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.     

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.      

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.      

Interleukin-1-like activity in human cerebrospinal fluid

Cerebrospinal fluid (CSF) samples were obtained from patients undergoing myelography, who were subsequently diagnosed as having degenerative neck or back disease with no significant CNS inflammation. Using a mitogen co-stimulation assay with mouse thymocytes, or interleukin-1 (IL1) dependent interleukin-2 (IL2) secreting tumour cell line, these CSF samples were shown to contain an IL1-like activity, with predominant activity located in molecules with size 15 kDa and 30 kDa (Sephadex size chromatography). The results are discussed in light of data implicating a role for IL1 in other physiological functions.     

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.      

Enhanced interleukin 1 generation by monocytes in vitro is temporally linked to an early event in the onset or exacerbation of rheumatoid arthritis.

Twenty-one patients with rheumatoid arthritis (RA) and 12 age and sex matched healthy controls were examined for the ability of their monocytes (adherent cells, AC) to spontaneously secrete interleukin 1 (IL-1) and for their peripheral blood mononuclear cells (PBMC) to secrete interleukin 2 (IL-2) induced by Staphylococcal Protein A (SPA). All RA patients had PBMC which secreted normal amounts of mitogen induced IL-2 regardless of disease activity or disease history. However, AC from RA patients who had a recent (less than 6 months) onset of their disease, or exacerbation of existing RA, had enhanced spontaneous IL-1 secretion. AC from patients with equally active RA but with historically stable disease generated normal amounts of IL-1. Enhanced in vitro IL-1 generation by circulating monocytes is temporally linked to an early event in the onset of exacerbation of RA.     

Impaired release of a T-cell specific suppressor factor in rheumatoid arthritis.

Peripheral blood T cells from patients with rheumatoid arthritis (RA) and scleroderma (PSS) were assessed for their ability to release T-cell-specific suppressor activity (TRSA) upon incubation with a suppressor activating factor (SAF) derived from a human lymphoblastoid cell line (CEM). T cells from 11/20 (55%) RA patients exhibited impaired TRSA release in contrast to 1/12 (8%) of PSS patients. RA patients demonstrating impaired TRSA release exhibited more active arthritis than patients demonstrating normal TRSA release.     

Effects of lymecycline on Mycoplasma pulmonis-induced arthritis in mice

The effect of lymecycline treatment on arthritis in C3H mice produced 5 months previously by i.v. inoculation of Mycoplasma pulmonis was examined. Treatment had little effect on the severity of the clinical disease. However, there was a marked reduction the severity of the histopathological inflammatory reaction in joints from lymecycline-treated mice when compared with untreated controls. This reduction was associated with eradication of viable mycoplasmas from the joints. The findings suggest that persistent arthritis in C3H mice is due to the continued presence of viable M. pulmonis organisms in the joint tissues.     

Reactivity of T-cells from patients with rheumatoid arthritis to anti-CD3 antibody

The ability of an anti-CD3 monoclonal antibody (OKT3) to induce proliferation was examined in peripheral blood mononuclear cells (PBM) from 30 patients with rheumatoid arthritis (RA). Controls consisted of 10 patients with osteoarthritis, 12 patients with psoriatic arthritis, and 12 healthy subjects. The results revealed enhanced PBM reactivity in patients with active RA relative to inactive RA patients and all control groups. PBM of patients with mild/moderate clinical disease activity exhibited augmented anti-CD3 reactivity while those with severe disease demonstrated impaired reactivity. Enhanced reactivity was also observed in the active RA group using another anti-CD3 monoclonal antibody (Leu-4). Differences in anti-CD3 dose-response or time kinetics could not account for the results. Studies of enriched T-cell preparations revealed a markedly enhanced anti-CD3 reactivity of RA T-cells relative to normal control T-cells. Monocyte/T-cell mixing experiments revealed no enhanced reactivity of RA monocytes in the anti-CD3 response. RA T-cell preparations depleted of monocytes by limiting dilution reacted significantly more to anti-CD3 in the presence of IL-2 relative to controls. The enhanced reactivity could be accounted for in part by hyperreactivity of the OKT8-bearing subpopulation of T-cells.