High-resolution 3D T2-weighted fast spin echo: new applications in the orbit

Recent developments have made available for ophthalmologic MR imaging a very high-resolution 3D fast spin echo T2 (3D FSE T2) sequence, which runs in a standard head coil. A modification of this technique, 3D FSEz T2, uses a zero-filled slice interpolation method during post-processing to further improve spatial resolution. We describe the technique and share our early clinical observations in patients with ocular masses. Briefly, the additional information from the 3D FSEz T2 resulted in a change in diagnosis from the conventional imaging series in 11 of (41%) 27 studies, usually through the identification of previously treated retinoblastoma lesions. The new sequence significantly increased diagnostic confidence in six (38%) of the remaining 16 cases, usually through better anatomical detail and lesion conspicuity, and did not change interpretation in 10 cases. Such an approach improves diagnostic confidence and may eliminate the need for a dedicated surface coil examination.     

The 17q23 amplicon and breast cancer

A novel region of amplification in breast tumors was recently identified on chromosome 17q23. Extensive mapping of the amplicon by Southern blotting and fluorescence in situ hybridization (FISH) in breast cancer cell lines determined that the amplicon can be up to 4 Mbp in size and may contain 50 genes. Copy number analysis at 50–75 kb resolution in breast cancer cell lines and breast tumors identified several independently amplified regions within the amplicon, suggesting that a number of genes are selected for amplification because they independently contribute to tumor formation and progression. Support for this hypothesis comes from studies demonstrating that many of the amplified genes are over-expressed in breast cancer cell lines and tumors, and that the RPS6KB1, TBX2, and PPM1D genes from the region, that are amplified and over-expressed in breast tumors and cell lines, contribute to tumor formation and/or tumor progression. In this review we summarize the structural studies of the amplicon that have been carried out, we outline the evidence implicating the RPS6KB1, TBX2, and PPM1D genes as oncogenes, and we describe some of the other candidate oncogenes from the region.     

Total meniscectomy in adolescence. A thirty-year follow-up

We have carried out a prospective, longitudinal 30-year review of 95 adolescents who underwent total meniscectomy in one knee, and have compared the results with those observed 13 years earlier. All the medical records were scrutinised. Of the 63 patients reviewed clinically, 47 reported decreased sporting activity, although subjective satisfaction rose by 3% to 71%. The scores on the WOMAC osteoarthritis index differed significantly between patients grouped by subjective global assessment. Satisfactory function scores increased from 48% to 60%. In the 53 patients consenting to bilateral radiography of the knee, the incidence of narrowing of the articular cartilage in the operated knee increased significantly between the reviews (19% to 36%). Progression of degenerative change paralleled reduction in activity. Outcome measures were best after medial, intermediate after lateral and worst after double meniscectomy.     

Reactive stroma as a predictor of biochemical-free recurrence in prostate cancer.

Extensive scientific literature data point to reciprocal interactions between prostate stromal cells and prostate cancer cells that likely regulate tumor progression. To investigate whether these intratumoral-reactive stromal cells in human prostate cancer are predictive of survival, tumor stroma volume and specific stroma markers were quantitated by using tissue microarrays (index tumors of 847 patients), and the results were analyzed relative to the recurrence-free survival data set for these patients. Tumor tissue was evaluated with Masson's trichrome stains and by immunohistochemistry with antibody probes to smooth muscle alpha-actin, desmin, vimentin, pro-collagen type I, and calponin. The relative volume of intratumor stroma (5% stroma, grade 0; 5-15%, grade 1; 15-50%, grade 2; >50%, grade 3) and the expression index of stromal marker (staining intensity grade x percentage of positive cells per field) were quantitated and analyzed. Interpretable data were obtained from 545 patients. Statistical analysis of the survival data set showed that the volume of reactive stroma in the tumor was a significant predictor of disease-free survival. Stroma volume was most optimal as an independent predictor in tumors containing stroma, defined as Gleason 7 and lower grades. Of interest, tumors with either little to no stroma or tumors with abundant stroma each showed reduced recurrence-free survival. For specific stromal markers, reduced desmin and smooth muscle alpha-actin were hallmarks of cancer-associated reactive stroma relative to normal fibromuscular stroma. Quantitative analysis of desmin and smooth muscle alpha-actin expression showed both to be significant and independent predictors of recurrence-free survival. This is the first study to demonstrate that nonepithelial-reactive stroma elements in prostate cancer tumors can be used as prognostic indicators. These data also add to the concept that tumors are not purely epithelial and the tumor-reactive stroma must be considered an important biological component of the cancer.     

Lower limb muscle dysfunction may contribute to foot ulceration in diabetic patients

OBJECTIVES: To investigate the relationship between in-shoe plantar foot pressure and the co-ordinated activity of five lower limb muscles of diabetic patients, who are known to have a higher risk of foot morbidity. DESIGN: A portable six channel electromyographic system has been designed, developed and synchronised in real time with a 16 channel piezoelectric transducer in-shoe pressure measuring device, Gaitscan. BACKGROUND: So far, no one has tried to establish a relationship between in-shoe foot pressure distribution and muscle activity of the lower limb in diabetes. The measurement of phasic muscle activity has been related to foot pressure and compared to a control group of normal volunteers. METHODS: Twenty nine diabetic subjects and 22 healthy non-diabetic volunteers have been studied by recording electromyography of lower leg muscles and in-shoe foot pressure measurements simultaneously. RESULTS: In diabetic subjects, the period of contact pressure was greater than in normal control subjects (P<0.003). The initial forefoot time to contact with the ground was shorter in diabetics when compared to controls, indicating a faster forefoot contact. Of the dorsiflexor muscles, the Anterior Tibialis, normally contracting eccentrically at heel strike, was subject to a measurable delay in the initiation of contraction, of mean difference of 180 ms (P<0.001), in diabetic subjects when compared to the normal controls. CONCLUSIONS: The late firing of Tibialis Anterior means that its normal modulating role in lowering the foot to the ground after heel strike through eccentric contraction is disturbed. The result is that the foot reaches the foot flat stage in a less ordered manner, subjecting it to high plantar pressures. RELEVANCE: The results obtained may assist in planning realignment procedures of the foot and help prevent development of ulcers on the sole of the foot in high risk diabetic subjects.     

Screening poly(dA/dT)- cDNAs for gene identification

Many genes expressed in the human genome have not been identified despite intensive efforts. We observed that the presence of long poly(dA/dT) sequences in the 3' end of cDNA templates contributes significantly to this problem, because the hybrids formed randomly between poly(dA) and poly(dT) sequences of unrelated cDNA templates lead to loss of many templates in the normalization/subtraction reactions. The low abundant copies, which account for the majority of the expressed genes, are affected in particular by this phenomenon. We have developed a strategy called screening poly(dA/dT)(-) cDNAs for gene identification to overcome this obstacle. Applying this strategy can significantly enhance the efficiency of genome-wide gene identification and should have an impact on many functional genomic studies in the postgenome era.     

Transplantation of ABO-incompatible bone marrow and peripheral blood stem cell components

Hemolysis may occur during infusion of an ABO-incompatible HSC component if the recipient has isoagglutinins directed against donor red blood cells, or later as a result of the production by donor lymphocytes of isoagglutinins directed against recipient ABO-antigens. Peripheral blood stem cell (PBSC) components collected by apheresis contain few red cells but considerably greater numbers of lymphocytes than marrow. We reviewed the transplant courses of 158 recipients of marrow (n = 90) or PBSC (n = 68) from HLA-identical, ABO-incompatible sibling donors. No patient experienced immediate or delayed hemolysis attributable to the ABO incompatibility. Recipients of minor ABO-incompatible red cell-replete marrow required fewer red cell transfusions during the first week after transplantation than recipients of PBSC or marrows depleted of red cells; the red cell transfusion requirements for the following 3 weeks did not differ. The maximum level of bilirubin did not differ for patients classified by ABO incompatibility or source of HSC. The development of positive antiglobulin tests occurred for eight marrow recipients from a separate group of 22 patients (17 marrow, five PBSC) for whom this testing was performed. None of these patients developed overt hemolysis. These data indicate that hemolysis complicating ABO-incompatible transplantation is not common after either marrow or PBSC transplantation. Bone Marrow Transplantation (2000) 26, 749-757.     

The influence of external knee moments on the outcome of total meniscectomy. A comparison of radiological and 3-D gait analysis measurements

Twenty one individuals who had undergone unilateral total meniscectomy, and had no significant antero-posterior (AP) laxity underwent three dimensional (3-D) gait analysis, bilateral radiological assessment of varus/valgus alignment and tibio-femoral osteoarthritis (TFOA). Average foot progression angle during the stance phase of gait was not related to knee adduction moment. The findings support the previously noted correlation between varus/valgus alignment and TFOA. The dynamic gait parameter of the adduction moment in early stance did not correlate with either hip–knee–ankle angle or TFOA, thus the expected influence of external moments on outcome after meniscectomy was not found. Thus the correlation between varus/valgus alignment and TFOA can not be explained by a simple loading algorithm.