Haemorrhagic cystitis and urinary retention in Henoch-Schönlein purpura.
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Child, Preschool↗
Biomedical subjects
S J Allen
Publications and source records attributed to S J Allen.
MHC and malaria: the relationship between HLA class II alleles and immune responses to Plasmodium falciparum.
In mice, immune responses to subunits of defined malaria antigens are regulated by genes mapping within the MHC and it has been suggested that such genetic restriction will be a major obstacle in the development of a human malaria vaccine. The relationship between class II human leukocyte antigen (HLA) genes and immune recognition of three candidate antigens for a vaccine against Plasmodium falciparum malaria has been investigated in a human population living in a malaria endemic area of West Africa. The study population was shown to be extremely heterogeneous for HLA class II alleles and marked differences in allelic frequency were detected between members of different ethnic groups. One class II DQA-DQB combination (serological specificity DQw2) was particularly common among members of the Fula ethnic group. This haplotype was significantly associated with higher than average levels of antibody to a peptide epitope, (EENV)6, of the malaria antigen Pf155/RESA. There was little evidence of association between HLA class II genotype and cellular proliferative or interferon gamma responses to the antigens tested. Overall, the number of significant associations between immune responses and specific HLA class II haplotypes was greater than would be expected by chance but less than would be expected if class II-dependent genetic restriction were a major factor governing human immune responses to malaria antigens. Thus, although some qualitative variation in the immune response to vaccine antigens may occur in ethnically different target populations, widespread HLA-associated nonresponsiveness to a multivalent subunit malaria vaccine is unlikely.
Adolescent↗
Naturally acquired cellular and humoral immune responses to the major merozoite surface antigen (PfMSP1) of Plasmodium falciparum are associated with reduced malaria morbidity.
We have investigated the pattern of acquired immune responses to the major surface protein of Plasmodium falciparum merozoites (gp 190, PfMSP1) in a malaria endemic population in West Africa. A prospective longitudinal study in 3- to 8-year-old children was conducted to examine the relationship between naturally acquired immune responses to PfMSP1 and subsequent susceptibility to malaria infection and clinical disease. A population cross-sectional survey was performed to investigate changes in immune response with age. The prevalence and concentration of antibodies to all regions of the molecule increased with age with the highest prevalence of antibodies being detected against regions of the molecule which are highly conserved between parasite isolates. In vitro lympho-proliferation and interferon-gamma production in response to recombinant proteins representing polymorphic regions of the molecule also increased with age. Interestingly, proliferative responses to some regions of the molecule, including some highly conserved sequences, were highest in young children and decreased markedly with increasing age. Significant associations were observed between antibody and lymphoproliferative responses to proteins from the C terminus of the molecule and resistance to episodes of fever associated with high parasitaemia in partially immune children. In addition, high concentrations of antibodies to a conserved region close to the N terminus of PfMSP1 were also significantly associated with protection.
Africa, Western↗
Cost of fluoridation: 44 Florida communities.
Previous data relating to the cost of fluoridation often do not include annualized costs or costs for labor and maintenance. The purpose of this study was to estimate accurately current costs for initiating and maintaining fluoridation and to develop a methodology that can be used to provide the cost basis for further cost-effectiveness studies. The data were collected from 44 Florida communities that had initiated community water fluoridation between 1981 and 1989. Equipment, installation, and engineering costs were derived from copies of actual invoices for equipment and services and then adjusted to 1988 dollars. The chemical costs were calculated from operational reports listing flow rate and pounds used. The cost was then adjusted according to whether the hydrofluosilicic acid was supplied as 15-gallon carboys, 55-gallon drums, in bulk, or as sodium silicofluoride or sodium fluoride. The initial cost was annualized at 2 percent and 4 percent over 15 years. Calculated operational costs included chemical costs, labor costs, and maintenance and repair costs. The operational costs were then added to the annualized depreciation costs and opportunity costs for the initial investment, to produce an estimated cost per person served. The total mean cost per person for all installations was $1.14 per year at 2 percent and $1.25 per year at 4 percent. The mean cost at 4 percent for communities of fewer than 10,000 was $2.12; for communities between 10,000 and 50,000 it was $0.68; and for communities over 50,000 it was $0.31. The total mean cost per person across all installations was $0.41 at 2 percent and 0.45 at 4 percent.(ABSTRACT TRUNCATED AT 250 WORDS)
Capital Financing↗
Turnover of hyaluronan in the rabbit pleural space.
Hyaluronan influences lung fluid balance. The clearance of lung hyaluronan by way of the pulmonary lymphatics and the pleural space is increased when fluid flux into the interstitium is increased. The purpose of this study was to determine the rate at which hyaluronan is removed from the pleural space. We injected hyaluronan, labeled with tritium in the acetyl group, into the pleural space of six rabbits. The appearance of [3H]H2O in serum was measured over time to calculate the turnover rate of hyaluronan. We found that the half-lives ranged between 8 and 15 h and were positively related to the amount of hyaluronan injected. At the end of the experiment, the contralateral pleural space was irrigated to determine the amount of pleural space hyaluronan, which was 0.3 micrograms/kg body wt.
Animals↗
Dentist-implemented contingent escape for management of disruptive child behavior.
We evaluated the effectiveness of a dentist-implemented intervention in which brief escape from dental treatment was provided to manage disruptive child behavior during restorative dental treatment. Within a multiple baseline design across subjects, 4 children, aged 3 to 7 years, were provided temporary escape from dental treatment contingent upon brief periods of cooperative behavior. Disruptive behavior decreased when the appropriate escape contingency was used at least 80% of the time. The escape contingency required no more time than traditional management procedures (e.g., tell-show-do, reprimands and loud commands, restraint) to bring disruptive behavior under control. Independent ratings by two dentists provided social validation of the efficacy of the escape contingency.
Child↗
Normal beta-NGF content in Alzheimer's disease cerebral cortex and hippocampus.
Nerve growth factor (beta-NGF) is known to have beneficial effects on cholinergic cell survival and to function both in vivo and in vitro. It has been speculated that this protein, or the lack of it, may be involved in the aetiology of Alzheimer's disease (AD). We describe the measurement of beta-NGF content in 4 regions of the cerebral cortex and the hippocampus in AD brain compared with brain tissue from age-matched normal subjects using a sensitive sandwich immunoassay (ELISA). There was no difference in beta-NGF content in any region examined in AD compared with normal values despite the marked loss of cortical cholinergic function.
Aged↗
Low affinity nerve growth factor receptor binding in normal and Alzheimer's disease basal forebrain.
The binding characteristics of radiolabelled beta-nerve growth factor ([125I]NGF) have been determined on membrane preparations of basal forebrain from Alzheimer's disease (AD) brain and age-matched normal brains. [125I]NGF binds in a specific fashion indicative of a single receptor and is not displaced with microM concentrations of cytochrome c, insulin or epidermal growth factor (EGF). The mean dissociation constant (Kd) and the mean capacity (Bmax) of the NGF receptor were not significantly different between the 5 AD and 5 normal basal forebrain samples examined. Choline acetyltransferase (ChAT) activity was significantly reduced (P less than or equal to 0.001) in AD cerebral cortical samples compared with normal tissue.
Aged↗
Immune response to soluble exoantigens of Plasmodium falciparum may contribute to both pathogenesis and protection in clinical malaria: evidence from a longitudinal, prospective study of semi-immune African children.
Some soluble exoantigens of Plasmodium have lipopolysaccharide (LPS)-like properties and are believed to contribute to the pathogenesis of acute malaria. We have studied cellular and humoral immune responses to several purified exoantigens of Plasmodium falciparum in a cohort of children and compared these responses with their subsequent susceptibility to malaria infection and clinical disease. We found no evidence that either lymphoproliferative or interferon-gamma (IFN-gamma) responses to these antigens were associated with protective immunity. On the contrary, children whose cells produced IFN-gamma after in vitro activation with one of the soluble antigens (Ag7) were more likely to experience clinical manifestations of malaria infection (fever and malaise) than were children whose cells did not produce IFN-gamma. It is possible that exoantigen-induced IFN-gamma may exacerbate the LPS-like effects of these antigens. However, serum antibodies to another antigen (Ag2) were more prevalent in children with asymptomatic infections or low parasitemia than in children with fever and higher parasitemia (confirmed clinical malaria), suggesting that these antibodies may contribute to the development of protective immunity.
Animals↗
Continuous monitoring of cerebral oxygenation in acute brain injury: assessment of cerebral hemodynamic reserve.
A new index of cerebral hemodynamics, cerebral hemodynamic reserve (CHR), was evaluated in 12 comatose adults with severe, acute, traumatic, diffuse swelling of the brain, who underwent continuous monitoring with a fiberoptic catheter of the saturation difference in arteriojugular oxyhemoglobin. CHR was assessed as the ratio of changes in global cerebral oxygen extraction to changes in cerebral perfusion pressure (CPP) as a result of spontaneous increases in intracranial pressure (ICP). During the course of hyperventilation (Pco2 in the range of 20 mm Hg) for ICP control below 20 mm Hg, 34 observations were made over the initial 48 hours postinjury. Despite normal CPP, in 25 of the observations (73.5%), ICP elevations to the range of 20 mm Hg were associated with compromised CHR, as evidenced by decreases in jugular oxygenation directly attributed to the ICP increases. In the remaining nine observations (26.5%), CHR was preserved, as evidenced by no changes or increases in jugular oxygenation when ICP increased. The CHR improved on the second day, suggesting an improved tolerance of the cerebral hemodynamics to ICP increases. Before the ICP elevations, in most of the observations, the global cerebral blood flow was estimated as being optimally decreased (by hypocapnia), in relation to cerebral oxygen consumption. This was reflected by the occurrence of baseline normalized cerebral oxygen extraction. It is concluded that in this group of patients, under circumstances of profound hyperventilation, ICP elevations within the normal CPP range may result in decreased cerebral oxygenation, even when the normal CPP would imply otherwise. It is suggested that CHR assessment may provide information regarding the status of intracranial "tightness," insofar as cerebral circulation and oxygenation are concerned.
Acute Disease↗
Lung hyaluronan during development: a quantitative and morphological study.
Hyaluronan, an important constituent of developmental interstitium in fetal lungs, mediates cell-to-cell interactions and thereby directs migrating cells. Furthermore, because of the polyionic nature of the molecule, hyaluronan forms open, hydrated matrices that provide channels for migrating cells. This hydrated matrix undergoes contraction before birth. However, continued growth of the lung in the perinatal period requires newly synthesized hyaluronan. This study's purpose was to elucidate the changes in lung hyaluronan concentration and distribution in the perinatal period. We studied rabbits at days -6, -4, -2, -1, 0, +2, and +4 with respect to term, as well as adult rabbits. We found that hyaluronan concentration was highest in the youngest fetuses studied [682 +/- 115 micrograms/g dry wt (means +/- SD)]. However, hyaluronan concentration decreased to 129 +/- 12 micrograms/g dry wt just before birth then returned to 366 +/- 111 micrograms/g dry wt at day +4; these values were similar to adult values. We found hyaluronan staining decreased during late gestation, particularly in the interalveolar region. In the postnatal period, hyaluronan staining increased in the visceral pleura and, to a lesser extent, beneath the epithelium of the bronchioles. Hyaluronan did not reaccumulate in the interalveolar region in the postnatal period. Our data suggest a change in the predominant role of lung hyaluronan during the perinatal period. Before term, hyaluronan facilitates morphogenesis. However, hyaluronan's major role in neonatal lung is most likely in regulation of fluid balance in interstitium.
Animals↗
Effect of thoracic duct drainage on hydrostatic pulmonary edema and pleural effusion in sheep.
Positive end-expiratory pressure (PEEP) increases central venous pressure, which in turn impedes return of systemic and pulmonary lymph, thereby favoring formation of pulmonary edema with increased microvascular pressure. In these experiments we examined the effect of thoracic duct drainage on pulmonary edema and hydrothorax associated with PEEP and increased left atrial pressure in unanesthetized sheep. The sheep were connected via a tracheostomy to a ventilator that supplied 20 Torr PEEP. By inflation of a previously inserted intracardiac balloon, left atrial pressure was increased to 35 mmHg for 3 h. Pulmonary arterial, systemic arterial, and central venous pressure as well as thoracic duct lymph flow rate were continuously monitored, and the findings were compared with those in sheep without thoracic duct cannulation (controls). At the end of the experiment we determined the severity of pulmonary edema and the volume of pleural effusion. With PEEP and left atrial balloon insufflation, central venous and pulmonary arterial pressure were increased approximately threefold (P less than 0.05). In sheep with a thoracic duct fistula, pulmonary edema was less (extra-vascular fluid-to-blood-free dry weight ratio 4.8 +/- 1.0 vs. 6.1 +/- 1.0; P less than 0.05), and the volume of pleural effusion was reduced (2.0 +/- 2.9 vs. 11.3 +/- 9.6 ml; P less than 0.05). Our data signify that, in the presence of increased pulmonary microvascular pressure and PEEP, thoracic duct drainage reduces pulmonary edema and hydrothorax.
Animals↗
Left ventricular myocardial edema. Lymph flow, interstitial fibrosis, and cardiac function.
We hypothesized that both acute and chronic accumulation of myocardial interstitial edema (extravascular fluid [EVF]) would compromise cardiac function. We also postulated that excess fluid within the myocardial interstitial space would potentiate interstitial fibrosis, thus further compromising function. Dogs were divided into three groups: 1) control, 2) chronic pulmonary hypertensive with right heart failure, and 3) chronic arterial hypertensive. The quantity of EVF, expressed as the unitless blood-free (wet weight-dry weight)/dry weight ratio, and interstitial fibrosis (collagen content) were determined and correlated with cardiac function at baseline and after acute elevation of coronary venous pressure and reduction of cardiac lymph flow. Control EVF was 2.90 +/- 0.20 (mean +/- SD), which increased to 3.45 +/- 0.16 after acute (3-hour) elevation of coronary sinus pressure. This EVF significantly compromised cardiac function. The EVF in chronically hypertensive dogs and in dogs with chronic right heart pressure elevations was 3.50 +/- 0.30 and 3.50 +/- 0.08, respectively. End-diastolic left ventricular interstitial fluid pressure increased from a control value of 14.9 +/- 3.1 (at EVF = 2.9) to 24.8 +/- 3.7 (at EVF = 3.5). An EVF of 3.5 produced approximately 30% reduction of the heart's ability to maintain cardiac output at a left atrial pressure of 15 mm Hg. The compromised function in these chronic models is exacerbated after acute elevation of coronary venous pressure and reduction of cardiac lymph flow. Collagen levels were elevated by at least 20% in the chronic hypertensive dogs and in the nonhypertrophied left ventricles of dogs with chronic right heart pressure elevation.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The pharmacokinetics and biodistribution of technetium-99m(V)dimercaptosuccinic acid in an animal tumor model.
This study used an established rabbit tumor model with squamous carcinoma to evaluate the pharmacokinetics and biodistribution of technetium-99m-(V)dimercaptosuccinic acid. A total of 54 rabbits were studied (25 with no tumor; 29 with tumor). Technetium-99m(V)dimercaptosuccinic acid had a bi-exponential blood clearance in rabbits with no tumors (28 and 325 min) and in rabbits with tumors (27 and 352 min). There was no significant difference (p greater than 0.05) in mean clearance times between the two groups and clearance appeared unaffected by tumor mass. Technetium-99m(V)dimercaptosuccinic acid had a bi-exponential cumulative urine excretion with no apparent difference in half-times between non-tumor and tumor rabbit groups (200 and 240 min, respectively). Technetium-99m(V)dimercaptosuccinic acid had a major organ biodistribution in rabbits which included bone, kidneys, bladder and the blood pool. The major route of excretion was via the urine. There was no significant difference (p greater than 0.05) in organ biodistribution between rabbits with no tumors and rabbits with tumors and there was no evidence of active uptake of technetium-99m(V)dimercaptosuccinic acid by either squamous carcinoma or inflammatory tissue.
Animals↗
Dental needs assessment survey: three Florida counties.
Dental needs assessment surveys were completed in three Florida counties (1987 - Lee County), (1988 - Pasco County) and (1989 - St. Lucie County). The data collected were then compared with the results from the national caries prevalence surveys in 1979-80 and 1986-87, by individual county and with the combined three-county total. Visual tactile examinations were done using the Radlike criteria for the DMFS index and the WHO Treatment Needs Index. Schools were selected based on the percent of students enrolled in the free or reduced lunch program and by geographic distribution. Although there were age group differences within individual counties, the combined data showed every age group except the seven year olds at a lower DMFS mean level than the data from the 1986-87 national survey for Region IV. The differences range from -.20 surfaces in 8-year-olds to -.57 surfaces in 13-year-olds. None of the differences were statistically significant from the national surveys. This indicates that these small scale surveys are a reliable method for needs assessment.
Adolescent↗
Cellular and humoral immune responses to Plasmodium falciparum gametocyte antigens in malaria-immune individuals. Limited response to the 48/45-kilodalton surface antigen does not appear to be due to MHC restriction.
We have examined immune responses to a cultured Plasmodium falciparum gametocyte lysate and to an affinity-purified preparation of the 48/45-kDa gamete surface Ag in a group of 30 malaria immune individuals and in 24 Europeans with no previous exposure to malaria. Cellular responses were assessed in vitro by lymphoproliferation and production of IFN-gamma; antigamete antibodies were detected by immunofluorescence, Western blotting, and competitive ELISA. Cells from all the malaria immune donors responded to the gametocyte lysate in both assays while cells from nonimmune donors gave only weak proliferative responses. Antigamete antibodies were detected in the serum of all the immune donors but not in serum from nonimmunes. Nonimmune donors were completely unresponsive to the purified 48/45-kDa surface Ag while cells from 40% of immune donors responded by either proliferation or IFN-gamma production. Only 3 of 30 immune donors had detectable antibodies to the 48/45-kDa Ag. Class II HLA type was determined for 27 of the immune donors but no relationship between HLA-DR or -DQ and responsiveness to the 48/45-kDa Ag was discerned. The possible reasons for limited recognition of this gamete surface Ag are discussed.
Animals↗
Aflatoxin-albumin adducts in human sera from different regions of the world.
An immunoassay now permits the determination of human exposure to aflatoxin at an individual level and consequently allows a better assessment of the role of aflatoxin, and its interaction with hepatitis B virus infection, in the aetiology of liver cancer. Measurements of aflatoxin bound to serum albumin in children and adults from various African countries show that between 12 and 100% contain aflatoxin-albumin adducts, with levels up to 350 pg AFB1-lysine equivalent/mg albumin. In Thailand, lower levels and prevalence of this adduct were observed, while no positive sera were detected from France or Poland. Data are presented showing that exposure to this carcinogen can occur throughout life and the relevance of these observations to the understanding of the multifactorial aetiology of liver cancer in these countries is discussed.
Adult↗
Beneficial effect of delivery in a patient with adult respiratory distress syndrome.
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Adult↗