Mechanical properties and metallurgical features of new and ex vivo used Reciproc Blue and Reciproc.

AIM: To compare the mechanical properties and metallurgic features of new and used Reciproc Blue and Reciproc instruments. METHODOLOGY: A total of 120 R25 Reciproc Blue and R25 Reciproc instruments were used. The morphological, chemical, mechanical, thermal and phase composition characteristics of new and ex vivo used files were investigated by scanning electron microscopy (FEG-SEM) with energy dispersive X-ray spectroscopy (EDS), focused ion beam analysis (FIB), micro-Raman spectroscopy, FEG-SEM metallography, X-ray diffraction (XRD), differential scanning calorimetry (DSC) and indentation tests. Usage-induce degradation was evaluated. Ten new and ten used instruments per type were run until fracture occurred in a stainless steel artificial canal (60° angle of curvature, 4-mm radius). Time to fracture and the length of the fractured fragment were recorded. Torque and angle of rotation at failure of ten new and ten used instruments for each type were measured according to ISO 3630-1. The fracture surface of each fragment was examined. Two-way analyses of variance was used to analyse the data statistically (α-level 0.05). RESULTS: SEM analysis revealed microcracks near the tip on both files after ex vivo usage tests. FIB imaging and micro-Raman spectroscopy confirmed the presence of an oxide layer on the Reciproc Blue surface. There was no thinning of the coating after use. XRD revealed a reduction of martensite and R-phase in Reciproc Blue after use. DSC analysis revealed different transformation temperatures for the instruments analysed. Reciproc Blue was significantly more flexible than Reciproc for both new and used samples (P < 0.05), and they were significantly more resistant to cyclic fatigue than Reciproc (P < 0.05). Ex vivo usage reduced the fatigue resistance of both files. Torsional resistance of Reciproc and Reciproc Blue was not reduced by simulated use (P > 0.05). CONCLUSIONS: The thermal treatment of Reciproc Blue was associated with a finer structure with smaller grains than Reciproc, which increased its fracture resistance and was also responsible for its reduced hardness and lower elastic modulus. Both files were safe during ex vivo usage in severely curved canals.

Structural analysis of HyFlex EDM instruments.

AIM: To compare the phase transformation behaviour, the microstructure, the nano-hardness and the surface chemistry of electro-discharge machined HyFlex EDM instruments with conventionally manufactured HyFlex CM. METHODOLOGY: New and laboratory used HyFlex EDM were examined by X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Nano-hardness and modulus of elasticity were also investigated using a maximum load of 20 mN with a minimum of 40 significant indentations for each sample. Raman spectroscopy and field emission-scanning electron microscope (FE-SEM) were used to assess the surface chemistry of HyFlex EDM. HyFlex CM were subjected to the same investigations and used as a comparison. Nano-indentation data were statistically analysed using the Student's t-test. RESULTS: XRD analysis on HyFlex EDM revealed the presence of martensite and rhombohedral R-phase, while a mixture of martensite and austenite structure was identified in HyFlex CM. DSC analysis also disclosed higher austenite finish (Af) temperatures for electro-discharge machining (EDM) instruments. Significant differences in nano-hardness and modulus of elasticity were found between EDM and CM files (P < 0.05). FE-SEM and EDS analyses confirmed that both new EDM and CM files were covered by an oxide layer. Micro-Raman spectroscopy assessed the presence of rutile-TiO2 . CONCLUSIONS: HyFlex EDM revealed peculiar structural properties, such as increased phase transformation temperatures and hardness. Present results corroborated previous findings and shed light on the enhanced mechanical behaviour of these instruments.

Microstructure and in vitro behaviour of 45S5 bioglass coatings deposited by high velocity suspension flame spraying (HVSFS).

The high-velocity suspension flame spraying technique (HVSFS) was employed in order to deposit 45S5 bioactive glass coatings onto titanium substrates, using a suspension of micron-sized glass powders dispersed in a water + isopropanol mixture as feedstock. By modifying the process parameters, five coatings with different thickness and porosity were obtained. The coatings were entirely glassy but exhibited a through-thickness microstructural gradient, as the deposition mechanisms of the glass droplets changed at every torch cycle because of the increase in the system temperature during spraying. After soaking in simulated body fluid, all of the coatings were soon covered by a layer of hydroxyapatite; furthermore, the coatings exhibited no cytotoxicity and human osteosarcoma cells could adhere and proliferate well onto their surfaces. HVSFS-deposited 45S5 bioglass coatings are therefore highly bioactive and have potentials as replacement of conventional hydroxyapatite in order to favour osseointegration of dental and prosthetic implants.

Uterine contractility: vaginal administration of the beta-adrenergic agonist, terbutaline. Evidence of direct vagina-to-uterus transport.

Spontaneous uterine contractility during the menstrual cycle is required for menstruation, gamete transport, and, most likely, embryo nidation. Abnormal uterine contractility has been linked to dysmenorrhea, a condition associated with painful uterine cramping. Based on previous studies with progesterone, we have postulated the existence of a portal system that is responsible for some degree of direct vagina-to-uterus transport of administered compounds (i.e., the "first uterine pass effect"). It is possible that treatment with uterorelaxing substances, particularly beta-adrenergic agonists, may alleviate the uterine discomfort that accompanies dysmenorrhea. However, side effects encountered with oral administration of beta-agonists limit their utility. Alternatively, vaginal delivery of beta-agonists could solve this dilemma by enhancing their efficacy and reducing side effects. Therefore, in the current study we used hysterectomy specimens and an in vitro uterine perfusion system to test the vagina-to-uterus transport of [3H]terbutaline, a well-known beta-agonist. With the use of autoradiographic and scintillation counting techniques, our results clearly show progressive diffusion of labeled terbutaline from the rim of vaginal tissue through the uterus during the first 12 hours of perfusion. This indicates that uterine targeting of terbutaline can be accomplished through vaginal administration, suggesting a new therapeutic modality in women's health care.

Why and how to measure urinary sex steroid metabolites in epidemiological studies in women.

BACKGROUND AND AIM: Although numerous investigations have evaluated the association between urinary hormone levels and chronic diseases such as breast cancer and coronary heart disease, there are few data about the reliability of urinary measurements, particularly among premenopausal women. METHODS AND RESULTS: Over a six-month period, levels of estrone-3-glucuronide and pregnandiol-3-glucuronide were measured in both morning spot and overnight urine samples from seven healthy premenopausal women (ages 33-46). During this period, each subject provided one morning spot urine sample and one overnight urine sample per menstrual cycle on the same day of her menstrual cycle. All these samples were taken out of the freezer simultaneously and sent in the same parcel on dry ice to the laboratory for hormone determinations. All samples from each person were assayed simultaneously in the same run and by the same laboratory technician in a blind fashion. The intraclass correlation coefficients (ICC) for estrone-3-glucuronide and pregnandiol-3-glucuronide for the morning spot and overnight urine samples were 0.78 and 0.46 and 0.75 and 0.64 respectively. CONCLUSIONS: These data suggest that morning spot urine determinations are reliable and constitute an efficient alternative to the more complex overnight urine collection for epidemiological evaluation of urinary hormonal profiles.

Effects of transportation and delay in processing on the stability of nutritional and metabolic biomarkers.

The effects of transportation and delay in processing of blood samples on the concentration of biomarkers are significant in epidemiological studies for which specimens are collected from participants at locations other than a designated center or laboratory. These sources of variability in measurement were studied by collecting two sets of blood samples from 51 men between 26 and 50 years of age. The first set was sent immediately to the laboratory for processing. The second set was transported by car for one hour and then returned to the laboratory for processing. Both sets were stored together at -80 degrees C until the end of the study. Several blood constituents were evaluated. Vitamins, liver enzymes, and electrolytes showed no changes in concentration after transport by car for one hour. There were decreases in the concentrations of red and white blood cells, high-density-lipoprotein cholesterol, glucose, and creatinine after transportation. The transported total cholesterol, total testosterone, free testosterone, alkaline phosphatase, total bilirubin, and thiobarbituric acid-reactive substances increased in concentration. Although transportation and delay in processing of blood samples do not appear to greatly impact relative risk estimates, epidemiologists should be aware of these potential sources of variability in measurement and consider the consequences in their particular study.

Alcohol consumption and total estradiol in premenopausal women.

The present paper analyzes the relation between alcohol intake and serum total estradiol in premenopausal women while attempting to control or reduce several sources of variability of serum estradiol. Sixty premenopausal women were recruited, and alcohol intake was estimated by a semiquantitative questionnaire. Interviews, anthropometric measurements, and blood drawings (after overnight fasting) were conducted twice, 1 year apart. Both blood samples were obtained on the same day of the luteal phase of the cycle, in the same month and in the same hour and minute of the day. Samples from the first drawing were stored at -80 degrees C. Serum from both drawings was assayed simultaneously and in blind fashion. A significant association between alcohol intake and estradiol was found when estradiol was averaged across the two visits (Spearman's r = 0.29; P < 0.05). To control for intraindividual variability of estradiol over time, participants were then divided into tertiles of hormone distribution for each of the two sets of measurements and classified based on their consistency in estradiol across the two visits. Women showing consistently high estradiol levels at both visits were characterized by a significantly higher alcohol intake (92.8 g/week) in comparison with those showing consistently low estradiol at both visits (31.6 g/week). Furthermore, the prevalence of drinkers in the group with consistently high estradiol was significantly higher than in the group with consistently low estradiol. The present report indicates that drinkers seem to be characterized by consistently higher estradiol than nondrinkers, and that when the variability of estradiol in premenopause is considered, it is possible to identify a relationship between alcohol intake and estradiol.

Development of a rapid and ultrasensitive RIA method for estrogen (E2, E1, E1-S) determination with selective solid phase extraction.

The inhibition of the proliferative stimulation exercised by estrogens on neoplastic cells is the goal of all endocrine therapies in breast cancer. Under various circumstances, e.g. with the use of aromatase inhibitors, this result can be obtained by blocking the synthetic pathway and, consequently, by lowering the circulating levels of estradiol (E2), estrone (E1), and estrone sulfate (E1-S). The evaluation of these hormones in plasma could therefore represent a useful indicator of the biological efficacy of the therapy. However, the measurement of circulating steroids in a large series of patients is often a complicated procedure. Indirect methods of extraction are time consuming and expensive while the analytical sensitivity of direct methods is not sufficient to measure the residual levels of E2, E1, and E1-S. In this paper we describe a novel extraction method for the evaluation of plasma levels of E2, E1, and E1-S. This new method consists of solid phase extraction followed by a highly specific radioimmunoassay. The sensitivity of the assay is 0.6 pg/ml, 2.0 pg/ml and 7.0 pg/ml for E2, E1, and E1-S, respectively.

A multicentre, randomized, pharmacokinetic, endocrine and clinical study to evaluate formestane in breast cancer patients at first relapse: endocrine and clinical results. The Italian Trials in Medical Oncology (I.T.M.O.) group.

BACKGROUND: In postmenopausal breast cancer (BC) patients, tamoxifen (TAM) is frequently used in first-line therapy, and for those relapsing under TAM, aromatase inhibitors would be the drug of choice. Formestane, a new aromatase inhibitor, has been demonstrated to be as effective as TAM in first-line therapy. This trial was carried out to investigate the pharmacokinetics and antitumor activity of two formestane doses in BC patients at first relapse, as well as their effects on estrogen levels, evaluated by means of a new analytical method. PATIENTS AND METHODS: One hundred fifty-two postmenopausal BC patients were randomly given formestane 250 mg or 500 mg intramuscularly every two weeks. The blood samples for estrogen measurements were taken on the first day of therapy, at 4 and 10 weeks, and every 12 weeks thereafter. Tumor response was first evaluated after 2.5 months, and then every three months. RESULTS: Seventy-three patients received formestane 250 mg and 79 received 500 mg. After four weeks, plasma estrone, estradiol and estrone sulphate levels were significantly (P < 0.001) suppressed in both groups. The overall response rates were 30% and 40% on 250 mg and 500 mg, respectively. CONCLUSIONS: Both of the formestane doses are effective in reducing plasma estrogen levels in BC patients at first relapse, and the new analytical method improved the quality of results. The antitumor response was highly satisfactory.

Targeted drug delivery in gynaecology: the first uterine pass effect.

The objective was to verify the hypothesis of a 'first uterine pass effect' or direct preferential vagina-to-uterus transport, suggested by the evidence of higher than expected uterine tissue concentrations after vaginal administration of progesterone; we used a human ex-vivo uterine perfusion model. A mixture of tritiated (3H) and unlabelled progesterone was applied to the cuff of vaginal tissue remaining attached to the cervix after hysterectomy. At the end of the perfusion period (up to 12 h), 3H and 14C radioactivity was measured in samples of uterine tissue. Tritiated water and [14C]dextran were tested to determine the extent of non-specific vagina-to-uterus transport (leaks). Finally, sections of uterine tissue exposed only to [3H]progesterone were prepared for autoradiography. By 4-5 h after application progesterone had diffused to the entire uterus and had reached a steady state; 4 h after application, progesterone concentrations reached 185 +/- 155 and 254 +/- 305 ng/100 mg of endometrial and myometrial tissue respectively. Endometrial extraction of progesterone was higher when the experiment was performed on uteri obtained during the luteal phase (280 +/- 156 ng/100 mg of endometrial tissue) than those removed during the proliferative phase of the menstrual cycle (74 +/- 28 ng/100 mg of endometrial tissue). These data demonstrate that a 'first uterine pass effect' occurs when drugs are delivered vaginally, thereby providing an explanation for the unexpectedly high uterine concentrations relative to the low serum concentration observed after vaginal administration. Hence, the vaginal route permits targeted drug delivery to the uterus, thereby maximizing the desired effects while minimizing the potential for adverse systemic effects.

Reliability of serum hormones in premenopausal and postmenopausal women over a one-year period.

Serum hormones have been intensively investigated in association with several chronic diseases, but limited information exists on the reliability of a number of hormone determinations. The one-year reproducibility of dehydroepiandrosterone sulfate (DHEAS), total and free testosterone, total estradiol, insulin, C-peptide, and prolactin was studied in 60 premenopausal and 47 postmenopausal women recruited in Varese province, Italy, 1991-1992. The hormonal determinations were made in blood samples collected twice, one year apart, after 12-h fast, in the same month, day, and hour and for premenopausal women on the same day of the luteal phase of the menstrual cycle. Samples from the first drawing were stored at -80 degrees C. Samples from both drawings were assayed simultaneously and in blind fashion. Total estradiol in postmenopause was not evaluated for limitation in the sensitivity of the laboratory method. The intraclass correlation coefficient in premenopausal women was 0.85 for DHEAS, 0.60 for total testosterone, 0.66 for free testosterone, 0.81 for insulin, 0.83 for C-peptide, 0.40 for prolactin, and 0.06 for total estradiol. In postmenopausal women, the coefficient was 0.90 for DHEAS, 0.88 for total testosterone, 0.71 for free testosterone, 0.67 for insulin, 0.73 for C-peptide, and 0.18 for prolactin. These data indicate that total estradiol measured during the luteal phase has a poor intraindividual reproducibility over time, and these findings may have important implications in studies of hormones in the etiology of chronic disease.

Serum sex hormone levels after menopause and subsequent breast cancer.

BACKGROUND: High levels of androgens and estrogens have been reported to be associated with breast cancer. However, the multiplicity of factors that influence hormone levels and methodologic issues complicate the study of the relationship between steroid sex hormones and breast cancer. PURPOSE: Using an improved study design, we assessed prospectively the relationship between the principal steroid sex hormones in serum and the subsequent occurrence of invasive breast cancer in postmenopausal women. METHODS: Four thousand fifty-three healthy postmenopausal women aged 40-69 years, were enrolled from June 1987 through June 1992 in a prospective investigation of hormones and diet in the etiology of breast tumors (ORDET study) as part of a larger volunteer cohort of 10 788 premenopausal and postmenopausal women from Varese Province, northern Italy. At recruitment, blood samples were taken between 8:00 AM and 9:30 AM (after overnight fasting), and sera were preserved in -80 degree Celsius freezers. Women who had received hormone treatment in the 3 months prior to enrollment, who had bilateral ovariectomy, or who had a history of cancer or liver disease were not recruited. Twenty-five women in the final eligible cohort of postmenopausal women developed histologically confirmed, invasive breast cancer during the first 3.5 years of follow-up for the cohort (13 537 women-years). For each case subject, four control subjects were randomly chosen after matching for factors possibly affecting hormone preservation in serum. One case subject and eight control subjects were excluded because premenopausal hormonal patterns were found; thus, after also excluding the four control subjects matched to the ineligible case subject, we included 24 case and 88 control subjects. In the spring of 1994, stored sera of case and control subjects were assayed in a blinded manner for dehydroepiandrosterone sulfate and estradiol (E2) by in-house radioimmunoassay and for total and free testosterone and sex hormone-binding globulin by commercially available nonextraction iodination kits. Mean differences in risk factors were tested by analysis of variance for paired data. Relative risks (RRs) were estimated by conditional logistic regression analysis. All P values resulted from two-sided tests. RESULTS: Age-adjusted mean values of total testosterone, free testosterone, and E2 were significantly higher in case subjects than in control subjects: total testosterone, 0.34 ng/mL versus 0.25 ng/mL (P<.001); free testosterone, 1.07 pg/ml versus 0.77 pg/mL (P= .006); and E2, 25 pg/mL versus 22 pg/mL (P= .027). Age-adjusted RRs for breast cancer in increasing tertiles were as follows: for total testosterone, 1.0, 4.8, and 7.0 (P for trend =.026); for free testosterone, 1.0, 1.8, and 5.7 (P for trend=.005); and for total E2, 1.0, 7.1, and 5.5 (P for trend= .128). CONCLUSIONS AND IMPLICATIONS: This prospective study provides further evidence in support of the already established association between elevated estrogen levels and breast cancer. Even more importantly, it provides new evidence that high serum testosterone levels precede breast cancer occurrence.

Validity for epidemiological studies of long-term cryoconservation of steroid and protein hormones in serum and plasma.

Prospective studies based on the storage of biological samples at low temperature have opened new perspectives in etiological research on cancer. In planning these studies a crucial question is to evaluate whether the long-term preservation of samples is able to affect the categorization of the subjects involved. In the frame of the ORDET project, a prospective study of hormones and diet in the etiology of breast cancer provided with a -80 degrees C biological bank, we have evaluated the stability of estradiol, free and total testosterone, and prolactin in serum and plasma samples over 3 years of cryoconservation. Study results showed that the subjects maintained almost the same rank by hormonal concentration throughout the 3-year period for all hormones. Looking at the stability over time, estradiol, prolactin, and total testosterone had fairly good performance for both serum and plasma. Serum-free testosterone increased in time up to 30%, whereas progesterone decreased by about 40% of the initial concentration. However, the reliability of the individual categorization by hormonal level suggests the validity of low temperature storage for epidemiological purposes, at least for hormonal parameters.

Prostaglandins and corticosterone in the oviparous female lizard, Podarcis sicula sicula, during reproduction.

The in vitro effects of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2) on corticosterone release by ovarian follicles, corpora lutea (CL), and interrenals were studied in the female lizard, Podarcis sicula sicula, during reproduction. Follicles and CL studied in the female lizard, Podarcis sicula sicula, during reproduction. Follicles and CL were divided according to their different developmental stages; follicles: previtellogenic, early-vitellogenic, mid-vitellogenic and fully-grown; CL: CL1 (unshelled eggs in the oviducts), CL2 (shelled eggs in the oviducts), CL3 (eggs laid 6 h previously) and CL4 (eggs laid 48 h previously). Interrenals were divided according to the reproductive stages: pre-vitellogenesis, vitellogenesis, ovulation, post-ovulation, and post-deposition. PGF2 alpha release was highest in fully-grown follicles and PGE2 in early-vitellogenic follicles, corticosterone was highest in pre-vitellogenic and lowest in early-vitellogenic follicles. PGE2 decreased corticosterone in pre-vitellogenic, mid-vitellogenic and fully-grown follicles. PGF2 alpha release was highest in CL4, and PGE2 in CL1 and CL2, corticosterone was highest in CL4. PGF2 alpha increased corticosterone in CL1, CL2 and CL3. In interrenals, PGF2 alpha release was highest and PGE2 lowest during ovulation, corticosterone was highest during ovulation. PGF2 alpha increased and PGE2 decreased interrenal corticosterone during vitellogenesis, ovulation, and post-ovulation. In the plasma, PGF2 alpha levels were highest and PGE2 lowest during ovulation, corticosterone was highest during ovulation. These results suggest that corticosterone, modulated by PGF2 alpha and PGE2, is implied in the reproductive processes with different roles. In fact this steroid could favour ovulatory and luteolytic processes. In addition the hypothesis of an anti-vitellogenic role of corticosterone is discussed.

Quality of clinical information: a new approach of EQA in Emilia-Romagna, Italy.

For correct enforcement of an external quality assessment (EQA) scheme, suitable parameters are required for the assessment of analytical performance. Traditional EQA schemes have always been chiefly concerned with the agreement of analytical results between laboratories. Although we consider this concept to be important, we also believe that particular attention must be paid to the quality of the clinical information, in relation to correct use of the results. On the basis of this principle, we have developed an EQA model which, besides considering the absolute value, also take the reference limits (RLs) into consideration by means of the normalization procedure. The evaluation of clinical information is of vital importance, especially in relation to immunoassays, since the low degree of standardization between methods, and the ensuing phenomenon of relative inaccuracy, make the use of suitable RLs essential. Actually, analysis of the results reveals a high degree of heterogeneity in the RLs used by the laboratories, even within the same method-groups.

Measurement of steroid hormones in plasma by isocratic high performance liquid chromatography coupled to radioimmunoassay.

The study of steroidal profiles requires simultaneous determinations of various steroid hormones that cannot be appropriately carried out with the conventional routine immunoassays. Moreover, there are several trials for which the assessment of multiple steroids from a single serum sample is mandatory. In this paper we describe a procedure for simultaneously measuring steroid hormones using a unified solid phase extraction which allows the measurement of both unconjugated and conjugated steroids from 1 ml of sample and a combination of HPLC with isocratic elution followed by RIA. The entire procedure was preliminary carried out for the measurement of testosterone, dehydroepiandrosterone and its sulphated conjugate, androstenedione and 17 hydroxyprogesterone. The use of this technique allows precise and accurate measurements of steroid profile with a single serum aliquot and could be helpful in the diagnosis of various form of endocrine disorders.

Validation of a high-performance liquid chromatographic-radioimmunoassay method for the determination of lacidipine in plasma.

A sensitive and reproducible method for the determination of lacidipine, a new potent antihypertensive dihydropyridine, is reported. The method involves solid-phase extraction, reversed-phase high-performance liquid chromatography and radioimmunoassay of the collected fraction. The assay provides a limit of detection of 20 pg/ml of plasma, allowing the determination of trough (24 h) plasma concentrations. The method is suitable for pharmacokinetic studies in man.

Seasonal changes in plasma prostaglandin F2 alpha and sex hormones in the male water frog, Rana esculenta.

Prostaglandin F2 alpha (PGF2 alpha), progesterone, androgens (testosterone + dihydrotestosterone), and 17 beta-estradiol were measured in the plasma of male frogs, Rana esculenta, by radioimmunoassays. Plasma concentrations of PGF2 alpha were higher from October to December and peaked in March (prereproduction) and in June (postreproduction). Plasma progesterone levels were relatively low but showed an increase from October to December and in June. Plasma androgen titres rapidly increased in early spring, started to fall during the reproductive period (May), and were lowest in July. 17 beta-Estradiol levels peaked in March and in June. The annual profile of the plasma PGF2 alpha levels was positively correlated with those of progesterone and androgens, while it was not correlated to the estradiol plasma pattern, except in March and June. The increase in plasma PGF2 alpha in the autumn may be related to gonadal recovery. The simultaneous increases in PGF2 alpha and 17 beta-estradiol, both in March and June, suggest a PGF2 alpha-dependent estradiol synthesis, a possibility also supported by the increased plasma 17 beta-estradiol previously observed in PGF2 alpha-treated postreproductive females. The effects of captivity and castration on plasma PGF2 alpha concentrations were also studied during the annual cycle. Captivity was associated with a reduced PGF2 alpha titre, while castration did not modify prostaglandin synthesis, which may point to an extragonadal source of plasma PGF2 alpha.

Seminal estrone, estrone sulfate, and estradiol-17 beta levels in fertile and infertile males.

The seminal levels of estrone (E1), estrone sulphate (E1S), and estradiol-17 beta (E2) were measured simultaneously after a chromatographic step in the semen samples of 79 men, including fertile volunteers, vasectomized subjects, and patients with oligozoospermia and secretory azoospermia. E1S concentrations in seminal plasma were higher than in serum (with a semen/serum ratio of approximately 2). Seminal E1 and E1S levels in oligozoospermic subjects were significantly decreased compared to controls (p less than 0.02 and p less than 0.03, respectively). The seminal E1S concentration was significantly reduced in azoospermic patients (p less than 0.02) and to a greater extent in vasectomized subjects (p less than 0.001). As seminal E1S is likely to be mainly of testicular origin, the decreased seminal E1S levels in oligoazoospermia are an index of impaired testicular function.

External quality assessment of assays for hormones and tumor markers in Italian laboratories.

External quality assessment (EQA) programs run by CNR/Tecnostandard for immunoassays of hormones and tumor markers, started in 1980, presently include as many as 20 analytes; about 300 laboratories are involved in these programs. For all immunoassays submitted to the EQA, the inspection of cumulative results allows the current situation to be documented for total variability and its within-kit and between-kit components (the former accounting for the reproducibility and robustness of the kits and the latter for their systematic differences of estimation). For 13 assays subjected to EQA for longer, the variability trends over time are depicted, and single factors affecting the overall quality of particular assays are identified. Among these, experimental simplification of kit structure, alignment of calibrators with an acknowledged reference material, and adoption of monoclonal-antibody based two-sites assays can be mentioned. On the contrary, neither automation of the procedures nor (more expectedly) increasing use of nonisotopic techniques has proved effective in significantly improving the analytical quality.