Hodgkin disease and non-Hodgkin lymphoma: plain chest radiographs and chest computed tomography of thoracic involvement in previously untreated patients

PURPOSE: To provide further information about the presentation of thoracic involvement in Hodgkin disease and non-Hodgkin lymphoma and to compare chest radiography with chest CT findings. MATERIALS AND METHODS: We reviewed the chest radiographs and the CT images of 100 Hodgkin and 100 non-Hodgkin patients, all of them untreated. Our data were compared with those of literature series: the latest study comparing the different patterns of Hodgkin and non-Hodgkin disease appeared in 1976 and it compared chest radiography with conventional tomography, not with CT. RESULTS: Intrathoracic involvement (75% vs 48%) and adenopathy (74% vs 28%) were more frequent in Hodgkin than in non-Hodgkin lymphoma. Ninety-nine per cent of the patients with intrathoracic involvement (74/75) had nodal disease. Paratracheal/prevascular nodes were most frequently involved, namely in 72/74 Hodgkin (97%) and in 27/28 non-Hodgkin patients (96%). The lung parenchyma was more often involved in non-Hodgkin (24%) than in Hodgkin (8%) patients; it was associated with mediastinal/hilar adenopathy in all Hodgkin and in 10/24 (42%) non-Hodgkin cases. Parenchymal involvement was demonstrated with chest radiography in 7/8 Hodgkin (88%) and in 13/24 non-Hodgkin patients (54%). Chest radiography showed paratracheal/prevascular adenopathy more often in Hodgkin (54/72, 75%) than in non-Hodgkin (15/27, 56%) cases. Subcarinal and internal mammary adenopathy was poorly depicted with plain films, while hilar adenopathy was generally identified with both CT and chest radiography. Chest radiography usually missed posterior mediastinal and anterior diaphragmatic adenopathy. CONCLUSIONS: The differences in the presentation of Hodgkin vs non-Hodgkin disease are not sufficiently distinctive to permit radiographic differentiation of the two conditions, but some patterns are helpful. Recognizing the frequency of thoracic involvement and that of the additional CT findings in Hodgkin and non-Hodgkin patients makes a sound basis for lymphoma imaging.     

Zebrafish organizer development and germ-layer formation require nodal-related signals

The vertebrate body plan is established during gastrulation, when cells move inwards to form the mesodermal and endodermal germ layers. Signals from a region of dorsal mesoderm, which is termed the organizer, pattern the body axis by specifying the fates of neighbouring cells. The organizer is itself induced by earlier signals. Although members of the transforming growth factor-beta (TGF-beta) and Wnt families have been implicated in the formation of the organizer, no endogenous signalling molecule is known to be required for this process. Here we report that the zebrafish squint (sqt) and cyclops (cyc) genes have essential, although partly redundant, functions in organizer development and also in the formation of mesoderm and endoderm. We show that the sqt gene encodes a member of the TGF-beta superfamily that is related to mouse nodal. cyc encodes another nodal-related proteins, which is consistent with our genetic evidence that sqt and cyc have overlapping functions. The sqt gene is expressed in a dorsal region of the blastula that includes the extraembryonic yolk syncytial layer (YSL). The YSL has been implicated as a source of signals that induce organizer development and mesendoderm formation. Misexpression of sqt RNA within the embryo or specifically in the YSL induces expanded or ectopic dorsal mesoderm. These results establish an essential role for nodal-related signals in organizer development and mesendoderm formation.     

Alloantigen gene therapy for squamous cell carcinoma of the head and neck: results of a phase-1 trial

OBJECTIVE: To determine the safety and efficacy of an immunogenic gene therapy using a drug designed to produce expression of a foreign class I major histocompatibility complex protein in patients with head and neck cancer. DESIGN: Phase 1 prospective clinical trial. SETTING: Academic medical setting. PATIENTS: Nine patients with advanced head and neck squamous cell carcinoma who had failed conventional therapy and did not express HLA-B7, a class I major histocompatibility complex protein. INTERVENTION: Patients were treated with Allovectin-7 (Vical Inc, San Diego, Calif) by direct intratumoral injection. Allovectin-7 contains a plasmid complementary DNA complexed with a cationic lipid, which results in expression of HLA-B7. MAIN OUTCOME MEASURES: Patients were assessed for any toxic effects and for any change in tumor volume. Biopsy specimens obtained before and after therapy were evaluated by immunohistochemistry to detect HLA-B7 expression and with the terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay to detect any induction of apoptosis. RESULTS: There were no toxic effects of the gene therapy. In 4 of these 9 patients there was a partial response to treatment, evidenced by a gradual reduction in tumor size. One patient has remained alive for more than 17 months since commencing treatment, with no clinical evidence of disease but with persistent histological evidence of cancer. Analysis of the biopsy specimens from 2 of the patients who responded to therapy demonstrated HLA-B7 expression. The TUNEL assay demonstrated extensive apoptosis in both of these patients, suggesting that this may be the mechanism of tumor reduction. CONCLUSIONS: These data demonstrate the potential efficacy and lack of toxicity of this form of alloantigen gene therapy. A multi-institutional study has been initiated to expand on these findings.     

Quantitative studies of splenic erythropoiesis in polycythaemia vera and myelofibrosis

A quantitative scanning method employing cyclotron-produced 52Fe has been developed to assess splenic erythropoiesis in patients with myeloproliferative disorders. In 12 patients with myelofibrosis splenic uptake of 52Fe was from 5.0% to 48% of the injected dose. Although a single patient with classical polycythaemia vera had a minor uptake of 2.8% of six other patients with this diagnosis showed no concentration of isotope in the splenic area. The fraction of 52Fe in the spleen of four patients with 'transitional' myeloproliferative disorders characterized by a high red cell mass, hypercellular bone marrow and a leucoerythroblastic blood film varied from 5% to 41%. No clear relationship was noted between the degree of splenic erythropoiesis as defined by this technique and the level of haemoglobin, the degree of splenomegaly, the effectiveness of erythropoiesis of traditional 59Fe surface counting. If splenectomy is considered in patients with myelofibrosis splenic 52Fe quantitation will provide more precise data on the contribution of splenic erythropoiesis than 59Fe surface counting alone.     

Ovarian-independent fluctuations of estradiol receptor levels in mammalian tissues

Three types of periodic fluctuation in tissue concentrations of estradiol receptor protein have been observed. A seasonal variation is described in the uteri of 12-16-week-old calves and of ovariectomized pigs, and in mammary tumor tissue obtained from postmenopausal women. A circadian rhythm has been demonstrated in uteri of ovariectomized rats. An irregular periodic fluctuation has been found in uteri of ovariectomized and of ovariectomized/hypophysectomized rats, with the period varying from 9 to 15 days. These observations establish that a substantial turnover of receptor occurs in the absence of hormone and that 'normal' baseline values of receptor concentration do not exist.     

P-selectin and MAC-1 mediate monocyte rolling and adhesion to ECM-bound platelets under flow conditions

Ultrasonic vocalizations were tape recorded from five pairs of copulating mice and subjected to spectrographic analysis. As expected, the mice emitted numerous 70-kHz vocalizations. At the beginning of the test, before copulation began, 70-kHz calls were emitted almost continuously, while calls with lower spectrographic frequencies were not observed. Subsequently, bursts of 70-kHz calling generally began shortly before mounts and intromissions and persisted until dismount. Intermixed with these 70-kHz calls were additional vocalizations of about 40 kHz. Calling rates were highest just prior to intromission. Once intromissions began, 70-kHz calls continued at a lower rate until dismount; however, 40-kHz calls occurred infrequently. In a second experiment, the male was found to emit the majority of the 70-kHz calls and all of the 40-kHz calls. When the male was devocalized, few calls were detected, regardless of whether the female was able to call. If the male was not devocalized, high rates of calling were detected, even if the female was devocalized.     

Treatment of patients with transitional-cell carcinoma of the urothelial tract with ifosfamide, paclitaxel, and cisplatin: a phase II trial

PURPOSE: A phase II trial of ifosfamide, paclitaxel, and cisplatin (ITP) was conducted in previously untreated patients with advanced transitional-cell carcinoma (TCC) to assess its efficacy and toxicity. PATIENTS AND METHODS: Thirty patients with metastatic or unresectable TCC were treated with ifosfamide 1.5 g/m2/d for 3 days with paclitaxel 200 mg/m2 over 3 hours and cisplatin 70 mg/m2 on day 1 of each 28-day treatment cycle. Therapy was continued for a maximum of six cycles. Prophylactic hematopoietic growth factor (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) was given on days 6 to 17 of each cycle. RESULTS: Twenty-three of 29 assessable patients (79%; 95% confidence interval [CI], 60% to 92%) demonstrated a major response (six complete [CR] and 17 partial [PR]) with response durations that ranged from 5 to 24+ months. Five patients with T4 bladder primary tumors had a major response, two with pathologic CR. At a median follow-up duration of 17.9 months, nine (31%) patients remain disease-free (range, 10+ to 24+). Hematologic toxicity included anemia, thrombocytopenia, and neutropenia; febrile neutropenia was observed in 17% of patients and 4% of cycles. No grade 4 nonhematologic toxicity was observed. Grade 3 nonhematologic toxicity included alopecia, allergy (3%), renal insufficiency (13%), and neuropathy (10%). Dose reductions or drug omissions were necessary for adverse events in seven (23%) patients. CONCLUSION: ITP is an active, well-tolerated regimen in previously untreated patients with TCC of the urothelial tract. Further study of this regimen in patients with both TCC and non-transitional-cell urothelial tumors is ongoing.