Solitary bronchioloalveolar carcinoma: CT criteria

The computed tomographic (CT) scans of 30 patients with solitary bronchioloalveolar carcinoma were reviewed. Common features at CT included the peripheral or subpleural location of a pulmonary mass (25 cases), pseudocavitation (18 cases), heterogeneous attenuation (17 cases), irregular margins forming a star pattern (22 cases), and pleural tags (21 cases). Using these CT criteria, four independent observers attempted to identify cases of bronchioloalveolar carcinoma from a larger sample of lung cancers and benign lesions by categorizing a series of test cases into four probability categories. Although the bronchioloalveolar carcinomas were correctly ranked in the two highest probability categories 75% of the time (in 45 of 60 cases), there was considerable overlap with other lung lesions, particularly with adenocarcinoma and large cell undifferentiated carcinoma. However, even though the typical features of bronchioloalveolar carcinoma are not invariable or highly specific, they are characteristic enough to suggest the diagnosis.     

Characterization of melanocyte stimulating hormone receptor variant alleles in twins with red hair

The association between MSHR coding region variation and hair colour in humans has been examined by genotyping 25 red haired and 62 non-red Caucasians, all of whom were 12 years of age and members of a twin pair study. Twelve amino acid substitutions were seen at 11 different sites, nine of these being newly described MSHR variants. The previously reported Val92Met allele shows no association with hair colour, but the three alleles Arg151Cys, Arg160Trp and Asp294His were associated with red hair and one Val60Leu variant was most frequent in fair/blonde and light brown hair colours. Variant MSHR genotypes are associated with lighter skin types and red hair (P < 0.001). However, comparison of the MSHR genotypes in dizygotic twin pairs discordant for red hair colour indicates that the MSHR gene cannot be solely responsible for the red hair phenotype, since five of 13 pairs tested had both haplotypes identical by state (with three of the five having both identical by descent). Rather, it is likely that additional modifier genes exist, making variance in the MSHR gene necessary but not always sufficient, for red hair production.      

Evaluation of bone resection margins of segmental mandibulectomy for oral squamous cell carcinoma

Resection margins are frequently studied in patients with oral squamous cell carcinoma and are accepted as a constant prognostic factor. While most evidence is based on soft tissue margins, reported data for bone resection margins are scarce. The aim of this retrospective study was to evaluate and determine the utility of surgical margins in bone resections for oral cavity squamous cell carcinoma (OCSCC). The status of bone resection margins and their impact on survival was investigated in patients who had undergone segmental mandibulectomy for OCSCC. Medical records were retrieved for the years 2000–2012; 127 patients were identified and included in the study. Tumour-positive bone resection margins were found in 21% of the patients. The 5-year overall survival was significantly lower in this group (P < 0.005). Therefore, there is a need for intraoperative feedback on the status of bone resection margins to enable immediate additional resection where necessary. Although the lack of intraoperative methods for the evaluation of bone tissue has been addressed by many authors, there is still no reliable method for widespread use. Future research should focus on an objective, accurate, and rapid method of intraoperative assessment for the entire bone resection margin to optimize patient outcomes.     

Failure of recombinant human interleukin-3 therapy to induce erythropoiesis in patients with refractory Diamond-Blackfan anemia [see comments]

In two previous studies, we observed that recombinant human interleukin- 3 (IL-3) induced an increase in marrow burst-forming unit-erythroid- derived colonies in vitro in some patients with Diamond-Blackfan anemia (DBA). To determine whether a similar erythropoietic response could be induced in vivo, we treated 13 patients with DBA (aged 4 to 19 years) with two preparations of IL-3. All patients had absent absolute reticulocyte counts and markedly reduced to absent recognizable bone marrow erythroid elements; patients with circulating reticulocytes in the previous 12 months were excluded from study. All patients except 1 had failed steroid therapy and had been transfusion-dependent since infancy; 1 patient was maintained on high-dose prednisone at the time of enrollment. On the first arm of the study, IL-3 (Immunex Corp, Seattle, WA) was administered subcutaneously using a dose escalation regimen of 125 to 500 micrograms/m2/day in divided dosage at 12-hour intervals, coadministered with 1.5 mg/kg/d of oral ferrous sulphate. Of the 13 patients that entered the trial, 4 stopped prematurely because of adverse side effects. In the other 9 evaluable cases, reticulocytes increased transiently in 1 patient from 0 to 65 x 10(9)/L after 35 days of IL-3 therapy at 250 micrograms/m2, but transfusion dependency persisted. One transient peak in absolute reticulocyte count was noted in 6 other patients, but no erythroid response was observed after completion of a full course of IL-3. Oral prednisone at 0.5 mg/kg/d was then coadministered with IL-3 at 500 micrograms/m2 to 5 of the patients without effect, and treatment was stopped. In 2 patients, a second preparation of IL-3 (Sandoz Canada Inc, Dorval, Quebec, Canada) was initiated in a dose escalation regimen of 2.5 to 10 micrograms/kg and was coadministered with ferrous sulphate. No erythroid response was observed in either patient, and in one of the two, alternate-day subcutaneous recombinant erythropoietin at 300 U/kg was administered for 3 weeks in combination with daily IL-3 at 10 micrograms/kg, but no increased erythropoiesis was seen. Significant increases in white blood cell and eosinophil counts during administration of both preparations of IL-3 were observed in all patients. These data show that the response of DBA patients to IL-3 in vivo is heterogeneous and cannot be predicted from in vitro studies. The absence of a corrective effect of IL-3 in these patients with DBA indicates that a deficiency of the cytokine is not central in the pathogenesis of the disorder.     

Double dissociation of letter and category fluency following left frontal and temporal lobe lesions

Background: A number of studies have suggested that temporal cortex is critical for the ability to generate exemplars belonging to a particular semantic category (i.e., category fluency), while frontal cortex is critical for generating words beginning with a particular letter (i.e., letter or phonemic fluency). However, previous studies have often focused on relative, quantitative differences in performance across groups of patients and primarily in the oral domain.

Aims: The current study analysed verbal fluency data from two individuals with chronic aphasia, one with a large left temporal lobe lesion and a severe Wernicke's aphasia, and a second individual with a large left frontal lobe lesion and a moderately severe non-fluent aphasia. The goal of the study was to do both qualitative and quantitative analyses of letter and category fluency performance in these two individuals across oral and written fluency domains.

Methods & Procedures: Participants were administered both oral and written versions of letter fluency (FAS) and category fluency conditions (fruits, animals, and supermarket items). Participants were given 90 seconds to generate as many items as possible, and their responses were scored for both overall output, as well as qualitative structure using a clustering analysis.

Outcomes & Results: The individual with an extensive temporal lobe lesion generated a large number of exemplars on the letter fluency task. Some of these items were neologisms (e.g., frest, anth, and swink), but remarkably all adhered to the phonological constraints of the task. However, this individual was very poor at generating items belonging to semantic categories. In contrast, the individual with a large frontal lesion generated many exemplars on the category fluency task but only two items on the letter fluency task. The same pattern was replicated in the written domain in both individuals, and results from the clustering analysis paralleled these quantitative findings.

Conclusions: This report describes two individuals with aphasia who exhibited a double dissociation between letter and category fluency performance in both oral and written domains. The current findings provide further evidence for the notion that left frontal cortex is critical for word retrieval based on phonology, while left temporal cortex is critical for word retrieval based on semantics. The findings have implications for the types of strategies that may be most effective in individuals with lesions to these brain regions critical for word retrieval.     

Stereotaxic core biopsy of breast lesions.

In 70 selected patients with suspect breast lesions at mammography, accurate, high-speed stereotaxic core-cut biopsy (SCCB) was performed with a biopsy gun. In 17 of the patients, no surgery was performed. The results of SCCB were normal in 11 of these patients; in six patients, the lesion disappeared after SCCB. In 53 of the patients, SCCB was followed by surgical biopsy. In 48 cases (91%), the results of SCCB and surgical biopsy were concordant. Of the 45 carcinomas found at surgery, 41 (91%) were correctly diagnosed with SCCB. There were no false-positive results. SCCB was nondiagnostic (no representative material sampled) in three patients (6%), and in two patients (4%) a false-negative result was obtained. The infiltrating character of the tumor was correctly diagnosed with SCCB in 80% of cases. These results confirm that this radiologic procedure is an acceptable alternative to excisional biopsy.     

汉族志愿者阿米替林代谢与异喹呱羟化代谢的关系

8名男性健康志愿者po阿米替林100 mg后,以阿米替林及其3种代谢物的血浓度曲线下面积(AUC₀^∞)计算阿米替林的脱甲基化代谢及羟基化代谢能力。结果提示个体间阿米替林及其3种代谢物的AUC差异很大。其中7名志愿者测定异喹呱羟化代谢表型,6例为异喹呱强代谢者,1例为弱代谢者。尿中异喹呱的羟化代谢率与阿米替林的羟基化代谢率、阿米替林和10-羟基阿米替林的AUC₀^∞呈显著相关。阿米替林总血浆清除率与异喹呱羟化代谢率呈弱相关。此结果表明阿米替林和异喹呱的羟化代谢可能由同一酶控制,阿米替林的羟基化代谢和脱甲基化代谢可能为两个独立的代谢途径。