Proton MRS imaging in the follow-up of patients with suspected low-grade gliomas

We compared the value of changes in proton magnetic resonance spectroscopic imaging (¹H-MRSI) with changes in clinical status and/or contrast-enhanced magnetic resonance imaging (MRI) in the monitoring of patients with suspected low-grade glioma (LGG). From June 1, 1999 till May 31, 2002, we included consecutive, neurologically intact adult patients suspected of having an LGG, demonstrating non-enhancing supratentorial lesions without edema or mass effect on MRI, and in whom all treatment (including a diagnostic biopsy) was deferred. Till January 1, 2003, patients were surveyed clinically and radiologically (contrast-enhanced MRI and ¹H-MRSI). Patients who showed progression on clinical examination and/or MRI were denoted as progressive disease. Other patients were denoted as stable disease. A decrease in NAA/CHO ratio of 20% compared to the baseline value was considered as indicative for progression on ¹H-MRSI. We included 14 patients with suspected LGG. Seven patients demonstrated progressive disease during the follow-up period, preceded or accompanied by concomitant ¹H-MRSI changes in five patients. Four of these five patients were operated on within the follow-up interval. The histological diagnosis demonstrated high-grade glioma in three and LGG in one patient. In the other two patients with progressive disease, no progression was found on ¹H-MRSI. The other seven patients demonstrated stable disease, but four of them showed progression on ¹H-MRSI. Our data do not show convincing evidence that ¹H-MRSI contributes to adequate monitoring and follow-up of patients with suspected LGG. Future research should preferably include pathological data at the time of ¹H-MRSI changes.     

Fulminant recurrence of atypical hemolytic uremic syndrome during a calcineurin inhibitor-free immunosuppression regimen

Recurrence of hemolytic uremic syndrome (HUS) after kidney transplantation is frequent, occurring almost exclusively in patients with atypical HUS, which is not caused by Escherichia coli gastroenteritis and in which diarrhea is absent. Calcineurin inhibitors are associated with recurrence of HUS. In two children who underwent living donor kidney transplantation for atypical HUS, we pre-emptively employed sirolimus in a calcineurin inhibitor-free immunosuppression regimen. Both children had excellent early graft function, yet both developed severe recurrent disease and subsequently lost their grafts. Avoidance of calcineurin inhibitors did not prevent recurrence of severe HUS and graft loss. Transplantation for severe atypical HUS remains problematic.     

Not so FAST

BACKGROUND: Focused assessment with sonography for trauma (FAST) as a screening tool in the evaluation of blunt abdominal trauma will lead to underdiagnosis of abdominal injuries and may have an impact on treatment and outcome in trauma patients. METHODS: From October 2001 to June 2002, a protocol for evaluating hemodynamically stable trauma patients with suspected blunt abdominal injury (BAI) admitted to our institution was implemented using FAST examination as a screening tool for BAI and computed tomographic (CT) scanning of the abdomen and pelvis as a confirmatory test. At the completion of the secondary survey, patients underwent a four-view FAST examination (Sonosite, Bothell, WA) followed within 1 hour by an abdominal/pelvic CT scan. The FAST examination was considered positive if it demonstrated evidence of free intra-abdominal fluid. Clinical, laboratory, and imaging results were recorded at admission, and FAST examination results were compared with CT scan findings, noting the discordance. RESULTS: Patients with suspicion for BAI were evaluated according to protocol (n = 372). Thirteen cases were excluded for inadequate FAST examinations, leaving 359 patients for analysis. There were 313 true-negative FAST examinations, 16 true-positives, 22 false-negatives, and 8 false-positives. Using CT scanning as the confirmatory test for hemoperitoneum, FAST examination had a sensitivity of 42%, a specificity of 98%, a positive predictive value of 67%, a negative predictive value of 93%, and an accuracy of 92%; chi analysis showed significant discordance between FAST examination and CT scan (5.85%, < 0.001). Six patients with false-negative FAST examinations required laparotomy for intra-abdominal injuries; 16 patients required admission for nonoperative management of injury. Of the 313 true-negative FAST examinations, 19 patients were noted to have intra-abdominal injuries without hemoperitoneum and 11 patients were noted to have retroperitoneal injuries. CONCLUSION: Use of FAST examination as a screening tool for BAI in the hemodynamically stable trauma patient results in underdiagnosis of intra-abdominal injury. This may have an impact on treatment and outcome in trauma patients. Hemodynamically stable patients with suspected BAI should undergo routine CT scanning.     

Intravenous immunoglobulin and thymoglobulin facilitate kidney transplantation in complement-dependent cytotoxicity B-cell and flow cytometry T- or B-cell crossmatch-positive patients

BACKGROUND: The aim of this study was to investigate the effect of Thymoglobulin and intravenous immunoglobulin (i.v.IG) therapy on the clinical outcome of a putatively high-risk group of kidney transplant recipients who have positive B-cell complement-dependent cytotoxicity (CDC) along with positive T- or B-cell flow cytometry (FC) crossmatch results. METHODS: We prospectively studied the effects of i.v.IG and Thymoglobulin induction treatment in B-cell CDC, and T- or B-cell FC crossmatch-positive kidney transplant recipients (seven women and one man; mean age, 43+/-12 years). RESULTS: Mean peak panel-reactive antibody (PRA) was 47+/-32. Three patients had donor-specific antibody by flow PRA (two anti-DR4 and one anti-A2). Each recipient received induction treatment with i.v.IG 100 mg/kg for 3 days and Thymoglobulin 1.5 mg/kg for 5 days after transplantation. No acute cellular rejections occurred during a median follow-up of 15 months (range, 12-17 months). Only one acute humoral rejection occurred 8 days after transplantation, which responded to plasmapheresis, i.v.IG, and rituximab. One allograft was lost because of polyoma nephritis. Patient survival was 100% and allograft survival was 88%. CONCLUSION: Our results indicate that i.v.IG and Thymoglobulin induction treatment may facilitate kidney transplantation in B-cell CDC and T- or B-cell FC crossmatch-positive patients.     

Interactions among proteins and hydrophobically modified polyelectrolytes

A special class of hydrophobically modified polyelectrolytes was studied wherein poly(acrylic acid) (PAA) was conjugated with Pluronic F127 NF surfactant. The Pluronic-PAA copolymer solutions form gels at low concentrations when exposed to bodytemperature. Such gels possess enhanced retention in topical applications. Circular dichroism spectra indicate that tertiary structures of human insulin, haemoglobin, and albumin were stabilized in solutions of Pluronic-PAA. Aggregation of insulin in gelled solutions of Pluronic-PAA was impeded as demonstrated in shaking tests. The presence of Pluronic-PAA hindered the insulin degradation by alpha-chymotrypsin by at least 7-fold. Extraction of calcium ions from trypsin by Pluronic-PAA led to the dramatic changes in the tertiary structure and total loss of enzymatic activity, suggesting that Pluronic-PAA could inhibit tryptic degradation of proteins.     

Study of the Breakup Under Shear of a New Thermally Reversible Water-in-Oil-in-Water (W/O/W) Multiple Emulsion

Purpose. Thickening of the external aqueous phase of W/O/W multiple emulsions is essential to increase the release under shear. However, it leads to globules bursting during fabrication. To reduce this problem, we have tested a novel thermally reversible hydrogel, EMP hydrogel. This way, the corresponding multiple emulsion (EMPME) would gel only at skin temperature, which may increase the active ingredient delivery when topically applied. Methods. Samples were sheared at different shear rates and temperatures (20, 30, and 35°C) with a controlled rheometer. A granulometric analysis was then performed with a laser diffraction granulometer, to assess the break up as a function of the shear rate at the three temperatures. Conductometric measurements (CDM 230 conductometer) provided the corresponding release curves. Results. As we expected, EMPME exhibited a thermally reversible behavior. Compared to a reference emulsion thickened by carbopol, this new thermo–sensitive multiple emulsion displayed higher break up and fraction released at 35°C. Conclusion. The first thermally reversible multiple emulsion has been developed in the present work. This one presents interesting advantages: (1) an easy fabrication process with a higher entrapment yield and (2) a higher fraction released at 35°C compared with the reference emulsion.     

Role of protease-activated receptor 1 in tumor metastasis promoted by tissue factor

Tissue factor (TF) is a transmembrane glycoprotein that complexes with factor VIIa to initiate blood coagulation. We previously reported that expression of high levels of TF in a human melanoma cell line promotes metastasis. Both the cytoplasmic domain of TF and its extracellular domain complexed with factor VIIa are required for the metastatic effect. To further explore the mechanism of TF-mediated metastasis, we investigated the possibility that a protease-activated receptor (PAR) might play a role. For this purpose, we first determined the expression levels of the known PARs (PAR1-4) in a human melanoma cell line, SIT1, that has low endogenous levels of TF and low metastatic potential. We found negligible levels of all of the known PARs and transfection of this cell line with human TF cDNA did not alter expression of the known PARs. To study the possible role of PAR1 in TF-mediated metastasis, we prepared a panel of transfected cell lines with varying levels of TF and PAR1. Our studies show that TF promotes metastasis by a pathway that does not involve high expression of known PARs by tumor cells. In addition, while overexpression of PAR1 is insufficient to induce metastasis in cells with low TF expression, it enhances the metastatic potential of cells with high TF expression, indicating a possible synergy between TF and PAR1 in promoting metastasis.     

Safety of using hepatitis B virus core antibody or surface antigen-positive donors in kidney or pancreas transplantation

Hepatitis B virus core antibody (HBcAb) or surface antigen (HBsAg)-positive organ donors have the potential to transmit infection to transplant recipients. We investigated the safety of using HBcAb(+) or HBsAg(+) donors in kidney or pancreas transplant recipients with 1 yr lamivudine prophylaxis. While HBsAb(-) recipients of HBcAb(+) donors received prophylaxis, HBsAb(+) recipients did not. HBsAg(+) organs were only used in patients who were both HBcAb and HBsAb(+). Forty-six patients received HBcAb(+) and four received HBsAg(+) organs (47 kidney, two pancreas, and one kidney/pancreas). All but one recipient were HBsAg(-), 25 were HBsAb(+), and 19 HBcAb(+). During a median 36 months of follow-up (range 6-66 months), with 43 of a total 50 patients having at least 1 yr follow-up and were off lamivudine, and none of the patients developed hepatitis B viremia or seroconversion to HBsAg or HBsAb(+). These results suggest that HBcAb(+) or HBsAg(+) organs can be used safely in selected recipients with lamivudine prophylaxis without requiring hepatitis B immunglobulin.     

A Comparison of the Prevalence of Lead-Contaminated Imported Chinese Ceramic Dinnerware Purchased Inside Versus Outside Philadelphia's Chinatown

Lead-contaminated ceramics can be a clinically significant source of lead poisoning, with the potential to cause illness in children and adults; one death in a child has been described. We hypothesized that the prevalence of lead-contaminated ceramics would be higher within Chinatown versus outside of Chinatown. The study was a prospective observational cross-sectional study. Two areas were defined geographically as being within and outside of Philadelphia''s Chinatown, and a predefined number of items were purchased in each area. Each item was screened for lead utilizing a colorimetric testing swab. Positive items were leached for lead using the ASTM C738-94 protocol for lead level quantification. The primary outcome was the prevalence of ceramics not compliant with the FDA standard for leachable lead within and outside of Philadelphia''s Chinatown. A total of 132 items were purchased, 46 outside of and 86 within Chinatown. More lead-positive items originated within Chinatown than outside of Chinatown [five positive items, 5.8 % prevalence within Chinatown (95 % confidence interval, CI, 2.5–12.9 %), and zero positive, 0 % prevalence outside of Chinatown (95 % CI 0–7.5 %)]. However, this difference was not found to be statistically significant (P = 0.1624). The leachable lead-positive items were up to 40-fold the acceptable FDA levels. Testing a larger number of items may demonstrate a significant source of lead exposure.