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.     

Perfluorochemicals as US contrast agents for tumor imaging and hepatosplenography: preliminary clinical results

In animals, perfluorochemicals (PFCs) are effective ultrasound (US) contrast agents that produce hepatic, splenic, and tumor enhancement. The use of Fluosol-DA 20%, an emulsion of perfluorodecalin and perfluorotripropylamine, was studied in nine non-critically ill patients with cancer who had liver lesions. US studies without Fluosol were compared with studies obtained 24, 48, and 72 hours after Fluosol infusion. Vital signs and extensive laboratory analyses are performed before and after Fluosol infusion. Liver metastases from colonic, pancreatic, and gastric carcinoma exhibited rim or diffuse enhancement after a Fluosol dose of 1.6 g/kg or greater. Fluosol produced echogenic enhancement of the liver and spleen relative to kidney at a dose of 2.4 g/kg, allowing the detection of nonenhancing lesions. In addition, Fluosol at a dose of 1.6 g/kg or greater allowed detection of lesions not seen before contrast medium was administered in three of the seven patients studied. There was a mild increase in the level of serum glutamic oxaloacetic transaminase in two patients, one given 2.4 and the other 3.2 g/kg of Fluosol. Mild and transient allergic reactions without change in vital signs were experienced by two patients.     

Surgical aspects of chronic peritoneal dialysis in the neonate and infant under 1 year of age.

Since 1982 eight patients under 1 year of age with end-stage renal failure have been treated by chronic peritoneal dialysis (CPD) following insertion of an abdominal Tenckhoff catheter. We routinely perform a partial omentectomy now, and in males undertake bilateral exploration of the groins at the time of catheter insertion, with herniotomy or ligation of the patent processus vaginalis as required. Up to January 1990, 19 straight double-cuff catheters had been inserted with a total follow-up of 244.5 patient months. The median age at the initial catheter insertion was 14.6 weeks (range, 2 days to 11 months) and the median weight was 3.89 kg (range, 2.2 to 5.5). Peritonitis was the most common complication, with 46 episodes, representing one episode of peritonitis per 5.3 patient months on dialysis. The frequency of peritonitis has decreased in the last 6 months since all patients have been dialysed by two caregivers. The present rate of peritonitis is 1 episode per 10 patient months on dialysis. One patient has died of septicemia secondary to associated congenital abnormalities, one patient has regained renal function, and two patients have been transplanted, one successfully. Five patients are currently dialysing via their abdominal Tenckhoff catheters and awaiting transplantation. We conclude that neonates and infants under 1 year of age can be treated satisfactorily by CPD to enable successful preparation for transplantation later in childhood.     

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.     

Physicians' information needs: analysis of questions posed during clinical teaching

OBJECTIVE: To describe information requests expressed during clinical teaching. SETTING: Residents' work rounds, attending rounds, morning report, and interns' clinic in a university-based general medicine service. SUBJECTS: Attending physicians, medical house staff, and medical students in a general medicine training program. METHODS: An anthropologist observed communication among study subjects and recorded in field notes expressions of a need for information. We developed a coding scheme for describing information requests and applied the coding scheme to the data recorded. Based on assigned codes, we created a subset of strictly clinical requests. MEASUREMENTS: Five hundred nineteen information requests recorded during 17 hours of observed clinical activity were selected for detailed analysis. These requests related to the care of approximately 90 patients by 24 physicians and medical students. Sixty-five requests were excluded because they were not strictly clinical, leaving a subset of 454 clinical questions for analysis. MAIN RESULTS: On average, five clinical questions were raised for each patient discussed. Three hundred thirty-seven requests (74%) concerned patient care. Of these 337 questions, 175 (52%) requested a fact that could have been found in a medical record. Seventy-seven (23%) of these questions, motivated by the needs of patient care, were potentially answerable by a library, a textbook, a journal, or MEDLINE. Eighty-eight (26%) of the questions asked for patient care required synthesis of patient information and medical knowledge. CONCLUSIONS: Clinicians in the study settings requested information frequently. Many of these information needs required the synthesis of patient information and medical knowledge and thus were potentially difficult to satisfy. A typology is proposed that characterizes information needs as consciously recognized, unrecognized, and currently satisfied.