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.     

Cerebellar toxicity with high-dose cytosine arabinoside

CNS dysfunction, especially impaired cerebellar function, is the dose-limiting toxicity associated with high-dose cytosine arabinoside, which precludes doses of greater than 48 g/m2. Four hundred eighteen patients between the ages of 2 and 74 years with leukemia or lymphoma received 36 to 48 g/m2 cytosine arabinoside either alone or with anthracycline antibiotics, 4'-(9-acridinylamino) methane sulfon-m-anisidine (m-AMSA), or total body irradiation. In only 35 of 418 patients (8%) did severe cerebellar toxicity develop; it was irreversible or fatal in four (1%) patients. The age of the patient was a critical factor in the incidence of severe cerebellar toxicity. Patients greater than 50 years old had a statistically significant greater incidence of cerebellar toxicity compared with younger patients (26/137, 19%, v 9/281, 3%; P less than .0005, chi 2). Neither the diagnosis, disease status, sex, nor the regimen altered the incidence of severe cerebellar toxicity (when corrected for age). A second course of high-dose cytosine arabinoside, administered to 62 patients, did not increase the incidence of severe cerebellar toxicity, which occurred in five (8%) of these patients. Two of the five patients had severe toxicity with the initial course. Of the 60 patients with no antecedent cerebellar dysfunction, three (5%) had severe toxicity with the second course: one of 41 patients were less than 50 years old; two of 19 patients were greater than or equal to 50 years. Since the occurrence of severe cerebellar dysfunction is greatly affected by age, reduced doses of high-dose cytosine arabinoside should be given to patients greater than 50 years old, and methods for reducing the cerebellar toxicity should be investigated in these patients.     

Rats with nucleus basalis magnocellularis lesions mimic mnemonic symptomatology observed in patients with dementia of the Alzheimer's type

College students, healthy elderly subjects, patients diagnosed with mild or moderate dementia of the Alzheimer's type, as well as rats with small or large lesions of nucleus basalis magnocellularis (NBM) were tested on an order memory task for a 6- or 8-item list of varying spatial locations. Similar patterns of order memory deficits as a function of serial order position were observed in rats with small or large NBM lesions and patients with mild or moderate dementia of the Alzheimer's type. The results provide support for the possibility that rats with NBM lesions might mimic the mnemonic symptomatology of Alzheimer's disease.     

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.      

Peripheral mechanical loading and the mechanism of the tremor of chronic alcoholism.

The tremor of chronic alcoholism, although clinically similar to essential tremor, has been considered a distinct syndrome. Its underlying mechanism was analyzed in five patients (none in the acute stages of alcohol withdrawal) hospitalized in an alcohol detoxification program. All five patients performed tracking tasks in which they pursued a linearly moving "target" light with a response light that they controlled by flexion-extension activity of the wrist. Stationary and dynamic targets were used with both isometric and unconstrained wrist mechanical interfaces. Frequency, torque, and displacement tremor characteristics were examined under varying inertial loading or isometric voluntary torque conditions. Two simultaneous tremor components were present in all patients: a prominent 4- to 7-Hz low-frequency peak and a smaller-amplitude 9.4- to 9.6-Hz high-frequency peak. As the inertia of the hand was augmented during unconstrained tasks, the low-frequency peak decreased, while the high-frequency peak was unaffected. As required voluntary effort was increased during isometric testing, the amplitude of the low-frequency peak increased. These findings suggest that the low-frequency peak represents the significant pathologic component of the tremor of chronic alcoholism and that it has a biomechanical reflex mechanism similar to that of the lower-amplitude normal physiologic tremor.     

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.      

Chemotoxicity of indium-111 oxine in mammalian cells

We have studied the uptake and toxicity of [111In]oxine in Chinese hamster V79 lung fibroblasts. The incorporation of the radionuclide into these cells reached a plateau within 2 hr. Uptake was proportional to the extracellular radioactive concentration. Both radioactive and "decayed" [111In]oxine exhibited similar toxicities, indicating that the observed toxicity was chemical in nature. These results are discussed in terms of the present status of this radiolabeling agent.     

Long-term survival of patients with multiple myeloma and acute renal failure at presentation

Eight patients presented with simultaneous multiple myeloma and acute renal failure requiring hemodialysis. Patients had no known pre-existing renal disease nor exposure to nephrotoxic agents or x-ray contrast dye. Renal failure was attributed to light chain nephropathy in all cases. In 4 of these patients the diagnosis of myeloma was initially unsuspected. Renal biopsies in 3 of these patients, and post-mortem material in a fourth revealed the changes of "myeloma kidney." No patient regained renal function and all required chronic hemodialysis. Among these eight patients, three survived for periods greater than 21 months.     

Selection and mortality differentials.

The Office of Population Censuses and Surveys Longitudinal Study provides reliable mortality data by a much wider range of characteristics than are available for other national sources. Although it is based on only a 1% sample of the population, it broadens the scope of mortality analysis and permits study of changes in relationships using different aspects of the time dimension. Data from this study have made us increasingly aware of the importance of selection to the interpretation and understanding of observed mortality differentials. Here we focus on that aspect of selection called "health-related mobility," which is associated with the relative health of people acquiring or losing individual characteristics. It is suggested that, for characteristics affected by health-related mobility, mortality differentials would narrow or widen with increased duration of follow-up. One of the basis of this argument the contribution of health-related mobility to mortality differentials by economic position and social class, to regional differentials, and to family and household differentials is investigated. Selection can thus be shown to operate when people change economic position, when they migrate, or when they change marital status. While the effects of these selection processes can be shown to contribute to social class gradients they do not explain regional differentials and contribute only to a limited degree to differentials by marital status. Differentials by household circumstances also reflect the product of selection processes.