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At least 1,171 records · Page 65Linked to original sources
PubMed1989

Has the increasing use of grommets influenced the frequency of surgery for cholesteatoma?

The number of operations for cholesteatoma, together with the number of cases undergoing insertion of ventilation tubes in the Tayside region of Scotland between 1966 and 1986 have been studied. During this period there has been a sixty fold increase in the use of ventilation tubes, but the incidence of cholesteatoma surgery has only varied between 0.94 and 1.88 operations per 10,000 of population per year. The mean annual incidence of cholesteatoma during this period was 1.32 cases per 10,000 of population. The results indicate that there has been neither a rise nor a fall in the incidence of cholesteatoma in Tayside despite a considerable increase in the use of ventilation tubes.

Child↗
PubMed1991

An assessment of the incidence of iron deficiency in paediatric otolaryngology inpatients.

The aims of this study were: to determine whether there is an increased incidence of iron deficiency in paediatric otolaryngology inpatients compared with other surgical controls; and to establish whether preoperative screening of haemoglobin level is warranted in such patients. Children aged 1-10 years admitted electively for ENT surgery or for general surgical procedures had blood taken for haemoglobin level, mean cell volume and serum ferritin. Their age, weight, socioeconomic class and ethnic background were recorded. A total of 100 patients entered the study, in a six-month period. The mean ages and weights for the two groups were statistically different, so allowance was made for this in calculations. Social class was not significantly different. No relationship could be established between haemoglobin level and ferritin level for individual patients. Multiple regression analysis for haemoglobin level, mean cell volume and for ferritin level showed that allowing for the age and weight differences these variables were not significantly different for the two groups. This study has therefore shown no increased incidence of iron deficiency in paediatric ENT inpatients. Each Department should formulate its own policy on pre-operative haemoglobin screening, based on local considerations.

Child↗
PubMed1993

One aid or two?--more visits please!

A prospective trial of hearing aid provision was undertaken to define factors which might be used to allow hearing aids to be fitted optimally. Patients referred for the provision of a hearing aid were studied prospectively at each of five visits when they were questioned by means of a proforma. Fifty-six patients completed the trial and gave adequate responses for analysis. No audiometric or symptomatic criteria were found to be of use in predicting the final choice of hearing aid combination. It may be that initial sequential monaural aiding leads to a higher uptake of binaural aids in the long term. Patients valued multiple visits to the clinic and sequential trials of monaural aiding, the majority felt that binaural aids should be tried.

Adult↗
PubMed2001

Covalent linkage of prosthetic heme to CYP4 family P450 enzymes.

An extensive body of research on the structural properties of cytochrome P450 enzymes has established that these proteins possess a b-type heme prosthetic group which is noncovalently bound at the active site. Coordinate, electrostatic, and hydrogen bond interactions between the protein backbone and heme functional groups are readily overcome upon mild acid treatment of the enzyme, which releases free heme from the protein. In the present study, we have used a combination of HPLC, LC/ESI-MS, and SDS-PAGE techniques to demonstrate that members of the mammalian CYP4B, CYP4F, and CYP4A subfamilies bind their heme in an unusually tight manner. HPLC chromatography of CYP4B1 on a POROS R2 column under mild acidic conditions caused dissociation of less than one-third of the heme from the protein. Moreover, heme was not substantially removed from CYP4B1 under electrospray or electrophoresis conditions that readily release the prosthetic group from other non-CYP4 P450 isoforms. This was evidenced by an intact protein mass value of 59,217 +/- 3 amu for CYP4B1 (i.e., apoprotein plus heme) and extensive staining of this approximately 60 kDa protein with tetramethylbenzidine/H(2)O(2) following SDS-PAGE. In addition, treatment of CYP4B1, CYP4F3, and CYP4A5/7 with strong base generated a new, chromatographically distinct, polar heme species with a mass of 632.3 amu rather than 616.2 amu. This mass shift is indicative of the incorporation of an oxygen atom into the heme nucleus and is consistent with the presence of a novel covalent ester linkage between the protein backbone of the CYP4 family of mammalian P450s and their heme catalytic center.

Amino Acid Sequence↗
PubMed2000

Dual X-ray absorptiometry detects disease- and treatment-related alterations of bone density in prostate cancer patients.

Metastatic bone disease is an important clinical problem which has proven difficult to study because of a lack of noninvasive investigative modalities. Here we show that dual-energy X-ray absorptiometry (DXA) scanning provides clinically useful information about the status of metastatic bone lesions in cancer patients undergoing palliative treatment. In the study group of 21 patients, a significant increase in metastatic bone mineral density (BMD) was confirmed in prostate (n = 14) relative to breast (n = 7) cancer patients. With respect to the prostate cancer cohort, further increases in lesional BMD were evident in all evaluable patients in whom biochemical progression occurred; conversely, lesional BMD declined in patients who had a partial response to therapy. BMD of uninvolved bone decreased with all types of androgen-deprivation therapy regardless of whether patients responded or relapsed. We conclude that BMD changes in both lesional and uninvolved bone are readily detectable in metastatic prostate cancer, and propose that DXA scanning represents a promising new approach to monitoring the natural history and therapeutic course of this disease.

Absorptiometry, Photon↗
PubMed2002

Natural killer cell receptor expression by human first trimester decidual granular leukocytes and T-lymphocytes.

PROBLEM: Detailed analysis of the expression of natural killer (NK) cell activatory and inhibitory receptors by human decidual leukocyte subpopulations has not been undertaken. METHOD OF STUDY: Expression of the natural cytotoxicity receptors NKp30, NKp44 and NKp46 by decidual leukocytes were studied by reverse transcriptase polymerase chain reaction. Expression of the killer cell Ig-like receptors CD158a and CD158b on decidual T cells were studied by flow cytometry. RESULTS: First trimester decidual leukocytes expressed mRNA for the NKp30 and NKp46 receptors but expression of NKp44, a marker of activated NK cells, was not detected. A mean of 11.8 and 15.8% of decidual T cells expressed CD158a or 158b, respectively, while only around 1% of peripheral blood T cells were CD158a+ or CD158b+. CONCLUSIONS: Like peripheral blood NK cells, decidual NK cells express the natural cytotoxicity receptors NKp30 and NKp46 but the significance of this will not become apparent until ligands for these molecules have been identified. Only a minority of decidual T cells express CD158, indicating that this is not a mechanism for inhibition of cytotoxicity mediated by all decidual T cells.

Cytotoxicity, Immunologic↗
PubMed2000

Combined suicide and granulocyte-macrophage colony-stimulating factor gene therapy induces complete tumor regression and generates antitumor immunity.

The use of prodrug-activated ("suicide") gene therapy has been shown to be effective in inducing tumor regression when only a small proportion of tumor cells contains the suicide gene. These experiments were designed to test whether additional therapeutic benefit may be obtained by stimulating the immune response. Murine MC26 colon carcinoma cells, either untransduced or transduced with genes for herpes simplex virus-1 thymidine kinase (HSV1-TK) or human GM-CSF, were injected subcutaneously into syngeneic BALB/c mice in various combinations. Inoculation of equal numbers of untransduced and HSV1-TK-containing cells followed by ganciclovir (GCV) treatment resulted in almost complete tumor regression, but by 7 weeks, tumors had recurred in all mice. A similar initial regression was obtained using equal numbers of cells containing HSV1-TK and GM-CSF genes, but >80% of these mice remained tumor-free after 3 months. Groups of tumor-free mice that had received GM-CSF-containing cells were left for different periods of time and rechallenged with unmodified MC26 cells on the opposite flank. Of the mice rechallenged 14, 28, and 108 days later, 100%, 88%, and 57%, respectively, showed complete resistance to unmodified tumor cells. In mice that showed tumor regrowth, tumor volume was much less than in control mice. Adoptive transfer of spleen cells from resistant mice to naïve syngeneic mice resulted in partial resistance to challenge with unmodified tumor cells. Specific cytotoxicity against MC26 cells was only demonstrable in mice receiving GM-CSF- and HSV1-TK-containing tumor cells. These experiments show that the presence of cells secreting GM-CSF in HSV1-TK-containing, regressing tumor is able to induce complete or partial resistance to tumor rechallenge. This indicates the potential usefulness of GM-CSF in enhancing other antitumor therapies.

Animals↗
PubMed2006

Diversity of TMPRSS2-ERG fusion transcripts in the human prostate.

TMPRSS2-ERG gene fusions have recently been reported to be present in a high proportion of human prostate cancers. In the current study, we show that great diversity exists in the precise structure of TMPRSS2-ERG hybrid transcripts found in human prostates. Fourteen distinct hybrid transcripts are characterized, each containing different combinations of sequences from the TMPRSS2 and ERG genes. The transcripts include two that are predicted to encode a normal full-length ERG protein, six that encode N-terminal truncated ERG proteins and one that encodes a TMPRSS2-ERG fusion protein. Interestingly, distinct patterns of hybrid transcripts were found in samples taken from separate regions of individual cancer-containing prostates, suggesting that TMPRSS2-ERG gene fusions may be arising independently in different regions of a single prostate.

Gene Expression Regulation, Neoplastic↗
PubMed1990

Annexin 1 is secreted by the human prostate.

The human prostate expresses very high concentrations of annexins 1, 4, and 5 and secretes high concentrations of annexins 1 and 5. Although the biological roles of these proteins in prostate secretions are not known, these studies emphasize the need to consider extracellular sites for physiological functions of annexins. The clear demonstration of secretion of proteins that have blocked N-termini and lack hydrophobic signal sequences raises the possibility that novel cellular secretory pathways exist. Preliminary immunohistochemical experiments in collaboration with Dr. James Fallon indicate that both annexins 1 and 4 are expressed in prostate ductal secretory epithelium. Since annexin 1, but not annexin 4, is secreted, a comparison of the cellular fate of these two related proteins in the prostate may provide a useful model system for determining the structural elements that direct the secretion of proteins which lack conventional signal sequences.

Annexins↗
PubMed2000

b3a2 BCR-ABL fusion peptides as targets for cytotoxic T cells in chronic myeloid leukaemia.

Peptide sequences spanning the BCR-ABL protein junction potentially constitute novel leukaemia-specific antigens. 9-mer b3a2 fusion peptides have been reported to bind with high affinity to HLA-A3, -A11 and -B8. We have studied the effect of b3a2 BCR-ABL junctional peptides on the cytotoxic T-cell (CTL) response against normal and chronic myeloid leukaemia (CML) cells. Antigen-presenting cells (APCs) were prepared from HLA-A3- or -B8-positive peripheral blood mononuclear cells (PBMCs) by incubation with phytohaemagglutinin (PHA) and interleukin (IL)-2 for 7 d. These APCs were pulsed with the respective b3a2 junctional peptide in the presence of beta2-microglobulin and were then used to challenge autologous PBMCs at 7-d intervals in the presence of IL-2, IL-6, IL-7 and IL-12. On subsequent exposure to target cells (either further pulsed normal APCs or unpulsed CML cells), specific HLA-restricted CTL responses were observed against all HLA-A3/-B8 matched normal target cells tested, but not to targets that were HLA mismatched. Cytotoxicity was also induced against HLA-A3/-B8 unpulsed CML cells, but not against unmatched CML cells. These data indicate (i) that endogenous BCR-ABL junctional peptides may be presented by CML cells and (ii) that exogenous peptides are potential stimulators of autologous antileukaemic CTLs.

Antigen-Presenting Cells↗
PubMed2002

Levels of the chemokines growth-related oncogene alpha and epithelial neutrophil-activating protein 78 are raised in patients with severe acute pancreatitis.

BACKGROUND: Multiple organ dysfunction syndrome secondary to systemic leucocyte activation is the major cause of death following an attack of acute pancreatitis. Although plasma levels of interleukin (IL) 8 are known to be raised in acute pancreatitis, levels of other CXC chemokines such as growth-related oncogene (GRO) alpha and epithelial neutrophil-activating protein (ENA) 78, which are also potent neutrophil chemoattractants and activators, have not been measured. METHODS: Timed plasma samples were obtained from 51 patients with acute pancreatitis, 27 with a severe attack and 24 with mild disease according to the Atlanta classification. Samples were analysed to determine levels of C-reactive protein (CRP), IL-8, GRO-alpha and ENA-78. RESULTS: Plasma levels of IL-8, GRO-alpha and ENA-78 were increased in patients with severe as opposed to mild acute pancreatitis as early as 24 h following disease onset. Using cut-off levels of 7 pg/ml for IL-8, 70 pg/ml for GRO-alpha and 930 pg/ml for ENA-78, peak levels within the first 24 h of admission had an accuracy of 81, 71 and 87 per cent respectively in predicting the severity of an attack of acute pancreatitis. CONCLUSION: In patients with severe acute pancreatitis plasma levels of GRO-alpha and ENA-78 were raised in addition to those of IL-8, suggesting that all three chemokines are involved in the inflammatory response in this condition.

Acute Disease↗
PubMed1996

Expression of functional molecules by human CD3- decidual granular leucocyte clones.

Cell surface and cytoplasmic antigen expression by 35 CD3- decidual granular leucocyte (DGL) clones, derived from human endometrial tissue in the first trimester of pregnancy, has been compared with both that of fresh CD3- decidual leucocytes and that of CD3- peripheral blood natural killer (PBNK) cell clones (n = 12). The majority of DGL clones retained the antigenic phenotype of fresh cells, although CD103 (HML-1) was expressed on 50% of DGL clones but only 17% of fresh DGL. Both cytoplasmic CD3 zeta and CD3 epsilon chains were detected in > 90% of DGL clones in the absence of cell surface CD3. Cytoplasmic CD3 zeta was present in almost all fresh CD3- DGL, whereas CD3 epsilon was not. Most DGL clones did not express surface Fc gamma receptors I-III (CD64, -32 and -16, respectively) and complement receptors (CR) types 1 and 2 (CD35 and 21, respectively), but 43% expressed CR3 (CD11b/18); in contrast, all PBNK clones were CR3+. The NK cell-associated molecules Kp43 (CD94) and the p58 molecule recognized by the HP3E4 monoclonal antibody were both present on a higher proportion of CD3- PBNK (91% and 50%, respectively) than DGL clones (31% and 14%, respectively), despite expression of CD94 by > 90% of fresh CD56+ decidual leucocytes. Five of 35 CD3- DGL clones expressed cytoplasmic CD3 zeta in the absence of expression of CD2, CD16 or the p58 molecule recognized by HP3E4. These variations between CD3- DGL and PBNK cell clones in expression of functional molecules may be related to previously reported differences in major histocompatibility complex-non-restricted cytotoxic activities between these two cell types.

Antigens, Surface↗
PubMed2001

Characteristics of patients with lung cancer under the age of 45 years: a case control study.

OBJECTIVE: The aim of this study was to define the clinical and pathological features associated with lung cancer diagnosed in persons under the age of 45 compared with lung cancer in an older population of greater than 45 years. METHODOLOGY: A case control study was undertaken. Cases were defined as patients diagnosed with lung cancer under the age of 45 years. Controls were lung cancer patients over 45 years matched only for the date of diagnosis. Up to four controls were selected for each case. A retrospective review was undertaken of the records of a single tertiary respiratory institution which served a population of 1.2 million. RESULTS: Forty-eight cases of lung cancer (< 45 years of age) were identified and were compared to 123 matched controls with lung cancer (> 45 years of age). Of the cases 67% were female compared with 32% female cases in the control group (P < 0.01). The rate of adenocarcinoma was significantly higher among cases (48% vs 27%, P=0.001), while squamous cell carcinoma was more common in the controls (35% vs 17% P =0.001). Smoking was common in both groups although less so among cases (79% vs 95%, P=0.001)). There was no difference in survival rates between the cases (11 months) compared with controls (8 months) (P=0.1). CONCLUSIONS: Young lung cancer patients were predominantly female and adenocarcinoma accounted for a disproportionate number of the histological types. Cigarette smoking appears to be the main aetiological agent but as 21% of the patients under 45 years were non-smokers, other factors (genetic/hormonal) may also contribute. This study has not demonstrated a worse outcome in younger patients.

Adenocarcinoma↗