZV) infections, only tissue culture yields an isolate available for antiviral susceptibility testing or pathogenesis studies. However, conventional tube tissue culture (TC) has a low sensitivity. OBJECTIVE: To increase the recovery rate of VZV in tissue culture. STUDY DESIGN: Clinical specimens submitted for VZV isolation were processed by TC and rapid shell vial (SV) techniques followed by a blind passage (BP). For SV, two incubation times and two mAbs, directed against viral-early or immediate-early antigens, were compared. RESULTS: Isolation of VZV using the SV stained at 72 h postinoculation was more sensitive (88-96%) than TC (50-67%), or the SV technique at 48 h (66-70%). It was also more rapid than TC (9.6 days). The comparison of mAbs yielded similar results in SV. Blind passage of SV at 7 days postinoculation further increased detection. CONCLUSIONS: SV combined with BP is the method of choice for VZV isolation.

Journal Article↗
PubMed1996

The varicella vaccine. Prevention of herpes zoster.

The live attenuated varicella vaccine offers some hope that the frequency or severity of herpes zoster might be reduced. Universal immunization with this vaccine should result in less latent varicella-zoster virus in dorsal root and cranial nerve ganglia than that which occurs following varicella. Moreover, the vaccine virus is not well adapted for growth in human cells at normal body temperature. Thus, reduced virus for reactivation, and less robust replication, may lessen the problem of herpes zoster in vaccinees. For those individuals who have already had varicella, the risk of herpes zoster is closely related to the loss of varicella-zoster virus cell-mediated immune responses, which decline with aging (or immune suppression). In aging individuals these immune responses can be enhanced by booster immunization with the varicella vaccine, suggesting that a vaccine to prevent herpes zoster is feasible.

Aged↗
PubMed1996

Varicella zoster virus-specific cytotoxicity following secondary immunization with live or killed vaccine.

Subjects > or = 55 years of age were immunized with attenuated varicella zoster virus (VZV) vaccine (live) or with the same vaccine, which had been heated to 56 degrees C for 7 days (killed). The ability of subjects' blood lymphocytes to lyse target cells infected with VZV was determined before and 3 months after immunization using autologous Epstein-Barr virus (EBV) lymphoblasts as targets for human leukocyte antigen (HLA) class I restricted cytotoxicity and human fibroblasts as targets for unrestricted (natural killer [NK]) cytotoxicity. The live vaccine recipients showed an increase in their class I-restricted lysis of targets compared with the recipients of the killed vaccine. The two populations showed equivalent increase in their NK-dependent lysis of fibroblast targets. The results support the view that both the live and killed vaccines stimulate cytotoxicity by VZV-specific lymphocytes but that the live vaccine stimulates relatively more class I-restricted killing.

Aged↗
PubMed1996

The frequency and consequences of varicella exposure and varicella infection in children receiving maintenance therapy for acute lymphoblastic leukemia.

PURPOSE: The frequency and cost of varicella and varicella exposure were determined in children receiving maintenance chemotherapy for acute lymphocytic leukemia, and the cost of a preventative strategy using the varicella vaccine was estimated. PATIENTS AND METHODS: Retrospective analysis of clinic and hospital records for 472 children at 12 sites who were receiving maintenance chemotherapy on Protocol 105 of the Childrens Cancer Group. RESULTS: During a mean maintenance period of 2 1/2 years there were 120 exposures to varicella among susceptible children (10/100 patient-years). During the same period there were 60 cases of varicella (4.6/100 patient-years). Half of the cases of varicella occurred without a known exposure. Exposures and varicella resulted in significant omission or delay in chemotherapy. Total medical charges for varicella-related events were $492,000 ($470 per varicella exposure; $7,450 per case of varicella). A proposed preventative strategy using varicella vaccine after 6 months of maintenance therapy would theoretically reduce varicella-related charges by 80%. CONCLUSIONS: Varicella exposure and varicella are common in this patient population. The use of varicella vaccine during the early maintenance period should be considered to prevent these events. This strategy is likely to be safe, and will save significant medical charges, drug omission, disease-related morbidity, hospitalization, and work and school disruption.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Comparison of two methods for detecting varicella-zoster virus antibody with varicella-zoster virus cell-mediated immunity.

We evaluated an enzyme-linked immunoassay (EIA; BioWhittaker) and a latex agglutination (LA; Becton Dickinson) for varicella-zoster virus (VZV) antibody determination, using cell-mediated immunity (CMI) as a "gold standard." VZV EIA had a sensitivity, specificity, positive predictive value, and negative predictive value of 87, 91, 87, and 91%, respectively, compared with CMI. Correlation was excellent except when the varicella index was 0.9 to 1.2. We defined sera with varicella indices of 0.9 to 1.2 as indeterminate. LA had a sensitivity, specificity, positive predictive value, and negative predictive value of 96, 91, 97, and 90%, respectively, compared with EIA. LA reactivity only at a 1:2 dilution did not correlate with CMI, but sera reactive at dilutions of > or = 1:8 indirectly did. We defined indeterminate sera as those reactive at 1:2 and nonreactive at 1:8. EIA and LA were equivalent for determining VZV immune status, and both methods required modified criteria of interpretation to increase their specificity.

Antibodies, Viral↗