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.     

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.     

Cell proliferation in human tumours growing in nude mice: renal cell carcinomas,larynx and hypopharynx carcinomas

Summary Cell proliferation of 51 human renal cell carcinomas and 9 larynx and hypopharynx carcinomas has been studied in vitro and using xenotransplants. The proliferative activity ([³H]thymidine labelling index) increases during the first passages in nude mice and then remains almost constant throughout subsequent passages. A comparison of cell kinetic parameters of 8 human renal cell carcinomas, 1 hypopharynx and 2 larynx carcinomas, with data of xenografts and of human tumours in situ published up to now, shows that the cell kinetic parameters of human tumour xenografts presently studied range between those of human tumours in situ and those of autochthonous or transplantable mouse tumours. S-phase durations and potential doubling times are considerably shorter in xenotransplants than in human tumours in situ, whereas the cycle time is about the same. This means that the growth fraction increases considerably after xenotransplantation. This change of human tumour cell proliferation after transplantation into nude mice should be kept in mind if one wishes to draw conclusions from the nude mouse model on conditions in human beings, particularly with respect to therapeutic regimens, which are frequently tested in the nude mouse model.Abbreviations used RCC renal cell carcinoma - HPC larynx or hypopharynx carcinoma - LI labelling index - PLM percentage of labelled mitoses - t _s S-phase duration - t _c cycle time - t _pot potential doubling time This work was supported by the Deutsche Forschungsgemeinschaft (Ma 876/2-1)     

Effect of amitriptylin on the growth-kinetics of 2 human cancer xenograft lines in nude-mice

With respect to the controversial discussion of the effect of antidepressants on the development of cancer in the literature, elicited by a recent report on growth stimulating effects of antidepressants (Brandes et al, Cancer Res 52: 3796, 1992), the effect of daily doses of amitriptylin (80 mg/m2 body surface, intraperitoneally) on the macroscopic growth of two human tumor xenograft lines in nude mice was studied (a malignant. melanoma, FO-1 and a renal cell adenocarcinoma, RCC). The application of the Gompertzian difference equation to compare the growth patterns of treated and untreated tumors shows that amitriptylin does modify the growth characteristics of both lines (p<0.05). however, in opposite directions: The growth of the melanoma FO-1 is stimulated whereas that of the RCC is inhibited. The growth pattern analysis further indicates, that this difference mainly consists of the differential effect of amitriptylin on the growth retarding processes of the tumors: amitriptylin inhibits the initial intrinsic growth rate of both tumor lines, however, only in the case of the FO-1 does it inhibit simultaneously also the growth retarding process and, thus, it ultimately stimulates its growth. On the contrary the near exponential growth of the RCC is not affected by amitriptylin. However, it cannot be excluded that at least some of the tumor growth modifying effects of the present treatment may be attributed to the potentiation of the animal weight loss by amitriptylin in the tumor-bearing animals (p<0.05).     

Phospholipase activity after β‐endorphin exposure discriminates Malassezia strains isolated from healthy and seborrhoeic dermatitis skin

Background Phospholipase activity and its induction by β‐endorphin have been associated with pathogenic Malassezia pachydermatis animal isolates. Objective To evaluate Malassezia phosholipase activity in human isolates from seborrhoeic dermatitis (SD) and healthy controls before and after β‐endorphin exposure. Methods Eighty‐four volunteers with or without SD (N = 41) were sampled. Isolated Malassezia strains were incubated in Dixon’s medium with and without 100 nmol/L β‐endorphin. Subsequently, phospholipase activity was assessed in egg‐yolk agar and the results were compared employing Wilcoxon sign test for paired data, chi‐squared test and multinomial logistic regression analysis. Results A total of 64 Malassezia strains were isolated. SD strains tended to have decreased phospholipase activity before (P = 0.057) and increased after exposure to β‐endorphin (P = 0.061) compared to isolates from healthy skin. Phospholipase activity after β‐endorphin exposure related to basal enzyme activity as a measure of per strain phospholipase inducibility by β‐endorphin did not depend on Malassezia species (P = 0.652). However, this latter biochemical trait discriminates strains isolated from SD lesional and healthy skin (P = 0.036). Conclusion β‐endorphin exposure modifies the in vitro phosholipase activity in Malassezia species isolated from SD lesional skin. This is in accordance with emerging evidence that enhanced local lipase activity is involved in the pathogenesis of SD.     

Neurocysticercosis in radiographically imaged seizure patients in U.S. emergency departments

Neurocysticercosis appears to be on the rise in the United States, based on immigration patterns and published cases series, including reports of domestic acquisition. We used a collaborative network of U.S. emergency departments to characterize the epidemiology of neurocysticercosis in seizure patients. Data were collected prospectively at 11 university-affiliated, geographically diverse, urban U.S. emergency departments from July 1996 to September 1998. Patients with a seizure who underwent neuroimaging were included. Of the 1,801 patients enrolled in the study, 38 (2.1%) had seizures attributable to neurocysticercosis. The disease was detected in 9 of the 11 sites and was associated with Hispanic ethnicity, immigrant status, and exposure to areas where neurocysticercosis is endemic. This disease appears to be widely distributed and highly prevalent in certain populations (e.g., Hispanic patients) and areas (e.g., Southwest).