Thyrotrophin-Releasing Hormone Raises Cytosolic Free Calcium Concentration in Human Adenomatous Somatotrophs and Corticotrophs; Comparison with in vivo Responsiveness to Thyrotrophin-Releasing Hormone in Patients with Acromegaly or Cushing's Disease

The effect of thyrotrophin-releasing hormone (TRH) on intracellular free Ca²⁺ concentration, [Ca²⁺)i, was investigated with the fluorescent dye fura-2 in cell suspensions obtained from 13 human growth hormone-secreting adenomas and 6 adrenocorticotrophin-secreting adenomas. Preoperatively, 9 out of 13 acromegalic patients showed a positive growth hormone response to TRH administration while none of the 6 patients with Cushing's disease had a plasma adrenocorticotrophin increase after TRH injection. In all the growth hormone-secreting adenomas the addition of TRH (100 nM) caused a significant rise in [Ca²⁺]i (from a resting level of 133±40 (±SD) to a value of 284±119 nM at 100 nM TRH, n = 42; P<0.001). The transient induced by TRH was found to have a dual origin, one due to Ca²⁺ mobilization from intracellular stores which was maintained in presence of EGTA (3mM) and verapamil (10 μM) and a plateau phase due to Ca²⁺ influx from the extracellular media. Somatostatin (0.1 μM) lowered both resting [Ca²⁺]i and TRH-induced transients. The effect of gonadotrophin-releasing hormone on [Ca²⁺]i was evaluated on cell suspensions obtained from 6 growth hormone-secreting adenomas. Gonadotrophin-releasing hormone (100 nM) caused a marked rise in [Ca²⁺]i (from 179±25 to 283±15nM) on the cell suspension obtained from the only in vivo responsive adenoma while it was ineffective in the remaining 5. Although TRH was ineffective in modifying plasma adrenocorticotrophin levels in all patients with Cushing's disease, in 5 out of 6 tumors the addition of 100 nM TRH caused a significant rise in [Ca²⁺]i (from 102.5 ± 36 to 163±66 nM, n = 22; P < 0.005). However, the effect of TRH on [Ca²⁺]i was significantly lower than that caused by arginine vasopressin, a physiological stimulator of adrenocorticotrophin release ([Ca²⁺]i values; 145±78 nM at 100 nM TRH versus 300±140 at 10 nM arginine vasopressin, n = 15; P<0.05). Moreover, the effect of arginine vasopressin on [Ca²⁺]i was detectable at concentrations as low as 0.1 nM while TRH was effective at concentrations higher than 1 nM. By contrast, gonadotrophin-releasing hormone was ineffective in increasing [Ca²]i in all the adrenocorticotrophin-secreting adenomas studied. Collectively, these data indicate that sensitivity to TRH is present in almost all the growth hormone- and adrenocorticotrophin-secreting adenomas independently of the responsiveness of the individual patients to the peptide.     

Open rhinoplasty for treatment of nasal tip haemangioma

Haemangiomas are the most common tumours of infancy. They typically proliferate then involute with considerable variation as regards to their rates of proliferation and involution. Haemangioma of the nasal tip is a lesion of special characteristics. During proliferation, it expands, contracts and deviates the nasal cartilages. Particularly, it regresses slowly and frequently involutes incompletely. That is why excision of the lesion is frequently suggested. The present study was conducted to evaluate open rhinoplasty after initial non-excision treatment modalities namely, intra-lesional corticosteroid injections and laser treatment, as a protocol of treatment for nasal tip haemangiomas. Twelve patients with nasal tip haemangiomas were included in the present study. Patients of both sexes, of different ages, with deep and mixed haemangiomas were studied. Disfigurement was the constant presenting symptom. Initial non-excision treatment reported different responses as denoted by the regression of the lesions’ size. Haemangiomas constantly extended between the medial crura of the alar cartilages as noted by the constant widening of the columella pre-operatively and the obvious separation of the nasal cartilages intra-operatively. This separation was constantly found to require approximation by sutures. The results of the present study concluded that whenever an early presentation with nasal tip haemangioma could be established, initial non-excision treatment followed by open rhinoplasty could be a useful protocol of treatment. Within the limitations of the present study, this protocol could achieve an early, safe and effective treatment for nasal tip haemangiomas with provisionally acceptable cosmetic outcomes so far.     

The spring-back phenomenon: does the final position of the nipple areola complex correspond to the pre-operative markings in reduction mammoplasty?

This study investigates whether tissue recoil or patient intrinsic factors influence the final position of the nipple areola complex (NAC) after reduction mammoplasty. The age, pre-operative ptosis, BMI and weight of the tissue resected were recorded as patient intrinsic factors in 37 patients undergoing reduction mammoplasty. The “spring-back” value was defined as the distance from the sternal notch to a nipple landmark on the breast meridian with the patient sitting up, minus the same measurement repeated with the patient recumbent to eliminate the pull of gravity on the breast. Spring back was measured pre-operatively for the nipple and nipple mark then post-operative for the nipple. The difference in centimeters between the final post-operative distance from the sternal notch to the nipple and the level intended by the pre-operative nipple mark was termed the “judgment error.” The final position of the post-operative nipple and the judgment error was compared to the spring-back values and patient intrinsic factors. Pre-operative ptosis was statistically related to increasing patient BMI and mass of tissue resected per breast. Pre-operative spring-back values for the nipple increased with increasing ptosis, BMI and decreasing age. Spring-back values were greater in the lower pole of the breast than in the upper pole. The final position of the nipple was higher than the pre-operative mark in 65% of cases, lower in 8% and as marked in 27% of cases. The post-operative NAC was, on average, 0.6 cm higher than planned pre-operatively. The post-operative distance from the sternal notch to the nipple increased with increasing pre-operative ptosis, mass of breast tissue resected per breast and all three spring-back values. The difference between the level of the pre-operative mark and the final nipple position showed a weak correlation with post-operative spring-back values. The parameters of ptosis, BMI, weight of tissue resected per breast and pre-operative nipple spring back reflect body habitus and breast size. Spring-back values vary between the upper and lower pole of the breast. The final NAC position was higher than that intended at pre-operative marking in the majority of cases. The surgeon instinctively marks the nipple lower in patients with greater pre-operative ptosis and in whom a larger resection is anticipated. Judgment error did not relate to intrinsic factors nor to pre-operative spring-back values; hence, these parameters cannot be applied as predictive tools for more accurate pre-operative marking of the nipple position. This study suggests that the pre-operative nipple mark should be placed, with the patient sitting up, at least 23 cm from the sternal notch and 0.6 cm lower than the final position estimated using the inframammary crease as a landmark. An invited commentary on this paper is available at .     

Early imaging in heart failure: Exploring novel molecular targets

Conclusions  Noninvasive imaging of neurohumoral upregulation in remodeled myocardium suggests that an imaging strategy can be developed for predicting the rate of remodeling and likelihood of HF development. This should allow a more judicious use of neurohumoral antagonists especially in subjects who do not have manifest HF.⁷⁴ In others specific targeted imaging may allow timely selection of individualized treatment strategies and ensure optimization of therapeutic intervention. Similar to ACE and AII receptors, multiple other targets in the hormonal cascades can identify the likelihood of adverse and favorable remodeling.⁷⁴     

Exercise tolerance after anaemia correction with recombinant human erythropoietin in end-stage renal disease

The aim of this study was to evaluate the effect of correction of chronic anaemia on the physical performance and the cardiovascular response to effort in children with end-stage renal disease (ESRD) maintained by haemodialysis. Seven patients (mean age 13.9 years) underwent triangular-type treadmill exercise testing before [haemoglobin (Hb) 6.3±0.9 g/dl] and after (Hb 11.2±1.2 g/dl) anaemia correction with recombinant human erythropoietin (rHuEPO). After treatment, the work-load reached, the peak oxygen uptake and average ventilatory anaerobic threshold (VAT) values were significantly increased (P<0.01,P<0.001,P<0.05 respectively). VAT values, expressed as a percentage of normal values, increased from 55.7±16.6% to 82.4±21%. This improvement correlated well with the increase in Hb (r=0.79). Oxygen pulse also increased significantly, when tested after anacmia correction. In conclusion, these data demonstrate that when the anaemia of children with ESRD is corrected with rHuEPO, there is a clear improvement in acrobic work capacity and effort tolerance.