PubMed Health⌕ Search

Biomedical subjects

D Simpson

Publications and source records attributed to D Simpson.

At least 145 records · Page 8Linked to original sources
PubMed1997

Tumour suppressor genes in the pathogenesis of human pituitary tumours.

Abnormal cell proliferation is controlled by opposing actions of oncogene products (stimulatory) and tumour suppressor gene (TSG) products (inhibitory). The former are dominantly acting, i.e. only one copy needed for tumorigenesis, whilst for TSG both copies of the gene must be inactivated so these are recessive at a cellular level. For anterior pituitary tumours only one oncogene (Gsp) has been identified in a variable proportion (4-40%) of a single tumour subtype (somatotrophinomas). Contrariwise, allelic deletion studies, using a PCR-based microsatellite polymorphism analysis of DNA extracted from archival specimens, have shown significant loss of heterozygosity in 20-40% of all tumour subtypes at the locus of the putative MEN-1 gene (chr. 11q13); the retinoblastoma gene (chr. 13q 12-14), and 10q26. Moreover, these DNA microdeletions were concentrated in radiologically invasive tumours compared to noninvasive tumours (modified Hardy gdes 3 and 4 vs. 1 + 2). In addition, 50% of Cushing's adenomas showed presence of p53 immunopositivity, though no point mutations in exons 4-9 were found, by SSCP analysis, to account for this. These studies show that analysis of TSGs in pituitary adenomas may provide clues to their pathogenesis, and more importantly relate to clinical behaviour of the tumour, and hence aid decisions regarding management.

Cell Division↗
PubMed1997

Evaluation of Bionike one-step tests for the detection of drugs of abuse in urine.

Bionike one-step tests were used to screen urine samples for amphetamines, methamphetamines, benzodiazepines, cannabinoids, methadone and opiates, and results were compared with those obtained using enzyme multiplied immunoassay technique d.a.u. assays. Taking into consideration different threshold levels and possible differences in cross-reactivities, there was good agreement between the methods. Results of Bionike tests correlated well with amphetamines, methadone and opiates detected in urine using gas chromatography-mass spectrometry. Bionike methods are rapid, simple to use, and relatively inexpensive for on-site testing of individual drugs or groups of drugs in urine.

Amphetamine↗
PubMed1997

Screening for drugs of abuse (II): Cannabinoids, lysergic acid diethylamide, buprenorphine, methadone, barbiturates, benzodiazepines and other drugs.

Requirements for the provision of an efficient and reliable service for drugs of abuse screening in urine have been summarized in Part I of this review. The requirements included rapid turn-around times, good communications between requesting clinicians and the laboratory, and participation in quality assessment schemes. In addition, the need for checking/confirmation of positive results obtained for preliminary screening methods was stressed. This aspect of the service has assumed even greater importance with widespread use of dip-stick technology and the increasing number of reasons for which drug screening is performed. Many of these additional uses of drug screening have possible serious legal implications, for example, screening school pupils, professional footballers, parents involved in child custody cases, persons applying for renewal of a driving licence after disqualification for a drug-related offence, doctors seeking re-registration after removal for drug abuse, and checking for compliance with terms of probation orders; as well as pre-employment screening and work-place testing. In many cases these requests will be received from a general practitioner or drug clinic with no indication of the reason for which testing has been requested. This also raises the serious problems of a chain of custody, provision of two samples, stability of samples, and secure and lengthy storage of samples in the laboratory-samples may be requested by legal authorities several months after the initial testing. The need for confirmation of positive results is now widely accepted but it may be equally important to confirm unexpected negative results. Failure to detect the presence of maintenance drugs may lead to the patient being discharged from a drug treatment clinic and, if attendance at the clinic is one of the terms of continued employment, to dismissal. It seems likely that increasing abuse of drugs and the efforts of regulatory authorities to control this, will lead to the manufacture of more designer drugs. Production of substituted phenethylamines was facilitated by the drug makers' cook book, 'PIHKAL' (Phenethylamines I Have Known And Loved) by Dr Alexander Shulgin and Ann Shulgin, and production of substituted tryptamines is promised in their next book, TIHKAL. Looking to the future, laboratories will need to ensure that they can detect and quantitate an ever-increasing number of drugs and related substances. The question of confidence in results of drugs of abuse testing raised in 1993 by Watson has assumed even greater importance as a result of attention focused on the OJ Simpson trial in Los Angeles. Toxicological investigations are likely to be challenged more frequently in the future. Even if analyses have been performed by GC-MS, there is a need to establish the level of match between the spectrum of the unknown substance and a library spectrum which is considered acceptable for legal purposes. It will also be essential to ensure that computer libraries contain spectra for all substances likely to be encountered in drugs of abuse screening.

Barbiturates↗
PubMed1997

Future faculty development in family medicine.

BACKGROUND AND OBJECTIVES: Several recurring conclusions about the changed conditions and future needs of faculty emerged from the articles in this dedicated issue. Faculty work is becoming more differentiated; time is increasingly constrained; and faculty are working in more diverse settings. Faculty reward structures and career ladders are changing, and acquiring additional competencies in new areas is essential. Although less then anticipated, there is some research to guide the development of programs to prepare faculty for these changes. Based on these conclusions, it is expected that in the future, faculty and program chairs will seek a tight match between what a faculty development effort addresses and the responsibilities of faculty participants and/or the goals of the department or program. The following trends are expected: 1) Regional/national comprehensive programs will often be the best choice for new faculty since many departments and residencies will not have sufficient resources to support their own faculty development programs. 2) Research-oriented faculty will be expected to devote 2 years or more to formal training. 3) Experienced faculty and department/program leaders, many of whom are graduates of our faculty development programs, will need advanced training in targeted areas, through on-site, contextualized education or through individualized programs--perhaps electronic. 4) Organizational development will be needed to help departments and programs make changes in missions and processes and to maintain a sense of community. At the same time that new models must be created to meet these future faculty development needs, support for such programs has decreased. Both local and national sources must be recommitted to support faculty development programs and research so we may advance our understanding of cost-effective approaches to faculty development. Funding agencies need to change their guidelines to match the current needs for development and limit funding to programs designed on evidence.

Career Mobility↗
PubMed1996

Hordein promoter methylation and transcriptional activity in wild-type and mutant barley endosperm.

B- and C-hordein gene transcription is severely reduced in the endosperm of the regulatory barley mutant lys3a, and this is correlated with persistent hypermethylation of the promoters. In contrast, D-hordein is expressed at normal levels in the mutant. To confirm the connection between methylation and transcriptional activity, a genomic D-hordein clone was isolated and sequenced. The nucleotide composition of the promoter region revealed a CpG island and methylation analysis, using bisulphite treatment of genomic DNA, confirmed that the D-hordein promoter is unmethylated in endosperm and leaf tissue. Immunocytochemical studies localized D-hordein to the reticular component of protein bodies in both the wild-type Bomi and lys3a. Transient expression of GUS reporter gene constructs in barley endosperm, following transfection by particle bombardment revealed the D-hordein promotors. Comparison of transient expression in Bomi and lys3a endosperm demonstrated that the activities of the unmethylated D-hordein and the Hor1-14 C-hordein promoters were equivalent, while the activities in the mutant of the Horl-17 C-hordein and the Hor2-4 B-hordein promoters were reduced two- and tenfold, respectively. Methylation of plasmids in vitro prior to expression severely inhibited B- and D-hordein promoter activities. Based on these observations two categories of promoters for endosperm-specific expression of storage proteins are recognized and a model involving methylation and modulation of chromatin structure in the regulation by the Lys3 gene is presented.

Base Sequence↗
PubMed1996

Blood alcohol and cardiac arrest.

Patients who suffer a cardiac arrest with alcohol present in their blood may, theoretically, differ from patients who arrest in the absence of alcohol. Alcohol may induce certain lethal arrhythmias, deter strenuous resuscitation in the pre-hospital phase and influence the effectiveness of resuscitative manoeuvres. In this study, 150 patients presenting to an Accident and Emergency department with cardiac arrest were tested for the presence of alcohol in their plasma. 49 patients had detectable plasma alcohol and analysis of their pre-hospital resuscitation revealed no significant differences when compared with the 101 patients in whom no alcohol was detected. No particular arrhythmia predominated in the alcohol group, and patients who had alcohol detected in their blood were just as likely to be successfully resuscitated, in terms of both restoration of spontaneous circulation and survival to hospital discharge. The effect of significantly elevated plasma alcohol levels on cardiac arrest outcome remains unclear, however, as only 7/150 patients had plasma alcohol levels above the legal driving limit.

Adolescent↗
PubMed1996

Helmets in surgical history.

The relevance of historical experience is evident in a consideration of helmets designed for head protection in war, industry, sport and road transport. Modern helmets are designed to minimize the risk of brain damage by penetration and by blunt impact; where facial or ocular injury is likely, facial protection may be provided by visors, goggles or full-face helmets. The effectiveness of helmets should be monitored by studies of actual injuries; historically, surgeons have done this, in war and peace, for centuries.

Head Protective Devices↗
PubMed1996

Avulsion of the popliteus muscle in a malinois dog.

A four-month-old malinois was presented for lameness which was attributed to an avulsion of the origin of the popliteus muscle. Surgical repair by internal fixation with a lag screw and washer resulted in resolution of the lameness.

Animals↗