Cervical carcinoma: can dynamic contrast-enhanced MR imaging help predict tumor aggressiveness?

PURPOSE: To determine whether fast dynamic contrast agent-enhanced magnetic resonance (MR) imaging can demonstrate tumor aggressiveness of cervical carcinoma in patients who are eligible for surgical treatment. MATERIALS AND METHODS: Dynamic contrast-enhanced MR imaging of cervical carcinoma was performed in 82 consecutive patients with stage I or IIA disease who were referred for radical hysterectomy. The maximum slope and amplitude of dynamic first-pass contrast enhancement were quantified. These parameters were correlated with histologic measures of tumor aggressiveness (tumor invasion depth, pelvic lymph node status). RESULTS: The analysis was based on tumors in 62 patients: 30 aggressive and 32 relatively nonaggressive tumors. Twenty patients were excluded from analysis owing to insufficient surgical data, tumor too small for accurate assessment, or technical problems. There were no significant differences between aggressive and nonaggressive tumors in terms of the first-pass contrast-enhancement parameters of slope (2.0 vs 2.1 arbitrary signal intensity units per second, P > .5) or amplitude (24.8 vs 27.8 arbitrary units, P > .2). CONCLUSION: Dynamic contrast-enhanced MR imaging does not facilitate differentiation between aggressive and nonaggressive tumors and therefore has no clinical role in assisting in treatment decisions in patients who are candidates for radical hysterectomy.     

Monocyte expression of tissue factor and adhesion molecules: the link with accelerated coronary artery disease in patients with chronic renal failure

OBJECTIVE: To investigate the expression of monocyte tissue factor (MTF) and adhesion molecules in patients with chronic renal failure (CRF) and to look for any correlation with thrombin generation and Lp(a) lipoprotein. DESIGN: A study of MTF expression and adhesion molecules, prothrombin fragments 1+2 (PTf1+2), an index of thrombin generation, and lipoproteins in patients with CRF and in normal control subjects. BACKGROUND: Patients with end stage renal failure have an increased risk of coronary artery disease despite advances in therapy. Stimulated monocytes are potent activators of blood coagulation through the generation of MTF, which was recently implicated in the aetiology of acute coronary ischaemic syndromes. METHODS: MTF expression and adhesion molecules were measured in whole blood using immunofluorescence of monocytes labelled with anti-tissue factor antibody and CD11b and c by flow cytometry. PTf1+2 and Lp(a) lipoprotein in plasma were measured by enzyme linked immunosorbent assay (ELISA). PATIENTS: 70 patients with CRF without documented coronary artery disease (30 patients with CRF undialysed, 20 patients undergoing chronic ambulatory peritoneal dialysis (CAPD), and 20 undergoing haemodialysis (HD)), together with 20 normal controls, were studied. RESULTS: The (mean (SD)) increased MTF of CRF (48.0 (29) v 33.3 (7.2) mesf unit/100 monocytes in controls, p = 0.04) was more pronounced in patients undergoing dialysis (HD 73.1 (32.8) (p < 0.003) and CAPD 62.8 (28.9) mesf unit/100 monocytes, p < 0.04). MTF activity showed a positive correlation with both PTf1+2 and serum creatinine (p < 0.003) but not with Lp(a) lipoprotein. Lp(a) lipoprotein was significantly increased in both dialysis groups compared with controls (p < 0.005) and non-dialysis CRF groups (p < 0.02). Monocyte adhesion molecule (CD11b) was significantly higher in all three CRF groups than in the controls (p = 0.006). Conclusion: This study has demonstrated a hypercoagulable state in patients with CRF. This was especially pronounced in the dialysis patients. These findings provide a possible explanation for the increased cardiovascular and cerebrovascular morbidity and mortality in these patients.     

Identification of tyrosine phosphorylation sites in the CD28 cytoplasmic domain and their role in the costimulation of Jurkat T cells

The cytoplasmic domain of CD28 contains four tyrosine residues. Because signal transduction by CD28 appears to involve its tyrosine phosphorylation, we determined sites of CD28 tyrosine phosphorylation using mutants of mouse CD28 that retained tyrosine at one position, with the remaining three positions mutated to phenylalanine. When expressed in Jurkat cells and stimulated by mAb, only the mutants with tyrosine at position 170 or 188 were tyrosine phosphorylated. Phosphorylation of Tyr170 recruits phosphatidylinositol 3-kinase to CD28. Tyr188 has not been associated with any specific signaling event, but we found that ligation of CD28 by the natural ligand B7.2 also induced phosphorylation of Tyr188, suggesting that this event is of physiological importance. Consistent with that possibility, mutation of Tyr188 to phenylalanine severely impaired the ability of mouse CD28 to deliver a costimulus for the expression of CD69 and the production of IL-2. The functional consequences of the mutation of Tyr188 were unique; mutation of the other three tyrosines, individually or in combination, did not impair costimulation. Therefore, of the four CD28 tyrosine residues only Tyr188 is required for signaling in Jurkat cells, suggesting that its phosphorylation is a key event in the costimulation of T cells.     

Significant reduction in circuit pressure with modified plasma separation chamber for a heparin removal device

OBJECTIVE: This study aimed to determine the maximum dose of radiation the CLARION 1.2 cochlear implant can withstand safely. INTRODUCTION: Cochlear implants restore functional hearing to patients with sensorineural deafness. Because some patients may need radiation therapy, it is important to investigate the influence of ionizing radiation on cochlear implant function. METHODS: This study tested the function of four CLARION 1.2 implants (Advanced Bionics, Sylmar, CA, U.S.A.) after varying radiation treatments with gamma rays. The first implant received a cumulative dosage of 69 Gy over nine treatments (single doses between 0.1-30 Gy). The second was irradiated with a total of 90 Gy, receiving three treatments of 30 Gy each. The third and fourth received doses more typical of patient therapy (i.e., 2 Gy) approximately 30 times, for a cumulative dosage of approximately 60 Gy. Implant function was tested after every treatment; the CLARION implant incorporates a back-telemetry system, allowing impedance and current output testing. RESULTS: Despite the type of treatment, the results were quite consistent: difficulties in function occurred when the cumulative dosage inside the implant was approximately 60 Gy. The first implant recovered completely and the second recovered partially. DISCUSSION: The CLARION 1.2 cochlear implant seems to safely withstand approximately 60 Gy of radiation before experiencing functional difficulties. In a clinical situation, the implant would not likely be in the target volume irradiated, and thus the patient's therapeutic cumulative dosage might be higher.     

Torsion of wandering spleen: the whorled appearance of the splenic pedicle on CT

Congenital deficiency or acquired laxity of the suspensory ligaments of the spleen may result in extreme splenic mobility. This rare condition, which is termed wandering or ectopic spleen predisposes the elongated splenic pedicle to torsion. We present a case of splenic torsion with a new CT finding consisting of a whorled appearance of the splenic pedicle. To our knowledge this finding has not been described before.     

Radiosensitivity of atomic bomb survivors as determined with a micronucleus assay

We have developed a system in which a unique double-stranded break (DSB) can be introduced into a yeast chromosome during mitotic growth. The recognition site for the endonuclease I-SceI was inserted at different places in the yeast genome in haploid and diploid cells expressing this endonuclease. Induction of the break in haploids results in cell death if no intact copy of the cleaved region is present in the cell. If such a copy is provided on a plasmid, as an ectopic gene duplication, or on a homologous chromosome, the break can be repaired. Repair results in two identical copies in the genome of the locus which has been cut. We call this phenomenon homozygotization by reference to diploids heterozygous for the cut site in which repair leads to homozygosis at this site. We have compared the efficiencies of repair in the various topological situations examined, and conclude that some mechanism must search for regions of homology to both sides of the DSB and that repair is successful only if the homologies are provided by the same template molecule.     

The Royal College of Obstetricians and Gynaecologists micro-invasive carcinoma of the cervix study: preliminary results

OBJECTIVES: To determine how micro-invasive carcinoma of the cervix is diagnosed and treated in the United Kingdom. To record the frequency of the various pathological features which comprise the histological diagnosis of micro-invasion, and to assess their relevance to outcome. DESIGN: Prospective observational study. SETTING: Hospitals throughout the United Kingdom. SUBJECTS: Two hundred and eighty-six cases were submitted for entry into the study. Following independent review of the histological material 116 cases were excluded: 41 were not accompanied by histological slides for review, 55 had no evidence of invasive disease, 17 had invasive disease greater than FIGO Stage 1a, and three were adenocarcinomas. The remaining 170 cases were registered for the study but follow up was incomplete in 18. This report concerns the 152 women with complete follow up to 1991. RESULTS: The age of the 152 women ranged from 22 to 65 years (median 36 years). In 116 women (76%) the diagnosis was made by cone biopsy (cold knife, loop diathermy, or laser) or wedge biopsy, in 9 women (6%) the diagnosis was made by hysterectomy, and in 27 women (18%) punch biopsy suggested an invasive lesion and subsequent excisional treatment (including radical hysterectomy with node dissection in three) demonstrated micro-invasion. The depth of invasion was up to 3 mm in 142 women (93%) and 3.1 to 5 mm in 10 women (7%). Capillary-like space involvement was present in 12 women (8%). Treatment methods used were local cervical surgery in 79 women (52%), simple hysterectomy in 63 (41%), and radical hysterectomy in 10 (7%). There was only one known recurrence and death due to cervical carcinoma. CONCLUSION: There is no uniformity in the management of micro-invasive carcinoma of the cervix. The frequency of recurrence, lymph metastases, and death is low. Nonradical surgery appears to give satisfactory results.