The downside of isoniazid chemoprophylaxis.
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Child↗
Biomedical subjects
J M Fitzgerald
Publications and source records attributed to J M Fitzgerald.
Identification of H-ras mutations in urine sediments complements cytology in the detection of bladder tumors.
BACKGROUND: Urinary cytology has long been used as a noninvasive screen for the detection of urinary tract cancer but is limited by the generation of false positive and false negative results. More recently, molecular changes associated with urothelial neoplastic progression have been identified in DNA from urine sediments, demonstrating an alternative approach for identifying neoplastic change in the bladder. PURPOSE: The purpose of this prospective study was to determine the value of detection of H-ras (also known as HRAS) mutations in urine sediment DNA as a clinical indicator of tumor presence, recurrence, and/or progression. METHODS: Urine sediments were collected from 100 patients presenting with bladder tumors, with follow-up samples collected from 19 patients. DNA extracted from urine sediments was analyzed for changes in exon 1 of the H-ras gene, using single-strand conformation polymorphism (SSCP) analysis. A representative number of aberrant H-ras/SSCP migrating bands were excised and sequenced to confirm the presence of a mutation. Human bladder specimens were obtained from patients (93 of the 100 patients initially and 18 of the 19 patients studied by follow-up) and histologically evaluated for tumor content and grade. RESULTS: Mutations in exon 1 of the H-ras gene were detected in urine sediments from 44% (44 of 100) of the patients; concordant results were obtained by cytologic analysis, where 33% (31 of 93) of the patients displayed positive cytology. Analysis of the distribution of abnormalities with tumor grade revealed greater detection of low-grade (1-2) lesions using ras analysis (47%) compared with cytology (16%). In contrast, cytology was more effective in identifying the presence of carcinoma in situ. Combined results from these two approaches substantially increased the sensitivity of tumor detection, resulting in the identification of tumors in 60% of patients. CONCLUSIONS: Identification of H-ras mutations in DNA from urine sediments facilitates the detection of low-grade bladder tumors and, in combination with cytology, increases the overall tumor detection from 33% to 60%. Preliminary results in patient follow-up suggest that detection of H-ras mutations may have some clinical utility in detecting the presence of abnormal cells in the absence of an overt lesion following cystoscopy or positive cytology.
Base Sequence↗
Human bladder carcinoma cell lines as indicators of oncogenic change relevant to urothelial neoplastic progression.
Analysis of human tumour-derived cell lines has previously resulted in the identification of novel transformation-related elements and provided a useful tool for functional studies of different genes. To establish the utility of such cell lines as indicators of change relevant to urothelial cancer, we have characterised the expression of five genes (p53, MDM2, Rb, E-cadherin, APC) within a panel of human bladder carcinoma cell lines. Using single-strand conformation polymorphism (SSCP) and direct sequencing, p53 mutations were identified in 7/15 (47%) cell lines reflecting events reported in bladder tumours. Immunohistochemical analysis of p53 in cultured cells and in paraffin-embedded sections of xenografts from the cell line panel revealed discordant results. An absence of p53 nuclear staining was associated with an exon 5 mutation in EJ and with multiple p53 mutations found in J82. Two cell lines positive for p53 staining in the absence of detectable mutation displayed overexpression of MDM2 (PSI, HT1197) in Western blot analysis. Loss or aberrant Rb expression was recorded in 5/15 (TCCSUP, SCaBER, 5637, HT1376, J82) cell lines. Absence of E-cadherin was recorded in 5/15 cell lines (TCCSUP, EJ, KK47, UM-UC-3, J82) with loss of alpha-catenin in immunoprecipitated E-cadherin complexes of CUBIII. Western blot analysis of APC revealed a truncated protein in 1/15 (CUBIII) cell lines. The characterisation of oncogenic events within this panel of human bladder carcinoma cell lines establishes a representation of change observed in bladder tumours and better defines the genotypic background in these experimental human cell models of neoplastic progression.
Base Sequence↗
Tuberculosis in the 1990s. Issues for primary care physicians.
After declining for many years, tuberculosis rates have begun to level off in Canada. Groups at particularly high risk include aboriginal Canadians, immigrants from high-prevalence countries, HIV-infected people, and elderly men. If disease is suspected, appropriate investigations, including sputum tests for bacteriology and chest x-ray examinations, should be done. Response to treatment is excellent. Chemoprophylaxis is recommended for certain patients. Vaccination with BCG has a limited but important role, especially for aboriginal Canadians.
Canada↗
A mathematical model for the prediction of the impact of HIV infection on tuberculosis.
A mathematical model is introduced to study the accelerating impact of HIV infection on the incidence rates of tuberculosis (TB) disease. A sexually active population (15-49 years) is followed cross-sectionally over a period of time. Beginning with the year in which HIV infection was probably first present in the population, the model calculates the growing yearly incidence rates of new TB disease in HIV-positive and in HIV-negative individuals. Model equations, derived by an actuarial method, are developed recursively. Input information required for the calculations includes the age distribution of the study population, pre-HIV annual TB infection rates, annual HIV infection and mortality rates, and estimates of annual TB disease breakdown rates in the absence and in the presence of HIV infection. With correct input data, the model provides a useful blueprint for health agencies in designing effective programmes for curbing the future course of these dual epidemics in the population.
AIDS-Related Opportunistic Infections↗
Transfusion in paroxysmal nocturnal haemoglobinuria: a change of policy.
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Anemia, Hemolytic↗
The combination of hydroxyurea and leucapheresis in the treatment of chronic myeloid leukaemia in pregnancy.
Treatment of malignancy during pregnancy is difficult because of the potential teratogenicity of chemotherapeutic agents. Leucapheresis was employed in the initial management of a pregnant patient with chronic myeloid leukaemia. It was subsequently replaced with oral hydroxyurea during the second trimester. Successful delivery of a live male infant was achieved and the child has normal growth and development to date.
Adult↗
An estimate of the future size of the tuberculosis problem in sub-Saharan Africa resulting from HIV infection.
The impact of the human immunodeficiency virus (HIV) on tuberculosis is well documented. Its effect in populations with a high proportion of dually infected individuals is likely to be significant. Sub-Saharan Africa is one such region and to better document the effect of HIV infection on tuberculosis there we developed a mathematical model to predict the likely extra numbers of tuberculosis cases due to it. A mathematical model was developed using a variety of scenarios giving a range of risks for the period 1980-2000. The four scenarios included (1) a low rate of 1% risk of tuberculosis infection in year 0 (1980) with 45% tuberculosis infection prevalence, and an HIV prevalence of 2% in 1989; (2) a 2% risk of tuberculosis infection in year 0 with 60% tuberculosis infection prevalence, and a 2% HIV prevalence in 1989; (3) a 2% risk of tuberculosis infection in year 0 with 60% tuberculosis infection prevalence, and a 10% HIV prevalence in 1989; and (4) a 2% risk of tuberculosis infection in year 0 with 60% tuberculosis infection prevalence and a 20% HIV prevalence in 1989. Under scenarios 1 and 2, a 50-60% increase in smear-positive rates in the subpopulation (15-45 years old) is predicted for the year 2000, under scenario 3, smear-positive rates in the subpopulation in the year 2000 are expected to increase four-fold from the 1980 baseline. Under scenario 4, a 10-fold increase in smear-positive rates in 2000 is expected in the subpopulation. Under this scenario, total disease will have increased 12-fold in the subpopulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Patient education, self management plans and peak flow measurement.
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Asthma↗
Incorrect positioning of nasogastric feeding tubes and the development of pneumothorax.
The authors describe 12 patients in whom feeding tubes were inadvertently placed in the bronchial tree a total of 14 times. All but four of the misplacements were complicated by pneumothorax. No deaths were directly attributable to the misplacements, although one cardiac arrest occurred as a late complication of intrapleural feeding. Careful, controlled insertion of feeding tubes and radiographic confirmation of their placement are essential to reduce morbidity and mortality.
Aged↗
A developmental account of early childhood amnesia.
This study was an attempt to demonstrate the utility of a developmental approach to the study of early childhood amnesia. Working from a model of early childhood memory development proposed by Nelson and Ross (1980), I hypothesized that children would show early childhood amnesia and that this could be tested by comparing obtained estimates of memory strength to values predicted by a standard retention function. The data confirm this hypothesis for 6- and 10-year-old children, and suggest that the early childhood amnesia period extends from birth to a point between the third and fourth birthdays. The data also support a prediction, derived from the aforementioned model, that children would report a disproportionate number of general memories from the amnesia period. Thus, the developmental model provides a useful vehicle for examining early childhood amnesia and helps to frame further questions such as why some specific memories from this period are retained even though most are lost.
Amnesia↗
Abdominal tuberculosis: a critical review.
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Adult↗
Mesalamine in ulcerative colitis.
Sulfasalazine has been used for many years in the management of ulcerative colitis. As many as 20 percent of patients treated with it experience intolerable adverse effects usually attributed to its sulfapyridine component. The other active component is 5-aminosalicylic acid (5-ASA); the only 5-ASA enema preparation currently available in the U.S. is mesalamine (Rowasa, Reid-Rowell) containing 5-ASA 4 g in 60 mL. In clinical trials, mesalamine has proved efficacious in treating refractory cases of distal ulcerative colitis, proctitis, and proctosigmoiditis. Because of its high cost compared with more conventional treatment modalities, it should be reserved for cases that are either refractory or intolerant to conventional treatment.
Administration, Rectal↗
Adenosine deaminase in the diagnosis of tuberculous pleural effusions. A report of 218 patients and review of the literature.
The activity of adenosine deaminase in the pleural fluid of 218 consecutive patients was studied. According to the etiology of exudative pleural effusions, the patients were divided into the following five groups: (1) tuberculosis; (2) lung cancer; (3) pneumonias; (4) miscellaneous; and (5) idiopathic. Patients with pleural tuberculosis presented significantly higher ADA activity than patients with nontuberculous pleural effusions (p less than 0.0001). The results indicated that in a population with a relatively high prevalence of tuberculosis, the analysis of ADA levels in pleural effusions constitutes a useful marker for the diagnosis which, in addition, can be made quickly and cheaply. Additionally, a comprehensive review of the literature on the role of ADA in the diagnosis of tuberculous pleural effusions is presented.
Adenosine Deaminase↗
A just alternative. Church tribunals may be the best forum for settling wrongful discharge disputes.
The threat of a wrongful discharge lawsuit should be a concern for every employer. However, Church employers can minimize their risk if they follow Church teaching in their employment practices and policies and if they use the Church tribunal system to settle employer-employee disputes. As it originally developed in common law, the "employment-at-will" concept stipulated that an employer could discharge an employee at any time, for any reason, or for no reason at all. Most states have adopted this common law concept, although courts and legislatures have created a number of exceptions to it. Despite these exceptions, employment-at-will has proven to be a powerful tool in the hands of employers. However, employees of Church institutions who feel they have been discharged wrongfully can turn to Church tribunals, which are governed by canon law. A Church tribunal can do virtually anything a civil court can do, with the exception of ordering someone to jail. Moreover, because the standards of justice and equity applied by Church tribunals are stricter than those applied by American courts, employees of Catholic institutions in the United States may make increasing use of them in the future. Disputes that come before a Church tribunal will be settled by either arbitration or mediation. Arbitration is a kind of informal litigation. Mediation, however, is preferable because it forces the parties involved to examine themselves, their motives, and their effects on each other and the Church as a whole.
Catholicism↗
The role of calcium channel blockers in the treatment of essential hypertension.
Calcium channel blockers, originally developed for the treatment of angina and supraventricular arrhythmias, have been shown to lower elevated blood pressure effectively in hypertensive patients. Verapamil, nifedipine, and diltiazem represent prototype compounds for unique chemical classes with differing pharmacologic properties. These drugs lower elevated blood pressure with efficacy comparable with other commonly used antihypertensives. Combination therapy with other agents usually results in an additive response. Side effects are usually mild and reversible and usually are an extension of the drug's pharmacologic effects. Moreover, adverse metabolic effects on lipid, glucose, or potassium levels are not common. Because of the excellent antihypertensive effects of calcium channel blockers and their potential importance in a variety of other disease states, these agents should be routinely considered for use as a first-line antihypertensive agent in appropriately selected patients with hypertension of any severity as part of a comprehensive plan to minimize cardiovascular risk.
Animals↗
Acute asthma: emergency department management and prospective evaluation of outcome.
To determine the current management of acute asthma in the emergency department and to evaluate outcome we reviewed the charts of 99 patients aged 15 to 55 years who presented to the emergency department of a tertiary referral, university-affiliated hospital and were subsequently discharged with a diagnosis of acute asthma. Outcome was evaluated prospectively, with a structured questionnaire, by telephone. During the visit pulsus paradoxus was documented in four patients. Spirometry was done in 63 patients; postbronchodilator values ranged from 0.9 to 4.1 L. A total of 92 patients received inhaled bronchodilator therapy, most by wet nebulization. Sixteen patients received anticholinergic agents and three received theophylline. Ingested corticosteroids were given to 27 patients. Of the 71 patients contacted, a mean of 12 days after the visit, 26 (37%) had sought further medical attention, 19 at the emergency department; 9 had required admission. Forty-six patients reported that their condition had improved, but over 60% continued to have cough, sputum production, nocturnal waking and early-morning chest tightness. The results indicate that asthma continues to be undertreated in the emergency department and highlight the importance of routine spirometry in all patients and the need for systemic corticosteroid therapy.
Acute Disease↗
A cost-effectiveness analysis of the routine use of isoniazid prophylaxis in patients with a positive Mantoux skin test.
The role of isoniazid prophylaxis in low-risk patients with positive Mantoux skin tests has recently been questioned. In general, recent research has focused on the risk/benefit ratio. We, therefore, decided to extend these data and apply a cost-effectiveness analysis of the routine use of isoniazid prophylaxis from a societal perspective. Costs per case prevented were calculated for a 20-, 50-, and 70-yr-old low-risk patient who had a positive Mantoux test with base, high, and low costings. Rates were also calculated based on the use of direct costs alone and direct and indirect costs combined. Costs varied from Canadian $8,586.00 in a 20-yr-old patient to $40,102.00 in a 70-yr-old patient per case prevented based on direct costs with costs ranging from $3,236.00 to $11,320.00 with both direct and indirect costs included. These costs could be considered reasonable from a societal perspective but do not address the issue of any increased life expectancy resulting from chemoprophylaxis.
Adolescent↗