Efficacy of boron neutron capture therapy on liver metastases of colon adenocarcinoma: optical and ultrastructural study in the rat

The effect of neutron boron capture therapy (BNCT) was studied in rat tumor liver cells after induction of the liver metastases by splenic inoculation of cells from DHA/K12/TRb line. Ten days following the treatment, the BPA was injected into rats and therefore the animals were sacrificed, the liver was exposed to neutron irradiation and processed. In some experiments the liver was reimplanted (after irradiation) in syngenic animals and studied 3 days later, following sacrifice. Samples of tissue obtained from metastasised and non-metastasised areas of the liver parenchyma, before and after the neutron irradiation, were examined in light microscopy and electron microscopy. The analysis pointed out damages induced by the neutron treatment in single tumor cells mostly localised in the synusoidal blood stream. Debris and apoptotic cells were sometimes observed in the neoplastic nodules before treatment, while the tumor cell death (apoptosis) increased in the tumor cells following BNCT treatment. An intense scavenger activity of Kupffer cells after irradiation was accompanied by a strong acid phosphatase reaction detectable in wide cytoplasmic areas. In the liver parenchyma of reimplanted animals, the presence of large collagen bundles spread among the hepatocytes was observed at electron microscopy.     

Risk factors associated with delayed thyrotropin elevations in congenital hypothyroidism

OBJECTIVES: To identify risk factors associated with delayed thyrotropin elevations in cases of congenital hypothyroidism. To determine whether routine rescreening of babies who have very low birth weight (VLBW) and babies in the neonatal intensive care unit is justified. STUDY DESIGN: Retrospective review of the New England Newborn Screening database (January 1989-June 2002) of newborns screened for hypothyroidism to determine the incidence of congenital hypothyroidism associated with delayed thyrotropin elevations and to characterize features associated with delayed thyrotropin elevations in newborns with VLBW and non-VLBW (NVLBW). RESULTS: The incidence of hypothyroidism was 14-fold higher for newborns with VLBW (1:250) compared with newborns with NVLBW (1:3500). Of the newborns with VLBW, two thirds were not detectable on the initial screening specimen. Among newborns with VLBW with delayed thyrotropin elevation, iodine exposure was found in 23%. Among newborns with NVLBW, 45% had congenital cardiac anomalies. For every 20 NVLBW cases of congenital hypothyroidism detectable by initial screening specimen, one additional case was detected with delayed thyrotropin elevation. CONCLUSIONS: Routine rescreening of babies with VLBW and babies in the neonatal intensive care unit is justified, and particular attention to follow-up testing of newborns known to have cardiac disease is warranted.     

Lack of cholesterol-lowering effect of graded doses of cholestyramine in children with Alagille syndrome: a pilot study

BACKGROUND: There is controversy about the potential risk of sustained high concentrations of cholesterol and triglyceride in patients with cholestatic chronic liver disease. However, it is currently accepted that cholesterol-lowering therapy may reduce morbidity and mortality rates in hypercholesterolemic patients without preexisting coronary heart disease, as well as in those with coronary heart disease. The objective of this study was to evaluate the effect of cholestyramine on the serum lipid profile of a group of children with Alagille syndrome and hypercholesterolemia. METHODS: Five children with Alagille syndrome and basal serum cholesterol concentrations greater than 230 mg/dL were included. Total serum cholesterol, triglyceride, low-density, and high-density lipoprotein cholesterol concentrations were measured on days 0, 10, 20, and 30 after the administration of oral cholestyramine 100, 250, and 500 mg(kg.d), respectively. Lipid fractions were reported as mean +/- 1 SD. Statistical analysis was performed with Friedman analysis of variance. RESULTS: The basal values and those of the three 10-day subsequent 100-, 250-, and 500-mg(kg.d) cholestyramine periods were as follows: total cholesterol: 327.6 +/- 77.1, 305.4 +/- 52.1, 290.6 +/- 24.1, and 320.6 +/- 32.3, respectively (P = 0.668); triglyceride: 136.4 +/- 14.6, 144.8 +/- 41.3, 161 +/- 30.9, and 165.4 +/- 40.7, respectively (P = 0.356); low-density lipoprotein cholesterol: 245.4 +/- 57.8, 239.8 +/- 48.6, 242.2 +/- 68.6, and 246.4 +/- 49.5, respectively (P = 0.782); and high-density lipoprotein cholesterol: 44.4 +/- 11.2, 41.8 +/- 12.8, 44.6.2 +/- 13.2, and 47 +/- 8.5, respectively (P = 0.431). CONCLUSION: Under the conditions of the current study, no significant effect of variable doses of cholestyramine could be demonstrated on the serum lipid profile of a series of children with Alagille syndrome. While the controversy on the potential atherogenic risk of low-density lipoprotein hypercholesterolemia in patients with chronic liver disease persists, new, prospective pharmacologic or nutritional trials are required.     

Are needle-free injections a useful alternative for growth hormone therapy in children? Safety and pharmacokinetics of growth hormone delivered by a new needle-free injection device compared to a fine gauge needle

The clinical safety, use and pharmacokinetics of a new needle-free device for delivery of growth hormone (GH) were compared with those of conventional needle injection devices. In an open-label, randomized, 4-period crossover study, 18 healthy adults received single subcutaneous injections of Genotropin administered by the Genotropin ZipTip needle-free device and by conventional injection. Bioequivalence was established between the devices. In a separate open-label, randomized, multicenter, 2-period crossover study, pediatric patients underwent 2-weeks Genotropin treatment administered by the Genotropin ZipTip and by a fine-gauge needle device (>95% used the Genotropin Pen). In total, 128/133 patients who were treated completed the study. Genotropin ZipTip was well tolerated and >50% of patients found no difference between the devices for all parameters assessed. After study completion, >20% patients preferred to continue using Genotropin ZipTip. Although statistical analyses demonstrated superiority of the Genotropin Pen versus Genotropin ZipTip for bleeding, pain, soreness, and bruising, Genotropin ZipTip was considered to provide a safe and bioequivalent alternative to needle injection.     

Spasticity in a child with myelomeningocele treated with continuous intrathecal baclofen

Patients with myelomeningocele may often suffer from severe spasticity. Surgical treatment of the underlying pathology such as hydromyelia and tethered cord may be successful, but failures are not uncommon. Those cases may offer a surgical challenge since further therapeutic options are limited. We present the case of a 7-year-old boy with myelomeningocele and related conditions suffering from severe spasticity and pain in his lower limbs. Surgical efforts with untethering and posterior fossa decompression failed to improve the symptoms. A test with 25 microg intrathecally delivered baclofen showed a total relief of spasticity and pain so that a pump for continuous baclofen delivery was implanted. During 32 months of follow-up, his spasticity has been under excellent control on 55-157 microg baclofen per day. Continuous delivery of intrathecal baclofen may be a surgical option to consider in patients with myelomeningocele and severe spasticity.     

Atopy in Norwegian and Russian adults: a population-based study from the common border area

Background: Several studies have concluded that atopy is more common in Western than in Eastern Europe. We aimed to study whether a similar difference exists between Norwegian and Russian adults living in geographically adjacent areas. Methods: A cross‐sectional population‐based study was performed in Sør‐ Varanger municipality (Norway) and in the cities of Nikel and Zapolyarny (Russia). The Russian cities are heavily polluted by sulfur dioxide from local nickel industry. In addition to questionnaire information, results on IgE sensitization (S‐Phadiatop, Pharmacia & Upjohn, Uppsala, Sweden) were obtained from 3134 Norwegian and 709 Russian participants. Results: A positive Phadiatop was found in 20.7% of the Norwegians (men 21.9%, women 19.7%) and in 27.5% of the Russians (men 35.7%, women 23.0%); the sex‐ and age‐adjusted relative risk of testing positive in Russia being 1.49 (95% CI 1.23–1.81). The Norwegian participants reported more atopic dermatitis and hay fever, although this difference was statistically significant only for atopic dermatitis in women. Conclusion: IgE sensitization was more common in Russia than in Norway, unlike findings from other east–west European studies. The Russians did not, however, report more atopic diseases. This discrepancy might reflect different awareness of allergies in the two countries and demonstrates the need for objective markers of atopy when comparing prevalence in different populations.