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Biomedical subjects

D Wright

Publications and source records attributed to D Wright.

At least 163 records · Page 9Linked to original sources

Light and heavy lysosomes: characterization of N-acetyl-beta-D-hexosaminidase isolated from normal and I-cell disease lymphoblasts.

We previously reported that I-cell disease lymphoblasts maintain normal or near-normal intracellular levels of lysosomal enzymes, even though N-acetylglucosamine-1-phosphotransferase activity is severely depressed or absent (Little et al., Biochem. J., 248, 151-159, 1987). The present study, employing subcellular fractionation on colloidal silica gradients, indicates that both light and heavy lysosomes isolated from I-cell disease and pseudo-Hurler polydystrophy lymphoblasts possess normal specific activity levels of N-acetyl-beta-D-hexosaminidase, alpha-D-mannosidase and beta-D-glucuronidase. These current findings are in contrast to those of cultured fibroblasts from the same patients, where decreased intralysosomal enzyme activities are found. Column chromatography on Ricinus communis revealed that N-acetyl-beta-D-hexosaminidase in both heavy and light I-cell disease lysosomal fractions from lymphoblasts possesses an increased number of accessible galactose residues (30-50%) as compared to the enzyme from the corresponding normal controls. Endo-beta-N-acetylglucosaminidase H treatment of N-acetyl-beta-D-hexosaminidase from the I-cell lysosomal fractions suggests that the majority of newly synthesized high-mannose-type oligosaccharide chains are modified to complex-type carbohydrates prior to being transported to lysosomes. This result from lymphoblasts differs from previous findings with fibroblasts, where N-acetyl-beta-D-hexosaminidase from I-cell disease and pseudo-Hurler polydystrophy lysosomes exhibited properties associated with predominantly high-mannose-type oligosaccharide chains.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The inter-relationship of factor VII and its activity state with plasma lipids in healthy male adults.

A close inter-relationship between raised factor VII clotting activity and elevated blood lipids, particularly serum triglycerides, is well established. A study of factor VII, its activation state and of plasma lipids has been undertaken in two groups of healthy middle-aged males to elucidate this mechanism. A control group with normal factor VII levels were closely matched for age and body-mass index with a second group with elevated levels. Factor VII assays, using rabbit and bovine thromboplastin and a factor VII Ag method, were employed. Triglycerides correlated with the rabbit factor VII thromboplastin assay and factor VII Ag (P < 0.05) but not with the bovine thromboplastin method. Higher HDL-cholesterol and apolipoprotein A-I levels were found in subjects with increased factor VII (P < 0.001) and appeared to be due to differences in alcohol consumption. Cholesterol levels were significantly higher with elevated factor VII. Differential testing suggests that higher factor VII is predominantly mediated through a rise in total VII, rather than an increase in its activity state.

Adult↗

Lymphomas of mucosa-associated lymphoid tissue arising in the urinary bladder.

The clinical, histological and immunohistochemical findings in five primary lymphomas of the urinary bladder are reported. One patient had both lymphoma and transitional cell carcinoma of the bladder. All of the lymphomas showed histological features of mucosa-associated lymphoid tissue (MALT) lymphomas with centrocyte-like cells in all cases. One patient with pre-existing cystitis glandularis showed lymphoepithelial lesions. Biopsies from four patients contained reactive germinal centres and, in two of these, there was follicular colonization by tumour cells. In three patients, repeat biopsies, over several years, showing the changes of MALT lymphoma, were diagnosed as cystitis. We suggest that a large proportion of primary lymphomas of the bladder are lymphomas of MALT and that the characteristic morphological and immunohistochemical features of these tumours should be sought in biopsies containing large numbers of lymphoid cells.

Adult↗

My son Andrew.

Explore the source record for details and available documents.

Adult↗

Prospective comparative study of computer programs used for management of warfarin.

AIMS: To compare the effectiveness of three computerised systems that are currently used for assisting warfarin control in outpatients with the customary dosing method used by experienced medical staff. METHODS: A pilot randomised study of three systems with a follow up independently randomised study of two of these was made on 186 patients receiving long term treatment or who had recently started warfarin treatment and had been discharged from hospital. RESULTS: All three computerised systems seemed to give satisfactory control compared with the traditional dosing method. For patients receiving more intensive treatment with an assigned target range of 3.0-4.5 computerised dosage programs achieved significantly better control; the medical staff undertreated such patients almost 50% of the time. CONCLUSION: Computer based programs can assist outpatient anticoagulant control with warfarin during both early and long term treatment. For most patients the control achieved is as good as that obtained by the customary method of dosing, by experienced clinic doctors, although the latter tend to be too conservative when dosing patients within the intense target range of 3.0 to 4.5 International Normalised Ratio (INR). The computers were significantly more successful in this higher range.

Adult↗

Dying to be big: a review of anabolic steroid use.

Anabolic steroids use is commonly perceived to be the domain of the higher echelons of competitive athletes. However, a great deal of anabolic steroid use occurs in private gymnasia (non-local authority) among non-competitive recreational athletes. Our study has attempted to give an insight into the prevalence of the use of these drugs, the hazards associated with it, and the public health responses which we have adopted.

Adult↗

The neurogenic locus brainiac cooperates with the Drosophila EGF receptor to establish the ovarian follicle and to determine its dorsal-ventral polarity.

We have characterized the function of a new neurogenic locus, brainiac (brn), during oogenesis. Homozygous brn females lay eggs with fused dorsal appendages, a phenotype associated with torpedo (top) alleles of the Drosophila EGF receptor (DER) locus. By constructing double mutant females for both brn and top, we have found that brn is required for determining the dorsal-ventral polarity of the ovarian follicle. However, embryos from mature brn eggs develop a neurogenic phenotype which can be zygotically rescued if a wild-type sperm fertilizes the egg. This is the first instance of a Drosophila gene required for determination of dorsal-ventral follicle cell fates that is not required for determination of embryonic dorsal-ventral cell fates. The temperature-sensitive period for brn dorsal-ventral patterning begins at the inception of vitellogenesis. The interaction between brn and DER is also required for at least two earlier follicle cell activities which are necessary to establish the ovarian follicle. Prefollicular cells fail to migrate between each oocyte/nurse cell complex, resulting in follicles with multiple sets of oocytes and nurse cells. brn and DER function is also required for establishing and/or maintaining a continuous follicular epithelium around each oocyte/nurse cell complex. These brn functions as well as the brn requirement for determination of dorsal-ventral polarity appear to be genetically separable functions of the brn locus. Genetic mosaic experiments show that brn is required in the germline during these processes whereas the DER is required in the follicle cells. We propose that brn may be part of a germline signaling pathway differentially regulating successive DER-dependent follicle cell activities of migration, division and/or adhesion and determination during oogenesis. These experiments indicate that brn is required in both tyrosine kinase and neurogenic intercellular signaling pathways. Moreover, the functions of brn in oogenesis are distinct from those of Notch and Delta, two other neurogenic loci that are known to be required for follicular development.

Animals↗

Sources and types of referral to a haematology department.

An audit was undertaken of the case notes of all new outpatients referred to the haematology department at the Leeds General Infirmary over a one-year period. The source, reason for referral, final diagnosis and outcome were determined in each case, along with essential biographical details. The results show that general practitioners initiated over half of all referrals, often prompted by written comments from a hematologist on a full blood count advising them that further tests were required. Almost a third came from other departments at the study hospital and the remainder originated from hospitals outside the district. Most general practitioner referrals were made with a request for a diagnosis. Hospital initiated referrals were more likely to have a final diagnosis of a malignant haematological disease, whereas those from general practice tended to have benign or self-limiting conditions. Ninety-one per cent of patients referred had an abnormality. There were low numbers of both clinic defaulters and those patients required to be re-referred to other specialties. These results suggest that the high quality of referrals is largely due to the general practitioner's decision to refer patients based on the full blood count result. This often occurs after discussion with haematology medical staff. The possible impact of the government's White Paper proposals on this outpatient service is discussed.

Adolescent↗

Critical incidents in the intensive therapy unit.

Preventable mishaps in an intensive therapy unit were studied over 12 months by the critical incident technique. Staff were encouraged to complete confidential questionnaires describing incidents in which they had participated or had observed. This allowed classification of the events and examination of the views of staff on causes, detection, and prevention. 110 (80%) of 137 events were felt to have been due to human error; the remainder were due to equipment failure. Inexperience with equipment and shortage of trained staff were the factors most often felt to contribute to incidents. The critical incident technique is a useful way of improving standards of clinical care.

Accident Prevention↗

Sequences more than 500 base pairs upstream of the human U3 small nuclear RNA gene stimulate the synthesis of U3 RNA in frog oocytes.

Small nuclear RNA (snRNA) genes contain strong promoters capable of initiating transcription once every 4 s. Studies on the human U1 snRNA gene, carried out in other laboratories, showed that sequences within 400 bp of the 5' flanking region are sufficient for maximal levels of transcription both in vivo and in frog oocytes [reviewed in Dahlberg and Lund (1988)]. We studied the expression of a human U3 snRNA gene by injecting 5' deletion mutants into frog oocytes. The results show that sequences more than 500 bp upstream of the U3 snRNA gene have a 2-3-fold stimulatory effect on the U3 snRNA synthesis. These results indicate that the human U3 snRNA gene is different from human U1 snRNA gene in containing regulatory elements more than 500 bp upstream. The U3 snRNA gene upstream sequences contain an AluI homologous sequence in the -1200 region; these AluI sequences were transcribed in vitro and in frog oocytes but were not detectable in HeLa cells.

Animals↗

Safety management vs. picking leaves.

A safety program will generally have as its base a comprehensive written document made available for everyone in the organization. The document should indicate a positive commitment to safety by management. It should not be a "how to" guide, but rather a broad outline to establish responsibilities, goals, and methods. The safety manager is appointed in writing and answers to the highest level of management. As opposed to a "doer," the safety manager acts as a director and administrator of the safety program. This is accomplished through the advisory capacity of the safety program for solicited and unsolicited problems. The focus of the safety manager is on the system and how it contributes to safety problems, rather than individual problems. Management has the ultimate responsibility for safety. Their efforts should reflect a proactive attitude to correct problems in the system. In order to identify areas of interest, technically competent input from the safety manager should be required. The support of the safety program by top management determines the success of the program. Without a clear and firm commitment by the organization, safety will receive no more than lip service from the employees. The benefits of a proactive approach will be realized in the organization's ability to manage safety issues, rather than reacting to them.

Administrative Personnel↗

Resuscitation of patients with cardiac arrest by ambulance staff with extended training in West Yorkshire.

OBJECTIVE: To investigate the results of resuscitation of patients with cardiac arrest by ambulance staff with extended training in West Yorkshire. DESIGN: Study of all such attempts at resuscitation over 32 months, based on the standard report form for each call made by the ambulance staff and the electrocardiogram that showed the initial rhythm in each patient. SETTING: Area covered by West Yorkshire ambulance service. SUBJECTS: 1196 Patients with cardiac arrests attended by 29 ambulance staff with extended training. MAIN OUTCOME MEASURE: Result of resuscitation. RESULTS: The initial rhythm was asystole or electromechanical dissociation in 740 patients and ventricular fibrillation in 456 patients; overall 65 patients survived to be discharged from hospital. Sixty four of the 456 patients in whom ventricular fibrillation was the initial rhythm recorded, and 46 in whom ventricular fibrillation persisted after the ambulance staff arrived, survived. Only one of the 740 patients who initially had asystole or electromechanical dissociation survived. Factors associated with a greater chance of ventricular fibrillation occurring were: age less than 71, the arrest being witnessed by a bystander, resuscitation by a bystander, the arrest occurring in a public place, and a response time by the ambulance staff of less than six minutes. For patients found in ventricular fibrillation a shorter response time was associated with improved survival but resuscitation by a bystander was not. Additional skills learnt during extended training were used for 51 of the 65 patients who survived. CONCLUSIONS: Ambulance staff with extended training can save the lives of patients with cardiac arrest due to fibrillation, though asystole and electromechanical dissociation have a poor prognosis and should perhaps receive little attention during extended training.

Age Factors↗

Computer-assisted analysis of transrectal ultrasound images.

We have developed a microcomputer based system with an application specific software package which permits the direct digitization and analysis of transrectal ultrasound (TRUS) images. The system is highly flexible and enables access to a wide range of image analysis tools through relatively simple software modifications, which cannot be implemented using a standard ultrasound instrument. We have demonstrated the capability of the system by an analysis of a number of morphometric parameters and by a correlation of these measurements with the presence of prostatic cancer. We found that the measurement of the ratio of the anterior-posterior axis to transverse axis and the presumed circular area ratio (PCAR) were significant predictors of prostatic cancer. The sensitivity of the PCAR measurement was 93%, the specificity was 50%, the positive predictive value was 57%, and the negative predictive value was 91%. The high negative predictive values of these parameters may provide objective criteria to allow for selective biopsy of patients. This system provides researchers with an efficient, economical, and flexible method to aid in the analysis of TRUS images in a quantitative manner.

Humans↗

Synthesis and pharmacological evaluation of a series of new 3-methyl-1,4-disubstituted-piperidine analgesics.

The synthesis and intravenous analgesic activity of a series of 3-methyl-4-(N-phenyl amido)piperidines, entries 34-79, is described. The methoxyacetamide pharmacophore produced a series of compounds with optimal analgesic potency and short duration of action. cis-42 was 13,036 times more potent than morphine and 29 times more potent than fentanyl; however, the corresponding diastereomer 43 was only 2778 and 6 times more potent, respectively. Compounds 40, 43, 47, and 57 are extremely short acting; all had durations of action of about 2 min, which was about 1/5 of that of fentanyl in the mouse hot-plate test at a dose equivalent to 2 times the ED50 analgesic dose. Among the many compounds that displayed exceptional analgesic activity, duration of action was one of the main factors for choosing a candidate for further pharmacological investigation. At present, cis-1-[2-(4-ethyl-4,5-dihydro-5-oxo-1H-tetrazol-1-yl)ethyl]-3-meth yl-4- [N-in equilibrium 2-fluorophenyl)methoxyacetamido]piperidine hydrochloride (40) (Anaquest, A-3331.HCl, Brifentanil) is in clinical evaluation. Opiate analgesics that possess short duration of action are excellent candidates for short surgical procedures in an outpatient setting where a rapid recovery is required.

Analgesics↗