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.

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.

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.

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.

Serum PSA levels are not affected by the menstrual cycle or the menopause, but are increased in subjects with polycystic ovary syndrome.

BACKGROUND/AIMS: Prostatic specific antigen (PSA) is the most specific prostatic tumor marker in man. Recently, PSA has been detected in a variety of tissues and fluids in women, and its determination suggested as a marker of hyperandrogenism. However, precise information about the physiology of PSA in females is not available. The goal of this study was to assess serum concentrations of PSA in healthy pre-menopausal women (healthy pre-menopausal group), menopausal women (menopause group) and patients with polycystic ovary syndrome (PCOS group). METHODS: PSA, androgens, LH, FSH, 17-beta-estradiol (E2), progesterone (Pg) were assessed in 40 post-menopausal women, 35 fertile controls and 35 women with PCOS. RESULTS: No significant difference in PSA concentrations could be demonstrated in different phases of the menstrual cycle in healthy pre-menopausal group and between pre- and post-menopausal groups. No correlations could be demonstrated between serum PSA levels and the following parameters: age, body mass index (BMI), LH, FSH, E2, testosterone (T), DHEAS, and SHBG, both in pre- and post-menopausal women. Significantly higher PSA levels (median=14 pg/ml) were found in the PCOS group compared to both pre-menopausal (median=5 pg/ml) and menopausal (median= 5 pg/ml) groups (p< 0.05). CONCLUSIONS: only minor fluctuations of serum PSA concentrations are observed in healthy pre- and post-menopausal women, while serum level is higher in PCOS, and therefore PSA can be considered a suitable marker of female hyperandrogenism.

Androgen receptor polymorphism (CAG repeats) and androgenicity.

Objective Polymorphism of the androgen receptor (AR) has been related to various pathophysiological conditions, such as osteoporosis and infertility. The objectives of this study were to evaluate the frequency of distribution in a normal Italian population and to assess CAG repeats (CAGr) in other conditions, such as hypoandrogenism, potentially influenced by AR polymorphism. Patients and measurements CAGr polymorphism was determined in a group of 91 healthy normoandrogenized subjects, 29 hypoandrogenized patients (hypoplasia of prostate and seminal vesicles, reduced beard or body hair, etc.) and 29 infertile patients by direct sequencing. Results The mean (+/- SD) number of CAG repeats [(CAGr)n] was 21.5 (+/- 1.7) in the control group, 21.4 (+/- 2.0) in the infertile patients and 24.0 (+/- 2.9) in the hypoandrogenic males. The difference was statistically significant between this last group and the other two (P < 0.0001), while there was no difference between normal controls and infertile patients. The frequency distribution showed a shift towards higher CAG length in hypoandrogenized patients compared to controls and infertile patients. If we used a cut-off point of 24.9 (2 SD above the mean), the percentage of patients with 25 or more CAGr repeats was 38% among hypoandrogenized patients, 7% among infertile patients and 5% among the control group. In hypoandrogenized subjects (CAGr)n correlated slightly with testis and prostate volume. The number of CAG repeats was not associated with any of the hormonal parameters, including testosterone, evaluated in the three groups. Conclusions Our normal population, representing subjects from Central Italy, is superimposable on other European populations with regard to (CAGr)n distribution. Hypoandrogenic males have a shift in the frequency distribution towards longer (CAGr)n. Infertile patients are not statistically different from the control group. These findings suggest that, given the same amount of circulating testosterone, as in our hypoandrogenized and control group, the final net androgenic phenotypical effect is due to AR polymorphism.

S. Weir Mitchell's prose and poetry on the American Civil War.

The prose and poetry of S. Weir Mitchell (1829-1914)--related to the American Civil War--encompass a very significant portion of his non-medical writings. The Civil War, more than any other single event, shaped his future career as one of the founders of American neurology. Indeed, it should not be surprising how the war was also such a driving force in his non-medical writings. His novels, once widely read, now are scarcely noted. His accounts of the social, political and economic events of the Civil War are of historical interest to students of the period. Neuroscientists as a group, like others, are apt to be unfamiliar with these writings, with the possible exception of "The Case of George Dedlow." A major purpose of this essay is to introduce readers, especially neuroscientists, to Weir Mitchell's fictional works in which neurological cases so often appear. One appreciates more the medical aspects of his novels, written as they were by a first-hand observer. His non-medical writings, poetry and prose, are to a large extent timeless and can be appreciated by today's readers.

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.

Civil war medicine from the perspective of S. Weir Mitchell's "The case of George Dedlow".

In 1866, a year following the close of the American Civil War, an anonymous article arousing much public interest appeared in the popular magazine, The Atlantic Monthly. The real author, Silas Weir Mitchell, who became one of America's most distinguished neurologists, wrote this short story early in his career while serving as a contract army surgeon and conducting his important clinical researches in nerve injuries. This article was the first literary effort in his long and prolific career as a physician/writer. Historians citing this article have focused almost exclusively on the early descriptions of causalgia and phantom limb syndrome, appearing as it did in a popular magazine. The present author proposes to show, for the first time, that Mitchell actually intended to describe many important medical consequences of the American Civil War, which was later shown to have so profoundly affected him throughout his medical and literary career. He cleverly accomplished this through the narration of Assistant Surgeon George Dedlow, who loses all four extremities by amputation.

A simple method to identify triatomine (Hemiptera: Reduviidae) feces in sensing devices used in vector surveillance programs.

We successfully applied the phenolphthalin (Kastle-Meyer) test used in forensic chemistry to distinguish between feces from triatomines and other domestic arthropods in sensing devices used for vector surveillance. All black or dark brown, but not white or yellow, fecal smears from laboratory-reared or field-collected Triatoma infestans Klug, Triatoma guasayana Wydgozinsky & Abalos, Triatoma sordida Ståhl (recently revalidated as Triatoma garciabesi Carcavallo, Cichero, Martínez, Prosen & Ronderos) tested positive, whereas dejecta from cockroaches and spiders, crickets, beetles, predatory bugs, and domestic flies tested negative. Black or dark brown dejecta from female Aedes aegypti L. and Cimex lectularius L. bedbugs also tested positive. In sellsing devices installed in bedrooms of 11 houses in Amamá, rural northwestern Argentina, where neither cimicid bedbugs nor argasid ticks had been found over the years, only 62% of the black or dark brown fecal smears attributed to triatomines by a skilled observer tested phenolphthalin-positive. After insecticidal spraying, when bedroom areas were not colonized by triatomines, only 33-40% of the black or dark brown fecal smears in sensor boxes attributed to triatomines by another skilled observer tested phenolphthalin-positive. Eleven (79%) ofthe 14 houses with dubious or nontypical triatomine feces tested phenolphthalin-positive at least once during 1993-1995. Our study introduces a low-cost, simple and effective procedure for the identification of triatomine feces. The test, as a helpful adjunct to sensing devices used in triatomine surveillance, will aid in the accurate detection of infestations and the determination of the need for insecticide application.

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.

Peridomestic distribution of Triatoma garciabesi and Triatoma guasayana in north-west Argentina.

The Reduviid bugs Triatoma garciabesi Carcavallo et al. (Hemiptera: Reduviidae: Triatominae), previously known as T. sordida Ståhl in the semi-arid chaco region, and T. guasayana Wygodzinsky & Abalos, vectors of Trypanosoma cruzi Chagas (Kinetoplastida: Trypanosomatidae), were found to occupy wide but different ranges of ecotopes in the peridomestic environment. At Amamá and nearby rural villages in north-western Argentina, a combined total of 1233 specimens were collected from 325/2314 (14%) sites surveyed at 6-monthly intervals from November 1994 to November 1996. Triatoma garciabesi and T. guasayana displayed a significantly different distribution among peridomestic ecotopes. Triatoma garciabesi predominated over T. guasayana in the prevalence of infested sites, the number of colonies and the number of bugs collected. For T. garciabesi, the predominant ecotopes most likely to yield T. garciabesi repeatedly were the rugged bark of Prosopis alba or P. nigra (Fabaceae) trees, where chickens roosted, and chicken coops. For T. guasayana the main ecotopes were goat or sheep corrals, piled materials and orchard fences. Triatoma garciabesi and T. guasayana were collected concurrently from the same site on 9/2314 (0.4%) occasions, and on different dates at the same site on 12 (0.5%) occasions. The observed low frequency of mixed populations (< 1%) was not significantly different from that expected from a hypothesis of independence. Triatoma garciabesi clearly outnumbered T. guasayana in four of the nine mixed populations, none of which persisted as such. Neither T. garciabesi nor T. guasayana colonized human habitations, even in the absence of T. infestans (formerly the predominant domestic vector of T. cruzi in this area), a situation that apparently has not changed in the last 50 years in northern Argentina.

The early history of neurosurgery in the American South.

As a specialty, neurosurgery was not on firm footing at the turn of the century (1900); however, it was brought into being in the American South early in the 20th century by seven young surgeons, all of whom performed neurosurgical procedures as part of their general surgery practice. A close look at the seven reveals that they were trained and/or influenced in varying degrees by either Dr. Harvey Cushing or Dr. Victor Horsley, two outstanding surgeons and teachers of this period. After overcoming many obstacles, these seven men firmly established the surgical specialty of neurosurgery in the South.

Breakpoint of a Y chromosome pericentric inversion in the DAZ gene area. A case report.

BACKGROUND: The presence of a spermatogenesis locus (gene or gene complex) in the euchromatic region of the long arm of the Y chromosome (Yq11), defined as azoospermia factor on the basis of gross structural rearrangement, was detected. The gene family responsible for different spermatogenetic defects is "deleted in azoospermia" (DAZ). CASE: A 34-year-old man had oligozoospermia, and a cytogenetic analysis carried out on peripheral lymphocytes with G banding revealed a 46,X, inv(Y)(p11q11)karyotype. The relation between the chromosomal breakpoint and the DAZ gene was more precisely defined by a fluorescent in situ hybridization technique. We revealed two signals for the DAZ gene, weaker than normal, one on the short arm and the other on the long arm of the Y chromosome, indicating that the breakpoint was located at the DAZ gene level. CONCLUSION: This is the first report documenting a chromosomal pericentric inversion with disruption in the DAZ gene area. We hope to obtain information on whether the disruption affects a functional zone of the gene and correlates with oligospermia at the chromosomal level.