Incidence of the prozone phenomenon in syphilis serology

OBJECTIVE: To determine the rate of the prozone phenomenon in our patient population. METHODS: Sera from 4328 patients--3504 females (2065 pregnant, 1439 nonpregnant) and 824 males--were tested for syphilis by the rapid plasma reagin (RPR) test, and then rechecked with serial twofold dilutions of up to 16-fold to detect the prozone phenomenon. Chi-square analysis with Yates correction was used, with P < or = .05 considered significant. RESULTS: The total positivity rate in females was 6% (213 patients); 13% (27) of the positive tests were false-positive reactions as confirmed by a negative anti-treponemal antibody test. Only one prozone reaction was detected, in serum from a male subject, but it was not missed on initial screening. CONCLUSION: The rate of prozone phenomenon is very low (95% confidence interval 0-0.4%), and routine serial dilutions are not cost effective.     

Systemic lupus erythematosus diagnosed during interferon alfa therapy

We describe a patient who had clinical manifestations of several autoimmune disorders: Sj?gren's syndrome, benign hypergammaglobulinemic purpura of Waldenstr?m, and systemic lupus erythematosus (SLE). The SLE was diagnosed during therapy with interferon alfa. Testing for anti-Ro and anti-La antibodies was negative until the serum was diluted to eliminate a possible prozone phenomenon of antibody excess.     

Cerebrospinal fluid findings in asymptomatic patients with reactive serum fluorescent treponemal antibody absorption tests

It is common to examine the cerebrospinal fluid in untreated or inadequately treated asymptomatic patients with a reactive serum fluorescent treponemal antibody absorption (FTA-ABS) test before initiating antibiotic therapy for syphilis. This prospective study evaluated the usefulness of such examination. Four hundred thirty-two patients over 40 years old, reporting for annual physical examination, had a serum FTA-ABS test. Thirty-seven (8.6%) patients and 2 of 4 spouses were reactive repeatedly. Of the 39 patients with reactive tests, 7 had a history of penicillin therapy for syphilis, 5 had received heavy metal therapy, and 27 had no history of syphilis. These 39 patients had a neurological examination, serum VDRL, Treponema pallidum immobilization (TPI), and repeat FTA-ABS tests by two other laboratories. The TPI test was reactive in 30 (77%). Four had nonspecific neurological signs. Routine CSF examination (cells, total protein, VDRL, glucose, IgG%) on 30 patients with a history of inadequate treatment had a low diagnostic yield. Two patients had an unexplained total protein elevation (57 and 61 mg/dl) and 1 had a mildly increased IgG% (15%). All cell counts, VDRL tests, and glucose levels were normal. Agarose electrophoresis demonstrated one or more CSF immunoglobulin bands in 10 (36%) of 28 patients, possibly representing an immunological marker of past or latent central nervous system infection.     

Warm IgM anti-IT causing autoimmune haemolytic anaemia

A patient with autoimmune haemolytic anaemia due to an autoagglutinin of anti-IT specificity is reported. The antibody was of the IgM class and bound complement; unexpectedly, it reacted optimally at 37 degrees C. A prozone was noted when testing serial dilutions of the patient's serum against appropriate red cells in saline, but was not found when testing an eluate prepared from the patient's red cells. Investigations suggested that the prozone was due to a blocking antibody of high molecular weight, which appeared to be specific for I and IT.     

Management of nevus spilus

BACKGROUND: Granulomatous gastritis is a rarely observed pathological diagnosis. This condition often mimics gastric adenocarcinoma clinically, resulting in gastric resection. However, granulomatous gastritis has long been viewed as a benign process not observed in association with adenocarcinoma of the stomach. This article describes a patient with granulomatous gastritis occurring in close proximity to an area of superficially invading gastric adenocarcinoma. METHODS: Acid-fast stains, fungal stains, standard cultures, tuberculosis cultures, and a VDRL serum test were all obtained. Both upper endoscopy and colonoscopy were performed. Chest radiographs were taken and pulmonary consultation was obtained. RESULTS: The gastric samples obtained from resection showed no evidence of foreign body reaction. The acid-fast stains, fungal stains, cultures, and VDRL were all negative. Endoscopic exams did not show granulomatous inflammation in any other part of the gastrointestinal tract. No pulmonary disease was evident on radiographic or pulmonary exam. CONCLUSION: Isolated granulomatous gastritis is a diagnosis of exclusion. The findings in this patient do not support a diagnosis of Crohn's disease, tuberculosis, sarcoidosis, syphilis, histoplasmosis, berylliosis, or foreign-body reaction. This is a unique case suggesting an association between isolated granulomatous gastritis and metaplastic mucosal changes.     

Recombinant antigen-based enzyme immunoassay for screening of Treponema pallidum antibodies in blood bank routine

This work reports a comparison of an enzyme immunoassay (EIA) using two major Treponema pallidum recombinant antigens with a T. pallidum hemagglutination (TPHA) assay and a nontreponemal Venereal Disease Reference Laboratory (VDRL) test. A total of 1,822 normal donor serum samples was tested for cardiolipin and T. pallidum antibodies, respectively, by the VDRL assay and EIA. Among these samples, 440 were further tested by TPHA technology. Four samples were found positive by EIA, while all were reported to be negative by both TPHA and VDRL routine assays. Subsequent testing of EIA-positive samples confirmed 100% (four of four samples) and 25% (one of four samples) positive results, respectively, by immunofluorescence assay and a Western blot (immunoblot) syphilis kit. The sensitivity of the recombinant EIA was estimated at virtually 100% with a reference panel of 50 syphilitic samples. According to this study, the newly developed EIA kit shows 100% sensitivity combined to a specificity greater than 99.8% for detecting treponemal immunoglobulin G antibodies in blood bank syphilis screening.     

Dementia paralytica in a fifteen-year-old boy

A 15-year-old boy, whose history revealed an unremarkable pregnancy, birth and neonatal period and who had shown a normal motor and mental development, presented at the hospital with deterioration of cognitive functions since the age of 7. He was bedridden with manifest ataxia involving all limbs, anisocoria and a sluggish to absent pupil reaction to light. Syphilis serology was positive with a Venereal Disease Research Laboratory (VDRL) titer of 1:256 and a Treponema pallidum Haemagglutination Assay (TPHA) titer of 1:163840. Cerebrospinal fluid (CSF) protein concentration was 55 mg/dl and CSF-leucocyte count was 14/mm3 (85% mononuclear cells). CSF-VDRL-titer was 1:16. A diagnosis of congenitally acquired dementia paralytica was made, since the boy's parents' clinical exam and serology results were suggestive for latent syphilis. Although cognition was still very much deteriorated five months following penicillin treatment, clinical examination revealed partial recuperation. Screening for syphilis should be part of routine testing in every subject presenting with cognitive deterioration, regardless of age.     

The usefulness of cerebrospinal fluid tests for neurosyphilis

To determine the usefulness of cerebrospinal fluid (CSF) tests for syphilis at a large academic hospital, clinical and laboratory data on 644 patients in whom such testing was requested over a 12-month period were analysed. In 198 cases (31%) the Treponema pallidum haemagglutination (TPHA) screening test could not be performed because of insufficient fluid. Thirty-eight of the remaining patients were diagnosed as having active neurosyphilis. Examination of 22 files of patients who had a positive TPHA and fluorescent treponemal antibody absorption (FTA-Abs) test together with a negative CSF Venereal Disease Research Laboratory (VDRL) test revealed that other CSF measures indicating disease activity (CSF protein, cells or IgG index) were not utilised optimally. In 10 (45%) of these patients neurosyphilis was not diagnosed despite either abnormal or incomplete CSF biochemical analysis, indicating that if the CSF VDRL is used as the sole marker for disease activity, some cases of neurosyphilis are likely to be missed.     

Cesium uptake studies on human erythrocytes

We compared the performance of second and third generation ELISA assays to detect antibodies to HIV-1 virus with conventional Western blotting (WB) and radioimmune Western blotting (RIWB). Both sera from commercial seroconversion panels and serial dilutions of a serum for HIV-1 antibodies were tested with Murex HIV Recombinant, Vidas bioMérieux HIV 1/2 (2nd generation ELISA) Murex HIV 1-2 (3rd generation ELISA), as well as with WB and RIWB. In seroconversion panels all ELISA assays were positive for the same serum with the exception of the first serum of Panel D which was negative with both sample Murex assays and borderline with Vidas assay. This serum was negative with WB but evidenced antibodies to gp160 p66, p51, p24 HIV-1 proteins when assayed by RIWB. In only two cases did WB reveal antibodies to HIV-1 proteins before ELISA assays (Panel A and E); not only did RIWB show the same sensitivity as WB in the two last panels, but it also detected antibodies to HIV-1 proteins earlier than WB, ranging from a few days (Panel C) to approximately 12 weeks (Panel D). The results obtained by testing the dilutions of the serum positive for anti HIV-1 antibodies showed the following degrees of sensitivity: Murex HIV 1-2 (the most sensitive), Murex HIV Recombinant and Vidas bioMérieux HIV 1/2. Although WB was more sensitive than the ELISA assays and picked out antibodies to gp160, gp120 and p24 HIV proteins at 1/4000 serum dilution, the most sensitive test was RIWB which at 1/20,000 serum dilution enabled detection of antibodies to gp160, p66 and p24 HIV proteins.     

Neurosyphilis. A comparative study of the effects of infection with human immunodeficiency virus

BACKGROUND: The course of neurosyphilis has been reported to be altered by human immunodeficiency virus (HIV) infection. Prior reports of neurosyphilis occurring in association with HIV infection have been largely anecdotal and have failed to compare neurosyphilis in patients with HIV infection with an uninfected control group. This study was performed to determine if the clinical presentation encountered is different in the presence of HIV infection. DESIGN: A retrospective, hospital-based, case series study based on chart review encompassing a 64-month period. SETTING: The study was performed in a large, university-affiliated, public health trust hospital in south Florida. PATIENTS: Forty-six hospitalized patients with neurosyphilis were identified; 13 patients fulfilled Centers for Disease Control and Prevention (Atlanta, Ga) criteria for acquired immunodeficiency syndrome (AIDS), 11 were HIV seropositive only, and 22 were HIV uninfected. Neurosyphilis was determined by a reactive cerebrospinal fluid VDRL slide test. RESULTS: The HIV-infected patients (both AIDS and HIV-seropositive groups) were younger and more frequently had features of secondary syphilis, such as rash, fever, adenopathy, headache, or meningismus. Significant differences were observed in cerebrospinal fluid measurements when the HIV-infected group was compared with the HIV-uninfected group, including a higher mean white blood cell count in patients with AIDS and a higher mean protein level and a lower mean glucose level in the HIV-infected group. Syphilitic meningitis was more common in HIV-seropositive patients, although the HIV-uninfected patients presented with a greater variety of types of neurosyphilis. Ophthalmic syphilis was observed more frequently in the HIV-infected group. CONCLUSIONS: Significant differences exist between neurosyphilis occurring in the presence and absence of HIV infection.     

False-negative syphilis screening due to change in temperature

BACKGROUND AND OBJECTIVES: Inaccurate test results for syphilis may cause an individual to experience serious effects. GOAL OF THE STUDY: Investigate potential sources of error and test limitations causing false-negative reactions. STUDY DESIGN: In 5 months, two laboratories screened 2,232 patients for syphilis by the Rapid Plasma Reagin (RPR) test. RESULTS: The hospital laboratory reported 5.3% (64/1,210) of patients' test as reactive on initial screening, and the research laboratory found 6.4% (78/1,210) reactive. Fourteen reactive patients were incorrectly reported negative by the hospital laboratory, as confirmed by both laboratories. A refrigerated centrifuge in the hospital laboratory possibly caused sera to be cooled before testing, producing false-negative results. When its temperature was adjusted from 4 degrees C to 27 degrees C, an additional 1,022 samples tested were consistent between the two laboratories. CONCLUSION: Cold temperature produces false-negative reactions for syphilis screenings in patients' samples with titers < 1:4 dilution. Patients' samples with titers > or = 1:16 dilution were not affected. According to this study, incorrect temperatures for test sera can alter testing outcomes. Therefore, test manufacturer's directions must be strictly followed.     

Maternal and congenital syphilis

Testing for syphilis during pregnancy reveals a positive serologic status in 0.02% of cases. However, a 66% rate of stillbirths is noted in women who are infected and who have not benefited from any treatment. Routine screening is at present performed during the early stages of pregnancy but a second serologic test during the third trimester is useful in the diagnosis of a late infection especially in drug users or HIV (human immunodeficiency virus) positive patients. Congenital syphilis is diagnosed in utero when a positive maternal serologic status is associated with ultrasound images showing fetal abnormalities; these include hepatosplenomegaly, hyperechogenic bowel, signs of bowel obstruction or fetal hydrops. Maternal syphilis is treated by delayed action penicillin and is indicated even for patients allergic to the antibiotic which in this particular case is delivered after desensitization. First line therapy by intravenous penicillin is indicated when confronted with the following high risk factors of congenital syphilis: an elevated titre of VDRL (venereal disease research laboratory) at the time of diagnosis or delivery, unknown date of the precise onset of the infection, the appearance of a rash or of a chancre during pregnancy, ultrasound fetal abnormalities or late therapy during the third trimester. Treatment of the new-born child will depend on the results of clinical, serologic and X-ray evaluation. Long term follow-up for at least a year is mandatory.     

No link between avascular necrosis of the femoral head and antiphospholipid antibodies

The rate of occurrence of antiphospholipid antibodies was compared in 47 patients with avascular necrosis of the femoral head and in 47 controls matched on age and sex. Antiphospholipid antibodies were looked for using three techniques in each patient, namely the VDRL test, an ELISA for anticardiolipin, and a circulating anticoagulant detection procedure involving three different tests. The VDRL and the tests for circulating anticoagulants were negative in all the patients and controls. No significant between-group difference was found for the ELISA, which was positive in three patients and two controls.     

Long-term follow-up evaluation in HCV chronic hepatitis treated with alpha-2b interferon. A comparison of two protocols

OBJECTIVE: To compare prospectively the concordance between the diagnosis of dementia based on clinical criteria and using the DAT Inventory. DESIGN, SETTING, AND PARTICIPANTS: A prospective study of 81 consecutive patients referred to a Memory Clinic. Only patients for whom a definitive diagnosis of dementia was established after 8 to 20 months follow-up were retained in the study (n = 76). MEASUREMENTS: The sensitivity, specificity, positive and negative predictive values, and overall diagnostic accuracy of the DAT Inventory were calculated. Kappa values were also computed. RESULTS: Based on all patients (n = 76), sensitivity and specificity were 71% and 95%, respectively, with 98% positive prediction, 56% negative prediction, 78% overall accuracy, and kappa of 0.54. Of 21 cases not meeting NINCDS/ADRDA criteria for DAT, one patient with multi-infarct dementia was misclassified as DAT on the DAT Inventory. Of 55 DAT cases (NINCDS/ADRDA criteria), 16 patients, predominantly very mild or mixed cases, were classified as non-DAT on the DAT Inventory. When mixed, very mild, and borderline cases were excluded (remaining n = 54), DAT Inventory sensitivity increased to 94%, and specificity remained unchanged at 95%, with 97% positive and 91% negative prediction, 94% overall accuracy, and kappa of 0.88. CONCLUSIONS: In general, scores above the designated cutoff point (> 14/20) on the DAT Inventory are consistent with a clinical diagnosis of DAT (NINCDS/ADRDA criteria). Concordance is best in cases of mild to moderate dementia (Clinical Dementia Rating 1-2). The Inventory is less discriminating as a differential diagnostic instrument in cases of very mild dementia, atypical presentations of DAT, or in cases of mixed pathology.     

A new look at the serology of treponemal disease

The serology of treponemal disease has become simpler and more rational in recent years, mainly as a result of the widespread adoption of specific antibody tests and the use of monospecific fluorescent antibody procedures which give information about the immunoglobulin class of antibodies. A set of tests which has proved particularly useful in routine diagnosis is the following: quantitative TPHA test, quantitative VDRL test, and monospecific (IgG and IgM) FTA-ABS tests. This combination is especially valuable in the assessment of new patients with positive results to serological tests and in the management of patients with treated syphilis.     

Antibody epitopes probed by immunoselected phage-display library peptides in members of a family with various rheumatic manifestations

OBJECTIVE: The random peptide combinatorial phage library approach overcomes the problem of lack of structural information about the aetiological agent or the antigen responsible for a given disease. Here, we used such a strategy to gain insight into the aetiology of rheumatoid arthritis (RA). METHODS: We analyzed the reactivity of serum antibodies from a family with various rheumatic manifestations against RA-immunoselected nanopeptides displayed on phage particles. RESULTS AND CONCLUSION: We found that within the same family, there was a difference in antibody reactivity against the peptides tested. The IgG isotype of the peptide reactive antibodies indicated that the observed reactivities were not related to the presence of polyreactive IgM antibodies. Furthermore, it is unlikely that the observed reactivity was due to rheumatoid factors (RF), since two patients who were positive for the immunoselected Pep3 peptide (LSSREPQAR) were RF negative. We also found that the serum of one patient with polyarthralgias also reacted with the same peptide bound by the RA serum, which may suggest the implication of a common aetiological agent in the apparition of this antibody reactivity. Finally, we noted that one patient with Sj?gren's syndrome had antibodies to the RA peptide, which may indicate a potential relationship between these two autoimmune diseases.     

Clinical significance of antiphospholipid autoantibodies in lupus erythematosus

The authors have determined the prevalence of antibodies of cofactor dependent anticardiolipin and beta 2-glycoprotein I and lupus anticoagulant and the frequency of false positive VDRL test in systemic lupus erythematosus. The aim of this retrospective study was to assess the presence of these antibodies and symptoms of antiphospholipid syndrome. The serum samples were examined by modified ELISA method for detecting of cofactor dependent anticardiolipin. The antibodies to beta 2-glycoprotein I were examined by ELISA. The lupus anticoagulant and VDRL test were performed by routine laboratory method. The authors have found that 19 of 58 patients with systemic lupus erythematosus had cofactor dependent anticardiolipin, 10 patients had antibodies to beta 2-glycoprotein I and 4 patients had positive VDRL test. 5 of 34 plasma samples were lupus anticoagulant positive. 19 patients with systemic lupus erythematosus had 14 neuropsychiatric disorders, 9 cardiovascular diseases, 7 thrombocytopenia, 6 histories of recurrent abortion and fetal loss, 5 livedo reticularis and 3 thromboembolic events in all of them had detected antibodies to cofactor dependent anticardiolipin, while these complications were diagnosed in 39 anticardiolipin negative patients much more rarely. The results of this retrospective study suggest that significant association exists between the presence of cofactor dependent anticardiolipin and symptoms of antiphospholipid syndrome in systemic lupus erythematosus.     

Ocular syphilis and neurosyphilis in a patient with human immunodeficiency virus infection

A patient who presented with severely decreased bilateral vision was found to have syphilis and neurosyphilis that responded well to a 14-day course of penicillin and prednisone. The patient tested positive for HIV, which can alter the natural course of syphilis, often making the diagnosis and treatment difficult. Conventional therapy for syphilis may not be effective in patients with HIV. Any patient with syphilis who is in a high-risk group should be tested for HIV; conversely, any patient with HIV should be tested for syphilis if signs or suspicions exist.     

The effect of recombinant human erythropoietin on hemostasis, fibrinolysis, and blood rheology in autologous blood donors

We report three cases of Castleman's disease mimicking the features of collagen disease. Case 1: A 39-year-old woman presented with intermittent arthralgia and fever. Laboratory findings were positive results for antinuclear antibody (80x speckled type), the LE test, anti-SSA antibody, anti-RNP antibody, and Coombs test. The patient was suspected to have systemic lupus erythematosus (SLE) or Sj?gren syndrome, but a lymph node biopsy revealed the plasma cell type of Castleman's disease. Steroid treatment led to resolution of her symptoms. Case 2: A 60-year-old man with mixed type Castleman's disease had proteinuria with renal dysfunction, autoimmune thrombocytopenia, antinuclear antibody, anti-RNP antibody, anti-DNA antibody and anti-cardiolipin antibody. The patient was suspected to have SLE but cervical lymph node biopsy revealed the mixed type of Castleman's disease. Symptoms were not controlled with steroid therapy. He developed renal failure that required for hemodialysis and died of gastrointestinal bleeding due to severe thrombocytopenia. Case 3: A 46-year-old woman had Raynaud's phenomenon, sclerodactylia, and nail fold bleeding. Laboratory tests were revealed positive for antinuclear antibody, anti-ENA antibody, and LE cell preparation. Radiographic study showed multiple masses in the retroperitoneal spaces, which necessitated laparotomy. Firstly, the patient was suspected to have systemic sclerosis or mixed connective tissue disease (MCTD). A biopsy revealed the hyaline-vascular type of Castleman's disease. The serum level of IL-6 by ELISA was high in all of three cases. In case 1, symptoms improved and the IL-6 level normalized after steroid treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quality of life and dementia

OBJECTIVE: To review the relationship between quality of life (QOL) and dementia. Development. QOL is a factor which takes into account all the different aspects of life which make a person feel that life is worth living, such as: 1. Physical health. 2. Functional status. 3. Psychological and cognitive sphere, and 4. Social health. There are two types of instruments for evaluating these aspects: firstly general ones which measure the QOL independently of illness, and secondly those which are specific to the illness concerned. In dementia, QOL covers the same traditional areas: cognitive competence, capacity to carry out everyday activities, social conduct and the balance between positive and negative emotions. However, evaluation of QOL in dementia has its own specific difficulties, since it is often impossible to determine such a fundamental factor as the subjective well-being of the patient, in which case the opinion of the person looking after the patient is essential. According to Lawton's approximation, as well as the subjective aspect of perceived psychic welfare and quality of life, the QOL in dementia is composed of external social and objective dimensions such as behaviorally competence and the quality of the patient's environment. In a review done in 1995 it was found that most of the instruments designed to measure the QOL have not been sufficiently validated for Alzheimer's disease. CONCLUSIONS: QOL in dementia has specific features including external aspects such as the opinion of the carer and the quality of the patient's environment in addition to the subjective aspects. It is necessary to develop and validate specific instruments for QOL in dementia.