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Biomedical subjects

J Stuart

Publications and source records attributed to J Stuart.

At least 55 records · Page 3Linked to original sources

Local graft irradiation after failure of modern immunosuppression in acute cellular and vascular graft rejection.

PURPOSE: With improved chemical immunosuppressive agents, approximately 90% of rejection episodes can be reversed. However, in situations of failed immunosuppression, graft loss becomes inevitable. Our objective is to assess the efficacy of local graft irradiation (LGI) as an effort of last resort in a contemporary group of patients in whom graft failure to irreversible cellular and vascular rejection is imminent. METHODS AND MATERIALS: A total of 308 renal transplantations were performed at our institution from 1992 to 1995, and an overall 1-year graft survival rate of 90% has been seen as a result of improvement in chemical immunosuppression. However, 6 patients were referred for LGI when all other measures failed to reverse the rejection crisis. Parameters that were studied in these patients included graft function and postirradiation graft histology. RESULTS: Irradiation was associated with reversal of the rejection crisis and resulted in documented histological long-term graft survival in 1 of the 6 patients (17%). Two of the six patients (33%) had reversal of the rejection episode based on postirradiation biopsy of the renal allograft. Three of the six patients showed some level of clinical improvement of graft function for varying periods of time. One patient maintained stable allograft function without deterioration and with continued independence from hemodialysis. One recipient died from sepsis despite histologic improvement after irradiation. CONCLUSIONS: Our impression is that LGI is indicated when all other measures have failed to reverse an acute rejection episode in the transplanted renal allograft. The role of radiation in this setting should be studied further.

Graft Rejection↗

Salm-Net facilitates collaborative investigation of an outbreak of Salmonella tosamanga infection in Europe.

Twenty-eight cases of Salmonella tosamanga infection were identified in six western European countries during the first half of 1995. Salm-Net, a European system for collaborative surveillance of gastrointestinal infection, detected the outbreak and coordinated its investigation. There were 28 cases, 14 of each sex, with a broad age distribution. Interviews with cases to identify common food and other exposures failed to generate a working hypothesis. The initial cluster occurred in a period of eight weeks and, since only one further case occurred in June, the investigation was closed. This incident shows that Salm-Net is effective in identifying international outbreaks of human salmonellosis. Practical difficulties in the field investigation of the outbreak are discussed.

Adult↗

Effects of density and of dehydration of sickle cells on their adhesion to cultured endothelial cells.

Abnormal adhesion of sickle cells to vascular endothelium may be a factor in the initiation of painful vaso-occlusive crisis. The sickle cell population contains an unusually large number of less dense reticulocytes that are known to be more adhesive than mature red cells, but there is contradictory evidence regarding the adhesiveness of dense sickle cells. We used a flow-based assay of adhesion to cultured human umbilical vein endothelial cells to test the properties of density fractions of sickle cells, prepared either by density gradient or by centrifugation of packed cells. We also examined the effects of incubating sickle cells with or without cyclical deoxygenation on their adhesion. After fractionation on a Percoll-isopaque gradient, the less dense 10% (reticulocyte-rich) cells and the most dense 10% cells adhered in greater number than the remainder (by about twofold). However, after centrifugation of packed cells, the less dense 10% were again more adhesive than the "middle" cells, but the most dense were not. Exposing sickle cells to constituents of the gradient had no consistent effect on adhesion, while centrifugal packing induced a degree of hemolysis, and tended to reduce adhesiveness of the dense fraction previously obtained from a gradient. Incubation in air at 37 degrees C for 15 hr reduced the number of reticulocytes and the adhesiveness of less dense sickle cells compared to those held at 4 degrees C. On the other hand, incubation at 37 degrees C for 15 hr with cyclical deoxygenation caused formation of dense cells and increased adhesiveness compared to incubation without cyclical deoxygenation. We conclude that young, less dense sickle cells are unusually adhesive, but that this adhesiveness is reduced during maturation. However, repeated sickling in vivo causes formation of an abnormally dense subpopulation of cells which either redevelop an increased tendency to adhere to endothelial cells or preserve their initial adhesiveness. Both adhesive cell populations may be implicated in promoting vascular obstruction.

Adult↗

Legal restraint.

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Aged↗

A study of the prevalence of and risk factors for ear diseases and hearing loss in primary school children in Hat Yai, Thailand.

2,184 primary school children in Hat Yai Municipality, Southern Thailand were screened for ear diseases and hearing loss using screening audiometry, portable tympanometry and otoscopy to identify children with possible ear problems, 754 children failed the initial screen, 728 were retested and a group of 243 were referred for ENT examination and standard audiometry-tympanometry. Children with hearing loss and otitis media were thus identified. A questionnaire to identify possible risk factors was administered. The prevalence of otitis media in this population was found to be 3.25 per cent (AOM 0.69%, OME 1.14%, COM 1.74%). No risk factor identified as significant were found. Non-significant factors included sex, age, URI last month, father smoking, mother smoking and method of transport to school as an indication of social status. This study contrasts with a previous study in 1990 which showed a 3.5 per cent prevalence of COM.

Adolescent↗

Functional haplodiploidy: a mechanism for the spread of insecticide resistance in an important international insect pest.

The coffee berry borer, Hypothenemus hampei, is the most important insect pest of coffee worldwide and has an unusual life history that ensures a high degree of inbreeding. Individual females lay a predominantly female brood within individual coffee berries and because males are flightless there is almost entirely full sib mating. We investigated the genetics associated with this interesting life history after the important discovery of resistance to the cyclodiene type insecticide endosulfan. Both the inheritance of the resistance phenotype and the resistance-associated point mutation in the gamma-aminobutyric acid receptor gene Rdl were examined. Consistent with haplodiploidy, males failed to express and transmit paternally derived resistance alleles. Furthermore, while cytological examination revealed that males are diploid, one set of chromosomes was condensed, and probably nonfunctional, in the somatic cells of all males examined. Moreover, although two sets of chromosomes were present in primary spermatocytes, the chromosomes failed to pair before the single meiotic division, and only one set was packaged in sperm. Thus, the coffee berry borer is "functionally" haplodiploid. Its genetics and life history may therefore represent an interesting intermediate step in the evolution of true haplodiploidy. The influence of this breeding system on the spread of insecticide resistance is discussed.

Alleles↗

What mothers say about why poor children fall behind on immunizations. A summary of focus groups in North Carolina.

OBJECTIVES: To develop a more thorough understanding of the factors that impede poor parents' utilization of health care services for their children and to refine interventions to improve immunization rates. METHODS: We conducted focus group sessions with mothers whose children received care at the health departments in five North Carolina counties. Mothers were uninsured or were receiving Medicaid. A total of 50 women participated; group size varied from three to seven mothers. RESULTS: Socially disadvantaged mothers faced barriers at multiple points in the process of obtaining preventive care for their children. Organizational barriers, such as a lack of flexibility in scheduling and long waiting times, were exacerbated by personal barriers, such as a lack of reliable transportation, chaotic home environments, and employment conflicts. Lack of knowledge regarding the timing of childhood immunizations and misperceptions about the safety of immunizations were also important obstacles. Mothers made several suggestions, such as changes in scheduling, greater assistance with transportation, improved waiting facilities, and increased health education. CONCLUSIONS: Our study suggests that even with improved financing of well-child care, many important barriers to adequate immunization will remain. Many of the changes that mothers in our focus groups advocated are not related to insurance coverage and would be simple and inexpensive to implement. To help with these changes, we developed a checklist for use by health departments to determine which organizational barriers exist at their facility and suggest strategies to overcome the problems. Organizational, personal, and attitudinal barriers pose serious problems for socioeconomically disadvantaged families. To improve vaccination rates for children, new personnel and programs are probably less important than careful strategies to maximize existing resources.

Adolescent↗

Importance of modified nucleosides to the structure and function of tRNAs.

Although a few modifications are found in DNA, 93 modified nucleosides have been found in the various RNAs. For the most part, the chemistry and structure that modified nucleosides, individually and in combination, uniquely contribute to DNA or RNA function have yet to be explained. However, there are ten physicochemical contributions that can be attributed to modified nucleosides. Of particular interest is the increasingly documented relationship between the presence of modified nucleosides in tRNAs, and the site and affinity of Mg2+ binding to RNA and its effect on function.

Binding Sites↗

Additive in vitro effects of anti-sickling drugs.

To study the effect of anti-sickling drugs on cellular dehydration induced by entry of Ca, sickle cells were subjected to cyclical oxygenation-deoxygenation for 15 h in Ca-containing buffer. The consequential loss of cation (K) via the Ca-dependent K efflux (Gardos) channel caused cell dehydration and loss of deformability. Inhibition of a specific fraction of Ca entry by verapamil had no rheologically protective effect, whereas inhibition of the Gardos channel by clotrimazole or nitrendipine had a marked protective effect. When Gardos channel inhibition (by either clotrimazole or nitrendipine) was combined with stabilization of the oxy-conformation of sickle haemoglobin (by the substituted benzaldehyde 12C79), an additive protective rheological effect was achieved with 60-78% reduction in clogging rate of 5 microns diameter pores when compared with no drug. Therapeutic use of anti-sickling compounds in combination may achieve increased efficacy with lower toxicity.

Anemia, Sickle Cell↗

Monitoring the acute phase response to vaso-occlusive crisis in sickle cell disease.

AIMS: To identify suitable acute phase proteins as objective markers of tissue ischaemia during painful vaso-occlusive crises in sickle cell disease. METHODS: The prodromal and established phases of 14 vaso-occlusive crises were studied longitudinally in 10 patients with sickle cell anaemia. Automated solid phase enzyme immunoassays were used to measure the fast responding acute phase proteins C-reactive protein and serum amyloid A protein. Slower responding glycoproteins (fibrinogen, orosomucoid, sialic acid and concanavalin-A binding) were measured in parallel. RESULTS: C-reactive protein and serum amyloid A protein increased early in crisis, sometimes within the early (prodromal) phase. Crises that resolved within 24 hours in hospital showed a minor and transient rise compared with crises that required treatment for four days or more. In eight crises treated by patients at home the acute phase response ranged from minor to a level consistent with extensive tissue ischaemia. CONCLUSIONS: Sensitive enzyme immunoassays for C-reactive protein and serum amyloid A protein are of potential value for monitoring the onset of tissue ischaemia in sickle cell crisis and for confirming subsequent resolution.

Acute-Phase Proteins↗

Progesterone receptor detection in paraffin sections of human breast cancers by an immunoperoxidase technique incorporating microwave heating.

We sought to establish an easily interpretable and highly sensitive immunohistochemical method for detecting progesterone receptor protein in formalin-fixed, paraffin-embedded samples of breast carcinomas. Beginning with a conventional immunoperoxidase staining procedure, we incorporated microwave heating to compensate for the effects of conventional fixation and processing and then applied the method to 90 samples of primary breast carcinomas. We used the results of hormone binding assays as true values to establish the sensitivity, specificity, positive predictive value, and negative predictive value of the staining method. Our technique yielded good preservation of morphological detail and low nonspecific staining of background tissue. Comparisons of the results of staining and biochemical assays revealed that this progesterone receptor immunostaining procedure shows high sensitivity and acceptable specificity. We believe its performance characteristics make reliable study of small specimens and archival material possible.

Adult↗