Citations

We have investigated the significance of the method of treatment on the oncological and functional outcomes and on the complications in 184 patients with soft-tissue sarcomas of the adductor compartment managed at three international centres. The overall survival at five years was 65% and was related to the grade at diagnosis and the size of the tumour. There was no difference in overall survival between the three centres. There was, however, a significant difference in local control with a rate of 28% in Centre 1 compared with 10% in Centre 2 and 5% in Centre 3. The overall mean functional score using the Toronto Extremity Salvage Score in 70 patients was 77% but was significantly worse in patients with wound complications or high-grade tumours. The scores were not affected by the timing of radiotherapy or the use of muscle flaps. This large series of soft-tissue sarcomas of the adductor compartment has shown that factors influencing survival do not vary across the international boundaries studied, but that methods of treatment affect complications, local recurrence and function.

Strict morphologic criteria must be used for patient selection to achieve durable success with endovascular aortic aneurysm repair (EVAR). The goal of this study was to assess morphologic suitability (MS) of abdominal aortic aneurysms (AAAs) for 2 currently approved bifurcated stent grafts and identify reasons for exclusion from EVAR. The authors reviewed the electronic charts of 1,795 consecutive patients who were diagnosed as having AAA between January 1999 and July 2001 at their institution. Three hundred and twenty patients had an AAA with a diameter of =5.0 cm, measured on computed tomography (CT). The records of 301 patients, 254 men, 47 women, with a mean age of 74 years were available for review, and these patients constituted the study cohort. Criteria used for MS included a proximal neck length =15 mm; neck diameter between 18 and 26 mm; neck angulation =60°; common or external iliac artery (CIA or EIA) diameters of 7–16 mm and 8–13 mm, respectively, for AneuRx (Medtronic Ave, Santa Rosa, CA) and Ancure (Guidant Cardiac and Vascular Division, Menlo Park, CA) bifurcated grafts. AAAs were suitable for AneuRx device in 14% of patients (43 of 301; 95% CI = 11–19%) and for Ancure in 5% (16 of 301; 95% CI = 3.1–9%). The main reason for exclusion was an inadequate proximal aortic neck (73%). The neck was too short in 49.5%, too wide in 64% and badly angulated in 12% of the patients. Iliac artery morphology precluded EVAR with AneuRx and Ancure devices in 52% and 80%. Both CIAs were too wide for EVAR in 43% and 77%, respectively. When iliac artery diameter =20 mm was accepted, iliac suitability for AneuRx increased from 49% to 70% and overall suitability increased from 14% to 20%. When more permissive criteria were used for MS (neck length =10 mm, neck diameter =30 mm, CIA =20), 39% of patients became candidates for EVAR. More than three fourths of the patients with an AAA =5.0 cm in size, seen in a tertiary referral center, are morphologically not suitable for EVAR using 2 currently approved bifurcated endografts. The main reasons for exclusion are a short or wide proximal aortic neck. Considerable changes in size of the devices and in proximal attachment techniques have to occur before most AAAs will be suitable for EVAR.

Abstract Purpose: Most colorectal cancers that have high levels of microsatellite instability (MSI-H) show loss of immunohistochemical expression of proteins that participate in the DNA mismatch repair process, most often involving MLH1 and MSH2. Less commonly, a third DNA mismatch repair protein, MSH6, may also be lost as the primary event. Rarely, tumors with MSI-H show normal expression of these three proteins. The genetic deficiency leading to the MSI-H phenotype in such cases is unknown. PMS2 is another member of the DNA mismatch repair complex. Its expression is generally lost in tumors with MLH1 loss of expression. Rarely, there is selective loss of PMS2 expression. We sought to describe the frequency and clinical correlates of selective loss of expression of PMS2 with the MSI-H tumor phenotype. Experimental Design: Two thousand seven hundred nineteen colorectal cancers from both clinic- and research-based ascertainment were studied. Tumor MSI testing and immunohistochemistry for MLH1, MSH2, MSH6, and PMS2 were conducted. Medical records were abstracted for age at diagnosis, gender, colorectal cancer site, and family history. Results: Five hundred thirty-five of the 2,719 tumors were MSI-H. Of these, 93% showed loss of expression of MLH1, MSH2, and/or MSH6. Thirty-eight showed normal expression for these proteins. PMS2 immunohistochemical staining was successful in 32 of 38 of these tumors. Of the 32, 23 showed selective loss of expression of PMS2. This was associated with young age of diagnosis and right-sided location but not with a striking family history of cancer. Conclusions: Overall, 97% of the MSI-H tumors showed loss of expression for one or more of these four mismatch repair proteins. Selective loss of expression of PMS2 was present in 72% of cases in which colorectal cancers had an MSI-H phenotype but no alteration of expression of MLH1, MSH2, and MSH6. The underlying mechanism involved cannot be determined from this study but could involve point mutations in other DNA mismatch repair genes with retention of immunohistochemical expression, somatic inactivation of PMS2, or germ line mutation of PMS2.

Clinical Pharmacology & Therapeutics (2003) 73, P29–P29; doi:

The decrease in abundance of a subset of highly conserved basic nuclear proteins is established to correlate with the loss of proliferative potential in association with the process of terminal differentiation in murine mesenchymal stem cells and human keratinocytes. These proteins, designated P2Ps for proliferation potential proteins, have apparent molecular masses of 30-40 kD, are associated with the 30-40S substructures of nuclear hnRNP complexes, and are recognized by antibodies made against core proteins of hnRNP particles. They also share an epitope in common with heat shock protein-90 (hsp90) and are recognized by two mAbs against hsp90. Two-dimensional electrophoretic Western blots furthermore show that P2Ps make up a subset of hnRNP proteins. Cells that possess these proteins express the potential to proliferate whether or not they are traversing the cell cycle. These include rapidly growing cells, reversibly growth-arrested cells, and nonterminally differentiated cells. In contrast, cells that have irreversibly lost their proliferative potential, such as terminally differentiated cells, show a marked reduction in the abundance of P2Ps as determined by immunodetection on Western blots. A correlation, therefore, exists between the presence of this subset of nuclear proteins and the proliferative potential in two cell types. These results raise the possibility that as a subset of hnRNP proteins, P2Ps may mediate posttranscriptional control of the processing of specific RNAs required for cell proliferation.

Renal artery stenosis (RAS) may cause hypertension, azotemia, episodes of flash pulmonary edema and congestive heart failure. Renal artery angioplasty and stenting was performed in 207 patients from 1991 to 1997. Thirty-nine of these patients (19%) underwent renal artery stenting for the control of recurrent episodes of congestive heart failure and flash pulmonary edema. All patients had angiographic evidence of severe (>70%) bilateral RAS (n = 18) or severe RAS to a solitary functioning kidney (n = 21). Sixteen patients (41%) were male and 23 (59%) were female, mean age 69.9 years (range 50- 85 years). Of the 18 patients with bilateral RAS, 12 (66.6%) underwent bilateral stenting. Mean blood pressure decreased from 174/85 6 32/23 mmHg to 148/72 6 24/14 mmHg (p < 0.001). Mean number of blood pressure medications decreased from 3 6 1 to 2.5 6 1 (p = 0.006). Twenty-eight patients (71.8%) had improvement in blood pressure control. The mean serum creatinine decreased from 3.16 6 1.61 to 2.65 6 1.87 (p = 0.06). Six of 39 patients (15.4%) used angiotensin converting enzyme (ACE) inhibitors prior to stenting whereas 19 of 39 patients (48.7%) used ACE inhibitors poststenting (p = 0.004). Twenty of 39 patients (51.4%) demonstrated improvement in serum creatinine, 10 of 39 patients (25.6%) had stabilization of serum creatinine and nine of 39 patients (23%) demonstrated worsening. The number of hospitalizations due to congestive heart failure in the year preceding renal artery stenting was 2.4 6 1.4 and poststenting was 0.3 6 0.7 (p < 0.001). The New York Heart Association Functional Class decreased from 2.9 6 0.9 prestenting to 1.6 6 0.9 poststenting (p < 0.001). Thirty of 39 patients (77%) had no hospitalizations for congestive heart failure during a mean follow-up period of 21.3 months. Nine patients expired during the course of follow up; eight of the nine patients died within the first year after renal artery stenting. Renal artery stenting decreased the frequency of congestive heart failure, flash pulmonary edema, and the need for hospitalization in most patients. Blood pressure was markedly improved in the majority of patients with improved or stabilized renal function. Evaluation for RAS is important in hypertensive patients who present with recurrent congestive heart failure or flash pulmonary edema.

ABSTRACT The performance of the Amplified Mycobacterium Tuberculosis Direct (AMTD) test (Gen-Probe Inc., San Diego, Calif.) was assessed in a large tertiary care mycobacteriology laboratory. Both acid-fast smear-positive and smear-negative respiratory and nonrespiratory clinical specimens were analyzed. From February 1998 to 4 October 2001, AMTD assays were performed on 391 respiratory specimens and 164 nonrespiratory specimens. The AMTD assay was compared to the “gold standard” of combined culture and clinical diagnosis. The overall sensitivity for all specimens, including those for which no smear result was available, was 91.2%. The overall sensitivities of the assay, including acid-fast smear-positive and -negative specimens, were 97.8 and 77.3% for respiratory and nonrespiratory specimens, respectively. The corresponding specificities for respiratory and nonrespiratory specimens were 99.1 and 98.5%, respectively. The overall specificity for all specimens was 98.9%. Positive and negative predictive values were 93.9 and 99.7% and 91.7 and 96.4% for respiratory and nonrespiratory specimens, respectively. The time saved by using the AMTD test for making a diagnosis of tuberculosis instead of using culture was 8.99 days. Inhibitors to the AMTD assay were found in 3.1% of respiratory specimens and 3.1% of nonrespiratory specimens. The assay, used in a general mycobacteriology laboratory setting, represents an important advance in improving the speed and accuracy of diagnosis in the management of patients with tuberculosis.

Heat shock protein (hsp)90 functions in a complex chaperoning pathway where its activity is modulated by ATP and by interaction with several co-chaperones. One co-chaperone, p23, binds selectively to the ATP-bound state of hsp90. However, the isolated ATP-binding domain of hsp90 does not bind p23. In an effort to identify the p23-binding domain, we have constructed a series of hsp90 deletion mutants fused with glutathione- S -transferase (GST). Full-length GST-hsp90 is able to bind p23, and also, to chaperone assembly of progesterone receptor complexes. Truncations from the C terminus of GST-hsp90 reveal a C-terminal boundary for the p23-binding domain at approximately residue 490. This fragment contains, in order, the ATP-binding domain, a highly charged region, and 203 residues beyond the charged region. p23 binding is unaffected by deletion of the charged region, indicating that two noncontiguous regions of hsp90 are involved in p23 binding. These regions are only effective when hsp90 is in a dimeric state as shown by loss of p23 binding upon removal of GST or as shown by use of FK506-binding protein12-hsp90 constructs that form dimers and bind p23 only in the presence of a bivalent drug. Thus, p23 binding requires an hsp90 dimer with close proximity between N-terminal regions of hsp90 and a conformation specified by ATP.