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Biomedical subjects

E Hughes

Publications and source records attributed to E Hughes.

At least 91 records · Page 5Linked to original sources
PubMed1995

Pholedrine: a substitute for hydroxyamphetamine as a diagnostic eyedrop test in Horner's syndrome.

Mydriatic responses to eyedrops containing the indirect acting sympathomimetic amines tyramine, hydroxyamphetamine, and pholedrine have been compared in 10 healthy subjects. Pholedrine, the n-methyl derivative of hydroxyamphetamine, at a concentration of 1% had effects similar to those produced by 0.5% hydroxyamphetamine itself. Pretreatment with topical guanethidine attenuated its responses and in 13 patients with unilateral Horner's syndrome it distinguished clearly those five patients who had preganglionic from the eight with postganglionic lesions. It is concluded that 1% pholedrine may be substituted for 0.5% hydroxyamphetamine, which is no longer available, as a diagnostic agent for use in Horner's syndrome.

Adolescent↗
PubMed1995

An aspect of sentence processing in Alzheimer's disease: quantifier-noun agreement.

We assessed sentence processing in Alzheimer's disease (AD) with measures of sentence-picture matching, grammaticality judgments of sentences, and sentence completion. The results demonstrated significant and consistent difficulty with a grammatical feature of sentences on all three experiments. This impairment could not be explained by factors such as sentence length, dementia severity, or a short-term memory deficit and was independent of difficulty interpreting the meanings of words. We hypothesize that AD patients are impaired at appreciating the conceptual relations that underlie certain grammatical features of sentences.

Aged↗
PubMed1995

Phonologic processing deficits in Alzheimer's disease.

We investigated phonologic production in patients with mild to moderate Alzheimer's disease (AD) on a repetition task. AD patients produced significantly more speech errors than age-matched controls. AD patients' errors, unlike those of controls, resulted in the transformation of real words into pseudowords, occurred disproportionately in word-initial positions, and were not influenced by the phonologic environment. This pattern of errors suggests a lexical phonologic retrieval deficit in AD.

Aged↗
PubMed1994

MHC class II-transfected tumor cells induce long-term tumor-specific immunity in autologous mice.

Many tumors express peptides that are potentially immunogenic; however, the host's immune system is often not sufficiently stimulated to mediate tumor rejection. The inability to mount a potent antitumor immune response has often been attributed to the lack of generation of sufficient tumor-specific T cell help. Efforts in this laboratory to improve tumor-specific immunity have therefore focused on improving the generation of tumor-reactive T helper cells. Previous studies have suggested that immunity to the murine SaI sarcoma can be significantly improved if the tumor is engineered to express syngeneic MHC class II molecules, and thereby directly present tumor peptides to Th lymphocytes. In the present study we demonstrate that vaccination with class II+ SaI transfectants results in immunity that is extremely effective against high-dose challenges of wild-type SaI tumor. The immunity induced by immunization with these transfectants is also exceptionally long-lived (greater than 6 months) and radiation resistant, suggesting that tumor-specific memory T cells are generated. The resulting immunity is specific for the immunizing tumor and protects autologous mice against challenges of both ascites and solid SaI variants. Depletion and adoptive transfer studies confirm the role of CD4+ T cells in the induced immunity, supporting the hypothesis that improving the generation of Th cells enhances the antitumor immune response. Inasmuch as irradiated or paraformaldehyde-fixed transfectants are as effective as live transfectants in stimulating tumor rejection, these genetically engineered tumor cells may serve as useful vaccines against wild-type neoplasms.

Animals↗
PubMed1994

Outcome prediction in childhood acute lymphoblastic leukaemia by molecular quantification of residual disease at the end of induction.

Methods to detect and quantify minimal residual disease (MRD) after chemotherapy for acute lymphoblastic leukaemia (ALL) could improve treatment by identifying patients who need more or less intensive therapy. We have used a clone-specific polymerase chain reaction to detect rearranged immunoglobulin heavy-chain gene from the leukaemic clone, and quantified the clone by limiting dilution analysis. MRD was successfully quantified, by extracting DNA from marrow slides, from 88 of 181 children with ALL, who had total leucocyte counts below 100 x 10(9)/L at presentation and were enrolled in two clinical trials, in 1980-84 and 1985-89. Leukaemia was detected in the first remission marrow of 38 patients, in amounts between 6.7 x 10(-2) and 9.9 x 10(-7) cells; 26 of these patients relapsed. Of 50 patients with no MRD detected, despite study of 522-496,000 genomes, only 6 relapsed. The association between MRD detection and outcome was significant for patients in each trial. In the first trial, patients relapsed at all levels of detected MRD, whereas in the later trial, in which treatment was more intensive and results were better, the extent of MRD was closely related to the probability of relapse (5 of 5 patients with > 10(-3) MRD, 4 of 10 with 10(-3) to 2 x 10(-5), 0 of 3 with levels below 2 x 10(-5), and 2 of 26 with no MRD detected). Early quantification of leukaemic cells after chemotherapy may be a successful strategy for predicting outcome and hence individualizing treatment in childhood ALL, because the results indicate both in-vivo drug sensitivity of the leukaemia and the number of leukaemic cells that remain to be killed by post-induction therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Artificial ultraviolet whole-body radiation does not modify serum lipoprotein, plasma fibrinogen, plasminogen or antithrombin III concentrations in post-myocardial infarction patients.

The relationship of ischaemic heart disease (IHD) to seasonal and latitude variation has prompted speculation that exposure to the ultraviolet component of solar radiation may reduce IHD risk. This hypothesis was partially tested by exposing 14 post-myocardial infarction patients to a 6 week course of artificial whole-body ultraviolet radiation (UVR). Serum lipoprotein and plasma coagulation factor concentrations were measured before and after the course of UVR. Results were compared with similar measurements from a placebo-controlled group of 13 post-myocardial patients. Despite a more than two-fold rise in mean serum 25-OHD, serum lipoprotein and plasma fibrinogen, antithrombin III and plasminogen concentrations did not change significantly in the UVR group. Significant but minor change in prothrombin time and thrombin time in the placebo group appear unlikely to be of biological significance. Seasonal and latitude variation in these IHD risk factors appear unrelated to corresponding variation in solar UVR exposure.

Antithrombin III↗
PubMed1994

A meta-analysis of the therapeutic role of oil soluble contrast media at hysterosalpingography: a surprising result?

OBJECTIVE: To evaluate the therapeutic effect of oil-soluble contrast media compared with water-soluble contrast media after hysterosalpingography (HSG) in infertile couples. DESIGN: Meta-analysis of four randomized clinical trials (RCTs) and six nonrandomized controlled studies evaluating pregnancy rates after the use of oil- or water-soluble contrast media during HSG. SETTING: Institute of Epidemiology and Health Services Research, Leeds, United Kingdom. PATIENTS: Four identified RCTs studied 800 patients and six nonrandomized studies comprised an additional 1,806 patients, all experiencing primary or secondary infertility. INTERVENTION: Hysterosalpingography as part of infertility investigation. MAIN OUTCOME MEASURE: Pregnancy rates after HSG. RESULTS: Pregnancy rates were significantly higher in the oil-soluble contrast media group compared with the water-soluble contrast media group in the RCTs. Inclusion of the six nonrandomized studies did not alter this conclusion. This apparent benefit was greatest for patients with unexplained infertility. CONCLUSIONS: Oil-soluble contrast media have a therapeutic effect compared with water-soluble media and this effect is greatest for patients who have been diagnosed as having unexplained infertility. New techniques for the evaluation of tubal patency support the hypothesis that tubal "plugs" may be involved in proximal tubal blockage.

Clinical Trials as Topic↗
PubMed1994

Effectiveness of injectable filler materials for smoothing wrinkle lines and depressed scars.

Both synthetic and biological materials have been used for smoothing wrinkle lines and depressed scars. Injectable fillers provide a convenient and easy alternative to surgical methods to treat dermal defects. Optimally, injectable fillers augmenting dermal tissue should exhibit properties similar to the dermal collagen network, providing a stable matrix for long-term correction but also being subject to the dynamic changes that occur to dermal tissue during the aging processes. At present, only biological materials are available on a commercial basis, although a number of synthetic injectables are being evaluated in clinical trials. The long-term effectiveness of most commercial materials has been limited prompting questions about the cost-benefits of such treatment. In this regard, the effectiveness of the injectable fillers, particularly of biological materials, will be discussed as will the difficulties involved in determining the expected result (effectiveness) for specific materials and in providing methods of measuring effectiveness.

Adipose Tissue↗
PubMed1993

Treatment of male infertility: is it effective? Review and meta-analyses of published randomized controlled trials.

There are few widely accepted treatments for male subfertility. Controlled trials are necessary to evaluate different subfertility treatments because pregnancies and spontaneous improvements in semen parameters occur without treatment. Properly randomized trials can find out whether pregnancy rates are higher or lower than expected after treatment. Quantitative meta-analysis improves precision where individual trials are not powerful enough to demonstrate moderate treatment effects. Only 174 published randomized treatment trials for male subfertility were found after extensive literature review, both by computerized search and hand searches of 41 journals. In 72 of the studies, pregnancy was an outcome measure and these are analysed and discussed. The quality of most trials is poor. Meta-analysis was possible on seven themes, but the results of this exercise appear to be unduly influenced by trials of poor quality. Few conventional treatments (i.e. those not involving assisted conception techniques) result in improved fertility rates.

Humans↗
PubMed1993

Implementing modular nursing in a long-term care facility.

Nurse administrators in long-term care are challenged to maintain the quality of nursing care under constant fiscal and staffing pressures. Restructuring nursing care delivery is one method often used to meet this challenge. The authors describe their experience of implementing a nursing care delivery model that resulted in improved continuity of care, accountability for client outcomes, and the effective use of different staff levels.

Communication↗
PubMed1993

Prognostic significance of detection of monoclonality in remission marrow in acute lymphoblastic leukemia in childhood. Australian and New Zealand Children's Cancer Study Group.

Techniques based on the polymerase chain reaction (PCR) to detect rearrangement of the immunoglobulin or T-cell receptor genes can detect residual disease in leukemia and hence have the potential to improve prognosis and treatment. Such techniques may involve either detection of monoclonality, which is simple and quick but has limited sensitivity, or specific detection of the leukaemic clone, which is complex and time-consuming but has high sensitivity. The PCR was used to detect monoclonal rearrangements of the immunoglobulin heavy chain and/or T-cell receptor gamma chain genes in archival marrow specimens from 185 children with acute lymphoblastic leukemia who achieved remission during two consecutive Australasian trials of treatment. A monoclonal rearrangement was detected at diagnosis in 152 (84%) patients and in these patients detection of the same rearrangement in the remission marrow at the end of induction therapy was highly significantly correlated with outcome. There were nine patients in whom polymerase chain reaction showed only the monoclonal rearrangement and eight (89%) relapsed; there were 26 patients in whom PCR showed the leukemic monoclonal rearrangement as well as polyclonal rearrangements from normal lymphocytes and 12 (46%) relapsed; and there were 117 patients in whom only polyclonal rearrangements could be detected and only 29 (25%) relapsed. In patients who relapsed, remissions were shorter in those patients in whom the leukemic rearrangements had been detected in the remission marrow. Treatment in the later trial was more intensive than in the earlier trial, the results were better and the PCR detected the leukemic rearrangement in the remission marrow in significantly fewer patients. We conclude that detection by PCR of the monoclonal gene rearrangement of the leukemic clone in remission marrow indicates that numerous leukemic cells have survived induction therapy and is a good predictor of relapse. However, due to limited sensitivity of the test, failure to detect the leukemic clone by PCR is not a sufficiently good predictor of ultimate cure.

Bone Marrow↗
PubMed1992

Proteasome subunits encoded in the MHC are not generally required for the processing of peptides bound by MHC class I molecules.

Antigen processing provides major histocompatibility complex (MHC) class I molecules with short peptides, which they selectively bind and present to cytotoxic T lymphocytes. The proteolytic system generating these peptides in the cytosol is unidentified, but their delivery into the endoplasmic reticulum is mediated by the TAP1-TAP2 transporter encoded in the MHC class II region. Closely linked to TAP1 and TAP2 are genes for the LMP2 and LMP7 proteins, which resemble components of proteasomes, proteolytic complexes known to degrade cytosolic proteins. This association has led to the common assumption that proteasomes function in this immunological pathway (discussed in ref. 15). We now show that the expression of stably assembled class I molecules and apparently normal peptide processing can be completely restored in the absence of LMP2 and LMP7 in the human lymphoblastoid cell line mutant 721.174 (refs 16, 17). The identity of LMP7 is directly confirmed by reconstitution of a proteasomal subunit after gene transfer. These results therefore dispute the hypothetical involvement of proteasomes in antigen processing, although a more subtle effect of LMP2 and LMP7 cannot be ruled out.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Should patients with post-resection locoregional recurrence of lung cancer receive aggressive therapy?

The outcome of thirty-seven patients with a post-resection locoregional recurrence of non-small cell lung cancer treated with radiation therapy alone between 1979 and 1989 was compared to that of 759 patients with unresected non-small cell lung cancer also treated with standard radiation during the same period. Each patient's locoregional recurrence was staged using the current American Joint Committee on Cancer staging system. Comparison of pretreatment characteristics between the two groups, including age, sex, extent of weight loss, performance status, stage, and histologic subtype revealed fewer patients with greater than 5% weight loss (35 vs. 47%, p = 0.04) and more cases with squamous histology (54 vs. 28%, p = 0.01) among the patients with locoregional recurrences than those with newly diagnosed lesions. Over 80% of both groups had clinical stage III lesions. The median radiation doses were 56 and 59 Gy for recurrent and newly diagnosed cases (p = NS). For the patients with locoregional recurrences, the median time from resection to recurrence was 13 months (range: 3-118 months), and the recurrences were predominantly nodal in 25 cases, chest wall/pleural in four and at the bronchial stump in eight. When measured from the date of documented recurrence, the median survival time and 2-year actuarial survival rate of the patients with recurrent lesions were 12 months and 22%, as compared to 12 months and 26% for the newly diagnosed patients (p = NS). Freedom from documented locoregional tumor progression at 2 years was 30% for both groups. Patients with bronchial stump lesions had superior survival to those with nodal or chest wall recurrences, with a median survival time of 36 versus 9 months. A therapeutic approach to selected patients with post-resection locoregional recurrence of non-small cell lung cancer equally aggressive to that for newly diagnosed lung cancer patients is justified by these results, especially for patients with bronchial stump recurrences.

Adult↗
PubMed1992

The maximizing urinary functioning program: an innovative approach to managing incontinence in long term care.

Urinary incontinence is a common occurrence in long term care and, given the client population, continence is often an unrealistic expectation. However, it was recognized that nursing plays a pivotal role in the maintenance and enhancement of clients' abilities with respect to their urinary functioning. In our facility, it was found that a need existed not only to assist clients to maximize their urinary functioning, but also to encourage the independent decision-making of our professional staff. The MUF Program developed to meet these needs was based upon the use of a systematic method for decision-making in nursing. The Maximizing Urinary Functioning Program was implemented on a pilot unit and evaluated using a pre-test/post-test design. Based upon the results of this evaluation and projections for the benefit to new admissions, the program is now being implemented hospital-wide. This project has also served to raise several research questions of interest to those working in long term care and levelled practice: how will the management of new admissions with urinary incontinence change over several years with a program of systematic decision-making in place? will there be a decline in the number of incontinent clients at our facility over a two-year period? is there a relationship between independent decision-making and job satisfaction for professional nursing staff working in levelled practice? and what is the effect of enhancing the independent decision-making skills of professional nursing staff on the job satisfaction of the nonprofessional staff?

Humans↗
PubMed1992

Quantitation of targets for PCR by use of limiting dilution.

We describe a general method to quantitate the total number of initial targets present in a sample using limiting dilution, PCR and Poisson statistics. The DNA target for the PCR was the rearranged immunoglobulin heavy chain (IgH) gene derived from a leukemic clone that was quantitated against a background of excess rearranged IgH genes from normal lymphocytes. The PCR was optimized to provide an all-or-none end point at very low DNA target numbers. PCR amplification of the N-ras gene was used as an internal control to quantitate the number of potentially amplifiable genomes present in a sample and hence to measure the extent of DNA degradation. A two-stage PCR was necessary owing to competition between leukemic and non-leukemic templates. Study of eight leukemic samples showed that approximately two potentially amplifiable leukemic IgH targets could be detected in the presence of 160,000 competing non-leukemic genomes. The method presented quantitates the total number of initial DNA targets present in a sample, unlike most other quantitation methods that quantitate PCR products. It has wide application, because it is technically simple, does not require radioactivity, addresses the problem of excess competing targets and estimates the extent of DNA degradation in a sample.

Base Sequence↗
PubMed1990

Long-term effect of mexiletine on left ventricular function and relation to suppression of ventricular arrhythmia.

The effects of oral mexiletine on left ventricular (LV) ejection fraction (EF) and ventricular arrhythmias--and a possible relation between these effects--were evaluated during 3 months of therapy in 29 patients with chronic ventricular premature complexes (VPCs) and a moderately reduced to normal LVEF by 24-hour Holter monitoring and by radionuclide ventriculography at rest and during maximum tolerable exercise testing. After an average titration period of 13 days, a mean daily mexiletine dose of 739 mg was maintained throughout the treatment. At the end of titration and after 3 months of treatment, patients with a baseline LVEF less than or equal to 40% (group 2) responded with a median reduction of the hourly VPC rate by 90 and 81%, respectively, compared with 79 and 72% in those with a baseline LVEF greater than 40% (group 1). Couplets and runs of ventricular tachycardia were almost completely suppressed in nearly all patients. A single patient had a proarrhythmic increase in VPCs during treatment. Compared with baseline, there were no significant changes in resting or exercise LVEF after 1 or 3 months of treatment in either of the 2 groups of patients. No correlation was found between treatment-induced changes in arrhythmia frequency and in resting EF. No symptoms of congestive heart failure developed. The study confirms that long-term use of mexiletine is efficacious and relatively free of cardiac depressant effects even in patients with diminished LV function.

Aged↗