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.      

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.     

Nanomagnetic Modulation of Tumor Redox State

Modulation of reactive oxygen and nitrogen species in a tumor could be exploited for nanotherapeutic benefits. We investigate the antitumor effect in Walker-256 carcinosarcoma of magnetic nanodots composed of doxorubicin-loaded Fe₃O₄ nanoparticles combined with electromagnetic fields. Treatment using the magnetic nanodot with the largest hysteresis loop area (3402 erg/g) had the greatest antitumor effect with the minimum growth factor 0.49 ± 0.02 day^–1 (compared to 0.58 ± 0.02 day^–1 for conventional doxorubicin). Electron spin resonance spectra of Walker-256 carcinosarcoma treated with the nanodots, indicate an increase of 2.7 times of free iron (that promotes the formation of highly reactive oxygen species), using the nanodot with the largest hysteresis loop area, compared to conventional doxorubicin treatment as well as increases in ubisemiquinone, lactoferrin, NO-FeS-proteins. Hence, we provide evidence that the designed magnetic nanodots can modulate the tumor redox state. We discuss the implications of these results for cancer nanotherapy.     

MR imaging of the breast

The results of clinical investigation suggest that MR imaging can provide clinically important information that cannot be obtained with conventional imaging methods, and that this modality will, in the future, be an invaluable adjunctive breast imaging tool, just as breast imaging is today. MR imaging as a method to detect, diagnose, and stage breast cancer remains in the investigational stage, but is emerging as perhaps the most promising imaging modality for breast cancer detection.     

MR imaging of the breast in patients with invasive lobular carcinoma

OBJECTIVE: Our objective was to assess the usefulness of MR imaging in patients diagnosed with invasive lobular carcinoma of the breast. MATERIALS AND METHODS: Between July 1993 and September 1999, 32 women (33 cases) diagnosed with pure invasive lobular carcinoma of the breast underwent contrast-enhanced MR imaging examination. One woman was excluded because of lack of follow-up. Correlation was made between the mammographic and sonographic findings, the MR imaging findings, and the final pathology results for the remaining 32 cases. RESULTS: In 18 women who did not undergo excisional biopsy before the MR imaging, MR imaging showed more extensive tumor burden or the detection of the primary lesion that was occult on conventional imaging in seven (38.9%) of 18 women. In nine (50%) of 18 women, MR imaging performed equally as well as mammography and sonography. In one case (5.6%), MR imaging and mammography underestimated disease extent. In another patient (5.6%), MR imaging overestimated tumor burden, although mammography failed to show the cancer. In 14 patients who had excisional biopsy before the MR imaging, residual tumor was shown in eight women (57.1%) with extensive tumor or additional separate foci in five of the eight patients. In two cases (14.3%) that were interpreted as equivocal, residual tumor was shown in both cases on reexcision. In three cases (21.4%), the MR imaging was interpreted as negative, but microscopic tumor was shown around seroma on reexcision. False-positive enhancement was seen in one case (7.1%). CONCLUSION: MR imaging showed more extensive tumor than conventional imaging and affected the clinical management in 16 (50%) of 32 patients with invasive lobular carcinoma.     

Multiple-organ pathology in septic shock in patients with hemoblastoses

A prospective study of 20 patients with hemoblastosis and septic shock (SS) was carried out by invasive monitoring of the central hemodynamics and oxygen transport, evaluation of biochemical and coagulological parameters, and assessment of the severity of clinical condition by the APACHE II and SOFA scores. Septic shock was effectively treated in 12 patients, 5 of them were discharged from the department (group 1) and 7 died in intensive care wards from various complications (group 2). Eight patients died during the first 2 days from SS resistant to therapy (group 3). Group 2 patients were in need of a longer inotropic support than group 1 patients (5.8 +/- 1.6 vs. 2.7 +/- 0.8 days, p < 0.01). The deficit of bases was more expressed in groups 2 and 3 in comparison with group 1 (-11.3 +/- 3 and -2.7 +/- 9.1 mmol/liter vs. 1.4 +/- 4.4 mmol/liter) and left ventricular stroke index (LVSI) and oxygen delivery were lower. LVSI and base deficit were in linear correlation (rho = 0.4, p < 0.05). XIIa-dependent fibrinolysis was suppressed in all patients, which was more pronounced in group 3 in comparison with groups 1 and 2 (135 +/- 47.4 vs. 103 +/- 27 and 88.3 +/- 42.3). According to SOFA score, the severity of cardiovascular disorders during day 1 of SS was the same in all groups, while starting from day 2 it decreased in patients who survived. Acute respiratory failure was lower in group 1 only on day 1 according to SOFA. More pronounced (according to SOFA) hepatorenal failure was observed in group 2 in comparison with other patients. Organ involvement in hemoblastosis was detected at autopsy in 8 out of 13 cases. Hence, the need in prolonged cardiovascular support of SS patients is associated with development of polyorgan involvement. Fibrinolysis suppression is a frequent early manifestation of hemostasis disorders. Specific neoplastic organ involvement was observed in 61.5% patients with hemoblastosis who died from SS and its complications.