Genetic analysis of second primary lung cancers in patients surviving small cell lung cancer

We performed genetic analysis on 12 second primary non-small cell lung cancers in patients surviving small cell lung cancer to assess the potential contribution of smoking to the development of these tumors. Mutations of TP53 were found in three (25%) tumors, KRAS2 in three (25%) tumors, and CDKN2 in two (18%) tumors. Four (50%) mutations (one each in TP53 and CDKN2 and two in KRAS2) were G:C to T:A transversions on the coding strand, a mutation accounting for approximately one-third of mutations in smoking-related tumors but uncommonly found in lung cancers not associated with smoking. The genetic changes in these second lung cancers are more representative of smoking-associated malignancies than lung cancers arising in patients occupationally exposed to irradiation and atomic bomb survivors.     

Perflubron as a gastrointestinal MR imaging contrast agent in the pediatric population

A microplate enzyme immunoassay (EIA) for the detection of lysergic acid diethylamide (LSD) in human urine was developed. The assay kit is designed around an LSD derivative coated on the wall of microplate wells with preservatives and stabilizers. Sample and rabbit anti-LSD are added to the microplate well. The immobilized LSD and LSD present in specimens compete for the opportunity to bind to the anti-LSD antibodies. An anti-rabbit antibody labeled with horseradish peroxidase is used to provide the assay signal, which is inversely proportional to the concentration of LSD in the sample. The assay requires a 25-microL urine sample and three consecutive incubation periods of 60, 30, and 30 min at room temperature. The assay was tested with a variety of drugs, including ergot alkaloids spiked into drug-free urine at up to 100,000 ng/mL without cross-reaction. Nor-LSD was shown to cross-react between 16% and 28%, depending on its concentration. Of the other compounds tested, only ergonovine demonstrated slight cross-reactivity at approximately 0.0008%. The assay is designed to be used with a qualitative cutoff of 0.5 ng/mL. Precision testing at 0.5 ng/mL gave a coefficient of variation (CV) of 6% based on 20 replicates. The CV at 0.375 ng/mL (cutoff, -25%) was 5.2% and at 0.625 ng/mL was 6.6%. Precision at other concentrations within the range of the calibration curve gave similar results both intra- and interassay. Clinical performance of the assay was compared with that of a commercial radioimmunoassay (RIA). Comparable performance was observed with both methods, each screening a total of 458 samples as negative and 17 samples as positive relative to a 0.5 ng/mL cutoff. The EIA found an additional three positive samples that were negative by RIA. The EIA is suitable for the screening of urine samples for the presence of LSD. Preliminary indications are that the assay is also suitable for use with whole blood specimens. The assay can be performed manually or be fully automated and without the need for radioactivity; it can be used in any laboratory.     

Addressing coronary heart disease risk in women

Contrary to popular perceptions, coronary heart disease (CHD) is a serious and widespread problem in US women. Public education, preventive interventions, and better data on CHD risk and prevention in women are needed.     

Scattering from a conductive rectangular plate covered by a thickdielectric layer and excited from a dipole source or a plane wave

The scattering of electromagnetic radiation from a conductive rectangular plate of infinitesimal thickness covered by a dielectric parallelepiped of arbitrary size is analyzed. An integral equation formulation is employed in terms of the electric field inside the dielectric layer and the surface current density on the conductive plate, and is solved approximately by using entire domain Galerkin technique. The electric field inside the dielectric layer is described in terms of a superposition of exponential waves while, in describing the surface current density on the conductive plate, two types of entire domain basis functions are utilized: either Fourier-exponential series or Chebyshev series type finite-term expansions are employed alternatively. Numerical results are computed and presented for several scatterer sizes and excitation types     

Oxygen is not required for degradation of DNA by glutathione and Cu(II)

Previous studies by others have shown that thiols, such as glutathione, cause cleavage of DNA in the presence of Cu(II) ions and that the hydroxyl radical derived from molecular oxygen is the major cleaving species. In this paper, we present several lines of evidence that strongly suggest that molecular oxygen is not essential for DNA cleavage and that thiyl radicals may also be involved. Indirect evidence is presented to indicate that glutathione may substitute oxygen as an electron acceptor. In addition, DNA degradation occurs to a significant extent under anaerobic conditions and no inhibition of single-strand cleavage of supercoiled plasmid DNA is seen in the presence of superoxide dismutase and catalase. In view of the ubiquitous presence of glutathione, these results could be of interest under certain diseased conditions where copper concentrations are elevated.     

Construction of a DNA probe to detect isoquinoline-degrading bacteria

To facilitate the cloning of DNA encoding isoquinoline degradation an assay was developed that allowed the rapid visual scoring of the isoquinoline degradation phenotype of single colonies. Transposon mutagenesis of one of the isolates. Comamonas acidovorans IQ3, was performed using Tn5, and nine Isq-mutants deficient in the ability to utilise isoquinoline as the sole nitrogen source were isolated. These mutants were also incapable of utilising the first metabolite of the isoquinoline degradation pathway, 1-hydroxyisoquinoline, as the sole carbon source. For each Isq-mutant, the EcoRI fragment containing the Tn5 insertion was cloned into pBR322. Restriction and Southern analyses of the cloned DNA revealed that of the nine Isq-mutants, six contained Tn5 insertions in a common 8.9-kb EcoRI fragment derived from the wild type, C. acidovorans IQ3. The cloned DNA thought to be involved in the degradation of isoquinoline proved to be specific when used as a probe in colony hybridization to some bacteria possessing the ability to degrade isoquinoline.     

Doxorubicin-based chemotherapy in elderly patients with metastatic breast cancer. Tolerance and outcome

BACKGROUND: Metastatic breast cancer in elderly patients is less often treated with chemotherapy than in younger patients because of concerns related to toxic effects and tolerance. This is especially the case with doxorubicin-containing regimens. METHODS: We conducted a retrospective study of 1011 consecutive patients with metastatic breast cancer treated with doxorubicin-based chemotherapy protocols between July 1973 and July 1984. Age was not an exclusion criterion. Patient characteristics, dose intensity, hematologic-related toxic effects, and the cause of death were analyzed. The Kaplan-Meier survival curves were plotted and tested by the generalized Wilcoxon test. RESULTS: Seven hundred sixty-seven patients aged between 50 and 64 years were identified. While the response rate was higher in the younger group, the overall survival curves were similar for the two groups (P = .06), as well as the time to progression of the disease (P = .15). The dose intensity was comparable between the groups (P = .49), as was the median platelet and white blood cell nadirs. Neutropenic fever occurred in 16% of each group (P = 83), and fever in 12% and 17% of each group, respectively (P = .05). Death from infections occurred in 3.1% and 3.2% of patients in the two groups, respectively (P = .82). CONCLUSION: Patients with metastatic breast carcinoma who are older than 65 years tolerate the acute side effects of doxorubicin-based combination chemotherapy as well as the younger age group. Time to progression of disease and the overall survival are similar for both groups. Doxorubicin-based regimens are safe and effective for patients older than 65 years.     

Achalasia of the esophagus

Achalasia, a disease of unknown cause, is characterized by absence of peristalsis in the esophagus body and incomplete relaxation of the lower esophageal sphincter (LES) in response to swallowing. This article reviews the history and pathogenesis of achalasia along with clinical manifestations, diagnosis and management options relating to the disease.     

Heat and moisture exchangers as a treatment option in the post-operative rehabilitation of laryngectomized patients

A multi-institutional, prospective clinical study was undertaken to investigate whether the use of a heat and moisture exchanger (HME) in the period following total laryngectomy could prevent the development or reduce the severity of respiratory symptoms. Fifty-nine patients from three hospitals were provided with HMEs, either immediately post-surgery or, in the case of post-surgical radiotherapy, upon completion of the radiotherapy. For the total sample (n = 59) statistically significant improvements over time (between 3 and 6 months) could be found in forced expectoration (P < 0.05), in the perceived voice quality (P < 0.001), social anxiety (P < 0.001), social interactions (P < 0.001) and in feelings of anxiety and depression (P < 0.05). Repeated measures analysis of variance indicated statistically significant group differences over time in forced expectoration and stoma cleaning (P < 0.05). No statistically significant differences over time were noted between the regular and non(regular) HME user groups in voice quality or in various aspects of daily living.