Immunocryosurgery for basal cell carcinoma: results of a pilot, prospective, open-label study of cryosurgery during continued imiquimod application

Background/aim  Theoretical considerations support the combination of cryosurgery and topical imiquimod to treat basal cell carcinomas (BCC). The aim of the present study was to test the feasibility and efficacy of 'cryosurgery during continued imiquimod application' ('immunocryosurgery') to treat 'high-risk-for-recurrence' BCCs.
Methods  Thirteen patients with 21 biopsy-proven tumours (4 of 21 relapses after prior surgery) were included. After 2–5 weeks (median, 3) of daily 5% imiquimod cream application, the tumours were treated by liquid N₂ cryosurgery (spray, two cycles, 10–20 s) and imiquimod was continued for additional 2–12 weeks (median, 4). The outcome after at least 18 months of follow-up (18–24 months) is currently reported.
Results  Nineteen of 21 tumours responded promptly to immunocryosurgery; two tumours required additional treatment cycles to clear. Thus, the clinical clearance rate was 100%. Only 1 of 21(5%) tumour relapsed after at least 18 months of follow-up (cumulative efficacy: 95%).
Conclusions  'Immunocryosurgery' is a promising non-surgical combination modality to treat 'high-risk-for-recurrence BCCs'. Initial evidence is suggestive of an at least additive effect of the two combined modalities. Further studies comparing immunocryosurgery directly with cryosurgery and imiquimod monotherapies will confirm the reported results.     

Effects of exercise on behavioral sensitivity to carbamate cholinesterase inhibitors

The interaction between exercise and drug response has not been studied extensively. The present study examined the relationship between both acute (15 minute) and chronic (10 week) treadmill exercise and behavioral response to the carbamates physostigmine and pyridostigmine. Rats trained on an operant task under a multi-component FR30 schedule were used to evaluate the interaction between exercise and performance following drug administration. The direct effects of both 10 weeks of exercise conditioning and a moderate exercise challenge, as well as the interaction between two were assessed. Results obtained with physostigmine show that acute exercise increased behavioral sensitivity. Chronic exercise resulted in behavioral tolerance. These results are consistent with previously reported studies of centrally acting compounds. In contrast, pyridostigmine, which has little or no central activity, produced no behavioral changes. This result was constant over exercise conditions.     

Increased salt retention and hypertension from non-steroidal agents in the elderly

We studied blood pressure and natriuretic responses to acute salt loading, and the effect of non-steroidal anti-inflammatory agents on these responses, in five healthy normotensive women aged 65 to 71 years. Five women aged 25 to 31 years acted as controls. Intravenous saline loading, with and without prior ingestion of ibuprofen, was 15 ml/kg/h for 3 h. Baseline blood pressures were higher in the elderly. Saline infusion without ibuprofen raised systolic blood pressure (SBP) by about 25 mmHg in the older group only. Ibuprofen increased baseline SBP in the elderly (129 +/- 6 vs. 116 +/- 5 mmHg, p < 0.05). Saline loading after ibuprofen again raised blood pressure by about 25 mmHg in the elderly only. The elderly group showed markedly increased sodium excretion during saline loading, but this was reduced by ibuprofen. Ibuprofen had no effect on SBP or sodium excretion in controls. Ageing appears to increase susceptibility to salt retention and hypertension from non-steroidal anti-inflammatory agents.      

Ascending general visceral pathways within the brainstems of two teleost fishes: Ictalurus punctatus and Carassius auratus.

The primary general visceral nucleus in goldfish (Carassius auratus) and catfish (Ictalurus punctatus) is located at the ventroposterior boundary of the vagal gustatory lobe and receives coelomic visceral, but not gustatory inputs. The neuronal tracer horseradish peroxidase (HRP) was employed to visualize sources of input to and ascending projections from the primary general visceral nucleus in these species. In addition, immunocytochemical techniques were utilized to define the cytological divisions within the pontine gustatory-visceral complex. The pontine secondary visceral nuclei in both catfish and goldfish contains numerous somata and fibers immunoreactive for calcitonin gene-related peptide (CGRP). In contrast, the secondary gustatory nuclei are devoid of fibers and cells immunoreactive for CGRP. In both the goldfish and the channel catfish, the primary general visceral nucleus receives input from the vagal gustatory lobe, as well as the medullary reticular formation. In the channel catfish, the primary general visceral nucleus projects bilaterally to the secondary visceral nucleus, which lies rostrolateral to the secondary gustatory nucleus in the dorsal pons. Fibers cross the midline via the rostral part of the isthmic commissure. Injection of HRP into the primary general visceral nucleus of a goldfish labels ascending fibers that project to a secondary visceral nucleus situated ventral, lateral, and rostral to the secondary gustatory complex. In general, the results indicate that general visceral systems ascend in parallel to gustatory systems within the brainstem, and that general visceral but not gustatory nuclei are immunoreactive for the peptide CGRP.     

Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.      

Spinocerebellar ataxia type 7 (SCA7): a neurodegenerative disorder with neuronal intranuclear inclusions

Autosomal dominant cerebellar ataxia with progressive macular degeneration is caused by a CAG/glutamine repeat expansion in the SCA7 gene/protein. Neuronal intranuclear inclusions were detected in the brain of an early onset SCA7 case with the 1C2 antibody directed against an expanded polyglutamine domain. Nuclear inclusions were most frequent in the inferior olivary complex, a site of severe neuronal loss in SCA7. They were also observed in other brain regions, including the cerebral cortex, not considered to be affected in the disease. Using confocal microscopy we showed that some inclusions were ubiquitinated, but to varying degrees, ranging from <1% in the cerebral cortex to 60% in the inferior olive. In addition, we also observed cytoplasmic staining using the 1C2 antibody, particularly in the supramarginal gyrus, the hippocampus, the thalamus, the lateral geniculate body and the pontine nuclei. These data confirm that the presence of intranuclear inclusions in neurons is a common characteristic of disorders caused by CAG/polyglutamine expansions, but unlike what has been reported for Huntington's disease, SCA1 and SCA3/MJD, in SCA7 the inclusions were not restricted to the sites of severe neuronal loss.      

Phenotypic characterization of human chondrocyte cell line C-20/A4: a comparison between monolayer and alginate suspension culture

DNA microarray analysis was used to investigate the molecular phenotype of one of the first human chondrocyte cell lines, C-20/A4, derived from juvenile costal chondrocytes by immortalization with origin-defective simian virus 40 large T antigen. Clontech Human Cancer Arrays 1.2 and quantitative PCR were used to examine gene expression profiles of C-20/A4 cells cultured in the presence of serum in monolayer and alginate beads. In monolayer cultures, genes involved in cell proliferation were strongly upregulated compared to those expressed by human adult articular chondrocytes in primary culture. Of the cell cycle-regulated genes, only two, the CDK regulatory subunit and histone H4, were downregulated after culture in alginate beads, consistent with the ability of these cells to proliferate in suspension culture. In contrast, the expression of several genes that are involved in pericellular matrix formation, including MMP-14, COL6A1, fibronectin, biglycan and decorin, was upregulated when the C-20/A4 cells were transferred to suspension culture in alginate. Also, nexin-1, vimentin, and IGFBP-3, which are known to be expressed by primary chondrocytes, were differentially expressed in our study. Consistent with the proliferative phenotype of this cell line, few genes involved in matrix synthesis and turnover were highly expressed in the presence of serum. These results indicate that immortalized chondrocyte cell lines, rather than substituting for primary chondrocytes, may serve as models for extending findings on chondrocyte function not achievable by the use of primary chondrocytes.     

Severe early malnutrition and DRL performance in the rat

Rats with a history of severe early malnutrition (6% casein) were compared to well-fed control animals on an ascending series of DRL values ranging from 5 to 60 seconds. The 6% rats who were dietarily-rehabilitated at weaning did not differ from control animals in efficiency, responses per reinforcement or response rate. In contrast, rats chronically exposed to 6% diets performed so poorly during training with continuous reinforcement that they did not advance to even the first DRL (5-sec) condition. These findings show that severely-undernourished rats can perform within normal limits on even high DRL values, provided they are well trained and that they have adequate nutritional rehabilitation.