Importance of total and measured free testosterone in diagnosis of male hypogonadism: immunoassay versus mass spectrometry in a population of healthy young/middle-aged blood donors.

PURPOSE: To meet clinicians' request for adequate results and reliable reference ranges for testosterone, this study was planned with the aims (i) to verify the reliability of the reference interval for total testosterone (TT) declared by immunoassay manufacturer and adopted by laboratory, (ii) to compare results for serum TT obtained by immunoassay and LC-MS/MS and (iii) to verify if the cutoff values for low TT and measured free testosterone (FT), defined by Endocrine Society Guidelines for diagnosis of hypogonadism, are applicable to our study group. METHODS: Sera from anonymous young/middle-aged male blood donors were selected for the study. TT was measured by immunoassay and LC-MS/MS. SHBG was measured by immunoassay and used with albumin concentration to calculate FT according to Vermeulen's formula. RESULTS: The reference interval declared by the manufacturer and adopted by the lab was validated. The two methods for TT evaluation correlated very well. TT and FT lower limits at 5th and 2.5th percentile are below the cutoffs reported in the literature for the diagnosis of hypogonadism. CONCLUSIONS: The immunoassay currently used in our lab can be considered an adequate tool for TT, but it's essential that clinical data agree with the biochemical ones, particularly in the presence of TT values between the lower limit of reference range and the cutoff values recommended by scientific societies.

Selective Insecticide Applications Directed Against Triatoma infestans (Hemiptera: Reduviidae) Affected a Nontarget Secondary Vector of Chagas Disease, Triatoma garciabesi.

The control of nondomiciliated triatomine species adapted to peridomestic habitats represents a challenge because they are connected to sylvatic colonies, and pyrethroid insecticides have limited effects outdoors. The effects of residual insecticide spraying have rarely been assessed on secondary triatomines. Triatoma garciabesi (Carcavallo, Martinez, Cichero, Prosen & Ronderos, 1967) is a nontarget vector that inhabits the dry western Chaco region, and a member of the Triatoma sordida Stål 1859 complex. Little is known on the capacity of T. garciabesi to invade and establish viable domestic or peridomestic colonies, and on its response to residual insecticide sprays directed against Triatoma infestans Klug 1834. The presence and abundance of triatomines were assessed by timed manual collections annually or biannually (spring and fall) during 10 yr after a community-wide insecticide spraying campaign and selective insecticide sprays directed against T. infestans in a rural village of northwestern Argentina. T. garciabesi mainly occupied peridomestic habitats associated with chickens, and was unable to colonize human sleeping quarters. Trees with chickens occurred in nearly all houses and were infested in >25% of the occasions. The abundance of bugs at house-compound level was best explained by a generalized estimating equation model that included selective insecticide sprays during the previous semester (negative effects), chicken abundance (positive effects), seasonality, and their interactions. Our results suggest that insecticide applications targeting T. infestans affected the abundance of T. garciabesi, and reduced the likelihood of future infestation.

Predictors and clinical consequences of starting androgen therapy in men with low testosterone: results from the SIAMO-NOI registry.

PURPOSE: Management of late onset hypogonadism (LOH) is not homogenous. The aim of the study is to observe the management of patients with low testosterone (T) in highly specialized Italian centres. METHODS: The SIAMO-NOI is an observational longitudinal disease registry for the evaluation of the clinical management of patients with low T levels (total T < 12 nmol/L, calculated free T < 225 pmol/l or already in treatment) in 15 Italian centers members of the Italian Society for Andrology and Sexual Medicine (SIAMS). Clinical and biochemical data were collected for four visits during 12 months of observation. RESULTS: 432 patients (mean age 50.9 ± 14.9 years) were enrolled. Of them, 247 men were receiving androgen therapy, whereas 145 were naive. After the first visit (V0), 80 men started androgen therapy, whereas 55 remained untreated during the entire observation. Younger age [odds ratio (OR) 0.57 (0.35-0.92)], total T < 8 nmol/l [OR 4.69 (1.59-13.81)], complaining at least one sexual symptom [OR 11.55 (2.01-66.35)] and reporting more severe lower urinary tract symptoms [OR 1.27 (1.01-1.60)] predicted starting an androgen therapy. Sixty-four men started therapy immediately after V0 and maintained it until the observation end. When compared to V0, they reported an increase in all the domains of the International Index of Erectile Function-15 (IIEF-15), in the sexual and physical subdomains of the Aging Male Scale as well as in the International Prostate Symptom Score. Conversely, the untreated group reported a significant improvement, although lower than the treated group, only in the erectile function domain of the IIEF-15. CONCLUSIONS: Management of LOH in SIAMS centres is in line with the international guidelines and the newest knowledge about the role of T on prostate health. Androgen therapy is associated with an improvement in all the aspects of sexual life and in the perception of physical strength.

Spatio-temporal distribution and acoustic characterization of haddock (Melanogrammus aeglefinus, Gadidae) calls in the Arctic fjord Kongsfjorden (Svalbard Islands).

In this study we analysed the acoustic properties and presence of haddock calls in the Arctic fjord Kongsfjorden (79° N-12° E, Svalbard Islands, Norway) in one year. Data were collected with three autonomous acoustic recorders located in the inner, middle, and outer parts of the fjord. The fjord is characterized by a gradient of oceanographic conditions from the inner to the outer part, reflecting changes from Arctic to Atlantic waters. Haddock sounds were more abundant in the outer fjord than in the middle fjord, whereas they were absent at the inner site. Mainly at the open-water site, the call abundance exhibited strong periodicity and a correlation with the cycles of neap tide (15 days) in August, with a clear diel cycle (24 h) in September and October. This result suggests that in this extreme environment with 24 h of light during summer, haddock regulate their acoustic activity according to the main available oscillating external physical driver, such as tide during the polar summer, while when the alternation of light/dark starts, they shift the periodicity of their calls to a diel cycle. Calls were recorded outside the spawning period (from July to October), and their characteristics indicated non-reproductive communicative contests. By using a detailed sound analysis based on previous laboratory studies for the first time, we suggest that the monitored population contains mainly juveniles (44% compared to 41% females and only approximately 15% mature males), showing the predominance of females in the middle fjord and juveniles at the open-water site.

Rudyard Kipling's medical addresses.

Rudyard Kipling was one of the most widely read writers of prose and poetry during his lifetime. His wide travels-he was born in India and lived in England and The United States and made frequent visits to South Africa-led to many encounters with physicians and medicine. His unique addresses to the medical profession reveal his knowledge of medical subjects. His three major medical addresses concern medical subjects in contrast to most laymen addressing physicians, who typically speak about their own areas of expertise. The influence of Sir William Osler on some of Kipling's stories is also examined.

The Botanical Monoterpenes Linalool and Eugenol Flush-Out Nymphs of Triatoma infestans (Hemiptera: Reduviidae).

Monoterpenes are the main components of essential oils. Some members of this chemical family present insecticidal activity. Triatoma infestans (Klug) is the main vector of Chagas disease in Argentina, Bolivia, Paraguay, and Perú. The objective of this work was to evaluate the effect of six monoterpenes (1,8-cineole, eugenol, linalool, menthol, α-terpineol, and thymol) on the locomotor and flushing out activity of T. infestans. A video tracking technique was used to evaluate the locomotor activity of nymphs exposed to different concentrations of these chemicals applied as films on filter paper. Papers treated with acetone alone were used as negative controls, while solutions of tetramethrin were applied as positive controls. Only linalool and menthol produced hyperactivation. Flushing out was assessed under laboratory conditions using a standardized aerosolization method. All monoterpenes were applied at 1.5 g/m3. 1,8-Cineole, α-terpineol, and thymol flushed out 10% or less nymphs. The average flushing out produced by eugenol was 36.7%. Values of median flushing out time (FT50) could only be calculated for linalool and menthol (16.67 and 42.98 min, respectively). The FT50 value for the positive control tetramethrin (applied at 0.006 g/m3) was 8.29 min. Following these results, the flushing out activity of a mixture of linalool and eugenol was evaluated. The FT50 of this 2:1 linalool:eugenol mixture was 40.73 min. Finally, flushing out assays performed in semifield conditions showed similar results to those obtained at the laboratory.

Hypercalcitoninemia in acute pancreatitis.

Calcitonin was measured in four patients with acute pancreatitis with hypocalcemia. A marked elevation of this hormone was noted in each case and persisted over several days. The peak level of calcitonin preceded the maximum fall in calcium. Among the various factors affecting calcium balance in pancreatitis, calcitonin probably plays an important role.

Treatment of abacterial prostato-vesiculitis with nimesulide.

The efficacy and tolerability of nimesulide were assessed in the treatment of patients with prostato-vesiculitis. In a noncomparative investigation, 30 patients received oral nimesulide 100mg twice daily for three 10-day cycles. Micturition-related symptoms were resolved in 20 patients and clear amelioration of inflammatory signs was observed with transrectal ultrasound in 16 patients. Abnormal sperm forms decreased from 57 to 49% (p < 0.001). In a comparative investigation, 40 patients received nimesulide 200mg twice daily or ketoprofen 100mg twice daily via the rectal route. Patients and physicians expressed an overall opinion on efficacy in favour of nimesulide. In a pharmacokinetic study of healthy volunteers who received oral nimesulide 100mg as a single dose, the mean maximum nimesulide concentration (0.58 +/- 0.13 mg/L) in seminal fluid was achieved after 2 hours while the maximum seminal fluid: blood plasma ratio 0.32 +/- 0.02 was observed after 4 hours. These data suggest that nimesulide is an effective NSAID in the treatment of abacterial prostato-vesiculitis and also demonstrate that this drug has a favourable disposition within the genital tract.

Effects of hormonal replacement treatment on bone mineral density and metabolism in hypogonadal patients.

We investigated 22 male patients affected by prepubertal hypogonadism with a mean age of 34.3+/-5.2. A significant reduction of bone mineral density (BMD) at both the lumbar spine (L2-L4, -14%, 1.039+/-0.11 vs. 1.217+/-0.16 g/cm(2), P=0.005) and femoral neck (-11%; 0.927+/-0.09 vs. 1.034+/-0.16 g/cm(2), P=0.01) was found in patients compared to age-matched controls. The mean Z score was -1. 55 for vertebrae and -1.33 for femur. Eleven and nine patients, respectively, had a lumbar and femoral BMD at least 1 S.D. below the normal mean; 8 and 4, respectively, 2 S.D. below. There was a strong positive correlation between BMD and duration of hormone replacement treatment (HRT) for both sites: respectively, r=0.71, P<0.005 for the vertebrae, and r=0.60, P<0.01 for the femur. A weak correlation was also present between onset of HRT and BMD: r=0.6, P<0.01 at the lumbar level, and r=0.47, P<0.05 at the femoral neck.

Combination drug therapy for the psychogeriatric patient: comparison of dosage levels of the same psychotropic drugs, used singly and in combination.

The dosage levels for a number of frequently prescribed psychotropic drugs, used singly or in combination, were determined in 902 long-term psychogeriatric hospital patients. The data failed to support the hypothesis that physicians prescribe lower dosages when combination therapy is used. Rather, the tendency was toward higher dosages under these circumstances.

Probability of infection with Trypanosoma cruzi of the vector Triatoma infestans fed on infected humans and dogs in northwest Argentina.

The probability that an uninfected Triatoma infestans would become infected with Trypanosoma cruzi after a single feed on people or dogs seropositive for T. cruzi was estimated in Amama, a rural village in northwest Argentina where transmission had resurged four years earlier. The prevalence of seropositivity for T. cruzi was 34.2% among 225 people tested, and 65.1% among 83 dogs tested. Parasitemia was detected by xenodiagnosis in 29.3% of 41 seropositive persons and in 85.3% of 34 seropositive dogs. Parasitemia decreased with age more sharply in seropositive people than in seropositive dogs. Seropositive humans infected 2.6% (95% confidence interval = 1.6%-3.6%) of 963 third or fourth instar nymphs fed once on them, whereas dogs infected 48.7% (44.7%-52.7%) of 610 nymphs. The probability of bug infection increased significantly with instar and was positively related to molting success. The infectivity to bugs of seropositive dogs was 12 times higher than that of seropositive children, and 100 times higher than that of seropositive adults. The weighted probability of infection of an uninfected bug fed randomly on any dog (0.3082) was about 50 times higher than that of bugs fed on any human (0.0062). Such differences in relative infectivity, combined with the relative host-feeding preference of domiciliary Triatoma infestans for dogs, reinforces the important role of domestic dogs as a risk factor for the domestic transmission of T. cruzi.

Genetic variability and geographic differentiation among three species of Triatomine bugs (Hemiptera-Reduviidae).

Three species of triatomine bugs, Triatoma sordida, T. guasayana, and T. patagonica, were examined by cytogenetic (C-banded karyotypes and male meiotic process) and isoenzymatic studies. These three species, with different importance as Chagas' disease vectors, were found to be closely related according to their known ethologic, ecologic, and morphologic traits. Although they have the same diploid chromosome number (2n = 22 constituted by 20 autosomes and an XY male/XX female sex mechanism), each species has a distinct chromosomal behavior during male meiosis and a specific amount and localization of C-heterochromatic blocks. Moreover, these chromosome characteristics allowed us to differentiate two T. sordida populations. Isoenzymatic data confirmed the taxonomic status of the three species and together with our cytogenetic results questioned the species homogeneity of T. sordida.

Pharmacologic induction of multiple follicular development improves the success rate of artificial insemination with husband's semen in couples with male-related or unexplained infertility.

The use of artificial insemination with husband's semen (AIH) as treatment for couples with male-related or unexplained infertility is often disappointing. The aim of the present study was to evaluate whether the induction of multiple ovulation can increase the pregnancy rates in couples treated with AIH. Multiple follicular development was induced by means of clomiphene citrate (CC) plus purified follicle-stimulating hormone (FSH) in 17 couples undergoing AIH for male-related or unexplained infertility. In spite of the long duration of infertility (greater than 6 years), 10 couples (58.8%) achieved pregnancy within 6 months of treatment. This figure was significantly higher than that obtained in 120 couples who underwent AIH either during spontaneous cycles or after induction of follicular development with CC alone. These results suggest that the availability of multiple mature oocytes increases the conception rate during each cycle, as reported for in vitro fertilization (IVF) programs. It is therefore suggested that a trial of induction of multiple follicular development be performed in couples with male-related or unexplained infertility before their inclusion in protocols for invasive procedures, such as IVF or gamete intrafallopian transfer.

Ultrasound monitoring of testis and prostate maturation in hypogonadotropic hypogonadic males during gonadotropin-releasing hormone treatment.

The effects of the administration of gonadotropin-releasing hormone (GnRH) on the increase of testis and prostate volume was monitored by ultrasound in six patients affected by idiopathic hypogonadotropic hypogonadism. A significant increase of testis volume was observed after 90 and 180 days (6.65 versus 3.32 mL, 99.1% net increase and 8.47 mL, 176.8% increase, respectively) of pulsatile GnRH treatment. A similar increase of prostate volume was observed at day 90 (12.67 versus 7.78 mL, 70.3% net increase) and day 180 (14.70 mL, 97.7% increase). The ultrasound monitoring of the modifications of testis and prostate volume may represent a biological assay of the effects of GnRH treatment and offer additional data on the response of target organs to the hormonal treatment.

Free L-carnitine in human semen: its variability in different andrologic pathologies.

Free L-carnitine was assayed in semen from patients with various andrologic diseases by an enzymatic-spectrophotometric method. Extremely low concentrations were found in semen from patients with agenesis of the vas deferens (31.8 +/- 18.8 nm/ml). Semen from men with vasectomies contains a higher concentration of free carnitine (105.0 +/- 8.1 nm/ml). When comparing these data with those of ten fertile control subjects (817.0 +/- 200 nm/ml), we assume that seminal free L-carnitine mainly originates from the epididymis. Semen from patients with azoospermia caused by testicular failure also contains a low carnitine concentration. In hypogonadotropic eunuchoids the gonadotropin treatment increased the low basal concentration. A correlation between semen carnitine content and sperm motility and number was also tested in 124 infertile patients. The results show a positive correlation between free L-carnitine and sperm count (r = 0.617; P less than 0.01), between free L-carnitine and sperm motility (r = 0.614; P less than 0.01), and between free L-carnitine and the number of motile spermatozoa per milliliter (r = 0.646; P less than 0.01).

Thyroid hormone receptors in neonatal, prepubertal, and adult rat testis.

Thyroid hormone (TH) is involved in the differentiation and development of rat testis, whereas its role in adult testis function is still undefined. The aim of our work has been to further analyze the presence in the testis of rats of various ages of messenger RNA (mRNA) coding the different TH receptor (TR) subtypes using a sensitive assay, such as reverse transcriptase-polymerase chain reaction (RT-PCR). To rule out the possibility of an "illegitimate transcription," we have analyzed both T3-binding capacity of adult rat testis and the presence in the same organ of TR proteins by immunohistochemistry, using specific antibodies directed against the various TR isoforms. Messenger RNA coding for TR alpha1 and alpha2 isoforms was clearly visible in gels prepared from RT-PCR samples obtained from the testis of rats of all ages, including adults, whereas mRNA for the TR beta1-beta2 was absent. The T3 maximal binding capacity (Cmax) by nuclear extracts of testicular homogenates gradually decreased from birth to adulthood, still remaining significantly detectable in adult testis, and represented approximately 1% of the Cmax observed in the liver. The immunostaining technique revealed an intense nuclear staining along the basement membrane of testicular tubules prepared from rats of all ages and incubated with an antipeptide antibody specific for TR alpha1 (alpha1-403). Staining with an antipeptide antibody specific for TR beta1 (beta-62) was never present. Our data show that mRNAs coding for the functional TR alpha1, and also for the still undefined alpha2, are present in the testis of rats of all ages. T3-binding activity and immunohistochemical studies confirmed that the message is translated into proteins. The transcriptional activity clearly decreased from birth to adulthood, but it still remained significantly present. The presence of a TR alpha1 message indicates that the adult rat testis may be directly responsive to T3 and, therefore, suggests an action of TH on rat testis that is not only developmental, but also metabolic.

Hypercalcitoninemia in infancy.

Immunoreactive calcitonin (iCT) was measured in 19 infants with neonatal hypocalcemia. The infants had a variety of neonatal diseases and stresses. iCT levels were generally elevated to two to 20 times the adult values. Poor correlation existed between the infant age and the level of iCT or between iCT alone and the serum calcium. However, there was significant correlation between the serum calcium and the ratio of the iCT to infant age from conception, suggesting that both infant age and iCT levels in combination may be related to hypocalcemia. Also, it appears that a variety of neonatal stresses may be associated with increased sensitivity to the hypocalcemic effect of iCT, as well as increased levels of iCT.

Effects of partial housing improvement and insecticide spraying on the reinfestation dynamics of Triatoma infestans in rural northwestern Argentina.

The long-term effects on domiciliary reinfestation by Triatoma infestans of smoothing the plaster of indoor walls prior to insecticide application (in Amamá village) relative to only insecticide application (in Trinidad-Mercedes villages) were evaluated in rural northwestern Argentina from 1992 to 1997. All domestic and peridomestic areas of each house were sprayed with 2.5% suspension concentrate deltamethrin at 25 mg/m(2) in October 1992, and infestations were assessed by various methods every 6 months. Domiciliary infestation decreased from 72-88% in 1992 to 6-17% in late 1995, to increase moderately thereafter without returning to baseline rates. Peridomestic sites were the first in becoming reinfested, and reached more abundant T. infestans populations than domiciliary areas. Domiciliary infestation rates and bug abundances were not significantly different between communities during surveillance. Domiciliary infestation rates in well-plastered houses were very low (5-9%) and approximately stable until 1996, but in houses with regular or bad plaster they consistently increased from 5 to 19-21% in both communities. Logistic multiple regression analysis showed that the likelihood of domestic infestation assessed through householders' collections was significantly and positively associated with the occurrence of an infested peridomestic site in the respective house, the occurrence of high-density domestic infestations before interventions, and well-plastered walls in 1996. Combining insecticide spraying and partial improvement of walls controlled domestic infestations and transmission of Trypanosoma cruzi effectively, but was not sufficient to eliminate T. infestans from the study area or increase the effectiveness of careful chemical control.

Monitoring house reinfestation by vectors of Chagas disease: a comparative trial of detection methods during a four-year follow-up.

Domestic reinfestations by triatomine bugs were monitored after application of deltamethrin and apparent elimination of Triatoma infestans in Amama and other nearby rural villages, north-west Argentina, from 1992 to 1996. The five methods used were sensor boxes, sheets of pink typing-paper, timed manual catches by a skilled three-person team aided by a flushing-out agent, collections by house-dwellers, and knockdown using insecticide fumigant canisters. In bedrooms, house-dwellers collected T. infestans significantly more frequently than the flushing-out method, but the reverse occurred in peridomestic sites. Both methods and sensor boxes revealed the frequent invasion of adult Triatoma guasayana and T. infestans, but neither T. guasayana nor Triatoma sordida colonized bedroom areas in spite of their rising abundance in nearby peridomestic sites. Sensor boxes were significantly more sensitive than the matched paper-sheets in three of five cross-sectional surveys. On average, each box recorded 2.0-3.2 times more triatomine fecal smears than each paper sheet. The frequency of dejecta in sensor boxes correlated positively with the proportion of houses where T. infestans, T. guasayana or T. sordida were captured by any method in bedroom areas. Triatomine fecal smears in sensor boxes were the earliest and most frequent sign of domiciliary infestation, followed by dwellers' collections of adult bugs. Analyzing the data prospectively, we provide a quantitative, predictive understanding of detection methods and review the validity and interpretation of the different signs of infestation obtained. The most sensitive and cost-effective combination of detection methods for vector surveillance in domestic areas was the use of sensor boxes and house-dwellers collections.