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.      

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.      

Spontaneous secretion of thyroid autoantibodies by cultured peripheral blood lymphocytes from patients with Hashimoto''s thyroiditis detected by micro-ELISA techniques

The spontaneous in vitro production of anti-thyroglobulin (aTg) and anti-microsomal (aM) antibodies by mononuclear cells (MNC) from patients with Hashimoto's thyroiditis (HT) was analysed by an ELISA detection system. MNC from 35 HT patients spontaneously produced detectable levels of both autoantibodies in vitro (i.e., without mitogenic or antigenic stimulation). aTg was quantified using a reference aTg IgG standard and ranged from 55 to 9,000 ng aTg. Specificity of aTg by ELISA was assessed using heterologous Tg antigen (Ag). Microsomal Ag obtained by gel filtration was far less contaminated with Tg than the ultracentrifugation pellet. Specificity of aM ELISA was assessed using insulinoma membrane as unrelated Ag and by blocking aM detection only with microsomal Ag. aM levels in the 35 supernatants ranged from 0.1 to 1.12 OD. A direct correlation was found between aM serum titres detected by haemagglutination and in vitro aM spontaneous production, but not for aTg. This lack of correlation for aTg might have biological relevance. Tg restimulation in vitro enhanced aTg production in only four out of 18 cases, of which only one was significant. This system provides a tool for studies of the immunoregulation of thyroid autoantibody formation in vitro.     

CT-Cephalometry—A study in Indian population

Determination of obstructive site in obstructive sleep apnoea (OSA) is of paramount importance is planning the management. Cephalometric evaluation of lateral X-rays when combined with clinical assessment and fibreoptic examination of the airway helps in locating the site of obstruction. The usual technique of cephalometry has been modified so as to give a better delineation of the soft tissues. Holding a 2mm card board in the mouth and using barium paste helped in more accurate calculations. Using our technique, various parameters have been quantified and a number of controls were studied and normal range derived. Further improvement in cephalometry has been done by using C.T. cephlometry topogram technique. A topogram is a scan done on a running table top cranio-caudally. Using the topogram technique 38 OSA patients were evaluated for all the parameters. The technique, its advantages over traditional cephalometry and the values obtained in the study are discussed in this paper.     

In vitro induction of anti-thyroid microsomal antibody-secreting cells in peripheral blood mononuclear cells from normal subjects

Secretion of immunoglobulin G (IgG) and IgM antithyroid microsomal antibodies (AMA) was induced in vitro by coculturing non-T cells (B lymphocytes) and autologous CD4 (helper/inducer) cells from normal subjects stimulated with pokeweed mitogen (PWM) or a combination of human thyroid microsomal antigen (McAg) and Staphylococcus aureus Cowan I (SAC) strain. With PWM stimulation, AMA production was induced in more IgM-secreting cells (AMA-M) than IgG-secreting cells (AMA-G). However, McAg plus SAC stimulation resulted in similar numbers of AMA-G- and AMA-M-secreting cells. PWM induced a significantly greater number of both AMA-M (and generalized IgM)-secreting cells than did McAg plus SAC, while the number of AMA-G-secreting cells induced by the two stimuli were similar. There were no significant differences between autologous or allogeneic CD4 cells from normal subjects or patients with autoimmune thyroid disease (AITD) when cocultured with B cells from normal subjects in terms of helper activity in the induction of AMA-M- or IgM-secreting cells with PWM stimulation. However, with McAg plus SAC, CD4 cells from patients with AITD induced a significantly greater number of AMA-M-secreting cells than did autologous or allogeneic CD4 cells from normal subjects. There was no difference in helper activity between autologous and allogeneic normal CD4 cells in the induction of generalized IgM-secreting cells regardless of the stimulus used. Normal autologous or allogeneic CD8 (suppressor/cytotoxic) cells cocultured with normal B cells and autologous CD4 cells suppressed the induction of AMA-M-secreting cells by PWM stimulation. On the other hand, CD8 cells from patients with AITD suppressed the induction of AMA-M-secreting cells significantly less effectively. All CD8 cells suppressed the induction of IgM-secreting cells equally well. We conclude that 1) B lymphocytes from normal subjects are capable of producing autoantibodies in vitro in the presence of CD4 cells; 2) the helper activity of CD4 cells from patients with AITD to induce AMA-M secreting cells is greater than that of normal CD4 cells with thyroid antigen stimulation; and 3) this helper activity may be due to relatively impaired suppressor activity in thyroid antigen-specific CD8 cells from patients with AITD, whereas the immunoregulatory function of CD8 cells from normal subjects appears to play an important role in the maintenance of self-tolerance.