The information highway for the pediatrician: an understanding of the Internet for the clinician

The author details the information highway available to the computer-literate pediatrician: the Internet, Electronic mail (E-mail), the World Wide Web, and explains how to access the information.     

Tumor cell cytotoxicity of a novel metal chelator

We have synthesized a novel six-coordinate metal chelator from the triamine cis-1,3,5-triaminocyclohexane by the addition of a 2-pyridylmethyl pendant arm on each nitrogen, which we term tachpyr. The experiments described here were designed to explore whether this compound exhibits potential antitumor activity. When added to MBT2 or T24 cultured bladder cancer cells, tachpyr was profoundly cytotoxic, with an IC50 of approximately 4.6 micromol/L compared with 70 micromol/L for desferioxamine. To explore the mode of action of tachpyr, several metal complexes were prepared, including Fe(II), Ca(II), Mn(II), Mg(II), Cu(II), and Zn(II) tachpyr complexes. Of these, the Zn(II), Cu(II), and Fe(II) complexes were without toxic effect, whereas the Ca(II), Mn(II), and Mg(II) complexes remained cytotoxic. To further probe the role of Zn(II) and Cu(II) chelation in the cytotoxicity of tachpyr, sterically hindered tachpyr derivatives were prepared through N-alkylation of tachpyr. These derivatives were unable to strongly bind Fe(III) or Fe(II) but were able to bind Zn(II) and Cu(II). When added to cells, these sterically hindered tachpyr derivatives were nontoxic, consistent with a role of iron depletion in the cytotoxic mechanism of tachpyr. Further, the addition of tachpyr to proliferating cultures resulted in an early and selective inhibition of ferritin synthesis, an iron storage protein whose translation is critically dependent on intracellular iron pools. Taken together, these experiments suggest that tachpyr is a cytotoxic metal chelator that targets intracellular iron, and that the use of tachpyr in cancer therapy deserves further exploration.     

Diamniotic placentation associated with omphalopagus conjoined twins: implications for a contemporary model of conjoined twinning

We have studied omphalopagus conjoined twins with a diamniotic monochorionic placenta. Although conjoined twins usually present in a single amniotic sac, one other example of diamniotic placenta has been reported in omphalopagus twins [Weston et al., 1990: Am J Med Genet 37:558-561]. Most theories concerning the pathogenesis of conjoined twinning exclude the possibility of diamniotic placentation. However, Spencer [1992: Teratology 45:591-602] recently elaborated a model for conjoined twinning based on duplication of organizing centers (primitive streaks) during gastrulation. We have considered the fate of embryonic membranes according to this model of omphalopagus twinning and show that diamniotic placentation is a predictable outcome.     

Efficacy of taxol in the orpk mouse model of polycystic kidney disease

Studies on conscious Sprague-Dawley rats using intracerebral dialysis in live animals combined with high-performance liquid chromatography with electrochemical detection showed that administration of apomorphine into the nucleus accumbens decreased the levels of dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid in the extracellular space of the dorsal striatum throughout the observation period and produced a transient reduction in the level of homovanillic acid in the dialysate from this structure. The studies demonstrated that reversible exclusion of the nucleus accumbens with procaine produced a transient increase in the levels of dopamine metabolites, without an increase in serotonin metabolites, in the extracellular space of the dorsal striatum. These results demonstrate that the nucleus accumbens affects dopamine metabolism in the striatum, this being mediated by the dopamine-reactive system in the nucleus accumbens.     

The effect of post-injury spinal position on canal occlusion in a cervical spine burst fracture model

STUDY DESIGN: The canal space of burst-fractured, human cervical spine specimens was monitored to determine the extent to which spinal position affected post-injury occlusion. OBJECTIVE: To test the null hypothesis that there is no difference in spinal canal occlusion as a function of spinal positioning for a burst-fractured cervical spine model. SUMMARY OF BACKGROUND DATA: Although previous studies have documented the effect of spinal positioning on canal geometry in intact cadaver spines, to the authors' knowledge, none has examined this relationship specifically in a burst fracture model. METHODS: Eight human cervical spine specimens (levels C1 to T3) were fractured by axial impact, and the resulting burst injuries were documented using post-injury radiographs and computed tomography scans. Canal occlusion was measured using a custom transducer in which water was circulated through a section of flexible tygon tubing that was passed through the spinal canal. Any impingement on the tubing produced a rise in fluid pressure that was monitored with a pressure transducer. Each spine was positioned in flexion, extension, lateral (and off-axis) bending, axial rotation, traction, and compression, while canal occlusion and angular position were monitored. Occlusion values for each position were compared with measurements taken with the spine in neutral position. RESULTS: Compared with neutral position, compression, extension, and extension combined with lateral bending significantly increased canal occlusion, whereas flexion decreased the extent of occlusion. In extension, the observed mechanism of occlusion was ligamentum flavum bulge caused by ligament laxity resulting from reduced vertebral body height. CONCLUSIONS: Increased compression of the spinal cord after injury may lead to more extensive neurologic loss. This study demonstrated that placing a burst-fractured cervical spine into either extension or compression significantly increased canal occlusion as compared with occlusion in a neutral position.     

Managing side effects of interferon-beta in patients with relapsing-remitting multiple sclerosis

In separate clinical trials, two preparations of recombinant interferon (IFN)-beta, IFN beta-1a and IFN beta-1b, reduced exacerbation rates in relapsing-remitting multiple sclerosis (RR-MS). Further, IFN beta-1a slows the progression of disability in patients with RR-MS. Although they are effective in the treatment of MS, use of these drugs is associated with both class-specific and agent-specific side effects. Class-specific side effects include fever, chills, myalgias, arthralgias, and other flulike symptoms beginning 2 to 6 hours after injection and resolving within 24 hours of injection. Transient worsening of preexisting MS symptoms also occurs infrequently. Agent-specific side effects include injection-site reactions with IFN beta-1b. Simple management strategies can be used to minimize these reactions, including patient education; tailoring the dose and time of administration of IFN-beta; and prescribing appropriate combinations of acetaminophen, non-steroidal anti-inflammatory drugs, and steroids. Although side effects tend to diminish with treatment, successful management allows long-term administration of these drugs to achieve a reduction in disease activity and commensurate improvement in outcomes.     

Influence of fluorochrome labeling density on the photobleaching kinetics of fluorescein in microscopy

The objective of this study was to identify, through kinetic analysis of individual elementary reactions, the conditions under which a simple first-order photobleaching kinetic model is sufficient for quantitative fluorescence measurements, and those under which more complex photobleaching kinetics must be considered. Three model systems of various fluorophore densities and distributions were employed to verify the kinetic analysis. The results showed that the photobleaching kinetics of free fluorescein at concentrations lower than 5 microM corresponded closely to a single exponential function and therefore involved predominantly simple unimolecular or pseudounimolecular photochemical reactions. When fluorescein was bound to polyvinyl alcohol (PVA) molecules, the photobleaching kinetics of the densely labeled PVA deviated more from a single-exponential function than sparsely labeled PVA. When fluorescein was bound to a DNA probe, the photobleaching kinetics were more complex and deviated significantly from a single-exponential function, due to one or more bimolecular processes with apparent concentration-dependent photobleaching rate constants. The practical applications of time-integrated fluorescence emission are discussed in the context of simple and complex photobleaching kinetics.     

Bovine IgG2a antibodies to Haemophilus somnus and allotype expression

AIMS/BACKGROUND: To characterise clinically a large kindred segregating retinitis pigmentosa and sensorineural hearing impairment in an autosomal dominant pattern and perform genetic linkage studies in this family. Extensive linkage analysis in this family had previously excluded the majority of loci shown to be involved in the aetiologies of RP, some other forms of inherited retinal degeneration, and inherited deafness. METHODS: Members of the family were subjected to detailed ophthalmic and audiological assessment. In addition, some family members underwent skeletal muscle biopsy, electromyography, and electrocardiography. Linkage analysis using anonymous microsatellite markers was performed on DNA samples from all living members of the pedigree. RESULTS: Patients in this kindred have a retinopathy typical of retinitis pigmentosa in addition to a hearing impairment. Those members of the pedigree examined demonstrated a subclinical myopathy, as evidence by abnormal skeletal muscle histology, electromyography, and electrocardiography. LOD scores of Zmax = 3.75 (theta = 0.10), Zmax = 3.41 (theta = 0.10), and Zmax = 3.25 (theta = 0.15) respectively were obtained with the markers D9S118, D9S121, and ASS, located on chromosome 9q34-qter, suggesting that the causative gene in this family may lie on the long arm (q) of chromosome 9. CONCLUSIONS: These data indicate that the gene responsible for the phenotype in this kindred is located on chromosome 9 q. These data, together with evidence that a murine deafness gene is located in a syntenic area of the mouse genome, should direct the research community to consider this area as a candidate region for retinopathy and/or deafness genes.