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Biomedical subjects

K Daly

Publications and source records attributed to K Daly.

At least 37 records · Page 2Linked to original sources
PubMed1998

Basaloid squamous carcinoma: a clinical comparison of two histologic types with poorly differentiated squamous cell carcinoma.

Basaloid squamous carcinoma (BSC) of the head and neck has been shown to have a poor prognosis when compared with conventional squamous cell carcinoma (SCC). Pathologically, specimens determined to be BSC can have nearly pure basaloid features (group 1) or a mixture of basaloid and squamous features (group 2). The clinical behavior in these 2 subgroups has not been compared previously. BSC is also commonly confused histologically with poorly differentiated SCC (PDSCC). A retrospective comparison of disease stage at presentation, rate of distant metastasis, rate of local recurrence in those offered surgical resection, and rate of survival is made to compare outcomes of the 2 BSC groups and the PDSCC group. The presence of particular histologic features may be associated with poorer outcomes. Patients with BSC have advanced disease at presentation. Survival in the BSC group was less than half that in the PDSCC groups. Statistical analysis shows the 2 groups to be well matched with regard to stage and site of disease. Presence of neck nodal disease on presentation predicts poor survival. In this study distant metastases occurred in 52% of patients with BSC and in 13% of patients in the PDSCC group. The local recurrence rate is comparable for BSC and conventional SCC, with even early tumors in the BSC group recurring distantly rather than locally or regionally. Considering the high distant metastatic rate of BSC and poorer overall survival rate, a more extensive metastatic survey is indicated in these patients before surgery is recommended. We recommend that patients with a diagnosis of BSC not be included with conventional SCC groups in prospective randomized cancer protocols.

Carcinoma, Basosquamous↗
PubMed1998

In vitro immunization and expansion of antigen-specific cytotoxic T lymphocytes for adoptive immunotherapy using peptide-pulsed dendritic cells.

The design of an effective procedure to sensitize and expand antigen-specific cytotoxic T lymphocytes (CTL) in vitro is essential for the development of effective adoptive cellular immunotherapy protocols for cancer. We have analyzed the capacity of tissue culture-derived dendritic cells (DC) to present specific peptide epitopes to CTL precursors. Our results demonstrate that peptide-pulsed DC were efficient in generating CTL responses specific for various viral and tumor epitopes. Furthermore, IL-7 and IL-10 potentiated the ability of the peptide-pulsed DC to trigger antigen-specific CTL responses. The CTL generated using this procedure efficiently recognized the naturally processed antigens and could be expanded approximately 100- to 1000-fold in tissue culture in 10 to 15 days without a loss of activity and specificity. The results and procedures described herein may facilitate the development of effective CTL-based adoptive immunotherapy for chronic viral diseases and cancer.

Adoptive Transfer↗
PubMed1997

Diversity among aromatic hydrocarbon-degrading bacteria and their meta-cleavage genes.

Sixty-one strains of bacteria capable of growth on 4-methyl benzoic acid (29 isolates) or naphthalene (32 isolates) as the sole source of carbon and energy were isolated from sediments and water samples from the River Tyne, UK. Random amplification of polymorphic DNA from genomic DNA extracted from the different strains demonstrated that 14 of the 4-methyl benzoate-degrading isolates were unique and the remainder fell into seven groups containing two or three isolates that produced identical banding patterns. Thirteen of the naphthalene-degrading isolates were unique and nine groups with two or three identical representatives encompassed all other isolates. Screening of the bacterial strains for the presence of genes homologous to xylE, nahC and bphC by polymerase chain reaction and dot blot hybridization demonstrated that most strains harboured xylE- and/or nahC-like genes and only a single isolate was found that did not harbour any of these genes. None of the isolates harboured bphC-like genes. It was concluded that, while considerable diversity existed in host strains isolated using a single simple enrichment procedure, the extradiol dioxygenase genes involved in aromatic ring cleavage, present in these strains, were conserved to a considerable degree.

Bacteria↗
PubMed1997

Blepharospasm: an Australian survey.

An overview of blepharospasm introduces an Australian survey into the condition. The survey findings are similar to the trends established in the literature. Blepharospasm occurs later in life, effects more women than men and is a relatively unknown condition. Diagnosis is difficult and the emotional implications of the condition are extreme due to its variability and lack of recognition. There is no cure. More education of the health and services sectors are required as is more support for the sufferer and his/her support network.

Adult↗
PubMed1996

Lethal synergism between influenza infection and staphylococcal enterotoxin B in mice.

Superantigen hyperactivation of the immune system has variable, sometimes lethal consequences for the host. Here we show that concurrent influenza infection enhanced the effects of the bacterial superantigen staphylococcal enterotoxin B (SEB) in mice. The effect was T cell-dependent, and maximal synergism was observed when SEB was administered 7 days after the virus, a timepoint during infection associated with high viral titers, a vigorous cytotoxic T cell response, and extensive lung pathology. The influenza infection enhanced the SEB-induced cytokine response in terms of higher absolute levels of cytokine, sustained secretion, and localization to the respiratory tract. In particular, TNF and IFN-gamma were implicated in the mechanism of death because their neutralization protected the mice from death, and recombinant IFN-gamma and TNFalpha mimicked the lethal effect of SEB in influenza-infected mice. This lethal synergism between concurrent influenza infection and superantigen exposure points to the danger of secondary bacterial involvement in viral pneumonia, and suggests mechanisms that may contribute to sudden and unexpected death from influenza infection. In addition, these data demonstrate that the in vivo effects of superantigen exposure can be strongly influenced by the immune activation status of the host.

Animals↗
PubMed1996

The prognosis for walking in osteogenesis imperfecta.

We report a postal survey of 59 families of children with osteogenesis imperfecta. From the 51 replies we collected data on developmental milestones and walking ability and related them to the Sillence and the Shapiro classifications of osteogenesis imperfecta. Twenty-four of the patients had been treated by intramedullary rodding. Both classifications helped to predict eventual walking ability. We found that independent sitting by the age of ten months was a predictor for the use of walking as the main means of mobility with 76% attaining this. Of the patients who did not achieve sitting by ten months, walking became the main means of mobility in only 18%. The developmental pattern of mobility was similar in the rodded and non-rodded patients.

Adolescent↗
PubMed1996

Established nonunion of the scaphoid treated by volar wedge grafting and Herbert screw fixation.

We reviewed 26 consecutive men of mean age 28 years who had wedge bone grafting and Herbert screw fixation for symptomatic established nonunion of the waist of the scaphoid. The period between injury and operation averaged 30 months (10 to 96), and 11 of the 26 patients had had previous operations, seven with bone grafts. At a mean follow-up of 14 months (6 to 42) 25 fractures (95%) had united at a median time of four months. Symptoms were improved in all patients. The outcome was not related to the time between injury and surgery or to pre-existing degenerative changes. Previous surgery carried a worse prognosis. The technique is difficult but can achieve union even when previous surgery and bone grafting have failed. The usual result is improved function and some relief of pain.

Adolescent↗
PubMed1995

Contribution of the TCR alpha-chain to the differential recognition of bacterial and retroviral superantigens.

The TCR alpha-chain has been implicated in superantigen recognition by some T cells. In this study, recognition of a retroviral (minor lymphocyte stimulating Ag-1, Mls-1) and a bacterial (staphylococcal enterotoxin B, SEB) superantigen by T cells expressing an identical (transgenic) V beta 8.1 beta-chain and either a V alpha 2+ or V alpha 11+ alpha-chain have been compared. Individual hybridomas were found to vary in their recognition of the two superantigens. Whereas some T cell hybridomas recognized both superantigens comparably, other hybridomas preferentially recognized either Mls-1 or SEB, indicating that the contribution of the TCR alpha-chain to recognition of these superantigens is not equivalent. The degree of heterogeneity in recognition varied between the V alpha 2+ and V alpha 11+ hybridomas, although there were individual hybridomas within each group with distinct patterns of reactivity that varied only in CDR3 alpha. These data are consistent with recent evidence that recognition of Mls-1 and SEB involves distinct TCR/MHC interactions.

Animals↗
PubMed1995

Immunodominance of major histocompatibility complex class I-restricted influenza virus epitopes can be influenced by the T-cell receptor repertoire.

We have used T-cell receptor beta-chain transgenic mice to determine the effects of a limited T-cell receptor repertoire on major histocompatibility complex class I-restricted epitope selection during the course of an influenza virus infection. Analysis of T-cell hybridomas generated from wild-type and transgenic mice demonstrated that the viral epitope recognized depended on the available T-cell receptor repertoire. Wild-type T-cell hybridomas recognized epitopes derived from the nucleoprotein and basic polymerase molecules, whereas hybridomas generated from transgenic mice recognized epitopes derived from the nonstructural protein and the matrix protein. There was no overlap in specificity between the two panels of hybridomas. This reciprocal pattern of specificity was also apparent in cytoxicity assays with brochoalveolar lavage cells isolated from the lungs of influenza virus-infected mice. T-cell receptor usage in the transgenic hybridomas was very restricted, with only one V alpha element used for ech of the two viral epitopes recognized. In the case of the hybridomas reactive to the nonstructural protein, sequence analysis showed that they all expressed V alpha 4J alpha 32 chains associated with the same junctional amino acids (Leu-Leu) that were encoded by five different nucleotide sequences, indicating a strong selection for T-cell receptor usage. Taken together, these data demonstrate that the available T-cell receptor repertoire can have a profound effect on the immunodominance of class I-restricted epitopes during a viral infection.

Amino Acid Sequence↗
PubMed1995

Comparison of five cardiac markers in the detection of reperfusion after thrombolysis in acute myocardial infarction.

OBJECTIVE: To investigate and compare the clinical usefulness of serial measurements of five cardiac marker proteins, namely creatine kinase (CK), CK-MB mass, myoglobin, troponin T, and myosin light chain 1, in the early detection of reperfusion after thrombolytic treatment. METHOD: Serial blood samples were taken from 26 patients presenting with acute myocardial infarction. Concentrations of the five markers were assayed in each sample. Thrombolytic treatment was given to the patients who were divided into those who reperfused (n = 17, group A) and those who failed to reperfuse (n = 9, group B) on the basis of clinical signs and angiography within 24 h. RESULTS: The release profiles of CK, CK-MB mass, myoglobin, and troponin T for patients in group A differed from those of patients in group B. No difference was observed in the release profile of myosin light chain 1 between the two groups. The time to peak concentration of CK, CK-MB mass, myoglobin, and troponin T occurred significantly earlier in patients of group A than in those of group B, with myoglobin peaking earlier than the other markers. An index, defined as the ratio of the concentration of each marker immediately before and 2 h after the start of thrombolytic treatment, was calculated for each marker in groups A and B. The 2 h myoglobin and troponin T indices were significantly different between groups A and B. The diagnostic efficiency of the myoglobin index, however, was best at 85%. CONCLUSIONS: These studies suggest that myoglobin has greater potential than the other markers examined in the detection of reperfusion after thrombolytic treatment.

Adult↗
PubMed1994

Identification of futility in intensive care.

Rising costs of intensive care and the ability to prolong the life of critically ill patients creates a need to recognise early those patients who will die despite treatment. We used changes in a modified APACHE II score (organ failure score) to make daily predictions of individual outcome in 3600 patients. 137 patients were predicted to die and of these, 131 (95.6%) died within 90 days of discharge from hospital (sensitivity 23.4%, specificity 99.8%); a false-positive diagnosis rate of 4.4%. 2 of the 6 survivors have subsequently died but 4 are alive with good quality of life. Patients predicted to die stayed 1492 days in intensive care and incurred 16.7% of total intensive care expenditure and 46.4% of the cost of all patients that died. Median survival after a prediction to die was 2 days, accounting for 62% of intensive care patient days in this patient group, giving an effective intensive care cost per survivor of UK 129,651 pounds. If used prospectively, this algorithm has the potential to indicate the futility of continued intensive care but at the cost of 1 in 20 patients who would survive if intensive care were continued.

APACHE↗
PubMed1994

The effect of the Persian Gulf Crisis on the psychiatric hospitalization of Navy children and adolescents.

The effect of the Persian Gulf Crisis on Navy families was studied through admission rates of children to a private psychiatric hospital, marital status and diagnostic categories. During that time there was a statistical increase in admission of young boys under age twelve and all children from remarried families. Almost one-half of these patients were diagnosed with Dysthymia whereas this diagnosis was given only once during the time period before or after the crisis.

Anxiety, Separation↗
PubMed1994

Reactive thrombocytosis and stroke following cardiopulmonary bypass surgery: case report on three patients.

Reactive thrombocytosis following cardiopulmonary bypass surgery is generally considered to be a benign condition which is transient and does not require specific therapy. We describe three patients who developed stroke in association with reactive thrombocytosis in the late recovery period following cardiopulmonary bypass surgery. No evidence of embolic or cerebrovascular disease was detected in any patient. Analysis of a larger group of patients is required in order to determine whether reactive thrombocytosis may contribute to the pathogenesis of stroke in some patients following cardiopulmonary bypass surgery.

Blood Coagulation Tests↗
PubMed1994

Virus-specific CD8+ T-cell responses in mice transgenic for a T-cell receptor beta chain selected at random.

The consequences of severely limiting the T-cell receptor (TCR) repertoire available for the response to intranasal infection with an influenza A virus or with Sendai virus have been analyzed by using H-2k mice (TG8.1) transgenic for a TCR beta-chain gene (V beta 8.1D beta 2J beta 2.3C beta 2). Analyzing the prevalence of V beta 8.1+ CD8+ T cells in lymph node cultures from nontransgenic (non-TG) H-2k controls primed with either virus and then stimulated in vitro with the homologous virus or with anti-CD3 epsilon showed that this TCR is not normally selected from the CD8+ T-cell repertoire during these infections. However, the TG8.1 mice cleared both viruses and generated virus-specific effector cytotoxic T lymphocytes (CTL) and memory CTL precursors, though the responses were delayed compared with the non-TG controls. Depletion of the CD4+ T-cell subset had little effect on the course of influenza virus infection but substantially slowed the development of the Sendai virus-specific CTL response and virus elimination in both the TG8.1 and non-TG mice, indicating that CD4+ helpers are promoting the CD8+ T-cell response in the Sendai virus model. Even so, restricting the available T-cell repertoire to lymphocytes expressing a single TCR beta chain still allows sufficient TCR diversity for CD8+ T cells (acting in the presence or absence of the CD4+ subset) to limit infection with an influenza A virus and a parainfluenza type 1 virus.

Animals↗
PubMed1994

Tympanic membrane perforations and tympanostomy tubes.

Tympanoplasty and tympanostomy tubes were developed at the same time and have dramatically changed the treatment of chronic middle ear disease. One hundred forty-nine children who had tubes inserted between ages 6 months and 8 years for chronic otitis media with effusion have been prospectively followed up for an average of 4 years. Fourteen percent developed tympanic membrane perforations. No preoperative factor completely predicted the development of perforation. A majority of the perforations closed spontaneously. Three ears had noncontiguous observations of perforations during follow-up. The implications of these findings are discussed with respect to tympanoplasty.

Child, Preschool↗
PubMed1994

Risk factors for otitis media sequelae and chronicity.

Otitis media (OM) is a very common childhood illness, with identified risk factors for chronicity and recurrence. Although a few treatment studies have described clinical factors that predict increased morbidity, there is little information on risk factors for middle ear sequelae of OM. These conditions have an estimated annual incidence of 0.5% to 4% among children with chronic OM with effusion. Prospective studies to identify risk factors for sequelae, although usually preferred by researchers, are expensive to conduct and impractical for rare conditions such as cholesteatoma. Knowledge of risk factors for chronicity and sequelae can be used clinically to target high-risk children for earlier, more aggressive therapy or more frequent surveillance and testing to prevent sequelae and increase early detection of these conditions. A clinician's advice about modifiable risk factors may motivate parents to decrease their child's exposure to factors that increase the risk of OM, OM chronicity, and sequelae. Research is needed to identify risk factors for OM sequelae by means of well-designed controlled studies.

Adolescent↗