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Biomedical subjects

T Heath

Publications and source records attributed to T Heath.

At least 19 recordsLinked to original sources

Pertussis vaccines: past, present and future in Australia.

In August 1997, a workshop was convened by the National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases to consider current issues in the use of pertussis vaccines and implications for the Australian immunisation schedule. Topics covered included the history, efficacy and reactogenicity of whole-cell and acellular vaccines and vaccine schedules. Acellular pertussis vaccine is preferred by the National Health and Medical Research Council for the primary course as well as the 18 month and 4-5 year old childhood doses. At the time of the workshop, a 3-component acellular vaccine (DTPa) had been approved (licensed) in Australia for all doses in the childhood schedule. It was the first vaccine subject to a cost-effectiveness evaluation under the new vaccine funding arrangements. Issues considered in the evaluation of the cost-effectiveness of the vaccine were discussed. These included comparative efficacy, adverse events and compliance, and the question of community as well as individual benefit from the use of the vaccine.

Australia

Pathways of interstitial fluid and lymph flow in the liver acinus of the sheep and mouse.

In the acinus of the sheep and mouse liver, lymphatic vessels are restricted to the portal tracts. Vessels less than about 25 microm across form a network around portal venules, and are closely associated with the limiting plate of hepatocytes. The perisinusoidal space of Disse is continuous with the interstitial space of the portal tracts at the origin of the sinusoids. It seems likely that excess interstitial fluid derived from the sinusoids flows along the perisinusoidal space of Disse to enter the portal tracts near the portal venules, and then enters the small lymphatics which lie adjacent to those venules. It then enters the larger vessels, which are adjacent to hepatic arterioles and bile ductules.

Animals

A community-wide hepatitis A outbreak in the Shoalhaven region, New South Wales.

We investigated a community-wide outbreak of hepatitis A virus infection in the Shoalhaven region of the New South Wales south coast. Epidemiological features of the outbreak suggested that transmission was predominantly person-to-person. These included: the prolonged course of the epidemic, the bimodal age-specific attack rate, the lower socioeconomic risk groups affected, and the large proportion of cases who reported prior contact with another case. Although widespread use of post-exposure immunoprophylaxis appeared to be effective in preventing symptomatic infection in individuals, it did not rapidly halt the outbreak. We review methods of mass intervention for community-wide outbreaks of hepatitis A virus infection, and define priorities for investigation of future outbreaks.

Disease Outbreaks

Lymph pathways associated with three types of follicle structure found in gut-associated lymphoid tissue of horse ileum.

In the horse ileum, lacteals in the villi are continuous with prelymphatic intercellular channels and a plexus of lymphatic sinuses in the lamina propria that encircle the domes of the follicle/dome structures and proprial follicles. These sinuses may act as the major entry site for many of the lymphocytes migrating from gut-associated lymphoid tissue via the lymphatic system. Vessels from this plexus penetrate the muscularis mucosae and lymph flows into lymphatic vessels within the interfollicular tissue between the follicles of both follicle/dome structures and lymphoglandular complexes (LGCs). No lymphatic vessels leave the follicles, but intercellular pathways of the follicles are continuous with those in the surrounding interfollicular tissue and follicular sinuses around the base of the follicles. These pathways appear to provide the only available lymphatic route for lymphocytes leaving LGCs to enter the lymphatic system. Lymph from the interfollicular tissue enters deep submucosal lymphatic vessels, containing prominent valves, which drain into other vessels transporting lymph from the surface of the ileum.

Animals

Lymphoid tissues of the ileum in young horses: distribution, structure, and epithelium.

Lymphoid tissues in the ileum of young horses form raised plaques that are macroscopically visible from the mucosal surface. These are termed "ileal lymphoid patches". These patches are variable in size, shape and position within the ileal wall, occasionally lying along the site of mesenteric attachment. Within lymphoid patches, follicles exist in three different morphological forms: follicle/dome structures, proprial follicles, and lymphoglandular complexes (LGCs). In follicle/dome structures, the majority of the follicle lies in the submucosa and merges with a dome in the lamina propria through a gap in the muscularis mucosae. In proprial follicles, the majority, or all, of the follicle is found in the lamina propria, and in LGCs, the follicles lie in the submucosa and communicate with the intestinal lumen via a central invagination of epithelium that extends vertically through a gap in the muscularis mucosae. Follicle-associated epithelium covers the follicle/dome structures and proprial follicles. It consists of enterocytes, cells morphologically resembling M cells, intraepithelial lymphocytes, goblet cells, and amine-precursor uptake and decarboxylation (APUD) cells. The epithelium of LGCs is mainly populated by immature enterocytes, intraepithelial lymphocytes and goblet cells. Cells with coarse, long microvilli are also present. Information regarding the presence of LGCs in the small intestine is scant, but LGCs have been well described in the large intestine of many species. Further investigation will be required to determine if factors exist that are common to both the ileum of the horse and the large intestine of other species to influence the development of LGCs at these specific sites.

Animals

Segmented filamentous bacteria associated with lymphoid tissues in the ileum of horses.

Segmented filamentous bacteria preferentially attached to the follicle-associated epithelium overlying the lymphoid tissue in samples of the terminal ileum from seven horses examined by scanning electron microscopy. The bacteria adhered to the apical membrane of the enterocytes by a holdfast segment. Each filament tended to be of uniform diameter, but the filaments ranged from 0.7 to 1.4 microns in diameter. The bacteria were usually absent from the adjacent villous epithelium.

Animals

Nosocomial and community-acquired Xanthomonas maltophilia infection in tropical Australia.

Xanthomonas maltophilia infection is recognized as a serious problem in association with immunosuppressive and invasive therapies, and with the use of broad-spectrum antibiotics. In Darwin Hospital in Australia's Northern Territory preliminary evidence of nosocomial transmission of X. maltophilia prompted this retrospective examination of all X. maltophilia isolates over a 30 month period. X. maltophilia was most frequently isolated in the 'wet season' corresponding to times of increased antibiotic treatment of the serious community-acquired pneumonias encountered in this tropical region. A relatively high proportion of community-acquired isolates (4/18; 22%) was documented. This study demonstrates that X. maltophilia infection is an emerging cause of morbidity in tropical regions where endemic infections require the use of broad-spectrum beta-lactams.

Adolescent

Ileal Peyer's patches in pigs: intercellular and lymphatic pathways.

BACKGROUND: The lymphatics of Peyer's patches disseminate immunological information from the gut and thus play a key role in protection of the body against environmental pathogens. The aim of this project was to describe the lymphatic pathways of these Peyer's patches in pigs, and the mucosal intercellular spaces which lead to these lymphatics. METHODS: Ileal tissue from living or freshly killed pigs was examined by light microscopy or electron microscopy, or was injected with Mercox (CL-2B, Japan Vilene Hospital, Tokyo) for scanning electron microscopy of corrosion casts. RESULTS: Intercellular fluid between intestinal epithelial cells passes through pores in the basal lamina to mix with that in the intercellular spaces and prelymphatic intercellular channels of the lamina propria and follicle domes. From there, lymph enters lacteals in the villi, or a branching network of vessels within the lamina propria. Small lymphatics penetrate the muscularis mucosae and are continuous with (1) lymphatic vessels which pass directly to the deep submucosa between follicles, or (2) lymphatic sinuses which lie adjacent to the follicles. This differs from the situation in sheep and rabbits. Basal lymphatics beneath the follicles convey lymph to vessels which leave the surface at the serosa. CONCLUSION: The differences in the structure and arrangement of the lymphatics of Peyer's patches between pigs, sheep, and rabbits will require further investigation to determine if such variation between species has an effect on the distribution of immune products to effector sites.

Animals

Lymphatic drainage from the distal small intestine in sheep.

Lymphatic drainage from the wall of the distal small intestine, important especially in young sheep as a major site of gut-associated lymphoid tissue, begins with a series of longitudinally oriented subserosal vessels. These vessels convey lymph to the mesenteric border of the intestinal wall and unite to form larger vessels which course through the mesentery to the mesenteric lymph nodes. These nodes lie towards the periphery of a broad, fan-shaped mesentery, adjacent to major arteries and veins. Mesenteric vessels convey lymph from the jejunum and part of the proximal ileum to the jejunal nodes. Lymph from most of the ileum is conveyed to caecal nodes. The larger mesenteric lymphatics have well formed smooth muscle and connective tissue layers surrounding the endothelium. They are often adjacent to, but rarely within, the connective tissue band anchoring the major arteries and veins to one or both lamellae of mesentery. Few anastomoses occur between vessels from opposing sides of the gut wall or the mesentery. Afferent lymphatics enter the subcapsular and trabecular sinuses of the nodes over most surfaces apart from the hilar region. Lymph flows through cortical tissue to the medulla, which occupies most of the node. In the medulla, sinuses occur within medullary cords as well as between them. Initial efferent lymphatics occur throughout medullary tissue. Efferent vessels emerge at a hilus then coalesce and drain into the jejunal or ileal trunk. The hilus of the node varies from a flat, poorly defined area on the lesser curvature, to a depression or groove. The latter commonly occurs in elongated jejunal nodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Lymph pathways associated with Peyer's patches in sheep.

Lymphatic drainage of the ileum associated with Peyer's patches begins with lymph entering a single lacteal of the villus, probably through intercellular flaps, which prevent retrograde flow to the interstitium. These lacteals are continuous with an interconnecting plexus of branching sinuses which surrounds the crypts and follicle domes in the lamina propria. Small vessels emanating from this plexus penetrate the muscularis mucosa, where lymph can either flow within septal vessels to the deep submucosa, or enter the follicular sinuses to move freely around follicles, and through gaps in septal walls. All lymph enters a deep submucosal network where retrograde flow is prevented by valves. Lymph is then conveyed through vessels passing between the fibres of the muscularis externa to other lymphatics, which transport lymph from the ileal surface to the mesenteric nodes.

Animals

Pulmonary intravascular macrophages and hemodynamic effects of liposomes in sheep.

We studied the effects of liposomes on the pulmonary circulation of sheep and found a close correlation between liposome retention in the lung and the intravascular macrophages. A test dose of liposomes (5.5 mumol of total lipids) injected intravenously transiently increased pulmonary arterial pressure from 24 +/- 2 to 55 +/- 16 (SD) cmH2O. The pulmonary arterial pressure responses were dose dependent and reproducible. The rise in pulmonary arterial pressure was blocked completely by indomethacin and 75% by a thromboxane synthase inhibitor. Systemic arterial thromboxane B2 concentration increased from a base-line level of less than 50 pg/ml to 250 +/- 130 pg/ml at the peak of the pressor response. Larger doses of liposomes (220 mumol of total lipids) infused intravenously over 1 h increased pulmonary arterial pressure maximally within the first 15 min. Lymph flow increased and lymph protein concentration decreased, suggesting venoconstriction. Over half (62.4 +/- 15.7%) of 111In-labeled liposomes remained in the lung after 2 h. Fluorescence and transmission electron microscopy showed that greater than 90% of the liposomes were associated with mononuclear cells in the lumen of the alveolar wall microvessels. We conclude that liposomes affect pulmonary arterial pressure transiently by a mechanism involving the arachidonate cascade, principally thromboxane. Our observations suggest that a population of pulmonary intravascular macrophages is likely to be the source of the thromboxane and the pulmonary hemodynamic and lymph dynamic changes that occur in a dose-dependent fashion, although interactions between liposomes, leukocytes, or endothelial cells, in addition to the macrophages, have not been completely ruled out. We believe this is the first demonstration that pulmonary intravascular macrophages may be the source of the arachidonate metabolites rather than endothelial cells, neutrophils, or perivascular interstitial cells.

Animals

Pathways of lymph flow through superficial inguinal lymph nodes in the pig.

The pig lymph node has an unusual structure in that tissue containing lymph nodules generally occupies a central position. Our aim was to describe the lymphatic pathways through this node. We studied the structure of these pathways with light and electron microscopy, made casts of lymphatic vessels and sinuses with Microfil, and studied the distribution within the node of subcutaneously injected carbon particles. Most afferent lymphatics penetrate deeply within the node, where they give off several branches to peritrabecular sinuses that ramify through centrally located nodular tissue. However, where an afferent lymphatic enters the node there is a subcapsular sinus over an area of nodular tissue that occupies a conventional superficial position. Some lymph reaches this sinus from the central peritrabecular sinuses, but there can also be direct communications between this sinus and the afferent lymphatic. After flowing through sinuses in nodular tissue, lymph enters tissue that is analogous to medullary tissue in other species. This tissue is of two types, one consisting mainly of a diffuse network of reticular cells around spaces up to 10-12 microns across, and one that more closely resembles conventional medullary tissue. Lymph then flows to collecting ducts, which lack valves, and then to efferent lymphatics. Our findings do not support suggestions that a purely physical obstruction of lymphocytes in the lymph node accounts for the dearth of lymphocytes in efferent lymph of pigs.

Animals

Arterial supply to the pig intestine: an unusual pattern in the mesentery.

The arrangement of arteries in the mesentery in pigs was studied with latex casts and light microscopy. Arterial arcades, which are characteristic of the mesentery in man and other species, are absent. Instead, a narrow band of numerous, anastomosing arteries gives rise to up to about 500 bundles of arteries and accompanying veins, which radiate out in the mesentery. Each bundle contains up to 30 arteries, but these recombine as they approach the jejunum, and form 1-4 arteriae rectae. The significance of the very large number of small arteries in the mesentery is not known, but they may play a role in the control of blood pressure in the intestinal wall, or as sites of countercurrent exchange.

Animals

New methodology for liposome targeting to specific cells.

The specificity of liposomes for different cell types was achieved by conjugation to monoclonal antibodies directed against various cell surface antigens. L929 mouse fibroblast cells were targeted with liposomes conjugated to anti-H2Kk. K562 cells, a human line derived from chronic myelogenous leukemia, were targeted with antiglycophorin. One murine T-lymphoma, AKR/J SL2, was targeted with anti-thy 1.1; another, R1.1, was targeted with anti-H2Kk. The following important parameters were established concerning efficacy of antibody-directed liposomes as a drug delivery system. (1) Targeted liposomes containing methotrexate-gamma-aspartate were 20-40 times more cytotoxic than the free drug or nonspecific liposomes. (2) The use of drugs such as methotrexate-gamma-aspartate, which are unable to enter cells without a carrier, eliminates the nonspecific effects of drug that may leak from the liposomes. (3) Liposomes conjugated to antibody have a higher valency than the soluble antibody and bind to cells with up to 1000-fold higher affinity constant. (4) Liposomes that interact with more than one type of ligand on the cell surface show marked resistance to inhibition of cell association by soluble ligands. (5) The optimal liposome size appears to vary from 0.05 to 0.1 mu, depending on target cell type.

Animals