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Biomedical subjects

S Hearn

Publications and source records attributed to S Hearn.

17 recordsLinked to original sources
PubMed1997

The role of active inducible nitric oxide synthase expression in the pathogenesis of capillary leak syndrome resulting from interleukin-2 therapy in mice.

Previously, we showed that nitric oxide (NO) plays a major role in the pathogenesis of IL-2-induced capillary leak syndrome in healthy or mammary adenocarcinoma-bearing C3H/HeJ mice. NO synthase (NOS) inhibitors, such as NG-nitro-L-arginine methyl ester (L-NAME) reduced all the manifestations of IL-2-induced capillary leakage, without compromising the antitumor effects of IL-2. The present study was carried out on healthy C3H/HeJ mice subjected to one or two 4-day rounds of systemic IL-2 therapy with or without oral L-NAME therapy to: (a) identify the tissue source of NOS activity and NOS protein induced by IL-2 therapy; (b) identify histologically the nature of the structural damage to the lungs associated with IL-2 therapy-induced pulmonary edema; and (c) evaluate the effects of additional L-NAME therapy on the above-mentioned parameters. Results revealed that IL-2 therapy in healthy mice resulted in the expression of inducible NOS in numerous tissues including the endothelium and muscles of the anterior thoracic wall as well as splenic macrophages. One round of IL-2 therapy resulted in high levels of inducible NOS (iNOS) activity in the anterior thoracic wall accompanied by pleural effusion. After two rounds of IL-2 therapy, there was neither pleural effusion nor high iNOS activity in the thoracic wall. IL-2-induced pulmonary edema after one round of therapy correlated to both a significant rise in NO production measured in the serum and structural damage to the lungs and its capillaries. Addition of the NOS inhibitor L-NAME totally eradicated NOS activity but not necessarily iNOS expression. It also reduced IL-2-induced pulmonary edema and pleural effusion, restrained the rise in the levels of NO metabolites (nitrites and nitrates) in the serum and pleural effusion, and significantly restored the structural integrity of the lungs after one round of therapy. Thus, NOS inhibitors may be beneficial adjuncts to IL-2 therapy for cancer and infectious diseases.

Animals↗
PubMed1996

The potential effect of the UK 1990 height centile charts on community growth surveillance.

The UK 1990 height charts are derived from an up to date dataset and introduce a change in the centile lines, particularly the addition of the 0.4th centile. This study examined the likely impact of these changes. Height data from London school children (1990-1993) were examined using Tanner and Whitehouse (TW) and UK 1990 charts. Numbers of children with height below TW 3rd centile were compared with numbers below the UK 1990 3rd and 0.4th centiles. The TW charts identified only 1% of children below the TW 3rd centile, while the UK 1990 charts identified 3% below the 3rd and 0.4% below the 0.4th centiles. If the 3rd centile remains as the referral 'cut off' for short stature, the introduction of the UK 1990 charts would increase current workload two- to three-fold, while a change to the 0.4th centile would reduce it by 50%. A significant number of children with abnormalities may be excluded from further assessment as a result of this latter change. In this small scale community study it is not possible to assess the consequences of this change. The heights at diagnosis of children with growth hormone (GH) deficiency (peak GH < 20 mU/l during a standard provocation test) were therefore compared to the 0.4th centile (UK 1990 charts). Sixty eight children with heights < 2nd centile (UK 1990 charts) currently receiving GH replacement (17 female, 51 male, aged 9.7, SD 3.5, years) were assessed, and of these, 28 (41%) had heights at diagnosis between 0.4th and 2nd centile, with a mean height standard deviation score of -2.32 (SD 0.21). This suggests that if the 0.4th centile were to be used as the sole criterion for referral for slow growth, a significant proportion of children with abnormality would not be referred for further assessment. The UK 1990 2nd centile should replace the TW 3rd centile. Children below this should undergo an intermediary medical assessment to confirm height measurement, to exclude from referral children with mild familial short stature and to identify concerns regarding the child.

Body Height↗
PubMed1995

Characteristics of trophoblast cells migrating from first trimester chorionic villus explants and propagated in culture.

We developed a method of propagating pure first trimester human trophoblast cells growing out of primary explants of mechanically derived chorionic villus fragments (Yagel et al, 1989; Graham et al, 1992). We have now extensively characterized these cells during their initial outgrowth and in long-term culture, employing a variety of markers and techniques as outlined below. By double label immunofluorescence using epithelial (cytokeratin) and mesenchymal (vimentin) cell markers, we identified the chorionic villus migrant cell populations as pure trophoblast (39 per cent of outgrowths) or a mixture of trophoblast and fibroblast (61 per cent). Further phenotyping of the pure trophoblast outgrowths by double label immunostaining using anti-cytokeratin antibody and a panel of other primary antisera revealed that these cells exhibit a variety of markers characteristic of extravillous invasive trophoblast cells in situ: insulin-like growth factor (IGF)-II, NDOG-5, proliferating cell nuclear antigen (PCNA), human leucocyte antigen framework antigen (W6/32) and a distinct set of integrins including alpha 1, alpha 3, alpha 5, alpha v and beta 1 subunits and alpha v beta 3/beta 5 vitonectin receptor. They were negative for alpha 6 and beta 4 integrin subunits. Immunogold electron microscopy of explants grown on type IV collagen gel revealed the production of conventional and oncofetal types of fibronectin by mononucleate trophoblast cells and human placental lactogen by multinucleate cells. Immunolabelling, flow cytometry and immunoprecipitation revealed that this phenotypic profile was retained with complete fidelity in the long-term culture; thus, trophoblasts migrating out of first trimester chorionic villus explants and their propagated progeny belong to the invasive extravillous trophoblast of the placenta.

Cell Movement↗
PubMed1995

Construction of a community height surveillance programme: the Hackney growth initiative.

OBJECTIVES: To determine why, in the London Borough of Hackney before 1990, fewer children than expected were identified with remedial causes of short stature. To construct a practical model for height surveillance of 5 and 11 year old school entrants to improve the quality of child growth surveillance. SETTING: City and Hackney Borough, London, United Kingdom. METHODS: School nurses were trained by a clinical auxologist to measure children's height at school entry accurately and reproducibly. New procedures for measurement technique, plotting of data, referral, and audit were established. A reference manual was provided and a continuing training programme was started. RESULTS: During the first year the percentage of the target group measured was low. Changes in work practice led to improvements from 77% measured in the first year to 91% in the second year and 87% in the third year for 5 year olds. Improvements for 11 year olds were from 36% to 86% to 87% over the three years. Only 1.2% of 5 year olds and 2.6% of 11 year olds measured had height less than the third centile (compared with Tanner's height standards). CONCLUSIONS: School nurses measured height reliably. New audit procedures led to rapid changes in working practice and improvements in the percentage of children measured. The low numbers of short children previously identified with unrecognised abnormality may indicate an upward trend in height in this inner city population.

Body Height↗
PubMed1994

Taperloc femoral component. A 2-6-year study of the first 100 consecutive cases.

The first 100 consecutive patients who underwent insertion of the Taperloc (Biomet, Warsaw, IN) femoral stem were prospectively studied with a mean follow-up period of 3.8 years (range, 2-6 years). Two of the original 100 patients were lost, giving a 98% follow-up rate. The diagnoses included osteoarthritis (76 patients), avascular necrosis (19), rheumatoid arthritis (3), chrondrolysis (1), and post-traumatic arthritis (1). The mean age at surgery was 56 years (range, 25-79 years), mean weight was 78 kg (range, 45-127 kg), and the female to male ratio was 29:71. Charnley pain and function scores were 3.0 and 2.8 before surgery and 5.5 and 5.4 after surgery. Thigh pain was present in 2% of the patients at the final follow-up evaluation. There were no revisions. Radiographic signs of bone-ingrowth fixation (calcar atrophy, spot welds) were seen in 92 of 94 components (98%). No component had complete demarcation of the porous-coated zones. Fifty-two of 94 patients were able to be matched for age, sex, weight, diagnosis, and length of follow-up period with a series of patients who received a contemporary cemented total hip. In this matched subset, the Charnley pain and function scores were 5.6 and 5.5 for the cementless Taperloc stem and 5.7 and 5.5 for the cemented control group; this is not a significant difference. These data indicate a clinical performance equivalent to a matched group of contemporary cemented total hip arthroplasties.

Adult↗
PubMed1993

Ultrastructural analysis of gap junctions in C6 glioma cells transfected with connexin43 cDNA.

In the past, we transfected C6 glioma cells with connexin43 cDNA, resulting in a significant increase in connexin43 mRNA and protein, as well as reduced proliferation and tumorigenesis. To investigate the morphological aspects of increased connexin43 expression in these cells, we have used a combination of immunocytochemistry, cytochemistry, and electron microscopy. By confocal immunofluorescence microscopy, connexin43 protein was localized to the plasma membrane of transfected cells and extensive intracellular accumulations of connexin43 were also demonstrated. Freeze fracture preparations showed large aggregates of particles typical of mature gap junction plaques in the plasma membrane of these cells. Ultrastructural immunogold labeling with anti-connexin43 serum revealed that connexin43 protein was present in gap junctions in the plasma membrane, some of which were found in proximity to clathrin-coated pits. In addition, various intracellular membranous profiles were immunoreactive for connexin43, including annular profiles, some with fuzzy coats and some associated with lysosome-like structures. Enzyme cytochemistry revealed that these annular gap junction profiles were often associated with acid phosphatase-positive lysosomes. These studies on the intracellular localization of gap junction protein in connexin43-transfected cells are consistent with the functional expression of the transfected connexin43 cDNA and provide a useful model to study the pathways of gap junction assembly and degradation.

Acid Phosphatase↗
PubMedDate not supplied

Mortality experience of employees with occupational exposure to DBCP.

Concern about the carcinogenic potential of 1,2-dibromo-3-chloropropane(DBCP) has arisen recently, focusing on six organ sites: stomach, liver, kidney, lung, testes, and skin. To examine the mortality experience of persons potentially exposed, a cohort of 550 employees involved in production and formulation from 1957 to 1976 was defined. A total of 35 deaths was observed through 1979 (39.2 expected). No statistically significant excess was observed for any cause of death. No cancer deaths were noted for five of the hypothesized sites. For the lung cancer category, five deaths were observed (2.7 expected, P greater than .135), two of which occurred in a subgroup directly exposed for at least 1 yr (0.5 expected, P greater than .077). Aside from arsenicals exposure, potential confounding resulting from smoking or multiple chemical exposures could not be evaluated.

Antinematodal Agents↗
PubMedDate not supplied

Comparison of school nurse and auxologist height velocity measurements in school children with short stature. (The Hackney Growth Initiative).

To examine the possible use of height velocity (HV) as a growth screening tool, annual HV data calculated from height measurements made by school nurses were compared with those based on an auxologist's measurements in 20 short school children. The subjects were 12 primary school children (seven girls, five boys) with a mean (+/- SD) age of 5.9(0.6) years and eight secondary school children (six girls, two boys) with a mean (+/- SD) age of 11.8 (0.4) years. Heights were measured by the school nurses, separated by an interval of 1 year. Mean HV of the primary school children when assessed by school nurses was 5.92 cm/year compared with 5.97 cm/year when assessed by the auxologist. Mean (+/- SD) HV standard deviation score (HVSDS) was 0.03 (0.97) and 0.10 (1.15) respectively. Mean HV of the secondary school children when assessed by school nurses was 6.04 cm/year compared with 5.63 cm/year when assessed by the auxologist. Mean (+/- SD) HVSDS was -0.8 (2.1) and -1.21 (1.54) respectively. Of eight children (three primary, five secondary) identified by the auxologist as having HV < 25th centile of Tanner and Whitehouse standards only four were identified by school nurses (one primary, three secondary). One child identified by school nurses to have HV < 25th centile was found by the auxologist to be above the 25th centile. We conclude that HV assessment may fail to identify significant pathology in the community and that accurate height measurement rather than HV should be the principal referral criterion.

Anthropometry↗
PubMedDate not supplied

Characteristics of successful distributors in the community-based distribution of contraceptives in Guatemala.

A study conducted by the Asociación ProBienestar de la Familia (APROFAM) of Guatemala among 177 urban and 233 rural distributors in its CBD programs indicates a number of characteristics related to distributor success (measured by volume of contraceptives sold). Among urban distributors the most important factors were number of months the distributor had worked in the program, location of the CBD post, and the fact of promoting the service by displaying a poster and organizing community meetings about family planning. Among rural distributors, performance was highest among those who received assistance from their spouse, had local competition in the sale of contraceptives, promoted family planning by visiting their neighbors and organizing group meetings, had a higher level of education, and received frequent supervision. In general, factors involving program design and task performance were better predictors of distributor performance than the sociodemographic characteristics of the distributor.

Community Health Services↗
PubMedDate not supplied

Fine needle aspiration of medullary carcinoma of the thyroid. Cytomorphology, immunocytochemistry and electron microscopy.

OBJECTIVE: To analyze of medullary carcinoma of the thyroid (MCT) diagnosed by fine needle aspiration (FNA) utilizing cytomorphologic features and ancillary studies. STUDY DESIGN: Nine cases of MCT were collected, and the cytomorphologic findings were reviewed. Additionally, immunocytochemistry, immunoelectron microscopy and ultrastructural examination results were reviewed for selected cases. RESULTS: In five cases, loose groups predominated over single cells, whereas single cells predominated in three cases. One case showed only highly cohesive groups of cells. Most cells were round to oval, and every case had some degree of plasmacytoid morphology. Spindle-shaped cells were predominant in one case and were occasionally noted as a subpopulation in the other cases. Binucleation was noted in seven cases, and scattered, abnormally large nuclei were identified in five cases. The cytoplasm was moderate to abundant and delicate in all cases. Routine immunocytochemical staining for calcitonin and chromogranin was positive in three of four cases, and staining positive for the markers was detected by immunoelectron microscopy in two cases. In four cases, electron microscopy revealed neurosecretory granules. CONCLUSION: The cytomorphologic appearance of medullary thyroid carcinoma is highly distinctive, and the diagnosis can be corroborated by appropriate ancillary studies.

Adult↗