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Biomedical subjects

C R Williams

Publications and source records attributed to C R Williams.

At least 19 recordsLinked to original sources
PubMed2004

Does routine blood bone biochemistry predict vitamin D insufficiency in elderly patients with low-velocity fractures?

PURPOSE: Vitamin D deficiency impairs bone mineralisation and can predispose individuals to fractures. This study aimed at testing whether measurement of plasma calcium, alkaline phosphatase, and phosphate levels could detect vitamin D insufficiency. METHODS: During a 10-week winter period from December 2000 to February 2001, all elderly patients presenting to a general hospital in Brighton--British seaside town--with a fracture of the proximal femur and without known bone mineralisation problems were invited to participate in the study. RESULTS: 23 (63.9%) of the 36 eligible patients had insufficient levels of vitamin D, with a plasma concentration of less than 30 nmol/L. The mean parathyroid hormone level was 56 pg/mL (range, 12-193 pg/mL). 11 of the 36 patients had an elevated level of parathyroid hormone were insufficient in vitamin D. The mean plasma concentration of calcium was 2.30 mmol/L (range, 2.05-2.98 mmol/L). The mean phosphate level was 0.98 mmol/L (range, 0.40-1.79 mmol/L), and the mean alkaline phosphatase level was 91 IU/L (range, 46-127 IU/L). There was poor correlation between vitamin D insufficiency and plasma calcium, alkaline phosphatase, or phosphate levels. CONCLUSION: Plasma calcium, alkaline phosphatase, and phosphate testing cannot detect vitamin D insufficiency. We recommend that vitamin D and calcium supplementation be considered for patients with low-energy hip fractures.

Accidental Falls↗
PubMed2002

Development and evaluation of a species diagnostic polymerase chain reaction-restriction fragment-length polymorphism procedure for cryptic members of the Culex sitiens (Diptera: Culicidae) subgroup in Australia and the southwest Pacific.

Members of the Culex sitiens subgroup are important vectors of arboviruses, including Japanese encephalitis virus, Murray Valley encephalitis virus and Ross River virus. Of the eight described species, Cx. annulirostris Skuse, Cx. sitiens Wiedemann, and Cx. palpalis Taylor appear to be the most abundant and widespread throughout northern Australia and Papua New Guinea (PNG). Recent investigations using allozymes have shown this subgroup to contain cryptic species that possess overlapping adult morphology. We report the development of a polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) procedure that reliably separates these three species. This procedure utilizes the sequence variation in the ribosomal DNA ITS1 and demonstrates species-specific PCR-RFLP profiles from both colony and field collected material. Assessment of the consistency of this procedure was undertaken on mosquitoes sampled from a wide geographic area including Australia, PNG, and the Solomon Islands. Overlapping adult morphology was observed for Cx. annulirostris and Cx. palpalis in both northern Queensland and PNG and for all three species at one site in northwest Queensland.

Animals↗
PubMed2001

Accuracy of renal-bladder ultrasonography as a screening method to suggest posterior urethral valves.

PURPOSE: We determine the usefulness of ultrasonography as a screening modality to support the diagnosis of posterior urethral valves. MATERIALS AND METHODS: A retrospective chart analysis was performed of 93 consecutive boys with newly diagnosed posterior urethral valves from August 1985 through February 1999. Of the 93 boys 65, including 62 who underwent renal and bladder ultrasonography, had preoperative renal sonography available and constitute our study population. Patient age range at presentation was newborn to 13 years, with 33 of the 65 boys presenting as infants (age 1 year or younger). Presentation included fetal hydronephrosis in 13 cases, urinary tract infection in 18, voiding dysfunction in 9, abdominal mass in 6, renal insufficiency in 5, failure to thrive in 4, hematuria in 1 and other in 9. RESULTS: Preoperative sonography identified bilateral hydronephrosis in 48 boys (74%), unilateral hydronephrosis in 9 (14%) and no hydronephrosis in 8 (12%). Bladder sonography revealed an abnormal bladder (thickened, trabeculated and/or significantly distended) in 54 boys (87%). An abnormal bladder was seen in 43 of the 46 boys with bilateral hydronephrosis, 6 of 8 boys with unilateral hydronephrosis and 5 of 8 with normal upper tracts. Only 3 of the 62 boys (5%) had a normal upper tract and bladder. The sensitivity of renal ultrasonography in suspecting posterior urethral valves was 88%, while sensitivity of renal-bladder ultrasonography was 95%. When stratifying for age younger than 4 years and 4 or older, the sensitivity of predicting posterior urethral valves with renal-bladder ultrasonography was 87% and 98%, respectively. CONCLUSIONS: While voiding cystourethrography remains the imaging gold standard for the diagnosis of posterior urethral valves, renal-bladder ultrasonography is an appropriate screening study for a boy suspected to have the condition. Renal-bladder ultrasonography may prove particularly useful in the evaluation of the boy with significant voiding dysfunction before deciding on a more invasive study, such as voiding cystourethrography.

Adolescent↗
PubMed2001

TNF-alpha downregulates murine hepatic growth hormone receptor expression by inhibiting Sp1 and Sp3 binding.

Children with chronic inflammatory diseases experience growth failure and wasting. This may be due to growth hormone resistance caused by cytokine-induced suppression of growth hormone receptor (GHR) gene expression. However, the factors governing inflammatory regulation of GHR are not known. We have reported that Sp1 and Sp3 regulate hepatic GHR expression. We hypothesized that TNF-alpha suppresses GHR expression by inhibiting Sp1/Sp3 transactivators. LPS administration significantly reduced murine hepatic GHR expression, as well as Sp1 and Sp3 binding to GHR promoter cis elements. TNF-alpha was integral to this response, as LPS did not affect hepatic Sp1/Sp3 binding or GHR expression in TNF receptor 1-deficient mice. TNF-alpha treatment of BNL CL.2 mouse liver cells reduced Sp1 and Sp3 binding to a GHR promoter cis element and downregulated activity of a GHR promoter-driven luciferase reporter. Combined mutations within adjacent Sp elements eliminated GHR promoter suppression by TNF-alpha without affecting overall nuclear levels of Sp1 or Sp3 proteins. These studies demonstrate that murine GHR transcription is downregulated by LPS, primarily via TNF-alpha-dependent signaling. Evidence suggests that inhibition of Sp transactivator binding is involved. Further investigation of these mechanisms may identify novel strategies for preventing inflammatory suppression of growth.

Animals↗
PubMed2000

Drug interactions with cisapride: clinical implications.

Cisapride, a prokinetic agent, has been used for the treatment of a number of gastrointestinal disorders, particularly gastro-oesophageal reflux disease in adults and children. Since 1993, 341 cases of ventricular arrhythmias, including 80 deaths, have been reported to the US Food and Drug Administration. Marketing of the drug has now been discontinued in the US; however, it is still available under a limited-access protocol. Knowledge of the risk factors for cisapride-associated arrhythmias will be essential for its continued use in those patients who meet the eligibility criteria. This review summarises the published literature on the pharmacokinetic and pharmacodynamic interactions of cisapride with concomitantly administered drugs, providing clinicians with practical recommendations for avoiding these potentially fatal events. Pharmacokinetic interactions with cisapride involve inhibition of cytochrome P450 (CYP) 3A4, the primary mode of elimination of cisapride, thereby increasing plasma concentrations of the drug. The macrolide antibacterials clarithromycin, erythromycin and troleandomycin are inhibitors of CYP3A4 and should not be used in conjunction with cisapride. Azithromycin is an alternative. Similarly, azole antifungal agents such as fluconazole, itraconazole and ketoconazole are CYP3A4 inhibitors and their concomitant use with cisapride should be avoided. Of the antidepressants nefazodone and fluvoxamine should be avoided with cisapride. Data with fluoxetine is controversial, we favour the avoidance of its use. Citalopram, paroxetine and sertraline are alternatives. The HIV protease inhibitors amprenavir, indinavir, nelfinavir, ritonavir and saquinavir inhibit CYP3A4. Clinical experience with cisapride is lacking but avoidance with all protease inhibitors is recommended, although saquinavir is thought to have clinically insignificant effects on CYP3A4. Delavirdine is also a CYP3A4 inhibitor and should be avoided with cisapride. We also recommend avoiding coadministration of cisapride with amiodarone, cimetidine (alternatives are famotidine, nizatidine, ranitidine or one of the proton pump inhibitors), diltiazem and verapamil (the dihydropyridine calcium antagonists are alternatives), grapefruit juice, isoniazid, metronidazole, quinine, quinupristin/dalfopristin and zileuton (montelukast is an alternative). Pharmacodynamic interactions with cisapride involve drugs that have the potential to have additive effects on the QT interval. We do not recommend use of cisapride with class Ia and III antiarrhythmic drugs or with adenosine, bepridil, cyclobenzaprine, droperidol, haloperidol, nifedipine (immediate release), phenothiazine antipsychotics, tricyclic and tetracyclic antidepressants or vasopressin. Vigilance is advised if anthracyclines, cotrimoxazole (trimethoprim-sulfamethoxazole), enflurane, halothane, isoflurane, pentamidine or probucol are used with cisapride. In addition, uncorrected electrolyte disturbances induced by diuretics may increase the risk of torsade de pointes. Patients receiving cisapride should be promptly treated for electrolyte disturbances.

Animals↗
PubMed1999

A new ligand for the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), GW7845, inhibits rat mammary carcinogenesis.

We have tested a new ligand for peroxisome proliferator-activated receptor-gamma, GW7845, as an inhibitor of experimental mammary carcinogenesis, using the classic rat model with nitrosomethylurea as carcinogen. Rats were first treated with a single dose of nitrosomethylurea (50 mg/kg body weight, i.p.). Starting 1 week later, they were fed GW7845, at either 60 or 30 mg/kg of diet, for 2 months. This agent significantly reduced tumor incidence, tumor number, and tumor weight at both doses. This is the first report of the use of a ligand for peroxisome proliferator-activated receptor-gamma to prevent experimental breast cancer.

Animals↗
PubMed1999

A novel synthetic oleanane triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, with potent differentiating, antiproliferative, and anti-inflammatory activity.

The new synthetic oleanane triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) is a potent, multifunctional molecule. It induces monocytic differentiation of human myeloid leukemia cells and adipogenic differentiation of mouse 3T3-L1 fibroblasts and enhances the neuronal differentiation of rat PC12 pheochromocytoma cells caused by nerve growth factor. CDDO inhibits proliferation of many human tumor cell lines, including those derived from estrogen receptor-positive and -negative breast carcinomas, myeloid leukemias, and several carcinomas bearing a Smad4 mutation. Furthermore, it suppresses the abilities of various inflammatory cytokines, such as IFN-gamma, interleukin-1, and tumor necrosis factor-alpha, to induce de novo formation of the enzymes inducible nitric oxide synthase (iNos) and inducible cyclooxygenase (COX-2) in mouse peritoneal macrophages, rat brain microglia, and human colon fibroblasts. CDDO will also protect rat brain hippocampal neurons from cell death induced by beta-amyloid. The above activities have been found at concentrations ranging from 10(-6) to 10(-9) M in cell culture, and these results suggest that CDDO needs further study in vivo, for either chemoprevention or chemotherapy of malignancy as well as for neuroprotection.

3T3 Cells↗
PubMed1998

Industry's perception and use of occupational exposure limits.

Market research was carried out to determine industry's perception of occupational exposure limits (OELs) and the extent to which they influence the selection of measures to control exposure. Telephone interviews were carried out with 1000 randomly selected users of chemicals, 400 from establishments with some use of chemicals and 600 from establishments with chemicals in daily use. 150 interviews were also carried out with Trade Union Health and Safety Representatives. The interviews covered basic information on chemicals used, sources of information, risk reduction measures used and understanding of COSHH and OELs. Most respondents came from firms with 10 employees or less (75%, all user group; 57%, heavy user group), closely reflecting the profile of British industry. In contrast, most (77%) Trade Union Health and Safety Representatives came from firms with at least 100 employees. Respondents in the all user group were drawn from across the whole range of industrial activity, whereas the heavy users were concentrated in manufacturing. The results showed that in making decisions on what control measures to use most users rely heavily on information from suppliers and personal experience and rather less on information from sources such as Trade Associations and HSE. Most respondents reported that steps were taken to protect employees. The use of personal protective equipment featured highly, followed by process controls. Little consideration was given to the possibility of substitution. Awareness of COSHH was limited with 65% of the all user group and 53% of the heavy user group being unaware of any legal requirements for establishments which manufacture or work with chemicals. Awareness of OELs was similarly limited with 19% of the all user group and 32% of the heavy user group having any real understanding. The results from Trade Union Representatives showed that overall they are somewhat better informed than chemical users in the small firms surveyed.

Air Pollutants, Occupational↗
PubMed1997

A more stable posterior approach for hemiarthroplasty of the hip.

The dislocation rate following the insertion of a hemiarthroplasty of the hip via the posterior approach is variously quoted as between 8 per cent and 15 per cent. We set out to determine if this could be reduced by preserving the labrum and capsular structures at the time of surgery. We used a modification of the posterior approach, in which the labrum and capsule are preserved which appears not to have been widely reported. This increases the stability of the joint by adding to the depth of the acetabulum. We look prospectively at a series of 150 patients who were treated with an Austin Moore hemiarthroplasty using this technique. There were only two dislocations within 1 year of surgery in the series (one of these being in a patient with a dysplastic acetabulum) making our dislocation rate 1.3 per cent. We conclude that preserving the labrum significantly increases the stability of a hemiarthroplasty when it is inserted via a posterior approach.

Aged↗
PubMed1997

A prospective trial of local versus general anaesthesia for arthroscopic surgery of the knee.

We set out to determine if arthroscopic knee surgery was acceptable to patients and their surgeon when carried out using a local anaesthetic infiltration technique. Patients awaiting arthroscopy were randomly allocated to have either a local or a general anaesthetic. The same surgeon (NPT) carried out all the procedures. The demographic profile was similar in the two groups, as were the diagnosis and the surgical procedures. The only difference between the two groups was that those performed under local anaesthesia did not have a limb tourniquet inflated. The time spent in the theatre suite was similar in each group. This did not include the recovery time in the general anaesthetic group. The duration of the operation was longer in the local anaesthetic group (P = 0.05). A simple 0 to 10 scoring system indicated that patients preferred a local anaesthetic but the surgeon preferred to have the patient asleep (P > 0.05). Those having a local anaesthetic required less physiotherapy (P = 0.025) and more of them returned to work and sport earlier (P = 0.05). We attributed this to not having sustained pressure-induced tissue damage to the thigh muscle as they did not have a tourniquet inflated. We had a 4% failure rate in the local anaesthetic group. Arthroscopic surgery is already a well-established day case procedure and our findings have a financial implication (a saving of 25 pounds per case) as well as identifying a safer technique in the medically unfit. Unfortunately, this technique is not suitable for the investigation and treatment of all knee problems. There are certain constraints, viz the very anxious patient, acute problems, children, larger arthroscopic procedures and the inability to perform an examination under anaesthetic but, overall, it is a useful and effective way of performing a common surgical procedure.

Adolescent↗
PubMed1996

Acute calcification of the peroneal tendons in a sheep shearer.

Acute calcification of periarticular tendons is known to occur at a variety of sites after subclinical trauma or after chronic overuse injuries. It can also be due to degeneration of the affected tendon. This problem is reported in the peroneal tendons of a sheep shearer.

Acute Disease↗
PubMed1996

Torticollis secondary to ocular pathology.

We report a series of 15 children, six male and nine female, of average age 20 months, seen at a paediatric orthopaedic clinic with torticollis. Orthopaedic examination revealed a normal range of neck movement in all cases but in seven there was palpable tightness in the absence of true shortening or contracture of the sternomastoid muscle. The patients were prospectively referred for ocular examination. In five of the 15 an ocular cause for the torticollis was detected with underaction of the superior oblique muscle in three, paresis of the lateral rectus muscle in one and nystagmus in one. Another two patients were found to have an abnormal ocular examination which was thought to be unrelated to their torticollis. Three of the patients with ocular torticollis required extra-ocular muscle surgery to abolish the head tilt and one of these had a tight sternomastoid muscle. Two of the non-ocular group had surgical release of the sternomastoid muscle; in the rest, the condition either resolved with physiotherapy or required no active treatment. We recommend that all patients with torticollis and no clear orthopaedic cause are referred for ocular assessment since it is not possible clinically to distinguish ocular from non-ocular causes.

Adolescent↗
PubMed1993

Case report: accessory lobe of the liver mimicking lesser omental lymphadenopathy.

An accessory lobe of the liver is an uncommon occurrence and often an incidental finding. We present the case of a middle-aged man whose upper abdominal pain was relieved following removal of an accessory lobe. His preoperative imaging had led us to believe that he had lesser omental lymphadenopathy. We draw attention to the fact that this congenital abnormality can cause diagnostic confusion.

Diagnosis, Differential↗
PubMed1991

Mutations permitting the anaerobic growth of Escherichia coli on trehalose.

Wild-type strains of Escherichia coli K-12 do not grow anaerobically on trehalose or galactose. We isolated two operon fusion mutants of E. coli which gained the ability to grow on trehalose anaerobically (tan). The tanA-lac mutation was located at 41 min on the E. coli genetic map and also abolished growth on glucuronic acid both aerobically and anaerobically. The tanB-lac mutation was mapped to 68 min and permitted anaerobic growth on galactose as well as trehalose. The tanB-lac fusion was induced anaerobically whereas tanA-lac showed more or less constitutive beta-galactosidase expression.

Anaerobiosis↗
PubMed1991

Ultrastructural study of the blood cells of the beluga whale, Delphinapterus leucas.

General cytological and ultrastructural features of cells found in the peripheral blood of three captive beluga whales (Delphinapterus leucas) are described. We noted all major peripheral cell types common to the circulation of mammalian species, including polymorphonuclear neutrophils, eosinophils, basophils, lymphocytes, and monocytes, as well as myelocytes, erythroblasts, and plasma cells. Platelets and two populations (normal and hypochromic) of red blood corpuscles were observed.

Animals↗