Overview and update on molecular testing in non-small cell lung carcinoma utilizing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples

Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples.     

PCV16 Smoking Related Costs in the United States

Smoking is a high-risk behavior that affects the health and economic welfare of society. Thus, it is important to quantify the economic burden smoking places on social institutions in the United States.
OBJECTIVE: The purpose of this review paper is to analyze smoking cost studies and to provide estimates that represent the economic costs of smoking from different perspectives of society, and as a whole.
METHODS: Current Contents (1996–), Health Star (1970–), and Medline (1966–) databases were searched through the use of pertinent subject headings and key words: tobacco use, smoking, cost, and economics. The internet was utilized to identify potential sources of epidemiological and cost information on smoking. Recent cost-of-illness studies using different methodologies: human capital, incidence, and prevalence were chosen for review based on their relevance.
RESULTS: Preliminary results indicate that the published cost studies available underestimate the "true" costs of smoking. The most current articles approximate annual direct medical costs to health care payers of $50 billion (1993); inflating to 1997 equals $59 billion or $1,200 per smoker. Although the latest cost studies do not attempt to estimate indirect costs, past studies have found indirect costs to be 1.5–2 times the direct costs. Therefore, using direct and indirect costs we estimate total smoking costs to be $150 billion (1993); inflating to 1997 equals $176 billion or $3,500 per smoker.
CONCLUSION: Quantifying the cost of smoking is a difficult task due to tobacco use infiltrating many aspects of life and the dependency of cost on perspective. Cost-of-illness studies provide cost estimation data which can be useful in aiding decision-makers who are allocating health care resources.     

Clonal evolution in B-lineage acute lymphoblastic leukemia by contemporaneous VH-VH gene replacements and VH-DJH gene rearrangements

B-cell acute lymphoblastic leukemia (B-ALL), more frequently than any other B-lineage neoplasm, exhibits oligoclonal Ig heavy chain (IgH) gene rearrangement in 15% to 43% of all cases studied. To study the molecular processes that promote multiple IgH rearrangements, a comprehensive sequence analysis of a B-ALL case was performed in which seven clonal IgH gene rearrangements were identified. The genetic profiles suggested that a single leukemic progenitor clone evolved into several subclones through dual processes of variable (VH) to preexisting diversity-joining (DJH) gene segment rearrangement and VH to VH gene replacement. Predominant IgH-V usage and the uniquely rearranged clonotype-specific VHDJH region gene sequences were identified using a novel DNA-based gene amplification strategy. Polymerase chain reaction (PCR) was directed by an IgH-J generic primer and a complement of family-specific IgH-V primers that defined the major B-cell IgH-V gene usage. Clonality of rearranged VHDJH bands was substantiated by high resolution denaturant gel electrophoretic analysis. Sequence patterns of the amplified VHDJH fragments segregated into two groups defined by common DJH sequences. Partial N region homology at the VHD junction as well as shared DJH sequences firmly established VH to VHDJH gene replacement as a mechanism generating clonal evolution in one group. In the second subset, oligoclonality was propagated by independent VH gene rearrangements to a common DJH precursor. The contributions of all clonal Ig-VHDJH repertoires for each group was approximately 50% and reflected a symmetric distribution of leukemic subclones generated by either process. Thus, oligoclonal rearrangements evolved by two independent, yet seemingly contemporaneous molecular genetic mechanisms. All seven clones displayed nonfunctional Ig-VHDJH recombinations. These observations may have relevance to the recombinatorial opportunities available during normal B-cell maturation.     

Magnetic resonance imaging: absence of in vitro cytogenetic damage

Human lymphocytes and Chinese hamster ovary (CHO) cells in culture were exposed for 12 1/2 hours to a magnetic resonance imaging apparatus with a 2.35-Tesla magnet and 100-MHz radio frequency emission. The cells were examined for cytogenetic damage manifested either as chromosome aberrations or sister chromatid exchanges (SCEs), which constitute very sensitive measures of genetic and cellular damage. In either unstimulated or stimulated human lymphocytes, as well as in exponentially growing CHO cells, no increase in either chromosome aberrations or SCEs was found as a result of exposure to these MR conditions. The data indicate that long-term exposure to MR imaging conditions far exceeding those to be found in the clinical situation does not cause cytogenetic damage.     

Measurement of chemically induced cell proliferation in rodent liver and kidney: a comparison of 5-bromo-2'-deoxyuridine and [3H]thymidine administered by injection or osmotic pump

Different labeling methods for quantitating cell proliferation were evaluated in livers and kidneys of control and chemically treated mice and rats. The percentage of cells in S-phase (labeling indices) were compared in tissues of animals given either 5-bromo-2'-deoxyuridine (BRDU) or [3H]thymidine. These DNA precursor labels were delivered either by a single i.p. injection 2 h prior to killing the animals or via the s.c. implanted osmotic pump for 3 or 6 days. B6C3F1 mice and male F344 rats were exposed to either a peroxisome proliferator and hepatocarcinogen, Wy-14,643 (WY), in the diet at 0.1% for up to 5 days, or a non-genotoxic mouse liver and male rat kidney carcinogen, 1,4-dichlorobenzene (DCB), in corn oil by gavage for up to 5 days in mice (600 mg/kg/day) or up to 3 weeks in rats (300 mg/kg/day, 5 days per week). Labeling indices (LIs) in the liver and kidney were similar in BRDU- and [3H]thymidine-labeled mice and rats. Cell proliferation was increased in livers of both species of WY- and DCB-treated animals when compared to controls. After 4 days of chemical treatment with continuous administration of a DNA precursor label during the last 3 days of treatment, LIs in controls, DCB- and WY-treated mouse livers were 0.7, 19 and 17% for BRDU and 0.9, 15 and 13% for [3H]-thymidine respectively. Furthermore, BRDU and [3H]-thymidine labeled the same population of cells as revealed by similar patterns of cell labeling in the livers and kidneys of treated animals. The LI for BRDU- and [3H]thymidine-labeled renal proximal tubular cells was 7.7 and 8.0% respectively, in rats receiving DCB for 4 days and DNA precursor label during the last 3 days of treatment, while the LI for controls was 4.3 and 3.7% respectively. The renal proximal tubular cell LI increased to 11% in BRDU-labeled rats treated with DCB for 3 weeks. LIs in both liver and kidney were greatest in control and treated animals that received the DNA precursor label via osmotic pumps for 6 days, and least in 2 h pulse-labeled animals. However, induction of hepatic LI in treated over control animals was greatest for treated animals labeled for 3 days. These results demonstrate comparable cell labeling of cells in S-phase with either BRDU and [3H]thymidine labeling methods. BRDU presents no radioactive containment problems, and results are obtained more rapidly than [3H]thymidine.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effect on medication errors of pharmacists charting medication in an emergency department

Objective To determine the frequency and clinical significance of medication errors when (a) pharmacists elicit medication histories in the Emergency Department after medications have been prescribed by doctors and (b) pharmacists obtain and chart medication histories prior to doctors’ approval. Setting The Queen Elizabeth Hospital, a 350 bed South Australian teaching hospital, serving the local adult community. Method Emergency Department patients at risk of medication misadventure were recruited in two phases with a ‘usual practice’ arm (6 weeks) and a ‘pharmacist medication charting’ arm (5 weeks) reflecting an alternative intervention. In the ‘usual care’ arm, medication histories were compiled by a pharmacy researcher after a doctor had completed the medication chart. The researcher-elicited medication histories were compared with the doctors’ medication charts and unintentional discrepancies were recorded. In the ‘pharmacist medication charting’ arm, the same process was followed except the researcher compiled the patients’ medication histories at triage, prior to patients seeing a doctor. The medication history was then transcribed onto a medication chart for authorisation by a doctor. In addition, whether resolution of unintentional discrepancies for patients in the ‘usual care’ arm had occurred by discharge was determined by examining patients’ medical records. Main outcome measure Frequency of unintentional discrepancies and medication errors. Results The study included 45 and 29 patients in the ‘usual care’ and intervention arms, respectively. In the ‘usual care’ arm, 75.6% of patients had one or more unintentional discrepancies compared with 3.3% in the ‘pharmacist medication charting’ arm. This resulted in an average of 2.35 missed doses per patient in the ‘usual care’ arm and 0.24 in the intervention arm. In addition, an average of 1.04 incorrect doses per patient were administered in the ‘usual care’ arm and none in the ‘pharmacist medication charting’ arm. The differences observed between the arms were statistically significant (P < 0.05) and deemed clinically significant by a multidisciplinary panel. Conclusion This study provides evidence for pharmacists eliciting medication histories to prepare medication charts at the earliest possible opportunity following a patient’s presentation to the Emergency Department     

Peripheral arterial occlusive disease: P-31 MR spectroscopy of calf muscle

The effect of a graded exercise protocol on phosphorus-31 magnetic resonance (MR) spectroscopy of calf skeletal muscle in nine healthy (control) subjects and 16 patients with symptomatic peripheral arterial occlusive disease (PAOD) was assessed. Ankle-brachial pressure indexes were obtained in all 16 patients, and 10 patients underwent peripheral arteriography. Temporal profiles of pH and the inorganic phosphorus (Pi) index were calculated from the spectra. A Pi-index recovery rate constant was calculated for each subject. Arteriograms were graded by calculating the runoff resistance in the limb of interest. The pH profiles during exercise did not differ significantly between the PAOD patients and control subjects. The Pi-index recovery rate constant in the PAOD patients was significantly (P less than .01) smaller than in the control subjects. There was no significant correlation between recovery rate and the ankle-brachial pressure indexes, but there was a strong negative correlation between recovery rates and angiographic resistance grades, with smaller recovery rate constants in patients with increased arterial resistance. It is concluded that P-31 MR spectroscopy shows promise as a direct measure of tissue perfusion.