User survey proves value of I/S strategy.
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Biomedical subjects
Publications and source records attributed to H Scott.
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A case of Papillon-Lefèvre syndrome that has been managed successfully for six years is reported. Papillon-Lefèvre syndrome is a rare form of early onset periodontitis that occurs at a rate of 1-3 per million. Diagnostic features include palmar-plantar hyperkeratosis and rapid periodontal destruction. Although the etiology of this syndrome is unknown, current theories on the nature of the underlying defect fall into three main categories: anatomical, bacterial and host response. Historically, Papillon-Lefèvre syndrome was thought to lead to the inevitable loss of both the primary and permanent dentitions. However, a recently proposed treatment involving antibiotic coverage, extraction of the primary dentition and a period of edentulism has been shown to be effective in maintaining the permanent dentition. Since treatment may begin prior to the eruption of the permanent dentition, early recognition of Papillon-Lefèvre syndrome is critical. Any young patient who exhibits palmar hyperkeratosis should be examined carefully for periodontal breakdown. Since the number of cases available for study is limited, referral of such individuals to University dental clinics may allow for a more specific analysis of immune or bacterial factors that may lead to a better understanding of this disease.
AIM: To quantify and describe the annual cost of ischaemic stroke to New Zealand society during 1992. METHODS: A prevalence or cross sectional approach employing incremental estimation was used to estimate costs from the perspective of society. The study used unit record hospital and mortality data. RESULTS: Direct costs ranged from $93 million to $140 m and loss of production was between $6 m and $14 m. Total quantified costs were estimated to lie between $99 m and $154 m. Hospital and continuing care costs when combined make up 90% of all quantified costs. CONCLUSION: Ischaemic stroke affects mainly older people many of whom are discharged into the community and require costly community support or continuing care. The combination of an ageing population, increasing survival rates and constant incidence rates will result in a substantial rise in the costs of continuing care and community support. Most of these costs are at present obscured because much of the care provided does not involve money payments and/or data are not recorded and collated on a national basis. Incorrect policy decisions will be made if the nonhospital costs of stroke are not taken into account.
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CD is an immunologic disease of the small intestine which is precipitated by ingestion of wheat gliadin. Most patients carry the HLA-DQ (alpha 1*0501, beta 1*0201) (DQ2) heterodimer. We recently reported that a preponderance of gliadin-specific T cells from the small intestinal mucosa of DQ2-positive CD patients were restricted by this DQ heterodimer. However, a small percentage of CD patients do not carry this DQ heterodimer, and most of them instead carry DQ (alpha 1*0301, beta 1*0302) (DQ8). Here we report that a majority of gliadin-specific T cells from the small intestinal mucosa of a DR4,DQ7/DR4,DQ8 heterozygous CD patient are restricted by DQ8. Thus, preferential presentation of gliadin-derived peptides to T cells by the CD-associated DQ2 and DQ8 molecules may be an initial and important immunopathogenic step in CD.
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Neonatal primary hyperparathyroidism is a life threatening disorder that is associated with severe hypercalcaemia, hypotonia, bone demineralization, fractures and respiratory distress. Treatment consists of total parathyroidectomy and without this affected infants will usually die by the age of three months. We report a patient with neonatal primary hyperparathyroidism who survived without fractures or parathyroidectomy to an age of nine months, and in whom the hypercalcaemia became masked by vitamin D deficiency. At surgery, four-gland hyperplasia was demonstrated and total parathyroidectomy followed by oral calcitriol treatment has restored well-being and normocalcaemia. An absence of skeletal complications, a survival beyond three months of age without parathyroidectomy and the masking of the hypercalcaemia by vitamin D deficiency represents a unique combination of metabolic abnormalities in a patient with neonatal primary hyperparathyroidism.
An increased level of immunoglobulin A (IgA) antibodies to food antigens has been found in Down syndrome. Biopsy did not show any anomaly of the gut. Increased IgA levels against specific proteins reflect increased transmucosal transport of antigens. The antigens presented may be immunogenic peptides or intact antigens. In this paper, we wished to exclude an institutional cause such as infections and also age differences.
A tumour of the iris with the morphological and immunohistochemical characteristics of a paraganglioma is presented. Neither this type of tumour, nor the specialized nerve cells giving rise to the tumour, have previously been reported in the eye. A successful local resection was performed. The diagnosis and concept of paragangliomas are discussed briefly.
Mucosal specimens from active Crohn's disease (ileum, n = 6; colon, n = 6), active ulcerative colitis (n = 9), normal ileum (n = 6), and normal colon (n = 6) were subjected to paired immunofluorescence staining for characterisation of macrophage subsets in situ. In the normal state, only few CD68+ macrophages (< 10%) expressing the myelomonocytic L1 antigen (calprotectin) were seen. In inflamed mucosa, especially near small vessels, the CD68+L1+ fraction increased with the degree of inflammation, near ulcers to median 65% (range 35-91%). Cells reactive with the monoclonal antibody RFD7 were also increased in inflammation but less than 5% of them costained for L1 antigen. It is concluded that L1 producing macrophages are distinct from the RFD7+ subset and probably recently recruited from peripheral blood monocytes. Like granulocytes, L1+ macrophages may be important in non-specific defence, providing calprotectin with putative anti-microbial and anti-proliferative properties.
A model of coronary artery thrombosis which: (1) provides a stable thrombus; (2) incorporates intimal injury; (3) has a low mortality rate; (4) responds predictably to thrombolytic therapy, and (5) is technically simple, was developed. Intimal injury was produced proximal to a critical stenosis and followed by the infusion of a blood and thrombin mixture into the injured segment. After thrombus formation flow remained absent in all control animals (n = 7). Microscopy showed intimal injury and coronary thrombosis with platelets adherent to the subendothelium. In animals treated with tissue plasminogen activator (n = 7) flow returned to > 60% of baseline at 20.2 +/- 7.7 min and was cyclical. Mortality and complications were infrequent. This model is useful in investigations of reperfusion therapy.
BACKGROUND: The early establishment of infarct artery reperfusion by intravenous thrombolytic therapy has improved survival after acute myocardial infarction. Investigations of reperfusion have focused on the effects of specific thrombolytic agents, anticoagulation, and platelet inhibition. However, little attention has been given to the relation of arterial blood pressure to thrombolysis, a factor that probably affects thrombolytic agent delivery to the obstructing thrombus. METHODS AND RESULTS: The effect of arterial diastolic pressure augmentation by intra-aortic balloon counterpulsation (IABP) on reperfusion after intravenous thrombolytic therapy was studied in a canine model. A critical left anterior descending coronary artery stenosis was created by an occluder. Acute thrombosis immediately proximal to the occluder was formed by local injection of a blood and thrombin mixture into a segment of the artery that had intimal damage (groups 1 through 3). Continuous coronary blood flow velocity was measured by an epicardial Doppler probe. Group 1 (n = 7) served as control. Group 2 (n = 6) received an intravenous, front-loaded recombinant tissue-type plasminogen activator (rTPA) regimen (1.25 mg/kg total dose, 15% as bolus, 50% in the first 30 minutes, and 35% for the following 60 minutes). Group 3 (n = 6) received the same rTPA regimen with IABP beginning at the start of rTPA administration. Coronary blood flow velocity, arterial pressure, and heart rate were observed for 150 minutes after the start of thrombolytic therapy. Five animals did not undergo coronary thrombosis (group 4) and had coronary blood flow velocity determined before and after IABP at baseline and after creation of critical stenosis. Mean systolic arterial blood pressure and heart rate were not statistically different between groups. Peak augmented diastolic pressure by IABP was 97.9 +/- 1.3% of systolic pressure in group 3 dogs. Spontaneous reperfusion did not occur in any group 1 dogs. All animals treated with rTPA reperfused. Reperfusion occurred in group 3 (13.1 +/- 2.1 minutes) earlier than in group 2 (39.2 +/- 9.4 minutes, P = .02). Overall duration of arterial patency did not differ between group 2 (81.4 +/- 16.6 minutes) and group 3 (94.9 +/- 15.3 minutes, P = .52). Reocclusions occurred with similar frequency (P = .85) in groups 2 and 3. In group 4, IABP did not increase baseline coronary blood flow velocity. CONCLUSIONS: This study demonstrates that augmentation of diastolic arterial pressure by IABP enhances thrombolysis, leading to faster reperfusion. This effect appears to be unrelated to an increase in coronary blood flow and may be due to an effect of the augmented diastolic blood pressure wave on the obstructing thrombus. These findings suggest that the time to reperfusion by rTPA may be blood pressure dependent. The relation of arterial blood pressure to successful thrombolysis may have important implications for future treatment strategies for myocardial infarction.
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BACKGROUND: Accelerated intravenous dosing is currently the preferred regimen for administering recombinant tissue-type plasminogen activator (rt-PA) in acute myocardial infarction (AMI). This regimen is recommended on the basis of clinical angiographic studies that reported superior 60 and 90 min patency rates. However, continuous infarct-vessel flow characteristics after reperfusion following this regimen are poorly described. The aim of our study was an improved definition of the characteristics of infarct-vessel flow induced by intravenous accelerated rt-PA using an animal model of acute coronary artery thrombosis. METHODS: We studied the characteristics of reperfusion induced by an accelerated intravenous rt-PA dosing regimen in a canine coronary artery thrombosis model that simulates AMI. We created a critical stenosis in the left anterior descending coronary artery (LAD) of 24 open-chest dogs. Thrombosis was caused immediately proximal to the stenosis by injection of a blood and thrombin mixture into a segment of the LAD which had intimal damage. Hemodynamics and distal LAD blood flow velocity were recorded continuously. Six animals did not complete the protocol. Animals in the treatment group (n = 10) received an intravenous accelerated rt-PA regimen (1.25 mg/kg total dose) and were observed for 150 min. Eight animals served as controls. RESULTS: None of the control animal arteries reperfused. In the treatment group, reperfusion occurred 31.5 +/- 7.3 min after starting rt-PA dosing in two general patterns. In one pattern, reperfusion onset was gradual and linear; in the other pattern, reperfusion was sudden. LAD flow was cyclical in all animals, with marked variations in magnitude compared with baseline (0-173% of baseline). Reocclusion was common and occurred 30.3 +/- 6.3 min after the initial reperfusion. There were 1.9 +/- 0.4 reocclusions per animal, and two distinct patterns were noted. In one, flow ceased abruptly and, in the second, flow declined gradually in a linear fashion before stopping. Infarct-vessel flow was evident for 103.1 +/- 14.1 min of the 150 min observation period. CONCLUSIONS: Reperfusion occurs rapidly after an accelerated dosing regimen of rt-PA. However, the infarct-vessel flow resulting from this therapy is unstable and is associated with early reocclusion and marked variation in flow magnitude. Analysis of continuous infarct-vessel flow velocity patterns suggests at least two different mechanisms for the onset of reperfusion and reocclusion after this therapy. Recognizing several mechanisms of arterial opening and closing may have important implications for methods of stabilizing infarct vessels after reperfusion by accelerated dosing of rt-PA.
Celiac disease (CD) is most probably an immunological disease, precipitated in susceptible individuals by ingestion of wheat gliadin and related proteins from other cereals. The disease shows a strong human HLA association predominantly to the cis or trans encoded HLA-DQ(alpha 1*0501,beta 1*0201) (DQ2) heterodimer. T cell recognition of gliadin presented by this DQ heterodimer may thus be of immunopathogenic importance in CD. We therefore challenged small intestinal biopsies from adult CD patients on a gluten-free diet in vitro with gluten (containing both gliadin and other wheat proteins), and isolated activated CD25+ T cells. Polyclonal T cell lines and a panel of T cell clones recognizing gluten were established. They recognized the gliadin moiety of gluten, but not proteins from other cereals. Inhibition studies with anti-HLA antibodies demonstrated predominant antigen presentation by HLA-DQ molecules. The main antigen-presenting molecule was established to be the CD-associated DQ(alpha 1*0501, beta 1*0201) heterodimer. The gluten-reactive T cell clones were CD4+, CD8-, and carried diverse combinations of T cell receptor (TCR) V alpha and V beta chains. The findings suggest preferential mucosal presentation of gluten-derived peptides by HLA-DQ(alpha 1*0501, beta 1*0201) in CD, which may explain the HLA association.
Jejunal biopsy specimens from 10 patients with treated coeliac disease and seven non-coeliac controls were challenged in vitro with peptic-tryptic gluten digest. Mucosal T cells were examined in situ by three-colour immunofluorescence staining for expression of the activation marker CD25 (the p55 alpha-chain of interleukin-2 receptor) and the nuclear proliferation marker revealed by monoclonal antibody Ki-67. Intraepithelial T cells expressed CD25 rarely whereas the proportion of activated lamina propria T cells increased (P < 0.002) from median 2.8% (cultured with 20% fetal calf serum alone for 24-48 h) to 10.0% after 24 h with gluten (n = 10; range 1.1-17.4%) and to 10.4% after 48 h (n = 7; range 1.4-17.5%). Such gluten-induced increase of CD25+ T cells was not observed in specimens from non-coeliac control subjects. Crypt-cell hyperplasia and T-cell proliferation (Ki-67+) were observed neither in the coeliac nor in the control mucosae after gluten stimulation. Three-colour staining combining a polyclonal antibody reagent to CD3 and a monoclonal antibody to CD25 with a monoclonal antibody to CD45R0, CD4, CD8, the p75 beta-chain of interleukin-2 receptor, integrin alpha E beta 7, or HLA-DR showed that most of the CD25+ T cells (> 90%) were CD4+CD8-, co-expressed CD45R0 and the p75 beta-chain, and often also the integrin alpha E beta 7 but not HLA-DR. In addition to these activated T cells, a dominating population of CD25+CD3-CD4+ subepithelial pan-HLA-class II+ macrophages (CD68+) with variable expression of the p75 beta-chain was often induced by gluten challenge.
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We have examined the disposition of the cinchona alkaloids quinine and quinidine in the rat recirculating isolated perfused liver preparation. When administered as separate 1 mg doses, the hepatic clearances of quinine and quinidine were similar to the hepatic perfusate rate of 10 mL min-1. When 1 mg of each was administered simultaneously, mean hepatic clearance of quinine was unchanged (9.00 +/- 2.20 mL min-1 separate dosage, n = 7; 6.87 +/- 1.77 mL min-1 simultaneous dosage, n = 7; P > 0.05). By contrast, mean hepatic clearance of quinidine was reduced significantly by concomitant quinine (10.6 +/- 1.72 mL min-1 separate dosage, n = 7; 4.82 +/- 1.25 mL min-1 simultaneous dosage, n = 7; P < 0.05). There was no significant difference in volumes of distribution when each alkaloid was administered separately (131 +/- 46 mL quinine, 129 +/- 21 mL quinidine; P > 0.05) but concomitant quinine administration increased quinidine volume of distribution to 169 +/- 30 mL (P < 0.05). Four further experiments with simultaneous dosages of 0.5 mg of each alkaloid produced similar findings, indicating that the interactions did not derive from nonlinear drug disposition.