Endotoxemic-like shock induced by Loxosceles spider venoms: pathological changes and putative cytokine mediators

The systemic symptoms, tissue lesions and release of cytokines were analysed in four isogenic mouse strains with distinct haplotypes injected with various doses of Loxosceles intermedia spider venom. The estimated LD50 were 24.5 microg for C57Bl/6, 17.6 microg for BALB/c, 6.3 microg for C3H/HeJ and 4.6 microg for A/Sn mice. Prostration, acute cachexia, hypothermia, neurological disorders and hemoglobinuria were the signals preceding death. Accumulation of eosinophilic material inside the proximal and distal renal tubules and acute tubular necrosis were the most common histopathological findings. Death was prevented by previous treatment of venom with specific antivenom serum. The protein F35 purified from the whole venom retained the ability to induce the symptoms of the whole venom. The cytokines tumor necrosis factor (TNF), interleukins IL-6 and IL-10 and the radical nitric oxide were detected in serum at different levels after venom injection. These findings indicate that the state of shock produced in mice by whole endotoxin-free L. intermedia venom or by its purified fraction, protein F35, mimics the endotoxemic shock, that susceptibility to the systemic effects of the venom varies among mice of different haplotypes and that the pattern of in vivo cytokine release resembles that of endotoxemic shock.     

Self-management of cystic fibrosis: short-term outcomes of the Cystic Fibrosis Family Education Program

This study tested the efficacy of the Cystic Fibrosis Family Education Program, a cystic fibrosis self-management program, on improving participants' knowledge, self-efficacy, self-management behavior, health, and quality of life. A quasi-experimental pretest-posttest nonequivalent comparison group design was employed. Participants made up 104 patient-primary caregiver dyads from the intervention site cystic fibrosis center and 95 from the usual care comparison center. The intervention, a self-paced print curriculum based on social cognitive theory, targeted behavioral capability, self-efficacy, and outcome expectations and was implemented as an integral part of medical care. Parents, early childhood, middle childhood, and adolescents received separate materials on respiratory, nutrition and malabsorption, communication, and coping issues. Significant intervention effects were found on the knowledge scores for caregivers, adolescents, and children; caregiver and adolescent total self-management scores; Child Behavior Checklist total score; one parent coping scale score; the modified NIH score; NIH pulmonary factor 1; and the Brasfield total score. Significant interaction effects were evident in the self-efficacy scores for caregivers and children.     

Comparative performance of high-density oligonucleotide sequencing and dideoxynucleotide sequencing of HIV type 1 pol from clinical samples

The performance of the high-density oligonucleotide array methodology (GeneChip) in detecting drug resistance mutations in HIV-1 pol was compared with that of automated dideoxynucleotide sequencing (ABI) of clinical samples, viral stocks, and plasmid-derived NL4-3 clones. Sequences from 29 clinical samples (plasma RNA, n = 17; lymph node RNA, n = 5; lymph node DNA, n = 7) from 12 patients, from 6 viral stock RNA samples, and from 13 NL4-3 clones were generated by both methods. Editing was done independently by a different investigator for each method before comparing the sequences. In addition, NL4-3 wild type (WT) and mutants were mixed in varying concentrations and sequenced by both methods. Overall, a concordance of 99.1% was found for a total of 30,865 bases compared. The comparison of clinical samples (plasma RNA and lymph node RNA and DNA) showed a slightly lower match of base calls, 98.8% for 19,831 nucleotides compared (protease region, 99.5%, n = 8272; RT region, 98.3%, n = 11,316), than for viral stocks and NL4-3 clones (protease region, 99.8%; RT region, 99.5%). Artificial mixing experiments showed a bias toward calling wild-type bases by GeneChip. Discordant base calls are most likely due to differential detection of mixtures. The concordance between GeneChip and ABI was high and appeared dependent on the nature of the templates (directly amplified versus cloned) and the complexity of mixes.     

Sex-specific regulation of marking behavior by sex hormones and conspecifics scent in tree shrews (Tupaia belangeri)

The question of whether the changes in telomerase activity and/or the alteration of the p53 gene are involved in the development of oligo-astrocytomas induced by N-ethyl-N-nitrosourea (ENU) in rats was addressed. Telomerase activity levels of oligo-astrocytomas, including early neoplastic lesions, were significantly increased as compared to the normal controls, correlating with the degree of malignancy. In contrast, no mutations of p53 exons 5-7 were found in early neoplastic lesions or oligo-astrocytomas. These results indicate that the activation of telomerase occurs during astrocytoma carcinogenesis and contributes to the development of brain tumors, but the alterations of p53, at least on exons 5-7, may not be involved in this process.     

The immunocorrective potentials of an antistaphylococcal immunosorbent in extracting staphylotoxin

The immunocorrective effect of antistaphylococcal adsorbent prepared on the basis of silochrome, a silica matrix, has been revealed in experiments on peripheral blood lymphocytes obtained from 18 donors. The expression of receptors on human immunoregulating cells has been suppressed by the addition of staphylotoxin at a toxic concentration into the system. The experiments have shown that immunosorption is capable of extracting the toxin from the solution to a considerable degree, thus preventing the suppression of the receptor apparatus of immunoregulating lymphocytes. Staphylotoxin has been found capable of forming complexes with plasma ingredients, which increases the adsorption capacity of the immunosorbent.     

Surgical revision of the problematic transmetatarsal amputation

Recurrent ulcerations may develop following transmetatarsal amputation in patients with diabetes mellitus. In many cases, these ulcerations require surgical intervention to achieve healing, especially in situations where conservative care has not been effective. These procedures range from the local resection of bone to skin grafting and flap techniques to successfully heal the wound. The ultimate goal of any surgical intervention is to prevent a more proximal amputation.     

Visuomotor processing in unilateral neglect

The extent to which visual information on the contralateral, unattended side influences the performance of patients with hemispatial neglect was studied in a visuomotor reaching task. We replicated the well-established finding that, relative to target-alone trials, normal subjects are slower to reach to targets in the presence of visual distractors which appear either ipsilateral or contralateral to the target, with greater interference in the former condition. Six patients with hemispatial neglect showed even greater interference than did the normal subjects when the distractor appeared ipsilaterally but showed no significant interference from contralateral distractors. This pattern of performance was qualitatively similar for patients with lesions restricted to posterior regions and for patients with more extensive lesions involving both posterior and anterior brain regions. These findings suggest that, in the visuomotor domain, information on the contralateral side is processed minimally, if at all, in patients with hemispatial neglect.     

Bcl-2 protein expression during murine development

Bcl-2 functions as a death repressor molecule in an evolutionarily conserved cell death pathway. To further explore the role of Bcl-2 in development, we assessed its pattern of expression during murine embryogenesis. Immunohistochemical analysis demonstrates that Bcl-2 is widely expressed early in mouse fetal development in tissues derived from all three germ layers and that this expression becomes restricted with maturation. Within epithelium, the E12.5 lung bud demonstrates a proximal to distal gradient of Bcl-2 expression which is enhanced by E18.5. Bcl-2 is expressed throughout the intestinal epithelium through E14.5, but by E18.5 only cells in the crypts and lower villi express Bcl-2. In the mesoderm-derived kidney, Bcl-2 is expressed in both the ureteric bud and metanephric cap tissue at E12.5. Tubular structures also express Bcl-2, although overall levels drop as the kidney matures. Retinal neuroepithelial cells uniformly express Bcl-2 until cells begin to differentiate and then display the topographic distribution maintained into adulthood. The developing limb provides a clear example where Bcl-2 is restricted to zones of cell survival; Bcl-2 is expressed in the digital zones but not in the interdigital zones of cell death. The wide distribution of Bcl-2 in the developing mouse suggests that many immature cells require a death repressor molecule or that Bcl-2 may have roles beyond regulating developmental cell death.     

Early risk factors in pediatric renal transplantation at a single center

BACKGROUND/PURPOSE: Renal transplantation is the preferred treatment for renal failure in childhood, but the incidence of graft failure is generally higher than that in adult recipients. A single center was studied to determine if there were any correctable factors that could contribute to graft failure. METHODS: Recipient, donor, and perioperative factors were analyzed using standard statistical tests in 59 pediatric renal transplants performed between 1992 and 1995 using standard cyclosporin-based immunosuppression. RESULTS: Three factors were found to be significantly different between those recipients with good graft function and those who either died or were returned to dialysis. Any history of donor hypotension was a detrimental factor (P < .05, chi(2) test). In addition, those with failed grafts were more likely to have received their grafts from younger donors (P = .025, Mann Whitney U test). A third risk factor was a low postoperative central venous pressure in those whose graft ultimately failed (P = .0012, Mann Whitney U test). CONCLUSIONS: With a pediatric recipient who is stable and has a low priority for a renal graft, small donors, particularly those who have experienced hypotension, should be considered not suitable for transplantation. The chances of a successful graft can be improved by good communication between surgeon, pediatrician, and anesthetist. The importance of maintaining a positive central venous pressure is emphasised.     

Reducing the burden of oral and pharyngeal cancers

In the United States, oral and pharyngeal cancers continue to result in significant morbidity and mortality. Dental professionals play a pivotal role in all facets of controlling the burden of oral and pharyngeal cancer-from efforts to prevent its occurrence, to ensuring that oral cancers are detected at the earliest possible stage, to treating these cancers, and to ensuring maximum quality of life and function for oral and pharyngeal cancer survivors. Individually and by making linkages within the community and beyond, dentists can help patients modify their risk of these cancers and can take steps to screen for them, thereby potentially improving survival and function of those who develop oral cancer. Creative partnerships between community dentists and academic and other research centers will help move knowledge of the biological processes involved in carcinogenesis and innovations in treatment into clinical practice. Partnerships between dental and medical professionals may also help efforts to reduce the morbidity related to oral and pharyngeal cancers. Local, state and national multidisciplinary initiatives are emerging that focus more broadly on risk factor control or oral and pharyngeal cancer issues. These many forms of cooperative approaches offer excellent opportunities to make a significant impact on reducing the incidence of and in treating these debilitating and disfiguring malignancies.