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.     

Factors influencing the absorption of iron from soya-bean protein products

The absorption of iron from soya-bean (Glycine hispida)-based and milk-based infant formulas was assessed in 138 multiparous Indian women, using the erythrocyte utilization of radioactive Fe method. Fe absorption was significantly greater from the basal milk formula (1.5 g protein) than it was from the basal soya-bean formula (2.3 g protein), with geometric mean values of 0.083 and 0.044 respectively. Ascorbic acid markedly increased Fe absorption from the milk-based formula in a dose-dependent fashion. The increase was fivefold when the ascorbic acid:Fe ratio on a weight-for-weight basis was 6:1 and over tenfold when it was 20:1. In contrast, ascorbic acid had a less-marked effect on the absorption of Fe from the soya-bean-based formula, with only a two- to threefold increase at an ascorbic acid:Fe ratio of 20:1. The geometric mean Fe absorption from the soya-bean formula (1.27 mg Fe, 2.3 g isolated soya-bean protein (ISP] was somewhat less than that from the same amounts of ISP and ascorbic acid made up in milk (0.075 and 0.113 respectively). However, a direct comparison between the soya-bean formula in milk and in water showed no significant difference (0.043 and 0.060 respectively). Fe absorption from a drink containing 10 g ISP and 30 mg ascorbic acid was significantly better than that from a similar drink containing the soya-bean flour from which ISP is extracted (0.044 and 0.027 respectively). Heating ISP to 200 degrees for 2 h before its use had no effect on Fe availability.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.      

Red blood cell distribution width in the anemia secondary to tuberculosis

A study was done to explore the claim that anisocytosis as measured by the red blood cell volume distribution width (RDW) is raised in iron-deficiency anemia, but is normal in the anemia of chronic disorders. Measurements were done on 283 normal patients, 22 iron-deficient patients, and 102 tuberculotic patients, using a model S plus Coulter Electronic Counter with standard calibration. Mean (+/- SD) values for RDW were as follows: normals, 7.36 (+/- 0.57); untreated iron deficiency, 10.39 (+/- 1.37); and 15 untreated anemic patients with tuberculosis, 10.44 (+/- 0.63). Mean values remained above 10.4 in 69 patients with tuberculosis during treatment, irrespective of whether or not the patients were anemic, but had fallen towards the normal mean (8.49 +/- 0.8) in the 18 subjects in whom it was measured at the end of therapy. By this time the mean corpuscular volume (MCV) and hemoglobin concentrations had risen to normal. It is concluded that RDW values in the chronic inflammatory disorder tuberculosis are not significantly different from those occurring in iron-deficiency anemia.     

A monoclonal antibody against nerve growth factor receptor. Immunohistochemical analysis of normal and neoplastic human tissue

The expression of human nerve growth factor (NGF) receptor in tumors and normal tissue was investigated with the use of a monoclonal antibody recently developed against that protein. This antibody, NGFR5, reacted strongly with 100% of 25 nerve sheath tumors. Eight of nine pheochromocytomas and three of three paragangliomas also had positive results, but the immunoreactivity was restricted to the sustentacular cell population. Within cells of melanocytic lineage, there was no immunostaining of melanocytes in normal epidermis, whereas 13 of 14 benign nevi had positive results, primarily involving spindled nevocytic structures within the dermis. NGF receptor was scarcely expressed in human melanoma; 9 of 19 melanomas had positive results, but immunoreactivity was generally restricted to rare cells within the larger tumor cell population. Among nonneurogenic mesenchymal tumors, results were generally negative: 0 of 5 chondrosarcomas, 0 of 6 malignant fibrous histiocytomas, 0 of 3 meningiomas, and 1 of 8 leiomyosarcomas were immunoreactive. Carcinomas were variable in immunoreactivity: 12 of 16 squamous cell carcinomas had positive results, whereas adenocarcinomas demonstrated focal, basal epithelial immunoreactivity and neuroendocrine tumors generally had negative results. Among normal tissues, in addition to expected neural immunostaining, NGFR 5 reacted positively with several nonneural cell types, including lymphoidal follicular dendritic cells, myoepithelial cells, vascular adventitia, and basal epithelium of oral mucosa and hair follicles. Antibodies to NGF receptor may play a role in the identification of benign and malignant soft tissue lesions.     

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.     

TMD before and after correction of dentofacial deformities by orthodontic and orthognathic treatment

The aims of the study were to investigate the alteration of temporomandibular disorders (TMD) after correction of dentofacial deformities by orthodontic treatment in conjunction with orthognathic surgery; and to compare the frequency of TMD in patients with dentofacial deformities with an age and gender matched control group. TMD were evaluated in 121 consecutive patients (treatment group), referred for orthognathic surgery, by a questionnaire and a clinical examination. 18 months after treatment, 81% of the patients completed a follow-up examination. The control group comprised 56 age and gender matched subjects, of whom 68% presented for follow-up examination. TMD were diagnosed according to research diagnostic criteria for TMD. At baseline examination, the treatment group had a higher frequency of myofascial pain (P = .035) and arthralgia (P = .040) than the control group. At follow-up, the frequencies of myofascial pain, arthralgia and disc displacement had decreased in the treatment group (P = .050, P = .004, P = .041, respectively). The frequency of TMD was comparable in the two groups at follow-up. Patients with dentofacial deformities, corrected by orthodontic treatment in conjunction with orthognathic surgery, seem to have a positive treatment outcome in respect of TMD pain.