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Biomedical subjects

D O'Sullivan

Publications and source records attributed to D O'Sullivan.

At least 55 records · Page 3Linked to original sources
PubMed1997

Comparison of alternative buffers for use with a new live oral cholera vaccine, Peru-15, in outpatient volunteers.

During development of Peru-15, a new live oral vaccine for cholera, the role of buffer needed to be evaluated. Generally, oral bacterial vaccines are acid labile and need to be administered by using a formulation which protects them from gastric acid. We compared three different buffers for use with Peru-15, including a standard bicarbonate-ascorbic acid buffer, Alka-Seltzer, and a new electrolyte-rice buffer, CeraVacx. Saline served as the control. Thirty-nine healthy adult volunteers received Peru-15 (10(8) CFU) with one of the three buffers or saline in a double-masked study. The volunteers were monitored for symptoms for 7 days after the dose, serum was tested for antibody responses by vibriocidal antibody and immunoglobulin G antitoxin enzyme-linked immunosorbent assays, and stool samples were tested for excretion of the vaccine strain. Side effects were minimal in all groups. All 30 volunteers who took Peru-15 with a buffer showed significant rises in vibriocidal antibody titer. The magnitude of the rises was higher in the CeraVacx group than in the other two buffer groups. Four of nine volunteers who took the vaccine with saline also showed increased titers, but they were lower than those in any of the three buffer groups. Excretion of the vaccine strain was similar in the buffer groups, but excretion was not associated with the magnitude of the vibriocidal responses. Excretion of Peru-15 was not detected in the saline group. We conclude that buffer does amplify the serological response to Peru-15 and that CeraVacx may provide benefits not provided by other buffers.

Administration, Oral↗
PubMed1996

Investigation of Z > or = 70 cosmic ray nuclei on the LDEF mission.

The ultra heavy cosmic ray experiment (UHCRE) on the Long Duration Exposure Facility (LDEF) collected approximately 3000 cosmic ray nuclei with Z > 65 in the energy region E > 1.5 GeV/n. Almost 40% of the sample has been analysed to date. Details of the overall charge abundance pattern is outlined with estimates of the actinide abundance.

Actinoid Series Elements↗
PubMed1996

Neutropenia and agranulocytosis in patients receiving clozapine in the UK and Ireland.

BACKGROUND: Clozapine can cause reversible agranulocytosis and neutropenia. This study documents the occurrence of blood dyscrasias and identifies predisposing risk factors. METHOD: An analysis was made of the haematological, demographic, and dosage data from a central database on 6316 patients receiving clozapine over four and a half years in the UK and Ireland. RESULTS: During the study period, 2.9% of the patients developed neutropenia and 0.8% developed agranulocytosis. The peak incidence of both disorders was in the first 6-18 weeks of treatment. Fatal agranulocytosis occurred in 0.03% of patients. After the first year of treatment, the incidence of agranulocytosis significantly decreased to the order noted with some phenothiazines. CONCLUSIONS: The use of a patient monitoring service kept the haematological risks associated with using clozapine within acceptable limits, particularly in view of the benefits of this medication in treatment-resistant schizophrenia.

Adult↗
PubMed1996

Physician directed networks: the new generation of managed care.

The external pressure to reduce cost while maintaining quality and services is moving the whole industry into a rapid mode of integration. Hospitals, vendors, MCOs, and now, physicians, are faced with the difficult decisions concerning how their operations will be integrated into the larger health care delivery system. These pressures have forced physicians to consolidate, build leverage, and create efficiencies to become more productive; thereby better positioning themselves to respond to the challenges and the opportunities that lie before them. This initial phase of consolidation has given many physicians the momentum to begin to wrestle back the control of health care and the courage to design the next generation of managed care: Physician Directed Managed Care. What will be the next phase? Perhaps, the next step will be fully-integrated specialty and multi-specialty groups leading to alternate delivery sites. "Everyone thinks of changing the world, but no one thinks of changing himself." - Leo Tolstoy

Community Networks↗
PubMed1995

Follow up of an immunocompromised contact group of a case of open pulmonary tuberculosis on a renal unit.

BACKGROUND: The organisation, management, outcome and cost of follow up of a large group of mainly immunocompromised patients and healthcare workers who were exposed to a staff member of a London renal unit with smear positive pulmonary tuberculosis are described. METHODS: Following British Thoracic Society (BTS) guidelines, 576 close contacts were identified and divided into three groups: (1) 303 renal patients including 61 with renal transplants; (2) 90 surgical patients; and (3) 183 staff members. Screened contacts were interviewed, completed a symptoms questionnaire, and were offered a chest radiograph and Heaf or Mantoux test if appropriate with referral to a chest physician if required. RESULTS: Overall, 524 (85%) living contacts have been screened: 243 (97%) renal (first screening), 63 (70%) surgical, and 135 (74%) staff contacts. Thirty one transplant patients were prescribed isoniazid chemoprophylaxis. Fifty two renal patients had died before screening and 11 deaths occurred after first interview. One case of tuberculosis epidemiologically related to the index case was diagnosed on clinical criteria. A review of the case records and/or death certificates and entries on to tuberculosis registers indicated no further cases. The cost of the investigation was estimated to be approximately franc25 000, or franc44 per contact screened, with staff costs comprising 79% of the total. CONCLUSIONS: Undiagnosed tuberculosis in healthcare workers working with immunosuppressed patients can lead to large and expensive follow up studies. The applicability of the 1990 and 1994 BTS guidelines to the investigation of tuberculosis in an immunocompromised nosocomial group, and the role of the infection control doctor and the consultant in Communicable Disease Control in overlapping nosocomial and community incidents, are discussed.

Adolescent↗
PubMed1995

Effective hospital leadership for quality: theory and practice.

Hospitals need excellent leadership to be efficient in the use of scarce stakeholder resources and to be effective in the competitive provision of services to multiple customers. This study was conducted with the cooperation of the executive team at a large government-funded hospital in Brisbane. It focused on understanding the conceptual models of leadership held by members of the executive and comparing this model with an externally derived model of leadership. Performance on the local model was estimated by cross-linking performance assessment on the external model. Members of the executive espoused, and were also rated by others in the hospital as practising, to a moderate degree, a transformational style of leadership. An overall evaluation of quality practice in the hospital revealed the use of data, the understanding of processes and the formation of supplier partnerships as the areas of hospital activity most limiting the ability to improve. The implications of the conceptual model and performance levels are discussed in relation to the introduction of quality management practice in the hospital, and in terms of management development. A complementary paper focusing on quality implementation as perceived at different staff levels in the hospital is in preparation.

Australia↗
PubMed1994

Application of the Scarff-Bloom-Richardson tumor grading system to fine-needle aspirates of the breast.

Assigning a tumor grade to breast cancers provides important prognostic information. This study evaluated the applicability of the Scarff-Bloom-Richardson (SBR) breast cancer grading system to aspiration biopsy cytology. Thirty-five consecutive breast cancer fine-needle aspirates and their surgical specimens were reviewed by two pathologists. An SBR grade of 1-3 was assigned by each pathologist to both the fine-needle aspirate and biopsy specimen, based on the sum of scores given to each of three features: tubular differentiation, nuclear pleomorphism, and mitotic index. Both pathologists assigned the same SBR score to 74.3% of biopsy specimens and 65.7% of fine-needle aspirates. The cytologic grade could be used to predict the histologic grade in as many as 57.1% of cases. The wide disparities in the cytologic and histologic grades in some cases were chiefly due to difficulties in detecting mitoses or tubules in the cytology.

Biopsy, Needle↗
PubMed1993

Determination of threshold UV-A elicitation dose in photopatch testing.

Photopatch testing, although widely used in the diagnosis of photosensitivity disorders, is not standardized. We performed this study to determine the threshold ultraviolet light A (UV-A) dose required to elicit photopatch test responses. 4 patients with previously positive tests were reexposed to the offending allergen, using an incremental dosage regime. Isopropyl dibenzoylmethane (Eusolex 8020), mexenone (benzophenone-10) and oxybenzone (benzophenone-3) produced positive responses at 1.0, 1.0 and 0.7 J/cm2, respectively. Responses to phenothiazines were deemed phototoxic. These results demonstrate that high doses of UV-A (e.g., 10-15 J/cm2) are unnecessary, and that 5 J/cm2 should become the current standard.

Adult↗
PubMed1992

Interaction of the pertussis toxin peptide containing residues 30-42 with DR1 and the T-cell receptors of 12 human T-cell clones.

The interaction of the immunodominant pertussis toxin peptide containing residues 30-42 (p30-42) with soluble DR1 molecules and the T-cell receptor (TCR) of 12 DR1-restricted human T-cell clones has been analyzed. Peptide analogues of p30-42 containing single alanine substitutions were used in DR1-binding and T-cell proliferation assays to identify the major histocompatibility complex and TCR contact residues. Each T-cell clone was found to recognize p30-42 with a different fine specificity. However, a common core comprising amino acids 33-39 was found to be important for stimulation of all T-cell clones. Within this core two residues, Leu33 and Leu36, interact with the DR1 molecule, whereas Asp34, His35, Thr37, and Arg39 are important for TCR recognition in most of the clones. Computer modeling of the structure of p30-42 showed that an alpha-helical conformation is compatible with the experimental data. The analysis of TCR rearrangement revealed that the peptide was recognized by T-cell clones expressing different variable region alpha (V alpha) and variable region beta (V beta) chains, although a preferential use of V alpha 8-V beta 13 and V alpha 11-V beta 18 combinations was found in clones from the same donor. Understanding the details of the interaction of antigenic peptides with the major histocompatibility complex and TCR molecules should provide the theoretical basis to design T-cell epitopes and obtain more immunogenic vaccines.

Amino Acid Sequence↗
PubMed1992

Effect of pH on MHC class II-peptide interactions.

The effect of pH on class II-peptide interactions has been analyzed using several mouse (IAd, IAk, IEd, IEk) and human (DR1, DR5, DR7) MHC specificities, and eight different class II-restricted determinants. In direct binding assays, acidic conditions led to increased binding capacity for many class II-peptide combinations. IE molecules seemed to bind optimally around pH 4.5, whereas IA molecules displayed binding optima in the 5.5 to 6.5 range. In contrast, the DR molecules studied were, in most cases, affected only marginally by pH changes in the 4.5 to 7.0 range. Despite these apparent isotype-specific trends, no general rule could be formulated, because even for the same class II molecules, the binding capacity could be increased for many peptides when the binding was performed under acidic conditions, was unaffected for some, and even decreased for others. The mechanisms responsible for this complex behavior were analyzed in more detail by kinetic and equilibrium analysis of three different class II-peptide combinations (IAd/OVA 323-339, IAk/HEL 46-61, and DR1/HA 307-319). It was found that acidic pH conditions could affect both on and off rates for class II-peptide complexes. Depending on the net balance of these effects, either increases, decreases, or no effect on overall affinities at equilibrium were detected. In the case of IAd/OVA 323-339, it was also found that acidic conditions influenced the binding capacity of class II molecules by increasing the fraction of sites available for peptide binding, presumably by favoring dissociation of endogenously bound, acid-sensitive peptides.

Amino Acid Sequence↗
PubMed1991

On the interaction of promiscuous antigenic peptides with different DR alleles. Identification of common structural motifs.

We have investigated the interaction between DR1 molecules and the two antigenic peptides, tetanus toxoid 830-843 and hemagglutinin 307-319, previously known to bind most DR alleles (degenerate binding) and to be recognized by the same T cell clones in the context of different DR alleles (promiscuous T cell recognition). The DR1 affinity of these two peptides was compared with that of two other different T cell epitopes (pertussis toxin 30-42 and ragweed allergen Ra3 51-65). It was found that degeneracy and promiscuity were associated with high affinity interactions, whereas binding and T cell selectivity were associated with weaker interactions. Thus, the selectivity of DR-peptide interactions, as is commonly observed with the antibody molecule, appears to be inversely correlated to affinity. Several singly substituted analogs of the hemagglutinin 307-319 determinant have also been tested for capacity to bind various DR alleles (DR1, DR2, DR5, and DR7). The results obtained suggest that this determinant may bind the different DR alleles in a similar orientation. Similar conclusions were reached when the interaction between the tetanus toxoid 830-843 determinant and three different DR alleles (DR1, DR2, and DR7) was studied following the same experimental approach. When crucial DR-binding residues of the two peptides were compared, it was found that they were very similar in both chemical nature and spacing in the peptide primary structure, suggesting that the two peptides may bind DR in a very similar orientation. Finally, a putative motif has been derived and shown to be present in a majority of the DR binders tested, but only in a minority of the non-DR binding peptides.

Alleles↗