High proportion of rare and compound epidermal growth factor receptor mutations in an Australian population of non-squamous non-small-cell lung cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation positivity in primary non-small-cell lung cancer (NSCLC) may confer increased sensitivity to EGFR tyrosine kinase inhibitor (TKI) therapy with improved progression-free survival over EGFR wild-type tumours. Some mutation subtypes may not confer such TKI sensitivity. The incidence of rare and compound subtypes in the Australian lung cancer population is not fully defined. AIMS: The aim of the study was to audit the incidence of EGFR mutation in serial cases of primary non-squamous NSCLC presenting to two multidisciplinary team meetings in metropolitan Sydney for incidence, type of mutation and phenotypic association with mutation positivity. METHODS: Serially presenting cases of primary non-squamous NSCLC were tested for EGFR mutation. The cases presented to either of two multidisciplinary team meetings in metropolitan Sydney and were referred for EGFR mutation testing on the basis of non-squamous NSCLC histopathology. Samples from the two sites were analysed for EGFR mutation at one of three different laboratories, each using a slightly different assay. Data on phenotypic characteristics, smoking history and clinicopathological features of the tumour were collected. RESULTS: There is a relatively high incidence of EGFR mutation in non-squamous NSCLC in a series of patients drawn from two metropolitan multidisciplinary team meetings in Sydney at a rate of 23.8%. A high proportion of rare and compound EGFR mutations were identified (6/32 mutation positive cases, 18.8%). CONCLUSIONS: The incidence of EGFR mutation may be higher in Australian populations than in other populations of predominantly European origin. Rare and compound EGFR mutations may occur and may have implications for treatment that differ from classically activating mutations.

Previewing distracters reduces their effective contrast.

In a visual search task, when half the distracters are presented earlier than the remainder ('previewed'), observers find the target item more efficiently than when all the items are presented together -- the preview benefit. We measured psychometric functions for contrast increments on Gabors that were presented as a valid preview for subsequent search, and when they were a non-predictive (dummy) preview. Sensitivity to contrast increments was lower (rightwards shift of the psychometric function) on valid, compared to dummy previews. This is consistent with an account of the preview benefit in terms of active inhibition, equivalent to lowering the contrast of previewed items that are being actively ignored.

A psychophysical investigation into the preview benefit in visual search.

In preview search, half of the distracters are presented ahead of the remaining distracters and the target. Search under these conditions is more efficient than when all the items appear together (Watson & Humphreys, 1997). We investigated the mechanisms contributing to this preview benefit using an orientation discrimination task. In a display of vertical Gabors (all equidistant from fixation) one Gabor (chosen at random) was tilted (left or right). When half the non-tilted Gabors were previewed, thresholds increased less with the number of Gabors, relative to when all the Gabors appeared together (a preview benefit). In a further experiment, orientation noise was added to some of the Gabors. When all Gabors were presented simultaneously, orientation thresholds for the target increased. The effects of noise on thresholds was reduced, however, when the noisy Gabors were presented as a preview. Furthermore, there was less effect of noise in the preview condition than when observers were cued to a subset of Gabors (with a cue presented prior to the Gabors, adjacent to their positions). Visual information can be effectively excluded from the previewed locations to a greater degree than when attention is directed to a subset of display items. The implications for understanding the mechanisms involved in preview search are discussed.

Slow discrimination of contrast-defined expansion patterns.

We compared observers' performance in the same complex motion discrimination task using stimuli defined by luminance or by contrast. They were asked to discriminate between a centred expansion pattern, constructed from four patches of outwards motion, and a distorted expansion pattern, constructed with one patch containing inwards motion and three patches containing outwards motion. We measured performance versus duration and found that for luminance-defined patterns, observers were able to discriminate correctly between these patterns in 75% of trials when the stimulus duration was 200 ms. For contrast-defined patterns, observers required over 2 s to reach this level of performance. Observers did not require such long durations to discriminate correctly between the contrast-defined expansion patterns when the patterns contained fewer patches or when the distorted patterns contained more patches of inwards motion. This suggests that observers performed the task by searching for a patch that contained a pattern moving inwards. There was no such effect on performance with the luminance-defined patterns. These results also suggest that contrast-defined patterns are processed too slowly to provide an input to specialised optic flow detectors that guide navigation in real time. Further, the differences in performance may be due to processing delays from sequential processing of the contrast-defined local motion signals.

The skin conductance orienting response as an index of attention.

In Experiment I 41 subjects performed one of three tasks while also hearing irrelevant tones tones. The three tasks were forewarned reaction time, vigilance and mental arithmetic and each was divided into discrete trials. The irrelevant tones either occurred during task performance (i.e., within a trial) or outside task performance (i.e., between trials). There was no difference in skin conductance OR magnitude to tones across the three tasks. Heart rate changes in contrast showed clear differences between tasks with a marked deceleration occurring during forewarned reaction time and a marked acceleration occurring during mental arithmetic. Skin conductance OR magnitude was significantly greater to tones occurring during task performance than to tones occurring outside task performance. This was interpreted as reflecting changes in the level of attention (higher during task performance) rather than direction of attention (away from tones during task performance). In Experiment II 39 subjects heard a series of irrelevant tones either while performing a forewarned reaction time task as in Experiment I or while performing no concomitant task. Rate of habituation was significantly faster for the subjects performing the concomitant task. This was interpreted as reflecting direction of attention which should be away from the tones when the subject was performing a concomitant task. Thus while rate of habituation to a class of stimuli may reflect direction of attention, short-term changes in OR amplitude probably reflect level of attention.

Vascular studies in the preoperative evaluation of pituitary adenomas before transsphenoidal surgery.

The transsphenoidal approach is being increasingly utilized in the surgical treatment of pituitary microadenoma. Even with high-resolution and dynamic computed tomography (CT) scanning, subtle vascular anatomic variants and other vascular anomalies involving the parasellar carotid arteries cannot always be clearly defined. Five cases are described in which evaluation by digital intravenous subtraction angiography or standard carotid arteriography provided useful preoperative information before transsphenoidal surgery. The implications of these findings are discussed.

Can all schizophrenic speech be discriminated from normal speech?

The study addressed whether the speech of non-speech disordered as well as speech disordered schizophrenics is discriminable from normal speech. An analysis, using a clinician's acumen to detect, not as is usually the case to specify, showed that schizophrenic speech (including that of non-speech disordered schizophrenics) can be accurately discriminated. This suggests that the speech of all schizophrenics does indeed differ from that of normals, but in as yet unspecified ways.

Dichotic monitoring and focused versus divided attention in schizophrenia.

The target detection performance of normals, chronic schizophrenics with positive symptoms and those with negative symptoms was compared in focused and divided attention conditions. The focused condition involved the monitoring of one, and the divided condition the monitoring of both, of the dichotically presented word lists. The amount and rate of list presentations were held constant across the conditions in an attempt to separate attentional from difficulty and capacity factors. Results showed that while the overall performance of both schizophrenic groups was lower than that of the normals, their performance change from the focused to the divided attention condition did not differ from that of the normals. These results do not support a schizophrenic selective attention deficit hypothesis.

Selective retrieval and free emission of category exemplars in schizophrenia.

In a free emission task, normals, chronic schizophrenics with only positive and those with only negative symptoms generated as many exemplars from natural language categories as they could in three minutes. While the overall output level of both schizophrenic groups was lower than that of the normals, neither showed intrusions of unrelated words, and the temporal distribution of the output was marked by a clustering pattern inconsistent with a selective attention deficit hypothesis. The schizophrenics with negative symptoms tended to produce consistently smaller clusters than the normals and the schizophrenics with positive symptoms, implicating a specific retrieval constriction. The relationship of this to the major negative symptom poverty of speech is discussed.

Do positive symptom and negative symptom subtypes of schizophrenia show qualitative differences in language production?

The present study examined a prominent symptom subtype conception of the psychopathology of schizophrenia. It analysed the presumed dichotomy between hallucinations, delusions and formal thought disorder as positive symptoms and flattening of affect and poverty of speech as negative symptoms, and tested predictions concerning the nature of the mediating processes of positive and negative symptoms. Four different analyses were applied to the transcripts of speech produced by 9 normals, 10 chronic schizophrenics with only positive symptoms of whom 7 had incoherence of speech, and 9 chronic schizophrenics with only negative symptoms of whom 4 had poverty of speech. The conception of the nature of the mediating processes of positive and negative symptoms was not supported by the results. Further, a clear dichotomy between positive and negative symptom groups was not shown to exist, because positive speech disorder and negative speech disorder did not follow the presupposed dichotomy. Thus, contrary to existing conceptions of speech disorder in schizophrenia, both positive and negative speech disorder are marked by poverty of thought, as measured by the production of fewer and shorter ideas and lower speech variability.

Positive and negative symptoms and the thematic organisation of schizophrenic speech.

This study questions the prevailing view that schizophrenic delusions, hallucinations and incoherence of speech (positive symptoms) reflect loss of cognitive control and that flattening of affect and poverty of speech (negative symptoms) reflect restriction of cognitive processing. The prevailing view was examined by analysing the thematic organisation of speech produced by 18 patients describing pictures. Results showed that (a) positive and negative symptom schizophrenics did not differ in the control and restriction of thematic speech organisation; (b) speech disordered schizophrenics, positive as well as negative, showed cognitive restriction, by producing fewer inferential ideas than non-speech disordered schizophrenics. The wider implications of these results are discussed, particularly the implications of (b) for the notion of concreteness in schizophrenia.

Positive symptoms and the organization within and between ideas in schizophrenic speech.

The study examined the performance of positive symptom schizophrenics vis à vis that of demographically well-matched negative symptom schizophrenics and normals in organizing words into ideas and ideas into integrated spoken discourse. This involved applying a series of analyses to speech produced when describing pictures in an unconstrained way. The results showed that, for the most part, positive symptom schizophrenics organized their speech, both within and between ideas, as well as negative symptom schizophrenics and normals. The results did, however, show an increased tendency by the positive speech disordered schizophrenics to omit referents for noun phrases requiring referents. This constitutes a specific failure to connect ideas and does, at least in part, explain what makes positive speech disorder (incoherence of speech) unintelligible. However, taken altogether, the results do not support the extant view that positive symptom schizophrenics suffer from a general loss of control in producing speech.

Midesophageal carcinoma metastatic to the stomach: its unusual appearance on an upper gastrointestinal series.

We report a case of midesophageal carcinoma with metastases to the gastric fundus. The gastric metastases were detected on a standard upper gastrointestinal series before other studies. Gastric metastases from esophageal carcinoma have rarely been described in the radiologic literature and in this case had atypical features which prompted this report.

Left ventricular outflow obstruction and necrotizing enterocolitis.

Two neonates had unusually rapid development of necrotizing enterocolitis within 24 hours of birth. Both patients had decreased systemic perfusion secondary to aortic atresia. Onset of either clinical or radiographic manifestations of necrotizing enterocolitis in the first day of life should alert one to the possible presence of severe left ventricular outflow obstruction.

Citrobacter koseri. II. Serological and biochemical examination of Citrobacter koseri strains from clinical specimens.

165 strains of Citrobacter koseri isolated from clinical specimens were studied and their biochemical reactions determined. They were examined serologically by means of a scheme consisting of 14 O antigens. The sources of the clinical specimens were tabulated and the epidemiological information was summarized. The clinical significance of these findings is discussed.

Bilateral ectopic pheochromocytomas: computed tomographic and sonographic correlation.

We describe a case of clinically unsuspected bilateral ectopic pheochromocytomas in a young woman. The bilateral retroperitoneal masses were located in the lower sympathetic ganglia at the level of the organ of Zuckerlandl. Computed tomography (CT) accurately identified the location and vascular characteristics of these neoplasms and provided access for percutaneous biopsy. Sonographic correlation is also presented.

Rock-climbing injuries in Yosemite National Park.

This study was presented in part at the annual meeting of the Wilderness Medical Society at Aspen, Colorado, in August 1986 and at "Mountain Medicine 1987," Leavenworth, Washington, in November 1987. We questioned 220 injured rock climbers or their partners seen consecutively at the Yosemite (California) Medical Clinic over 3 (1/2) years regarding details of their accidents. Injury type and location were extracted from medical records and severity quantified. The National Park Service rescued 27% of the climbers. Injured climbers were characteristically male (88%) and experienced (mean 5.9 years) and typically fell while leading climbs (66%). Among 451 injuries, 50% were to the skin or subcutaneous tissues, while 28% involved the lower extremity and were predominantly fractures. In terms of each climber's most severe injury (n = 220), 45% involved the lower extremities (30% from the ankle alone). Head injury or hypothermia caused 12 of 13 fatalities, showing the lowest case-fatality rate reported to date among injured climbers (6%). Rescue personnel successfully managed airways in victims of head injuries, anticipated and treated complications of hypothermia, and stabilized fractures. Victims requiring immediate extensive surgical intervention or blood transfusion usually died before rescue could be effected.