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Biomedical subjects

D R Chadwick

Publications and source records attributed to D R Chadwick.

At least 19 recordsLinked to original sources
PubMed2006

Optimization of thyroxine replacement therapy after total or near-total thyroidectomy for benign thyroid disease.

BACKGROUND: Total or near-total thyroidectomy is increasingly used to treat benign thyroid conditions. Lifelong treatment with thyroxine (T4) is then required, but the optimal dose is difficult to predict. This study investigated factors that might predict the ideal T4 dose, with the aim of reducing delays in achieving normal thyroid function after surgery. METHODS: Data on 98 patients who underwent total or near-total thyroidectomy for benign disease were reviewed retrospectively. Patient and operative variables that might predict time to achieve normal thyroid function and optimal T4 replacement dose were examined. These data were then used to formulate an algorithm for T4 dosage, based on patient weight, that was subsequently applied prospectively to a comparable group of 27 patients. RESULTS: The median time to achieve normal thyroid function was 14.5 (range 2-120) weeks before introduction of the algorithm, and was greater in patients needing large changes in T4 dose. In multivariate analysis, the best predictors of optimal T4 dose were bodyweight (r = 0.46, P < 0.001) and age (r = -0.32, P = 0.002). Subsequent use of a weight-related algorithm improved time to achieve normal thyroid function. CONCLUSION: The T4 replacement dosage after total or near-total thyroidectomy is largely influenced by bodyweight. Use of a weight-related algorithm improves patient care compared with use of standard T4 dose-titration methods.

Adolescent↗
PubMed2002

Construction of disturbed and intact soil blocks to develop percolating soil based treatment systems for dirty water from dairy farms.

Intact soil blocks with a surface area of 1.8 x 1.6 m, 1.0 m deep, were excavated in a coarse sandy loam. The sides of the soil blocks were supported with plywood before using hydraulic rams to force a steel cutting plate beneath them. Disturbed soil blocks of the same depth as the intact blocks were also established. Experiments were conducted to determine purification efficiencies for biological oxygen demand (BOD), molybdate reactive phosphorus (MRP), nitrate and ammonium-N after the application of dirty water. A preliminary experiment is described where a low application of dirty water was applied to the soil blocks, 2 mm day(-1). In addition, a chloride tracer was conducted for the duration of the experiment. Disturbed soil had a purification efficiency for BOD of 99% compared to 96% from intact soil (P<0.001). Purification efficiencies for MRP and ammonium-N were 100 and 99%, respectively, for the intact and disturbed soils. Nitrate-N concentration increased in leachate from both treatments reaching maximum concentrations of 15 and 8 mg l(-1) from disturbed and intact soils, respectively. Chloride traces for each soil block followed similar patterns with 47 and 51% loss from disturbed and intact soils, respectively.

Agriculture↗
PubMed2002

The impact of new diagnostic methodologies in the management of meningitis in adults at a teaching hospital.

BACKGROUND: Suspected meningitis is a frequent reason for admission to hospital in the UK. While bacterial meningitis requires prompt antibiotic therapy to reduce mortality and morbidity, enteroviral meningitis, the most frequent viral cause, is almost invariably a benign disease. AIM: To determine the clinical presentation, laboratory findings and outcome of meningitis by microbiological aetiology and patient age, and to assess the clinical management of adults presenting with meningitis, with reference to national guidelines. DESIGN: Retrospective case-note review. METHODS: Adult (>14 years) admissions to Addenbrooke's Hospital with meningitis or meningococcal septicaemia March 1996-September 2001 were audited retrospectively. The case definition was: symptoms compatible with meningitis, and either abnormal CSF (leukocytes >5x10(9)/ml) or meningococcal disease. The only exclusion criterion was the presence of a ventricular shunt. RESULTS: Only 30% of patients seen by a General Practitioner were given pre-admission antibiotics. In a substantial number of cases, including those with bacterial meningitis, antibiotic administration was delayed either because patients were sent for CT head scans (delaying a lumbar puncture) or because the diagnosis was not considered, especially in elderly patients with reduced conscious levels. There were no confirmed cases of H. influenzae meningitis. Overall outcomes in terms of mortality and disability were similar to UK national data. A surprising number of patients (40%) were afebrile on admission. DISCUSSION: The proportion of patients with meningitis given pre-hospital antibiotics by GPs is still worryingly low, although early hospital management has improved. Improved diagnostic facilities, particularly viral PCR assays, reduce antibiotic usage and hospital stay, with considerable financial savings.

Adolescent↗
PubMed2000

Antisense RNA sequences targeting the 5' leader packaging signal region of human immunodeficiency virus type-1 inhibits viral replication at post-transcriptional stages of the life cycle.

Antisense RNA has proven a potent inhibitor of gene expression and has the potential to inhibit retroviral replication at a number of stages in the virus life cycle by targeting both viral and cellular RNA sequences. Antisense RNA complementary to three target regions in the 5' leader/LTR of human immunodeficiency virus type-1 (HIV-1), the TAR region, the primer binding site and the splice donor (SD)-packaging signal (psi) region were stably expressed from the CMV IE promoter in Jurkat cells, and expression confirmed by RT-PCR. When challenged with HIV-1, cell lines expressing antisense RNA targeting the SD/psi region showed significant inhibition of replication (at up to 10(6) TCID 50/ml). These sequences were also expressed in lymphocytes after transduction using recombinant retroviruses and one sequence complementary to the SD/psi region inhibited replication of HIV-1. A co-transfection assay using COS-1 cells was also developed both to confirm the antiviral potential of these sequences, and to determine the predominant site of action of these molecules. Antisense RNAs targeting the psi region and one sequence complementary to the TAR region inhibited expression of viral protein; furthermore, analyses of relative levels of cellular and virion RNA from these assays suggest each of these antisense molecules exerts its effect at an early stage in the transcription-translation pathway, while the longer of the sequences also inhibited packaging of virion RNA. These results suggest that the packaging signal (psi) of HIV-1 represents an attractive target for antisense RNA-based gene therapy, although the main mode of action of such molecules may well be through antisense effects at an earlier stage of replication than packaging.

3T3 Cells↗
PubMed2000

Vasoactive and proliferative effects of parathyroid hormone and parathyroid hormone-related peptide on human vascular smooth muscle.

BACKGROUND: Hyperparathyroidism is associated with an increased incidence of hypertension and cardiovascular disease. Experiments in rats suggest that this results from desensitization of the normally inhibitory effects of parathyroid hormone-related peptide (PTHrP) on vascular smooth muscle cells (VSMCs) by previous exposure to parathyroid hormone (PTH). METHODS: Isometric tension in vitro was measured in segments of vessels obtained at neck surgery from six normotensive patients with hyperparathyroidism and 12 eucalcaemic controls undergoing thyroid surgery. Vessels were precontracted with noradrenaline to allow the vasodilatory effects of PTH and PTHrP to be observed. Human VSMCs were cultured in 0.5, 5 and 15 per cent serum with or without PTH (10(-11) to 10(-7) nmol l-(1)) and proliferation was assessed by cell counts after 14 days. RESULTS: Vasodilatation of arterial segments produced by both PTH 20 nmol l(-1) and PTHrP 100 nmol l(-1) did not differ significantly between control and hyperparathyroidism groups (P > 0.08, Mann-Whitney U test). Vasodilatation by PTHrP was not reduced by preincubation of vessels in vitro with PTH 50 nmol l(-1) for 1 h (P > 0.36, Wilcoxon test). No effects of PTH on serum-induced proliferation of human VSMCs were observed. CONCLUSION: These data imply that homologous desensitization to PTHrP is not implicated in the pathogenesis of vascular disease in patients with hyperparathyroidism.

Aged↗
PubMed1998

The role of fine-needle aspiration cytology and frozen section histology in management of differentiated thyroid cancer: the UK experience.

OBJECTIVE: A review of the literature was undertaken to determine the use by UK surgeons of fine-needle aspiration cytology (FNAC) and frozen section histology in management of differentiated thyroid carcinoma. RESULTS: The extent of FNAC use was highly variable, but commoner amongst more specialised surgeons who performed more than 25 thyroid operations per year. Such surgeons generally perform ipsilateral total lobectomy and isthmectomy for solitary thyroid nodule and use FNAC to assist in planning surgical strategy for differentiated thyroid cancer mainly by determining the likely extent of contralateral lobe resection and nodal dissection required. The use of frozen section histology to aid this decision intra-operatively is largely unreported in the UK literature.

Biopsy, Needle↗
PubMed1997

Wire-directed localization biopsy of the breast: an audit of results and analysis of factors influencing therapeutic value in the treatment of breast cancer.

Fine-wire localization biopsy is an accurate technique for diagnosis of mammographically-detected breast abnormalities, and may also be therapeutic in the management of impalpable malignant lesions. A number of factors were therefore examined regarding their influence upon therapeutic success in a consecutive series of 129 localization biopsies. Factors included type of radiological abnormality, method and accuracy of wire localization and pre-operative cytology. Primary malignancy was detected at initial localization in 64 cases (malignant:benign ratio, 1.11:1); 26 (41%) achieving adequate local tumour excision margins without further surgery, and 38 undergoing further surgery to clear margins (mastectomy in 23, further wide excision in 15). Therapeutic success was related to the accuracy of pre-operative needle localization (needle hook within 1 cm of target lesion in 26/26 (100%) therapeutic biopsies, compared to 29/38 (76%) non-therapeutic biopsies (P<0.01, Fisher's exact test)); and to pre-operative cytology (suspicious/malignant cytology in 15/24 therapeutic, compared with only 9/29 non-therapeutic biopsies (P=0.013, chi-squared)). Localization biopsy has a high diagnostic success rate and a therapeutic value dependent upon accurate pre-operative cytological diagnosis, supplemented by precise needle localization of the target lesion.

Adenocarcinoma↗
PubMed1995

Functional studies of rat, porcine, and human pancreatic islets cultured in ten commercially available media.

There have been no extensive studies investigating the effect of tissue culture media on the in vitro functional characteristics of rat, porcine and human Islets of Langerhans. We therefore aimed to compare ten commercially available tissue culture media on the basis of their ability to maintain islet viability. Following isolation, islets were cultured free-floating in the ten media (RPMI 1640-11mM glucose (control), RPMI 1640-2.2mM glucose, Dulbecco's MEM, TCM 199, CMRL 1066, Iscove's MEM, Waymouth's MEM, Serum-Free medium, Ex-cell 300, Ham's F-12) and viability was assessed after 24 hr, 3 days, and 7 days on the basis of macroscopic appearance, cell membrane integrity, and insulin secretion in response to glucose stimulation both by dynamic incubation and by perifusion. Each islet species demonstrated physiological insulin release characteristics in all media--however, it was possible to distinguish between the media by comparing the stimulation indices calculated from the insulin release studies. Significantly higher stimulation indices were produced in Iscove's MEM for rat islets, in Ham's F-12 for porcine islets and in CMRL 1066 for human islets. Over the entire culture period a significant deterioration in function was observed in all species cultured in the control media, although this was reversed when islets were cultured in the optimal media. Furthermore, in the case of porcine and human islets a significant improvement in function over the seven-day period was noted in the optimal media. In conclusion, of the commercially available media, the optimal tissue culture medium for rat islets is Iscove's MEM, for porcine islets is Ham's F-12, and for human islets is CMRL 1066.

Animals↗
PubMed1994

Storage of pancreatic digest before islet purification. The influence of colloids and the sodium to potassium ratio in University of Wisconsin-based preservation solutions.

The density-dependent purification of islets from several species of mammalian pancreata is improved by prior storage of the dispersed, collagenase-digested pancreas in suitable storage solutions, such as University of Wisconsin (UW) solution. The optimal composition of such solutions, however, is not fully established, although previous investigations have suggested separately that cellular impermeants and colloids are important components. To investigate this issue further, dispersed tissues from 7 porcine and 7 human pancreata were stored in UW or in solutions containing the impermeants lactobionate and raffinose, with either no added colloid or in the presence of the colloids hydroxyethyl starch, dextran 40, dextran 250, or Ficoll 400; hydroxyethyl starch-containing solutions in which the principal cation was sodium, rather than potassium, were also studied. Subsequent purification of islets on continuous linear density gradients of BSA was then assessed by insulin/amylase assay of gradient fractions. Islet purity was slightly reduced using solutions containing impermeants but lacking a colloid, compared with using UW. In the combined presence of impermeants and a colloid, however, islet purity was similar to that obtained with UW, and for porcine pancreata, solutions containing Ficoll 400 or dextran 40 were slightly superior to UW. Purity was not, however, influenced by the sodium to potassium ratio of storage media. In conclusion, impermeants and colloids are both essential components of solutions used to preserve pancreatic tissue before islet purification, findings which may be relevant when designing media for use during other phases of islet isolation, e.g., during collagenase digestion/density gradient purification.

Adenosine↗
PubMed1994

The effectiveness of components of University of Wisconsin solution in improving human pancreatic islet purification.

The purification of human pancreatic islets before transplantation relies on the density-dependent separation of islets from exocrine fragments after collagenase digestion of the donor pancreas. The results vary among pancreases despite increasing automation of the digestion and purification processes, reflecting variations in the overlapping densities of islets and contaminating exocrine tissue. Hypothermic storage of both the pancreas and the pancreatic digest alters cell volumes and tissue densities, thereby affecting islet purification. By biochemical analysis of the isopycnic distribution of islets and exocrine tissue fragments from 23 human pancreases on linear continuous density gradients, the effect of various solutions for cold storage of pancreatic digest was studied. The use of the University of Wisconsin cold storage solution, which resulted in a significant decrease in digest volume (P = 0.006) and increase in the densities of both exocrine tissue (P = 0.001) and islets (P = 0.005), produced a significant improvement in islet purity compared with tissue culture medium (P = 0.035), predominantly due to the inclusion of a colloid, which increased the difference in density between exocrine tissue and islets. The addition of large molecular weight cellular impermeants without alteration in the concentration of permeable anions produced no effect. The results of this study support the concept that the use of solutions that minimize cell swelling throughout the process of islet purification would result in significant improvements in density-dependent islet separation, and that such solutions should contain a colloid.

Adenosine↗
PubMed1993

Porcine islet isolation: prospective comparison of automated and manual methods of pancreatic collagenase digestion.

A prospective study was undertaken to compare an automated method of porcine pancreatic digestion with a simpler manual procedure. These techniques have not previously been compared directly. After intraductal distension with collagenase, seven porcine pancreata were divided longitudinally; half of each was digested by the automated method and half by the manual technique. Islet yield and purity were measured. Compared with the manual technique, the automated method isolated a significantly greater total volume of islet tissue (median (range) 3.56 (1.39-5.30) versus 1.07 (0.46-1.92) mm3/g, P = 0.022), increased the median (range) number of 105-microns islet equivalents isolated (5875 (2294-8746) versus 1766 (759-3168) per g, P = 0.022) and improved the islet cleavage index (median (range) 92 (89-99) versus 82 (78-92) per cent, P = 0.035). It is concluded that, although the automated method is more complicated to set up, it greatly improves the yield of intact islets from the porcine pancreas.

Animals↗