Fractures of the first rib in child abuse

PURPOSE: To evaluate the incidence and specificity of fracture of the first rib as an indicator of child abuse and to determine a mechanism of fracture. MATERIALS AND METHODS: All infants and young children with rib fractures who were seen at the radiology department of an academic medical center over a 2-year period were identified from the radiology data base. RESULTS: Rib fractures were attributed to child abuse in 12 of 35 children identified. Apart from a neonate with congenital osteogenesis imperfecta, only three children, all abused, had first-rib fracture, one bilaterally. Two additional children with first-rib fracture were identified from years prior to the study period. In four children, first-rib fractures were "isolated," without fractures of adjacent bones. CONCLUSION: Child abuse should be considered in cases of pediatric rib fracture, particularly fracture of the first rib. Possible mechanisms for first-rib fracture include impact force, compressive force, and shaking or acute axial load (slamming), which cause an indirect fracture.     

A de novo satellited short arm of the Y chromosome possibly resulting from an unstable translocation

A satellited long arm of the Y chromosome (Yqs) is considered a normal variation, whereas the presence of a satellite on the short arm of the Y (Yps) has never been described in the literature. A Yps chromosome could be clinically significant if the translocation resulting in Yps has relocated the testis-determining gene, SRY, to another chromosome. A carrier of such a translocation would therefore be at increased risk for having XX male and XY female offspring. Here we describe the first reported case of de novo Yps present in a phenotypically normal male. This Yps chromosome was positive for C-banding and nucleolus organizer region (NOR) staining and showed a hybridization signal for the beta-satellite sequence. Fluorescence in situ hybridization (FISH) analysis indicated that SRY was retained on the Yps and the translocation breakpoint on Yps was distal to the pseudoautosomal region. At prenatal diagnosis, a normal appearing Y chromosome was found in his son, and thus the satellite on Yps was lost during meiotic Xp-Yp pairing. This Yps chromosome was likely the product of an "unstable" translocation.     

Effects of cellular pharmacology on drug distribution in tissues

The efficacy of targeted therapeutics such as immunotoxins is directly related to both the extent of distribution achievable and the degree of drug internalization by individual cells in the tissue of interest. The factors that influence the tissue distribution of such drugs include drug transport; receptor/drug binding; and cellular pharmacology, the processing and routing of the drug within cells. To examine the importance of cellular pharmacology, previously treated only superficially, we have developed a mathematical model for drug transport in tissues that includes drug and receptor internalization, recycling, and degradation, as well as drug diffusion in the extracellular space and binding to cell surface receptors. We have applied this "cellular pharmacology model" to a model drug/cell system, specifically, transferrin and the well-defined transferrin cycle in CHO cells. We compare simulation results to models with extracellular diffusion only or diffusion with binding to cell surface receptors and present a parameter sensitivity analysis. The comparison of models illustrates that inclusion of intracellular trafficking significantly increases the total transferrin concentration throughout much of the tissue while decreasing the penetration depth. Increasing receptor affinity or tissue receptor density reduces permeation of extracellular drug while increasing the peak value of the intracellular drug concentration, resulting in "internal trapping" of transferrin near the source; this could account for heterogeneity of drug distributions observed in experimental systems. Other results indicate that the degree of drug internalization is not predicted by the total drug profile. Hence, when intracellular drug is required for a therapeutic effect, the optimal treatment may not result from conditions that produce the maximal total drug distribution. Examination of models that include cellular pharmacology may help guide rational drug design and provide useful information for whole body pharmacokinetic studies.     

Bradykinin increases the proportion of neonatal rat dorsal root ganglion neurons that respond to capsaicin and protons

A number of studies have examined bradykinin-induced sensitization of primary afferent neurons to mechanical or thermal stimuli. However, bradykinin-induced sensitization to other chemical stimuli has not been systematically addressed. We used primary cultures of dorsal root ganglion neurons from neonatal rats to determine whether bradykinin alters the responsiveness of individual neurons to capsaicin and protons. An increase in the concentration of free intracellular Ca2+ was used as a measure of a response to capsaicin or low pH. Pretreatment with bradykinin (30 nM) increased the proportion of "intermediate-size" (240-320 microm2) dorsal root ganglion neurons that responded to capsaicin (100 nM) or low pH (6.1). However, among "small-size" (160-239 microm2) neurons, bradykinin increased the proportion of neurons that responded to low pH (6.1) but not to capsaicin (10 or 100 nM). Because treatment with arachidonic acid (10 microM) did not mimic the effect of bradykinin and inhibition of cyclo-oxygenase and lipoxygenase with 5,8,11,14-eicosatetraynoic acid (10 microM) did not inhibit the effect of bradykinin on the response to capsaicin, it is not likely that the bradykinin-induced enhancement of neuronal responsiveness is mediated by arachidonic acid or its metabolites in this model. These results support the hypothesis that bradykinin sensitizes primary afferent neurons to other chemicals such as protons that are present in inflamed tissue, particularly by recruiting additional sensory neurons to respond to a given chemical stimulus. An increase in the number of responsive nociceptors that innervate inflamed tissue would contribute to hyperalgesia via spatial summation on spinal neurons in the pathway for pain. Furthermore, since bradykinin enhanced the responsiveness of small-size neurons that responded to protons but not to capsaicin, these data suggest that bradykinin-induced sensitization to protons and capsaicin occur by different mechanisms.     

Injection techniques to anesthetize the difficult tooth

Failure to achieve anesthesia can be a significant problem in the day-to-day practice of dentistry. The usual strategy following an anesthetic failure is to reinject. Therefore, a good understanding of conventional anesthetic techniques is important. But the practitioner also needs to have a broad armamentarium of injection strategies available for the "difficult-to-anesthetize cases". These strategies include the use of 5 percent lidocaine, intrapulpal injection, periodontal ligament injection and intraosseous injection. This paper will be a brief discussion of those techniques with an emphasis on the intraosseous injection.     

Resting respiratory tract dendritic cells preferentially stimulate T helper cell type 2 (Th2) responses and require obligatory cytokine signals for induction of Th1 immunity

Consistent with their role in host defense, mature dendritic cells (DCs) from central lymphoid organs preferentially prime for T helper cell type 1 (Th1)-polarized immunity. However, the "default" T helper response at mucosal surfaces demonstrates Th2 polarity, which is reflected in the cytokine profiles of activated T cells from mucosal lymph nodes. This study on rat respiratory tract DCs (RTDCs) provides an explanation for this paradox. We demonstrate that freshly isolated RTDCs are functionally immature as defined in vitro, being surface major histocompatibility complex (MHC) II lo, endocytosishi, and mixed lymphocyte reactionlo, and these cells produce mRNA encoding interleukin (IL)-10. After ovalbumin (OVA)-pulsing and adoptive transfer, freshly isolated RTDCs preferentially stimulated Th2-dependent OVA-specific immunoglobulin (Ig)G1 responses, and antigen-stimulated splenocytes from recipient animals produced IL-4 in vitro. However, preculture with granulocyte/macrophage colony stimulating factor increased their in vivo IgG priming capacity by 2-3 logs, inducing production of both Th1- and Th2-dependent IgG subclasses and high levels of IFN-gamma by antigen-stimulated splenocytes. Associated phenotypic changes included upregulation of surface MHC II and B7 expression and IL-12 p35 mRNA, and downregulation of endocytosis, MHC II processing- associated genes, and IL-10 mRNA expression. Full expression of IL-12 p40 required additional signals, such as tumor necrosis factor alpha or CD40 ligand. These results suggest that the observed Th2 polarity of the resting mucosal immune system may be an inherent property of the resident DC population, and furthermore that mobilization of Th1 immunity relies absolutely on the provision of appropriate microenvironmental costimuli.     

Dynamics of glucose-induced insulin release from mouse islets transplanted under the kidney capsule

Mouse pancreatic islet grafts under the kidney capsule of syngeneic hosts were removed and perifused in vitro 1-40 weeks after the transplantation. In comparison with fresh islets, 12- to 40-week-old grafts exhibited an attenuated first phase of glucose-stimulated insulin release. In grafts 1, 12, 28, or 40 weeks old, but not in fresh islets, the mean secretory rate during the initial 10 min of stimulation was significantly lower than that during the subsequent 15 min. When expressed in relation to insulin content, the insulin output in response to 11 mmol/L glucose was no less from grafts than from fresh islets; in grafts 12 or 40 weeks old at 16.7 mmol/L glucose, the fractional output above baseline was significantly diminished during the initial 10 min, but not subsequently. Immediately on switching from basal to stimulatory glucose concentration, there was a transient drop in insulin secretion from the grafts, especially after more than 12 weeks of transplantation and in response to 16.7, as compared with 11, mmol/L glucose. When glucose was switched back from stimulatory to basal concentration, grafts also frequently exhibited a transient increase in the insulin secretory rate. Neither initial drops nor "off responses" were seen in untransplanted islets. The modifications of the secretory dynamics in islet grafts suggest that transplantation influences the balance between the stimulatory and inhibitory influences of glucose on the beta-cell's secretory machinery.     

Voltage sensitivity of the osteoclast calcium receptor

We demonstrated previously that osteoclasts possess a divalent cation-sensitive "receptor", the Ca2+ receptor. Activation of the Ca2+ receptor by the surrogate cation Ni2+ was shown to elicit an increase in cytosolic [Ca2+] to a peak value followed by an exponential decline. In the present study we examined the influence of surface membrane voltage on the kinetics of Ca2+ receptor inactivation. The K+ ionophore, valinomycin was applied to intercept the declining phase of the cytosolic [Ca2+] transient elicited by application of between 50 microM- and 5 mM-[Ni2+]. This resulted in a sustained elevation of cytosolic [Ca2+] or even a 'hump' followed by a gradual decline. Such a kinetic alteration persisted in a Ca(2+)-free solution, but was abolished in high extracellular [K+] (105 mM). Thus, we demonstrate for the first time to our knowledge, a modulatory effect of membrane potential on the function of the osteoclast Ca2+ receptor.