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Biomedical subjects

S Hunter

Publications and source records attributed to S Hunter.

At least 73 records · Page 4Linked to original sources

Necrotizing cerebritis in an allogeneic bone marrow transplant recipient due to Cladophialophora bantiana.

We describe a necrotizing cerebritis in an allogeneic bone marrow transplant recipient caused by the neurotropic, dematiaceous fungus Cladophialophora bantiana. The patient presented 7 months after bone marrow transplantation with fever and sudden onset of left-sided weakness, followed shortly by cranial nerve III and VI palsies. The patient had a lesion (3.0 by 2.0 by 2.0 cm) of the right midbrain with extension to the pons, the left brain stem, and the right superior and the middle cerebellar peduncles. The diagnosis was made by microscopic examination and culture of a brain biopsy.

Adult↗

Haemodynamic features at presentation in persistent pulmonary hypertension of the newborn and outcome.

Thirty four newborns presenting with persistent hypoxaemia in the first three days of life underwent detailed haemodynamic assessment using Doppler echocardiography, including measurements of pulmonary arterial pressure (PAP), left ventricular (LV) function, and left ventricular output (LVO). Results were compared with values from 51 healthy babies, and those of survivors were compared with non-survivors. Four of the 34 babies were excluded from this analysis because one was found to have transposed great arteries, one had a large left-to-right shunt with no evidence of persistent pulmonary hypertension, and two had diffuse skeletal myopathy. Tricuspid regurgitation was present in 70%, permitting systolic PAP estimation. The pulmonary:systemic arterial pressure ratio range was 0.7:1 to 1.83:1 (mean 1.02:1). A patent duct was present in 83%, and flow patterns indicated PAP approaching, or above, systemic pressure in all. Systolic time interval ratio TPV/RVET (time to peak velocity at the pulmonary valve/right ventricular ejection time) was mostly (65%) in the normal range, and did not correlate with other PAP measurements. LV function was below the 10th centile in only 11%, but values for LVO lay below the 10th centile in 41%, and for left ventricular stroke volume index (LSVI) in 66%. Results of 18 survivors were compared with 10 non-survivors (excluding two premature babies who died early with pulmonary interstitial emphysema). There were no significant differences for any parameter of PAP or LV function, but LVO and LSVI were significantly lower in non-survivors: LVO survivors (mean (SD)), 205 (57), non-survivors 138 (63) ml/kg/minute (P < 0.01); LSVI survivors, 1.29 (0.51), non-survivors 0.86 (0.31) ml/kg (P < 0.05). All four babies with LVO < 100 ml/kg/minute died, and 6/7 babies with LSVI < 1 ml/kg died. Detailed echocardiographic evaluation shows that the haemodynamic features of persistent pulmonary hypertension are diverse and that clinical diagnosis can be incorrect. Low LV output and stroke volume, usually with normal LV function, were the only Doppler echocardiographic parameters to predict subsequent death. This correlation with outcome requires further prospective evaluation.

Blood Pressure↗

Natural history of trisomy 18.

It has been suggested that survival in babies with trisomy 18 may be better than previously recognised, and that cardiac surgery may be justified. A population based study spanning seven years in one English health region is presented. The fetal prevalence at 18 weeks was 1 in 4274 and birth prevalence 1 in 8333 live births. Trisomy 18 was detected antenatally in 43% of cases, but almost 90% of those born without a diagnosis were known to be growth retarded in utero. More than 50% of liveborn infants were delivered by caesarean section. The median survival of those born alive was 3 days with no babies living longer than one year. Cardiac malformations were not universal but were present in more than 87% of those for whom there were data. However, in only three cases were cardiac problems implicated in the death of the infants. Cardiac surgery is not likely to improve the survival of infants with trisomy 18 and at present cannot be justified. The most common mode of death was central apnoea.

Adult↗

Family planning requirements in the adult congenital heart disease clinic.

OBJECTIVE: To determine whether women with congenital heart disease were receiving appropriate advice on contraception. SETTING: Adult congenital heart disease clinic in a tertiary cardiac referral centre. DESIGN: Questionnaire administered to 35 consecutive female patients attending the adult congenital clinic. The cardiologist assessed what the risk would be if each patient used an oestrogen containing contraceptive pill (OCP). RESULTS: Of the 33 patients admitted to the study 6 patients thought their heart condition precluded them from taking an OCP when in fact it did not and 3 incorrectly said that an OCP would be suitable for them. Three women with relatively minor lesions had been incorrectly denied the OCP and 2 further patients were using inappropriate methods. There had been 6 unwanted pregnancies in the total group. CONCLUSIONS: Many women with congenital heart disease do not know the most appropriate method of contraception for them or have received incorrect advice. It is often patients with less severe lesions who receive the most inappropriate advice. It is clear that the family planning needs of this population are currently poorly catered for. Each unit must ensure that the information necessary in making informed decisions on contraception is available to the doctor advising on family planning.

Adolescent↗

The molecular dissection of Fc gamma receptor mediated phagocytosis.

Because hematopoietic cells express multiple Fc gamma receptor isoforms, the role of the individual Fc gamma receptors in phagocytosis has been difficult to define. Transfection of Fc gamma receptors into COS-1 cells, which lack endogeneous Fc gamma receptors but have phagocytic potential, has proved valuable for the study of individual Fc gamma receptor function. Using this model system, we have established that a single class of human Fc gamma receptor mediates phagocytosis in the absence of other Fc receptors and that isoforms from each Fc gamma receptor class mediate phagocytosis, although the requirements for phagocytosis differ. In investigating the relationship between structure and function for Fc gamma receptor mediated phagocytosis, the importance of the cytoplasmic tyrosines of the receptor or its associated gamma chain has been established. For example, two cytoplasmic YXXL sequences, in a configuration similar to the conserved tyrosine-containing motif found in Ig gene family receptors, are important for phagocytosis by the human Fc gamma receptor, Fc gamma RIIA. Fc gamma RI and Fc gamma RIIIA do not possess cytoplasmic tyrosines but transmit a phagocytic signal through interaction with an associated gamma subunit that contains two YXXL sequences in a conserved motif required for phagocytosis. The human Fc gamma RII isoforms Fc gamma RIIB1 and Fc gamma RIIB2 do not induce phagocytosis and have only a single YXXL sequence. Cross-linking the phagocytic Fc gamma receptors induces tyrosine phosphorylation of either Fc gamma RIIA or the gamma chain, and treatment with tyrosine kinase inhibitors reduces both phagocytosis and phosphorylation of the receptor tyrosine residues. Activation of protein tyrosine kinases follows Fc gamma receptor engagement of IgG-coated cells. The data indicate that coexpression of the protein tyrosine kinase Syk, which is associated with the gamma chain in monocytes/macrophages, is important for phagocytosis mediated by Fc gamma RI and Fc gamma RIIIA. Furthermore, phosphatidylinositol-3 kinase is required for phagocytosis mediated by Fc gamma RIIA as well as for phagocytosis mediated by Fc gamma RI/gamma and Rc gamma RIIIA/gamma.

Amino Acid Sequence↗

Molecular dissection of Fc gamma receptor-mediated phagocytosis.

Using an experimental model in COS-1 cells, we have examined the structural requirements for phagocytosis of IgG-sensitized cells by Fc gamma receptors. We have established that isoforms of each of the 3 classes of the Fc gamma receptors, Fc gamma RI, Fc gamma RII and Fc gamma RIII, are able to transmit a phagocytic signal in the absence of the other receptor class. Fc gamma I and Rc gamma RIIIA require a gamma-subunit for this signaling event, but Fc gamma RIIA does not. Fc gamma RIIA and the gamma-subunit associated with Fc gamma RI and Fc gamma RIIIA contain 2 copies of a conserved tyrosine-containing cytoplasmic sequence, YXXL. This sequence is important for phagocytosis and is phosphorylated on tyrosine after receptor ligation. The Fc gamma receptors Fc gamma RIIB1 and Fc gamma RIIB2 which contain only 1 copy of the YXXL cytoplasmic sequence do not include the phagocytosis of IgG-coated cells. Thus, the Fc gamma receptor isoforms differ in their ability to transmit a phagocytic signal. Structure/function studies also indicate that the Fc gamma receptors which induce phagocytosis differ in their requirements for phagocytic signaling.

Amino Acid Sequence↗

Structure/function relationships of Fc gamma receptors in phagocytosis.

An important function of Fc gamma receptors is the ingestion or phagocytosis of IgG sensitized cells. It has been difficult to clearly define the individual function of each receptor in phagocytosis because hematopoietic cells express multiple Fc gamma receptor isoforms. To examine this issue, an in-vitro model system in COS-1 cells has been developed. When transfected with an appropriate Fc gamma receptor, COS-1 cells which lack endogeneous Fc receptors, ingest IgG-sensitized cells. Using this model, a single class of human Fc gamma receptor in the absence of other Fc receptors was observed to mediate phagocytosis. Furthermore, isoforms from each Fc gamma receptor class can mediate phagocytosis although the requirements for phagocytosis differ. Investigation of the relationship between structure and function for Fc receptor-mediated phagocytosis established the importance of the cytoplasmic tyrosines of the receptor or its associated gamma chains. For example, two cytoplasmic YXXL sequences, in a configuration similar to the conserved tyrosine containing motif found in immunoglobulin gene family receptors, are important for phagocytosis by the human Fc gamma receptor, Fc gamma RIIA. Fc gamma RI and Fc gamma RIIIA do not possess cytoplasmic tyrosines, but transmit a phagocytic signal through interaction with an associated gamma-subunit which contains two YXXL sequences in a conserved motif required for phagocytosis. The human Fc gamma RII isoforms, Fc gamma RIIB2, do not induce phagocytosis and have only a single YXXL sequence. Crosslinking of the phagocytic Fc gamma receptors induces tyrosine phosphorylation of either Fc gamma RIIA or the gamma chain and treatment with tyrosine kinase inhibitors reduces both phagocytosis and phosphorylation of the receptor tyrosine residues. The protein tyrosine kinase Syk, which is associated with the gamma chain in monocytes/macrophages, dramatically enhances phagocytosis mediated by Fc gamma RI and Fc gamma RIIIA and also induces non-phagocytic Fc gamma RI or Fc gamma RIIIA expressing cells to acquire phagocytic capability.

Amino Acid Sequence↗

Susceptibility of human monocytes to HIV type 1 infection in vitro is not dependent on their level of CD4 expression.

Monocytes from HIV-seronegative persons were analyzed for CD4 expression and susceptibility to infection with HIV-1 on the day of isolation and following 1, 2, and 7 days in culture. Although surface CD4 was readily detected on freshly isolated monocytes, these cells were relatively resistant to infection. After 1 to 2 days in culture, when surface expression of CD4 had decreased over 90% to near background levels, cells became susceptible to infection with HIV-1. CD4 expression on monocytes cultured for 7 days was more than four times higher than that on freshly isolated cells, and the cultured cells were fully permissive to infection. These observations suggest that the differing susceptibility of monocytes and monocyte-derived macrophages to infection with HIV-1 is not simply proportional to the level of surface CD4 expression.

Antigens, CD↗

Analysis of epidermal growth factor receptor gene amplification and alteration in stereotactic biopsies of brain tumors.

In recent years, results from molecular-based investigations of central nervous system neoplasms have indicated that the occurrence of specific genetic alterations correlates with tumor malignancy and clinical behavior. One such example is epidermal growth factor receptor gene amplification and alteration in association with tumors histologically classified as glioblastoma multiforme. As our understanding of the implications of these changes develops, detection of epidermal growth factor receptor alteration and amplification may have diagnostic, prognostic, and ultimately, therapeutic value. The goal of this communication is to demonstrate the usefulness of stereotactic specimens for molecular genetic analysis, in this case, the analysis of the epidermal growth factor receptor gene for amplification and alterations. The techniques used here will maximize the number of cases from which useful information can be obtained. Properly adapted, the value of these techniques for expanding our understanding of these lesions is enormous.

Biopsy↗

Analysis of patient doses for myelogram and discogram examinations and their reduction through changes in equipment set-up.

Patient doses for myelogram and discogram examinations performed on two C-arm X-ray units have been measured using dose-area product meters. Contributions to the dose from fluoroscopy and radiography have been obtained from analysis of results for a selection of examinations. Information was recorded about the individual beam projections used, in order to allow estimates of effective dose. Effective doses for lumbar myelograms were 3-4 mSv and for cervical myelograms and discograms were 1 mSv. The doses on the two units were similar, but contributions from the various parts of the examinations were different. Quality assurance (QA) measurements of dose variables were used to determine reasons for these differences in performance. Fluoroscopic doses are influenced by image intensifier dose rate and by the way in which exposure factor selection has been set up for the automatic exposure control (AEC) system. Doses from digital fluorography on units for specialized applications may be greater than those with standard film/screen systems. Recommendations have been made concerning ways in which doses on each unit might be reduced. Detailed assessments of doses resulting from AEC set-up options, made during QA tests, can help to ensure that the optimum balance between patient dose and image quality is achieved.

Fluoroscopy↗

The economic impact of corporate wellness programs: past and future considerations.

1. A primary goal of health promotion is to motivate individuals to make positive life-style changes. 2. Health promotion is multifaceted and each company must select the most appropriate method(s) of intervention for their employees. 3. In any company, a successful health promotion program requires an advocate or champion who functions as the initiator and leader for program development. Employee involvement, from inception to ongoing development of all programs, is also necessary for success. 4. To positively impact health care costs, health promotion programs should be well planned, well timed, and appropriately marketed. Needs of all workers (i.e., blue collar, minorities) should be considered.

Forecasting↗

Interposition of 'wide' cycloperistaltic segments into isolated segments of jejunum--influence on fluid perfusion.

Two isolated jejunal segments (Thiry-Vella (T-V) loops) were created in 7 dogs. One contained a 'wide' cycloperistaltic (C-P) segment while the other, acting as a control, did not. The C-P segment had the same diameter as the jejunum. Fluid perfusion experiments showed that there were no changes in the volume of output, absorption and pooling of the fluid in the T-V loops containing the 'wide' C-P segment. This was in contrast with significant changes shown in earlier experiments using 'narrow' C-P segments.

Animals↗