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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 685 records · Page 38Linked to original sources

Immunohistochemical evaluation of the developing outflow tract in the rat: achieving aortic to mitral fibrous continuity.

OBJECTIVES: To study the development of aortic to mitral fibrous continuity in the normal rat heart. METHODS: The hearts and great vessels of normally developed rat embryos and fetuses aged between 13.25 and 19.75 days of gestation were studied in conjunction with those of newborns aged 2 and 7 days post-partum. Standard histological methods and monoclonal antibodies raised against alpha smooth muscle actin (clone 1A4) and ventricular beta myosin heavy chain were used to demonstrate the ventricular outlets, ventriculo-arterial junction, inner heart curve and aortic infundibulum from the early stages of aortopulmonary septation to attainment of their definitive morphology. RESULTS: The two antibodies demonstrated temporal specificity (actin specificity increased post-partum; myosin specificity maximal during fetal period) in the labelling of their intended structures which correlated with their known developmental profile. Full-thickness fibrous continuity between aortic and mitral valves was not complete until 1 week after birth. After ventricular septation was complete, and thereafter towards the end of fetal life and beyond, separation was maintained by a muscular structure histologically identical to the vestigial netro-aortic root branch of the conduction tissue, a structure known to be derived from the primitive ventricular myocardium within the environs of the inner heart curve. CONCLUSIONS: Ventricular septation (occurring relatively early) and the attainment of fibrous continuity (occurring relatively late in development) are two independent processes. Muscular tissue separating left-sided arterial and atrioventricular valves is not derived from the aortic infundibulum but from the inner heart curve. Persistence of this structure is a feature of normal rat heart development and needs to be recognised when working with rodent-based animal models of congenital heart disease aimed at studying the disruption of the development of the ventricular outflow tracts.

Actins↗

Carbon dioxide volume and intra-abdominal pressure determination before the creation of a pneumoperitoneum.

Laparoscopic surgery generally is regarded as a safe procedure when a preset pressure is used in the carbon dioxide insufflator. However, a fixed pressure setting is not appropriate when insufflating a very large or a very small abdomen. Presently, extrapolation from the commonly used 15 mm Hg to an appropriate and safe pressure cannot be easily determined except by a crude trial and error method. We developed an anthropometric formula to calculate the total abdominal cavity capacity and the corresponding pressure necessary to obtain safe pneumoperitoneum. This anthropometric formula calculates the total abdominal capacity by measuring one diameter from the symphysis pubis to the xyphoid bone, a second diameter as half the initial measurement, and a third diameter by dividing the waist measurement (minus an estimated percentage of body fat) and dividing that product by pi. The product of the three diameters is then multiplied by a constant (K = 0.5). We studied prospectively 20 patients whose indications for laparoscopic surgery necessitated creation of a pneumoperitoneum. The patients were divided into two groups: group A (n = 10), patients who were observed with the intra-abdominal pressure fixed at 15 mm Hg while recording the amount of distension produced in the abdominal cavity during creation of the pneumoperitoneum; and group B (n = 10) in whom pneumoperitoneum was obtained based on the initial volume of carbon dioxide-insufflation previously calculated using our formula. Based on our observations, we conclude that this anthropometric formula can be used successfully in predicting a safe level of insufflation in relation to the patient's size.

Abdomen↗

Addressing domestic violence in the African American community.

This paper focuses on the problem of spouse abuse in the African American community and discusses intervention programs designed to reduce domestic violence. The problem of domestic violence is not new. However, there is increased concern about it, such that the criminal justice system has changed its policy toward this act. This policy considers domestic violence a crime, and arrest the most efficient way to prevent it. Further, providing counseling programs to men is one of the efforts some criminal justice departments are now using. The two programs discussed in this paper are programs used by the criminal justice system. They are designed to prevent repeated domestic violence by focusing on the education of conflict resolution to deal with anger, denial, and jealousy, and the development of interpersonal skills that assist in channeling anger and poor interpersonal communication into positive modes of conduct. Some characteristics of batterers are noted.

Adult↗

The utility of the CCK DISIDA scan in the treatment of occult biliary tract disease.

The vast majority of biliary tract disease is correlated with calculi, and the diagnosis of biliary disease is made simpler when calculi are detected. There are good screening studies for the detection of calculi; however, a reproducible objective test for biliary tract disease in the absence of gallstones has been lacking. Occult biliary tract disease should be considered when symptoms typical of biliary tract disease are present, gallstones cannot be demonstrated, and other diseases have been ruled out. This is characteristically a diagnosis of exclusion, with only the subjective criteria of pain relief to validate surgical intervention. Recently, we have used a nuclear medicine test that simulates the gallbladder response to normal postprandial physiologic stress, to study in an objective fashion the gallbladder function of a group of patients who have symptoms typical of biliary tract disease, but no demonstrable calculi. We have found that the CCK DISIDA study has correlated well with occult pathology. The experience at Easton Hospital has confirmed that the CCK augmented DISIDA scan with calculation of ejection fraction is a reasonably accurate study, with a sensitivity of 88% in detecting previously suspected but undemonstrable pathology in this selected population. This corresponds closely to the observed finding that the pathology reports of 77% of the resected gallbladders noted some abnormality. Of further interest is the long term symptomatic relief achieved in 85% of the patients available for follow up interviews, including a symptomatic benefit in eight of the 11 patients with a normal pathology report.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Immunisation against hepatitis B viral infection--a study of South African anaesthesiologists.

INTRODUCTION: The practice of anaesthesia involves exposure to blood or bloodstained secretions which may be contaminated with transmissible pathogens including the hepatitis B virus (HBV). This study was undertaken to assess the impact of freely available hepatitis B vaccine and applications of universal precautions against blood exposure on the uptake of immunisation and prevalence of HBV markers in South Africa anaesthesiologists. METHODS: Anaesthesiologists from the Department of Anaesthesia of the University of Natal and those attending a continuing medical education course in Cape Town in March 1993 participated in the study. Each participant completed a questionnaire giving details of previous exposure to HBV, immunisation status and details of immunisation. Blood samples were obtained on a voluntary basis for determination of HBV serology. RESULTS: One hundred and twenty-one anaesthesiologists participated in the study; 36 were unimmunised, of whom 18 (50%) were seropositive for HBV markers. More experienced anaesthesiologists (> 10 years) tended both not to be immunised and to be seropositive, indicating previous exposure to HBV. Eighty-five participants were immunised. Intradermal immunisation caused significantly less seroconversion than the intramuscular route (35% v. 81%; P < 0.05). Of 7 non-responders to intradermal immunisation, 5 responded to a single intramuscular booster injection. DISCUSSION: Exposure to HBV is common in anaesthetic practice, as evinced by the 50% seropositivity in unimmunised anaesthesiologists, which means that routine serological testing before immunisation is warranted. Intramuscular immunisation provides the best protection against HBV. Post-immunisation serological testing should be performed to demonstrate an adequate antibody response. The intradermal route may save cost with similar efficacy if combined with post-immunisation testing and a single intramuscular booster injection for non-responders.

Anesthesiology↗

Seeing the light.

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Computer Terminals↗

Common arterial trunk and pulmonary atresia: close developmental cousins? results from a teratogen induced animal model.

OBJECTIVES: To examine morphological similarities between "classically different" congenital heart lesion types induced in fetal rats by the cardiac teratogen N,N'-bis(dichloroacetyl)-1,8-octamethylenediamine (bis-diamine). METHODS: A single 200 mg oral dose of bis-diamine was given to 50 pregnant rats on the 9th gestational day. Eleven controls were fed an inert vehicle. Experimental and control rats were sacrificed from 15.4 days to term and embryos delivered by caesarean section. Age-matched embryos were processed for histology and sectioned at 7 microns. Cardiac morphology was compared between normal and bis-diamine exposed groups. RESULTS: Hearts from control embryos were morphologically normal. Those from bis-diamine treated embryos exhibited common arterial trunk (32%), overriding aortic valve with valvar pulmonary stenosis (40%) or infundibular atresia (4%), or ventricular septal defect (24%). Development of the outlet septum was affected in all hearts and the arterial duct was absent in 72% of cases. Whilst most hearts demonstrated the anatomy expected for their lesion, some with a common arterial valve demonstrated a pulmonary blood supply similar to that in human cases of pulmonary atresia, where, in the absence of an arterial duct, an essential systemic to pulmonary conduit was provided by a "persistent fifth aortic arch artery". In one such case the proximal part of the aortopulmonary septum was identified above a common valve. The septum was deviated to the left and was not continuous throughout the length of the arterial trunk, causing atresia of the pulmonary component. Others had muscular infundibular atresia but with a pulmonary blood supply arising directly from the solitary trunk as seen in common arterial trunk "type III". CONCLUSIONS: Bis-diamine consistently affects development of those structures which partition the arterial segment of the developing heart at one or more levels, often coexistent with agenesis of the sixth aortic arch arteries. Whilst the aortopulmonary and outlet septums were absent in most cases of common arterial trunk, some morphological duality was shared by classically different lesion types in these rat hearts, which may suggest a common aetiology for common arterial trunk "type III" and aortic overriding with absence of the outlet septum and pulmonary atresia.

Abnormalities, Drug-Induced↗

A variety of genetic mechanisms are associated with the Prader-Willi syndrome.

An extensive set of chromosome 15 DNA polymorphisms and densitometric analysis with four markers mapping to the Prader-Willi chromosome region (PWCR) of chromosome 15 have been used to characterize a cohort of 30 subjects with classical Prader-Willi syndrome (PWS). Molecular analysis enabled the classification of the PWS subjects into four groups: (A) 18 subjects (60%) had deletions of paternal 15q11-13 involving a common set of DNA markers. Two subjects had differently sized deletions, one larger and one smaller than the other cases. (B) Eight (27%) had maternal uniparental disomy for chromosome 15. (C) One (3%) had a marker chromosome carrying an extra copy of the PWCR. The marker chromosome was demonstrated to be of paternal origin and the two intact chromosomes were maternally derived. This case represents an apparent exception to the generally held view that PWS is associated with an absence of paternally inherited gene(s) located in the PWCR. (D) The remaining three cases (10%) had none of the above abnormalities. This last subgroup of patients has not previously been well characterized but could represent limited deletions not detectable with the markers used or abnormalities in the imprinting process. These cases represent potentially valuable resources to elucidate more precisely the fundamental disorders responsible for PWS.

Adolescent↗

Search for linkage to schizophrenia on the X and Y chromosomes.

Markers for X chromosome loci were used in linkage studies of a large group of small families (n = 126) with at least two schizophrenic members in one sibship. Based on the hypothesis that a gene for schizophrenia could be X-Y linked, with homologous loci on both X and Y, our analyses included all families regardless of the pattern of familial inheritance. Lod scores were computed with both standard X-linked and a novel X-Y model, and sib-pair analyses were performed for all markers examining the sharing of maternal alleles. Small positive lod scores were obtained for loci pericentromeric, from Xp11.4 to Xq12. Lod scores were also computed separately in families selected for evidence of maternal inheritance and absence of male to male transmission of psychosis. The lod score for linkage to the locus DXS7 reached a maximum of 1.83 at 0.08% recombination, assuming dominant inheritance on the X chromosome in these families (n = 34). Further investigation of the X-Y homologous gene hypothesis focussing on this region is warranted.

Chromosome Mapping↗

Dicistronic targeting constructs: reporters and modifiers of mammalian gene expression.

To investigate the activity of candidate regulatory molecules in mammalian embryogenesis, we have developed a general strategy for modifying and reporting resident chromosomal gene expression. The picornaviral internal ribosome-entry site was incorporated into gene targeting constructs to provide cap-independent translation of a selectable marker from fusion transcripts generated following homologous recombination. These promoterless constructs were highly efficient and have been used both to inactivate the stem-cell-specific transcription factor Oct-4 and to introduce a quantitative regulatory modification into the gene for a stem-cell maintenance factor, differentiation-inhibiting activity. In addition, the inclusion of a beta-galactosidase reporter gene in the constructs enabled accurate and sensitive detection of cellular sites of transcription. This has allowed visualization of putative "stem-cell niches" in which sources of elevated expression of differentiation-inhibiting activity were localized to the differentiated cells surrounding colonies of stem cells.

Animals↗

The use of fluorescence in-situ hybridisation to clarify abnormal Y chromosomes in two infertile men.

OBJECTIVE: To characterise the structurally abnormal Y chromosomes present in two infertile men by means of the molecular technique of fluorescence in-situ hybridisation (FISH). METHODS: Both men were phenotypically normal and had azoospermia. In Case 1 the karyotype with routine cytogenetics was 46,XX; in Case 2 it was complex, with 3 cell lines--45,X/46,X,i(Yp)/46,X,+?del(Y)(q11). We used probes from the Y chromosome and FISH to clarify these karyotypes. RESULTS: In Case 1 a translocation of Y chromosome to the X chromosome was identified with FISH--t(X;Y). In Case 2, an isochromosome of the short arm of the Y chromosome was confirmed in one cell line, and another cell line was shown to contain a small Y chromosome with heterochromatic deletion. These findings explained the underlying pathogenesis in both cases. CONCLUSIONS: Molecular investigation with FISH should become part of the routine investigation of infertile men with an abnormal Y chromosome.

Adult↗

Novel karyotype in the Ullrich-Turner syndrome--45,X/46,X,r(X)/46,X, dic(X)--investigated with fluorescence in situ hybridization.

A 10-year-old girl with Ullrich-Turner syndrome was found to have the novel karyotype 45,X/46,X,r(X)(p11q11)/46,X,dic(X)(p11). Fluorescence in situ hybridization (FISH) with the alpha satellite X centromere probe established the origin of the small ring chromosome. Scanning a large number of cells by interphase FISH showed that the dicentric (X) was the least prevalent cell line. The common breakpoint of Xp11 suggests a sequence of errors as the mechanism whereby these 3 distinct cell lines have arisen.

Cells, Cultured↗

The provision of oral surgery services in England and Wales 1984-1991.

Data from the Department of Health and the Dental Practice Board demonstrate substantial increases in the volume of oral surgery performed in England and Wales both in the General Dental and Hospital Services during the period 1984-1991. In the General Dental Service, although the number of routine extractions decreased by 10%, the number of surgical procedures increased by 20%, with a substantial increase (33%) in the number of third molar extractions in the period 1988-1991. There have been no decreases in the annual rate of extractions of permanent and deciduous teeth in the GDS since 1987. In at least one Regional Health Authority, there was a five-fold increase in the number of oral surgery patients aged 0-9 years treated in the hospital service (1982-1991). Overall, although this study takes no account of extractions carried out in the Community Service, these findings suggest that numbers of deciduous extractions may have actually risen in some areas, particularly after 1987. In the Hospital Service there was a 55% increase in numbers of day-cases, from 30,090 (1984) to 46,499 (1990); a 10% increase in throughput of in-patients and a 13% decrease in numbers of people waiting for in-patient surgery. These changes were in the same direction as those in plastic and ENT surgery; though plastic surgery achieved a greater utilisation of day-care services. The implications of these changes and their possible effect on the future provision of oral and maxillofacial surgery services are discussed.

Apicoectomy↗

Glutathione S-transferase GSTM1 phenotypes and protection against cutaneous tumours.

Multiple allelism at loci encoding detoxicating enzymes is associated with cancer risk. We have studied genetic variation at the glutathione S-transferase GSTM1 locus to see whether phenotypes confer altered susceptibility to basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma (MM), or multiple skin tumours of different histological types. The frequency of GSTM1 null in cases and controls (52%) was similar, except for patients with two or more tumours of different types (71%, p = 0.033). GSTM1 A/B was reduced in frequency (p < 0.05) in patients with single or multiple BCC. Thus GSTM1 A/B may be protective, and effectiveness of detoxication may be a factor determining susceptibility to skin cancer.

Aged↗

Isolation and characterization of the mouse heme oxygenase-1 gene. Distal 5' sequences are required for induction by heme or heavy metals.

Mouse genomic fragments encoding heme oxygenase-1 (HO-1) were isolated from a recombinant lambda library by in situ plaque hybridization. The mouse HO-1 gene, approximately 7 kilobase pairs (kbp) in length, is organized into 5 exons and 4 introns. The primary structure of the exons and 1287 base pairs (bp) of the 5'-flanking region was determined. The deduced amino acid sequence of the mouse HO-1 gene is identical to that of p32, initially identified as a stress-induced protein in mouse BALBc/3T3 cells. A single, major transcription initiation site is utilized for constitutive and heme- or metal-induced expression of the HO-1 gene in mouse hepatoma (Hepa) cells. The transcriptional activity of the 5'-flanking region was examined by transient expression assays using the chloramphenicol acetyltransferase gene as the reporter gene. Basal promoter activity in several cell lines was localized to within 149 bp of the upstream sequence by deletion analysis. This proximal promoter region of the mouse HO-1 gene contains several sequence elements that are not only conserved in both the rat and human HO-1 genes but also resemble consensus binding sites of various transcription factors including AP-1, AP-4, C/EBP and c-Myc:Max/USF. Heavy metals activate HO-1 gene transcription and the rat gene contains a putative metal regulatory element (Müller, R. M., Taguchi, H., and Shibahara, S. (1987) J. Biol. Chem. 262, 6795-6802) that is completely conserved in the mouse gene. Transient expression analyses, however, indicate that this sequence, which contains a core heptanucleotide, TGCACTC, identical to that of the strongest metal regulatory element of the mouse metallothionein-1 gene, is not responsive to Cd2+ or Zn2+. Stable transfection of constructs containing the entire mouse HO-1 gene and various portions of the 5'-flanking region into rat C6 glioma cells and simultaneous, quantitative analysis of the mouse and rat HO-1 mRNAs indicate that distal 5' sequences, between positions -3.5 and -12.5 kbp, are required for induction of mouse HO-1 gene transcription by both heme and heavy metals. A 5-7-fold difference in the levels of induction between stably integrated and transiently expressed mouse HO-1 gene constructs is observed in this cell line.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗