Characterization of non-human primate antisera to acute lymphoblastic leukemia (ALL): evidence for unique antigen(s) on childhood ALL of "T" phenotype

A non-human primate antiserum was prepared to acute lymphoblastic leukemia of T-cell phenotype (T-ALL) and, after absorptions with normal blood elements, reacted by immunofluorescence and microcytotoxicity to all the T-ALL tested. In addition, the antiserum reacted with cells from about 70% of the common ALL studied and immunoprecipitated the common ALL antigen of 100,000 daltons. However, when the anti-T-ALL serum was absorbed with with lymphoblasts from common ALL, it failed to react with common ALL lymphoblasts, yet reacted significantly with cells from patients with T-ALL phenotype and defined a 100,000-dalton membrane component not found on common ALL lymphoblasts. In addition, sequential immunoprecipitation of 125I-labeled T-ALL membranes by anti- common-ALL serum followed by anti-T-ALL serum detected the T-ALL membrane component of 100,000 daltons that was not found on common ALL. Thus, our results demonstrate the presence of of a unique human T-ALL antigen present on all T-ALL distinct from the common ALL antigen.     

Flow cytometric analysis of peripheral blood lymphocytes in ulcerative colitis and Crohn''s disease.

Using two colour immunofluorescence with fluorescein isothiocyanate and phycoerythrin labelled monoclonal antibodies, multi-parameter flow cytometry was used to examine the antigenic characteristics of peripheral blood lymphocytes in whole blood of patients with ulcerative colitis and Crohn's disease who were not taking immunosuppressive drugs. The numbers of CD4+ and CD8+ lymphocytes in patients with ulcerative colitis and Crohn's disease remained unchanged so that the CD4/CD8 ratio was the same as that of normal control subjects. In Crohn's disease there were many activated T cells (CD3+, CD25+). Although natural killer cells in active Crohn's disease were lower than in normal control subjects, cytotoxic T lymphocytes, as defined by CD3+, CD16+, did not differ in patients with inflammatory bowel disease compared with normal control subjects. For B cell subsets, there were differences in Leu-1+ B cells, Leu-8+ B cells, Fc epsilon R+B cells (Leu-16+, Leu-20+), and activated B cells (Leu-12+, Leu-21+) between patients with inflammatory bowel disease and normal control subjects. These differences are compatible with local activation of B cells in the inflamed colon.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

Platelet-derived growth factor in vivo: levels, activity, and rate of clearance

Platelet-derived growth factor (PDGF) is a potent mitogen for many cultured connective tissue cells. It is present in concentrated form within the platelet alpha-granules and is believed to be released during platelet degranulation at sites of vascular injury. We have used a sensitive radioreceptor assay to measure PDGF levels in whole blood serum from normal humans [17.5 +/- 3.1 (SD) ng/mL] and baboons (2.7 +/- 1.2 ng/mL). PDGF was not detected in plasma from either species. In addition, plasma was found to substantially reduce the ability of added purified PDGF to bind to the cell surface PDGF receptor on cultured cells, suggesting that plasma may contain a PDGF-binding protein that would serve to inactivate PDGF released into plasma. Calculations of PDGF concentrations in serum have been corrected for the effects of the binding protein. 125I-PDGF injected intravenously into normal baboons was cleared rapidly from the plasma (t1/2 = two minutes). The rapid clearance of 125I-PDGF did not result from iodination damage, as purified unlabeled PDGF was cleared with comparable kinetics. The rapid clearance of purified and iodinated PDGF did not result from changes in PDGF structure during purification or from removal of PDGF-associated proteins during purification, as PDGF present in freeze-thaw lysates of fresh platelets was cleared equally rapidly. We conclude that release of PDGF at sites of vascular injury would greatly increase the local concentration of PDGF and that PDGF not localized to the site of injury would be rapidly cleared from the circulation.     

The effect of age on complications in women undergoing minimally invasive sacral colpopexy

Introduction and hypothesis

Previous research has demonstrated similar complication rates in older and younger women undergoing abdominal sacral colpopexy via laparotomy. The objective of this study was to compare perioperative complications in older and younger women undergoing minimally invasive sacral colpopexy.

Methods

This was a retrospective study of laparoscopic and robotic sacral colpopexies performed from January 2009 to May 2012 at a large academic center. Patient demographics, surgical data, and perioperative complications were compared in women Results A total of 302 women underwent minimally invasive sacral colpopexy during the study period. Mean age was 58.5?±?8.8 years and 84 subjects (27.8 %) were ≥65 years. Older women were more likely to have had a prior hysterectomy (60.7 vs 39.0 %, p?=?0.001) and had more severe preoperative prolapse (86.9 % vs 71.9 %?≥ POPQ stage III, p?=?0.01). There was no significant difference in duration of hospitalization (1.4 vs 1.4 days, p?=?0.54). Overall, there were significantly more major complications in women ≥?65 years (unadjusted OR 1.84, 95 % CI 1.02–3.35, p?=?0.04). After controlling for BMI, route of surgery, estimated blood loss (EBL), and operating room time, age ≥?65 remained a significant predictor of complications (adjusted OR 2.28, 95 % CI 1.21–4.29, p?=?0.01).

Conclusions

Our findings suggest that older women have a higher rate of major complications following minimally invasive sacral colpopexy, even after controlling for BMI, route of surgery, EBL, and operating room time. This increased risk should be addressed during preoperative counseling and may influence surgical planning.     

Utility of dipstick urinalysis in peri- and postmenopausal women with irritative bladder symptoms

Introduction and hypothesis

Previous studies of dipstick urinalysis (UA) in asymptomatic peri- and postmenopausal women demonstrate poor sensitivity to detect a urinary tract infection (UTI). We hypothesized that sensitivity of this test would be improved in symptomatic peri- and postmenopausal women.

Methods

This was a cross-sectional study of 76 women seeking urogynecology care for irritative bladder symptoms. Subjects with a positive clean-catch (CC) dipstick UA for leukocyte esterase (LE) or nitrites (NIT) were offered enrollment. Dipstick UA was performed on CC and catheterized specimens, followed by microbiologic culture. Test characteristics were calculated for CC and catheterized UA. CC culture was compared with catheterized culture (gold standard) using Spearman’s correlation coefficient.

Results

Data was available for analysis in 75/76 (98.7 %) enrolled subjects. Mean age was 68?±?11 years. Most subjects were postmenopausal (98.7 %) and Caucasian (97.3 %). Dipstick sensitivity ranged from 48 % to 87 % and 35 % to 57 % in CC and catheterized specimens, respectively. Dipstick UA from a CC specimen positive for NIT had the highest sensitivity (60.9), specificity (100), negative predictive value (85.2), and positive predictive value (100) in this population. Dipstick UA from CC and catheterized specimens had similar sensitivity for detecting UTIs. When culture results of 10³ colony-forming units were considered positive, CC and catheterized specimens were moderately correlated (ρ?=?0.470).

Conclusions

Dipstick UA in this study had improved sensitivity compared with previously published results in both CC and catheterized samples. Initiation of empiric antibiotic treatment in women with irritative bladder symptoms and NIT-positive CC dipstick UA prior to obtaining urine culture results is a reasonable option.     

Percutaneous radiofrequency ablation of renal tumours: Case series of 11 tumours and review of published work

Detection of renal cell carcinoma (RCC) is increasing with the greater use of cross‐sectional imaging and up to two‐thirds of RCCs are discovered incidentally in asymptomatic patients. The traditional option of nephrectomy or partial nephrectomy may not always be appropriate. A minimally invasive treatment alternative is radiofrequency ablation (RFA). We retrospectively reviewed the RFA cases for renal tumours at our institution between January 2004 and June 2006. Thirteen RFA treatment sessions were conducted for 11 neoplasms in 11 patients. Mean patient age was 74.4 years (61–88 years). Imaging was carried out after ablation with a mean follow up of 8.0 months (2–26 months). No residual tumour was observed after the first RFA treatment in 82% of patients (nine of 11). Two patients required a second RFA treatment for residual (one) or recurrent tumour (one). RFA is emerging as a useful technique for treatment of small renal tumour. A number of short‐term studies reflect this, however, long‐term findings are still lacking.