Treatment of hypogonadal adolescent boys with long acting subcutaneous testosterone pellets

AIMS: Long acting subcutaneous testosterone pellets are of proved efficacy for the treatment of hypogonadal men, but have not been reported as a treatment modality in adolescent boys. Pharmacodynamic studies of subcutaneous testosterone release have shown prolonged normalisation of testosterone levels for at least four months. Administration of a long acting, safe, effective, and convenient form of treatment is desirable when life-long treatment is indicated. PATIENTS AND METHODS: Eighteen boys (aged 13.9-17.5 years at the start of treatment)-seven with primary hypogonadism, nine with secondary hypogonadism, and two boys being treated with testosterone for tall stature--were given testosterone pellets (8-10 mg/kg) every six months for 18 months. Height, weight, pubertal status, and psychosocial parameters were assessed and follicle stimulating hormone, luteinising hormone, testosterone, prolactin, and lipids were measured at 0, 1, 3, 6, 12, and 18 months. Bone age was measured at 0 and 12 months. RESULTS: In all boys growth velocity continued appropriately for bone age. Puberty continued to progress in all boys and in two boys the amount of virilisation exceeded that seen with previous treatment with intramuscular testosterone. After testosterone administration, follicle stimulating hormone and luteinising hormone suppressed incompletely in the boys with primary hypogonadism. Serum testosterone ranged from 4.3 to 26.7 nmol/l at three months to less than 10 nmol/l at six months after implantation. Prolactin and lipid levels were normal throughout the study. By report, there was an improvement in mood and emotional wellbeing. No pellet extrusions occurred in a total of 156 pellet insertions. CONCLUSIONS: All boys preferred this mode of testosterone administration to intramuscular injections. Long acting subcutaneous testosterone pellets are safe, efficacious, well tolerated, and convenient, and result in normal physical growth and improved psychological outlook in adolescent hypogonadal boys.     

Analysis and interpretation of serial position data

The representation of serial position in sequences is an important topic in a variety of cognitive areas including the domains of language, memory, and motor control. In the neuropsychological literature, serial position data have often been normalized across different lengths, and an improved procedure for this has recently been reported by Machtynger and Shallice (2009) Machtynger, J. and Shallice, T. 2009. Normalizing serial position analyses: The Proportional Accountability algorithm. Cognitive Neuropsychology, 26: 217–222. [Taylor & Francis Online], [Web of Science ®] , [Google Scholar]. Effects of length and a U-shaped normalized serial position curve have been criteria for identifying working memory deficits. We present simulations and analyses to illustrate some of the issues that arise when relating serial position data to specific theories. We show that critical distinctions are often difficult to make based on normalized data. We suggest that curves for different lengths are best presented in their raw form and that binomial regression can be used to answer specific questions about the effects of length, position, and linear or nonlinear shape that are critical to making theoretical distinctions.     

Metabolic transitions at menopause: In post-menopausal women the increase in serum uric acid correlates with abdominal adiposity as assessed by DXA

Objectives

The present study aimed to investigate any associations between parameters of body fat mass distribution and levels of serum uric acid (sUA), a well-documented cardiovascular risk factor, among non-obese women ranging from pre- to post-menopausal status.

Methods

In this cross-sectional population-based study we assessed body fat distribution by dual-energy-X-ray absorptiometry (DXA), and sUA levels in 101 pre- and 134 post-menopausal non-obese apparently healthy women.

Results

Multivariate stepwise regression analysis revealed that sUA was independently associated to the indicators of overall fatness, i.e. body mass index (β = 0.339, p < 0.001) and DXA-assessed total and percentage body fat (β = 0.366, p < 0.001 and β = 0.412, p < 0.001, respectively), only among post-menopausal women. Within this sample subset, trunk (i.e. central) fat mass emerged as a strong predictor of sUA (β = 0.408, p < 0.001), after taking the potential confounders (including body mass index) into account.

Conclusion

Central fat accumulation was found to be independently associated with higher sUA levels among non-obese women in post- but not among those in pre-menopause.     

The effect of three human recombinant hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor, granulocyte colony- stimulating factor, and interleukin-3) on phagocyte oxidative activity

Hematopoietic growth factors not only modulate blood progenitor cell activity but also alter the function of mature phagocytes. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 1 ng/mL for 60 min) did not stimulate luminol-enhanced chemiluminescence of polymorphonuclear leukocytes (PMNs) in suspension but primed PMN for as much as a 15-fold increase in chemiluminescence in response to f-met- leu-phe (fMLP). Mixed mononuclear leukocytes (monocytes [approximately 20%] and lymphocytes [approximately 80%]; MNL) chemiluminescence was very low even after rhGM-CSF priming, but MNLs added to the PMNs (PMN- MNL) resulted in near doubling of rhGM-CSF-primed PMN fMLP-stimulated chemiluminescence. The enhancing factor(s) from MNLs were inherent rather than induced by the GM-CSF, and purified lymphocytes increased GM-CSF-primed PMN chemiluminescence equal to mixed MNLs. We could not detect cell-free "enhancing factor(s)," but cell-to-cell contact further enhanced rhGM-CSF-primed fMLP-stimulated PMN-MNL oxidative activity by 40%. Polyclonal rabbit anti-tumor necrosis factor (TNF) (but not preimmune serum) decreased both fMLP-stimulated rhGM-CSF- primed PMNs and PMN-MNL chemiluminescence, suggesting that TNF on the PMN surface is enhancing GM-CSF-primed chemiluminescence. GM-CSF priming markedly increased PMN superoxide release (sevenfold), but PMN superoxide release was not further enhanced by the presence of MNLs. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) and interleukin-3 (rhIL-3) displayed much smaller effects on pure PMNs and mixed PMN-MNL chemiluminescence and superoxide release than rhGM-CSF. rhGM-CSF primes PMNs for increased oxidative activity more than rhG-CSF and rhIL-3. Maximal oxidative activity was observed when mixed PMN-MNL were primed with GM-CSF in a cell pellet-promoting cell-to-cell contact. This enhanced activity can be attributed, in part, to both inherent enhancing factor(s) on lymphocytes and PMN-associated TNF induced by GM-CSF.     

Obésité et diabète. Les variations des acides gras libres circulants sous charge orale en glucose

Résumé L'étude des variations des acides gras libres (AGL) du plasma est entreprise chez 58 sujets obèses et 18 sujets normaux témoins, mis dans des conditions d'exploration identiques. On constate chez les sujets obèses un comportement global des AGL qui est différent de celui des sujets normaux témoins dans la mesure où la dépression initiale de leur taux est plus lente et le maximum de chute est différé aux temps tardifs de l'épreuve. Il en résulte une tendance globale à une absence de réascension secondaire du taux des AGL circulants, à l'inverse de ce qui succède chez le sujet normal, où la valeur moyenne des AGL à la 4^ème h de l'épreuve est plus élevée que le taux moyen de base. Tant chez le sujet normal que chez le sujet obèse, on constate d'importantes variations individuelles. Les anomalies rencontrées chez les obèses sont d'autant plus évidentes que la tolérance glucidique se rapproche des conditions du diabète; cela laisse à penser qu'il existe, chez ces sujets, des relations étroites entre la dégradation de la tolérance glucidique et les anomalies du comportement des AGL circulants. Ce dernier problème est discuté en fonction des relations entre l'obésité et la maladie diabétique.

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Summary The variations of plasma non-esterified fatty acids (NEFA) in 58 obese subjects and 18 normal controls have been studied in identical conditions of investigation. The overall behavior of NEFA in the obese differed from that in the controls in that the initial fall was slower and the maximum depression occurred late in the test. Hence the overall tendency was for the secondary rise in the NEFA level to be missing, which was the reverse of what happened in the normals, in whom the mean NEFA value at the 4th h was above the starting value. Both in normals and in obese subjects there was a considerable individual variation. The anomalies in the obese became more marked as carbohydrate tolerance approached diabetic level; this suggests that there is in these subjects a close connexion between the decline of carbohydrate tolerance and the anomalies of plasma NEFA behavior. The latter is discussed in terms of the relationships between obesity and diabetes.

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Zusammenfassung Bei 58 Fettsüchtigen und 18 Normalpersonen wurden unter identischen Versuchsbedingungen die Variationen der freien Fettsäuren des Plasma (FFA) verfolgt. Bei Fettsüchtigen wurde ein von den Normalpersonen verschiedenes Gesamtverhalten der FFA festgestellt; der Unterschied ist umso grösser je langsamer die anfängliche Senkung des FFA-Spiegels bei den Fettsüchtigen erfolgt und je mehr das Maximum der Abnahme verzögert ist. Daraus ergibt sich eine Gesamttendenz zum Fehlen des sekundären Anstiegs des zirkulierenden FFA-Spiegels, im Gegensatz zu den Verhältnissen bei Normalpersonen, wo der Mittelwert der FFA in der 4. Stunde der Probe höher ist als der mittlere Ausgangswert. Sowohl bei Normalpersonen als auch bei Fettsüchtigen werden erhebliche individuelle Unterschiede beobachtet. Die bei Fettsüchtigen beobachteten Anomalien sind umso ausgesprochener je mehr sich ihre Kohlehydrattoleranz einer diabetischen Stoffwechsellage nähert; das lässt den Verdacht aufkommen, dass bei diesen Individuen eine enge Beziehung zwischen der verminderten Glukosetoleranz und dem abnormen Verhalten der zirkulierenden FFA besteht. Dieses Problem wird im Hinblick auf die Beziehungen zwischen Fettsucht und Diabetes mellitus besprochen.

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Resumen Se emprendió el estudio de las variaciones de los ácidos grasos libres (AGL) del plasma en 58 individuos obesos y 18 testigos normales, puestos en idénticas condiciones de exploración Se constata que en los sujetos obesos un comportamiento global de los AGL es diferente al de los individuos testigos normales en la medida o la depresión de su porcentaje es más lento y el máximo de caída se difiere a los tiempos tardíos de la prueba. Resulta una tendencia global a una ausencia de reascensión secundaria del porcentaje de los AGL circulantes, al contrario de lo que sucede en el individuo normal, en el que el valor medio de los AGL a las cuatro horas de la prueba es más elevado que el porcentaje medio de base. Tanto en el sujeto normal como en el sujeto obeso, se comprueban importantes variaciones individuales. Las anomalías encontradas en los obesos son mucho más evidentes cuando la tolerancia se acerca a las condiciones de la diabetes; esto lleva a pensar que existe, en estos individuos, estrechas relaciones entre la degradación y la tolerancia glucídica y las anomalias del comportamiento de los AGL circulantes. Este último problema se discute en función de las relaciones entre la obesidad y la enfermedad diabética.

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Riassunto Le variazioni dei NEFA plasmatici sono state studiate in 58 pazienti obesi e in 18 individui normali di controllo, posti in condizioni sperimentali identiche. Nei soggetti obesi è stato osservato un comportamento globale dei NEFA diverso da quello degli individui normali di controllo, nel senso che la depressione iniziale è più lenta e la massima caduta si verifica nelle fasi tardive della prova. Ne risulta una tendenza globale all'assenza di risalita secondaria dei NEFA circolanti, contrariamente a quanto avviene nel soggetto normale, in cui il valore medio dei NEFA alla 4^a ora del test è più elevato rispetto al livello medio di base. Sia nel soggetto normale che nell'obeso, si riscontrano importanti variazioni individuali. Le anomalie rilevate negli obesi sono tanto più evidenti quanto più la tolleranza al glucosio si avvicina alle condizioni esistenti nel diabete: ciò induce a ritenere che in questi soggetti esistano stretti rapporti tra la diminuzione della tolleranza al glucosio e le anomalie del comportamento dei NEFA circolanti. Quest'ultimo problema viene discusso alla luce delle relazioni tra obesità e malattia diabetica.