A 3'-UTR KRAS-variant is associated with cisplatin resistance in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.

BACKGROUND: A germline mutation in the 3'-untranslated region of KRAS (rs61764370, KRAS-variant: TG/GG) has previously been associated with altered patient outcome and drug resistance/sensitivity in various cancers. We examined the prognostic and predictive significance of this variant in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: We conducted a retrospective study of 103 HNSCCs collected from three completed clinical trials. KRAS-variant genotyping was conducted for these samples and 8 HNSCC cell lines. p16 expression was determined in a subset of 26 oropharynx tumors by immunohistochemistry. Microarray analysis was also utilized to elucidate differentially expressed genes between KRAS-variant and non-variant tumors. Drug sensitivity in cell lines was evaluated to confirm clinical findings. RESULTS: KRAS-variant status was determined in 95/103 (92%) of the HNSCC tumor samples and the allelic frequency of TG/GG was 32% (30/95). Three of the HNSCC cell lines (3/8) studied had the KRAS-variant. No association between KRAS-variant status and p16 expression was observed in the oropharynx subset (Fisher's exact test, P = 1.0). With respect to patient outcome, patients with the KRAS-variant had poor progression-free survival when treated with cisplatin (log-rank P = 0.002). Conversely, KRAS-variant patients appeared to experience some improvement in disease control when cetuximab was added to their platinum-based regimen (log-rank P = 0.04). CONCLUSIONS: The TG/GG rs61764370 KRAS-variant is a potential predictive biomarker for poor platinum response in R/M HNSCC patients. CLINICAL TRIAL REGISTRATION NUMBERS: NCT00503997, NCT00425750, NCT00003809.

Late wisconsinan sea levels on the southeast u.s. Atlantic shelf based on in-place shoreline indicators.

A new interpretation of late Pleistocene sea levels on the U.S. Atlantic continental shelf is based on in-place lagoonal and salt-marsh sediments obtained from vibra-cores. These data show sea levels during the last Wisconsinan transgression were about 30 meters shallower than is indicated by existing sea-level curves.

Application of growth factor stimulants improves cytogenetic analysis of chronic myeloproliferative disorder patients without alteration to cell lineage or clonality.

Conventional cytogenetic methods rely on culturing bone marrow aspirates to obtain suitable and sufficient mitotic figures for G-banded analysis. Samples from patients with chronic myeloproliferative disorders (CMPD) often have increased failure rates due to reduced growth and poor morphology, all of which hamper the conventional karyotyping investigation. The application of growth factor (GF) stimulants to bone marrow aspirates has been shown to yield significant increases in both the quality and quantity of bone marrow metaphases obtained in 53 CPMD patient samples. All cultures were stimulated using the conditioned supernatant from the human bladder carcinoma cell line 5637, which contains IL-3, IL-6, and G-CSF. Results were assessed qualitatively on G-banded preparations and quantitatively by mitotic index (MI = % dividing cells). To assess whether the application of GF stimulants leads to clonal selection, culture samples from 15 patients were analyzed by fluorescence in situ hybridization, which supported the theory that clonal selection remains unaltered in GF-stimulated cultures. In addition to this immunophenotyping of cells, we demonstrated the lineage of cells propagated under these conditions. Cell markers were chosen to characterize B-lymphoid, T-lymphoid, myeloid, and primitive cell types. Results indicated that T cells were maintained in culture and B-lymphoid markers remained negative. In the myeloid subset, there was an overall reduction in the pan-myeloid markers. We believe this represents the loss of terminally differentiated cells (e.g., neutrophils) in culture. Overall, the study clearly demonstrates that the application of GF stimulants does not alter clonality or cell lineage propagated in these samples and is therefore suitable for application in diagnostic cytogenetic laboratories.

Epithelial denudement in the gastrointestinal tracts of two bone marrow transplant recipients.

Examination of autopsy specimens from two patients revealed extensive denudement of gastrointestinal (GI) tract epithelium but preservation of basic mucosal structure otherwise. Each patient had received an allogeneic bone marrow transplant for acute leukemia. Although both patients experienced transient episodes of graft-versus-host disease (GVHD), neither experienced significant GI tract symptomatology. The usual explanations for GI epithelial denudement in such patients focus on the mechanisms of accelerated epithelial cell loss. Also considered in these two patients was the possibility that previous treatment(s) had severely interfered with the capacity for epithelial cell renewal. Chemotherapy, total body irradiation, or GVHD, alone or in some combination, may have depleted the stem cell populations and interfered with proliferative epithelial repair.

Maximum bilateral contractions are modified by neurally mediated interlimb effects.

The force exerted by a single limb during a maximal bilateral contraction has been found to be less than the force associated with a maximal unilateral contraction. The purpose of this study was to determine whether this bilateral deficit is due to neural mechanisms. For one experiment, three groups of subjects (untrained, cyclists, and weight lifters) performed maximal one- or two-limb isometric tasks for which the two-limb combinations were either both legs or the left arm and the right leg. The untrained subjects exhibited a bilateral deficit, the cyclists did not, and the weight lifters produced a bilateral facilitation. Although the changes in electromyogram did not completely parallel the changes in force, variability in the filtered electromyogram associated with the maximal contraction was too great for reliable interpretation. The arm-leg task demonstrated that the bilateral deficit affects only homologous contralateral muscles. For the second experiment, two groups of subjects (bilateral deficit and bilateral facilitation) performed maximal left leg contractions while the right leg either rested or was activated with electrical stimulation. All subjects produced an increase in the maximal voluntary left leg force during right leg electromyostimulation. The magnitude of the increase was greatest for the bilateral facilitation subjects. These results suggest that interlimb interactions during maximal bilateral contractions are mediated by neural mechanisms.

Death following accidental sodium azide ingestion.

Two college students developed symptoms of poisoning following ingestion of a salt solution during a college physiology laboratory exercise. Symptoms included nausea, vomiting, diarrhea, and altered consciousness. The ingested solution was identified as isotonic buffered saline containing sodium azide in a concentration of 1.0 g/L. The solution was commercially prepared for instrumentation use only and was used inadvertently for the exercise instead of freshly preparing sodium chloride in water. One student drank three sips of the solution and survived. The other student drank 700 to 800 mL and over several days became progressively ill, suffering myocardial damage and cardiac dysrhythmias, and, finally, died. Toxicologic studies confirmed the presence of azide in an antemortem urine sample from the deceased. Sodium azide is an uncommon but potent poison which can cause serious illness and death.

New method for assessing hand disinfection shows that pre-operative alcohol/chlorhexidine rub is as effective as a traditional surgical scrub.

BACKGROUND: Several studies have shown that rubbing hands with an alcohol/chlorhexidine solution provides equivalent microbial decontamination to a conventional surgical scrub using aqueous chlorhexidine. However, the authors believe that these studies have methodological flaws that limit their applicability to the operating theatre environment. As such, a method was developed to compare products in an everyday operating theatre environment using working operating theatre personnel. AIM: To determine whether or not an alcohol/chlorhexidine rub is as efficacious as a traditional surgical scrub using a novel method. METHODS: Bacterial counts at baseline were collected from 20 anaesthetists using the glove juice method. Subsequently, with sequential exchange of sterile gloves, one hand underwent a 3-min scrub using 4% aqueous chlorhexidine, and the other hand underwent a 60-s rub with a 70% isopropyl alcohol/0.5% chlorhexidine solution. The residual bacterial count was collected for each hand after 30 min using the glove juice method. These counts were converted to log10 values to compare the baseline counts of right and left hands, and efficacy between the treatment groups. FINDINGS: Mean [± standard deviation (SD)] bacterial counts at baseline were (log10) 4.42 ± 0.81 for left hands and 4.64 ± 0.60 for right hands (P > 0.05). The mean (± SD) reduction from baseline was (log10) 1.45 ± 0.50 for 4% chlorhexidine and 2.01 ± 0.98 for alcohol/chlorhexidine (P > 0.05). CONCLUSION: An alcohol/chlorhexidine hand rub was found to be as efficacious as a traditional scrub after 30 min; this study differs from previous work as it was undertaken in a population of practising anaesthetists in their working environment. The McKenzie method allows baseline and study evaluations to be performed contemporaneously on the same individual. Each subject was his/her own control. This method offers a more clinically relevant way to compare disinfectant solutions than standard methods.

Anaphylaxis and other adverse reactions to blue dyes: a case series.

We report three cases of anaphylaxis during anaesthesia confirmed on intradermal testing to be related to patent blue V dye (Guerbet - Chemical Abstract Service 3536-49-0). All three cases were associated with moderate to severe hypotension. Two cases had delayed onset, and two were associated with a rash. None of the cases were associated with bronchospasm. In all three patients the interference with pulse oximetry readings contributed to difficulties in management. We recommend the use of a test dose of blue dye prior to surgery, as suggested in the manufacturer's product information. We also recommend high vigilance for possible allergic reactions when patent blue dyes are used for sentinel lymph node mapping, because the presentations may be atypical and the reduced pulse oximetry readings may be a distraction.

Suffocation from use of modified gas mask.

We report a case of suffocation caused by use of a gas mask modified by the attachment of a plastic bag with evidence of halothane inhalation. Gas masks and plastic bags are sometimes used to aid in the inhalation of volatile substances. Improper use or modification of gas masks or other respiratory protection devices may result in asphyxial death.

Effects of methylmercury on the morphogenesis of the rat cerebellum.

Developing rat cerebellums were examined following continuous methylmercury exposure via maternal drinking water at 12.5 ppm during gestation and the suckling period. The continuous exposure resulted in reductions of the total cerebellar cell population and higher mercury tissue burdens than previous acute-dose studies. Cell necrosis was not evident, but rather alterations in the pattern of mitotic figures were observed. A decreased number of cells in the methylmercury exposed cerebellums was associated with an increased number of mitotic figures in the early stages of mitosis and a decrease in the number in the middle and late stages. These in vivo exposure observations are consistent with in vitro cell cycle studies in which the cells were found to have accumulated in G2 and early M phases. Impaired cell proliferation is suggested to be a major mechanism of developmental neurotoxicity following continuous low-dose exposure to methylmercury.

Temporal bone: three-dimensional CT. Part I. Normal anatomy, techniques, and limitations.

Three-dimensional (3D) surface renderings of the temporal bone were created from routine axial computed tomographic (CT) images in 15 subjects and in cadaver specimens. The displayed anatomy was correlated with these specimens, as well as with images from the routine study. Six sets of viewing angles were derived for optimal display of surgically important surface landmarks, such as the suprameatal triangle and supramastoid crest. The 3D CT images were found to be of excellent quality and permitted a global view of the temporal bone surface anatomy. Bone depletion artifacts ("pseudoforamina") posed a potentially serious problem in evaluating the tegmen and wall of the sigmoid sulcus, being present in eight of 20 cases. Three-dimensional CT may be a useful adjunct to routine temporal bone imaging.

Temporal bone: three-dimensional CT. Part II. Pathologic alterations.

Three-dimensional (3D) surface renderings were obtained from routine axial computed tomographic (CT) images in 15 patients with a variety of complex temporal bone abnormalities. The 3D CT reformations served as an adjunct to conventional sectional CT examination. While no diagnosis was substantially changed because of the 3D CT images, they did provide a more global perspective in cases of large tumors and fractures and at the postmastoidectomy site. Three-dimensional CT surface reformations are now practical and may be potentially useful for visualizing temporal bone lesions characterized by complex destructive change.

Processing of skeletal remains. A medical examiner's perspective.

A multidisciplinary approach to the investigation of skeletal remains is presented. Guidelines for recovery, documentation, examination, processing, storage, and release of skeletal material are offered and discussed.

Effects of positional restraint on oxygen saturation and heart rate following exercise.

This report assesses the effects on peripheral oxygen saturation and heart rate that positional restraint induces when a person is prone, handcuffed, and "hog-tied." Peripheral oxygen saturation and heart rate were monitored at rest, during exercise, and during recovery from exercise for 10 adult subjects. The effects of positional restraint produced a mean recovery time that was significantly prolonged. Consequently, the physiological effects produced by positional restraint should be recognized in deaths where such measures are used.

Relative activation of two human elbow flexors under isometric conditions: a cautionary note concerning flexor equivalence.

We examined the electromyographic (EMG) activity of two human elbow-flexor muscles, biceps brachii and brachioradialis, during isometric contractions. The task required subjects to match the EMG level of one of the muscles (the control muscle) to one of four target levels (5, 10, 15, or 20% of maximum) at various elbow angles. A new technique was developed for the target-matching task. The activity of the other muscle (the test muscle) was simultaneously recorded during the task. For the notion of flexor equivalence to be supported, the EMG levels for the two muscles should have covaried. This was not the case. The results revealed three features: (1) while the control-muscle EMG remained constant across joint angles, the test-muscle EMG varied with joint angle, and the trend of this variation differed among subjects; (2) in nine out of ten subjects the trend of test-muscle EMG variation with joint angle was reversed when the other muscle served as the test muscle; and (3) the test-muscle EMG associated with the four target levels was subject-, muscle-, and angle-dependent. These results caution against the generalization of the flexor equivalent concept to isometric conditions. In particular, the activity of one muscle is not a reliable indicator of the activity of other muscles subserving the same joint action.

The credibility of a source influences the rate of unconscious plagiarism.

Three experiments were conducted to investigate the relationship between the credibility of information and later unconscious plagiarism of that information. In each experiment, ideas concerning ways to reduce traffic accidents were presented from a more credible source (traffic planners) and a less credible source (college freshmen). After a distractor task, participants were asked to generate novel ways to reduce traffic accidents. In Experiments 1 and 2, unconscious plagiarism of ideas presented from the more credible source was greater than from the less credible source. In neither experiment was explicit memory for ideas from each source different in tests of source monitoring or free recall. However, the difference in unconscious plagiarism was eliminated in Experiment 3 by having participants generate the implications of ideas at study. The results are discussed in terms of the explicit factors that affect the incidence of unconscious plagiarism.

Geriatric trauma: injury patterns and outcome.

Over a 2-year period, 100 consecutive patients more than 70 years of age with multiple injuries were evaluated at a metropolitan trauma center for injury patterns and factors that affected survival. The analysis incorporated mechanism of injury, body region affected, Injury Severity Score, shock, change from level of prehospital function, and mortality. The mortality for the group was 15%. It was found that the Injury Severity Score was not predictive of survival in the elderly injured. However, central nervous system injury (p less than 0.01) and hypovolemic shock (p less than 0.001) were predictive of survival. While 85% of the injured patients survived, 88% of these did not return to their previous level of independence.