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Biomedical subjects

J Schachter

Publications and source records attributed to J Schachter.

At least 91 records · Page 5Linked to original sources

Detection of anti-Chlamydia pneumoniae IgE in children with reactive airway disease.

An association of Chlamydia pneumoniae infection and reactive airway disease has been demonstrated in children. To determine if C. pneumoniae infection triggers production of C. pneumoniae-specific IgE, sera were examined from 45 children with and without C. pneumoniae infection. Anti-C. pneumoniae IgE was demonstrated by immunoblotting in 12 (85.7%) of 14 culture-positive asthmatic patients with wheezing compared with only 1 (9.1%) of 11 culture-positive patients with pneumonia, 2 (18.2%) of 11 culture-negative asthmatic children with wheezing, and 2 (22.2%) of 9 culture-negative asymptomatic patients. The most commonly recognized proteins were at 98 (82.4%), 78 (58.8%), 58-60 (70.6%), and 36 kDa (64.7%). The presence of anti-C. pneumoniae IgE by immunoblotting was not associated with the presence of anti-C. pneumoniae IgG and IgM by microimmunofluorescence. These results suggest that production of specific IgE may be an underlying mechanism leading to reactive airway disease in some patients with C. pneumoniae infection.

Adolescent↗

Major outer membrane protein variants of Chlamydia trachomatis are associated with severe upper genital tract infections and histopathology in San Francisco.

Cervical and endometrial samples from 33 women with lower genital tract infection (LGTI) or pelvic inflammatory disease (PID) were evaluated for Chlamydia trachomatis major outer membrane protein gene (omp1) polymorphism. Polymorphism was correlated with symptoms, clinical findings, and histopathology. F, E, I, D, H, K, and G genotypes were represented. Thirty-seven genotyped samples (66%) displayed omp1 mutations compared with prototype sequences. Significantly, 7 of 7 women with variant F infections had PID compared with 6 non-variant F infections in women with LGTI (P = .003). PID was defined by clinical findings or plasma cells on endometrial biopsy. Of interest, F variants were associated with histopathology. Eleven women (92%) with E genotypes were asymptomatic. Our data suggest that F variants are associated with symptomatic, severe endometrial disease, whereas E genotypes are associated with asymptomatic, milder infections. Detection of virulent genotypes may provide a prognostic indicator for serious sequelae. Larger studies are required to evaluate the molecular, immunologic, and epidemiologic basis for these findings.

Amino Acid Sequence↗

Noninvasive tests for diagnosis of Chlamydia trachomatis infection: application of ligase chain reaction to first-catch urine specimens of women.

Ligase chain reaction (LCR) to diagnose Chlamydia trachomatis infection was evaluated using first-catch urine (FCU) specimens from 4053 women. Results were compared with those of cell culture (TC) isolation from cervix (all) and urethra (2812 women). The reference standard was TC positivity or positive LCR for chlamydial plasmid DNA confirmed by direct fluorescent antibody test or LCR for another chlamydial gene. Compared with cervical culture, LCR was 88.2% sensitive and 100% specific. Adding urethral culture increased TC sensitivity from 67.1% to 74% and reduced LCR sensitivity to 85.9%. The prevalence of chlamydial infection was 5% (142/2812) by the dual culture system and 5.9% (165/2812) by LCR on FCU specimens. LCR on FCU specimens is highly sensitive and specific for diagnosing chlamydial infection. It is more sensitive than TC and may well present public health authorities with a useful noninvasive screening test for chlamydial infection in asymptomatic women.

Cells, Cultured↗

Sexual behavior, sexually transmitted diseases, and risk of cervical cancer.

To explore sexually transmitted diseases and sexual behavior as risk factors for cervical cancer, we analyzed data from a population-based case-control study of breast and cervical cancer in Costa Rica. Data from 415 cases of cervical carcinoma in situ, 149 cases of invasive cervical cancer, and 764 controls were included in the analysis. Multivariate analysis showed that lifetime number of sex partners, first intercourse before age 15 years, number of livebirths, herpes simplex virus type 2 seropositivity, and serologic evidence of previous chlamydial infection were predictors of carcinoma in situ. Serologic evidence of previous syphilis was not associated with carcinoma in situ. Predictors for invasive cervical cancer included lifetime number of sex partners, first intercourse before age 15 years, number of livebirths, serologic evidence of previous syphilis, herpes simplex type 2 infection, and chlamydial infection. Cigarette smoking, socioeconomic status, self-reported history of sexually transmitted diseases, and douching were not associated with either carcinoma in situ or invasive cervical cancer.

Adult↗

Role of CD8 T cells in primary Chlamydia infection.

The role of CD4 and CD8 T cells in primary Chlamydia trachomatis pneumonia was investigated by using in vivo depletion techniques to eliminate T-cell populations. Reduction of either CD4 T cells or CD8 T cells caused a significant increase in organism burden in the lungs, as measured by both quantitative culture and detection of chlamydial antigen on day 14 postinfection. Chlamydia-specific antibody levels in plasma or antigen-induced gamma interferon (IFN-gamma) production by spleen cells was dramatically reduced by depletion of CD4 cells. The reduction in IFN-gamma achieved by depletion of CD8 cells did not reach statistical significance. In the survival studies, depletion of CD4 cells led to a significant increase in mortality. Although there was a trend toward higher mortality, depletion of CD8 cells did not significantly increase mortality. The role of CD8 T cells in host defense was clarified in studies using beta 2-microglobulin-deficient (major histocompatibility class I antigen-deficient, C1D) mice which are defective in CD8 T-cell function. In this model, a significant increase in organism burden was seen during infection in C1D mice compared with that C57BL/6 controls and a significant increase in mortality was observed as well. However, surviving C1D mice were able to clear the infection by day 34. C1D mice had increased numbers of CD4 T cells in both the spleen and the lungs during infection compared with those of C57BL/6 controls. IFN-gamma in C57BL/6 mice was produced by both CD4 and CD8 cells. Thus, there is a protective role for both CD4 and CD8 cells in host defense against Chlamydia infection, but the former appear to be dominant.

Animals↗

Cytochemical localization of glycogen in Chlamydia trachomatis inclusions.

The origin and distribution of glycogen in inclusions of Chlamydia trachomatis were demonstrated with silver proteinate stain for electron microscopy. Glycogen particles were detected in all developmental stages of C. trachomatis, as well as free in the inclusions. Intrachlamydial glycogen was most common in elementary bodies but was also detected in intermediate forms and reticulate bodies (RBs). Abnormal divisions and breakdown of cytoplasmic membranes were common in RBs. Cytoplasmic contents, including glycogen particles, were released into the inclusions after rupture of the outer membranes of abnormal RBs and intermediate forms. From these observations, we conclude that glycogen in inclusions of C. trachomatis originates in the organisms themselves.

Amylases↗

The association of Chlamydia pneumoniae infection and reactive airway disease in children.

OBJECTIVE: To determine the possible association of Chlamydia pneumoniae infection and reactive airway disease in children. DESIGN: Prospective observational study. SETTING: Pediatric emergency department in Children's Medical Center of Brooklyn (NY), Kings County Hospital Center. PARTICIPANTS: One hundred eighteen children with acute episodes of wheezing and 41 age- and sex-matched healthy controls, aged 5 to 16 years. INTERVENTIONS: Children with cultures positive for C pneumoniae were treated with antibiotics. MEASUREMENTS/MAIN RESULTS: Cultures for C pneumoniae and serum samples for antibody testing were obtained from subjects and healthy controls. We isolated C pneumoniae from 13 (11%) children with wheezing and from two (4.9%) controls. Seven (58.3%) of 12 children with positive cultures had no detectable antibody to C pneumoniae and only three (25%) children had serologic evidence of acute infection. Six children had positive cultures on multiple occasions, ranging from 1 to 5 months. The children with wheezing were treated with erythromycin or clarithromycin, a new macrolide antibiotic approved for use in adults; all eventually had a negative culture. Nine (75%) of these children demonstrated clinical and laboratory improvement of the reactive airway disease after the eradication of chlamydial infection. CONCLUSIONS: Infection with C pneumoniae can trigger acute episodes of wheezing in children with asthma. Treatment of C pneumoniae infection may improve the course of reactive airway disease in these patients.

Adolescent↗

Protective effect of albuterol delivered via a spacer device (Babyhaler) against methacholine induced bronchoconstriction in young wheezy children.

Nine young asthmatic children aged 2-5 years underwent methacholine challenge after placebo or albuterol administered by metered dose inhaler through a spacer device (Babyhaler) with a face mask in a double-blind, cross-over, randomized study. The methacholine challenge was performed using chest auscultation to define the provocative concentration of methacholine that causes wheezing (PCW). The PCW increased from a geometric mean of 0.28 mg/mL after placebo to 3.59 mg/mL after albuterol (P < 0.0001). The protective effect of albuterol against methacholine-induced bronchospasm was 3.7 +/- 1.2 doubling doses. We conclude that administration of drugs from a metered dose inhaler through the Babyhaler with a face mask is effective. Albuterol causes a major reduction in the bronchial hyperreactivity in young wheezy children shortly after administration.

Albuterol↗

Chlamydial serologic characteristics among intrauterine contraceptive device users: does copper inhibit chlamydial infection in the female genital tract?

OBJECTIVE: Our objective was to assess the association between copper intrauterine contraceptive device use and the level of antichlamydial antibodies. STUDY DESIGN: Fifty-four women (29 with history of ectopic pregnancy, 2 with non-tubal factor infertility, 1 with tubal factor infertility, and 22 with intact intrauterine pregnancies) with current or prior intrauterine contraceptive device use were compared with 60 prenatal control subjects with respect to antichlamydial antibodies. RESULTS: When the intrauterine contraceptive device user group was subdivided into copper users and Lippes Loop device users, a significantly lower geometric mean serum antibody titer among copper intrauterine contraceptive device users was detected. The odds ratio estimates for past chlamydial exposure (> or = 1:64 immunoglobulin G, > or = 1:128 immunoglobulin G) in users of noncopper versus copper intrauterine contraceptive devices were 9.1 (95% confidence interval 1.9 to 43.0) and 10.5 (95% confidence interval 1.5 to 71.8), respectively. CONCLUSIONS: The lower geometric mean serum antibody titer of antichlamydial antibody among copper versus Lippes Loop device users and the large association measured between past chlamydial infection and noncopper intrauterine contraceptive device use suggest that copper may have a protective effect against Chlamydia trachomatis infection or a suppressive effect on development of antichlamydial antibodies.

Adult↗

Docetaxel (Taxotere) in advanced malignant melanoma: a phase II study of the EORTC Early Clinical Trials Group.

The antitumour activity of docetaxel was investigated in patients with advanced malignant melanoma. Docetaxel, 100 mg/m2, intravenous, over 60 min, was administered every 3 weeks. Response evaluation was performed after two cycles. No prophylactic treatment with steroids or antihistamines was given. 38 patients were included, 36 were eligible and evaluable for toxicity and 30 patients were evaluable for response. The main haematological toxicity was neutropenia [17 patients with common toxicity criteria (CTC) grade 4 and 11 CTC grade 3] with nadir after 5-8 days and rapid recovery. The most frequent non-haematological toxicity was generalised alopecia (83% of the patients). Asthenia, malaise and fatigue were also seen in 58%. Skin toxicity was also frequent. Hypersensitivity reactions (erythematous rash, urticaria, blood pressure changes and tachycardia), seen in 42% of the patients, were mild to moderate. Oedema was registered in one fifth of the patients and developed after four or more treatment cycles. The overall response rate in the evaluable patients was 17% (five partial responders). We conclude that docetaxel has activity in advanced malignant melanoma.

Adult↗

Diagnosis of Chlamydia trachomatis urethral infection in symptomatic and asymptomatic men by testing first-void urine in a ligase chain reaction assay.

A multicenter study compared ligase chain reaction (LCR) of Chlamydia trachomatis plasmid DNA with culture of urethral swab specimens from 542 men (study A); a second study (B) compared LCR of first-void urine (FVU) with urethral swab cultures from 1043 men. Discordant results were resolved with direct fluorescent antibody staining of sediments from the FVU or urethral culture specimen and with a second LCR directed against a fragment of the major outer membrane protein gene. Test performance was calculated on the basis of an expanded reference standard. The LCR plasmid assay had a sensitivity of 98.0% in study A and 93.5% in study B; specificity was 99.8%-100%. The sensitivity of culturing urethral swabs from all study sites was 68.2% (range by sites, 40.0%-84.6%). The presence or absence of urethral symptoms did not alter the results. Use of this LCR test should allow more meaningful investigation and treatment of C. trachomatis infections in men.

Bacteriuria↗

Risk factors associated with pelvic inflammatory disease of differing microbial etiologies.

OBJECTIVE: To compare the prevalences of demographic, historic, and behavioral risks for pelvic inflammatory disease among women with sexually transmitted disease (STD) pelvic inflammatory disease versus those with non-STD pelvic inflammatory disease. METHODS: Subjects included patients diagnosed with acute pelvic inflammatory disease at San Francisco General Hospital between January 1, 1981 and August 20, 1989, who had been entered into clinical treatment trials. At a minimum, endocervical cultures for Neisseria gonorrhoeae and Chlamydia trachomatis were required for study eligibility. All but nine women also had upper reproductive tract cultures for N gonorrhoeae, C trachomatis, and anaerobic and facultative bacteria. Five hundred eighty-nine patients were included in this analysis. The medical records of study subjects enrolled between January 1981 and October 1986 were abstracted (n = 321). Subjects recruited after October 1986 were interviewed during hospitalization using a standardized data base instrument (n = 268). Independent variables examined included age, race, insurance status, education, pregnancy history, menstrual history, contraceptive history, sexual history, douching history, STD history, and pelvic inflammatory disease history. Both univariate associations and multivariate (multiple logistic regression) analysis were performed. RESULTS: An STD organism was present in 65% of pelvic inflammatory disease cases. Neisseria gonorrhoeae and C trachomatis were recovered from 324 (55%) and 129 (22%) of the patients, respectively. In 30% of cases only anaerobic and/or facultative bacteria were isolated. In univariate analysis of STD versus non-STD pelvic inflammatory disease, statistically significant increases in STD risks were found for the following: black race (relative risk [RR] 1.76; 95% confidence interval [CI] 1.39-2.24), two or more sexual partners in the past 30 days (RR 1.25; 95% CI 1.08-1.45), no contraception (RR 1.36; 95% CI 1.18-2.57), N gonorrhoeae with previous episode of pelvic inflammatory disease (RR 1.97, 95% CI 1.39-2.80), and reported duration of pain 3 days or less (RR 1.17; 95% CI 1.02-1.35). Risks associated with non-STD pelvic inflammatory disease included: current intrauterine device (IUD) use (RR 0.25; 95% CI 0.11-0.61), history of IUD use (RR 0.82; 95% CI 0.68-0.98), and pelvic surgery in the past 30 days (RR 0.48; 95% CI 0.30-0.76). Multivariate analysis of the risks found that black race was associated with STD pelvic inflammatory disease (odds ratio 2.56; 95% CI 1.68-3.90), and current IUD use was associated with non-STD pelvic inflammatory disease (odds ratio 3.87; 95% CI 1.30-11.53). Neither univariate nor multivariate analysis identified douching as a risk differentiating STD from non-STD pelvic inflammatory disease. CONCLUSIONS: Pelvic inflammatory disease is a complex polymicrobial disease. This study demonstrates that risk factors associated with pelvic inflammatory disease cases can be differentiated by microbial etiology. We found that black race was associated with STD pelvic inflammatory disease and recent IUD use was associated with non-STD pelvic inflammatory disease.

Acute Disease↗

Ligase chain reaction to detect Chlamydia trachomatis infection of the cervix.

We performed a multicenter evaluation of ligase chain reaction (LCR) in the diagnosis of Chlamydia trachomatis infection of the cervix. This LCR provides an amplification of target sequences within the chlamydial cryptic plasmid. The LCR results were compared with those of isolation in cell culture. Discrepant (tissue culture-negative and LCR-positive) test results were resolved by the application of a direct immunofluorescent-antibody test to detect chlamydial elementary bodies and by the use of alternate DNA primers that targeted the chlamydial major outer membrane protein gene. A total of 234 of 2,132 specimens (10.9%) could be confirmed as containing C. trachomatis. Of these, 152 were detected by isolation in cell culture and 221 were detected by LCR. The corresponding sensitivities were 94% for LCR and 65% for cell culture. There was greater variability among study site results for cell culture sensitivity (52 to 92%) than for LCR sensitivity (87 to 98%). The specificity of each test was greater than 99.9%. Thus, LCR offers a highly sensitive nonculture method for detecting chlamydial infection of the cervix.

Chlamydia Infections↗

Diagnostic utility of PCR-enzyme immunoassay, culture, and serology for detection of Chlamydia pneumoniae in symptomatic and asymptomatic patients.

To assess the utility of PCR-enzyme immunoassay (EIA) for diagnosis of acute infection with Chlamydia pneumoniae, we compared tissue culture, PCR-EIA, direct fluorescent-antibody (DFA) stain, and serology in studies with 56 patients with respiratory symptoms and 80 asymptomatic persons. Thirty-five patients were positive by either culture or PCR-EIA, and 101 were negative by both assays. Thirty specimens from symptomatic patients and one from an asymptomatic patient were culture positive; 23 of these were also PCR-EIA positive. Of the eight culture-positive, PCR-EIA-negative specimens, five were DFA negative and three were DFA positive. Four additional specimens were culture negative and PCR-EIA positive; of these, three were DFA positive and one was DFA negative. When we used culture- and/or DFA-positive results as a reference or "gold standard," the sensitivity and specificity of PCR were 76.5 and 99.0%, respectively. When we used PCR- and/or DFA-positive results as the reference, the sensitivity of culture was 87.5%. On the basis of single acute serum specimens, only 8 of these 35 patients had diagnostic antibody titers. Of the asymptomatic patients, 75% had immunoglobulin G or immunoglobulin M antibody to C. pneumoniae; 15 (18.8%) of these had antibody levels considered to be diagnostic of acute infection. This multicenter study indicates that culture and/or PCR-EIA is more reliable for prompt diagnosis of C. pneumoniae infection than single-point serology alone.

Adult↗

Abstinence and neutrality: development and diverse views.

Usually, Freud adopted a technical device for personal or practical reasons and only later formulated its theoretical basis. His conception of abstinence initially seemed designed to curb his own troublesome erotic countertransference. These speculations, while having no bearing on the clinical value of abstinence and related neutrality, do emphasise the necessity to assess their utility objectively, on the basis of clinical data. Diverse views of abstinence and neutrality persist in part because early inconsistencies in Freud's conceptions remain unresolved, and in part because these views are derived from the analyst's personality and character, are not based upon clinical data, but are buttressed by iteration. An approach to empirical assessment is suggested using multiple analyst-observers: (1) to develop reliable criteria for four analyst behaviours: abstinence, neutrality, gratification and suggestion; and (2) to evaluate enhancement or impairment of analytic work. Utilisation of this approach in the supervision of candidates would enhance analytic pedagogy and to some degree facilitate a research orientation in candidates.

Character↗

Evaluation of urine-based screening strategies to detect Chlamydia trachomatis among sexually active asymptomatic young males.

OBJECTIVE: To evaluate the performances of diagnostic screening tests alone or in combination to detect asymptomatic chlamydial urethral infection in young males. DESIGN: Comparisons of the performance profiles of the following chlamydia screening strategies were done: urethral culture; identification of polymorphonucleocytes (PMNs) on spun first-void urine (FVU); urinary leukocyte esterase test (LET) on unspun FVU; chlamydial enzyme immunoassay (EIA) applied to FVU sediment; combining LET on unspun FVU followed by EIA with or without direct fluorescent antibody (DFA) confirmation on FVU sediment; and combining PMNs on spun FVU followed by EIA with or without DFA confirmation. SETTING: General clinics at a youth detention center, university-based teen clinic, college health service, and a military screening clinic. PATIENTS: A total of 618 males aged 12 to 35 years (mean, 17 years) were recruited as a convenience sample; site participation rates ranged from 50% to 80%. Eligible subjects were sexually active, denied symptoms of urethritis, and had taken no antibiotics in the prior 2 weeks. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values of each test strategy's ability to detect Chlamydia trachomatis infection, and cost to confirm each positive case. RESULTS: With a 7% prevalence of chlamydial infection, tissue culture had a sensitivity of only 61%. However, two strategies yielded significantly better performance profiles compared with the others: EIA confirmed by DFA test with a sensitivity of 84%, a specificity of 100%, and a cost to identify each positive case of $434; and PMNs followed by EIA confirmed by DFA test with a sensitivity of 78%, a specificity of 100%, and a cost to identify each positive case of $199. The LET followed by EIA-DFA had a similar performance profile to the PMN test strategies. CONCLUSIONS: A combination of a nonspecific screening of FVU for PMNs or LET followed by specific testing with EIA with DFA confirmation has superior clinical and cost-effective performance for detecting asymptomatic C trachomatis urethritis in young males compared with other strategies. However, an evaluation of the medical, fiscal, and psychological benefits and risks associated with a specific screening strategy for sexually transmitted diseases must be made before adopting a specific strategy for a particular population.

Adolescent↗