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Biomedical subjects

A Williams

Publications and source records attributed to A Williams.

At least 37 records · Page 2Linked to original sources
PubMed2005

A mixture of ammonium perchlorate and sodium chlorate enhances alterations of the pituitary-thyroid axis caused by the individual chemicals in adult male F344 rats.

Ammonium perchlorate (AP) and sodium chlorate (SC) have been detected in public drinking water supplies in many parts of the United States. These chemicals cause perturbations in pituitary-thyroid homeostasis in animals by competitively inhibiting iodide uptake, thus hindering the synthesis of thyroglobulin and reducing circulating T(4) (thyroxine). Little is known about the short-term exposure effects of mixtures of perchlorate and chlorate. The present study investigated the potential for the response to a mixture of these chemicals on the pituitary-thyroid axis in rats to be greater than that induced by the individual chemicals. Adult male F-344 rats were exposed, via their drinking water, to the nominal concentrations of 0.1, 1.0, 10 mg/L AP or 10, 100, 1000 mg/L SC and their mixtures for 7 days. Serum T(4) levels were significantly (p < 0.05) reduced in rats following exposure to the mixtures, but not after exposure to the individual chemicals. Serum T(3) (triiodothyronine) was not altered by treatment and TSH (thyroid stimulating hormone) was only increased after the high-dose chlorate treatment. Histological examination of the thyroid gland showed colloid depletion and hypertrophy of follicular epithelial cells in high-dose single chemical and all mixture-treated rats, while hyperplasia was observed only in some of the rats treated with mixtures (AP 10 + SC 100, AP 0.1 + SC 1000, and AP 10 + SC 1000 mg/L). These data suggest that short-term exposure to the mixture of AP and SC enhances the effect of either chemical alone on the pituitary-thyroid axis in rats.

Animals↗
PubMed2005

Validity of sleep nasendoscopy in the investigation of sleep related breathing disorders.

OBJECTIVE: To validate the technique of sleep nasendoscopy using target controlled infusion in symptomatic patients and a control group of asymptomatic individuals. DESIGN: Prospective cohort study. SETTING: Department of otolaryngology-head and neck surgery and anesthesia in a teaching hospital. PARTICIPANTS: Two groups of patients were compared and matched for their body mass index. The first group consisted of 53 patients with a history suggestive of obstructive sleep apnea. The second group consisted of 54 patients with partner-confirmed history of no snoring. These patients were undergoing anesthesia for other reasons. Both groups of patients were free of associated otorhinolaryngologic symptoms. MAIN OUTCOME MEASURE: Assessment of production of snoring or obstruction in patients with no documented history of snoring when sedation was administered as part of general anesthesia using target controlled infusion with propofol. RESULTS AND CONCLUSIONS: None of the patients in the asymptomatic group snored or obstructed at any level of propofol, and this was clearly significant on comparison with the symptomatic group (P < .001). All of the symptomatic patients were induced to become symptomatic (snoring/obstruction).

Body Mass Index↗
PubMed2005

Boosting with poxviruses enhances Mycobacterium bovis BCG efficacy against tuberculosis in guinea pigs.

Tuberculosis is rising in the developing world due to poor health care, human immunodeficiency virus type 1 infection, and the low protective efficacy of the Mycobacterium bovis BCG vaccine. A new vaccination strategy that could protect adults in the developing world from tuberculosis could have a huge impact on public health. We show that BCG boosted by poxviruses expressing antigen 85A induced unprecedented 100% protection of guinea pigs from high-dose aerosol challenge with Mycobacterium tuberculosis, suggesting a strategy for enhancing and prolonging the efficacy of BCG.

Animals↗
PubMed2005

Sleep disordered breathing and its treatment in congestive heart failure.

Sleep disordered breathing (SDB) is a common problem with adverse cardiorespiratory, endocrinological, and endothelial effects. Recent studies demonstrate an even higher prevalence of SDB in congestive heart failure (CHF) than in a randomly selected population, with up to 40% and 11% having Cheyne Stokes respiration-central sleep apnoea and obstructive sleep apnoea-hypopnoea syndromes, respectively. Randomised controlled trials of nocturnal respiratory support for SDB associated with CHF for up to three months demonstrate significant benefits in terms of improvements in left ventricular ejection fraction, markers of sympathetic system activity, and quality of life. Further randomised controlled trials of larger scale and longer duration are required to establish the role and benefit of this intervention for the treatment of this debilitating condition. The evidence for the higher prevalence of SDB in CHF, its pathogenesis, its pathophysiological consequences, and the emerging benefits of respiratory support are reviewed.

Continuous Positive Airway Pressure↗
PubMed2005

Silver absorption and antibacterial efficacy of silver dressings.

OBJECTIVE: To evaluate the patterns of silver release from selected sustained silver-release dressings and the protective role of proteins in wound exudate and wound scale. The bactericidal action of silver in chronic wound therapy is also examined. METHOD: Sequential microbiological examination of wound swabs from seven patients with chronic wounds and sampling of wound exudate and wound scale. Silver content was measured using atomic absorption spectrometry. The ability of Contreet Foam to absorb exudate and release silver was studied in punch biopsy wounds in a rodent model. RESULTS: Silver accumulation in wound exudate correlated well with its viscosity and protein content. Silver bound to wound scale and debris was approximately proportional to the silver ion release from dressings. Bacterial burden was controlled, but not eliminated, following chronic silver therapy. CONCLUSION: Silver dressings (Acticoat-7, Actisorb Silver, Contreet Foam, Aquacel Ag and Flamazine) were found to be safe for use in chronic wound therapy. Excess silver ion is bound by wound exudate and wound scale as a protective mechanism. Silver-release dressings are not likely to result in germ-free wounds. Further studies are needed to examine potential silver resistance.

Aged↗
PubMed2005

Displacement of the common peroneal nerve in posterolateral corner injuries of the knee.

We reviewed the relationship between the pattern of damage to the posterolateral corner of the knee and the position of the common peroneal nerve in 54 consecutive patients with posterolateral corner disruption requiring surgery. We found that 16 of the 18 patients with biceps avulsions or avulsion-fracture of the fibular head had a displaced common peroneal nerve. The nerve was pulled anteriorly with the biceps tendon. None of the 34 proximal injuries resulted in an abnormal nerve position. Whenever bone or soft-tissue avulsion from the fibular head is suspected, the surgeon should expect an abnormal position of the common peroneal nerve and appreciate the increased risk of iatrogenic damage.

Fibula↗
PubMed2004

Randomized clinical trial of low molecular weight heparin with thigh-length or knee-length antiembolism stockings for patients undergoing surgery.

BACKGROUND: This was a randomized clinical trial to determine the efficacy and safety of a 'blanket' protocol of low molecular weight heparin (LMWH) and the best length of antiembolism stocking, for every patient requiring surgery under general anaesthesia. METHODS: Of 426 patients interviewed, 376 agreed to be randomized to receive one of three types of stocking: thigh-length Medi thrombexin climax (Medi UK, Hereford, UK), knee-length thrombexin climax and thigh-length Kendall T.E.D. (Tyco Healthcare UK, Redruth, UK). All patients received LMWH thromboprophylaxis. Duplex ultrasonography was used to assess the incidence of postoperative deep vein thrombosis (DVT). RESULTS: No postoperative DVT occurred in 85 patients at low or moderate risk. Nineteen DVTs occurred, all in the 291 high-risk patients: two with the Medi thigh-length stockings, 11 with the Medi knee-length stockings (odds ratio 0.18 (95 per cent confidence interval 0.04 to 0.82); P = 0.026) and six with the Kendall T.E.D. thigh-length stockings. No patient developed a pulmonary embolism. Stocking groups were similar for age, sex, thromboembolic risk, type of operation and compliance. One significant bleeding complication occurred. CONCLUSION: A single protocol comprising LMWH and thigh-length stockings abolished DVT in low- and moderate-risk patients, and reduced the rate of DVT to 2 per cent in high-risk patients.

Adolescent↗
PubMed2004

Hydrofluoric acid burns.

OBJECTIVE: The purpose of this article is to report our experience with hydrofluoric acid (HF) burns and to present our management guidelines for these burns, which include a novel way of delivering calcium combined with dimethyl sulphoxide (DMSO) for cutaneous burns. METHOD: We reviewed our institutional experience from 1977 to 1999 for patients presenting with burns caused by hydrofluoric acid and collected data on age, sex, burn size, anatomical site, method of contact, surgical procedure, and outcome. RESULTS: Of a total of 2310 admissions, 42 HF burns patients were identified during the study period. The average age was 34 years. There were 35 males and 7 females. Seventy-four percent of cases received burns to the upper limb. Median burn size was 1% of the total body surface area. Seventeen percent of patients required a surgical procedure. In 24% of cases, the method of contact was work related and 40% were injured using cleaning products at home or on boats. No deaths were recorded. CONCLUSION: HF injury is uncommon but problematic burns often requiring surgery. RECOMMENDED MANAGEMENT: In cases of cutaneous exposure, treatment should commence immediately with 30 min lavage followed by application dimethyl sulphoxide 50% + calcium gluconate 10% in surgical jelly. If hand or forearm is affected, regional intravenous calcium 'Bier's block' using 40 ml 10% calcium gluconate with 5000 U heparin in total final volume of 40 ml may be indicated. Subcutaneous infiltration may be indicated for elsewhere at 0.5 ml/cm(2) burn of 10% calcium gluconate. Persisting pain may require nail removal or arterial calcium infusion.

Administration, Topical↗
PubMed2004

Does supervised exercise offer adjuvant benefit over exercise advice alone for the treatment of intermittent claudication? A randomised trial.

OBJECTIVE: Exercise advice is the main treatment for symptom relief in the UK for patients with mild to moderate Intermittent Claudication (IC). Would a weekly exercise and motivation class for 6 months offer adjuvant benefit over written and verbal exercise advice alone? PATIENTS AND METHODS: Fifty-nine patients attending a regional vascular centre for whom IC was the main factor affecting mobility were randomised to either exercise advice alone (n=30) or exercise advice with a once a week 45 min supervised exercise/motivation class (n=29). The mean age was 68 years. Baseline and 6-month assessment included a Quality of Life Questionnaire--the Short-Form-36, the Charing Cross Symptom Specific Claudication Questionnaire (CCCQ) and treadmill walking distance (3.5 km/h 12%). RESULTS: At 6-month follow-up the supervised exercise group had improved their treadmill walking by 129% compared to 69% in the advice alone group (p=0.001). This significant improvement was maintained at the subsequent 9 and 12-month follow-up assessments. By the 9-month stage the advice only group CCCQ score had improved 16% from baseline, while the supervised exercise group had a significantly better 43% improvement in base line score (p<0.05). Self reported frequency of walks was higher in the exercise class group being significant for improvement in CCCQ score. CONCLUSION: A weekly, supervised exercise and motivation class for a 6-month period provides a significant improvement in patients' symptoms, quality of life, and distance walked compared with advice alone and this improvement continues after attendance at class has ceased.

Aged↗
PubMed2004

Morphometry of bovine dilated cardiomyopathy.

Bovine dilated cardiomyopathy (BDCM) is a primary disease of the myocardium that has been described in Holstein-Friesian cattle worldwide in the last 20 years. The principal morphological changes in the myocardium are interstitial fibrosis and increased variability in cardiomyocyte size. Sections of heart muscle from nine cases of BDCM and nine unaffected controls matched for age, sex and breed were studied by means of a computer-assisted image analyser to measure the degree of fibrosis, and the cardiomyocyte cellular and nuclear cross-sectional area and length. The amount of connective tissue in the hearts of BDCM cases was increased by 6.7 times, the nuclear transverse cross-sectional area by 1.9 times, and the cardiomyocyte length and cross-sectional area by 1.7 and 1.6 times, respectively. This resulted in an estimated 2.5-fold increase in mean cardiomyocyte volume. Animals with clinical signs of BDCM showed a mean loss of 51% of the total number of cardiomyocytes as compared with controls. Of the five parameters studied, the percentage of fibrosis was found to be the most consistent discriminator for BDCM. It is possible that the degree of fibrosis could be used to distinguish BDCM from other cardiac diseases of cattle.

Animals↗
PubMed2004

Generation of a functional, soluble tapasin protein from an alternatively spliced mRNA.

The loading of newly synthesised MHC class I molecules (MHCI) with peptides requires the involvement of several endoplasmic reticulum (ER)-resident cofactors including calnexin, calreticulin, transporter associated with antigen processing, ERp57 and tapasin. In the absence of tapasin, MHC I complexes are loaded with suboptimal peptides and their recognition by cytotoxic T cells raised to high-affinity, immunodominant peptide epitopes is impaired. Here, we describe the cloning and functional assessment of an alternative spliced form of tapasin. From the EST database, we obtained a partially spliced tapasin cDNA that retained introns 4-6. When transfected into the tapasin-deficient cell line 0.220, the cDNA produced an alternatively spliced tapasin transcript that contained intron 5 (74 bp). This introduced a new stop codon that terminated translation immediately before the putative transmembrane domain and led to a tapasin molecule containing the lumenal domain plus 8 extra novel amino acids at its C-terminus. This molecule promoted peptide loading of HLA-B5 in 0.220 cell line, and restored normal HLA-B5 surface expression. However, the peptides loaded onto HLA-B5 were suboptimal compared to those loaded onto HLA-B5 in the presence of wild-type tapasin.

Alternative Splicing↗
PubMed2004

Intranasal bacille Calmette-Guerin (BCG) vaccine dosage needs balancing between protection and lung pathology.

Intranasal vaccination may offer practical benefits and better protection against respiratory infections, including tuberculosis. In this paper, we investigated the persistence of the Mycobacterium bovis-strain bacille Calmette-Guerin (BCG) Pasteur, lung granuloma formation and protection against pathogenic tuberculous challenge in mice. A pronounced BCG dose-dependent granulomatous infiltration of the lungs was observed following intranasal, but not after subcutaneous, vaccination. Corresponding doses of BCG, over a 100-fold range, imparted similar protection against H37Rv challenge when comparing the intranasal and subcutaneous vaccination routes. Interestingly, a BCG dose-dependent reduction of the H37Rv challenge infection was observed in the lungs, but not in the spleens, following both intranasal and subcutaneous vaccination. In the light of the observed concurrence between the extent of granuloma formation and the level of protection of the lungs, we conclude that intranasal vaccination leading to best protective efficacy needs to be balanced with an acceptable safety margin avoiding undue pathology in the lungs.

Administration, Intranasal↗
PubMed2004

Identification of up-regulated genes by array analysis in scrapie-infected mouse brains.

The major neuropathological features of the transmissible spongiform encephalopathies (TSEs) are well documented, however, the underlying molecular events are poorly defined. We have applied cDNA expression arrays and quantitative RT-PCR to the study of gene expression in the brain, and more specifically in the hippocampus, of the well-characterized ME7/CV mouse model of scrapie. The number of genes showing consistent, scrapie-associated changes in expression was limited, and was primarily restricted to glial-associated genes. Increased expression of genes encoding glial fibrillary acidic protein, vimentin, complement component 1q (alpha and beta polypeptides), cathepsin D, clusterin and cystatin C was evident in the hippocampus from 170 days after inoculation (dpi), with expression increasing thereafter to terminal disease (225-235 dpi). Elevation of gene expression preceded clinical disease by approximately 30 days, and coincided with a 20-day period in the ME7/CV model during which 50% of the CA1 hippocampal neurones are lost. Increased expression of cystatin C, an inhibitor of lysosomal cysteine proteases, is a novel finding in the context of TSE neuropathology and was confirmed by Western analysis and immunocytochemistry.

Animals↗
PubMed2004

Thoracic high-resolution computed tomography in the diagnosis of metastatic carcinoma.

Three dogs were presented for investigation of recurrent pyrexia of unknown origin, chronic vomiting and respiratory distress, respectively. One dog was markedly underweight and the other two were cachexic. Physical examination and initial diagnostic tests failed to establish the underlying cause of the presenting signs. Thoracic radiographs were within normal limits for the age of the dog. In each case there was a high index of suspicion for an occult neoplastic process in view of the profound unexplained weight loss present. High-resolution computed tomography (HRCT) of the thorax was performed. The lung fields were divided into three zones for analysis and a novel classification scheme was used to describe the HRCT findings in each zone. Postmortem examination and histopathology confirmed the presence of an infiltrating metastatic carcinoma in all three cases. The HRCT changes correlated closely with the pathological findings. The authors conclude that HRCT of the lung should be considered for pulmonary metastatic screening in the dog and introduce a classification system for HRCT findings, based on terminology used in human medicine.

Adrenal Gland Neoplasms↗
PubMed2004

How safe is silver in wound care?

Use of silver in burns, chronic ulcers and diabetic ulcers can lead to circulatory absorption and deposits in wound sites, liver, kidney and other organs. Despite this, the risks of lasting tissue damage or functional disorders are low.

Anti-Infective Agents, Local↗
PubMed2004

The posterior cruciate ligament during flexion of the normal knee.

The posterior cruciate ligament (PCL) was imaged by MRI throughout flexion in neutral tibial rotation in six cadaver knees, which were also dissected, and in 20 unloaded and 13 loaded living (squatting) knees. The appearance of the ligament was the same in all three groups. In extension the ligament is curved concave-forwards. It is straight, fully out-to-length and approaching vertical from 60 degrees to 120 degrees, and curves convex-forwards over the roof of the intercondylar notch in full flexion. Throughout flexion the length of the ligament does not change, but the separations of its attachments do. We conclude that the PCL is not loaded in the unloaded cadaver knee and therefore, since its appearance in all three groups is the same, that it is also unloaded in the living knee during flexion. The posterior fibres may be an exception in hyperextension, probably being loaded either because of posterior femoral lift-off or because of the forward curvature of the PCL. These conclusions relate only to everyday life: none may be drawn with regard to more strenuous activities such as sport or in trauma.

Adult↗