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.

Negative features, retrieval processes and verbal fluency in schizophrenia.

Twenty chronic schizophrenic patients, ten matched normal controls and nine depressed controls performed categorical verbal fluency tasks for three minutes each on five separate occasions. On each occasion the schizophrenic patients generated significantly fewer words than the controls. Comparison of the different occasions showed that the schizophrenic patients had as many words available in their inner lexicons but were inefficient in retrieving them. The schizophrenic patients also generated fewer clusters of related words and more words outside the specified category. Reduced ability to generate words while the lexicon remained intact was more marked in patients with negative features. Patients with incoherence, in contrast, were more likely to produce inappropriate words. We propose that both poverty of speech and incoherence of speech reflect problems in the retrieval of words from the lexicon. To cope with these problems patients with poverty of speech terminate their search prematurely while the patients with incoherence commit errors in selecting words for output.

Parasternal sonography of the internal mammary vessels: technique, normal anatomy, and lymphadenopathy.

Metastasis to the internal mammary lymph nodes adversely affects the disease-free interval and long-term survival in women with breast carcinoma. Since staging of disease in this lymphatic chain is rarely performed at the time of definitive surgical treatment, noninvasive methods have been advocated. The authors present their preliminary experience with a sonographic technique for evaluating the internal mammary lymph nodes, artery, and vein. Longitudinal and transverse images of the first through fourth parasternal rib interspaces were acquired with a 5.0- or 7.5-MHz linear-array real-time system. The method was evaluated prospectively in 36 control subjects and in seven patients (six with metastatic breast cancer and one with lymphocytic lymphoma) who had enlarged internal mammary lymph nodes at thoracic computed tomography (CT). The longitudinal scans routinely demonstrated the internal mammary vessels in the upper interspaces. Lymphatic structures were not identified in the control group. In contrast, sonographic findings corresponding to the CT findings of lymphadenopathy were present in all seven patients. The authors believe that parasternal sonography is a promising technique that merits further study.

CT demonstration of the appendix in asymptomatic adults.

We prospectively examined 103 consecutive adults (67 women, 36 men; mean age: 58.7 years) referred for abdominal and pelvic computed tomography (CT) in whom there was no history of right lower quadrant symptoms or appendectomy. Contiguous 5-mm CT images through the pericecal region were obtained in each subject, once routine scanning was completed. Three radiologists reviewed all CT images and reached a consensus on appendiceal visualization and the quantity of intraperitoneal fat. Statistical methods were applied to the collected data to seek significant associations between a visualized appendix and the following factors: patient age, sex, intraperitoneal fat grade, and the presence of oral contrast in the cecal lumen. The appendix was definitely visualized in only 45 of the 103 patients (43.7%). Analysis of variance revealed no statistically significant correlation between a CT-demonstrated appendix and the four variables examined. The clinical implications of these findings are discussed.

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.

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.

Actinomycosis: CT findings in six patients.

Actinomycosis is an uncommon disease with clinical and radiographic findings that overlap those of other inflammatory and neoplastic conditions. A retrospective review of CT scans in six proved cases revealed a spectrum of findings, including soft-tissue mass with various degrees of infiltration and abscess formation. Administration of IV contrast material was helpful in defining the loculations of the abscess in two cases. Areas of involvement included the neck (two cases), liver (one case), abdominal wall (one case), thorax (one case) and kidney and retroperitoneum (one case). CT findings of a soft-tissue mass in the neck, lungs, or abdomen, with or without a draining sinus or fistula, raise the possibility of actinomycosis in patients with clinical findings that suggest a subacute or chronic inflammatory process.

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.

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.

Diffuse mesenteric amyloidosis: CT, sonographic, and pathologic findings.

We report an unusual case of diffuse infiltration of the mesentery by amyloidosis. The CT, sonographic, and operative findings mimicked abdominal carcinomatosis.

Abdominal pseudotumor caused by gastric displacement of the spleen: sonographic demonstration.

An infant with a factitious abdominal mass due to splenic displacement by the distended stomach is described. Two other cases of this phenomenon have been previously reported, both in infants and both diagnosed by radionuclide scans and plain radiographs. In our patient, diagnosis was made with ultrasound without the need for further studies.

Sonography of emphysematous pyelonephritis.

Emphysematous pyelonephritis is a rare gas-producing bacterial infection of the renal parenchyma seen primarily in patients with diabetes mellitus. Sonographic findings in four patients with this disease are described. Sonographic features consist of multiple high-amplitude echoes within the renal parenchyma, renal sinus, and/or perirenal space accompanied by acoustic shadowing. Computed tomography confirmed bilateral involvement in one case. Plain abdominal radiographs demonstrated abnormal extraluminal gas in three of four cases. The role of sonography in diagnosis is discussed.

Traumatic renal artery occlusion: CT diagnosis with angiographic correlation.

Traumatic renal artery occlusion is a rare injury and may be clinically silent or vague in its presentation. In the appropriate clinical setting CT findings are diagnostic, enabling prompt arteriographic evaluation and early surgical intervention.

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.

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.