Lamotrigine for generalised epilepsies.
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Adult↗
Biomedical subjects
E Hughes
Publications and source records attributed to E Hughes.
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↗
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↗
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↗
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↗
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↗
Reversal of hepatic encephalopathy and alteration in amino acid profiles after blocking a surgical splenorenal shunt by interventional radiological techniques.
Portal-systemic shunts are effective in preventing haemorrhage from varices in portal hypertension, but at the price of hepatic encephalopathy. We describe the blockage of a splenorenal shunt using interventional radiology, in a patient with incapacitating chronic encephalopathy. The procedure successfully reversed encephalopathy, without haemodynamic disturbances or haemorrhage from recurrent varices and was associated with a return of the plasma amino acid profile towards normal, with a reduction in aromatic amino acids and an increase in branch chain amino acids. This observation supports the hypothesis that changes in plasma amino acid profiles in patients with portal-systemic shunting are due to the diversion of portal blood rather than the underlying chronic liver disease.
Amino Acids↗
Immunoreactive trypsin in acute pancreatitis: elevated levels do not correlate with hyperamylasaemia.
Immunoreactive trypsin (IRT) was measured in the serum of patients presenting with acute pancreatitis (AP) and compared to serum amylase levels. Both were elevated beyond the normal range at presentation (mean IRT 557 +/- 252 micrograms/l, range 181-1000 micrograms/l, mean control IRT 42 +/- 14 micrograms/l, range 15-82 micrograms/l; mean amylase 4500 +/- 3200 IU/l, range 600-10,500 IU/l, control amylase mean 175 +/- 43 IU/l, range 48-320 IU/l). There was minimal correlation between IRT and amylase elevation but both returned to normal at the same rate in patients who recovered. In 2 patients with persistently elevated IRT levels, one was found to have a pancreatic pseudocyst and the other subsequently died from alcoholic haemorrhagic pancreatitis. IRT is no better than amylase as a single diagnostic assay in AP but may be greatly elevated when amylase elevation is minimal. The combination of the two may improve diagnostic accuracy and persistent elevation of IRT may be of prognostic importance.
Acute Disease↗
Pulmonary lymphangiomyomatosis complicating pregnancy. A case report.
A 32-year-old primigravida presented with cough and dyspnea at 16 weeks' gestation. Chest roentgenogram revealed a large pleural effusion and diffuse interstitial infiltrates. Moderate arterial hypoxemia and a significant reduction in vital capacity were present. Thoracentesis revealed sterile chyle with no evidence of malignancy. Spontaneous delivery of a healthy infant occurred at 38 weeks, but no change was seen in either the pulmonary infiltrates or chylothorax. Open lung biopsy confirmed the clinical impression of pulmonary lymphangiomyomatosis, and a pleurodesis was performed. Progesterone and estrogen receptor assays on the lung biopsy material revealed only minimal binding. Following two years of therapy with tamoxifen citrate and megestrol acetate, the chylothorax has not recurred, and there has been no other appreciable change in pulmonary function.
Adult↗
Screening for intrauterine growth retardation using ratio of mid-arm circumference to occipitofrontal circumference.
Uncritical application of standard weight percentile charts, derived from white infants, to infants from different ethnic groups may result in an overestimate of the incidence of intrauterine growth retardation in those groups. The ratio of mid-arm circumference to occipitofrontal circumference was studied in 194 babies (49 Asian, 58 black, and 87 white). In contrast with birth weight the ratio did not vary among the ethnic groups; it was also independent of sex. In a prospective study of 64 neonates whose weight was below the 10th percentile on standard charts the ratio of mid-arm circumference to occipitofrontal circumference was a more accurate predictor than weight of those infants who would develop symptoms associated with intrauterine growth retardation. The ratio of mid-arm circumference to occipitofrontal circumference therefore provides a simple, accurate, and cheap way of assessing intrauterine growth retardation in areas with a large multiethnic population, where birth weight varies greatly.
Anthropometry↗
A balanced de novo X/autosome translocation in a girl with manifestations of Lowe syndrome.
The Oculo-cerebro-renal syndrome of Lowe is an X-linked recessive disorder characterised by mental and growth retardation, renal rickets with renal tubular acidosis, generalised aminoaciduria, hypotonia, cataracts, glaucoma and frontal bossing. Manifestations of this syndrome were seen in a girl with no family history of the disorder, but who was found to have a de novo balanced X/3 translocation, with a breakpoint at Xq25. She had also inherited a balanced 14/17 translocation from her father. It is postulated that the clinical picture may be the result of disruption of the X chromosome within the gene at the locus for Lowe syndrome, with non-random inactivation of the normal X, which may permit the expression of this X-linked recessive disorder in a girl.
Child↗
No section of the NHS can consider itself exempt from the impact of the Griffiths Report.
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Humans↗
You are what you wear.
Uniforms and professional roles are frequently tied in the minds of both staff and patient, so it may be advisable to return to greater use of uniforms by hospital professional staffs.
Attitude of Health Personnel↗
Institutionalized older adults and their future orientation.
This study hypothesized: 1) that as the duration of institutional living increases, the future orientation of active older adults contracts; and 2) that this constriction in future temporal orientation means less opportunity for interaction in the institutional environment. To test the first hypothesis, 100 active female residents in six institutions for the aged were evaluated regarding future orientation, by means of Cottle's Experiential Inventory. The opportunity for interaction was measured by Pincus's Psychosocial Dimensions in the Institutional Environment. The findings indicated that, irrespective of age, the residents became less future-oriented or their orientation became less recent, as the length of institutional residence increased. The second hypothesis was not supported; in fact, the reverse was true.
Aged↗
Helping staff to manage conflict well.
A hospital that trains its staff to deal assertively with conflict can become more effective in terms of productivity, cost effectiveness, and patient satisfaction. A training model for handling conflict in the work setting is described.
Aggression↗