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This article extends the analysis of 2*2 tables considered in the preceding paper of this three-part series. The methods described in the previous paper for analysis of frequency counts of categorical variables in 2*2 tables, including overall tests, partitioned tests, odds ratios, and estimation of required sample size, are applied to tables with multiple levels, such as those with more than two response factors and/or more than two levels for each factor.

Objective: This study was designed to investigate whether acid suppression and bismuth medications interfere with the performance of diagnostic tests for Helicobacter pylori (H. pylori) infection., Methods: Sixty patients with previous diagnoses of atrophic gastritis and H. pylori infection made in gastric biopsies taken at Hospital Departmental, Pasto, Colombia, were enrolled in the study. 13C breath urea test (UBT) and stool antigen test (HpSA) were performed simultaneously. Two baseline tests were performed: one 7 days before and another the day before starting medications. A total of 20 patients received for 2 wk one of the following treatments: a) ranitidine; b) lansoprazole; or c) bismuth subsalicylate. The tests were repeated while the patients were on the prescribed medication on days 7 and 14 and then 2 wk after finishing the medication., Results and Conclusions: Utilizing standard cut-off values for the tests, our results indicate that in the case of the 13C UBT test, ranitidine does not interfere with the results, whereas lansoprazole and bismuth may be expected to yield a significant proportion of false negative results (30-40% for lansoprazole and 45-55% for bismuth). In the case of the HpSA test, ranitidine does not interfere, whereas lansoprazole and bismuth may be expected to yield a nonsignificant proportion of false negative results (15-25% for lansoprazole and 10-15% for bismuth). Absolute values for both tests may be used to study the effects of the pharmacological agents on the characteristics of the infection.

Background: Somatostatin receptors are present in most human breast cancers. We performed a pilot trial of intraoperative tumor-gamma detection using the radiolabeled somatostatin analog 125I-lanreotide in 13 women with 14 primary breast carcinomas., Methods: All patients were given 125I-lanreotide intravenously before surgery. Patients underwent lumpectomy, and postresection margins were evaluated with the gamma probe. Axillary dissection specimens were evaluated ex vivo., Results: Seven of 13 women had gamma probe-positive or clinically suspicious margins re-excised at the time of lumpectomy. Four of six probe-positive margins were histologically positive, and two of six probe-positive margins were histologically negative; a single clinically suspicious margin was histologically positive. A total of 270 axillary lymph nodes were evaluated ex vivo by gamma probe and histology. McNemar's contingency tests demonstrated a highly statistical correlation between histology and gamma probe counts (P < .0001)., Conclusions: The overall accuracy of nodal evaluation with 125I-lanreotide/intraoperative gamma detection was 77%; the negative predictive value of this technique was 97%, however. This technique predicted the presence of tumor in 20% of axillary lymph nodes that were negative by routine histology. This technique appears safe and is able to detect positive tumor resection margins and accurately predict axillary lymph node negativity. Further trials of this technique are required to validate its utility.

Eight hundred sixty-three subjects with atrophic gastritis were recruited to participate in an ongoing chemoprevention trial in Nariño, Colombia. The participants were randomly assigned to intervention therapies, which included treatment to eradicate Helicobacter pylori infection followed by daily dietary supplementation with antioxidant micronutrients in a 2 x 2 x 2 factorial design. A series of biopsies of gastric mucosa were obtained according to a specified protocol from designated locations in the stomach for each participant at baseline (before intervention therapy) and at year three. A systematic sample of 160 participants was selected from each of the eight treatment combinations. DNA was isolated from each of these biopsies (n = 320), and the first exon of KRAS was amplified using PCR. Mutations in the KRAS gene were detected using denaturing gradient gel electrophoresis and confirmed by sequence analysis. Of all baseline biopsies, 14.4% (23 of 160) contained KRAS mutations. Among those participants with atrophic gastritis without metaplasia, 19.4% (6 of 25) contained KRAS mutations, indicating that mutation of this important gene is likely an early event in the etiology of gastric carcinoma. An important association was found between the presence of KRAS mutations in baseline biopsies and the progression of preneoplastic lesions. Only 14.6% (20 of 137) of participants without baseline KRAS mutations progressed from atrophic gastritis to intestinal metaplasia or from small intestinal metaplasia to colonic metaplasia; however, 39.1% (9 of 23) with baseline KRAS mutations progressed to a more advanced lesion after 3 years [univariate odds ratio (OR), 3.76 (P = 0.05); multivariate OR adjusted for treatment, 3.74 (P = 0.04)]. In addition, the specificity of the KRAS mutation predicted progression. For those participants with G-->T transversions at position 1 of codon 12 (GGT-->TGT), 19.4% (5 of 17) progressed (univariate OR, 2.4); however, 60.0% (3 of 5) of participants with G-->A transitions at position 1 of codon 12 (GGT-->AGT) progressed (univariate OR, 8.7; P = 0.004 using chi2 test).

This is the fifth installment in a series of articles devoted to a simplified description of statistical techniques. Here we are concerned with the analysis of nominal and ordinal categorical variables where the outcomes are counts or frequencies of events that are observed in an experiment. Examples are given for chi-square analysis of 2 * 2 tables, for the calculation and interpretation of odds ratios, and for the estimation of sample sizes in experiments where outcomes are categorical.

This is the fourth in a series of articles devoted to a simplified description of experimental design, statistical analysis and interpretation. This article deals with a basic description of the analysis of variance (ANOVA) and its methods of computation and hypothesis testing. Examples are provided in which a one-way ANOVA is analyzed; methods for post-ANOVA pair-wise comparisons of treatment means are also discussed.

Background: E. coli strains producing specific virulence factors are frequently cited as causes of pediatric diarrhea in developing areas, although many well children from the same areas are colonized with these organisms. The role of these Escherichia coli in day-care center (DCC)-associated diarrhea in the United States has not been evaluated., Methods: A cohort of 112 DCC attendees from 5 DCC in urban New Orleans were followed longitudinally with demographic data, biweekly routine stool samples and additional stool samples with episodes of diarrhea. E. coli isolates were routinely saved; diarrhea stool samples were tested to detect enterotoxigenic, enterohemorrhagic and enteroadherent strains; and the prevalence of these E. coli in children with and without diarrhea was investigated., Results: During 225 child months of observation 21 episodes of diarrhea were documented and microbiologic data were available for 18. HEp-2 cell enteroadherent E. coli [mostly enteroaggregative (EAggEC) pattern] were identified in 6 of 18 (33.3%) diarrhea cases vs. 6 of 36 (16.6%) age-matched controls. However, the prevalence of EAggEC was very DCC-specific, with EAggEC found in 12 of 22 routine specimens from a DCC with recent EAggEC-related diarrhea vs. 0 of 11 routine specimens from age-matched children in another DCC without EAggEC-related diarrhea (P=0.002). Enterotoxigenic E. coli were uncommon in both ill and well children, and no enterohemorrhagic E. coli were detected., Conclusion: EAggEC were commonly isolated from children with and without diarrhea in certain DCC settings, although we cannot determine whether these strains caused diarrhea. Diarrhea-producing E. coli were not associated with diarrhea in this DCC population.

Despite increased screening and public education efforts, there continues to be a subset of patients with breast carcinoma who do not seek medical attention until their lesions are locally advanced. Recently, there has been increasing interest in administering preoperative chemotherapy to these patients. The purpose of this study was to evaluate the Charity Hospital experience with preoperative chemotherapy for locally advanced breast carcinoma. Thirty-three poor urban women with T3 or T4 breast lesions were treated with preoperative chemotherapy before surgical resection, between 1987 and 1995. Their charts and pathology were reviewed and analyzed. Local treatment was in the form of radical mastectomy (n = 3), modified radical mastectomy (n = 26), or lumpectomy with axillary dissection (n = 4). After preoperative chemotherapy, 4 patients had a complete histologic response (12%), 19 had a partial response (58%), and 10 had no response (30%). After a mean follow-up of 40.6 months, stage IIIA (n = 16) and stage IIIB (n = 12) patients were found to have 5-year survival rates of 50.2 and 26.7 per cent, respectively. Stage IV (n = 5) patients had a median survival of 23.1 months with no survivors at 3 years. Patients who had a complete or partial response to chemotherapy had a median survival of 43.0 months versus 23.1 months for the nonresponders. We conclude that our response rate, for poor urban women with locally advanced breast carcinoma, to preoperative chemotherapy, is comparable with that found in the literature. Furthermore, the initial response to this chemotherapy may be an important indicator of ultimate prognosis.

This is the second in a series of articles devoted to a simplified description of experimental design, statistical analysis, and interpretation. The present article deals with the proper use of Student's t-test. Examples are provided of nutritional experiments in which a two-tailed Student's t-test may be properly applied and a second example in which the F-test in the analysis of variance is more useful.

This is the first in a series of articles devoted to a simplified description of experimental design, statistical analysis, and interpretation, using actual laboratory data as examples. The present article deals with sample size calculation for a single factor experiment and for a repeated measures design.

This is the third in a series of articles devoted to a simplified description of experimental design, statistical analysis, and interpretation. The present article deals with an overview of time to event methods, the importance of censored information, and the utilization of survival methods with three concrete examples. These methods can be used to design experiments with increased power to detect significant differences. Experiments planned with time to event methods usually have reduced sample size requirements.

Approximately 2 to 9% of all soft tissue sarcomas are leiomyosarcomas (LMS). LMS arises nearly exclusively as tumors in adults, with peak incidence occurring in the fifth and sixth decades. The purpose of this study was to analyze disease-specific survival and define prognostic factors in patients with this disease who were treated and followed at a single institution. Fifty-eight cases of LMS were identified in the Tumor Registry of the Medical Center of Louisiana at New Orleans (charity Hospital) from 1950 to 1995. Charts were reviewed and tissue blocks reexamined to confirm the diagnosis. Follow-up information was available for 56 of 58 (96%) patients. Univariate and multivariate analyses were performed to analyze which factors predict outcome. The median survival time was 138 months. Univariate analysis identified age (> 48 years), location (retroperitoneal vs other sites), and extent of disease as prognostic factors. Multivariate analysis revealed that only age and the extent of disease at presentation are independent prognostic indicators. Race, sex, and adjuvant therapy were not significant prognostic factors. Surgical resection remains the therapeutic mainstay for patients with LMS. The value of other treatment modalities is largely limited to surgical failures. The data show that the age of the patient and the extent of disease at presentation are the best predictors of long-term survival. LMS has a good prognosis when complete resection of localized lesions can be achieved.

Mutation of the K-ras oncogene occurs frequently in human malignancy. However, there are few reports concerning K-ras mutations in soft-tissue sarcoma, including leiomyosarcoma. We therefore designed a study to determine the prevalence of mutations in the first exon of K-ras in leiomyosarcoma and to evaluate its prognostic potential. Fifty-one leiomyosarcomas were reviewed, and their diagnoses were confirmed on pathological review. Tissue blocks were retrieved, and new sections were prepared for confirmation of diagnosis. Additional tissue sections were used for DNA isolation. PCR and denaturing gradient gel electrophoresis (DGGE) were used to detect K-ras mutations in the first exon of genomic DNA isolated from the specimens. Seven (14%) K-ras mutations were detected using DGGE. Subsequent sequencing of the K-ras gene from each of the mutated tumors confirmed the DGGE results in each case. The median survival for patients whose tumors did not contain mutations of K-ras was 42 months (n = 42) versus 25 months (n = 7) for those with mutations (P = 0.06). However, patients with stages I and II tumors had a median survival of 82 months (n = 28) compared to 28 months for those with stages III and IV disease (n = 20, P = 0.02). The results suggest that K-ras codon 12 mutations are uncommon in leiomyosarcoma; however, when such mutations are found, there is a trend toward worse survival. Furthermore, the data confirm that stage is a significant prognostic indicator.

Adenocarcinomas of the lung remain a significant public health problem. Locally defined (stage I) tumors are considered amenable to resection with curative intent. However, only about 45% of these patients survive for 5 years. The median survival for more advanced tumors is drastically lower. Much research has been focused on identifying a valid genetic biomarker of prognosis. Mutations of the proto-oncogene KRAS have been identified by some groups as being a valid prognostic indicator for adenocarcinoma of the lung. To evaluate the effect of KRAS gene mutation on the survival of patients with lung adenocarcinoma, 181 archival tumors were examined by PCR and denaturing gradient gel electrophoresis. Mutations in either codon 12 or 13 were found in 31.5% of the samples. The most common mutation was a G-->T transversion in codon 12, representing 66.7% of the mutations. No difference was observed in the survival of patients with a KRAS mutation versus those whose tumors contained wild-type KRAS. This lack of difference was also observed when the analysis was restricted to those with stage I tumors or when patients with stage I or II disease were grouped together. However, certain amino acid substitutions, including cysteine, arginine, and aspartate, indicated a significantly poorer prognosis, whereas hydrophobic amino acid substitutions showed a significantly better prognosis than wild-type (P = 0.04). Sample sizes were small for this analysis due to the number of possible mutations. As expected, the stage of tumor at resection was the most significant predictor of outcome. Based on this study of 181 patients from two major medical centers located in different cities, we conclude that KRAS mutation status is not a satisfactory predictor of prognosis in lung adenocarcinoma, but the substitution of a polar or charged amino acid for the wild-type glycine residue may be a negative prognostic indicator.

Background: To characterize the New Orleans tuberculosis (TB) patient population and determine what factors might influence outcome, we followed inpatients with active disease at a large, public hospital who then received outpatient treatment at a public clinic., Methods: A total of 61 patients were enrolled from January 1, 1993 through July 1994 and followed until no patients were actively receiving treatment. Demographic and psychosocial data were collected and associated with the number of months of treatment received and final outcome., Results: Of the 61 patients, 26 (43%) completed treatment, 15 (25%) were lost to follow-up, 11 (18%) died, and 9 (14%) were referred out of the area during treatment. Among those lost to follow-up, 60% received only one month of treatment. Homelessness was the only factor significantly related to whether or not a patient completed outpatient therapy (p = .02) with almost 60% of all homeless patients becoming lost to follow-up. Assignment to directly observed therapy (DOT) did not significantly raise compliance rates. HIV status did not significantly alter the duration of treatment, but these patients had a mortality rate 3 times that of the other patients., Conclusions: Efforts to improve TB control should focus on increasing compliance, particularly among the homeless. Although expansion of DOT is essential, raising therapy completion rates to acceptable levels may require additional social services, financial incentives and enforceable legal remedies for noncompliance. More rigorous treatment guidelines are needed to assure consistent management of patients who receive interrupted treatment.

The recombinant oncotoxin AR209 [e23(Fv)PE38KDEL; formerly OLX-209] was developed to treat neoplasia that expresses the c-erbB-2 (HER-2/neu) protein product p185(erbB-2). The AR209 compound contains a single-chain antibody domain specific for p185(erbB-2), coupled with a portion of the Pseudomonas exotoxin. The drug has been shown to be effective in inhibiting cells that overexpress erbB-2 due to gene amplification and in cells that do not contain amplified erbB-2 but express slightly higher levels of the protein than normal cells do. To test the efficacy of AR209 on human lung tumors, athymic nude mice were inoculated intrathoracically with a cell line derived from a poorly differentiated lung adenocarcinoma. This cell line, termed 201T, expresses moderately elevated levels of p185(erbB-2) 7.6-fold over normal bronchial epithelium. Mice treated with i.v. injections of AR209 for 5 weeks after orthotopic tumor implantation had smaller tumors and in 20% of cases showed no evidence of disease. The data from this study indicate that AR209 may be an effective treatment for patients with non-small cell lung cancers that express p185(erbB-2).

Helicobacter pylori infection is a known risk factor for gastric cancer. We hypothesized that H. pylori infection would lead to the sustained production of the reactive nitrogen species nitric oxide and peroxynitrite as part of the host immune response. We further hypothesized that H. pylori infection would lead to increased apoptosis of gastric epithelial cells, possibly in response to free radical-mediated DNA damage. Using immunohistochemistry, we stained and scored gastric antral biopsies from 84 Colombian patients with nonatrophic gastritis before and after treatment for H. pylori infection. We examined expression of inducible nitric oxide synthase (iNOS); nitrotyrosine, a marker for peroxynitrite; and DNA fragmentation, a marker for apoptosis. Patients were treated with triple therapy (amoxicillin, 500 mg three times a day for 2 weeks; metronidazole, 400 mg three times a day for 2 weeks; and bismuth subsalicylate, 262 mg four times a day for 2 weeks, followed by 262 mg every day for 4-12 months). Eradication of H. pylori infection resulted in a significant reduction in iNOS and nitrotyrosine staining and a marginally significant reduction in apoptosis. Dietary supplementation with beta-carotene (30 mg every day for 4-12 months) resulted in a significant decrease in iNOS staining. Supplementation with ascorbic acid (1 g twice a day for 4-12 months) led to a significant reduction in nitrotyrosine staining. In patients supplemented with either ascorbic acid or beta-carotene, there was a trend toward a reduction in apoptosis, but this was not statistically significant. We conclude that H. pylori infection is accompanied by the formation of endogenous reactive nitrogen intermediates, which may contribute to DNA damage and apoptosis. In addition to antimicrobial therapy, dietary supplementation with beta-carotene and ascorbic acid may prevent the formation of these potential carcinogens.

A 44-yr-old male presented with abdominal and back pain following coronary bypass surgery (CABG). Total inferior vena cava (IVC) thrombosis was then documented by computed tomography as well as IVC contrast cineangiography. Furthermore, the patient developed multiple pulmonary emboli. This presentation with severe abdominal and back pain with lack of early peripheral edema without apparent hepatic or renal dysfunction and with extreme elevation of erythrocyte sedimentation rate seems rather unusual. To our knowledge, such massive IVC thrombosis has not been reported following CABG. Thrombolytic and anticoagulant therapy was utilized with good recovery.

The article reports on a survey conducted in Colombia to evaluate the part played by the nurse in the functions covered by what has come to be called "the expanded role of nursing." According to the survey, there are 2,213 practicing nurses, who are clustered in the principal cities of the country. Those who participated in the study are young nurses holding staff positions in such institutions as university and social security hospitals. Their training is mostly at the university level, and they have had five years or less of experience. The article notes that, to perform the duties of the expanded role, the nurse must participate in accordance with her training, interest and motivation. The participation may be conditioned by factors in the nurse herself (prior knowledge, former training, previous participation, and responsibility) and by factors in the working environment (the person who instructed her on her role, the post she holds, her length of service/length of her work day, permission received from the institution to exercise her function, and the medical and nursing agreement). Parodoxically, the nurse is being made a participant in new functions at hospitals where there are medical resources and not in regions and places where those resources are scarce or nonexistent. The expanded role of nursing opens to the nurse a range of activities that enable her to provide quality care to the patient and to his or her family and community, to extend the coverage of health services, and offer treatment effectively.