Use of split-liver allografts does not impair pediatric recipient growth.

The use of split-liver (SL) allografts continues to be an excellent option for many pediatric recipients. Patient and graft survival with this graft type are comparable to patient and graft survival with whole organ grafts. Quality-of-life issues, specifically growth, for SL recipients have not been compared to those of recipients of more conventional whole-organ recipients. Pediatric recipients of SL and whole allografts at 2 institutions were identified. Height, z score, and delta z score were calculated for all recipients for each year after transplant. Between 1995 and 2004, 201 pediatric liver transplants were analyzed. Data were collected on 39 split-graft recipients and 36 whole-size recipients. Only subjects 3 years or younger were included in the study. Growth retardation was present in all recipients at transplant. Height z score post split and whole-size transplant were not statistically different at 1- (P = 0.65), 2- (P = 0.13), and 3-year (P = 0.32) anniversaries, respectively. Catch-up growth was present only in recipients of split grafts. In conclusion, the use of split grafts as opposed to whole-size grafts revealed no significant differences in terms of linear growth. Our report indicates that split-liver transplantation does not impair recipient growth.     

In vivo gene therapy for pyridoxine-induced neuropathy by herpes simplex virus-mediated gene transfer of neurotrophin-3.

Neurotrophic factors have been demonstrated to prevent the development of peripheral neuropathy in animal models, but the therapeutic use of these factors in human disease has been limited by the short serum half-life and dose-limiting side effects of these potent peptides. We used peripheral subcutaneous inoculation with a replication-incompetent, genomic herpes simplex virus-based vector containing the coding sequence for neurotrophin-3 to transduce sensory neurons of the rat dorsal root ganglion in vivo, and found that expression of neurotrophin-3 from the vector protected peripheral sensory axons from neuropathy induced by intoxication with pyridoxine assessed by electrophysiological (foot sensory response amplitude, and conduction velocity, and H-wave), histological (nerve morphology and morphometry), and behavioral measures of proprioceptive function. In vivo gene transfer using herpes simplex virus vectors provides a unique option for treatment of diseases of the sensory peripheral nervous system.     

Abnormal Digital Pressure Measurements in Diabetic Neuropathic Foot Ulceration

The diabetic neuropathic ulcer is typically slow to heal and recurrent. Macrovascular insufficiency is usually excluded as foot pulses are present and ankle:brachial pressure ratios are not decreased. These assessments cannot however exclude more distal vascular disease. Digital pressure measurements enable a reliable assessment of the distal peripheral vascular status to be made. The aim of this study was therefore to use toe pressures to assess the contribution of distal ischaemia in the pathogenesis of the neuropathic ulcer. Sixteen diabetic patients with recurrent neuropathic foot ulceration had their toe pressures compared to 10 neuropathic patients without a history of foot ulceration, 10 diabetic control subjects, and 11 normal subjects. Four non-diabetic patients with neuropathy and foot ulceration were also assessed. All subjects had ankle:brachial pressure indices ≧ 1. Toe pressure was assessed using laser Doppler flowmetry to record the return of skin blood flow. The toe:brachial pressure index (TBI) was then calculated. The diabetic patients with a history of recurrent neuropathic ulceration, had the lowest mean TBI, 0.63 ± 0.14 (SD), compared to the non-ulcerated diabetic neuropathy patients, the diabetic control subjects, and the normal subjects. 0.84 ± 0.11, 0.82 ± 0.1, and 0.81 ± 0.07, p < 0.01, respectively. Three of the four non-diabetic patients with neuropathic foot ulceration also had an abnormally low TBI. Reduced toe pressure measurements are thus found to be associated with neuropathic foot ulceration. The contribution of distal ischaemia in the pathogenesis of the diabetic neuropathic foot ulcer needs to be evaluated. One hundred and eight non-insulin-dependent diabetic patients who had been tested for autonomic dysfunction in 1984/85 were re-evaluated 5 years later. Autonomic function was assessed by means of four cardiovascular tests (heart rate variation during deep breathing and standing, and blood pressure variation after standing and sustained handgrip). Eighteen subjects were lost to follow-up; in the 90 patients who completed the study, both the deep breathing and the handgrip test significantly worsened (respectively from 13.7 ± 7.8 to 11.6 ± 6.3 beats min^?1 p < 0.01, and from 16.9 ± 8.2 to 12.7 ± 7.1 mmHg, p < 0.001), whereas both the 30:15 ratio and the variation of blood pressure on standing did not change. The impairment of a comprehensive evaluation score (from 2.5 ± 1.7 to 3.0 ± 1.5; p < 0.05) also confirmed the gradual deterioration of autonomic function over the study period.     

Ultrasound for diagnosis of apophyseal injuries

Avulsion injuries of the apophysis is a problem in young athletes. A correct diagnosis is necessary for establishing the appropriate treatment and the rehabilitation program. However, it is often difficult to distinguish between a simple muscle strain and an avulsion fracture. The X-ray examination is helpful only when an ossification center of the apophysis exists. Ultrasonography is considered the suitable diagnostic tool for these cases. From June 1988 to June 1993, 243 young athletes were seen with an anamnestic and clinically suspected apophyseal injury of the lower extremity. In all cases X-ray examination and ultrasound examination were performed. In 80 cases the diagnosis was confirmed by X-ray examination and in 97 by ultrasonography. Four criteria were defined for the sonographic examination: (a) a hypoechogenic zone, (b) increased distance to the apophysis, (c) dislocation of the apophysis, and (d) mobility of the apophysis on dynamic examination. These criteria are correlated to (a) edema, (b) lysis, (c) avulsion, and (d) unstable avulsion of the apophysis. Ultrasonography is a proven technique for the detection of apophyseal injuries. In comparison to X-ray examination, it has the advantages of no radiation exposure, early detection even without ossification center, and dynamic examination.     

Short-term pharmacologically induced growth study of ontogenetic allometry of oxygen uptake in children

BACKGROUND: A range of allometric coefficients have been proposed in describing the maximal oxygen uptake (VO2max): body mass relation in children using weight-bearing ergometry. However, a wide deviation in the allometric coefficients for VO2max may be apparent when selected pediatric cohorts are studied in conjunction with clinical intervention for growth abnormalities. AIM: The purpose of this study was to determine the allometric coefficients for VO2max after short-term pharmacologically induced growth in pre- and early pubescent children. SUBJECTS AND METHODS: The treatment group consisted of nine subjects with non-growth hormone (GH)-deficient short stature and one with GH-deficient short stature (mean age: 13.7+/-1.7 years). Ten pre- and early pubescent children matched for age, height, weight, VO2max and body mass index (BMI) were controls. The treatment group were evaluated before (Pre-GH) and after (Post-GH) 4 months of subcutaneous GH therapy (0.05 mgkg(-1)day(-1) x 6 days week(-1)). RESULTS: The mean ontogenetic coefficient for the treatment group was 1.50+/-0.20 and for the control group was 0.77+/-0.34. The mean allometric coefficient for body mass relative to VO2max was significantly higher in the treatment group compared with the control group (p<0.05). Height, weight, fat free mass (FFM), VO2max indexed to body mass (mLkg(-1)min(-1)) and FFM (mLkgFFM(-1)min(-1)) increased (p<0.05) with GH therapy. GH therapy also increased insulin-like growth factor-I (IGF-I) and served as a biochemical marker of GH therapy (p<0.05). The control group had no significant differences in all the variables tested (p<0.05). CONCLUSION: The scaling for oxygen uptake (VO2) for body mass varies with GH treatment and the increase in VO2max that commonly occurs in conjunction with physical growth in the pre-and early pubescent individual may be linked to an increase in FFM and linear size.     

Neoplasia in the rat induced by N-hydroxyphenacetin, a metabolite of phenacetin.

N-hydroxyphenacetin, a phenacetin metabolite, was fed to rats as a 0.05-0.5% dietary supplement. After 9 months, tumours of the liver were found in 36 of 64 animals. One animal also developed a renal tumour. No tumours were found in control animals. The findings implicate phenacetin as a carcinogen and suggest that N-hydroxyphenacetin may be the metabolite responsible.     

The impact of SARS-CoV-2 on the cystic fibrosis foundation therapeutics development network

The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) global pandemic significantly impacted CF clinical research within the Cystic Fibrosis Foundation Therapeutics Development Network (CFF TDN). A Research Electronic Data Capture (REDCap) survey was developed and sent to network sites to monitor and understand the impact on research teams, ongoing and anticipated clinical research, and specific clinical and research procedures. Key findings indicated an early impact on participant enrollment, research team stability, and procedures such as spirometry and sputum induction. These trends steadily improved over the months as research activities began to recover across the TDN. While SARS-CoV-2 created a significant challenge it also highlights new opportunities to expand CF research with greater focus on data collection outside of research centers and increased access for remote participation.     

The radiologic morphology of asymptomatic temporomandibular joints

A high frequency of remodeling changes was demonstrated radiographically in a series of 200 female patients with asymptomatic temporomandibular joints. Fewer than 10% of joints were completely radiologically "normal". Generally, there was an increasing incidence of changes with increasing age and for edentulous patients, but these relationships were by no means direct or mutually exclusive.