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Biomedical subjects

R Morrow

Publications and source records attributed to R Morrow.

At least 19 recordsLinked to original sources

Neuromedin U can exert colon-specific, enteric nerve-mediated prokinetic activity, via a pathway involving NMU1 receptor activation.

BACKGROUND AND PURPOSE: The neuromedin U (NMU) receptors, NMU1 and NMU2, are expressed in the gut but their functions are unclear. This study explores the role of NMU in gastrointestinal motility. EXPERIMENTAL APPROACH: The effects of NMU were examined in the forestomach and colon isolated from NMU2R wild-type and NMU2R-/- (knockout) mice, looking for changes in muscle tension and in nerve-mediated responses evoked by electrical field stimulation (EFS), and in models of peristalsis in mouse colon and faecal pellet transit in guinea-pig colon. KEY RESULTS: In the mouse forestomach, NMU (1 nM-10 microM) concentration-dependently induced muscle contraction, in the presence of tetrodotoxin and atropine, in preparations from both wild-type and NMU2R-/- mice (pEC50: 7.9, 7.6, Emax: 0.26, 0.20g tension, respectively, n=8 each concentration). The same concentrations of NMU had no consistent effects on the responses to EFS (n=8). In the mouse colon, NMU (0.1 nM-1 microM) had no significant effect on baseline muscle tension (n=8), but concentration-dependently potentiated EFS-evoked contractions in preparations from both wild-type and NMU2R-/- mice, pEC50: 8.1, 7.8, Emax: 24%, 21%, respectively, n=6-11. NMU (0.01 nM-0.1 microM, n=5-7) concentration-dependently decreased the interval between waves of peristalsis in the mouse colon (pEC50: 8.8) and increased the rate at which a faecal pellet moved along the guinea-pig colon. CONCLUSIONS AND IMPLICATIONS: These results demonstrate that NMU exerts colon-specific, nerve-mediated, prokinetic activity, via a pathway involving activation of NMU1 receptors. This suggests that this receptor may represent a molecular target for the treatment of intestinal motility disorders.

Animals↗

Performance of a novel test for IgM and IgG antibodies in subjects with culture-documented genital herpes simplex virus-1 or -2 infection.

Novel tests (BioPlex) for herpes simplex virus-1 (HSV-1) and HSV-2 IgG were compared with HerpeSelect HSV-1 and HSV-2 ELISAs for type-specific IgG. The sensitivity and specificity of BioPlex HSV-1 IgG were 94% (84/89) and 96% (119/124), respectively, with unselected sera, while the sensitivity and specificity of BioPlex HSV-2 IgG were 92% (109/118) and 98% (95/97), respectively. BioPlex IgM was compared with Diamedix IgM against sera from patients with culture-documented genital herpes. The test results were concordant in 81% of sera from HSV-1 patients and in 90% of sera from HSV-2 patients. Use of BioPlex IgM in addition to BioPlex IgG tests increased HSV-2 seroconversion detection from 47% of subjects to 70%. Use of Diamedix IgM in addition to Focus IgG ELISA increased HSV-2 detection from 40% of subjects to 70%. IgM was detected by BioPlex in 63% of sera from patients with early HSV-2 infection (< 30 days) and in 59% of sera by Diamedix. IgM was also detected in a large proportion of sera from subjects with established HSV-2 infection (33% by BioPlex and 29% by Diamedix). Addition of IgM testing substantially increased the ability to detect seroconversion early in infection. IgM is an indicator of recent infection only in subjects who lack detectable IgG.

Antibodies, Viral↗

Baculovirus expression and antigenic characterization of the capsid proteins of three Norwalk-like viruses.

Human caliciviruses (HuCVs) are antigenically diverse. The antigenic relationships among different HuCVs have been difficult to study because HuCVs cannot be passaged in the laboratory. In this study, we describe cloning, sequencing and expression of the viral capsid proteins of three HuCVs that were identified in outbreaks of acute gastroenteritis in Virginia in 1997-1998. Yields of the capsid proteins similar to previously expressed recombinant Norwalk virus were obtained using the baculovirus expression system. Recombinant VA97207 capsid protein (rVA97207) and rVA98387, but not rVA98115, formed virus-like particles (VLPs). All three recombinant capsid antigens detected seroresponses in patients involved in outbreaks of acute gastroenteritis associated with genetically homologous or related HuCVs. The antigenic relationships of the three strains were further characterized using hyperimmune antisera against the three capsid antigens as well as four previously characterized recombinant capsid antigens of Norwalk (rNV), Mexico (rMxV), Hawaii (rHV), and Grimsby viruses (rGrV). VA98387 shared 98% aa identity with GrV; rVA98387 was detected by antisera to GrV. VA98115 shared 87% aa identity with Desert Storm virus and 65% aa identity with prototype Norwalk virus (NV); rVA98115 reacted weakly with NV antisera. VA97207 shared 80% aa identity with Amsterdam and 75% aa identity with Leeds strains and rVA97207 was not detected by any of the heterologous antibodies. In conclusion, VA97207 and VA98115 may belong to CV antigenic types not previously expressed, while VA98387 is a GrV-like virus. Low levels of cross-reactive antibodies were detected between types. Further studies to characterize these antigens and to develop enzyme immune assays (EIAs) for these strains are in progress.

Animals↗

Vagal nerve stimulation: adjustments to reduce painful side effects.

Vagal nerve stimulation is an approved adjunctive treatment for medically intractable epilepsy. Although it is generally well tolerated, some patients experience pain, coughing, or hoarseness during stimulation. Lowering the pulse width in these patients alleviates pain and reduces voice alteration without loss of efficacy. This allows more optimal programming of stimulation intensities.

Adult↗

Characterisation of gene expression changes following permanent MCAO in the rat using subtractive hybridisation.

Failure of several putative neuroprotectants in large multicentred clinical trials has re-focussed attention on the predictability of pre-clinical animal models of stroke. Model characterisation and relationship to heterogeneous patient sub-groups remains of paramount importance. Information gained from magnetic resonance imaging (MRI) signatures indicates that the Zea Longa model of rat middle cerebral artery occlusion may be more representative of slowly evolving infarcts. Understanding the molecular changes over several hours following cerebral ischaemia will allow detailed characterisation of the adaptive response to brain injury. Using a fully characterised model of Zea Longa middle cerebral artery occlusion we have used the representational difference analysis (RDA) subtractive hybridisation method to identify transcripts that accumulate in the ischaemic cortex. Along with a number of established ischaemia-induced gene products (including MCP-1, TIMP-1, hsp 70) we were also able to identify nine genes which have not previously been shown to accumulate following focal ischaemia (including SOCS-3, GADD45gamma, Xin).

Animals↗

Quantification of urinary excretion of ethosuximide enantiomers and their major metabolites in the rat.

A chiral gas chromatographic assay has been developed for quantitative analysis of ethosuximide and its major metabolites in rat urine. The extraction procedure was found to be precise and reproducible. Recovery was in the range of 94-98%, intraday CV(%) was 0.92% for (S)-ethosuximide (50 microg/ml) and 0.51% for (R)-ethosuximide (50 microg/ml). Interday CV(%) was 1.12% for (S)-ethosuximide and 0.72% for (R)-ethosuximide. The limit of detection was determined to be around 0.01 microg/ml for each enantiomer. Following administration of rac-ethosuximide by i.v., i.p. and oral routes, unchanged ethosuximide was detected in urine up to 72 h after drug administration. The appearance of all detected metabolites occurred within 24 h of drug administration. Significantly more (S)-ethosuximide was excreted unchanged than (R)-ethosuximide with all three routes studied. A substantial amount of the drug was eliminated as the 2-(1-hydroxyethyl)-2-methylsuccinimide (2 pairs of diastereoisomers). Much less drug was eliminated as the 2-ethyl-3-hydroxy-2-methylsuccinimide with only one diastereoisomer observed. Examination of the one pair of diastereoisomers of 2-(1-hydroxyethyl)-2-methylsuccinimide that was resolved showed preferential excretion of one isomer. Comparison of both pairs of diastereoisomers showed that one pair was formed in preference to the other with a ratio of approximately 0.8:1. It is concluded that stereoselective metabolism of ethosuximide occurs.

Animals↗

The Morehouse Faculty Development Program: methods and 3-year outcomes.

BACKGROUND AND OBJECTIVES: Faculty development is an established method for increasing the number and effectiveness of faculty in family medicine. However, few published studies focus specifically on the use of faculty development to increase minority representation among faculty. Underrepresented minorities comprise 20% of the nation's population but only 3% of medical school faculty. In the entire nation, only 52 full-time teachers of family medicine are African-Americans. Morehouse School of Medicine has developed an effective model for training large numbers of underrepresented minority physicians to become academic family physicians. From 1993-1996, we trained 23 community-based physicians, three new faculty, six existing faculty, and three full-time fellows as teachers of family medicine. Of 35 participants, 33 were underrepresented minorities. Cultural issues in teaching and communication are an integral part of the curriculum. Seventy-three percent of graduates now teach medical students or residents either full-time or part-time. Further studies are needed to test the replicability of this model in non-minority institutions, as well as to achieve greater cost-effectiveness and improve academic outcomes such as publications and research. Significant faculty diversity is necessary and achievable, if institutions are willing to commit significant resources and network with minority health professionals and institutions.

Black or African American↗

Survival and risk factors for death after cardiac transplantation in infants. A multi-institutional study. The Pediatric Heart Transplant Study.

BACKGROUND: Despite the increasing application of cardiac transplantation in infants, reported survival rates vary, and risk factors for death are poorly understood. METHODS AND RESULTS: To examine early survival and risk factors for death in infants (< 1 year of age) undergoing cardiac transplantation, 141 infants (36 < 1 months of age) underwent primary cardiac transplantation between January 1, 1993, and January 1, 1995, at 23 centers in the Pediatric Heart Transplant Study (PHTS). Diagnoses were hypoplastic left heart syndrome (66%), other congenital heart disease (17%), cardiomyopathy (14%), and other (3%). Actuarial survival after cardiac transplantation was 84% at 1 month, 70% at 1 year, and 69% at 2 years, with the greatest hazard for death within the first 3 months. The principal cause of death was early graft failure in 20 patients (52% of deaths), infection in 10 (26% of deaths), and rejection in 4 (10%). On the basis of multivariate analysis, risk factors for early mortality were history of previous sternotomy (P = .0003), nonidentical blood type donor (P = .01), recipient non-blood group A (P = .02), and donor cause of death other than closed head trauma (P = .04). Diagnosis at listing, waiting time (mean, 1.3 months), graft ischemic time (mean, 228 minutes; range, 68 to 479 minutes), and recipient ventilatory or inotropic support at listing were not predictive for mortality after transplant. CONCLUSIONS: The higher mortality rate observed with infant heart transplantation is due to a higher mortality within the first month after transplantation as a result of early graft failure. Strategies to improve donor heart function at implantation would have the greatest impact on survival after infant cardiac transplantation.

Actuarial Analysis↗

Structural features of collapsin required for biological activity and distribution of binding sites in the developing chick.

We have used Fc-chimeras of collapsin-1/Sema III to study the structure-function activity of this recently identified repulsive axonal guidance molecule and to map the distribution of its binding sites during chick development. Our results show that the biological activity of the collapsin-Fc in an in vitro collapse assay is independent of both the Ig-domain and the positive charged carboxy terminus. Collapsin binding sites were found on a number of neuronal fiber tracts, and in two instances (DRG tracts and the retinotectal projection) this expression is both highly dynamic and consistent with them playing a role in axonal growth and guidance. Collapsin-1 binding sites were also found on a number of nonneuronal structures that do not produce collapsin-1 mRNA. We postulate that these sites may act to localize or concentrate collapsin-1 released from growing axons and in this way allow for an autocrine axonal guidance mechanism to function during development.

Animals↗

Essential obstetric care: assessment and determinants of quality.

This paper reports on a study to develop and to apply methods for measuring the quality of essential obstetric care (EOC) in health centers. Based on a Nigerian guideline and an international guideline, and in consultation with local experts in primary care obstetrics, norms were established for equipment, personnel, supplies and the process of EOC, focusing on critical tasks. A combination of assessment methods was used, including observation of tasks performed during intrapartum care; use of data from records of care kept by midwives during the period of observation; use of data from records kept by midwives in the calendar year preceding the period of observation; exit interviews with clients; and inventories of equipment and supplies. Twelve health centers in three Local Government Areas (LGAs) and 360 clients in labor were included in the study. Quality of care was measured quantitatively as a score, calculated for each task and for each delivery in the health center. The results show that the methods developed are useful for: identifying quality score differences among health centers, and the effects of methods of assessment on quality scores; identifying aspects of EOC requiring improvements within each health center; and identifying factors influencing the quality of care, as a basis for effective quality improvement efforts. Regression models show that the most consistent and important predictor of quality scores is the use of printed forms (i.e. routine records of labor) during intrapartum care. Printed forms served as job aids, providing prompts that reminded midwives to perform specific tasks.

Female↗

Introducing quality management into primary health care services in Uganda.

In 1994, a national quality assurance programme was established in Uganda to strengthen district-level management of primary health care services. Within 18 months both objective and subjective improvements in the quality of services had been observed. In the examples documented here, there was a major reduction in maternal mortality among pregnant women referred to Jinja District Hospital, a reduction in waiting times and increased patient satisfaction at Masaka District Hospital, and a marked reduction in reported cases of measles in Arua District. Beyond these quantitative improvements, increased morale of district health team members, improved satisfaction among patients, and greater involvement of local government in the decisions of district health committees have been observed. At the central level, the increased coordination of activities has led to new guidelines for financial management and the procurement of supplies. District quality management workshops followed up by regular support visits from the Ministry of Health headquarters have led to a greater understanding by central staff of the issues faced at the district level. The quality assurance programme has also fostered improved coordination among national disease-control programmes. Difficulties encountered at the central level have included delays in carrying out district support visits and the failure to provide appropriate support. At the district level, some health teams tackled problems over which they had little control or which were overly complex; others lacked the management capacity for problem solving.

Child↗

The prognostic factors in the prenatal diagnosis of the echogenic fetal lung.

The prenatal diagnosis of an echogenic fetal lung (EFL) is now often made in the early second trimester using high-resolution ultrasound. This ultrasound appearance is usually caused by a congenital cystic adenomatoid lung malformation (CCAM), an intrapulmonary lung sequestration or obstruction of a major airway. In order to provide prognostic guidelines to parents who may be considering termination of a fetus with these findings, we have analysed a series of 11 cases diagnosed in our centre over the past 2 years in conjunction with 60 cases from major published series. The data suggest that in the absence of non-immune hydrops fetalis (NIHF) or other anomalies, the outcome for the fetuses is excellent, with over 90 per cent survival. Neither early diagnosis (24 weeks) nor the presence of mediastinal shift is a poor prognostic indicator. In addition, it appears that if NIHF is absent at diagnosis, the chance that it will develop as the pregnancy continues is small (6 per cent). Furthermore, there is a significant (up to 30 per cent) chance that this ultrasound finding will resolve in utero. The development of in utero fetal surgical techniques may be the only hope for those hydropic fetuses who appear to have a dismal prognosis.

Bronchopulmonary Sequestration↗

Value of faecal alpha-1-antitrypsin, haemoglobin and a chemical occult blood test in the detection of gastrointestinal disease.

Specimens from hospital out-patients and in-patients sent for faecal occult blood tests were also analysed for faecal alpha-1-antitrypsin and faecal haemoglobin. 453 stool specimens from 222 patients were analysed. The clinicians were only aware of the faecal occult blood test results, and diagnoses were made using conventional clinical and investigative criteria. Gastrointestinal bleeding or putative sites of bleeding were diagnosed in 98 patients, whereas in 81 patients putative sites of bleeding were not found or other cause of anaemia diagnosed. In 41 patients there was insufficient information to reach a definitive diagnosis. Comparison of the 3 faecal tests using these grouping methods showed that faecal alpha-1-antitrypsin performed best, with an accuracy of 89%, specificity of 90% and sensitivity of 88%, all significantly better (P < 0.001) than the faecal occult blood test (68%, 60% and 73%, respectively). There was no significant difference between the performance of the faecal occult blood and faecal haemoglobin tests. Faecal alpha-1-antitrypsin measurement may be a useful investigation in situations where a faecal occult blood test would normally be requested.

Adolescent↗