Urinary leukocyte esterase screening for asymptomatic sexually transmitted disease in adolescent males

The objective of this study was to evaluate the effectiveness of urinary leukocyte esterase on random urine specimens as a screening test for chlamydial and gonococcal urethral infections in asymptomatic males. Random urine specimens were obtained on 106 consecutive asymptomatic adolescent males during intake physical examination at a residential vocational training program. Results of urinary leukocyte esterase were compared to those of urethral cultures for Chlamydia trachomatis and Neisseria gonorrhoeae. Five subjects had positive chlamydia cultures, three subjects had positive gonococcal cultures, and one patient had positive cultures for both organisms. Sixteen subjects had leukocyte esterase tests reported as "trace" or greater. When compare to positive culture results for either Chlamydia or gonorrhea, urinary leukocyte esterase activity had a sensitivity of 78%, specificity of 91%, and positive predictive value of 44%. A random urine specimen for urinary leukocyte esterase activity is a cost-effective screening method for chlamydial and gonococcal urethral infections in asymptomatic adolescent males.     

Elimination of an artificial immune complex by plasmapheresis in rabbits

The behavior of an artificial immune complex was investigated in 15 rabbits. The immune complex was labeled with iodine-125 (125I). The advantage was that the immune complex could not be metabolized without being eliminated by the kidney. This artificial immune complex was injected in a dosage of 0.8 microgram, in 2 rabbits, 5.0 micrograms in 4 rabbits, 10 micrograms in 3 rabbits, 20 micrograms in 2 rabbits, and 40 micrograms in 4 rabbits on two consecutive days. One group (n = 9) was treated with plasmapheresis: the other (n = 6) was a control group that did not undergo plasmapheresis. A miniaturized plasmapheresis system eliminated the immune complex very effectively with an average exchange volume of 95.7 ml per treatment. The increasing concentration of the immune complex in the blood before the next plasmapheresis treatment was probably an expression of mobilization of the immune complex from different organs. The animals of the plasmapheresis group were in better condition than the control group.     

Circulating growth factor levels are associated with tumorigenesis in neurofibromatosis type 1.

PURPOSE: Neurofibromatosis type 1 (NF1) is characterized by systemic development of neurofibromas. Early clinical diagnosis can be ambiguous, and genetic diagnosis can be prohibitively difficult. Dysregulation of a number of growth factors has been suggested to be a mechanism of pathogenesis. This study was performed to assess the contribution of circulating growth factors for diffuse tumorigenesis and the diagnostic value of circulating growth factor identification in serum. EXPERIMENTAL DESIGN: The growth stimulation of neurofibroma-derived cells by serum from NF1 patients was tested, and serum growth factor levels in a cohort of NF1 patients (n = 39) between the ages of 7 and 70 years were analyzed. RESULTS: Concentrations of midkine (MK) and stem cell factor, but not epidermal growth factor, were substantially increased in serum of NF1 patients when compared with healthy controls. Within the NF1 group, MK levels increased dramatically at puberty from an average of 0.79 ng/mL in patients <18 years to 1.18 ng/mL in patients >18 years old. Stem cell factor and MK concentrations above a defined threshold in serum of NF1 patients are of diagnostic benefit for 96% of patients in the cohort tested. Furthermore, serum from NF1 patients enhanced proliferation of human neurofibroma-derived primary Schwann cells and endothelial cells substantially better than normal serum. CONCLUSIONS: Enhanced circulating growth factor levels contribute to diffuse tumorigenesis in NF1 and may provide the basis for molecular diagnosis.     

Comparison of a new video-optical intubation stylet versus the conventional malleable stylet in simulated difficult tracheal intubation

Handling and efficacy of a new video-optical intubation stylet were assessed in a simulated difficult tracheal intubation setting and compared with a conventional malleable stylet. Forty-five anaesthetists performed 10 tracheal intubations using both techniques. Laryngoscopy was performed by the observer, who created a grade 3 view according the classification by Cormack and Lehane. The time taken to place the tracheal tube and the final tracheal tube positions were documented. Mean (SD) intubation time for the video-optical stylet was 20.4 (7.7) s and for the malleable stylet 10.2 (3.3) s (p<0.01). With the video-optical stylet the trachea was correctly intubated in all 225 attempts; with the malleable stylet 44 (19.6%) oesophageal and 44 (19.6%) endobronchial intubations occurred (p<0.01). The video-optical intubation stylet enabled us to recognise inappropriate tracheal tube positions and to correct them immediately. This equipment can be considered a reliable and effective tool for management of the difficult airway.     

Selective targeted delivery of TNFalpha to tumor blood vessels

We sought to enhance the selective toxicity of tumor necrosis factor alpha (TNFalpha) to permit its systemic use in cancer therapy. Because ligand-targeted therapeutics have proven successful in improving the selective toxicity of drugs, we prepared a fusion protein (L19mTNFalpha) composed of mouse TNFalpha and a high-affinity antibody fragment (L19 scFv) to the extradomain B (ED-B) domain of fibronectin, a marker of angiogenesis. L19mTNFalpha was expressed in mammalian cells, purified, and characterized. L19mTNFalpha was an immunoreactive and biologically active homotrimer. Radiolabeled L19mTNFalpha selectively targeted tumor neovasculature in tumor-bearing mice, where it accumulated selectively and persistently (tumor-to-blood ratio of the percentage of injected dose per gram [%ID/g] of 700, 48 hours from injection). L19mTNFalpha showed a greater anticancer therapeutic activity than both mTNFalpha and TN11mTNFalpha, a control fusion protein in which an antibody fragment, irrelevant in the tumor model used, substituted for L19. This activity was further dramatically enhanced by its combination with melphalan or the recently reported fusion protein L19-IL2. In conclusion, L19mTNFalpha allows concentrating therapeutically active doses of TNFalpha at the tumor level, thus opening new possibilities for the systemic use of TNFalpha in cancer therapy.     

Morphologic Study of the Participation of the Complement System in Hyperacute Rejection of Renal Xenotransplants

The role of polymorphonuclear leukocyte (PMN) and platelet infiltration in the hyperacute rejection of renal xenotransplants was studied. In a first group, a dog kidney was grafted to rabbit recipients with intact immune adherence and chemotaxis. A second group included recipients depleted of PMN's with nitrogen mustard, and in a third group, immune adherence and chemotaxis were modified by depleting the third component of complement by means of cobra venom factor. Serial kidney biopsies were studied with light and electron microscopic technics. A semiquantitative evaluation of PMN and platelet glomerular infiltration indicated that a reduction in the number of PMN's or platelets is associated with an increased survival time of the transplanted kidney.     

Brominated Flame Retardants and Other Persistent Organohalogenated Compounds in Relation to Timing of Puberty in a Longitudinal Study of Girls

Background

Exposure to hormonally active chemicals could plausibly affect pubertal timing, so we are investigating this in the Breast Cancer and the Environment Research Program.

Objectives

Our goal was to examine persistent organic pollutants (POPs) in relation to pubertal onset.

Methods

Ethnically diverse cohorts of 6- to 8-year-old girls (n = 645) provided serum for measure of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and lipids. Tanner stages [breast (B) and pubic hair (PH)], and body mass index (BMI) were measured at up to seven annual clinic visits. Using accelerated failure time models, we calculated time ratios (TRs) for age at Tanner stages 2 or higher (2+) and POPs quartiles (Q1–4), adjusting for confounders (race/ethnicity, site, caregiver education, and income). We also calculated prevalence ratios (PRs) of Tanner stages 2+ at time of blood sampling.

Results

Cross-sectionally, the prevalence of B2+ and PH2+ was inversely related to chemical serum concentrations; but after adjustment for confounders, only the associations with B2+, not PH2+, were statistically significant. Longitudinally, the age at pubertal transition was consistently older with greater chemical concentrations; for example: adjusted TR for B2+ and Q4 for ΣPBDE = 1.05; 95% CI: 1.02, 1.08, for ΣPCB = 1.05; 95% CI: 1.01, 1.08, and for ΣOCP = 1.10; 95% CI: 1.06, 1.14, indicating median ages of about 6 and 11 months older than least exposed, and with similar effect estimates for PH2+. Adjusting for BMI attenuated associations for PCBs and OCPs but not for PBDEs.

Conclusions

This first longitudinal study of puberty in girls with serum POPs measurements (to our knowledge) reveals a delay in onset with higher concentrations.

Citation

Windham GC, Pinney SM, Voss RW, SjÖdin A, Biro FM, Greenspan LC, Stewart S, Hiatt RA, Kushi LH. 2015. Brominated flame retardants and other persistent organohalogenated compounds in relation to timing of puberty in a longitudinal study of girls. Environ Health Perspect 123:1046–1052; http://dx.doi.org/10.1289/ehp.1408778     

R353Q polymorphism, activated factor VII, and risk of premature myocardial infarction in Japanese men.

BACKGROUND: The association between myocardial infarction (MI) and the R353Q polymorphism of the Factor VII (FVII) gene, which reportedly influences FVII concentrations, activated Factor VII (FVIIa), or FVII antigen (FVIIag), remains controversial. METHODS AND RESULTS: The present case - control study in 127 Japanese men with their first MI at or before 45 years of age and 150 matched healthy controls was designed to clarify this association in premature MI. R353Q polymorphism was determined by polymerase chain reaction, and plasma concentrations of FVIIa and FVIIag were assayed. The distribution of the RR, RQ, and QQ genotypes with respect to R353Q polymorphism was 117, 10, and 0 in the patients, and 131, 17, and 2 in the controls. The Q allele was negatively associated with premature MI (odds ratio =0.41, p=0.038). The plasma concentration of FVIIa was slightly higher in patients (55.1+/-40.9 U/L) than in controls (44.8+/-20.2 U/L), but not significantly (p=0.078); the plasma concentration of FVIIag did not differ between patients (88.7+/-15.7%) and controls (87.0+/-9.0%) (p=0.557). Plasma FVIIa concentrations were influenced by R353Q polymorphism (p<0.001). CONCLUSIONS: The Q allele may be protective against premature MI.