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.      

Acute systemic heat stress increases glial fibrillary acidic protein immunoreactivity in brain: experimental observations in conscious normotensive young rats.

The possibility that astrocytes participate in the pathophysiology of thermal brain injury caused by systemic heat exposure was examined in conscious young rats. The temporal and regional pattern of the astrocytic response to thermal injury was characterized by demonstrating the immunoreactivity of glial fibrillary acidic protein (GFAP) using monoclonal antibody and avidin-biotin complex technique. Exposure of conscious young animals to heat at 38 degrees C for 4 h in a biological oxygen demand incubator resulted in a marked increase of the GFAP immunoreactivity in specific brain regions as compared with the intact controls. The intensity of the increased GFAP immunoreactivity was mainly noted in pons, medulla and cerebellum, followed by thalamus, hypothalamus, hippocampus and caudate nucleus. The cerebral cortex of heat-exposed animals showed only a mild increase in GFAP immunoreactivity which was predominantly concentrated in cingulate, parietal and pyriform cortices. The immunostaining in general was seen in the perivascular glia, within the neuropil and the glia limitans. This increase in GFAP immunoreactivity was absent in animals exposed to the same ambient temperature (38 degrees C) for 1 h and 2 h, or at a lower temperature (36 degrees C) for 4 h. These results show that (i) astrocytes actively participate in the pathophysiology of heat stress, (ii) endogenous thermal brain injury elicits activation and hypertrophy of astrocytes ("reactive gliosis") depending on the magnitude and duration of the ambient heat stimulus, and (iii) the astrocytic reaction (observed as increased GFAP immunostaining) could be induced much more rapidly within a very short survival period of 4 h, not reported earlier.     

Treatment feasibility of a digital tool for brief self-help behavioural therapy for insomnia (FastAsleep)

Cognitive behavioural therapy for insomnia is efficacious and recommended for insomnia, but availability is scarce. Cognitive behavioural therapy for insomnia self-help interventions could increase availability, especially if unguided. Optimizing cognitive behavioural therapy for insomnia methods and system user-friendliness, we developed a short, digital, self-help programme—FastAsleep—based on the behavioural components of sleep restriction and stimulus control. This study investigated its feasibility and preliminary effects. Thirty media-recruited participants with moderate to severe insomnia were assessed via telephone before using FastAsleep for 4 weeks, and were interviewed afterwards. Self-ratings with web questionnaires were conducted at screening, pre-, mid- and post-treatment, and at 3-month follow-up. Primary outcomes were feasibility (credibility, adherence, system user-friendliness and adverse effects), and secondary outcomes were changes in symptom severity (insomnia, depression and anxiety). Adherence was generally high, participants' feasibility ratings were favourable, and adverse effects matched previously reported levels for cognitive behavioural therapy for insomnia. Symptoms of insomnia decreased after the treatment period (Hedge's g = 1.79, 95% confidence interval = 1.20–2.39), as did symptoms of depression and anxiety. FastAsleep can be considered feasible and promising for alleviating insomnia symptoms among patients fit for self-care. Future controlled trials are needed to establish the efficacy of FastAsleep and its suitability in a stepped care model.     

Validation of Pouch Size Measurement Following the Swedish Adjustable Gastric Banding Using Endoscopy,MRI and Barium Swallow

Background: Pouch volume appears to be of major importance for subsequent weight loss following any gastric restriction type of surgery for morbid obesity. In order to be able to evaluate pouch volume following Swedish Adjustable Gastric Banding (SAGB), an endoscopic pouch volume classification system was designed in which pouch volume is classified in five categories. The aim of this study was to validate the endoscopic classification system using MRI and barium swallow as reference methods for pouch volume measurement. Methods: Twenty patients (13 women and seven men) were operated for obesity with SAGB. They were investigated a mean of 3 years (6 weeks-5.5 years) after surgery and had at that time lost a mean of 60 (12-112) kg. During the same afternoon they sequentially underwent endoscopy, MRI and barium swallow with an empty stomach. Results: The mean pouch volume measured with MRI was 70 ml (0-180 ml) and with barium swallow was 72 ml (0-195 ml). In 17/20 patients the volume as measured by MRI and barium swallow was in the same volume category as with endoscopy. The correlation measured according to Pearson was significant between endoscopy on one hand and MRI/barium swallow both independently and together (p < 0.001). Conclusion: Based on these results we are confident in using our endoscopic classification system for postoperative follow-up of pouch volume.     

Thyroid dysfunction after mantle irradiation of Hodgkin's disease patients

Thyroid dysfunction can develop in patients with Hodgkin's disease who are treated with mantle irradiation. During the period 1970-89, the records of 320 patients who received mantle irradiation and who had thyroid function tests (TFT) were retrospectively reviewed. The median age was 30 years (range, 7-69 years). The median mantle and thyroid dose was 36 Gy (range, 30-40 Gy) and 39.8 Gy (range, 32-65 Gy), respectively. Overall thyroid dysfunction was present in 39% of the patients. Clinical hypothyroidism was seen in 10% and biochemical hypothyroidism was noted in 25%. Hyperthyroidism was found in 4% of patients. Thyroid nodules had developed in six patients (2%), of which those in four patients were malignant. Age, sex, histological subtype, stage of disease, dose, lymphangiogram and treatment with chemotherapy were not significant factors in the development of thyroid dysfunction. The narrow dose range prevented adequate analysis of dose effect. The results indicate that the incidence of thyroid abnormalities is high enough to warrant regular TFT assessment with pre-irradiation levels and follow-up testing for life because the development of abnormalities can occur many years later. Thyroid examination should form part of the routine follow-up examination and any abnormality should be promptly investigated.     

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.     

The Cognitive Behavior Survey: Testing for Factorial Validity and Time Invariance Across Two Years of Medical School

Background: The Cognitive Behavior Survey (CBS) assesses learner behavior in healthcare-related fields. Purpose: The study aims were to evaluate the factorial validity of the CBS, which purports to measure three dimensions of learner behavior—conceptualization, reflection, and memorization—and propose and test an alternative model including its time invariance. Methods: The CBS was administered to 3 cohorts of medical students upon matriculation and at the end of their 1st and 2nd year. Results: Confirmatory factor analysis (CFA) did not support the original CBS model. Exploratory factor analysis (EFA) with an independent sample provided a new model. Retesting the EFA model using CFA with the original sample yielded a model with improved fit and time invariance. Conclusions: This study provides evidence for the original CBS 3-factor structure but requires alternative scoring for a time-invariant model.