Effect of gonadotrophin-releasing hormone agonist treatment on growth hormone secretion in women with polycystic ovarian syndrome

The suppression of the pituitary-gonadal axis by the administration of gonadotrophin-releasing hormone agonists (GnRH-a) is used occasionally as an adjunct therapy with gonadotrophins for ovulation induction in women with polycystic ovarian syndrome (PCOS). A number of recent clinical studies have suggested that women with polycystic ovaries (PCO) may have disturbances of normal growth hormone (GH) kinetics and alterations in the GH/insulin-like growth factor (IGF)-I system. The purpose of this study was to determine the effect of GnRH-a administration on GH-releasing hormone (GHRH)-stimulated GH release in women with PCOS. Eight women with PCO and six control women were studied before and after 2 months of treatment with the long acting GnRH-a triptoreline (3.75 mg monthly injections). GHRH was given as a single i.v. injection and blood samples for GH measurements were obtained at -15, 0, 30, 60, 90 and 120 min. The GH responses were expressed as the area under the curve (AUC) or the differences from the basal value (delta(max)). The GH response to GHRH (mean +/- SEM) was lower in women with PCO (AUC 114.9 +/- 43.1 versus 206.2 +/- 28.7 ng/ml/120 min, P < 0.05 and delta(max) 31.6 +/- 8.2 versus 49.4 +/- 5.8 ng/ml, P < 0.05). After treatment with the GnRH-a, the GH response to GHRH was significantly smaller than before treatment in both groups (PCO AUC 34.6 +/- 9.0 ng/ml/120 min and delta(max) 12.4 +/- 3.1 ng/ml; controls AUC 148.8 +/- 28.4 ng/ml/120 min and delta(max) 31.2 +/- 6.1 ng/ml), but the PCO group had a significantly smaller response. These data demonstrate that women with PCO have a reduced GH response to GHRH compared with normal controls and that GnRH-a administration causes a further GH reduction in both groups. Women with PCO have a greater suppression of GH response to GHRH during treatment with GnRH-a. This suggests that a different level of sensitivity in the somatotrophic axis exists in PCOS.      

Identification of signaling motifs within human Fc gamma RIIa and Fc gamma RIIb isoforms

To assess the functional capacity of the heterogeneous Fc gamma RII (CD32) family and to identify critical regions for functioning, we generated a panel of B-cell transfectants. The Fc gamma R-negative B- cell line IIA1.6 was transfected with wild-type or mutant human Fc gamma RIIa and IIb molecules. Solely Fc gamma RIIa-expressing IIA1.6 cells were capable of phagocytosing opsonized Staphylococcus aureus bacteria, and cross-linking of Fc gamma RIIa triggered a rapid induction of tyrosine phosphorylation after 20 seconds. Analysis of Fc gamma RIIa mutants identified the immunoreceptor tyrosine-based activation motif (ITAM; previously described as ARH-1 motif) within the IIa cytoplasmic tail to be critical for B-cell activation. In contrast, Fc gamma RIIb isoforms triggered tyrosine phosphorylation on cross- linking with much slower kinetics (> 3 minutes) than Fc gamma RIIa. Furthermore, solely Fc gamma RIIb molecules proved capable of downregulating [Ca2+]i and interleukin-2 production on co-cross-linking with sIgG in IIA1.6. The Fc gamma RIIb-mediated functions were absent in Fc gamma RIIb mutants in which the tyrosine or leucine within the YSLL motif in a conserved 13-aa region (now known as immunoreceptor tyrosine-based inhibitor motif [ITIM]) were changed into phenylalanines. In conclusion, these data show the presence of functionally critical motifs within Fc gamma RII cytoplasmic tails. Fc gamma RIIa contains an ITAM involved in B-cell activatory functions, whereas the downregulatory activity of Fc gamma RIIb isoforms is linked to an ITIM.     

Adapted motivational interviewing for brief healthcare consultations: A systematic review and meta-analysis of treatment fidelity in real-world evaluations of behaviour change counselling

Background

Behaviour change counselling (BCC) is an adaptation of motivational interviewing (MI) designed to maximize the effectiveness of time-limited health behaviour change consultations. To improve intervention quality and understanding of treatment effects, it is recommended that evaluations of health behaviour change interventions incorporate existing fidelity frameworks (e.g. The National Institutes of Health [NIH] Behaviour Change Consortium) and ensure that treatment fidelity is assessed and reported.

Purpose

This systematic review was designed to examine (a) adherence to NIH fidelity recommendations, (b) provider fidelity to BCC and (c) impact of these variables on the real-world effectiveness of BCC for adult health behaviours and outcomes.

Methods and Results

Searches of 10 electronic databases yielded 110 eligible publications describing 58 unique studies examining BCC delivered within real-world healthcare settings by existing providers. Mean study adherence to NIH fidelity recommendations was 63.31% (Range 26.83%–96.23%). Pooled effect size (Hedges g) for short-term and long-term outcomes was .19 (95% CI [.11, .27]) and .09 (95% CI [.04, .13]), respectively. In separate, random-effects meta-regressions, neither short-term nor long-term effect sizes were significantly modified by adherence to NIH fidelity recommendations. For the subgroup of short-term alcohol studies (n = 10), a significant inverse relationship was detected (Coefficient = −.0114, 95% CI [−.0187, −.0041], p = .0021). Inadequate and inconsistent reporting within the included studies precluded planned meta-regression between provider fidelity and BCC effect size.

Conclusions

Further evidence is needed to clarify whether adherence to fidelity recommendations modifies intervention effects. Efforts to promote transparent consideration, evaluation and reporting of fidelity are urgently needed. Research and clinical implications are discussed.