Females have stronger neurogenic response than males after non-specific nasal challenge in patients with seasonal allergic rhinitis.

Epidemiological studies show female predominance in the prevalence of non- allergic rhinitis (NAR) and local allergic rhinitis (LAR). Experimental studies show female patients with allergic rhinitis (AR) demonstrate higher levels of sensitivity to irritants and airway hyperresponsiveness than males. Bronchial asthma shows female predominance in post-puberty patients, and gender interaction with severe asthma endotypes. Fibromyalgia, chronic fatigue syndrome, migraine and chronic cough, syndromes, which are commonly related to neurokinin substance P (SP) in the literature, also show strong female predominance. Studies have demonstrated that sex hormones, primarily oestrogens, affect mast cell activation. Mast cell proteases can amplify neurogenic inflammatory responses including the release of SP. Based on human epidemiological data and animal experimental data we hypothesized that female patients have different interaction between mast cell activation and neurogenic inflammation, i.e. substance P release, resulting in a different nasal symptom profile. To test the hypothesis we performed allergen and non-specific nasal challenges in patients with seasonal allergic rhinitis (SAR) out of season and looked for gender differences in subjective and objective responses. The interaction between subjective and objective reactivity was evaluated through the comparison of subjective symptom scores, concentrations of neurokinin substance P (SP) and cellular markers in nasal lavages after low doses of nasal allergen challenges. Female allergic subjects tended to have higher substance P (SP) concentrations both before and after non-specific challenges. The difference between post-allergen and post - hypertonic saline (HTS) challenge was highly significant in female patients (p = 0.001), while insignificant in male subjects (p = 0.14). Female patients had significantly stronger burning sensation after HTS challenge than male. These data indicate difference in the interaction between inflammatory cells and the neurogenic response, which is gender- related, and which may affect symptom profiles after challenges. Different regulation of neurogenic inflammation in females may have impact on symptoms and endotyping in respiratory disorders, not only in allergic rhinitis, but also asthma, chronic rhinosinusitis and irritant -induced cough.

Nasal and ocular responses after specific and nonspecific nasal challenges in seasonal allergic rhinitis.

BACKGROUND: Different nasal challenges induce neural and immune response leading to nasal and ocular symptoms in patients with seasonal allergic rhinitis (SAR). The release of neural mediators from nasal mucosa and conjunctiva after no-specific challenges in patients with SAR remains unknown. OBJECTIVES: To compare the release of mediators from the nose and conjunctiva with symptoms after different nasal challenges in patients with SAR. METHODS: Three types of consecutive nasal challenges were performed outside the pollen season in 25 patients with SAR. Challenges consisted of 500 biological units (BU) of allergen, 80 µg of histamine, and 1 mL of 2% hypertonic saline per nostril, within 24-hour and 72-hour intervals, respectively. Before and 15 minutes after challenges, evaluation of symptoms was performed with a visual analog scale. Concentrations of tryptase, eosinophil cationic protein in nasal lavages after 15 minutes, and substance P in tears after 5 minutes were measured with enzyme immunoassays. RESULTS: Concentrations of substance P in tears were significantly higher after nonspecific challenges. Substance P concentration in tears significantly correlated with eye itchiness after histamine and hypertonic saline and with tearing after allergen. Ocular symptoms correlated significantly with tryptase concentration in nasal lavage collected 15 minutes after allergen challenge. There is a significant correlation in tear volume comparing different nasal challenges. CONCLUSIONS: Nasal challenges with allergen, histamine, or irritants outside the pollen season induce a significant increase in nasal and ocular symptoms in patients with SAR. Interaction of the early-phase response and neurogenic inflammation define the pattern and severity of eye symptoms.

Advanced Age, High ß-CTX Levels, and Impaired Renal Function are Independent Risk Factors for All-Cause One-Year Mortality in Hip Fracture Patients.

Risk factors for increased mortality in hip fracture patients include older age, male sex, fracture type, bone mineral density, and pre-existing co-morbidities. The role of biochemical and other anthropometric parameters on hip fracture mortality remains unclear. The aim of this study was to identify the risk factors for one-year mortality in patients with hip fractures. A total of 236 consecutive patients (59 males) with hip fractures were followed over a one-year period. Patient age, gender, type of fracture, type of treatment, time from admission to surgery, type of anesthesia, body mass index, and electrocardiograms were recorded. Complete blood counts, serum electrolytes, urea, creatinine, d-dimers, calcium, phosphate, osteocalcin, and beta-isomerised C-terminal telopeptide of collagen type I (ß-CTX) were measured at admission and estimated glomerular filtration rate (eGFR) was calculated. Multivariate Cox regression models were used to analyze the association of these parameters with survival. One-year mortality rate was 28.4%. Age was independently associated with mortality (HR 1.117, 95% CI 1.062-1.174, P < 0.001). In a multivariable model, mortality was increased in patients with higher ß-CTX (HR 4.63 95% CI 1.87-11.45, P = 0.001) and lower eGFR (HR 0.972, 95% CI 0.956-0.987, P < 0.001). Patients younger than 84 years, with eGFR < 55.4 ml/min had ten times higher mortality rates (3.2 vs. 24.5%, HR 9.73, 95% CI 2.06-45.93) as well as those with ß-CTX > 0.276 g/L (3.5 vs. 25.7%, HR 9.5, 95% CI 2.11-42.76). Advanced age, high ß-CTX levels, and impaired renal function are independent risk factors of mortality in patients with hip fractures.

Reference intervals for reproductive hormones in prepubertal children on the automated Roche cobas e 411 analyzer.

OBJECTIVES: To establish reference intervals for luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), progesterone (P), total and free testosterone (T) and sex-hormone binding globulin (SHBG) in prepubertal children and to assess age- and gender-related differences. DESIGN AND METHODS: A total of 948 subjects, 480 girls and 468 boys, between 1 and 11 years of age, were included in this study. All assays were performed on a Roche cobas e 411 immunoassay analyzer. Reference intervals have been evaluated according to the most recent CLSI guidelines. RESULTS: Median values of LH, FSH and T were significantly higher in subgroups ranging from ≥ 8 to < 11 years, for both genders. In girls of that age, reference values of E2 were significantly higher than in younger ones, and in boys of the corresponding age. CONCLUSION: Established reference intervals are applicable to other laboratories that use the same instrumentation.

Anti-Müllerian hormone: a unique biochemical marker of gonadal development and fertility in humans.

Anti-Müllerian hormone (AMH) is a glycoprotein belonging to the transforming growth factors (TGF-P). AMH plays a fundamental role in the regression of Müllerian ducts in male embryo. In its absence, Müllerian ducts develop into female inner reproductive organs. In boys, it is significantly produced in Sertoli cells of testes until puberty and then slowly decreases to residual values for the rest of the men's life. AMH serves as a biochemical marker of the presence of testes in cryptorchidic males. In females, AMH is secreted by granulosa cells of small follicles in the ovary. Serum values are almost undetectable during infancy and then rapidly increase with the onset of puberty, reflecting the initial recruitment of primordial follicles. AMH is produced in growing follicles until they reach a stage when dominant follicle is detached from a cohort of antral follicles. The measurement of serum AMH levels during woman's reproductive life represents an ideal tool for the assessment of the ovarian follicular reserve. The advantage of AMH in relation to the ovarian steroid hormones is that serum levels do not fluctuate significantly during the menstrual cycle. In addition, circulating AMH strongly correlates with antral follicle count (AFC), visualized by ultrasound in the follicular phase of the cycle. As the number and quality of the oocytes diminish throughout the woman's reproductive life, serum concentrations of AMH gradually decrease and fall below detectable levels in menopause. This could be of particular interest in subfertile and infertile women undergoing assisted reproductive techniques (ART) in achieving pregnancy.

The impact of temporal variability of biochemical markers PAPP-A and free beta-hCG on the specificity of the first-trimester Down syndrome screening: a Croatian retrospective study.

BACKGROUND: The variability of maternal serum biochemical markers for Down syndrome, free beta-hCG and PAPP-A can have a different impact on false-positive rates between the 10+0 and 13+6 week of gestation. The study population comprised 2883 unaffected, singleton, spontaneously conceived pregnancies in Croatian women, who delivered apparently healthy child at term. Women were separated in 4 groups, dependently on the gestational week when the analyses of biochemical markers were performed. The concentrations of free beta-hCG and PAPP-A in maternal serum were determined by solid-phase, enzyme-labeled chemiluminiscent immunometric assay (Siemens Immulite). Concentrations were converted to MoMs, according to centre-specific weighted regression median curves for both markers in unaffected pregnancies. The individual risks for trisomies 21, 18 and 13 were computed by Prisca 4.0 software. FINDINGS: There were no significant differences between the sub-groups, regarding maternal age, maternal weight and the proportion of smokers. The difference in log10 MoM free beta-hCG values, between the 11th and 12th gestational week, was significant (p = 0.002). The difference in log10 MoM PAPP-A values between the 11th and 12th, and between 12th and 13th week of gestation was significant (p = 0.006 and p = 0.003, respectively). False-positive rates of biochemical risk for trisomies were 16.1% before the 11th week, 12.8% in week 12th, 11.9% in week 13th and 9.9% after week 13th. The differences were not statistically significant. CONCLUSIONS: Biochemical markers (log10 MoMs) showed gestation related variations in the first-trimester unaffected pregnancies, although the variations could not be attributed either to the inaccuracy of analytical procedures or to the inappropriately settled curves of median values for the first-trimester biochemical markers.