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.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

Imprecision of prothrombin time monitoring of oral anticoagulation. A survey of hospital laboratories.

Prothrombin time monitoring of oral anticoagulation is highly dependent on the tissue thromboplastin used. In the United States, patients have received a higher level of anticoagulation because of the use of a less sensitive thromboplastin. Many advocate the use of an International Normalized Ratio to rectify this problem. Laboratory supervisors from all acute care hospitals in Massachusetts were surveyed to determine the disparity in thromboplastin use and reporting practices for prothrombin time testing. Eighty-eight of 103 (86%) hospitals responded. Fifty-eight lots from six manufacturers of thromboplastin were in use. The International Sensitivity Index of these lots ranged from 1.89 to 2.74. Ninety-nine percent of hospitals reported prothrombin times in raw seconds. Only 5% reported an International Normalized Ratio. Sixteen different coagulation instruments were in use. Close to 70% of laboratory supervisors had little or no understanding of the significance of an International Sensitivity Index or an International Normalized Ratio. The management of oral anticoagulation appears far less precise than had been believed. Prothrombin times in the same individual from different laboratories may have poor correlation. Based on the level of understanding of laboratory supervisors, extensive education will be necessary to change practices and improve accuracy and comparability of prothrombin time testing.     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

Does desmopressin acetate prophylaxis reduce blood loss after valvular heart operations? A randomized, double-blind study.

The effectiveness of prophylactic desmopressin acetate in reducing hemorrhage after cardiopulmonary bypass operations is controversial. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine its effectiveness and safety in such patients. Eighty-three evaluable patients undergoing valvular heart operations were randomized to receive desmopressin (0.3 microgram/kg) (41) or placebo (42) after cardiac bypass. Demographic characteristics were similar in both groups. There was no significant difference in total 24-hour blood loss between groups (desmopressin 1064.8 +/- 647.1 ml versus placebo 844.4 +/- 507.6 ml; p greater than 0.05), or in the requirement for red blood cell, platelet, or fresh frozen plasma transfusion, or for reexploration for control of hemorrhage. Neither was there a difference in the occurrence of thrombotic complications between groups. Analysis of factor VIII activity, von Willebrand factor, or von Willebrand factor multimers failed to show significant correlations with blood loss or differences between groups except for factor VIII activity, which was significantly higher in the desmopressin group 1 hour after operation than in the placebo group. A detailed comparative analysis of similar trials to determine the reasons for different outcomes suggests that desmopressin should not be used routinely as a prophylactic agent to reduce postsurgical hemorrhage, but that it may be beneficial when used in patients who already manifest excessive bleeding postoperatively.     

Spicular arrangement of amyloid in renal biopsy

A spicular arrangement of amyloid on the epithelial aspect of the glomerular basement membrane has been seen to a variable degree in silver-stained sections of renal biopsies in eight of 38 patients with amyloidosis. Electron microscopical examination revealed a spectrum of appearances of the amyloid fibrils which would account for this finding. Only two of these eight patients had amyloidosis secondary to chronic infection, a much lower proportion than in the group as a whole. The possibility of confusion with membranous nephropathy is discussed with relevance to possible modes of treatment.     

Physical and biological properties of a novel siloxane adhesive for soft tissue applications

The aim of this study was to investigate the adhesive properties of an in-house aminopropyltrimethoxysilane-methylenebisacrylamide (APTMS-MBA) siloxane system and compare them with a commercially available adhesive, n-butyl cyanoacrylate (nBCA). The ability of the material to perform as a soft tissue adhesive was established by measuring the physical (bond strength, curing time) and biological (cytotoxicity) properties of the adhesives on cartilage. Complementary physical techniques, X-ray photoelectron spectroscopy, Raman and infrared imaging, enabled the mode of action of the adhesive to the cartilage surface to be determined. Adhesion strength to cartilage was measured using a simple butt joint test after storage in phosphate-buffered saline solution at 37 degrees C for periods up to 1 month. The adhesives were also characterised using two in vitro biological techniques. A live/dead stain assay enabled a measure of the viability of chondrocytes attached to the two adhesives to be made. A water-soluble tetrazolium assay was carried out using two different cell types, human dermal fibroblasts and ovine meniscal chondrocytes, in order to measure material cytotoxicity as a function of both supernatant concentration and time. IR imaging of the surface of cartilage treated with APTMS-MBA siloxane adhesive indicated that the adhesive penetrated the tissue surface marginally compared to nBCA which showed a greater depth of penetration. The curing time and adhesion strength values for APTMS-MBA siloxane and nBCA adhesives were measured to be 60 s/0.23 MPa and 38 min/0.62 MPa, respectively. These materials were found to be significantly stronger than either commercially available fibrin (0.02 MPa) or gelatin resorcinol formaldehyde (GRF) adhesives (0.1 MPa) (P < 0.01). Cell culture experiments revealed that APTMS-MBA siloxane adhesive induced 2% cell death compared to 95% for the nBCA adhesive, which extended to a depth of approximately 100-150 microm into the cartilage surface. The WST-1 assay demonstrated that APTMS-MBA siloxane was significantly less cytotoxic than nBCA adhesive as an undiluted conditioned supernatant (P < 0.001). These results suggest that the APTMS-MBA siloxane may be a useful adhesive for medical applications.