The Use of Diphenylcyclopropenone in the Treatment of Recalcitrant Warts

Background: The treatment of recalcitrant palmoplantar and periungual warts using topical immunotherapy with diphenylcyclopropenone (DPC) was reviewed retrospectively over a seven-year period. Methods: Two hundred eleven patients were sensitized during this time. The patients consisted of 90 males and 121 females and were between 5 and 78 years old. Twenty-three patients were lost to followup. Of the remaining, 4 were undergoing treatment at the time of evaluation, 1 patient failed sensitization, and 1 patient became pregnant. Four discontinued because of side effects, 3 because of financial reasons, and 18 patients discontinued treatment prior to completing the minimum required applications (defined as 6), producing a dropout rate of 12% (25/211). Three patients had additional treatment during the course of DPC and were not included in the study. The remaining 154 patients were classified as nonresponders or responders. Results: The responders consisted of 135 individuals (87.7%) that had complete clearance of warts. Reported adverse effects were local and included with pruritus (15.6%), with blistering (7.1%), and with eczematous reactions (14.2%). The majority of the patients tolerated the treatment very well. One patient developed local impetigo. Patients had an average of 5 treatments over a 6-month period. Conclusions: Topical immunotherapy using DPC is an effective treatment option for recalcitrant warts. It should be considered as first-line treatment for warts based on its high response rate, absence of scarring, and painless application.     

Phase 1 study to identify tumour hypoxia in patients with head and neck cancer using technetium-99m BRU 59-21

The aim of this study was to assess the safety and biodistribution of technetium-99m BRU 59-21, a novel radioactively labelled 2-nitro-imidazole hypoxic marker, in head and neck cancer patients and to correlate uptake with pimonidazole staining. (99m)Tc-BRU 59-21 was administered intravenously (mean dose 824 MBq, range 780-857 MBq) to ten head and neck cancer patients scheduled for primary surgery, and whole-body images and SPET scans were then obtained. Uptake of radioactivity in the regions of interest was determined and tumour to normal tissue ratios were calculated after correlative evaluation with MRI/CT. Twelve to 16 h before surgery (up to 2 weeks after the scan), patients received pimonidazole intravenously. Tumour sections were stained immunohistochemically for pimonidazole binding. No serious adverse events were reported. In five patients there were ten adverse events, which were mild in intensity and resolved completely without intervention. Uptake of (99m)Tc-BRU 59-21 was observed in eight of the ten primary tumours. Tumour to normal tissue ratios on the SPET scans for primary tumour and lymph nodes increased from 1.8 (range 0.9-2.7) to 2.1 (range 0.8-3.7) between 30 min and 3 h post injection. Tumour to normal tissue ratios in the primary tumour were significantly correlated with pimonidazole staining for SPET scans performed 30 min and 3 h post injection ( P=0.016 and P=0.037, respectively). When primary tumour and involved lymph nodes were considered in conjunction, correlation between the tumour to normal tissue ratio and pimonidazole staining was observed for early ( P<0.001) but not for late SPET scans ( P=0.076). However, late scans showed better tumour delineation than early scans. Administration of (99m)Tc-BRU 59-21 in head and neck cancer patients appears to be safe and feasible. Uptake and retention in tumour tissue was observed, suggestive of tumour hypoxia, and this was supported by correlations with staining for the hypoxic marker pimonidazole.     

Intravenously administered short interfering RNA accumulates in the kidney and selectively suppresses gene function in renal proximal tubules.

Different gene-silencing methods, like antisense and short interfering RNA (siRNA), are widely used as experimental tools to inhibit gene expression. In the present study, the in vivo behavior of siRNA in rats and siRNA-mediated silencing of genes in the renal proximal tubule were investigated. To study the biodistribution of siRNA, rats were injected i.v. with radiolabeled siRNA or radiolabel alone (control), and scintigraphic images were acquired at different time intervals postinjection. The siRNA preferentially accumulated in the kidneys and was excreted in the urine. One hour after injection, the amount of siRNA present in both kidneys (1.7 +/- 0.3% of injected dose/g tissue) was on average 40 times higher than in other tissues (liver, brain, intestine, muscle, lung, spleen, and blood). Besides the biodistribution, the effect of siRNA on multidrug resistance protein isoform 2 (Mrp2/Abcc2, siRNAMrp2) in renal proximal tubules was investigated. Mrp2 function was assessed by measuring the excretion of its fluorescent substrate calcein in the isolated perfused rat kidney. Four days after administration, siRNAMrp2 reduced the urinary calcein excretion rate significantly (35% inhibition over the period 80-150 min of perfusion). This down-regulation was specific because another siRNA sequence directed against a different transporter in the proximal tubule, Mrp4 (Abcc4, siRNAMrp4), did not alter the Mrp2-mediated excretion of calcein. In conclusion, siRNA accumulates spontaneously in the kidney after i.v. injection, where it selectively suppresses gene function in the proximal tubules. Therefore, i.v. administered siRNA provides a novel experimental and potential therapeutic tool for gene silencing in the kidney.     

Microsatellite alterations in head and neck squamous cell carcinoma and relation to expression of pimonidazole, CA IX and GLUT-1.

BACKGROUND AND PURPOSE: Because the locoregional control for HNSCC is still disappointing, research efforts focus on the exploration of new molecular markers located in both tumour and microenvironment, which could help stratify patients. The aim of the present work was therefore first to assess microsatellite alterations and hypoxia in HNSCC as possible molecular markers. Second, a relation between both was investigated, as hypoxia is known to select for genetic alterations. MATERIAL AND METHODS: Forty-eight patients with advanced HNSCC treated by surgery+/-radiotherapy were included. MSI and LOH were investigated with microsatellite markers using automatic fragment analysis. The presence of hypoxia was assessed by immunohistochemistry for pimonidazole, CA IX and GLUT-1. The mutual relationship between MSI/LOH and hypoxia was evaluated. RESULTS: No MSI was detected in this patient group. LOH occurred mostly on chromosomal arms 3p, 5q, 9p, 17p and 17q. Patients with LOH at D17S799, located in the near environment of p53, showed a higher CA IX expression (p=0.01). CONCLUSIONS: LOH is a possible molecular marker in HNSCC. The positive correlation between LOH at D17S799 and CA IX is in full concordance with previous publications linking hypoxia to selective pressure on the p53 gene.     

Eosinophilic granuloma of the bone: Ultrasonographic imaging

Eosinophilic granuloma is a rare disease of unknown aetiology that affects the bones. Two cases of eosinophilic granuloma are presented. Ultrasonographic, CT and histopathological findings are described. Ultrasonographic‐guided core‐needle biopsy was performed. Treatment was initiated by installing steroid suspension into the lesions, which resulted in complete healing of the bone in both cases.     

Recurrence of blackwater fever: triggering of relapses by different antimalarials

Five cases of blackwater fever (BWF) are described, all of whom had a history of recent quinine therapy. In two cases a second haemolytic crisis was induced by halofantrine, in one case also a third. Increasing frequency of this syndrome with its dramatic clinical presentation is to be expected as imported P. falciparum infection, parasite resistance to chloroquine and the use of quinine and other related antimalarials become more frequent.     

Complexes of technetium-99m with tetrapeptides containing one alanyl and three glycyl moieties

Recently, we have shown that tetrapeptides can be efficiently labelled with technetium-99m by direct labelling at alkaline pH. Tetrapeptides can be considered derivatives of mercaptoacetyltriglycine (MAG3) in which the mercaptoacetyl moiety is replaced by an amino acid residue. In view of the interesting biological properties of some C-methyl substituted derivatives of^99mTc-MAG3, we have now synthesised and evaluated the complexes of^99mTc with tetrapeptides containing three glycyl (G) moieties and oned- orl-alanyl (A) moiety. In mice,^99mTc-l-GAGG,^99mTc-d-GGAG and^99mTc-l-GGAG showed a rapid and high renal excretion, comparable to that of^99mTc-MAG3. Renal handling was somewhat reduced for isomersd andl of^99mTc-AGGG and^99mTc-d-GAGG and markedly inferior for^99mTc-l-GGGA and^99mTc-d-GGGA. In the baboon,^99mTc-l-AGGG,^99mTc-d-AGGG and^99mTc-l-GAGG showed a comparable or even higher 1-h plasma clearance than^99mTc-MAG3.^99mTc-d-GAGG,^99mTc-l-GGAG and^99mTc-d-GGAG were characterised by a lower plasma clearance and the clearance of^99mTc-l-GGGA and^99mTc-d-GGGA was remarkably low. The three^99mTc-labelled tetrapeptides with the highest plasma clearance in a baboon were compared with^99mTc-MAG3 in a human volunteer.^99mTc-l-AGGG and^99mTc-l-GAGG had a roughly similar plasma clearance as^99mTc-MAG3. The clearance of^99mTc-d-AGGG was significantly lower and liver uptake was clearly visible with this compound. Left kidney renograms of^99mTc-l-AGGG and^99mTc-d-AGGG indicated moderate kidney accumulation. On the other hand, the renogram obtained after injection of^99mTc-l-GAGG had an excellent shape and the maximum kidney concentration was slightly higher than for^99mTc-MAG3. These results show the importance of the position of the methyl substituent on the^99mTc-tetrapeptide with respect to its biological behaviour.     

Increased carotid wall thickening after radiotherapy on the neck

Patients treated for head and neck tumours with local radiotherapy (RT) on the neck harbour an increased risk of stroke. This may be due to accelerated atherosclerotic changes within the RT-field; however, the real impact of local RT on the carotid artery remains debatable. The aim of the present study was to assess the difference in carotid wall thickness (intima-media thickness) in 42 unilaterally irradiated parotid tumour patients by performing B-mode ultrasonography. A mean difference in intima-media thickness (IMT) of the irradiated compared with the non-irradiated carotid artery of 0.30 mm (P=0.031) was found. A significant correlation was established with a longer post-RT interval (P=0.008). RT on the neck is associated with increased thickening of carotid IMT. Screening and treatment of additional cerebrovascular risk factors which contribute to further IMT thickening and stroke development is recommended, especially in radiotherapy patients with a favourable prognosis.     

Congenital hemangiomas: rapidly involuting and noninvoluting congenital hemangiomas

While infantile hemangiomas are a very common lesion seen in infants and young children, congenital hemangiomas are much more rare and have been only recently described. Two types of congenital hemangiomas exist: rapidly involuting congenital hemangiomas and noninvoluting congenital hemangiomas. The goal of this article is to describe rapidly involuting and noninvoluting congenital hemangiomas as they differ from infantile hemangiomas in their presentation, natural history, histopathologic features, and treatment.