Clinical significance of periportal tracking as an extrarenal manifestation of acute pyelonephritis

Purpose  

The purpose of this study was to evaluate whether hepatic periportal tracking (PPT) in patients with acute pyelonephritis correlates with the severity of pyelonephritis.     

Increased prevalence of human papillomavirus in hairs plucked from patients with psoriasis treated with psoralen-UV-A

BACKGROUND: Patients with psoriasis treated with psoralen-UV-A (PUVA) are at increased risk of skin cancer; however, the exact causes of this increased incidence are not well understood. It has been suggested that PUVA may increase expression of the tumorigenic agent human papillomavirus (HPV) in skin by directly stimulating virus replication, immune suppression, or both, thereby leading to skin cancer formation. OBJECTIVE: To determine whether HPV DNA prevalence in the skin is increased after long-term PUVA treatment. DESIGN: Screening for the presence of HPV sequences in DNA isolated from plucked body hairs of patients with psoriasis with a history of PUVA exposure and a history of skin cancer (group A), PUVA exposure and no history of skin cancer (group B), and no PUVA exposure and no history of skin cancer (group C). SETTING: University hospital.Patients and METHODS: Hair samples were obtained from 81 patients with psoriasis (56 men and 25 women; mean age, 52 years), including 16 in group A (mean number of PUVA exposures, 702), 35 in group B (mean number of PUVA exposures, 282), and 30 in group C. DNA was isolated from the hair samples and analyzed by polymerase chain reaction with the use of 2 nested primer systems specific for epidermodysplasia verruciformis-associated or related and genital or mucosal virus types, respectively. RESULTS: The rate of HPV DNA positivity was significantly higher in groups A (73% [11/15]) and B (69% [24/35]) than in group C (36% [10/28]) (A + B vs C, P =.009; chi(2) test; age adjusted).Conclusion The prevalence of HPV in the skin (hair follicles) is increased in patients with psoriasis who have a history of PUVA exposure.     

Does insulin‐like growth factor 1 receptor (IGF‐1R) targeting provide new treatment options for chordomas? A retrospective clinical and immunohistochemical study

Scheipl S, Froehlich E V, Leithner A, Beham A, Quehenberger F, Mokry M, Stammberger H, Varga P P, Lazáry A, Windhager R, Gattenloehner S & Liegl B
(2012) Histopathology  60, 999–1003 Does insulin‐like growth factor 1 receptor (IGF‐1R) targeting provide new treatment options for chordomas? A retrospective clinical and immunohistochemical study Aims: The overall prognosis of chordoma is poor, and current treatment options are limited. The insulin‐like growth factor 1 receptor (IGF‐1R) pathway is important for cell signalling, and attractive for selective inhibition. We investigated the expression of IGF‐1R and its ligands, IGF‐1 and IGF‐2, in a series of 50 chordomas, in order to assess whether IGF‐1R‐signalling could be a potential target for specific inhibition in chordomas. Methods and results: Fifty chordomas (34 primary tumours, 16 recurrences) from 44 patients were evaluated immunohistochemically for the expression of IGF‐1R, IGF‐1 and IGF‐2. Thirty‐eight chordomas (76%) expressed IGF‐1R, 46 (92%) expressed IGF‐1 and 25 (50%) expressed IGF‐2. Semi‐quantitative analyses revealed a moderate to strong staining intensity in ≥50% of tumour cells for IGF‐1R, IGF‐1 and IGF‐2 in 18 (36%), 32 (64%) and eight (16%) chordomas, respectively. Tumour volume correlated significantly with IGF‐1R‐staining intensity in primary chordomas (P = 0.042). Conclusions: IGF‐1R and IGF‐1 are expressed in the majority of chordomas. IGF‐1 expression is much stronger than IGF‐2 expression. Patients whose chordomas show a moderate to strong staining intensity in ≥50% of tumour cells for IGF‐1R (36%) might benefit most from IGF‐1R targeting, particularly if they suffer from large and surgically non‐resectable chordomas.     

Prediction of time-averaged concentration of haemoglobin in haemodialysis patients.

BACKGROUND: Haemoglobin (Hb) concentration is not stable in most haemodialysis patients due to ultrafiltration-induced haemoconcentration. Pre-dialysis Hb concentrations might therefore significantly deviate from the time-averaged concentration (Hb-tac) which is more likely to represent the patients 'true' Hb. This study was performed to quantify these differences in our chronic haemodialysis population and to develop a formula for prediction of Hb-tac. METHODS: In 55 stable patients, serial blood samples were taken over a period of 2 weeks before and immediately after each haemodialysis as well as 30 min post-haemodialysis to account for post-dialytic fluid rebound. Hb-tac was calculated for every patient from the area under the time-dependent Hb curve. We compared the differences between Hb-tac and pre-dialysis Hb (Hb-pre) and various prediction formulae for Hb-tac generated by multiple linear regression analysis which included Hb-pre and post-dialysis Hb (Hb-post) and/or ultrafiltration rate (UFR). RESULTS: Mean Hb-pre after the long dialysis interval was significantly lower than after the short interval (11.47 vs 11.85 g/dl, P < 0.0001), both underestimating mean Hb-tac (11.97 g/dl). More interestingly, Hb-pre after the long interval deviated >0.5 g/dl from Hb-tac in 50% of measurements. After the short interval, 20% still lay outside this tolerance range. The best formula to predict Hb-tac was Hb-pre x 0.5 + Hb-post x 0.38 + 1.28 (6% outside +/- 0.5 g/dl). Hb-pre +(Hb-post - Hb-pre)/3 may be used for quick estimation of Hb-tac. CONCLUSIONS: Hb-tac can be predicted from pre- and post-dialysis blood samples after the short interval, using a simple new formula. Because Hb-tac more reliably reflects a 'true' Hb level of haemodialysis patients, it represents a potentially useful tool for future scientific and clinical work.     

Rituximab (anti-CD20 monoclonal antibody) as consolidation of first-line CHOP chemotherapy in patients with follicular lymphoma: a phase II study

Advanced stages of follicular lymphoma are deemed incurable by conventional approaches. Immunotherapy with the humanised monoclonal anti-CD20 antibody rituximab represents a new therapeutic option. The aim of our study was to determine the effectiveness and safety of rituximab in the consolidation setting of first-line treated patients with follicular lymphomas. Thus the goal was first to reduce tumour burden using the CHOP regimen as induction treatment followed by consolidation with rituximab administered on a standard 4 wk schedule at a dosage of 375 mg m-2 body surface area. Between August 1998 and April 2001, 41 patients were enrolled in the study. All patients were evaluable with regard to tumour response and toxicity. The overall remission rate in the intent-to-treat analysis was 100%. On subgroup analysis, 20 [83% (95% CI: 63-95%)] of the 24 patients with grade 1 or 2 histology entered complete remission (CR), in 10 cases (42%) after additional rituximab therapy. Rituximab thus led to CR in 10/14 patients [71% (95% CI: 42-92%)] who had merely achieved partial remission (PR) with CHOP. Of 16 evaluable patients with grade 3 histology (excluding one patient achieving CR on CHOP who refused further treatment with rituximab), 15 [94% (95% CI: 63-97%)] achieved CR, 13 (81%) of these while still receiving CHOP. Two of the three patients achieving only PR on CHOP entered CR following rituximab. Thirty-four patients (83%) continued to be in remission during a median follow-up period of 24.3 (9-40) months. Our data suggest that the use of rituximab for consolidation after CHOP may improve CHOP-induced remission and thus increase the CR rate. Furthermore, it was accompanied by a reduced rate of infusion-related side-effects.     

Cell surface expression of mouse macrosialin and human CD68 and their role as macrophage receptors for oxidized low density lipoprotein

We have previously identified a 94- to 97-kDa oxidized low density lipoprotein (LDL)-binding protein in mouse macrophages as macrosialin (MS), a member of the lamp family. Earlier immunostaining studies have shown that MS and its human homolog, CD68, are predominantly intracellular proteins. However, using sensitive techniques such as flow cytometry (FACS) and cell-surface-specific biotinylation, we now show that there is significant surface expression of these proteins. FACS analysis of intact cells using mAb FA/11 showed small but definite surface expression of MS in resident mouse peritoneal macrophages but this was greatly enhanced with thioglycollate elicitation. Biotinylation of intact cells and detergent-solubilized cell preparations followed by immunoprecipitation revealed 10–15% of the total MS content of elicited macrophages on the plasma membrane. Similar results were obtained with untreated RAW 264.7 cells. FACS analysis of intact THP-1 monocytic cells showed minimal surface expression of CD68 on unactivated cells (4% of total cell content). Stimulation with phorbol 12-myristate 13-acetate increased both surface and total CD68 expression considerably. Furthermore, the specific binding at 4°C and uptake at 37°C of ¹²⁵I-labeled oxidized LDL by activated THP-1 cells was inhibited by 30–50% by CD68 mAbs KP-1 and EBM-11. Thus, although the surface expression of MS/CD68 at steady-state represents only a small percentage of their total cellular content, these proteins can play a significant role in oxidized LDL uptake by activated macrophages in vitro and could contribute to foam cell formation in atherosclerotic lesions.