Are patients at increased risk?
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Biomedical subjects
Publications and source records attributed to J Sloan.
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PURPOSE: Stomatitis is a major dose-limiting toxicity of bolus fluorouracil (5FU)-based chemotherapy regimens, despite the use of oral cryotherapy. Pursuant to preliminary data that suggested a sucralfate oral solution could alleviate chemotherapy-induced oral mucositis, we developed a prospective trial to test this contention. PATIENTS AND METHODS: A phase III, double-blind, placebo-controlled clinical trial was designed. Patients were entered onto the study at the time of the first cycle of 5FU-based chemotherapy. All patients received oral cryotherapy for 30 minutes with each dose of 5FU. In addition, each patient was randomized to receive either a sucralfate solution or a placebo solution to be used if they developed mouth tenderness or mouth sores. The study solution was to be used four times daily for 7 days starting on the first day of mouth tenderness or mouth sores. Stomatitis scores were determined by health care providers and by patients themselves. RESULTS: There was a total of 131 assessable patients entered onto this trial, 50 of whom developed mucositis and used the study medication (27 sucralfate and 23 placebo). There was no suggestion of any difference in stomatitis severity or duration on either protocol arm. CONCLUSION: The resultant data from this clinical trial did not support the prestudy hypothesis that sucralfate would be beneficial for the treatment of 5FU-induced stomatitis.
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Primary health care (PHC) has been proposed as a key strategy for improving the health of the world community, and nurses are acknowledged as key health-care professionals in meeting this goal. Efforts to have nurses implement PHC policies presuppose that they are knowledgeable about this approach to health care and have positive attitudes. The underlying aim of this study was to develop a measure of knowledge, attitudes, and practices in PHC and to assess the reliability and validity of the measure with a sample of student nurses and faculty in degree and diploma programs. The Primary Health Care Questionnaire (PHCQ) is a three-part self-report measure that provides quantitative data on knowledge and attitudes and qualitative data on practices of PHC. The instrument was developed from a rigorous review of the literature and systematic feedback from two panels (local and national) expert in PHC. Data were collected from 457 students and faculty in one four-year degree program (three sites), one post-diploma degree program, and three diploma programs, in a western Canadian province. Internal consistency reliability estimates using Cronbach's alpha were .76 (knowledge) and .85 (attitudes). Test-retest reliability at two weeks was r = .67 (knowledge) and .76 (attitudes). Content validity was enhanced through a systematic review of the instrument by a two-phase local and a national expert panel. Findings indicated greater knowledge and more positive attitudes among senior compared to junior students, degree compared to diploma students, and faculty compared to students. These findings lend support to the validity of the measure. The qualitative data revealed that learning opportunities related to PHC were built into both the diploma and the degree program through classroom teaching, clinical practice, and written assignments.
The emergence of multidrug-resistant tuberculosis has renewed interest in the study of drug resistance in mycobacteria with the objective of improved chemotherapy. The genetic basis of isoniazid resistance in a model mycobacterium was studied. Eleven isoniazid-resistant mutants of Mycobacterium smegmatis were created using transposon mutagenesis. Genetic and enzymatic characterisation of the mutants showed that katG, encoding T-catalase, was inactivated. The nucleotide sequence of M. smegmatis katG was determined and the mutation sites mapped demonstrating that both the amino and carboxyl halves of T-catalase are important for enzymatic activity.
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OBJECTIVE: To describe the variation in the incidence of colorectal cancer across Northern Ireland and relate it to factors associated with community deprivation. DESIGN: This was a cross sectional descriptive study. SETTING: Incidence data were obtained from a population based register for the period 1990-91. Small areas were characterised by their "affluence", or lack of it, by deriving a Townsend deprivation score for each electoral ward, using information from the 1991 census. PARTICIPANTS, MAIN OUTCOME MEASURES, AND STATISTICAL METHODS: The age standardised incidence was calculated for all colorectal cancer cases diagnosed histologically in 1990-91. Electoral wards were grouped into quintiles of the population after ranking of their Townsend scores and the association with incidence was studied using Poisson regression. RESULTS: The age standardised colorectal cancer incidence ranged from 22.5 (for quintile 1) to 29.9/100,000 (quintile 5) for men but the trend for women was less regular and rates were 18.4, 23.8, 27.3, 26.5, and 23.9/100,000 for quintiles 1-5 respectively (that is, from the most "affluent" to the most "deprived" fifths of the population). After adjusting for age and sex in Poisson regression, there was a significant association between the total colorectal cancer incidence and levels of community deprivation. The rate ratio for the most deprived quintile of the population (compared with the least) was 1.28 (95% CI 1.06,1.53). The effect was stronger for rectal cancer than for colonic cancer. There was no association between community deprivation and the cancer stage at diagnosis. CONCLUSIONS: In this population, the colorectal cancer incidence is associated with the level of material deprivation. The disease stages at the time of diagnosis in patients from more deprived areas seem to be comparable with those of patients from affluent areas. As others have shown, associations such as these are not explicable entirely on the basis of the distribution of known risk factors. Further research is needed to determine plausible mechanisms for the association.
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Basal cell adenoma is a well recognized histopathologic variant of monomorphic adenoma of salivary gland, but in recent years there have been occasional reports of malignant basal cell tumors of major salivary glands. We present a case report of one such basal cell adenocarcinoma arising in the submandibular gland and discuss the differential diagnosis and distinction from a basal cell adenoma. We also review the published literature on basal cell adenocarcinoma. This is the first case of basal cell adenocarcinoma to be studied in detail by both immunohistochemistry and electron microscopy. There has been debate in the past as to the cell of origin of salivary gland basal cell tumors and specifically as to whether myoepithelial differentiation occurs in these tumors. The immunohistochemical and ultrastructural features of this case provide evidence for a dual population of ductal and myoepithelial cells. A flow cytometric analysis of nuclear deoxyribonucleic acid content showed the presence of DNA aneuploidy within one tissue block.
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The complete nucleotide sequence and mechanism of action of the tetracycline-resistance determinant, Tet P, from Clostridium perfringens has been determined. Analysis of the 4.4 kb of sequence data revealed the presence of two open reading frames, designated as tetA(P) and tetB(P). The tetA(P) gene appears to encode a 420 amino acid protein (molecular weight 46,079) with twelve transmembrane domains. This gene was shown to be responsible for the active efflux of tetracycline from resistant cells. Although there was some amino acid sequence similarity between the putative TetA(P) protein and other tetracycline efflux proteins, analysis suggested that TetA(P) represented a different type of efflux protein. The tetB(P) gene would encode a putative 652 amino acid protein (molecular weight 72,639) with significant sequence similarity to Tet(M)-like cytoplasmic proteins that specify a ribosomal-protection tetracycline-resistance mechanism. In both C. perfringens and Escherichia coli, tetB(P) encoded low-level resistance to tetracycline and minocycline whereas tetA(P) only conferred tetracycline resistance. The tetA(P) and tetB(P) genes appeared to be linked in an operon, which represented a novel genetic arrangement for tetracycline-resistance determinants. It is proposed that tetB(P) evolved from the conjugative transfer into C. perfringens of a tet(M)-like gene from another bacterium.
The anaerobic bacterium Clostridium perfringens mediates clostridial myonecrosis, or gas gangrene, by producing a number of extracellular toxins and enzymes. Transposon mutagenesis with Tn916 was used to isolate a pleiotropic mutant of C. perfringens that produced reduced levels of phospholipase C, protease and sialidase, and did not produce any detectable perfringolysin O activity. Southern hybridization revealed that a single copy of Tn916 had inserted into a 2.7 kb HindIII fragment in the C. perfringens chromosome. A 4.3kb PstI fragment, which spanned the Tn916 insertion site, was cloned from the wild-type strain. When subcloned into a shuttle vector and introduced into C. perfringens this fragment was able to complement the Tn916-derived mutation. Transformation of the mutant with plasmids containing the 2.7 kb HindIII fragment, or the 4.3 kb PstI fragment, resulted in toxin and enzyme levels greater than or equal to those of the wild-type strain. The PstI fragment was sequenced and found to potentially encode seven open reading frames, two of which appeared to be arranged in an operon and shared sequence similarity with members of two-component signal transduction systems. The putative virR gene encoded a protein with a deduced molecular weight of 30,140, and with sequence similarity to activators in the response regulator family of proteins. The next gene, virS, into which Tn916 had inserted, was predicted to encode a membrane-spanning protein with a deduced molecular weight of 51,274. The putative VirS protein had sequence similarity to sensor proteins and also contained a histidine residue highly conserved in the histidine protein kinase family of sensor proteins. Virulence studies carried out using a mouse model implicated the virS gene in the pathogenesis of histotoxic C. perfringens infections. It was concluded that a two-component sensor regulator system that activated the expression of a number of extracellular toxins and enzymes involved in virulence had been cloned and sequenced. A model that described the regulation of extracellular toxin production in C. perfringens was constructed.
A cross sectional survey was conducted in a hydroelectric power plant in which the workforce was exposed to large numbers of caddis flies. 28 of 57 employees participated. About 50% of the participants reported work related eye, nose, and sinus symptoms and wheezing. Working in locations with greater exposure to caddis flies was significantly associated with work related symptoms. 17 workers (61%) were skin prick positive to a laboratory prepared caddis fly antigen (LCFA) made from the remains of caddis flies present in the plant and 11 (39%) had positive reactions to a commercial caddis fly antigen (CCFA). Workers stationed in heavily exposed areas were 3.7 times as likely to have a positive response to the LCFA (p = 0.009) and 5.3 times as likely to have a positive response to the CCFA (p = 0.036). 13 (46%) of survey respondents reported three or more work related symptoms. 10 (91%) CCFA positive workers reported three or more work related symptoms. Pulmonary function studies revealed slight, but not significantly decreased forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1/FVC ratios in workers who were skin test positive to either caddis fly preparation when compared with those who were negative. One worker who was skin test positive to both antigens had a cross shift fall in FEV1 of 20% predicted. Occupational allergy to caddis flies proved to be a significant health problem at this work site.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in the treatment of ophthalmic inflammatory disease. Currently four topical preparations are available: flurbiprofen and suprofen for the prevention of miosis during surgery; diclofenac for postoperative inflammation following cataract extraction, and ketorolac for the treatment of itching associated with seasonal allergic conjunctivitis. Caution should be exercised, however, as topical and systemic adverse effects may occur including stinging, photophobia, gastric sensitivity, and increased bleeding time. The mechanism of action of NSAIDs is discussed, complications associated with use, and the current and future roles of therapy.
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