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Biomedical subjects

W Greer

Publications and source records attributed to W Greer.

At least 19 recordsLinked to original sources

Systemic amphotericin B versus fluconazole in the management of antibiotic resistant neutropenic fever--preliminary observations from a pilot, exploratory study.

A pilot exploratory study was undertaken to collect preliminary information relating to safety and overall outcome in using intravenous fluconazole (FLUC) for managing antibiotic resistant neutropenic fever (ARNF), with the objective of assessing feasibility of performing a larger prospective controlled study. Patients who were neutropenic from treatment for leukaemia or bone marrow transplantation, received either fluconazole (FLUC) or amphotericin B (AB). Eight of 16 patients (50%) on FLUC and 21 of 25 patients (84%) on AB defervesced; the mean time to defervescence was 11.0 +/- 10.0 days for FLUC compared to 7.7 +/- 6.3 days for AB, and a similar proportion in each treatment group defervesced within 5 days (50% vs. 52%), respectively. Six of 16 patients (37.5%) on FLUC and three of 25 patients (12%) on AB developed overt invasive fungal disease, including pulmonary aspergillosis (FLUC 4 cases, AB 2 cases) and invasive candidiasis (FLUC 2 cases, AB 0 cases). The mean time to these events was 19.5 +/- 13.4 (FLUC) and 9.0 +/- 3.6 (AB) days. The fungal related mortality rates were higher in the FLUC group: five of 16 patients (31%) vs. two of 25 patients (18%) died respectively; the time to fungal death was 43.2 +/- 18.2 (FLUC) and 25.0 +/- 18.4 (AB) days. This tendency towards a more favourable outcome in patients on AB may have been due to absence of prior fluconazole prophylaxis in patients subsequently receiving IV FLUC. Analysis of a small subgroup of patients who had all received prior prophylaxis with clotrimazole only, indicated that a greater number of patients subsequently receiving IV FLUC died from fungal disease (5/16 vs.0/6, P = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Alpha-1-antichymotrypsin inhibits the NADPH oxidase-enzyme complex in phorbol ester-stimulated neutrophil membranes.

The generation of superoxide anion and release of granule contents are essential to the bactericidal function of neutrophils, but may also contribute to host tissue damage during inflammation. In previous studies (J. Immunol. 146:2388), we have demonstrated that the acute phase reactant alpha-1-antichymotrypsin (ACT), a potent inhibitor of the serine protease cathepsin G, also suppresses superoxide anion generation. The inhibitory effect of ACT was not directly linked to its antiproteolytic activity and may reflect interaction at a site other than its reactive loop. To further characterize the mechanism of inhibition, we investigated the direct effects of ACT on the NADPH oxidase enzyme complex and the signaling pathways that regulate motivation of the respiratory burst. We present evidence that ACT does not intefer with agonist-stimulated calcium mobilization or translocation and activity of protein kinase C. ACT was an effective inhibitor of superoxide anion generation in membrane preparations isolated from PMA-activated cells. These results support the notion that ACT is acting on a component of the active assembled NADPH oxidase complex. Thus, ACT may have an important role in regulation of specific aspects of the inflammatory processes and the modulation of toxic oxygen-based host tissue damage.

Arachidonic Acid

Unknown dysmorphic syndromes and development delay in Saudi Arabia.

Forty-four Saudi Arabian patients with unknown dysmorphic syndromes were studied with respect to their level of cognitive delay. The relationship between such delay and particular patterns of dysmorphic features, as well as various demographic and historical data, were also investigated. Prognostication and genetic counseling are difficult for this group because little is known about morbidity or other factors. These concerns, along with broader issues, stimulated this study. Significant associations were found between level of cognitive function and consanguinity, abnormal motor and language milestones, and abnormal electroencephalograms. No significant relationship was found between various dysmorphic feature clusters and measured cognition. Concerns were expressed about demands on family and community for these children, as well as possible larger issues in this heavily consanguineous society. Further research, including epidemiologic studies, was recommended.

Abnormalities, Multiple

Skin fibroblast cell lines derived from non-Hodgkin's-lymphoma (NHL) patients show increased sensitivity to chronic gamma irradiation.

Cultured fibroblast cells from 19 patients with non-Hodgkin's lymphoma (NHL), 3 patients with ataxia telangiectasia (AT), 3 AT heterozygotes and 11 (presumed) normal subjects were studied for impaired colony-forming ability after chronic gamma irradiation. Five cell lines from the NHL patients were also examined for the sensitivity to acute gamma irradiation, as compared with those of normal subjects. To ascertain the degree of radiosensitivity of different cell lines, a comparison was made of the D10 values (radiation dose resulting in 10% survival) for each cell line, estimated "by eye" from the actual survival curves, and also from the calculated curves fitted to a log-linear model. It was observed that the acute gamma irradiation failed to show any appreciable difference in the radiation response of the cell lines from NHL patients as compared with those of normal subjects. However, chronic irradiation demonstrated significantly increased radiosensitivity in at least 10-12 NHL patients with a p value of less than 0.05, when the D10 values of each patient's cell line were compared with the calculated composite values for the normals. When the D10 values of the NHL patients and the normal subjects were compared as 2 groups, the former appeared to be significantly more sensitive to chronic gamma irradiation (p less than 0.0001). The same level of significant difference in radiosensitivity was found between the 2 groups when their D37 values (radiation dose resulting in 37% survival) were compared. In general, the radiation response of the NHL patients was similar to that of the AT homozygotes and heterozygotes used as a positive control group. Our data thus show that increased radiosensitivity is associated with the NHL patients studied, indicating an underlying abnormality of their DNA repair.

Adult

Effect of sustained serum prolactin elevation on breast epithelial and myoepithelial cell proliferation.

Oral administration of the dopamine antagonist perphenazine (0.01% in drinking water) to adult female Sprague-Dawley rats led to a three- to fourfold increase in serum prolactin by the first time point sampled (day 2) and a sustained fourfold elevation from day 4 of treatment to the end of the experiment (day 54). In response, five- to sixfold (day 7) and three- to fourfold (day 4) peak elevations in the epithelial cell metaphase indices were seen in the breast lobular and ductular compartments respectively. Both indices fell to basal levels on day 14 but returned to a second, but diminished, peak on day 27. By day 54, the mitotic activity of the epithelium had fallen to just above basal levels in both compartments. A similar mitotic response occurred in the myoepithelial cells, clearly indicating that these must be considered an important cell kinetic component during breast stimulation. Breast epithelial cell number increased 13-14 fold in the lobular but only two- to threefold in the ductular compartments in response to perphenazine administration. Again, similar responses were seen in the myoepithelial cell population. The major proliferative response therefore occurred within the lobular as opposed to the ductular compartment. A considerable discrepancy was shown between the cell number at each time point and that predicted on the assumption of constant cell death rate. We conclude that a growth desensitizing mechanism exists in the rat breast which limits breast growth in the presence of a sustained trophic hormone stimulation. Furthermore, we suggest that this limitation in breast growth is brought about by a mechanism which involves increased cell death in addition to decreased mitotic activity.

Animals

Responses of two mammalian cell lines to low gamma-ray doses.

We have observed that low gamma-ray doses regularly improve the survival (plating efficiency) above that of unirradiated control cultures, which we postulate could arise through inducible DNA repair, and would have profound effects on the interpretation of cell culture experiments.

Animals

Relative biological effectiveness (RBE) of p(26) + Be neutrons from the King Faisal Specialist Hospital and Research Centre CS-30 cyclotron measured by testis weight loss.

Testis weight loss of C3H and Swiss-Webster (SW) mice was used as endpoint to determine the relative biological effectiveness (RBE) of p(26) + Be fast neutrons with respect to Co-60 gamma irradiation. Percent weight loss versus dose curves showed two components. Comparing first component effects, the RBE was 3.4 (C3H) and 3.7 (SW); when the second component was used, the RBE was 2.6 and 2.7 (C3H), and 3.5 (SW). When percent weight loss was plotted versus log dose, parallel lines were obtained, giving an RBE of 3.9 and 4.1 (C3H), and 4.2 (SW). Results were compared with published values and RBE as a function of fast neutron energy was plotted. A good correlation was found. Discrepancies seem to be mostly due to the use of different baseline radiation. When a constant correction is made, most of the values fit a single line. The possibility of using this approach as a substitute for international comparisons is discussed.

Animals

Chicken mucin-cross-reactive antigen.

We have previously described a chicken heterophile antigenic determinant (CHAD-1) shared by Mycobacterium smegmatis and chicken tissues. We then demonstrated that CHAD-1 is present on several chicken glycoproteins and that its immunoreactive domains are highly branched asparagine-linked oligosaccharides terminating in N-acetylglucosamine residues. In the present study, we have shown that CHAD-1 is also expressed by mucin purified to homogeneity from a soluble mucus of chicken intestine. Another antigen found on chicken mucin is a chicken mucin-cross-reactive antigen (CMCRA). Antisera to this antigen were produced by immunization of rabbits with an enriched preparation of CHAD-1 isolated from the bursa of Fabricius. These antisera were absorbed with Mycobacterium smegmatis (to block the anti-CHAD-1 antibody) and with chicken serum, and then used for immunoperoxidase staining of chicken tissue sections for CMCRA. The latter antigen was detected in most medullary cells of the bursa, in epithelial cells and Hassal's corpuscles of the thymus, and in mucus-producing cells of the intestine, esophagus, trachea, and bronchi. Using Western immunoblot analysis, we demonstrated that CMCRA is expressed by a number of polypeptides extracted from bursal lymphoid cells. These polypeptides could not be detected in extracts of thymus, spleen, peripheral blood or bone marrow mononuclear cells.

Animals

Nasopharyngeal carcinoma in Saudi Arabia: a retrospective study of 166 cases treated with curative intent.

A retrospective review was performed of the medical records of 166 adult patients with biopsy-proven carcinomas of the nasopharynx treated with curative intent at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. All patients were treated between June 1975 and December 1985 using megavoltage therapy equipment. Most patients presented with advanced nodal disease: 23 patients (13.9%) were N0, 16 patients (9.6%) were N1, 29 patients (17.5%) were N2, and 98 patients (59%) were N3. The overwhelming majority of patients had nonkeratinizing lesions (158/166). At the time of analysis, mean follow-up time was 24.2 months (range 2-108). Actuarial curves are presented for local/regional control as a function of T-stage and N-stage and for survival and time to development of distant metastases as a function of N-stage. At 4 years local/regional control was 70% for T1 lesions, 59% for T2 lesions, 30% for T3 lesions, and 35% for T4 lesions. There was little correlation between local/regional control and N-stage being about 50% at 4 years for all nodal subgroups. Only six patients exhibited an isolated first failure in the regional nodes alone, whereas 60 patients failed initially at the primary site (either alone or in conjunction with a simultaneous nodal failure). The development of distant metastases correlated to some extent with nodal disease ranging from 20% at 4 years for T1/T2 N0 patients to 70% for patients who initially presented with N3 disease. Survival data was more difficult to obtain due to cultural biases in a medically unsophisticated patient population. True survival curves are bounded by calculating actuarial curves in two ways: death as the failure endpoint and death plus lost-with-active-disease as failure endpoints. In terms of the latter curves, at 4 years "survival" ranged from 39% for patients with T1/T2 N0 lesions to 23% for patients with N3 lesions.

Adult

A software package for the manipulation, display and analysis of electron and light microscope data.

Quantitative light and electron microscopy is an expanding field which has found applications in many biological disciplines. Computer-enhanced data-acquisition has led to increased speed and accuracy, and combined with computational analysis, stereological parameters can be quickly derived and spatial hypotheses can be easily tested. A software package is described, which controls the manipulation, display and analysis of two-dimensional microscope data. Features include alignment of specimens, rotations, translations, deletions, recoding, perimeter and area measurement, point-counts, tests of dispersion and tests of spatial distributions. The programme is graphics-orientated and supports various point-plot modes and histograms. It includes linear and non-linear curve-fitting options and has been specifically designed to encourage new analysis procedures, which automatically benefit from existing graphics options.

Data Collection

A prime number approach to biological sequencing.

Computational sequencing of nucleic acid and amino acid sequences is placing increasing demands on computer resources. The use of prime numbers is explored as a convenient means of improving program speed and reducing storage requirements. It is concluded that the application of the prime number approach leads to significant increases in speed and some reduction in storage requirements.

Amino Acid Sequence

Neurological mapping using an electron microscope/microprocessor data acquisition system.

Quantitative electron microscopy is used widely in many neurobiological laboratories but can be greatly enhanced by the computer storage, display and analysis of features or boundaries observed under the microscope. An interactive system is described, in which a microprocessor and microcomputer combination controls the data acquisition and display; more detailed analysis can be carried out on a mainframe computer. The performance of this system is examined and it is shown to be a cheap and effective solution, capable of expansion in many directions.

Animals

A versatile closed circuit.

A versatile closed circuit with new features is described. It may be used in a totally closed manner, without continuous gas inflow. As gas is absorbed from the circuit, it is replaced through a demand valve. Facilities for continuous gas input and use of a ventilator are included, and one control converts it to a non-rebreathing circuit. The circuit has excellent mechanical characteristics in all modes, and has been used extensively in routine clinical practice.

Adolescent

Mass spectrometry in anesthesia. Problems in using mass spectrometer for monitoring anesthetic gases and vapours.

The use of mass spectrometers for total gas monitoring during anesthesia presents a number of problems which stem from the Cracking Pattern of the gases present, inlet design, viscosity variations, water vapour and machine deterioration. Some of these have been adequately solved, by making mechanical modifications to the inlet system, and by using more complex electronic circuitry to process the signals obtained. Remaining problems, however, still limit accuracy and ease of operation. CO2 measurements are particularly prone to error, especially when sampling halothane-containing gas which leads to significant internal production CO2. A study of the principal sources of error remaining in the machine suggests that the only definitive solution is to develop a microprocessor system which could cope with complex Cracking Patterns and non-linearities, and which would allow complete automation of the calibration procedure.

Anesthetics