Ureaplasma urealyticum modulates endotoxin-induced cytokine release by human monocytes derived from preterm and term newborns and adults.

We previously observed that Ureaplasma urealyticum respiratory tract colonization in infants with a birth weight of < or =1,250 g was associated with increases in the tracheal aspirate proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) relative to the counterregulatory cytokine IL-6 during the first week of life (A. M. Patterson, V. Taciak, J. Lovchik, R. E. Fox, A. B. Campbell, and R. M. Viscardi, Pediatr. Infect. Dis. J. 17:321-328, 1998). We hypothesized that U. urealyticum alters the host immune response in the presence of a coinflammatory stimulus (e.g., bacterial infection or hyperoxia) by shifting the balance of cytokine expression towards the proinflammatory cytokines. To test this hypothesis, we compared the release of TNF-alpha, IL-8, IL-6, and IL-10 in vitro by unstimulated and U. urealyticum (with or without lipopolysaccharide [LPS])-stimulated human monocytes from adult peripheral blood and from term and preterm cord blood. U. urealyticum alone and in combination with LPS induced concentration- and development-dependent changes in cytokine release. In vitro inoculation with low-inoculum U. urealyticum (10(3) color-changing units [CCU]) (i) partially blocked the LPS-stimulated IL-6 release by all cells and reduced LPS-stimulated IL-10 release by preterm cells, (ii) stimulated TNF-alpha and IL-8 release by preterm cells, and (iii) augmented LPS-stimulated TNF-alpha release in all cells. In preterm cells, high-inoculum U. urealyticum (10(6) CCU) (i) stimulated TNF-alpha and IL-8, but not IL-6 or IL-10, release and (ii) augmented LPS-stimulated TNF-alpha and IL-8 release. High-inoculum U. urealyticum (i) stimulated release of all four cytokines in term cells and IL-8 release in adult cells and (ii) augmented LPS-induced TNF-alpha, IL-10, and IL-8 release in term cells but did not significantly affect LPS-induced cytokine release in adult cells. We speculate that U. urealyticum enhances the proinflammatory response to a second infection by blocking expression of counterregulatory cytokines (IL-6 and IL-10), predisposing the preterm infant to prolonged and dysregulated inflammation, lung injury, and impaired clearance of secondary infections.

Cytomegalovirus infection and non-neutropenic fever after autologous stem cell transplantation: high rates of reactivation in patients with multiple myeloma and lymphoma.

In a retrospective study, we examined the association between cytomegalovirus (CMV) infection and non-neutropenic fever immediately following autologous peripheral blood stem cell transplantation for a variety of haematological malignancies and solid tumours. Sixty non-neutropenic febrile episodes (41 in CMV-seropositive and 19 in CMV-seronegative patients) were evaluated. CMV reactivation, documented by CMV antigenaemia, was detected in 16 out of 41 (39%) seropositive patients compared with 0 out of 19 seronegative patients. In 12 of these 16 patients, CMV infection was considered the sole cause of fever. Thirteen patients had maximum antigenaemia levels > 5 cells/slide. Specific antiviral treatment led to the resolution of the fever in all, but two, patients, who developed fatal CMV pneumonia. Patients with multiple myeloma and lymphoma, possibly owing to a combination of disease-related characteristics and prior immunosuppressive treatment, had high rates of CMV reactivation and may require more frequent diagnostic evaluation and prompt therapeutic intervention.

Hypophosphatemia induced in mice by transplantation of a tumor-derived cell line from a patient with oncogenic rickets.

A cultured cell line was derived from a hemangiopericytoma obtained at surgery from a 9 year-old boy with hypophosphatemic rickets. Hypophosphatemia and metabolic bone disease were cured in the patient after tumor removal. Cells from passage 5 were transplanted into 8 week-old athymic female mice. Additional animals received innocula of cells thawed from the stored original tumor tissue, as well as MRC-5 fibroblasts. Serum phosphate levels 3-7 months post-transplantation were lowest in mice which received the cultured cell line (n = 5) 6.1 +/- 0.6 mg/dl (p < 0.05 compared to the other groups), thawed tumor cells (n = 8) 7.2 +/- 0.7 mg/dl, MRC fibroblasts (n = 4) 8.1 +/- 1.0 mg/dl, no transplant (n = 10) 8.7 +/- 1.9 mg/dl. Repeat of the experiment with cultured tumor cells from passage 12 no longer altered phosphate levels. A substance produced and release by the tumor in situ and by tumor-derived cultured cells is capable of producing hypophosphatemia. Experimental manipulation of functional tumor-derived cell lines may help elucidate the factor(s) causing hypophosphatemia in oncogenic osteomalacia/rickets.

A prospective study of microorganisms in urine and bladder biopsies from interstitial cystitis patients and controls.

OBJECTIVES: Interstitial cystitis (IC) is a chronic inflammatory condition of the bladder of unknown etiology. We tested the hypothesis that a microorganism would be found at higher prevalence in urine or bladder tissue from women with IC than from control women. METHODS: Urine and bladder tissue were obtained at cystoscopy from 11 IC patients and 7 control subjects. These specimens were cultured for a variety of fastidious and nonfastidious bacteria, mycobacteria, fungi, and viruses. In addition, special staining techniques were used to examine biopsy specimens and cytospun urine, and tissue sections and outgrowths of explanted bladder cells were examined by electron microscopy. RESULTS: Cultures of urine from 6 of 11 IC patients grew five different bacteria (Corynebacterium sp. Klebsiella pneumoniae, Lactobacillus sp, Streptococcus constellatus, and Streptococcus morbillorum), human cytomegalovirus, or Torulopsis glabrata; one of these organisms (Lactobacillus sp) was found in urine from 2 patients. Although contamination by urethral organisms is possible, the prevalence of microorganisms in urine of IC patients (6 of 11) was significantly greater than in urine of control subjects (0 of 7) (P < 0.05). Acridine orange staining revealed rods with appropriate morphology in urine from 4 of the 5 IC patients who had positive bacterial cultures and yeastlike organisms in urine and bladder tissue specimens that grew Torulopsis. Additionally, rodlike organisms were seen in urine from 2 IC patients with negative bacterial cultures and cocci were seen in the urine of 1 control patient. Biopsy specimens from 2 IC patients grew Torulopsis sp or Lactobacillus sp, in agreement with the results of acridine orange staining and culture of urine from these patients; in contrast, specimens from 3 control subjects grew small numbers of Pseudomonas sp or Staphylococcus epidermidis, but no organisms were cultured from urine or seen in acridine orange-stained tissue smears. All other cultures and stains were negative. CONCLUSIONS: These data do not provide evidence that IC is associated with infection or colonization by a single microorganism. However, they do generate the hypothesis that the prevalence of microorganisms, especially bacteria at low concentrations, is greater in the urine of IC patients than of control subjects. If these results are confirmed by other controlled studies, the question of whether the presence of these organisms is a cause or a result of IC should be addressed.

Double-blind randomized study comparing amoxicillin and erythromycin for the treatment of Chlamydia trachomatis in pregnancy.

OBJECTIVE: To compare the efficacy and patient tolerance of amoxicillin to that of erythromycin in the treatment of lower genital tract chlamydia infections during pregnancy. METHODS: A double-blind, randomized study was conducted comparing oral amoxicillin 500 mg three times daily versus oral erythromycin 500 mg four times daily for 7 days. One hundred forty-three women with positive cervical cultures for chlamydia at less than 36 weeks' gestation were enrolled. A test-of-cure culture was obtained 4 weeks after entry into the study and side effects were assessed. Success of the regimen was defined as completing the course of medication and having a negative test-of-cure culture. RESULTS: Thirty of the 65 women in the erythromycin group (46.1%) developed symptoms while taking the medication and 15 of them were unable to continue treatment (23.1%). In contrast, five of the 65 women (7.7%) in the amoxicillin group became symptomatic, with only one of these patients intolerant of the side effects (1.5%) (P < .001). Of the 50 patients in the erythromycin group who were able to complete their course of medication, only three had a positive test of cure (6.0%). In comparison, nine of the 64 patients (14.1%) taking amoxicillin who completed their course had positive cultures at test of cure. This difference was not statistically significant (P = .14). Forty-seven of the 65 patients (72.3%) in the erythromycin group successfully completed their regimen, compared to 55 of the 65 women (84.6%) in the amoxicillin group. This difference was not statistically significant. CONCLUSIONS: These findings suggest that amoxicillin is a reasonable alternative for the treatment of chlamydia in pregnant patients intolerant to erythromycin. The incidence of side effects and intolerance to therapy for amoxicillin are less than those for erythromycin.

Comparative efficacy of clindamycin versus erythromycin in eradication of antenatal Chlamydia trachomatis.

Antenatal Chlamydia trachomatis infections are associated with both maternal and neonatal morbidity. Erythromycin, the only drug recommended for treatment during pregnancy, is often poorly tolerated, thus preventing successful cure. We have done a prospective, randomized, double-blind, placebo-controlled trial to compare the efficacy of clindamycin with that of erythromycin base in eradication of antenatal chlamydia. A total of 126 patients with documented cervical infection were enrolled before 24 weeks' gestation to receive clindamycin (450 mg), erythromycin (333 mg), or placebo orally four times daily for 14 days. Partners received doxycycline, 100 mg, twice daily for 7 days. Both clindamycin and erythromycin were effective agents with cure rates of 92.7% and 83.8%, respectively. Erythromycin therapy was associated with significantly more gastrointestinal complaints than was placebo therapy (23.1% (9/39) vs. 2.4% (1/41), p less than 0.02) whereas clindamycin was not. Patients who experienced side effects were more likely to be poorly compliant (p less than 0.03) and patients with moderate-to-good compliance were more likely to be cured than were women who were poorly compliant (p less than 0.002). Results of test of cure cultures performed immediately on completion of therapy did not differ significantly from those taken 4 weeks later.

Screening for pharyngeal gonorrhea in adolescents. A reexamination.

The cost-effectiveness of screening for pharyngeal gonorrhea (PG) in an adolescent clinic population was examined in the context of dramatically decreasing prevalence. Chart review revealed that the apparent PG prevalence had decreased from 15/555 (2.7%) 8 years ago to 0/319 (0.0%) recently in the clinic population studied. The earlier high prevalence of PG probably represented poor laboratory test specificity. Cost analysis showed that only at very high prevalence of PG (greater than 8%) would pharyngeal screening be cost-effective unless PG can be shown to be an important source of genital infection. We concluded that continued pharyngeal screening is not justified in our clinic because prevalence is so low.

The association of Chlamydia trachomatis, Neisseria gonorrhoeae, and group B streptococci with preterm rupture of the membranes and pregnancy outcome.

There is conflicting evidence regarding a possible causal role for Chlamydia trachomatis in the development of preterm premature rupture of the membranes. We investigated the relative prevalence of endocervical infection with C. trachomatis and group B streptococci in patients with preterm premature rupture of membranes compared with a control group taken from the same obstetric population. C. trachomatis was isolated from 23/52 (44%) patients with preterm premature rupture of membranes versus 13/84 (15%) women in the control group (p less than 0.001). This association was independent of infection with group B streptococci or Neisseria gonorrhoeae. Group B streptococci were isolated from 16% of the patients with preterm premature rupture of membranes versus 4% of the control population (p less than 0.05). The risk of preterm premature rupture of membranes associated with group B streptococcal infection was independent of infection with C. trachomatis and N. gonorrhoeae. Endocervical infection with C. trachomatis did not significantly affect early maternal complication rates after delivery.

Growth without growth hormone: the "invisible" GH syndrome.

Growth hormone (GH) deficiency, diagnosed by radioimmunoassay (RIA) measurements of GH in blood after provocation or in continuous 24 h samples of venous blood, is usually associated with growth failure. 4 non-obese boys have been identified who had normal linear growth despite apparent GH deficiency by standard RIA. All 4 patients had normal GH concentrations as measured with an IM-9 cell radio-receptor assay (RRA). The RRA/RIA ratio of the 4 patients significantly exceeded that of controls. Thus, these patients secrete a molecule with normal GH receptor binding and bioactivity which is "invisible" to the standard GH RIA. This variant GH is possibly expressed from the human GH-V gene or a mutant allele.

Chlamydia trachomatis infection in sexually active adolescents: prevalence and risk factors.

The prevalence of Chlamydia trachomatis genital infection was studied in a sexually active urban Baltimore adolescent population. Possible risk factors such as age, past history of sexually transmitted disease, number of sexual partners, contact with sexually transmitted disease, oral contraceptive use, and concomitant gonococcal infection were also evaluated. The prevalence of chlamydial infection in the 280 adolescents studied was 26%: 35% in male adolescents, 27% in pregnant female adolescents, and 23% in nonpregnant female adolescents. Chlamydia was almost three times as prevalent as gonorrhea in the same population. Age, past history of sexually transmitted disease, oral contraceptive use, and concomitant gonorrhea were not significantly associated with chlamydial infection. However, multiple current sexual partners, contact with sexually transmitted disease, genitourinary symptoms, and cervical ectopy were significantly associated with chlamydial infection. Testing for chlamydial infection in sexually active urban teenagers is recommended for those with genitourinary symptoms, those with cervical ectopy, or those who are contacts of persons with sexually transmitted disease. Considering the reservoir of infection in the asymptomatic female adolescents, screening for chlamydial infections in family planning clinics warrants consideration.

Immune responses in vitro. VI. Genetic control of the in vivo-in vitro discrepancies in 19S antibody synthesis.

The finding that the relationship of the in vitro and in vivo responses of different strains of mice is under genetic control indicates that at least two mechanisms must operate under in vivo conditions to control 19S antibody synthesis. One is involved in the termination of 19S antibody synthesis; the other has a regulatory role on the magnitude of the response. In light of these findings, various concepts based on other genetically controlled immune responses and on the limiting dilution technique should be reassessed. Furthermore, the suppressive in vivo mechanism may be an important type of control in the resistance or susceptibility to the establishment or maintainance of neoplasms.