High-resolution anorectal manometry: A comparison of solid-state and water-perfused catheters.

BACKGROUND: Anorectal manometry is the most commonly performed investigation for assessment of anorectal dysfunction. Findings from previous studies comparing water-perfused (WP) and solid-state (SS) techniques in the anorectum are conflicting. We compared anal sphincter pressure at rest and during dynamic maneuvers (squeezing and coughing) in healthy volunteers using SS and WP high-resolution anorectal manometry (HR-ARM) employing equivalent catheter configurations, a standardized protocol, and identical data acquisition and analysis software. METHODS: Sixty healthy volunteers (40F; median age: 40; range: 18-74) underwent WP and SS HR-ARM in randomized order. Anal resting pressure, and squeeze and cough increments were measured. Median pressure and 5th and 95th percentiles were calculated for each maneuver and compared using Wilcoxon signed-rank test. Bland and Altman plots were used to assess agreement between the systems. The impact of gender and parity was also explored. KEY RESULTS: Anal sphincter pressure measurements during squeeze (P<.001) and cough (P<.001) were significantly higher using SS HR-ARM than WP HR-ARM. No differences were seen at rest between the two types of catheter (nulliparous: P=.304; parous: P=.390; males: P=.167). Normal ranges for SS and WP manometry from this small group of healthy volunteers are presented. CONCLUSIONS & INFERENCES: Greater sensitivity to rapid pressure change is one of the advantages associated with SS HR-ARM. This is reflected in the differences observed during dynamic maneuvers performed during this study. Catheter type should be taken into consideration when selecting normal ranges for comparison to disease states.

Dominant versus recessive traits conveyed by allelic mutations - to what extent is nonsense-mediated decay involved?

Mutations in ROR2, encoding a receptor tyrosine kinase, can cause autosomal recessive Robinow syndrome (RRS), a severe skeletal dysplasia with limb shortening, brachydactyly, and a dysmorphic facial appearance. Other mutations in ROR2 result in the autosomal dominant disease, brachydactyly type B (BDB1). No functional mechanisms have been delineated to effectively explain the association between mutations and different modes of inheritance causing different phenotypes. BDB1-causing mutations in ROR2 result from heterozygous premature termination codons (PTCs) in downstream exons and the conveyed phenotype segregates as an autosomal dominant trait, whereas heterozygous missense mutations and PTCs in upstream exons result in carrier status for RRS. Given that the distribution of PTC mutations revealed a correlation between the phenotype and the mode of inheritance conveyed, we investigated the potential role for the nonsense-mediated decay (NMD) pathway in the abrogation of possible aberrant effects of selected mutant alleles. Our experiments show that triggering or escaping NMD may cause different phenotypes with a distinct mode of inheritance. We generalize these findings to other disease-associated genes by examining PTC mutation distribution correlation with conveyed phenotype and inheritance patterns. Indeed, NMD may explain distinct phenotypes and different inheritance patterns conveyed by allelic truncating mutations enabling better genotype-phenotype correlations in several other disorders.

Predictors of workplace sexual health policy at sex work establishments in the Philippines.

Based on the literature, we identified manager and establishment characteristics that we hypothesized are related to workplace policies that support HIV protective behavior. We developed a sexual health policy index consisting of 11 items as our outcome variable. We utilized both bivariate and multivariate analysis of variance. The significant variables in our bivariate analyses (establishment type, number of employees, manager age, and membership in manager association) were entered into a multivariate regression model. The model was significant (p<.01), and predicted 42) of the variability in the development and management of a workplace sexual health policy supportive of condom use. The significant predictors were number of employees and establishment type. In addition to individually-focused CSW interventions, HIV prevention programs should target managers and establishment policies. Future HIV prevention programs may need to focus on helping smaller establishments, in particular those with less employees, to build capacity and develop sexual health policy guidelines.

Evaluation of a pilot regimen for postoperative pain control in patients receiving oral morphine pre-operatively.

Postoperative analgesia in patients who receive regular oral opioids pre-operatively is frequently suboptimal. To improve management we introduced a regimen using subcutaneous diamorphine infusions with incremental doses. Infusion doses were calculated as half the daily pre-operative dose of oral morphine with the increments as one-sixth of the infusion dose. Results were recorded on the first two postoperative days before (n = 13) and after (n = 23) commencing the new regimen. The percentage of patients reporting severe pain at rest and on movement were significantly reduced by the new regimen (54% and 69% vs. 13% and 40%, respectively) since the opioid dose as a percentage of the pre-operative dose was significantly higher (160% vs. 352%). There were no instances of excessive sedation or slow respiratory rate in any patient. The use of the regimen has resulted in greater doses of opioids being administered with fewer patients in severe pain without significant complications.

Aeromedical evacuation of biological warfare casualties: a treatise on infectious diseases on aircraft.

A basic understanding of the transmission and isolation of infections would be essential to the safe and effective aeromedical evacuation (AE) of biological warfare (BW) casualties. First, the airframe as microbial environment is considered, and relevant preventive and disinfecting measures are discussed. A survey of past infectious disease transmission on civilian aircraft (including tuberculosis, influenza, measles, smallpox, and viral hemorrhagic fevers) is presented, and the communicability and stability of likely BW agents is described. A brief history of U.S. military aeromedical evacuation (as it relates to contagious diseases and U.S. Air Force BW doctrine) is also outlined. Special containment procedures (especially as used by the U.S. Army Aeromedical Isolation Team) are described. Finally, international legal and regulatory aspects of the AE of BW casualties are considered, and some unanswered questions and suggestions for future research are offered. It is concluded that, given adequate foresight, expertise, and resources, the AE of even contagious BW casualties could be safely and effectively accomplished.

Molecular mechanism for duplication 17p11.2- the homologous recombination reciprocal of the Smith-Magenis microdeletion.

Recombination between repeated sequences at various loci of the human genome are known to give rise to DNA rearrangements associated with many genetic disorders. Perhaps the most extensively characterized genomic region prone to rearrangement is 17p12, which is associated with the peripheral neuropathies, hereditary neuropathy with liability to pressure palsies (HNPP) and Charcot-Marie-Tooth disease type 1A (CMT1A;ref. 2). Homologous recombination between 24-kb flanking repeats, termed CMT1A-REPs, results in a 1.5-Mb deletion that is associated with HNPP, and the reciprocal duplication product is associated with CMT1A (ref. 2). Smith-Magenis syndrome (SMS) is a multiple congenital anomalies, mental retardation syndrome associated with a chromosome 17 microdeletion, del(17)(p11.2p11.2) (ref. 3,4). Most patients (>90%) carry deletions of the same genetic markers and define a common deletion. We report seven unrelated patients with de novo duplications of the same region deleted in SMS. A unique junction fragment, of the same apparent size, was identified in each patient by pulsed field gel electrophoresis (PFGE). Further molecular analyses suggest that the de novo17p11.2 duplication is preferentially paternal in origin, arises from unequal crossing over due to homologous recombination between flanking repeat gene clusters and probably represents the reciprocal recombination product of the SMS deletion. The clinical phenotype resulting from duplication [dup(17)(p11.2p11.2)] is milder than that associated with deficiency of this genomic region. This mechanism of reciprocal deletion and duplication via homologous recombination may not only pertain to the 17p11.2 region, but may also be common to other regions of the genome where interstitial microdeletion syndromes have been defined.

Characterization of calcium/calmodulin-dependent protein kinase II activity in the nervous system of the lobster, Panulirus interruptus.

Nervous system tissue from Panulirus interruptus has an enzyme activity that behaves like calcium/calmodulin-dependent protein kinase II (CaM KII) This activity phosphorylates known targets of CaM KII, such as synapsin I and autocamtide 3. It is inhibited by a CaM KII-specific autoinhibitory domain peptide. In addition, this lobster brain activity displays calcium-independent activity after autophosphorylation, another characteristic of CaM KII. A cDNA from the lobster nervous system was amplified using polymerase chain reaction. The fragment was cloned and found to be structurally similar to CaM KII. Serum from rabbits immunized with a fusion protein containing part of this sequence immunoprecipitated a CaM KII enzyme activity and a family of phosphoproteins of the appropriate size for CaM KII subunits. Lobster CaM KII activity is found in the brain and stomatogastric nervous system including the commissural ganglia, commissures, stomatogastric ganglion and stomatogastric nerve. Immunoblot analysis of these same regions also identifies bands at an apparent molecular weight characteristic of CaM KII.

Use of videophones and low-cost standard telephone lines to provide a social presence in telepsychiatry.

Research findings suggest that the value added by the video channel of currently available video conferencing technology is limited to the creation of a social presence of the other party. Almost all clinical information exchange takes place on the audio channel, while the interpersonal interactions (nods, blinks, facial expressions, and body language), which are so important in a face-to-face meeting, may not be adequately captured by the video. Several of our case studies are presented which suggest that, consistent with the social presence role for video, low-cost videophones may be effectively substituted for expensive ISDN-based systems in many mental health applications.

Embryonic rat spinal cord neurons change expression of glycine receptor subtypes during development in vitro.

The expression of functional glycine receptors (GlyRs) by embryonic rat spinal cord neurons during development in vitro was investigated using whole-cell patch-clamp recordings. Functional GlyRs were expressed by most neurons within 1 day in vitro, and by all neurons from 4 days onward. However, the extent to which responses to glycine were blocked by the antagonist strychnine differed significantly between the first few days and 8 days in culture. Responses to glycine by neurons during the first few days in culture exhibited significantly less blockade by strychnine than those in neurons after 1 week in culture. Responses to glycine at both ages reflected an increased conductance to chloride ions, ruling out involvement of N-methyl-D-aspartate type glutamate receptors, and were not due to cross activation of gamma-aminobutyric acid receptors. Monoclonal antibody 4a, which recognizes multiple subtypes of rat GlyR alpha subunits, labeled most neurons as early as 1 day in vitro, confirming that neurons express some form of GlyR alpha subunits by the first day in culture. These results show that rat spinal cord neurons express GlyRs early in their differentiation in vitro, and they suggest that individual neurons express as functional, cell-surface GlyRs a strychnine-insensitive isoform of the GlyR, possibly the previously described alpha 2* subunit. In addition, these results indicate that the expression of GlyR isoforms changes from predominantly a strychnine-insensitive isoform to other, strychnine-sensitive isoform(s) GlyR during development in vitro.

Physical characteristics of infant endotracheal tubes.

A change in the incidence of post-intubation complications in infants was the stimulus for the evaluation of the deformability of two brands of endotracheal tubes. The stiffness of each tube was evaluated at room and body conditions in the longitudinal axis of the tubes as well as a cross sectional plan. Shiley brand endotracheal tubes sizes 2.5 to 4.0 were less deformable than Portex brand of the same sizes.

Enteropathogenic Escherichia coli enteritis: evaluation of the gnotobiotic piglet as a model of human infection.

The pathogenicity of classical enteropathogenic Escherichia coli strains of human origin was investigated in gnotobiotic piglets. One to two day old piglets in groups of four were infected perorally with approximately 10(8) colony forming units of one of eight enteropathogenic E coli strains or a non-pathogenic control strain. Animals were necropsied 24 or 48 hours after infection and their intestines were subjected to histological examination, quantitative bacterial culture and estimation of lactase activity. Four enteropathogenic E coli strains caused mild to moderate diarrhoea in nine of the 16 piglets inoculated with them. Piglets given two of these strains later became moribund. One enteropathogenic E coli strain caused a severe illness unaccompanied by diarrhoea. Inflammation of the intestinal mucosa occurred with all eight enteropathogenic E coli strains, but not with the control strain. Pathological changes were most pronounced in the distal ileum and colon and adherent bacteria were seen on the surface of the inflamed mucosa. The extent of the inflammatory response in infected piglets for the most part paralleled the severity of the clinical signs, the degree of bacterial colonisation and the reduction in lactase activity. Electron microscopic examination of tissue from piglets infected with three different strains showed that bacterial adherence to the apical plasma membrane of epithelial cells was accompanied by distinctive ultrastructural changes. These included degeneration of the microvillous brush border, together with cupping and pedestal formation of the plasma membrane at sites of bacterial attachment. The same changes have been seen in naturally occurring enteropathogenic E coli diarrhoea in humans and rabbits. The combined clinical and pathological findings indicate that the neonatal gnotobiotic piglet is a suitable model of infection with enteropathogenic E coli.

The pathogenesis of Yersinia enterocolitica infection in gnotobiotic piglets.

Yersinia enterocolitica is an important cause of enteritis and mesenteric adenitis in many countries. However the pathogenesis of the disease caused by this organism has not been fully elucidated. Most isolates from clinical material possess two independent properties associated with virulence whose relative contribution to the development of disease is not known. These are the ability to penetrate the intestinal wall, which is thought to be controlled by a plasmid gene, and the production of heat-stable enterotoxin, which is controlled by a chromosomal gene. In this study, we infected neonatal gnotobiotic piglets with strains of Y. enterocolitica expressing these two properties in various combinations. The suitability of the piglet model was shown in experiments in which piglets fed virulent Y. enterocolitica serogroup O3 developed a clinical illness related to the size of the inoculum, which was accompanied by intestinal lesions similar to those reported in naturally and experimentally infected people and animals. The results confirmed the key role of a 47 X 10(6)-mol. wt plasmid in the pathogenicity of Y. enterocolitica, but suggested that penetration of the intestinal wall may be governed by chromosomal rather than plasmid-borne genes. No role for enterotoxin in the pathogenesis of yersiniosis was shown, although there was evidence that enterotoxin may promote intra-intestinal proliferation of Y. enterocolitica, thus favouring increased shedding of bacteria and encouraging their spread between hosts.

Attachment of E. coli-bearing K88 antigen to equine brush-border membranes.

Equine small intestinal brush-border membranes, from 40 adult horses were tested in vitro for the presence of receptors for the Escherichia coli adhesive antigens K88ab, K88ac and K99. Only K88-positive strains of E. coli adhered strongly to horse brush-border membranes. In contrast, a K88-negative mutant strain J2, 2 K99-positive strains and 3 E. coli strains isolated from foals failed to adhere to horse brush-border membranes. Purified K88ac pili when reacted with equine brush-border membranes inhibited to a great extent the adhesion of K88-positive E. coli. Similarly, K88-positive E. coli previously reacted with K88 antibody, did not attach to equine brush-border membranes. Oral inoculation of 4 newborn foals with strains of K88-positive enterotoxigenic E. coli, producing either heat-stable or heat-labile enterotoxin, caused diarrhoea in 1 animal.

Streptococcus durans: an unexpected enteropathogen of foals.

Streptococcus durans was isolated from a foal with profuse watery diarrhea and caused a similar syndrome when inoculated into foals via the orogastric route. The most consistent and striking histological feature was the extensive colonization of the mucosal surface of the small intestine by S. durans. Associated mucosal changes were mild to modeate, and brush border lactase and alkaline phosphatase production were depressed. S. durans also induced acute diarrhea in young gnotobiotic piglets. Mucosal changes were mild and, as with foals, the mucosal surface of the small intestine was colonized by the organism.

A comparative study of passive haemagglutination methods for the detection of hepatitis B surface antigen in routine hospital practice.

Two passive haemagglutination methods for detecting HBsAg were compared. In general, the method using turkey erythrocytes was found preferable to the method employing sheep cells since it is more rapid and more sensitive, and less frequently gave rise to false positive reactions with sera from staff, blood donors, and patients not receiving haemodialysis. The turkey cell test gives rise to more false positive screen tests than the sheep cell test when monitoring renal dialysis patients since approximately 10% of the sera of these patients were found to contain turkey cell agglutinins, but this presents no particular difficulty if the recommended absorption procedures are used.