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.     

Repeat pregnancy associated with cardiac pacemaker.

Two pregnancies in a patient with a fixed-rate pacemaker are reported. The first pregnancy was uneventful. The second had no maternal complications either. A moderate tachysystolia was detected during the second period. The newborn was delivered with forceps applied under spinal anesthesia. Newborn infant evolution presented no hazards, but umbilical cord analysis revealed a severe acidosis, in spite of a normal scalp analysis 45 min earlier. Epidural anesthesia is recommended for such patients.     

3D imaging and pathology of the base of the skull in children]

Three dimensional computed tomography was performed in 150 children suffering from a bone lesion of the base of the skull and face. These lesions were either malformative, neoplastic, infectious or traumatic. 3D CT provided an essential anatomical approach to the lesions facilitating the choice of the most appropriate treatment. 3D CT is also indicated in the follow-up of these operated children, particularly of the growth of the operated bone segment and its relations with adjacent structures.     

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.     

Aplasia cutis congenita of the scalp with large underlying skull defect: a case report

Localised agenesis of the scalp is the most frequent patern in aplasia cutis congenita (ACC), a congenital absence of the skin and occasionally of deeper layers. Several clinical groups are characterised by the location and pattern of skin defects, associated malformations and the mode of inheritance. Death occurs in 20% of cases, secondary to the associated anomalies, to infections or to haemorrhage from ulceration of the sagittal sinus when there is also a defect of the underlying skull. In this latter case, we close the defect by two rotational scalp flaps (Orticochea technique) at birth. A three-dimensional CT study is useful for showing the extent of the skull defect and the deformity of the craniofacial complex and the changes in the bone after treatment.     

Detection of St. Louis encephalitis virus antigen in mosquitoes by capture enzyme immunoassay.

Surveillance methods that measure St. Louis encephalitis (SLE) virus activity in nature may provide forewarning of its epidemic occurrence in humans. An antigen capture enzyme immunoassay was developed to detect SLE virus in infected mosquitoes. The assay detected purified SLE viral antigen at a concentration of 62 pg/0.1 ml when antigen was incubated overnight; 250 pg/0.1 ml was detected in a single-day assay (antigen incubated for 3 h). The assay detected 67.9 and 70.8% of laboratory-prepared pools of infected mosquitoes after 3 h and overnight incubation, respectively. The sensitivity of the procedure was 90.5% in identifying pools with infectious titers greater than dex 3.0. The specificity of the assay was controlled by retesting positive pools preincubated with SLE virus and normal antibodies, which led to a diminution of signal in the pools containing viral antigen. The procedure was suitably specific in discriminating between SLE and related flaviviruses, detecting only high infectious doses of heterologous antigens.     

Analysis of polyadenylated RNA from human heart mitochondria

Summary The content of the mitochondrial poly(A)-RNA fraction of human heart has been analyzed by electrophoresis through agarose slab gels in the presence of methyl mercury hydroxide and staining with ethidium bromide. It is possible to identify all the heavy strand coded mRNAs in the electrophoretic pattern. This pattern is qualitatively similar to that obtained from the mitochondria of cells cultured in vitro (HeLa cells), although differences in the relative amount of some components have been detected.     

Peripheral blood mononuclear cell human immunodeficiency virus type 1 proviral DNA quantification by polymerase chain reaction: relationship to immunodeficiency and drug effect.

Human immunodeficiency virus type 1 (HIV-1) proviral DNA from peripheral blood mononuclear cells (PBMCs) was quantitated in 61 HIV-1-seropositive individuals by a nonisotopic polymerase chain reaction assay. Primers from the gag region (SK38, SK39) were used to determine the log10 HIV-1 proviral copy number per 10(6) CD4+ T lymphocytes (peripheral blood proviral load). A standard curve was generated for each assay by using ACH-2 cell DNA. The peripheral blood proviral load was followed in 15 individuals in a longitudinal study and was measured in 45 individuals in a cross-sectional analysis. Three of four untreated patients who were followed for 14 months had stable PBMC proviral loads and CD4+ T lymphocyte counts; one untreated patient had a sustained increase in PBMC proviral load followed 5 months later by a significant decline in the CD4+ T lymphocyte count. Eleven previously untreated individuals were monitored for 1 year following initiation of zidovudine and/or 2',3'-dideoxyinosine therapy. The mean log10 number of proviral HIV-1 copies per 10(6) CD4+ T cells decreased from 4.3 +/- 0.4 at the baseline to 3.5 +/- 0.6 after 2 to 4 months of therapy (P < 0.01). This initial 0.8 log10 fall in the PBMC proviral load after the initiation of therapy was followed by a rise in the PBMC proviral load by the sixth month of therapy. The PBMC proviral load in 45 subjects, both treated (n = 25) and untreated (n = 20), correlated inversely with the CD4+ T lymphocyte count (P < 0.01, R = 0.49). PBMC proviral DNA quantification by a nonisotopic polymerase chain reaction assay correlates with HIV-1 disease progression and could be used to monitor the effect of antiretroviral therapy.