Skin Cancer Prevention: A Time for Action

Skin cancer is the most common malignancy in the United States accounting for more than 840,000 cases and 9,400 deaths annually. It is estimated that 90% of non-melanoma skin cancers and much of melanoma incidence can be attributed to sun exposure. The evidence suggests that regular use of sunscreen (Sun Protective Factor (SPF) of 15 or higher), wearing protective, tightly woven clothing and wide brimmed hats, and avoiding sun exposure when the ultraviolet rays are strongest (between 11:00 a.m. and 3:00 p.m.) can dramatically reduce the risk of skin cancer. Interventions to promote sun-protection behaviors that target children and adults are necessary to reduce the growing incidence rate of skin cancer in the United States.MA during the time of this research     

Low sodium haemodialysis reduces interdialytic fluid consumption but paradoxically increases post-dialysis thirst.

BACKGROUND: Interdialytic weight gain (IDWG) can be reduced by lowering the dialysate sodium concentration ([Na]) in haemodialysis patients. It has been assumed that this is because thirst is reduced, although this has been difficult to prove. We compared thirst patterns in stable haemodialysis patients with high and low IDWG using a novel technique and compared the effect of low sodium dialysis (LSD) with normal sodium dialysis (NSD). METHODS: Eight patients with initial high IDWG and seven with low IDWG completed hourly visual analogue ratings of thirst using a modified palmtop computer during the dialysis day and the interdialytic day. The dialysate [Na] was progressively reduced by up to 5 mmol/l over five treatments. Dialysis continued at the lowest attained [Na] for 2 weeks and the measurements were repeated. The dialysate [Na] then returned to baseline and the process was repeated. RESULTS: Baseline interdialytic day mean thirst was higher than the dialysis day mean for the high IDWG group (49.9+/-14.0 vs 36.2+/-16.6) and higher than the low weight gain group (49.9+/-14.0 vs 34.1+/-14.6). This trend persisted on LSD, but there was a pronounced increase in post-dialysis thirst scores for both groups (high IDWG: 46+/-13 vs 30+/-21; low IDWG: 48+/-24 vs 33+/-18). The high IDWG group demonstrated lower IDWG during LSD than NSD (2.23+/-0.98 vs 2.86+/-0.38 kg; P<0.05). CONCLUSIONS: Our results indicate that patients with high IDWG experience more intense feelings of thirst on the interdialytic day. LSD reduces their IDWG, but paradoxically increases thirst in the immediate post-dialysis period.     

MRI relaxation fluctuations in acute reperfused hemorrhagic infarction.

MRI evaluations of intramyocardial hemorrhage in acute infarction have relied on T(2) and T(2)(*) shortening only. We propose a more comprehensive evaluation of hemorrhagic infarction based on the concept that fluctuations in T(2) and T(1) relaxation in acute reperfused infarction will reflect transient edema and hemoglobin oxidative denaturation to uncompartmentalized methemoglobin. Anteroapical infarction was created via percutaneous balloon in young swine (22-25 kg, N = 12). T(2), T(1), diastolic wall thickness (DWT), and the Gd-DTPA partition coefficient (lambda) were measured on days 0, 2, and 7. DWT was elevated at 1 hr postreperfusion (128% +/- 53%, P = 0.0001), and alleviated on days 2 and 7 (48% +/- 10%, P = 0.008; 53% +/- 24%, P = 0.003). T(2) and T(1) elevations were coincident with early edema (DeltaT(2) = 55% +/- 24%, P < 0.0001; DeltaT(1) = 27% +/- 18%, P < 0.04). T(2) and T(1) were nearly normal on day 2 (DeltaT(2) = 8% +/- 8%, P = 0.27; DeltaT(1) = 0% +/- 1%, P = 0.65). On day 7, T(2) increased while T(1) decreased (DeltaT(2) = 27% +/- 16%, P = 0.005; DeltaT(1) = -14% +/- 10%, P = 0.02). Lambda was elevated by >150% at all time points (P < or = 0.002). Histology verified hemorrhagic injury. T(1) and T(2) fluctuations are consistent with transient edema, as well as hemoglobin oxidative denaturation to decompartmentalized methemoglobin. This methodological development may broaden our understanding of hemorrhagic microvascular injury and improve its detection in clinical populations.     

Quantitation of photochemically induced focal cerebral ischemia in the rat

This study was carried out with a recently developed model of focal cerebral ischemia in the rat based on the photochemical induction of thrombotic stroke using the dye Rose Bengal. We examined the change in the volume of the lesion and brain water content, in separate groups of rats, at different times (1, 4, 24, 72, and 168 h) after the induction of the ischemic lesion. The volume of ischemic damage increased rapidly between 1 and 24 h after the ischemic insult and decreased between 24 and 168 h. The lesion at 168 h was significantly larger than that following 1 h of ischemia and similar to that obtained at 4 h, suggesting that the maximum extent of tissue damage (without the involvement of significant edema) was reached within the first 4 h in this model. The enlargement of the lesion after 4 h correlated closely with changes in brain water content.     

Percutaneous balloon pericardiotomy in the management of recurrent malignant pericardial effusions

Two patients with recurrent symptomatic pericardial effusions secondary to malignant disease were successfully treated by percutaneous balloon pericardiotomy. Open surgery was avoided and the procedure was completed under local anaesthesia in less than 40 minutes. The first patient was free of recurrence at nine months but pericardial effusion recurred at two months in the second patient.Percutaneous balloon pericardiotomy offers a potentially important new means of relieving recurrent tamponade and substantially reduces trauma to the patient.     

Cardiac calcification causing arrhythmia detected by technetium-99m MDP and SPECT

SPECT was used to identify a focal accumulation of cardiac calcification using Tc-99m MDP in a patient with an arrhythmia and known metastatic calcification elsewhere.     

Biliary excretion of radioactivity after intravenous administration of [3H]25-hydroxyvitamin D3 in man

The biliary excretion of radioactivity after intravenous [3H]25-hydroxyvitamin D3 was studied in nine patients with T-tube bile drainage. The mean +/- SD 24-hr radioactivity excretion in T-tube bile expressed as a percentage of the administered dose was 6.7 +/- 2.9%; after correction for incomplete bile collection, the value obtained was 16.0 +/- 11.1%. Chloroform solubility of biliary radioactivity increased from 27.4 +/- 8.9% to 72.9 +/- 10.1% following incubation with beta-glucuronidase. High-performance liquid chromatographic analysis of chloroform extracts of bile revealed that most of the eluted radioactivity was more polar than [3H]25-hydroxyvitamin D3. No free [3H]25-hydroxyvitamin D3 was demonstrated. Thus in man, most of the biliary radioactivity excreted following [3H]25-hydroxyvitamin D3 is in the form of water-soluble compounds, mainly glucuronides. However, our results suggest that glucuronides of metabolites other than 25-OHD3 are predominantly formed.     

Detection and partial purification of a potent mitogenic factor for human thyroid follicular cells.

Normal adult human thyroid follicular cells have an extremely limited proliferative capacity in vitro. No previously studied mitogen, including thyrotropin (TSH) or epidermal growth factor (EGF), has in our hands resulted in a significant improvement over the 3-4% nuclear [3H]thymidine pulse-labelling index (LI) obtainable with 10% fetal calf serum. Here we report the detection in the conditioned medium from a sub-clone of NIH3T3 fibroblasts of a mitogenic activity capable of increasing this response up to 10-fold, to an LI of over 20%, together with an even greater relative stimulation of mitotic activity. Preliminary characterisation has excluded EGF and TGF alpha, and demonstrated that the activity is bound reversibly by heparin-Sepharose, thus pointing to a member of the heparin-binding fibroblast- or hepatocyte-growth factor families. This material should have wide practical application in facilitating primary culture of follicular cells, and may reveal new mechanisms of stromal-epithelial interaction regulating normal and neoplastic thyroid growth in vivo.     

Studies on the molecular pharmacology of GR63178A. A novel pentacyclic pyrolloquinone anticancer drug.

GR63178A (NSC D611615) is the second pentacyclic pyrolloquinone to be evaluated clinically as an anticancer drug. Its mechanism of action is unknown but may be related either to its quinone group or planar ring system. In this report we have investigated the ability of GR63178A to bind non-covalently to DNA, inhibit topoisomerase II and undergo reduction to reactive free radical species. Using two DNA duplexes, a 12-mer oligonucleotide which is a preferred sequence for minor groove binders and a hexamer which is a preferred sequence for intercalators, no evidence of significant binding with GR63178A was found. Neither GR63178A nor GR54374X (its 9-hydroxy metabolite) inhibited purified human topoisomerase II in a decatenation assay. Free radical chemistry was studied by both pulse radiolysis and ESR spectroscopy as well as by in vitro drug incubations with NADPH-fortified rat liver microsomes and purified cytochrome P450 reductase. The one-electron reduction potential of GR63178A was -207 mV +/- 10 which is much more positive than other quinone-containing anticancer drugs such as doxorubicin, mitomycin C and mitozantrone. GR63178A underwent enzyme-catalysed quinone reduction more readily than doxorubicin but produced significantly fewer reactive oxygen species. No evidence was detected of drug-induced, radical-mediated DNA damage in vitro using pBR322 plasmid DNA. Disproportionation of the GR63178A semi-quinone free radical proceeded with a rate constant of 1 x 10(9) M-1 sec-1 under anaerobic conditions, one order of magnitude faster than doxorubicin. The preferential disproportionation of the semi-quinone may explain our inability to detect a free radical signal by ESR. The hydroquinone of GR63178A was stable and exhibited strong visible absorption with a bathochromic shift of 120 nm over the parent drug. These unusual properties may be due to the hydroquinone undergoing a form of keto-enol tautomerization. Thus, GR63178A free radical formation does not appear to result in significant drug activation. In conclusion, GR63178A is unlikely to mediate its antitumour activity by DNA binding, topoisomerase II inhibition or free radical formation in direct contrast to similar anthracycline- and anthraquinone-based anticancer drugs.