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Theophylline for Irreversible Chronic Airflow Limitation: Protocol

Jul 28, 2014 Author: Walter Mcneil | Filed under: Health

Theophylline for Irreversible Chronic Airflow Limitation: ProtocolThe diagnosis of irreversible CAL required: (1) an FEV1 of < 70% predicted and an FEV/FVC ratio of < 70% predicted on two occasions within 1 month; and (2) an increase in FEV1 of < 15% and < 200 mL after the use of inhaled salbutamol. Patients were recruited from four outpatient clinics in two tertiary care Canadian centers. Two strata were defined before randomization. “Prior-theophy]line-use” patients were taking theophylline at the time of recruitment and were using inhaled bronchodilators (ipratropium bromide, 40 μg qid, salbutamol, 200 μg bid, or another inhaled p2-agonist in adequate dosage). “No-prior-theophylline-use” patients were also using inhaled bronchodilators but were not taking theophylline at the time of recruitment. Before being entered into the study, these patients were prescribed open-label theophylline (Theo-Dur; Key Pharmaceuticals; Kenilworth, NJ), to be used for at least 2 weeks, and the dose was adjusted as required to obtain theophylline blood levels between 30 and 110 ixmol/L without side effects. (more…)

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  • AIDS-Related Bronchogenic Carcinoma. Fact or Fiction: Conclusion

    Mar 30, 2014 Author: Walter Mcneil | Filed under: Health

    AIDS-Related Bronchogenic Carcinoma. Fact or Fiction: ConclusionTobacco smoking is a common practice among both young patients and IV drug users. Additionally, usage of marijuana, a recreational drug rich in carcinogens, has been noted in young patients with lung cancer. Reports of tobacco usage have been as high as 95% in some series. Some of these investigators have speculated on the role of cigarette smoking in the pathogenesis of lung cancer in HIV-positive patients. Smoking status is not collected by the state HIV-AIDS or surveillance program or the CRD and therefore we were not able to assess the impact of tobacco consumption on lung cancer risk in our study. It is possible to estimate the number of lung cancer cases that would be expected in this study population in the improbable event that every individual in the cohort was a smoker. By applying the lung cancer mortality rates among male smokers to the total HIV-AIDS cohort and assuming the number of deaths expected would correlate closely with the number of cases expected due to the high mortality rate for this disease, we were able to calculate a range of expected numbers given a 100% smoking rate. Using the lung mortality rate for ages 50 to 54 years (approximately 100/100,000 population), a conservative rate that would actually be higher than that expected in our younger study population, we would expect a total of 26 cases. Applying the rate for male smokers ages 45 to 49 years of age (approximately 55/100,000 population) gives an expected number of approximately 14 cases. We observed 36 cases, indicating that the incidence of primary lung cancer in our HIV-AIDS cohort is greater than one would predict on the basis of smoking alone. (more…)

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  • Discussion

    Our study was designed to determine if the chest radiographic appearance at presentation of the different cell types of lung cancer has changed in the last 30 to 40 years. We wished to reexamine this issue because of a reported increased frequency of adenocarcinoma in both sexes and a higher lung cancer incidence in women since prior reports were published. We do not possess any significant number of original chest radiographs of lung cancer patients from the 1950s and 1960s. Therefore, we compared our series of newly diagnosed lung cancer cases with a widely referenced report from the Mayo Clinic compiled in that time period.

    Our patient population included 33.6% women, in contrast to 13.7% in the older Mayo Clinic series. The American Cancer Society estimates that 44% of new lung cancer cases in 1996 will occur in women/ Furthermore, in 1992 (the last year of our study), the same source reported that 37% of lung cancer deaths were in women.’ Therefore, our numbers are in accord with current national trends. (more…)

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  • We have reported a prospective study of all patients with newly diagnosed biliary strictures from a single institution over 12 months. Although statistically significant differ­ences were found in most biochemical parameters, ALT and bilirubin best discriminated between malignant and benign strictures. In this series, a serum bilirubin level of 75 pmol/L or greater was highly predictive of a malignant etiology for the stricture (Table 2). This suggests that a more critical nar­rowing exists in the malignant strictures. Furthermore, the stricture length on cholangiography was significantly greater in malignant versus benign strictures (30.3 versus 9.2 mm, P=0.001), suggesting that malignant strictures are more ex­tensive at presentation.

    There were important differences in the ultrasound char­acteristics of patients with malignant versus benign stric­tures. Malignant strictures were more likely than benign ones to induce intrahepatic duct dilation (93% versus 36%, P=0.002). The degree of obstruction was not assessed in prior ultrasound series as a discriminator between malignant and benign etiologies. Furthermore, sonographic evi­dence suggestive of malignancy (visualization of primary tu­mour or metastases) was present in 14 of 15 patients. The abdominal ultrasound, therefore, plays an important role both in the estimation of stricture severity as judged by the presence or absence of intrahepatic duct dilation and in the assessment of malignant etiology because tumour can usually be directly visualized. It is relatively insensitive, however, for the diagnosis of benign strictures, many of which are associ­ated with only low grade obstruction. We did not assess the role of CT scanning in this study because ultrasound per­forms as well and is less expensive. Helical CT may have a future role, but further study is required.

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    predictors of malignancy: RESULTS

    Biochemistry: Mean serum values for ALT, AST, AP, biliru- bin and BA were significantly higher in the malignant stric­ture group than in the benign stricture group (Figure 1). The most striking difference between the two groups was in the serum bilirubin levels – 317.8±43 pmol/L (SEM) versus 22.1±5 pmol/L (P<0.001) for the malignant versus the be­nign group.

    To examine the clinical utility of these biochemical dif­ferences, ROC curves were constructed for each variable. Threshold values and likelihood ratios are provided in Ta­ble 2.

    Ultrasound: Intrahepatic duct dilation, defined by a visible lumen within the intrahepatic ducts, was detected in 19 of the 29 strictures (66%). This finding was observed in 93% of malignant strictures versus 36% of benign strictures (P=0.002, Fisher’s exact test). Common hepatic duct dila­tion tended to be greater in malignant than in benign stric­tures (13.5 versus 9.6 mm; P=0.11, two-tailed t test). Where duct dilation was found, the stricture location could be deter­mined on the ultrasound. Additional helpful ultrasono- graphic findings were frequently found in the malignant subgroup and included a pancreatic mass in nine of 15, of whom three patients also showed evidence of metastases to the liver or regional lymph nodes. Four patients were shown to have a biliary ductal mass, of whom two had evidence of nodal metastases. In one patient, only liver metastases were demonstrated. Only one patient with a malignant stricture had none of the above abnormalities. Ultrasound was, there­fore, highly sensitive (93%) in the detection of malignant ob­struction by visualizing the actual mass or metastases. Conversely, in benign disease, ultrasound was insensitive in diagnosing biliary obstruction with more than half of the cases lacking both intrahepatic and extrahepatic biliary dila­tion.

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    Statistical analysis was performed using SPSS. Between-groups differences in mean values of con­tinuous variables were tested by independent samples t tests or by nonparametric Mann-Whitney Rank Sum tests when the distributions were not normal. The differences in fre­quencies of categorical variables were tested by % test with Yates’ correction for continuity or by Fisher’s exact test when the expected number of observations per cell was less than five. Associations between continuous variables were assessed by Pearson correlation coefficient.

    Logistic regression analysis was used to analyze the asso­ciation of dichotomous outcome variable (malignant versus benign) with continuous and categorical predictor variables. The statistical inferences were based on the level of signifi­cance P<0.05. Receiver operating characteristic (ROC) curves were constructed for the biochemical variables.

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    Patients: All patients with biliary strictures referred to the Division of Gastroenterology at the University of Alberta Hospitals for investigation between January 1, 1995 and De­cember 31, 1995 were prospectively entered into the trial. The inclusion criteria were age 16 years or older and noncal- culus biliary obstruction. Patients were excluded if subse­quent evaluation did not show a stricture. Ethics committee approval was obtained.

    Protocol: The following information was obtained:

    • Clinical history and careful physical examination.
    • Blood tests including serum bilirubin, alkaline phosphatase (AP), alanine transaminase (ALT), aspartate transaminase (AST), gamma glutamyl transpeptidase (GGT) and serum bile acids (BA) (Sigma Diagnostics, St Louis, Missouri).
    • Abdominal ultrasound examination with particular attention to intrahepatic biliary dilation, extrahepatic duct calibre, presence or absence of gallbladder and other relevant pathology such as tumour mass or ductal stones.
    • Disida scan. Patients were examined after a 4 h fast. Opiates were withheld for the proceeding 24 h. In addition to the standard scan, data were collected for deconvolutional analysis to determine hepatic extraction fraction and time activity curve so that the half-life of biliary excretion and time to peak activity could be analyzed.
    • Cholangiography. ERCP was attempted first in all patients with failures proceeding to PTC. Cefazoline 1 g was administered intravenously 30 to 60 mins before cholangiography. The biliary system was filled as completely as possible using 50% Conray 60 (Mallenchrodt, St Louis, Missouri) contrast injected under low pressure. The information obtained from each cholangiogram included site of stricture, multiplicity, character (smoothly tapered versus irregular or shouldered), stricture(s) length, minimal stricture width, maximal proximal biliary dilation and other information (ampullary mass, primary sclerosing cholangitis, cancer of the pancreas).

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    predictors of malignancy

    Biliary strictures are a challenging problem for the clini­cian. By the time that patients with biliary strictures are referred to a specialist, the diagnosis is usually already known or strongly suspected because clinical evaluation and nonin- vasive investigations alone have a high specificity and sensi­tivity. The job of the medical or surgical specialist is not only to confirm the diagnosis of biliary stricture but also, importantly, to define the etiology and the exact anatomic location, which is vital to therapeutic planning. The differ­entiation between benign and malignant strictures can be difficult but is of obvious importance in regard to prognosis and optimal therapy. Numerous imaging modalities are available for the investigation of biliary strictures, including abdominal ultrasound, computed tomographic (CT) scan­ning, nuclear imaging, percutaneous transhepatic cholangi- ography (PTC), endoscopic retrograde cholangiopancrea­tography (ERCP) and most recently magnetic resonance cholangiopancreatography (MRCP). Comparative and de­scriptive studies in this area are lacking, primarily because rapid technological improvements and developments out- date them. We, therefore, embarked on a prospective de­scriptive trial with the following aims:
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