Simple electromyographic biofeedback treatment for chronic pediatric constipation/encopresis: Preliminary report

Pediatric constipation/encopresis is thought to be due, in part, to paradoxical constriction of the external anal sphincter (EAS) muscle during attempted defecation. This inappropriate contraction can lead to delayed, impacted, painful, and infrequent bowel movements. Standard Medical Care (SMC) involves disimpaction with enemas, followed by laxative therapy and diet modification, to maintain frequent soft stools. Using the case control method, the efficacy of SMC alone was compared with SMC plus EAS electromyographic biofeedback aimed at eliminating paradoxical contraction. Thirteen consecutive chronically constipated children received SMC plus biofeedback, and were compared with 13 age- and sex-matched children who received only SMC. Biofeedback subjects demonstrated post-treatment elimination of EAS paradoxical constriction. At 16 months follow-up parents of biofeedback children reported significantly greater improvement in constipation, encopresis, laxative use, and painful bowel movements compared to SMC.This research report was supported by the NIH under grant No. RO1 HD 28160.     

Physical mapping of four serpin genes: alpha 1-antitrypsin, alpha 1-antichymotrypsin, corticosteroid-binding globulin, and protein C inhibitor, within a 280-kb region on chromosome I4q32.1.

Alpha 1-antitrypsin (alpha 1AT; protease inhibitor [PI] locus), alpha 1-antichymotrypsin (alpha 1ACT; AACT locus), corticosteroid-binding globulin (CBG; CBG locus), and protein C inhibitor (PCI; PCI locus) are members of the serine protease inhibitor (serpin) superfamily. A noncoding PI-like (PIL) gene has been located 12 kb 3' of the PI gene. The PI, PIL, and AACT loci have been localized to 14q32.1, the CBG locus has been localized to 14q31-14q32.1, and PCI has been mapped to chromosome 14. Genetic linkage analysis suggests tight linkage between PI and AACT. We have used pulsed-field gel electrophoresis to generate a physical map linking these five serpin genes. The order of the genetic loci is AACT/PCI-PI-PIL-CBG, with a maximum distance of about 220 kb between the AACT/PCI and PI genes. These genes form a PI cluster at 14q32.1, similar to that of the homologous genes on murine chromosome l2. The close proximity of these genes has implications for disease-association studies.     

On the mechanism of a 60-Hz electric field induced growth reduction of mammalian cellsin vitro

Data on 60-Hz electric field (EF) induced reduction in growth rate of plant roots have strongly supported the hypothesis that the effect is related to an EF-induced transmembrane potential (V ⁱ _m). An investigation was undertaken to determine if this hypothesis is also applicable to 60-Hz EF-induced reductions in growth rate of mammalian cells in vitro. Human lymphoblastic (RPMI 1788) and human carcinoma (HeLa) cells were selected for study, the former having a relatively small diameter (11.2 m), and the latter having a relatively large diameter (15.4 tm). The 60-Hz EFs ranged from 430–1200 V/m in the culture medium. The growth rate of RPMI 1788 cells after 4-days was depressed by about 42% at a 60-Hz EF of 1000–1200 V/m with a response threshold occurring at 950 V/m; theV ⁱ _m at the response threshold was 8 mV There was no 60-Hz EF-induced effect on HeLa cell growth rate of aV ⁱ _m of 8 mV (60-Hz EF=700 V/m); a statistically significant effect was achieved atV ⁱ _m of 11 mV (950 V/m). The data support the hypothesis that above a threshold 60-Hz EF,V ⁱ _m acts as the initial signal leading to growth rate reductions.     

Ontogeny of pituitary cell-types and the hypothalamo-hypophysial relationship during early development of chum salmon,Oncorhynchus keta

Tissue non-specific alkaline phosphatase is a membrane-bound glycoprotein enzyme which is characterized by its phosphohydrolytic, protein phosphatase, and phosphotransferase activities. This enzyme is distributed virtually in all mammalian tissues, particularly during embryonic development. Its expression is stagespecific and can be demonstrated in the developing embryo as early as the 2-cell stage. It has been suggested that tissue non-specific alkaline phosphatase might play a role in tissue formation. In the study reported here, a genetransfer approach was employed to investigate possible roles for this enzyme by inserting the cDNA for rat tissue non-specific alkaline phosphatase into CHO and LLC-PK1 cells. Permanently transfected cell-lines expressing varying levels of alkaline phosphatase were estblished. The data showed that functional enzyme was expressed in the transfected cells. Cell spreading and attachment were enhanced in transfected CHO cells expressing high levels of tissue non-specific alkaline phosphatase but not in the LLC-PK1 cells. Further, in CHO cells, proliferation was shown to be inversely proportional to the level of the tissue non-specific alkaline phosphatase expression. Homotypic cell association was demonstrated in both alkaline phosphatase-positive and alkaline phosphatase-negative cells in both CHO and LLC-PK1 celllines. Taken together, these findings suggest that in addition to a role in mineralization of bone, tissue nonspecific alkaline phosphatase might also play a role in other cell activities, including those related to differentiation, such as cell-cell or cell-substrate interaction and proliferation.     

Fishers' Knowledge Reveals Ecological Interactions Between Fish and Plants in High Diverse Tropical Rivers

Ecosystems - Frugivory and seed dispersal by fish is an important mutualistic interaction in complex and species-rich tropical rivers. The local ecological knowledge (LEK) held by fishers can...     

An instrument for assessment of videotapes of general practitioners' performance.

OBJECTIVES--To identify those important characteristics of doctors'' and patients'' behaviour that distinguish between "good" and "bad" consultations when viewed on videotape; to use these characteristics to develop a reliable instrument for assessing general practitioners'' performance in their own consultations. DESIGN--Questionnaires completed by patients, general practitioner trainers, and general practitioner trainees. Reliability of draft instrument tested by general practitioner trainers. SETTING--All vocational training schemes for general practice in the Northern region of England. SUBJECTS--First stage: 76 patients in seven groups, 108 general practice trainers in 12 groups, and 122 general practice trainees in 10 groups. Second stage: 85 general practice trainers in 12 groups. MAIN OUTCOME MEASURES--Trainers'' ratings of importance; alpha coefficients of draft instrument by trainee, group, and consultation. RESULTS--6890 characteristics of good and bad consultations were consolidated into a draft assessment instrument consisting of 46 pairs of definitions separated by six point bipolar scales. Nine statement pairs given low importance ratings by trainers were eliminated, reducing the instrument to 37 statement pairs. To test reliability, general practitioner trainers used the instrument to assess three consultations. With the exception of one group of trainers, all alpha coefficients exceeded the acceptable level of 0.80. CONCLUSION--The instrument produced is reliable for assessing general practitioners'' performance in their own consultations.     

An optimized live bacterial delivery vehicle safely and efficaciously delivers bacterially transcribed therapeutic nucleic acids

There is an unmet need for delivery platforms that realize the full potential of next-generation nucleic acid therapeutics. The in vivo usefulness of current delivery systems is limited by numerous weaknesses, including poor targeting specificity, inefficient access to target cell cytoplasm, immune activation, off-target effects, small therapeutic windows, limited genetic encoding and cargo capacity, and manufacturing challenges. Here we characterize the safety and efficacy of a delivery platform comprising engineered live, tissue-targeting, non-pathogenic bacteria (Escherichia coli SVC1) for intracellular cargo delivery. SVC1 bacteria are engineered to specifically bind to epithelial cells via a surface-expressed targeting ligand, to allow escape of their cargo from the phagosome, and to have minimal immunogenicity. We describe SVC1's ability to deliver short hairpin RNA (shRNA), localized SVC1 administration to various tissues, and its minimal immunogenicity. To validate the therapeutic potential of SVC1, we used it to deliver influenza-targeting antiviral shRNAs to respiratory tissues in vivo. These data are the first to establish the safety and efficacy of this bacteria-based delivery platform for use in multiple tissue types and as an antiviral in the mammalian respiratory tract. We expect that this optimized delivery platform will enable a variety of advanced therapeutic approaches.     

Alkaline Phosphatase Content and the Effects of Prednisolone on Mammalian Cells in Culture

The alkaline phosphatase content of different tissue culture cell lines has been shown to vary from no detectable activity to high enzyme concentration. Within the epithelial lines studied alkaline phosphatase is either constitutive or inducible. Two epithelial cell strains in which alkaline phosphatase was "absent" could be induced to develop significant amounts of the enzyme when grown in the presence of Δ¹-hydrocortisone. Phosphate did not repress enzyme induction by prednisolone. Under conditions of deadaptation the induced enzyme was diluted by cell multiplication. The mouse fibroblastic L line and several human fibroblastic lines did not contain alkaline phosphatase when grown under the conditions described nor could they be induced to produce the enzyme when cultivated in medium with prednisolone. Δ¹-Hydrocortisone has other characteristic effects on established mammalian cell cultures which vary among cell lines. Human epithelial lines show reduction in cell multiplication with increase in mitotic index. The cytoplasm is increased and cell volume is nearly doubled. Mouse fibroblasts show a similar reduction in cell multiplication with a decrease in mitotic index. There is no increase in cell cytoplasm. Human fibroblast strains show no inhibition of multiplication or alteration in total cell protein when grown in medium containing prednisolone. Antisera prepared against "negative" prednisolone-inducible human cell lines and against a positive human line inhibited alkaline phosphatase activity to an equal degree.