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.      

Surgical treatment of liver injuries by application of Fibrinkleber

The combination of highly concentrated fibrinogen, thrombin, clotting factor XIII, and fibrinolytic inhibitor aprotinin represents a new biological hemostatic, and adhesive system, known as Fibrinkleber. Liver injuries and injuries of parenchymatous organs, with the difficulties inherent in their surgical repair, are a suitable field of application for the new substance. In our experimental work, standardized sharp liver injuries in 29 rabbits were treated only by application of Fibrinkleber. In all cases, this procedure resulted in a complete control of bleeding as well as in a stable and lasting closure of wounds. Five of these animals died from causes unrelated to the liver trauma but rather to parasitosis. During the postoperative observation period, from 2 days to 2 months, microscopic and histological examination showed ideal repair of the glued wounds. In the control group, 5 rabbits were kept without application of Fibrinkleber. Three of the rabbits with liver injuries and all of the control group histological examinations showed separation of the wounds with minimal healing.

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Resumen Debido a su tamaño y ubicación, el hígado es un órgano muy vulnerable en casos de trauma abdominal. Las heridas hepáticas varían considerablemente y su severidad dépende del tipo y magnitud del trauma. En virtud de la vascularidad del hígado y, según la localización de la herida, el tratamiento del trauma hepático con frecuencia es difícil. La hemorragia resultante y los consiguientes complejos problemas postoperatorios significan un desafío formidable.La combinación de fibrinógeno altamente concentrado, trombina, factor XIII de coagulación y aproptinina, un inhibidor de fibrinolisis, ha venido a representar un nuevo sistema biológico hemostático y adhesivo, el cual se conoce como Fibrinkleber. Las lesiones hepáticas y en general las heridas de los órganos parenquimatosos, por las dificultades que presentan en el momento de la reparación quirúrgica, constituyen un campo propicio para la aplicación de esta nueva sustancia. En nuestro trabajo experimental se trataron heridas hepáticas estandarizadas en 29 conejos mediante la sóla aplicación de Fibrinkleber. Tal procedimiento resultó, en todos los casos, en un completo control del sangrado y en un cierre estable y duradero de las heridas por la firme adherencia de las superficies hepáticas. Cinco de los animales fallecieron por causas no relacionadas con el trauma hepático sino con parasitosis. En el curso del período de observación postoperatoria, desde el segundo día hasta dos meses, los exámenes microscópicos e histológicos mostraron una cicatrización ideal de las heridas así adheridas. En el grupo de control se incluyó a cinco conejos que no recibieron la aplicación de Fibrinkleber. Tres de estos perecieron poco tiempo después de infligida la lesión, y en todos el examen histológico demostró separación de la herida con mínima cicatrización.

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Résumé La combinaison à haute concentration de fibrinogène, de thrombine du facteur XIII et de l'aprotinine (inhibiteur de la fibrinolyse) permet de constituer un agent biologique d'hémostase et de coalescence dénommé Fibrinkleber. Les blessures du foie et plus généralement les blessures des organes parenchymateux dont la cure est difficile à assurer chirurgicalement sont susceptibles d'être traitées efficacement par cette nouvelle substance. A titre expérimental des blessures du foie identiques chez 29 lapins ont été traités uniquement par ce nouvel agent. Dans tous les cas l'hémorragie pu être arrêtée et la coalescence définitive de la plaie pu être obtenue. Cinq des 29 lapins moururent non de leur plaie hépatique mais de parasitose. Pendant la période d'observation postopératoire s'étendant du deuxième jour jusqu'à la fin du deuxième mois l'examen macroscopique et l'examen microscopique permirent de constater la cicatrisation parfaite de la plaie. Un groupe de contrôle comprenant cinq lapins qui présentaient une blessure hépatique de type identique mais traitée sans l'aide de l'agent coagulant et coalescent permit de constater que la plaie persistait et que sa cicatrisation était minime.

     

Chemotherapy of brain tumors

This is a review of chemotherapy options for patients with brain tumors, both at the time of initial diagnosis and at recurrence. Gliomas, the most common malignant brain tumors, represent the main focus of the review; chemotherapeutic options for supratentorial, brain stem, and optic track gliomas are discussed.     

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.     

Measles virus expressed Helicobacter pylori neutrophil-activating protein significantly enhances the immunogenicity of poor immunogens

Helicobacter pylori neutrophil-activating protein (NAP) is a toll-like receptor 2 (TLR2) agonist and potent immunomodulator inducing Th1-type immune response. Here we present data about characterization of the humoral immune response against NAP-tagged antigens, encoded by attenuated measles virus (MV) vector platform, in MV infection susceptible type I interferon receptor knockout and human CD46 transgenic (Ifnarko-CD46Ge) mice. Immunogenicity of MV expressing a full-length human immunoglobulin lambda light chain (MV-lambda) was compared to that of MV expressing lambda-NAP chimeric protein (MV-lambda-NAP). MV-lambda-NAP immunized Ifnarko-CD46Ge mice developed significantly higher (6–20-fold) anti-lambda ELISA titers as compared to the MV-lambda-immunized control animal group, indicating that covalently-linked NAP co-expression significantly enhanced lambda immunogenicity. In contrast, ELISA titers against MV antigens were not significantly different between the animals vaccinated with MV-lambda or MV-lambda-NAP. NAP-tagged antigen expression did not affect development of protective anti-measles immunity. Both MV-lambda and MV-lambda-NAP-immunized groups showed strong virus neutralization serum titers in plaque reduction microneutralization test. These results demonstrated that MV-encoded lambda-NAP is highly immunogenic as compared to the unmodified full-length lambda chain. Boost of immune response to poor immunogens using live vectors expressing NAP-tagged chimeric antigens is an attractive approach with potential application in immunoprophylaxis of infectious diseases and cancer immunotherapy.