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Biomedical subjects

N Weir

Publications and source records attributed to N Weir.

At least 19 recordsLinked to original sources
PubMed2002

Tumour targeting of humanised cross-linked divalent-Fab' antibody fragments: a clinical phase I/II study.

Antibody engineering has made it possible to design antibodies with optimal characteristics for delivery of radionuclides for tumour imaging and therapy. A humanised divalent-Fab' cross-linked with a bis-maleimide linker referred to as humanised divalent-Fab' maleimide was produced as a result of this design process. It is a humanised divalent antibody with no Fc, which can be produced in bacteria and has enhanced stability compared with F(ab')(2). Here we describe a clinical study in patients with colorectal cancer using humanised divalent-Fab' maleimide generated from the anti-carcinoembryonic antigen antibody A5B7 radiolabelled with iodine-131. Ten patients received an i.v. injection of iodine-131-labelled A5B7 humanised divalent-Fab' maleimide, and positive tumour images were obtained by gamma camera imaging in eight patients with known lesions, and one previously undetected lesion was identified. True negative results were obtained in two patients without tumour. Area under the curve analysis of serial blood gamma counting and gamma camera images showed a higher tumour to blood ratio compared to A5B7 mF(ab')(2) used previously in the clinic, implying this new molecule may be superior for radioimmunotherapy. MIRD dose calculations showed a relatively high radiation dose to the kidney, which may limit the amount of activity that could be administered in radioimmunotherapy. However the reduction in immunogenicity was also a major advantage for A5B7 humanised divalent-Fab' maleimide over murine versions of this antibody suggesting that humanised divalent-Fab' maleimide should be a useful vehicle for repeated therapies.

Area Under Curve↗
PubMed2001

Towards a national system for monitoring the quality of hospital-based stroke services.

BACKGROUND AND PURPOSE: We sought to evaluate a system for monitoring the quality of hospital-based stroke services that uses routinely collected case fatality data, adjusted for case mix, as well as simple measures of the process of stroke care. METHODS: We compared the process of care and case fatality after stroke between 5 Scottish hospitals (A through E) during 1995-1997. We retrospectively identified 2724 patients with acute stroke using routine discharge data and obtained case mix and process of care data from the medical record. We ascertained case fatality by record linkage and adjusted for case mix using a simple, externally validated regression model. RESULTS: Crude case fatality varied by 21 deaths per 100 admissions between the 5 hospitals. After adjustment, case fatality still differed significantly (P=0.047), with 5 to 7 more deaths per 100 admissions at Hospital A than at Hospitals B through E. There were major shortcomings in the specialization and organization of care, the use of CT scanning, and the completeness of documentation at Hospital A compared with the other hospitals. There were smaller, but clinically important, differences in care between Hospitals B through E but no significant differences in adjusted case fatality. CONCLUSIONS: Once adjusted for important prognostic variables, routinely collected case fatality data might identify hospitals with major shortcomings in the processes of stroke care. More moderate, but still clinically important, variations in stroke care can only be identified by monitoring the process of care directly.

Aged↗
PubMed2001

Community ear care delivery by community ear assistants and volunteers: a pilot programme.

Hearing impairment is a major public health problem in Nepal. The present service delivery, however, is mainly hospital based and is limited to large towns. Those people residing in rural areas lack many basic needs including ear care services. The collaborative community volunteer-based ear care pilot programme implemented in Banke, Nepal aims to reach out to those rural areas by establishing sustainable primary ear care services, empowering and utilizing local resources. The focus of the programme is to promote multi-sector improvement in sanitation, nutrition, immunization, breast-feeding and timely care and support to ear patients to help prevent hearing impairment mainly from the sequelae of otitis media.

Community Health Services↗
PubMed2000

Otorhinolaryngology.

Otorhinolaryngology, a product of the early 20th century, developed from the joining together of the separate departments of otology, whose practitioners were surgeons, and laryngology which was managed by physicians who also treated diseases of the nose and chest. The 20th century opened with brave attempts to perform skilful surgery under conditions of primitive anaesthesia and no antibiotics. The stimulus of two world wars led to significant advances in technology and greater opportunities to explore new and resurrect old surgical procedures. The discovery of antibiotics saw an end to acute mastoiditis and the complications of otitis media and sinusitis, as well as a decline in the number of tonsillectomy and adenoidectomy operations. Over the last 30 years the specialty has undergone dramatic development and has taken advantage of new advances in endoscopy, microsurgery, the use of lasers, cytotoxic drugs, flap reconstruction and microchip technology. During the same period, although still calling themselves otorinolaryngologists, individual surgeons have subspecialised in otology, otoneurosurgery and skull-base surgery, head and neck surgery, phonosurgery, rhinology and facioplastic surgery, and paediatric otothinolaryngology. Each of these subspecialties has its own societies and specialist journals.

History, 20th Century↗
PubMed1998

The distribution and latency of the auditory P300 in schizophrenia and depression.

In a study of 19 right-handed patients with positive symptoms of schizophrenia, fulfilling DSM-III-R criteria, a deficit in the left central-temporal distribution of the auditory P300 was shown compared to a group of 31 controls, who showed a symmetrical distribution. In contrast, 14 right-handed patients fulfilling DSM-III-R criteria for major depressive illness without any psychotic features showed a deficit in the right auditory P300 distribution. These changes did not appear to depend on either age, gender or amount of medication. There was an increase in the P300 latency of 22 and 10 ms over that of the controls in schizophrenia and depressive patients, respectively. Only for those with schizophrenia was the increased latency statistically significant. This increased latency in the schizophrenic group did not appear to be related to medication.

Acoustic Stimulation↗
PubMed1997

Measuring the quality of life of older persons: a model with implications for community and public health nursing.

Measuring the quality of life (QOL) of older persons can assist health professionals in achieving a number of important objectives. These include assessing the effects of illness and treatment, identifying need for support services, and developing health enhancing environments. Most QOL models focus unduly on illness and disability, define QOL too narrowly, and do not consider aspects of personal control and potential opportunities for change. A new model of QOL with associated instrumentation, the Quality of Life Profile: Seniors Version (QOLPSV), is described. Administration of the QOLPSV to 205 older persons in Ontario, Canada found it to be reliable and valid. Limitations of the instrument are presented and potential uses explored.

Aged↗
PubMed1996

Co-expression of human protein disulphide isomerase (PDI) can increase the yield of an antibody Fab' fragment expressed in Escherichia coli.

Secretion to the periplasm of Escherichia coli enables production of many eukaryotic extracellular proteins in a soluble form. The complex disulphide bond arrangement of such proteins is probably a major factor in determining the low yield of correctly folded product observed in many cases. Here we show that co-expression of human protein disulphide isomerase increased the yield of a monoclonal antibody Fab' fragment in the periplasm of E. coli.

Amino Acid Sequence↗
PubMed1996

Vocal fold palsy after use of the laryngeal mask airway.

We report two cases of left vocal fold palsy following use of the laryngeal mask airway. In both cases anaesthesia was uneventful with a duration of about 60 minutes. It is proposed that high intra-cuff pressures induced during anaesthesia resulted in distension of the hypopharynx and subsequent neuropraxia of the motor branches of the recurrent laryngeal nerve and the external branch of the superior laryngeal nerve.

Anesthesia, Inhalation↗
PubMed1995

Human protein disulfide isomerase functionally complements a dsbA mutation and enhances the yield of pectate lyase C in Escherichia coli.

Human PDI was expressed to the Escherichia coli periplasm, by using a plasmid encoded ompA-PDI fusion under the control of the trp promoter. Periplasmic extracts were shown to contain active PDI using the scrambled ribonuclease assay. PDI activity was also demonstrated by complementation of two phenotypes associated with a dsbA mutation. Alkaline phosphatase activity, which is reduced in dsbA cells, was restored to wild type levels by PDI. PelC, a pectate lyase from Erwinia carotovora, was shown to be DsbA dependent in E. coli. PDI was able to restore its activity to that seen in wild type cells. Increased expression of PDI was found to increase the yield of active PelC above that seen in wild type cells. PDI also enhanced the yield of PelC in DsbA- cells but only in the presence of exogenous oxidized glutathione. PDI is thus able to functionally substitute for DsbA in the folding of disulfide-bonded proteins in the bacterial periplasm and to enhance the yield of highly expressed protein when the ability of the E. coli periplasm to fold protein may be saturated. However, our results suggest that the activities of DsbA and PDI in vivo may be different.

Base Sequence↗
PubMed1993

Expression, purification and characterization of B72.3 Fv fragments.

The Fv fragment of the antibody B72.3 has been produced by expression in both a mammalian and microbial system, namely Chinese hamster ovary (CHO) cells and Escherichia coli. In both cases secretion of the Fv into the culture medium was achieved, with equivalent amounts of Vh and Vl produced. The yield of Fv from CHO cells was 4 mg/l in roller-bottle culture. E. coli proved to be a more productive system with yields of 40 mg/l in shake flasks rising to 450 mg/l in fermentations. B72.3 Fv from both sources was capable of binding to antigen with similar binding ability to the Fab' fragment. A detailed sedimentation analysis, both by velocity and equilibrium techniques, revealed that the two domains of Fv are associated at high concentrations at pH values close to neutral, but dissociate at concentrations lower than approx. 0.5 mg/ml. Individual Vh or Vl polypeptides are not able to bind to the antigen and thus these results suggest that the antigen promotes assembly of Fv at the low concentrations used in the antigen-binding assays. At a pH value of 1.9, Vh and Vl are completely dissociated even at very high concentrations and are apparently unfolded at low solute concentrations. Small-angle X-ray scattering was used to measure a radius of gyration of 1.75 +/- 0.2 nm (17.5 +/- 2 A) for Fv.

Animals↗