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.      

Prostatectomy by transurethral balloon Laserthermia™ (PROSTALASE™) in the canine

Prostatectomy by transurethral balloon Laserthermia (PROSTA-LASE?) was performed in a canine model. This balloon device monitored by transrectal ultrasound can cylindrically irradiate with a laser beam. The treatment was performed in 8 canines using 15 watts for 20 minutes at 60°C at a 5 mm depth of the prostate from the urethral surface. Immediately following the laser therapy, an area of coagulation necrosis was observed around the urethra to a depth of 4–5 mm from the surface. After 1 week, cavitation formation was seen in 3 or 4 canines by ultrasound, and the urethral reepithelialization was shown in 1 of 2 canines. After 2 weeks, cavitation formation was observed in both canines, and the urethra was completely reepithelialized in one canine. There was no tissue damage in the bladder neck of urethral sphincter and no urinary incontinence in any animal. This system is thought to be simple and, satisfactorily performed, is an effective transurethral prostatectomy. © 1994 Wiley-Liss, Inc.     

Systemic effects of inflammation in bronchiectasis

A group of bronchiectatic subjects in the clinically stable state were studied for systemic evidence of inflammation. The following parameters were evaluated: body weight, serum albumin, serum globulin, serum alpha 1-antitrypsin (alpha 1 AT) and peripheral white cell count. For serum albumin and globulin, comparison was made between subjects with bronchiectasis and control subjects with no known pulmonary disease matched for sex and age, and for serum alpha 1 AT and peripheral white cell count, matched for smoking habit as well. The bronchiectatic subjects showed systemic effects of inflammation as indicated by lower body weight and serum albumin (P less than 0.01), higher serum globulin (P less than 0.001), serum alpha 1 AT (P less than 0.05) and total leucocyte count (P less than 0.05). Differential white cell count showed that the elevation was distributed in most cell types. Correlation matrix was done for the above systemic parameters and indices of airway inflammation including sputum volume, purulence, and polymorph count and FEV1. There was an inverse correlation between total peripheral WBC count and FEV1 in percentage of predicted (P less than 0.01), and a positive correlation between sputum purulence and sputum polymorph score (P less than 0.05). This suggests that host peripheral leucocyte response may be a factor in the determination of lung function.     

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.      

Genetic imbalances in pleomorphic xanthoastrocytoma detected by comparative genomic hybridization and literature review.

Pleomorphic xanthoastrocytoma (PXA) is a rare, low-grade astrocytic tumor found in the central nervous system. Histologically, the tumor is characterized by markedly pleomorphic and lipidized cells. Although most of the patients have a favorable prognosis, a small number of cases undergoing recurrence or progression to anaplastic astrocytoma were reported. Very few genetic studies have been performed on PXA because of its rarity and the pathogenesis of this neoplasm is largely unknown. In order to provide an overview of genetic alterations in PXA, we performed comparative genomic hybridization to identify chromosomal imbalances (DNA gains and losses) in three cases of PXA. Genetic imbalance was detected on at least one chromosome for each case. One case, which revealed multiple genetic alterations, showed a poor prognosis. DNA gain on chromosome 7 and loss on 8p were demonstrated in two of three cases, suggesting that the candidate gene(s) located on these regions may play a role in the development of PXA. Further studies are needed to identify the residing candidate genes that are involved in the tumorigenesis of PXA. In addition, the histopathological features and previous genetic studies on PXA are reviewed.     

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.      

Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease

Background

Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD), and are especially prevalent in the Ashkenazi Jewish (AJ) population. However, most studies on GBA in AJ genotype only seven selected Gaucher-associated pathogenic variants rather than sequencing the whole gene, which may leave carriers of PD-associated GBA variants undiscovered.

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.