Growth Hormone Treatment in Short Children -Short-Term and Long-Term Effects on Growth

Short children with normal GH responses to arginine-insulin provocation testing and various amounts of spontaneously secreted GH over 24 hours participated in an ongoing study with GH, 0.1 IU/kg/day. A total of 40 prepubertal children have been treated for 1 year. Their mean height velocity increased from 4.6 to 7.5 cm/year. The children with the slowest pretreatment height velocity showed the best increment. An inverse relationship was found between the endogenous GH secretion and the increment in growth; 80% of the children had an endogenous GH secretion of less than 300 milliunits/litre/24 hours, estimated as area under the curve above the calculated baseline. They all showed an increment in height above 2 cm. The remaining 20% all had an endogenous GH secretion of more than 300 milliunits/litre/24 hours, estimated as area under the curve above the calculated baseline, Twenty-four of the children were prepubertal for the following 4 years, and their GH therapy continued. Their Deight velocity changed from 4.2 cm/year before therapy to 8.1,6.7,6.0 and 4.9 cm/year for the 1st, 2nd, 3rd and 4th years on treatment. Many of them have passed their expected final height, but have still not stopped growing. Those children who were in early puberty when GH treatment started went into a rapid growth spurt and have now stopped growing. They have all reached but not improved their expected final height. In 15 of the children GH treatment was stopped after 1-3 years. Their mean height velocity for the first post-treatment year was 5.1 cm/year; thus, for the group as a whole no'catch down'was observed. Of the 15 children, only 4 decreased in height velocity despite increasing age. Further studies on the long-term results of GH treatment in larger groups of short children are needed to verify the findings in this study.     

Pediatric intestinal transplantation

Advancements in donor management, organ preservation and operative techniques, as well as immunosuppressive therapies, have provided children with intestinal failure and its complications a chance not only for enteral autonomy but also long-term survival through intestinal transplantation (ITx). First described in the 1960’s, experience has grown in managing these complex patients both pre- and post-transplant. The goals of this review are to provide a brief history of intestinal transplantation and intestinal rehabilitation in pediatric patients, followed by focused discussions of the indications for ITx, induction and maintenance immunosuppression therapies, common post-operative complications, and outcomes/quality of life post-transplant.     

Aftereffects of mechanical vibration and muscle contraction on limb position-sense

Mechanical vibration (MV) of a muscle causes position-sense errors during and after application. Isometric muscle contraction at a shorter (hold-short conditioning) or longer (hold-long conditioning) length causes limb position-sense errors after the muscle returns to its intermediate length by means of intrafusal muscle thixotropy. However, it is unclear whether MV enhances these thixotropic position-sense errors. We studied the after-effects of MV on position-sense errors induced by hold-short and hold-long conditioning in the biceps of 12 healthy men. After hold-short conditioning, subjects perceived that the conditioned forearm was placed in a more extended position than occurred in reality; after hold-long conditioning, a more flexed position was perceived. Use of MV with hold-short or hold-long conditioning enhanced both errors, which were most obvious at 100 HZ. These results suggest that MV and muscle conditioning work together efficiently to develop intrafusal muscle thixotropy. MV combined with hold-long conditioning may alleviate thixotropically increased muscle stiffness, such as in spastic hypertonia.     

Functional liver recovery parallels autologous gut salvage in short bowel syndrome

Background/purpose

Parenteral nutrition (PN) is life saving in short bowel syndrome. However, long-term parenteral nutrition is frequently complicated by a syndrome of progressive cholestatic liver disease that is considered to be irreversible beyond the early stages of cholestasis, particularly in the presence of any degree of fibrosis in the liver. The purpose of this study was to examine apparent improvement in PN-associated liver dysfunction in a cohort of children with short bowel syndrome.

Methods

A retrospective case-record review of all patients managed within a dedicated Intestinal Rehabilitation Program (IRP) identified 13 patients with short bowel who had PN-associated liver dysfunction, defined for this purpose as hyperbilirubinemia or an abnormal liver biopsy.

Results

At referral, 12 of the 13 patients were exclusively on PN, and one was on 50% PN. At current follow-up, 3 patients have achieved complete enteral autonomy from PN, and 7 patients have had smaller decrements in PN requirements. Specific operative procedures to improve intestinal function were undertaken in 11 patients; 4 patients also underwent cholecystectomies with biliary irrigation at the time of intestinal reconstruction. The median highest bilirubin level in these 13 patients was 10.7 mg% (range, 3.2 to 24.5 mg%). Liver biopsy results indicated that 5 patients were cirrhotic, 3 had bridging fibrosis, and 4 had severe cholestasis or lesser degrees of fibrosis. Of 10 survivors in this series, 9 patients currently have a serum bilirubin less than 1 mg% with a median bilirubin in the group of 0.6 mg% (range, 0.3 to 6.4 mg%). Twelve of the 13 patients in this series were initially referred for liver-small bowel transplantation.

Conclusions

This preliminary experience suggests that PN-dependent patients with advanced liver dysfunction in the setting of the short bowel syndrome may, in some instances, experience functional and biochemical liver recovery. The latter appears to parallel autologous gut salvage in most cases. As a corollary, the authors believe that even advanced degrees of liver dysfunction should not preclude attempts at autologous gut salvage in very carefully selected patients. Such a policy of “aggressive conservatism” may help avoid the need for liver/intestinal transplantation in some patients who appear to be not responding to PN.     

Sudden cardiac death with left main coronary artery occlusion in a patient whose presenting ECG suggested Brugada syndrome

This article describes a patient who died suddenly during Holter ECG monitoring. A ventricular premature systole with an extremely short coupling interval of 240 ms was immediately followed by torsades de pointes, soon degenerating into ventricular fibrillation. Retrospective survey of the patient's medical records revealed an incomplete right bundle branch block (iRBBB) configuration with fluctuating saddle back-type ST elevation in leads V1 and V2, these suggesting Brugada syndrome. Autopsy showed complete thrombotic occlusion of the left main coronary artery.     

Prospective evaluation of two stimulation protocols for low responders who were undergoing in vitro fertilization-embryo transfer

OBJECTIVE: To compare two stimulation protocols designed for low responders undergoing IVF. DESIGN: Randomized, prospective study. SETTING: University hospital IVF unit. PATIENT(S): Sixty low responders who were recruited on the basis of results in previous cycles. INTERVENTION(S): Modified flare protocol in which a high dose of GnRH agonist was administered for the first 4 days, followed by a standard agonist dose, or a modified long protocol in which a standard agonist dose was used until pituitary down-regulation, after which the agonist dose was halved during stimulation. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved. RESULT(S): Twenty-nine cycles were performed with the modified flare protocol and 31 were performed with the modified long protocol. Significantly more oocytes were obtained with the modified long protocol than the modified flare protocol (4.42 +/- 2.6 vs. 3.07 +/- 2.15). The number and quality of embryos available for transfer was similar in both groups. One clinical pregnancy (3.4%) was achieved with the modified flare protocol, and 7 pregnancies (22.5%) were achieved using the modified long protocol. CONCLUSION(S): These preliminary results substantiate the poor prognosis and outcome for low responders undergoing IVF. A modified long "mini-dose" protocol appears to be superior to a modified mega-dose flare protocol in terms of oocyte yield and cycle outcome.     

Quantitative calcaneal ultrasound parameters and bone mineral density at final height in girls treated with depot gonadotrophin-releasing hormone agonist for central precocious puberty or idiopathic short stature

To evaluate the effect of gonadotrophin-releasing hormone (GnRH) agonist treatment on bone quality at final height, we studied girls with central precocious puberty (CPP) and with idiopathic short stature (ISS). A total of 25 Caucasian girls were included: group A ( n =14) with idiopathic CPP (mean age at start 7.4 years) and group B ( n =11) with ISS (mean age at start 11.7 years). Treatment duration was 3.8 and 1.7 years respectively. The quantitative ultrasound parameters (QUS) broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured at the calcaneus (UBIS 3000 device). Lumbar spine bone mineral density (BMD; L2–L4) was measured by dual energy X-ray absorptiometry (DXA) (Hologic QDR1000). Measurements were performed at final height and expressed as Z-scores corrected for bone age. Mean Z-scores of QUS parameters, areal BMD and volumetric BMD (BMDvol) were above –1 in both groups (group A: BUA Z-score –0.21, SOS Z-score –0.29, BMD Z-score 0.02, BMDvol Z-score 0.05, group B: BUA Z-score –0.93, SOS Z-score –0.40, BMD Z-score –0.86, BMDvol Z-score –0.68), although mean Z-scores of BUA and areal BMD in group B were significantly different from zero ( P =0.03 and P =0.02 respectively). Mean Z-score BMDvol was not significantly different from zero ( P =0.05), we found no significant difference between the groups for BMDvol ( P =0.13). Conclusion:although quantitative ultrasound parameters parameters and bone mineral density were normal in girls with central precocious puberty at final height after gonadotrophin-releasing hormone agonist treatment, mean Z-score for broadband ultrasound attenuation and areal bone mineral density were significantly different from zero and mean Z-score for volumetric bone mineral density was (just) not significantly different from zero in idiopathic short stature girls with normal puberty treated with gonadotrophin-releasing hormone agonists. Therefore we cannot say that this treatment is safe in these girls with regard to bone health.Abbreviations BMD bone mineral density - BMDvol volumetric bone mineral density - BMI body mass index - BUA broadband ultrasound attenuation - CPP central precocious puberty - DXA dual X-ray absorptiometry - GnRH gonadotrophin-releasing hormone - ISS idiopathic short stature - QUS quantitative ultrasound - SDS standard deviation score - SOS speed of sound     

Phonological short-term memory networks following recovery from Landau and Kleffner syndrome

Landau-Kleffner syndrome (LKS) is a rare acquired aphasia occurring in otherwise healthy children, together with spike-wave discharges predominating over superior temporal regions and activated by sleep. Although the outcome of language abilities is variable, a residual impairment in verbal short-term memory (STM) is frequent. This STM deficit might be related to the persistent dysfunction of those temporal lobe regions where epileptic discharges were observed during the active phase of the disorder. We tested this hypothesis by measuring brain activation during immediate serial recall of lists of 4 words, compared to single word repetition, using H(2) (15)O positron emission tomography (PET), in 3 LKS patients after recovery and in 14 healthy controls. The patients (TG, JPH, and DC) had shown abnormally increased or decreased glucose metabolism in left or right superior temporal gyrus (STG) at different stages during the active phase of their disease. At the time of this study, the patients were 6-10 years from the active phase of LKS. Results showed that Patients JPH and DC had impaired performance in the STM condition, whereas TG showed near normal performance. PET data showed that JPH and DC activated significantly less than controls left and right posterior STG. TG, having near normal STM performance, showed increased activity in the posterior part of the right STG. These data suggest that impaired verbal STM at late outcome of LKS might indeed be related to a persistent decrease of activity in those posterior superior temporal gyri that were involved in the epileptic focus during the active phase.