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Biomedical subjects

J B Peter

Publications and source records attributed to J B Peter.

At least 19 recordsLinked to original sources

Risk factors for subclinical atherosclerosis in a prospective cohort of patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate traditional and non-traditional risk factors for subclinical atherosclerosis in systemic lupus erythematosus (SLE). METHODS: A prospective cohort of 78 patients with SLE without overt atherosclerotic disease was studied. SLE clinical and laboratory parameters, disease activity and damage, treatment and traditional risk factors for atherosclerosis were evaluated. At baseline (T1) and after five years' follow up (T2), the serum levels of anti-oxidised palmitoyl arachidonoyl phosphocholine (oxPAPC), anti-heat shock protein 65, and anti-beta(2)-glycoprotein I antibodies and C reactive protein were tested. At T2, intima-media thickness (IMT) was measured using duplex carotid sonography. Thickened intima, plaque, mean IMT (m-IMT), and maximum IMT (M-IMT) were assessed. RESULTS: A thickened intima was seen in 22/78 (28%) patients and plaque in 13/78 (17%). M-IMT and m-IMT were (mean (SD)) 0.77 (0.34) mm and 0.55 (0.15) mm, respectively. Patients with carotid abnormalities were significantly older, had higher blood pressure and total serum cholesterol levels, and had taken a higher prednisone cumulative dosage than those without any lesions. The carotid abnormalities were associated with renal disease and ECLAM >2 at T1, and with azathioprine treatment. In multivariate analysis, age and cumulative prednisone dose were associated with carotid abnormalities; age, hypertension, and anti-oxPAPC at T2 were correlated with higher M-IMT and m-IMT. CONCLUSIONS: In patients with SLE some non-traditional risk factors for atherosclerosis were identified, the most important of which was the cumulative prednisone dose. The role of some traditional risk factors, such as age and hypertension, was also confirmed. The predictive value of the new immunological and inflammatory markers of atherosclerosis seems to be masked by some disease related features.

Adult↗

In vitro antiviral and antibacterial activity of commercial intravenous immunoglobulin preparations--a potential role for adjuvant intravenous immunoglobulin therapy in infectious diseases.

The identification of specific antimicrobial activity of intravenous immunoglobulin (IVIG) preparations against particular microbial pathogens can assist in determining their therapeutic potential for specific infectious diseases. We analysed five different commercial IVIG preparations for the presence of antibodies directed against a large panel of viral, bacterial, fungal and parasitic pathogens. All IVIG batches contained high activity against herpesviruses types 1, 2, 6 and 7, as well as against varicella zoster virus, Epstein-Barr virus (EBV), measles, mumps, rubella and parvovirus B19. Some IVIG batches also had a significant activity against adenovirus and Saint Louis encephalitis virus. The IVIGs held high activity against several bacterial pathogens, including Mycoplasma pneumonia, Chlamydia pneumonia, Helicobacter pylori and tetanus. No activity was found against various parasitic and fungal pathogens. Our findings may provide further support for the use of IVIG for the prevention and treatment of infections caused by specific viral and bacterial pathogens.

Animals↗

Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs.

Cerebrospinal fluid (CSF) analysis is a basic tool for diagnosis of neurological diseases. Knowledge regarding blood-CSF barrier function (molecular flux/CSF flow theory) and neuroimmunology is reviewed to aid understanding and evaluation of CSF data. Disease-related immunoglobulin patterns (IgG, IgA, IgM with reference to albumin) are described in CSF/serum quotient diagrams with the hyperbolic reference range for blood-derived protein fractions in CSF. Clinical relevance of complementary analyses (cytology, PCR, oligoclonal IgG, antibody detection and brain-derived proteins) is briefly discussed. Integrated CSF data reports are shown with numerical and graphical data representation, reference range-related interpretation and diagnosis-related comments. The principles and rationale of general CSF analysis reported in this review should enable the reader to accurately interpret CSF data profiles, and to plan a proper evaluation of new brain- or blood-derived analytes in CSF.

Albumins↗

Review of 3200 serially received CSF samples submitted for type-specific HSV detection by PCR in the reference laboratory setting.

Previously, studies of CNS infection have indicated substantially greater prevalence of HSV1 than HSV2. In reviewing unexpectedly high numbers of HSV2 infections among CSF specimens submitted to our laboratories for PCR testing, we discovered an age and gender bias suggesting a need to examine the demographics of those patients whose specimens tested positive for HSV. Some 3200 CSF specimens submitted for HSV testing were randomly selected for analysis. HSV1 was detected in 26 specimens (nine male, 17 female; average age 51 years) and HSV2 in 36 specimens (13 male, 23 female; average age 34 years). In general, there were almost twice as many HSV1 and HSV2 infections detected in females as in males. The entire group (22 male, 40 female) exhibited a preponderance of HSV2 over HSV1 infections (36:26). In contrast, the ratio of HSV2 to HSV1 infection was 3:13 in the over 60 age group of our study (11 of the 13 HSV1 infections in this age group occurred in females). In the subgroup of 21 patients aged 15-40 years (six male, 15 female), the ratio of HSV2 to HSV1 was 16:5. In the 15 infections in the group aged 41-60 years, the ratio of HSV2 to HSV1 was 12:4. In summary, our data indicate extraordinary differences in the relative frequency of HSV1 vs HSV2 CNS infections in teenagers, young adults (15-40 years), middle age (41-60) and in the elderly (>60 years), including a particular bias for HSV1 CNS infection in females over age 70 years.

Adolescent↗

Effects of the American College of Rheumatology systemic sclerosis trial guidelines on the nature of systemic sclerosis patients entering a clinical trial.

OBJECTIVES: To compare the systemic sclerosis (SSc) patients entered into the d-penicillamine trial with SSc patients entered into previous controlled SSc trials. It was hypothesized that the d-penicillamine trial patients, who conformed to the American College of Rheumatology (ACR) guidelines for clinical trials in SSc were different from patients entered into previous trials. METHODS: Patients entering a double-blind, randomized trial of low- vs high-dose d-penicillamine were described carefully and completely. Their characteristics were then compared with previously published data on SSc and its treatment. RESULTS: One hundred and thirty-four patients had early [mean duration 9.5 (s.d. 4.2) months], diffuse [skin score 21 (8)] disease. Organ involvement in the patients was as follows: pulmonary 54%, cardiac 20%, joints 38%, muscular 20%. Thirty-three per cent had mild proteinuria and 13% were hypertensive when first seen. Compared with patients in most previous studies, these SSc patients had earlier disease and uniformly had diffuse disease. They had less muscular involvement, less dyspnoea, less abnormal pulmonary function and less cardiac and less renal involvement than patients in earlier studies. CONCLUSIONS: The use of the new ACR guidelines for SSc trials may change the nature of patient populations entering future studies.

Adult↗

Rapid detection of smear-negative Mycobacterium tuberculosis by PCR and sequencing for rifampin resistance with DNA extracted directly from slides.

Conventional methods for identification of Mycobacterium tuberculosis from culture can take 6 weeks. To facilitate the rapid detection of M. tuberculosis and to assess the risks of drug resistance, we developed a technique of eluting DNA directly from sputum slides and performing PCR for the detection of M. tuberculosis DNA, followed by sequencing the rpoB gene to detect rifampin resistance. This entire process requires only 48 h. Forty-seven sputum specimens submitted for microscopy for detection of acid-fast bacilli (AFB) and for mycobacterial culture and susceptibility testing were assessed after elution from the slides and extraction. M. tuberculosis-specific DNA was amplified in a nested PCR with previously described primers (primers rpo95-rpo293 and rpo105-rpo273), followed by analysis on a 4% agarose gel for a 168-bp product. Automated sequencing was performed, and the sequences were aligned against a database for detection of anomalies in the rpoB gene (codons 511 to 533) which indicate rifampin resistance. Of the 47 sputum specimens tested, 51% (24 of 47) were culture positive (time to positive culture, 2 to 6 weeks). Smears for AFB were positive for 58% (14 of 24) of the specimens and were negative for 42% (10 of 24) of the specimens. All 24 culture-positive sputum specimens (14 microscopy-positive and 10 microscopy-negative sputum specimens) were positive by PCR with eluates from the smears. Forty-nine percent (23 of 47) of the sputum specimens were negative for M. tuberculosis by smear, culture, and PCR. Of the isolates from the culture-positive samples, five were rifampin resistant by sequencing; all five were also rifampin resistant by in vitro susceptibility testing. Of these rifampin-resistant M. tuberculosis isolates, two were microscopy negative for AFB. Patients who are negative for AFB and culture positive for M. tuberculosis can now be identified within a day, allowing institution of therapy and reducing isolation time and medical costs.

Antitubercular Agents↗

Coronary artery disease but not coronary calcification is associated with elevated levels of cardiolipin, beta-2-glycoprotein-I, and oxidized LDL antibodies.

BACKGROUND: Autoimmune factors have been shown to play a role in atherosclerosis. The aim of this study is to correlate 5 autoantibodies (anticardiolipin, anti-CL, beta2-glycoprotein-I, beta2GPI, phosphatidylcholine, oxidized low-density lipoprotein, oxLDL, endothelial cell) with the presence of coronary heart disease, angiographic findings, and with coronary artery calcification. METHODS: The levels of the 5 autoantibodies and a control antifibroblast line of 126 coronary heart disease patients and 20 healthy controls were measured. Fifty-one patients underwent coronary angiography, and 98 patients had coronary artery calcium determination using spiral computerized tomography (dual mode). RESULTS: Levels of 3 autoantibodies (anti-CL, beta2GPI, oxLDL) were significantly elevated in coronary heart disease patients compared with controls (p < 0.001, p = 0.001, p < 0.001, respectively). Within the subgroup of patients with significant coronary artery stenosis, anti-CL antibodies were also elevated (p = 0.008). No correlation was found between anti-CL, and anti-beta2GPI autoantibody levels and coronary calcium scores as measured by spiral computerized tomography. However, anti-oxLDL antibodies were raised in patients with no calcification detected by spiral computerized tomography, compared with the patients with any coronary calcification (p = 0.046). CONCLUSION: Anti-CL, beta2GPI and oxLDL antibodies are elevated in coronary heart disease patients regardless of coronary calcification.

Aged↗

Antiphospholipid antibody levels in intravenous immunoglobulin (IVIg) preparations.

The antiphospholipid syndrome (APS) is characterized by various clinical manifestations and by elevated levels of antiphospholipid antibodies. Passive induction of APS by infusion of these antibodies has been demonstrated in animal models. Intravenous immunoglobulin (IVIg) is one of the therapeutic options in APS. In this study, five commercially used preparations of IVIg were tested for the presence of elevated levels of cardiolipin, beta-glycoprotein-I, phosphatidylserine, antinuclear, and double-stranded DNA autoantibodies, as well as for lupus anticoagulant activity. The absence of abnormal elevated levels of any of these autoantibodies in five different IVIg preparations provides additional evidence for the safety of IVIg use in APS.

Antibodies, Anticardiolipin↗

Are autoantibodies present in patients with subacute and chronic urticaria?

Since several forms of autoimmunity have been associated with urticaria, we performed a detailed survey of autoantibodies in patients with idiopathic subacute and chronic urticaria. Sera from 25 consecutive patients referred for evaluation of urticaria were tested for the presence of autoantibodies and compared to sera from seventy-five control samples examined from individuals being treated for other allergic diseases. Study patients ranged in age from 15 to 73 years, with a mean of 48. One patient had a diagnosis of inflammatory bowel disease and one had multiple myeloma, but otherwise there were no other diagnoses of disease specifically involving immunity other than atopy. No study patients had a concurrent diagnosis of autoimmune thyroid disease. The test sera were examined for autoantibodies and for antibodies to H. pylori. Antibodies to thyroid peroxidase (TPO) were found significantly (p < 0.01) more common in urticaria (20%] than in controls (0%). Rheumatoid factor(RF) was also found in significantly (p < 0.05) increased in urticaria (16%) compared to controls [0%). Neither H. pylori antibody nor other autoantibodies were present in significant numbers of urticaria patients when compared to controls. Tested autoantibodies included those to thyroglobulin, sDNA, SSA/SSB, ENA, cardiolipin, beta2-glycoprotein I, myeloperoxidase, proteinase-3, smooth muscle, ANA, human lysosomal-associated membrane protein, and bactericidal permeability increasing protein. Thus, patients with urticaria were somewhat more likely to have a thyroid autoantibody to TPO or to have RF. This survey demonstrates that while some markers of autoimmunity may be increased in urticaria patients, broad nonspecific autoimmunity is not found.

Adolescent↗

Cytokine levels in various intravenous immunoglobulin (IVIg) preparations.

The mechanisms of action of intravenous immunoglobulin (IVIg) in autoimmune diseases include modulation of cytokine levels. We examined therefore whether direct infusion of abnormally high levels of 13 different cytokines or cytokine-inhibitors within 5 different IVIg preparations have any role in modulation of their levels. None of the measured cytokines in any of the IVIg preparations tested were above the normal levels, and regarding some no traces could be detected. Hence, modulation of cytokine levels following IVIg therapy involves other mechanisms such as interference with their secretion or cytokine-specific blocking antibodies, rather than direct infusion of cytokines.

Cytokines↗

Serum autoantibodies in patients with primary sclerosing cholangitis.

BACKGROUND/AIM: Primary sclerosing cholangitis is a chronic cholestatic syndrome with a presumed autoimmune basis frequently associated with inflammatory bowel disease. The aim of this study was to determine the profile and significance of serum autoantibodies in patients with primary sclerosing cholangitis. METHODS: Serum samples taken from 73 untreated patients (32 female and 41 male, median age 45 years) with well-defined primary sclerosing cholangitis, and from 75 healthy age- and sex-matched controls were assayed for 20 different autoantibodies. RESULTS: Of 73 patients, 71 (97%) were positive for at least 1 autoantibody; whereas 59/73 patients (81%) were positive for > or =3 antibodies. Patients with primary sclerosing cholangitis had a significantly greater rate of positivity than controls for antinuclear, anticardiolipin, antineutrophil cytoplasmic, and antithyroperoxidase antibodies as well as rheumatoid factor. The rate of positivity and serum levels of any of these 20 autoantibodies were not significantly different between patients with primary sclerosing cholangitis and inflammatory bowel disease and those without inflammatory bowel disease. Anticardiolipins were the single group of antibodies that had a significant correlation with the Mayo risk score (r=0.49, p<0.001) and histologic stage of disease (r=0.30, p<0.01). CONCLUSIONS: Primary sclerosing cholangitis is associated with a high proportion of non-organ specific autoantibodies. Anticardiolipin antibodies appear to be related to the severity of primary sclerosing cholangitis and may be a useful prognostic marker.

Adult↗

Permanence of Fungi-Fluor epifluorescence stain to detect microsporidia.

OBJECTIVE: Epifluorescence microscopy, a methodology for the screening of bodily fluids and tissue specimens for microsporidia species, was directed to evaluate the retention of epifluorescence of fixed and stained specimens over time. METHODS: Thirty samples of stool, bodily fluids, duodenal touch preparations, and biopsies, were tested for the retention of their epifluoresence using the Fungi-Fluor procedure. Specimens were examined under a 330- to 380-nm UV filter at the time of preparation, 3 wk later, and then at monthly intervals for 18 months. All specimens were reevaluated for the presence or absence of fluorescence and any decrement of fluorescence over time. No special preservation techniques were used on any of the slides. RESULTS: All 30 specimens maintained their epifluorescence from the time of slide preparation to 18 month later. No decrement in fluorescence was noted in any sample examined. Accuracy and ease of spore identification was maintained. CONCLUSIONS: Epifluorescence microscopy demonstrates the utility of this technique for archival study of microsporidia-containing specimens over prolonged periods of time.

Animals↗

Central nervous system involvement in systemic lupus erythematosus: cerebral imaging and serological profile in patients with and without overt neuropsychiatric manifestations.

The aim of this study was to evaluate morphological and functional abnormalities by cerebral imaging in a series of systemic lupus erythematosus (SLE) patients with and without overt central nervous system (CNS) manifestations, and to detect possible relationships with clinical parameters and a large panel of autoantibodies, including those reactive against neurotypic and gliotypic antigens. 68 patients with SLE were investigated in a cross-sectional study which included clinical evaluation of symptoms, cerebral magnetic resonance imaging (MRI) and brain single photon emission tomography (SPECT) analysis, electroencephalography (EEG), and serological tests for antibodies directed against nuclear, cytoplasmic neuronal and glial cell-related antigens. The results of this study showed: (1) a significant positive association of (a) anti-glial fibrillary acidic protein (GFAP) serum antibodies with neuropsychiatric (NP) manifestations and (b) anti-serin proteinase 3 (anti-PR3/c-ANCA) serum antibodies with pathological cerebral SPECT; (2) the presence of significantly higher values of (a) SLICC organ damage index in patients with abnormal MRI and (b) SLAM activity index in patients with abnormal SPECT; and (3) the association of (a) abnormal MRI with nonactive NP manifestations and (b) combined abnormality of brain SPECT and MRI with the occurrence of overall overt NP manifestations and with those of the organic/major type. Neuropsychiatric manifestations, namely those of the organic/major type, appeared to be significantly associated to the presence of a serum antibody against GFAP, a gliotypic antigen. There was also evidence of an association between SPECT abnormality and the presence of anti-PR3 (c-ANCA). Furthermore, brain imaging by MRI and SPECT applied to SLE patients appears to express CNS involvement significantly related to specific categories of NP manifestations. The abnormalities detected by the two tests seem to be preferentially associated with different activity phases of the NP disorder or of the lupus disease.

Adolescent↗

Detection of antibodies to gangliosides and glycolipids in various intravenous immunoglobulin (IVIg) preparations.

The aim of this study was to examine the presence of antibodies to GM1 and sulfatide in various IVIg preparations. Five brands of commercially available human IVIg (Sandoglobulin, Isiven, Cytogam, Omrigam and Cutter) were examined and compared. Serial dilutions of each of the above preparations were prepared at a working range of 0.009 to 25.0 mg/ml IVIg, and screened by a standard 96-well microplate EIA for autoantibodies to the ganglioside GM1 and to the glycolipid sulfatide. The various IVIg preparations (Omrigam, Cytogam, Sandoglobulin, Isiven), except for Cutter IVIg, contained low to medium titers of the autoantibodies tested. Omrigam and Cytogam IVIg contained low titer of antibodies to GM1, and medium-titer of antibodies to sulfatide, whereas Sandoglobulin and Isiven contained only low-titer of autoantibodies to sulfatide. The presence of natural autoantibodies to myelin in human sera may explain the presence of the tested antibodies within IVIg preparations. Measurements of antibodies to ganglioside and glycolipid in sera of Guillain-Barré patients immediately following IVIg, would probably not reveal antibody decrease. Alternatively, long-term (several weeks) follow-up of titers might result in their modification due to inhibition of antibodies production by IVIg.

Autoantibodies↗

Glutamine synthetase in cerebrospinal fluid, serum, and brain: a diagnostic marker for Alzheimer disease?

OBJECTIVES: To determine whether the glutamine synthetase (GS) level in cerebrospinal fluid (CSF) is a useful biochemical marker in the diagnosis of Alzheimer disease (AD), and to assess the source of GS (brain vs. blood derived) in CSF. METHODS: Sandwich enzyme immunoassay and immunoblotting were applied to detect GS in CSF and in serum from neurologically healthy control subjects and patients with neurodegenerative diseases, including AD. The origin of GS was estimated by the concentration gradients of CSF to serum and ventricular to lumbar CSF. In addition, postmortem brain tissue from controls and patients with AD was analyzed using immunohistochemistry for expression of GS. RESULTS: Levels of GS were significantly increased in lumbar CSF from patients with AD (20+/-12 pg/mL; P = .01) and to a lesser extent in patients with vascular dementia and amyotrophic lateral sclerosis. In CSF of controls, GS levels were 4+/-3 pg/mL. The GS concentration gradients were less than 1:10 for CSF to serum and 2:1 for ventricular to lumbar CSF. Immunoreactivity of GS was most prominent in astrocytes from temporal neocortex of patients with AD, suggesting a relationship between astrocyte reactions and increased GS levels in CSF. CONCLUSIONS: Level of GS in lumbar CSF of patients with AD is increased significantly but nonspecifically, probably related to the strong astrogliosis in brain. Glutamine synthetase in lumbar CSF is mainly brain derived.

Adolescent↗

Hantavirus-specific IgG, IgM, and IgA in acute and chronic renal disease versus congenital renal disease in the United States.

In a blinded fashion, 165 serum samples from patients with biopsy-characterized acute and chronic renal diseases (ACRDs), 34 serum samples from patients with congenital renal diseases (CRDs), and 100 serum samples from healthy adults were assayed for immunoglobulin G (IgG), IgM, and IgA antibodies to Hantaan and Puumala viruses by enzyme immunoassay (EIA). Twenty-six percent (44 of 165) of ACRDs, 3% (1 of 34) of CRDs, and none (0 of 100) of the healthy serum samples were positive for hantavirus-specific antibodies (P < 0.001, Fisher's exact test). Thirty of 44 positive serum samples (68%) were from three groups: ie, acute tubulointerstitial nephritis (AIN), 20% (9 of 44); necrotizing glomerulonephritis (NG), 27% (12 of 44); and IgA nephropathy, 20% (9 of 44). The remaining 14 positive samples were from patients with a varied group of renal conditions. IgA antibody levels alone were elevated in 37%, IgG alone in 33%, IgM alone in 17%, and all three isotypes in 13% of the AIN-, NG-, and IgA-positive samples. These data indicate that three renal diseases account for approximately 68% of the hantavirus-positive sera tested and that serological evaluations should include all three isotypes of antibodies.

Acute Kidney Injury↗