Prenatal sonographic diagnosis of Majewski syndrome

Majewski syndrome is an autosomal recessive disorder characterized by short ribs, polydactyly, short limbs, and a cleft lip. A 26-year-old woman with no family history of genetic diseases presented at 31 weeks' menstrual age with preterm labor and underwent prenatal sonography to screen for fetal anomalies. Sonography revealed a small thorax, markedly short ribs, micromelia, polydactyly, a cleft lip, dolichocephaly, and severe oligohydramnios. The other structures appeared normal. The most likely diagnosis was Majewski syndrome. Vaginal breech delivery was allowed to proceed. The 1,850-g male newborn died of respiratory failure shortly after birth. The postnatal appearance and radiographs confirmed the prenatal diagnosis.     

No Improvement of Adult Height in Non-growth Hormone (GH) Deficient Short Children with GH Treatment

It is still in doubt whether the standard-dose growth hormone (GH) used in Japan (0.5 IU/kg/week, 0.167 mg/kg/week) for growth hormone deficiency is effective for achieving significant adult height improvement in non-growth hormone deficient (non-GHD) short children. We compared the growth of GH-treated non-GHD short children with that of untreated short children to examine the effect of standard-dose GH treatment on non-GHD short children. GH treatment with recombinant human growth hormone (rhGH) was started before the age of 11 yr in 64 boys and 76 girls with non-GHD short stature registered at the Foundation for Growth Science who have now reached their adult height. In 119 untreated boys and 127 untreated girls whose height standard deviation score (SDS) was below –2 SD at the age of 6 yr, height growth was followed until 17 yr. Height SDS was significantly lower before GH treatment in the GH-treated group than at the age of 6 yr in the untreated group, in both sexes. Adult height and adult height SDS were significantly greater in the untreated group than in the GH-treated group, in both sexes, although the change in height SDS did not differ significantly. Height SDS was significantly lower before GH treatment in the GH-treated group than at the age of 6 yr in the untreated group, so 57 boys and 57 girls whose height SDS at the age of 6 yr in the untreated group closely matched the height SDS before GH treatment in the GH-treated group were chosen for comparison. Height SDS did not differ significantly between the GH-treated group before GH treatment and the untreated group at the age of 6 yr, nor were there differences between these subgroups in adult height, adult height SDS, or height SDS change, in either sex. The effect of GH treatment is reported to be dose-dependent and doses over 0.23 mg/kg/week are reported to be necessary to improve adult height in non-GHD short children. Currently, the GH dose is fixed at 0.175 mg/kg/week in Japan, and we expected to find, and indeed concluded, that ordinary GH treatment in Japanese, non-GHD short children does not improve adult height.     

Plasticity of skeletal muscle phenotype: mechanical consequences

Muscles are complex biological machines that perform a wide variety of mechanical activities. Over the past 30 to 40 years, a large amount of effort has been devoted to understanding cellular/molecular responses of skeletal muscle to various altered physiological states (e.g., altered loading state induced via immobilization/spaceflight, resistance training). Many cellular/molecular adaptations brought about by such interventions act on underlying processes that regulate activation, force and velocity of shortening/lengthening, and relaxation. In this context, measurements of mechanical properties (e.g., force-velocity relationship) are important, because they can provide insight into the physiological consequences of such adaptations. During the course of the past 10 to 15 years, a number of investigators have employed the work-loop technique to provide a more realistic approach toward understanding muscle function. Additionally, the work-loop technique provides a unique conceptual perspective that integrates: (1) the length-tension relationship, (2) activation kinetics, (3) the force-velocity relationship in the shortening domain, (4) relaxation kinetics, (5) the force-velocity relationship in the lengthening domain, and (6) the compliance of the passive elastic elements. A discussion of those factors (i.e., factors 2-5) that appear to be highly malleable forms the basis of this paper.     

Growth hormone deficiency in Dubowitz syndrome

Severe short stature as a result of intra-uterine growth retardation is one of the characteristics of Dubowitz syndrome. There have been few reports elaborating growth hormone secretory status in this syndrome. A child with Dubowitz syndrome, who was found to have complete growth hormone (GH) deficiency and who responded to growth hormone therapy, is described. This appears to be the first documentation of GH deficiency in this syndrome.     

Assessment of short stature in very low birthweight children

Abstract  The aims of this study of short very low birthweight (VLBW) children at or after 8 years of age were to determine: (i) if there were any unsuspected organic causes for their growth failure; and (ii) whether any children might be suitable for treatment with synthetic growth hormone. Thirty-seven of 195(19%) VLBW children seen at 8 years had heights <10th centile, and of these only 40% (10/25) of families offered an assessment were concerned enough to have the child fully evaluated. No child had an unsuspected organic cause of short stature. The children's parents were significantly shorter than expected for Caucasians (mean parental height s.d. score =– 1.06 (s.d. 0.72), t =– 5.9, P<0.001). On average, the bone age of the short children was delayed by 14.9 months (s.d. 18.8 months) compared with chronological age ((=–3.4, P<0.01). When compared with their parents, the children's mean height s.d. score for their bone age was not significantly different (mean height s.d. score for bone age = - 0.83 (s.d. 1.3), t = 0.6, NS). Only three children qualified for treatment with synthetic growth hormone; all three had been small for gestational age at birth and had birthweights <1000 g. In conclusion, in short VLBW children, only a minority of families and children are likely to be concerned enough about short stature to be fully assessed; an unsuspected organic cause for growth failure is unlikely, and only a few will qualify for synthetic growth hormone therapy.     

Auxology and response to growth hormone treatment of patients with intrauterine growth retardation or Silver-Russell syndrome: analysis of data from the Kabi Pharmacia International Growth Study

Using the database from the Kabi Pharmacia International Growth Study, 105 patients with intrauterine growth retardation (IUGR) (82 males, 23 females) and 45 with Silver-Russell syndrome (SRS) (32 males, 13 females) with persistent postnatal growth failure were studied. Patients with IUGR had a birth length and birth weight more than 2 SD below the mean for gestational age. Their height deficit at the start of GH treatment was -3.0 SDS at a median chronological age of 8.7 years and a median bone age of 7.0 years. Mean paternal and maternal heights were 166 and 153 cm, respectively. The median dose of GH was 0.5 IU/kg/week, given at a median frequency of five injections/week. The median height SDS for chronological age after 1, 2 and 3 years of GH treatment were -2.5, -2.1 and -1.9, respectively. In the 45 patients with SRS, median chronological age and median bone age at the start of treatment were 6.7 and 3.2 years, respectively, and mean paternal and maternal heights were 167.5 and 160 cm, respectively. The median dose of GH was 0.7 IU/kg/week, given at a median frequency of six injections/week. The median height SDS for chronological age at the start of treatment and after 1, 2 and 3 years were -3.5, -2.9, -2.8 and -2.2, respectively. Although the criteria used by physicians when diagnosing SRS were not controlled or verified in this study, it appears that patients with SRS can be differentiated from those with IUGR with persistent growth failure by their reduced bone age for chronological age at the start of treatment, and by the fact that patients with SRS tended to be born to parents of normal height. GH treatment in both groups induced catch-up growth, though long-term follow-up studies will be required to assess the effects of treatment on final height.     

截骨加楔形植骨术治疗创伤性踝成角并短缩畸形（附7例分析）

目的：对创伤性踝成角并短缩畸形行截骨加楔形植骨手术的治疗效果进行评价。方法：对7例因外伤致踝成角并短缩畸形患者行截骨加楔形植骨术矫形并延长肢体，术后进行平均39．7个月的随访，就疼痛，行走能力，活动度、日常生活能力等进行百分制评分。结果：术后患肢恢复或接近等长，疼痛，行走能力和日常生活能力均有改善，但踝关节活动度无改善。结论：本手术方法是治疗创伤性踝关节成角短缩畸形合并早期骨性关节炎十分有效的方法。     

Carnitine depletion during total parenteral nutrition despite oral L-carnitine supplementation

Carnitine (CAR) plays an important role in the β-oxidation of fatty acids. Less attention, however, has been paid to CAR compared to other nutrients even in total parenteral nutrition (TPN). To examine CAR metabolism during TPN and the effect of simultaneous oral L-CAR supplementation on CAR levels, the blood CAR level was measured in a 3-year-old boy receiving long-term TPN because of short bowel syndrome. Both the total and acyl CAR in the serum were evaluated under various nutritional conditions including oral supplementation of L-CAR. Low CAR concentrations were observed especially when lipid containing TPN regimens were in place. Oral L-CAR supplementation was not sufficient to restore the low CAR levels in the present index patient even when the dose was increased to 120 mg/kg in accordance with the result of the L-CAR absorption test that revealed poor intestinal absorption of this nutrient. Moreover, a markedly low CAR level was measured during the onset of sepsis in the patient, and the blood CAR was depleted when lipid metabolism was activated by lipid loading or sepsis. To date, the late effects of CAR depletion on child growth have not been well examined. It is recommended that the blood CAR level be maintained at normal levels before any prominent manifestations of the deficiency have developed. The intravenous administration of CAR appears to be necessary to supply a sufficient amount of CAR for patients with severe malabsorption.     

Intestinal adaptation in short bowel syndrome

Regaining enteral autonomy after extensive small bowel resection is dependent on intestinal adaptation. This adaptational process is characterized by hyperplastic growth of the remaining gut, which is accompanied by both an increase of cell division at the level of the crypt cells and by an increased rate of programmed cell death (apoptosis). Apart from the absorptive function, the small bowel also has a barrier function and plays an important role in interorgan metabolism. Also, these functions are greatly affected by a massive intestinal resection and subsequent recovery by intestinal adaptation. This review aims to give an overview of the debilitating effects of massive intestinal resection on gut function and subsequently discusses intestinal adaptation and possible factors stimulating adaptation.