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Biomedical subjects

A C Jones

Publications and source records attributed to A C Jones.

At least 19 recordsLinked to original sources

Home based exercise programme for knee pain and knee osteoarthritis: randomised controlled trial.

OBJECTIVES: To determine whether a home based exercise programme can improve outcomes in patients with knee pain. DESIGN: Pragmatic, factorial randomised controlled trial of two years' duration. SETTING: Two general practices in Nottingham. PARTICIPANTS: 786 men and women aged >/=45 years with self reported knee pain. INTERVENTIONS: Participants were randomised to four groups to receive exercise therapy, monthly telephone contact, exercise therapy plus telephone contact, or no intervention. Patients in the no intervention and combined exercise and telephone groups were randomised to receive or not receive a placebo health food tablet. MAIN OUTCOME MEASURES: Primary outcome was self reported score for knee pain on the Western Ontario and McMaster universities (WOMAC) osteoarthritis index at two years. Secondary outcomes included knee specific physical function and stiffness (scored on WOMAC index), general physical function (scored on SF-36 questionnaire), psychological outlook (scored on hospital anxiety and depression scale), and isometric muscle strength. RESULTS: 600 (76.3%) participants completed the study. At 24 months, highly significant reductions in knee pain were apparent for the pooled exercise groups compared with the non-exercise groups (mean difference -0.82, 95% confidence interval -1.3 to -0.3). Similar improvements were observed at 6, 12, and 18 months. Regular telephone contact alone did not reduce pain. The reduction in pain was greater the closer patients adhered to the exercise plan. CONCLUSIONS: A simple home based exercise programme can significantly reduce knee pain. The lack of improvement in patients who received only telephone contact suggests that improvements are not just due to psychosocial effects because of contact with the therapist.

Arthralgia↗

Quantification of histologic regression of rectal cancer after irradiation: a proposal for a modified staging system.

PURPOSE: Long-course preoperative radiotherapy has been recommended for rectal carcinoma when there is concern about the ability to perform a curative resection, for example, in larger tethered tumors or those sited anteriorly or near the anal sphincter. "Downstaging" of the tumor may occur, and this is of importance when estimating the prognosis and selecting postoperative therapy for patients. We studied the effects of preoperative chemoradiotherapy on the pathology of rectal cancer, and we propose a simplified measurement of tumor regression, the Rectal Cancer Regression Grade. METHODS: We have reviewed those patients who received preoperative chemoradiotherapy followed by surgical resection for carcinomas of the mid or distal third of the rectum found to be Stage T3/4 on transrectal ultrasound or CT between January 1995 and December 1998. Patients received 45 to 50 Gy irradiation and an infusion of 5-fluorouracil. The surgical specimens were examined by one pathologist, and the Rectal Cancer Regression Grade was quantified. RESULTS: Forty-two patients, mean age 60 (range, 42-86) years, underwent chemoradiotherapy before surgery for rectal carcinoma. There were 28 anterior resections (67 percent; 9 with a colonic pouch), 12 abdominoperineal resections (27 percent), and 2 Hartmann's procedures (5 percent). Comparison of preoperative and pathologic staging revealed that the depth of invasion was downstaged in 17 patients (38 percent), and the status of involved lymph nodes was downstaged in 13 (50 percent) of 26 patients. Tumor regression was more than 50 percent (Rectal Cancer Regression Grades 1 and 2) in 36 patients (86 percent), with 7 patients (17 percent) having complete regression with absence of residual cancer cells. CONCLUSION: Significant tumor regression was seen in 86 percent of cases after chemoradiotherapy, with 19 patients showing a "good" responsiveness. We propose a modified pathologic staging system for irradiated rectal cancer, the Rectal Cancer Regression Grade, which includes a measurement of tumor regression. The utility of the proposed Rectal Cancer Regression Grade must be tested against long-term outcomes before its value in predicting prognosis and survival can be determined.

Adult↗

A nurse-delivered advice intervention can reduce chronic non-steroidal anti-inflammatory drug use in general practice: a randomized controlled trial.

OBJECTIVE: To find out whether a nurse-delivered educational package can reduce chronic oral non-steroidal anti-inflammatory drug (NSAID) usage in general practice. METHOD: A prospective randomized controlled trial with assessment of economic cost/benefits was carried out in five general practices in Nottinghamshire with computerized prescribing systems, representing a mix of rural/urban and fundholding/non-fundholding practices. Patients suffering from non-malignant, non-inflammatory musculoskeletal pain received repeat prescriptions for oral NSAIDs. Two hundred and twenty-two patients were randomized to a control group (simple advice regarding NSAID use) or an intervention group (asked to withdraw their NSAIDs and employ appropriate alternative drug and non-drug therapies). All advice was supported by patient literature and delivered by a nurse practitioner trained in musculoskeletal assessment. The primary outcome measure was change in NSAID use 6 months after the intervention. Secondary outcome measures were changes in health and quality of life (SF-36 and EQ-5D questionnaires) and drug, health service and patient costs. RESULTS: An extra 28% of patients in the intervention group either stopped taking oral NSAIDs or reduced dosage by > or =50% at 6 months compared with controls. There was no detrimental effect on health and well-being. Oral NSAID prescription costs were significantly lowered in the intervention group but not in the control group. A non-significant increase in total drug prescription costs occurred in both groups. CONCLUSIONS: Nurse-based intervention can reduce chronic NSAID usage and costs in primary care and would be cost-effective if maintained in the long term. This intervention package would be readily applicable in primary care.

Adult↗

Pharmacology of INS37217 [P(1)-(uridine 5')-P(4)- (2'-deoxycytidine 5')tetraphosphate, tetrasodium salt], a next-generation P2Y(2) receptor agonist for the treatment of cystic fibrosis.

INS37217 [P(1)-(uridine 5')-P(4)-(2'-deoxycytidine 5')tetraphosphate, tetrasodium salt] is a deoxycytidine-uridine dinucleotide with agonist activity at the P2Y(2) receptor. In primate lung tissues, the P2Y(2) receptor mRNA was located by in situ hybridization predominantly in epithelial cells and not in smooth muscle or stromal tissue. The pharmacologic profile of INS37217 parallels that of UTP, leading to increased chloride and water secretion, increased cilia beat frequency, and increased mucin release. The combined effect of these actions was confirmed in an animal model of tracheal mucus velocity that showed that a single administration of INS37217 significantly enhanced mucus transport for at least 8 h after dosing. This extended duration of action is consistent with the ability of INS37217 to resist metabolism by airway cells and sputum enzymes. The enhanced metabolic stability and resultant increased duration of improved mucociliary clearance may confer significant advantages to INS37217 over other P2Y(2) agonists in the treatment of diseases such as cystic fibrosis.

Animals↗

Primary extracranial meningioma of the mandible: A report of 2 cases and a review of the literature.

Three cases of primary extracranial meningioma arising in the jaws have been reported in the English-language literature. The purpose of this report is to document 2 additional cases that arose in the mandible. Both cases occurred in women and appeared as radiolucent lesions. Microscopic examination revealed an unencapsulated tumor composed of uniform spindle-shaped cells arranged in whorls and interconnecting fascicles. Occasional nuclear pseudoinclusions and psammoma bodies were identified. The tumor cells demonstrated immunohistochemical reactivity for epithelial membrane antigen and vimentin. Both cases were treated by surgical excision. Based on previously published examples in the jaws, these neoplasms do not appear to be aggressive.

Adult↗

Cooperativity between KorB and TrbA repressors of broad-host-range plasmid RK2.

The KorB and TrbA proteins of broad-host-range plasmid RK2 are key regulators of the plasmid genes required for conjugative transfer. trbBp is the primary promoter responsible for expression of mating pair formation genes. We show that despite the targets for KorB and TrbA at trbBp being about 165 bp apart, 189 bp upstream of the transcription start point and overlapping the -10 region, respectively, these two proteins show up to 10-fold cooperativity for the repression of trbBp. Deletion analysis of TrbA showed that the C-terminal domain (CTD), which has a high degree of sequence conservation with the CTD of KorA, is required for this cooperativity with KorB. Western blotting demonstrated that the apparently mutual enhancement of repression is not due simply to elevation of repressor level by the presence of the second protein, suggesting that the basis for cooperativity is interaction between KorB and TrbA bound at their respective operators.

Amino Acid Sequence↗

Non-penetrance in tuberous sclerosis.

As a result of extreme clinical variability in tuberous sclerosis, with one well-documented example of non-penetrance, phenotypically normal siblings or children of patients with tuberous sclerosis are thought to be at increased risk of having children with the disease. We report that the case of apparent non-penetrance that was previously described is the result of two independent tuberous-sclerosis mutations in the same family.

Exons↗

Parasite control methods used by horse owners: factors predisposing to the development of anthelmintic resistance in nematodes.

One hundred and fifty horse owners, primarily private owners and riding schools, replied to a questionnaire concerning the practices they used to control parasites. Twenty-seven had experienced a parasite problem. Faecal samples from 188 horses selected at random showed that worm control practices were generally successful; however, many owners were not following recommendations for slowing the development of resistant parasites. In 1996, 86 per cent of the owners were using either three or two classes of anthelmintic a year, and they used a median of six doses with a range from one to 11. Approximately half the owners, more commonly owners of up to five horses, picked up their horses' faeces at least once a week, but these owners also used more doses of anthelmintic a year than owners who did not pick up faeces. One-third of the owners manually removed Gasterophilus species eggs from the horses' hairs, but 94 per cent of them also used ivermectin. Many owners treated specifically for Anoplocephala species, cyathostome larvae and Gasterophilus species, and these owners were the most likely to use three classes of anthelmintic a year. One-hundred-and-seven owners replied to a second questionnaire asking for information about the factors that influenced their anthelmintic control practices. Many owners, particularly private owners, were not influenced by the cost of the anthelmintic. For the timing and frequency of treatment, and the choice of drug, owners were most influenced by advertisements, magazine articles and veterinary surgeons. In two magazines aimed at horse owners, the brands of drugs most frequently advertised were the brands most commonly used by the owners, and articles in the magazines recommended the use of three classes of drug per year. These results are discussed in relation to their influence on the development of anthelmintic-resistant nematodes.

Animal Husbandry↗

Application and evaluation of denaturing HPLC for molecular genetic analysis in tuberous sclerosis.

Tuberous sclerosis (TSC) is an autosomal dominant disorder characterised by the development of hamartomas in multiple tissues and organs. TSC exhibits locus heterogeneity with genes at 9q34 (TSC1) and 16p13.3 (TSC2) that have 21 and 41 coding exons, respectively. The mutational spectrum at both loci is wide and previous studies have shown that 60%-70% of cases are sporadic and represent new mutations. We have formatted denaturing high performance liquid chromatography (DHPLC) for rapid screening of all coding exons of TSC1 and TSC2. DHPLC analysis detected likely disease-causing mutations in 103 of 150 unrelated cases (68%), compared with 92/150 (61%) and 87/150 (58%) for single-strand conformation polymorphism analysis (SSCP) and conventional heteroduplex analysis (HA), respectively. Capital, consumable and labour costs were determined for each exon screening procedure. Estimated costs per patient sample depended on throughput, particularly for DHPLC, where a high proportion of costs are fixed, and were pounds sterling 257, pound sterling 216 and pound sterling 242 for DHPLC, SSCP and HA, respectively, assuming a throughput of 252 samples per year, or pound sterling 354, pound sterling 233 and pound sterling 259, assuming a throughput of 126 samples per year. DHPLC had the advantages of increased sensitivity and reduced labour costs when compared with more traditional approaches to exon screening but, unless expensive DHPLC equipment is being efficiently utilised for a very high proportion of the time available, overall costs are slightly higher.

Chromatography, High Pressure Liquid↗

Prenatal origins of allergic disease.

The prevalence of asthma and related allergic disorders has increased considerably over the last 25 years. Because genetic stock has not changed, environmental factors must have influenced the phenotype. Infants who experience the development of allergy already have an altered immune response at birth. We have investigated the development of immune responses during gestation and the effect of maternal allergen exposure during pregnancy and infant exposure in the first month of life on the development of allergy and disease. There was higher specific peripheral blood mononuclear cell proliferation to house dust mite and birch pollen in the third trimester compared with the second trimester, with the first positive responses seen at 22 weeks gestation. Maternal exposure to birch pollen after 22 weeks resulted in higher infant peripheral blood mononuclear cell responses to birch pollen at birth. Infants born at term, with at least 1 atopic parent with asthma, who experienced the development of allergic symptoms and positive skin prick test by 1 year of age had raised proliferative responses to house dust mite at birth compared with those infants with no symptoms. In genetically predisposed individuals, antenatal factors including maternal and thereby fetal exposure to allergens and materno-placental-fetal immunologic interactions are active in determining whether an allergic predisposition is manifested as disease.

Antibody Formation↗

Necrotizing ulcerative stomatitis in human immunodeficiency virus-seropositive individuals: a review of the histopathologic, immunohistochemical, and virologic characteristics of 18 cases.

OBJECTIVE: The purpose of this retrospective study was to delineate the histopathologic, immunohistochemical, and virologic characteristics of 18 cases of necrotizing ulcerative stomatitis. STUDY DESIGN: Eighteen examples or oral ulcerations in human immunodeficiency virus-seropositive individuals were identified that displayed unique histopathologic features. Immunohistochemic staining for CD1a, CD3, CD23, CD68, HLA-DR, p24, cytomegalovirus, HSV-1, and HSV-2 was performed, along with in situ hybridization for Epstein-Barr virus RNA and special staining for bacteria and fungi. RESULTS: The lesions demonstrated ulceration, extensive necrosis, leukocytoclasia, histiocytic vasculitis with luminal fibrin clots, and a prominent infiltrate of large atypical cells with amphophilic cytoplasm, vesicular nuclei, and prominent nucleoli, interspersed with crescentic histiocytes, a histologic picture resembling extranodal Kikuchi's disease. Immunohistochemical findings suggested that the large atypical cells were histiocytes. Fifty-six percent (10/18) of the cases were immunoreactive for human immunodeficiency virus p24 within focal histiocytes, whereas Epstein-Barr virus RNA was identified in 1 (6%) of 17 cases. CONCLUSIONS: Necrotizing ulcerative stomatitis is an inflammatory disease characterized by specific, reproducible microscopic features. We postulate that the histopathologic resemblance of necrotizing ulcerative stomatitis to extranodal Kikuchi's disease reflects a similar immune response to differing pathogens.

AIDS-Related Opportunistic Infections↗