Optimized Photodynamic Therapy with Systemic Photosensitizer Following Debulking Technique for Nonmelanoma Skin Cancers

BACKGROUND: The thickness and depth of invasion of skin tumors may be limiting factors for topical photosensitizer-based photodynamic therapy (PDT). The use of PDT with systemic photosensitizer needs to be further explored as a modality of treatment for nonmelanoma skin cancer (NMSC). OBJECTIVE: The objective was to present six patients with multiple, nodular, and/or pigmented NMSC treated successfully with purified hematoporphyrin derivative (PHD) and PDT using prior debulking. METHODS: After 24 hours of systemic PHD (1.5 mg/kg), 12 lesions of NMSC were selected for PHD-PDT alone and 6 nodular/elevated lesions for PHD-PDT following a debulking procedure. The tumor area was illuminated in one single-dose session of 300 J/cm(2), at an intensity range of 130 to 150 mW/cm(2), with a 630-nm-wavelength diode laser. RESULTS: The prior curettage provided significant reduction in volume and/or pigmentation of lesions. After the session of PHD-PDT with prior curettage and additional topical 20% ALA-PDT in two lesions or PHD-PDT alone, 83% (5/6) of lesions and 58% (7/12) of lesions, respectively, maintained a complete clinical response, 22.2+/-8.9 months of follow-up. CONCLUSIONS: The combination of prior debulking with systemic agents-PDT appears to be a good option for multiple, pigmented, and/or nodular lesions of NMSC and can allow the improvement of clinical results.     

Lack of Influence of Atrioventricular Delay on Stroke Volume at Rest in Patients with Complete Atrioventricular Block and Dual Chamber Pacing

Dual chamber pacing (DDD) maintains atrioventricular (AV) sequence; AV delay programmability modifies the relationship between atrial and ventricular contraction. To evaluate the hemodynamic effects of such a modification, ten patients with a DDD unit for complete AV block were studied by time-motion (M-mode) and Doppler echocardiography during inhibited ventricular pacing (VVI), atrial-triggered ventricular pacing (VDD) and atrioventricular sequential pacing (DVI) at different AV delay (90, 140, 190, 240 msec). A significant improvement in stroke volume (SV) (15%-20%, P less than 0.05) was seen during DDD versus VVI pacing; no changes, however, were observed in the same patient with different AV delay or during DVI versus VDD pacing. These data suggest that programming of AV delay does not affect systolic performance at rest; longer diastolic filling times recorded during DDD pacing with "short" AV delay (90-140 msec) do not seem to be a hemodynamically relevant epi-phenomenon of PM programming.     

INDUCTION OF ALCOHOL DEHYDROGENASE IN LIVER AND GASTRO-INTESTINAL TRACT

Experiments were designed to determine whether the increased rate of ethanol clearance previously demonstrated in alcoholics, in normal humans and in rats following prolonged alcohol ingestion is due to an increase in activity of enzymes involved in its metabolism. Alcohol was given in various doses to 56 rats, and alcohol dehydrogenase (ADH) and lactic dehydrogenase (LDH) assayed in liver, bile, colon, stomach and small intestine. Results were compared with 13 controls and rats given either actinomycin D or cycloheximide. Results of our experiments clearly show that the activity of ADH and LDH in liver, stomach and small intestine significantly increases with administration of single and repeated doses of alcohol, and the effect persists for a significant time. The effect of alcohol appears to be specific, as increased activity in enzymes not involved in its metabolism was not found. Increased ADH activity could be blocked by actinomycin and cycloheximide which suggests that alcohol induced de novo synthesis of this enzyme protein. The increase in activity of the rate-limiting enzyme, ADH, by its substrate ethanol, provides a plausible explanation for the observed tolerance in both rats and man conditioned by prior administration of alcohol. The increase in LDH, a terminal enzyme involved in ethanol metabolism, provides further indirect evidence that ethanol can be metabolized at a faster rate through the normal pathway. The finding of both ADH and LDH in significant amounts in stomach and small intestine in both normal and alcohol-fed rats suggests that ethanol can be metabolized to a significant extent in extrahepatic sites. This is contrary to the current view that alcohol is metabolized entirely by the liver, and that the multiple metabolic derangements in the alcoholic are the consequence of its obligatory metabolism in that organ.     

Molar incisor hypomineralization: prevalence,severity and clinical consequences in Brazilian children

International Journal of Paediatric Dentistry 2010; 20: 426–434 Background. The prevalence of molar incisor hypomineralization (MIH) varies considerably around the world; however, few studies have examined MIH in South American countries. Objective. To evaluate the prevalence, severity, and clinical consequences of MIH in Brazilian children residing in rural and urban areas of the municipality of Botelhos, Minas Gerais, Brazil. Methods. Children aged 6 to 12 years (n = 918) with all four‐first permanent molars erupted had these teeth evaluated according to the European Academy of Paediatric Dentistry (EAPD) criteria. The examinations were conducted by two previously trained examiners, and the dental impact caused by MIH was evaluated with the Decayed, Missing and Filled Teeth (DMFT) index (WHO). Results. Molar incisor hypomineralization was present in 19.8% of the 918 children, with a higher prevalence in rural areas. The majority of the defects presented were demarcated opacities without post‐eruptive structural loss, which has been considered as mild defects. Children with MIH had higher DMFT values. Conclusion. Despite the high prevalence of MIH, the severity of the defects was mild. The results indicate a positive association between MIH and the presence of dental caries.     

Malignancy: Changes in Circulating Immature and Mature Dendritic Cells During IL-2 Cancer Immunotherapy and Their Relation with Lymphocyte Increase and Clinical Response

Lymphocytosis is the main biomarker predicting the efficacy of subcutaneous IL-2 anticancer immunotherapy. In addition, it has been demonstrated the fundamental role of dendritic cells (DC) in the generation of an effective anticancer immunity. However, the relation between IL-2 and DC system needs to be further understood. This preliminary study was performed in an attempt to analyze changes in circulating DC during IL-2 cancer immunotherapy in relation to lymphocyte variations and clinical efficacy of treatment. The study included 20 metastatic renal cell cancer patients, who underwent subcutaneous low-dose IL-2 immunotherapy (6.000.000 IU/day for 6 days/week for 4 weeks). To evaluate DC, venous blood samples were collected before and after 2 weeks of IL-2 injections, corresponding to the period of maximum lymphocytosis. Immature (CD123(+) ) and mature (CD11c(+) ) DC were measured by FACS and monoclonal antibodies. IL-2 induced a significant increase in the mean number of circulating mature DC, whereas no substantial change occurred in immature DC mean number. The increase in mature DC was associated with a control of disease, whereas no rise was observed in patients who had progressed on IL-2 immunotherapy. Moreover, the increase in mature DC mean number was significantly higher in patients showing evident lymphocytosis, with lymphocyte enhancement greater than 1000 cells/mmc, than in patients with less pronounced lymphocytosis, even though no significant correlation was seen in between mature DC and lymphocyte increase. This preliminary study would suggest that IL-2 may stimulate DC system and that the clinical anticancer efficacy of IL-2 is associated with the increase in circulating mature DC, which could be considered as a new favourable biomarker during IL-2 immunotherapy.