Dibenzo[a,l]pyrene-induced DNA adduction, tumorigenicity, and Ki-ras oncogene mutations in strain A/J mouse lung

Dibenzo[a,l]pyrene (DB[a,l]P), an environmental polycyclic aromatic hydrocarbon, is the most potent carcinogen ever tested in mouse skin and rat mammary gland. In this study, DB[a,l]P was examined for DNA adduction, tumorigenicity, and induction of Ki-ras oncogene mutations in tumor DNA in strain A/J mouse lung. Groups of mice received a single i.p. injection of 0.3, 1.5, 3.0, or 6.0 mg/kg DB[a,l]P in tricaprylin. Following treatment, DNA adducts were measured at times between 1 and 28 days, while tumors were counted at 250 days and analyzed for the occurrence of point mutations in codons 12 and 61 of the Ki-ras oncogene. DB[a,l]P in strain A/J mouse lung induced six major and four minor DNA adducts. Maximal levels of adduction occurred between 5 and 10 days after injection followed by a gradual decrease. DB[a,l]P-DNA adducts in lung tissue were derived from both anti- and syn-11,12- dihydroxy-13,14-epoxy- 11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]PDE) and both deoxyadenosine (dAdo) and deoxyguanosine (dGuo) residues in DNA as revealed by cochromatography. The major adduct was identified as a product of the reaction of an anti-DB[a,l]PDE with dAdo in DNA. DB[a,l]P induced significant numbers of lung adenomas in a dose- dependent manner, with the highest dose (6.0 mg/kg) yielding 16.1 adenomas/mouse. In tricaprylin-treated control animals, there were 0.67 adenomas/mouse. Based on the administered dose, DB[a,l]P was more active than other environmental carcinogens including benzo[a]pyrene. As a function of time-integrated DNA adduct levels, DB[a,l]P induced lung adenomas with about the same potency as other PAHs, suggesting that the adducts formed by DB[a,l]P are similar in carcinogenic potency to other PAHs in the strain A/J mouse lung model. Analysis of the Ki- ras mutation spectrum in DB[a,l]P-induced lung tumors revealed the predominant mutations to be G-->T transversions in the first base of codon 12, A-->G transitions in the second base of codon 12, and A-->T transversions in the second or third base of codon 61, concordant with the DNA adduct profile.      

TREATMENT OF PALMOPLANTER HYPERHIDROSIS BY IONTOPHORESIS

Twenty-seven patients with idiopathic palmoplanter hyperhidrosis were treated with Iontotherapy over a one year period. In twenty-four cases there was a good response but maintenance therapy was required every 3-4 weeks.KEY WORDS: Iontophoresis, Palmoplanter hyperhidrosis     

Decrease in inner retinal thickness at para- and perifoveal areas before vascular retinopathy in patients with metabolic risk factors

BackgroundHypertension, dyslipidemia, and hyperglycemia are major risk factors for vascular retinopathy. The relationship between retinal thickness at the macular area and metabolic risk factors, as well as visual impairment, in elderly patients before developing vascular occlusion needs to be investigated.MethodsIn this prospective, case-control study, patients >60 years old, without objective visual threatened ocular diseases or systemic abnormalities, except for hypertension, dyslipidemia or/and hyperglycemia, were included for measurement of retinal thickness at the macular area by optical coherence tomography (OCT).ResultsFifty-four patients were analyzed; 11 patients had no metabolic risk factors, 16 had one, 17 had two, and 10 had three. There was no significant difference in age, and full and outer retinal thickness, but there was a significantly lower inner retinal thickness at the parafoveal (p = 0.0013) and perifoveal (p = 0.018) areas in patients with at least one metabolic risk factor. The superior (p = 0.040) and inferior (p = 0.046) inner retina at the perifovea and superior (p = 0.013) inner retinal thickness at the parafovea were sensitive to metabolic abnormalities. Only patients with three factors had significantly reduced best corrected visual acuity (BCVA).ConclusionElderly patients with metabolic risk factors had decreased inner retinal thickness at the para- and perifoveal areas before retinal vascular diseases. Accelerated inner retinal degeneration occurred prior to visual impairment.     

Atypical respiratory complications of dengue fever

In last decade, dengue has emerged as one of the most important vector born disease. With increasing cases, uncommon presentations and complications are now commonly recognized. Here, we report two cases of rare pattern of respiratory involvement in dengue: acute respiratory distress syndrome and bronchiolitis with respiratory failure.     

Serum retinoic acid levels in patients with resected benign and malignant colonic neoplasias on β‐carotene supplementation

To determine whether patients with colon cancer metabolize β‐carotene differently from benign colon polyp patients, a normal control group (n = 13) and groups of resected colon polyp patients (n = 29) or resected colon cancer patients (Dukes A and BI, n = 21) were supplemented with placebo or β‐carotene (30 mglday) taken with their morning meals for three months. Serum samples at zero and three months of the study were anlayzed blindly for retinoic acid and β‐carotene. The results showed that β‐carotene levels in the serum of colon polyp and colon cancer groups were 8‐ to 12‐fold higher than in the untreated control or the placebo‐treated groups. The benign polyp subjects (n = 17) receiving β‐carotene showed a significant rise in serum trans‐retinoic acid at three months compared with Time 0. The trans‐retinoic acid values from the colon cancer group receiving β‐carotene (n = 11) or placebo (n = 10) were significantly lower than the values from the β‐carotene‐supplemented colon polyp group. It appears that trans‐retinoic acid levels in response to β‐carotene supplementation are different between treated cancer and benign patients because of different body demands for retinoic acid.     

Reflection and critical thinking of humanistic care in medical education

The purpose of this paper is to stress the importance and learning issues of humanistic care in medical education. This article will elaborate on the following issues: (1) introduction; (2) reflection and critical thinking; (3) humanistic care; (4) core values and teaching strategies in medical education; and (5) learning of life cultivation. Focusing on a specific approach used in humanistic care, it does so for the purpose of allowing the health professional to understand and apply the concepts of humanistic value in their services.     

Decreased expression of phospholipase C-beta 2 isozyme in human platelets with impaired function

Platelets from a patient with a mild inherited bleeding disorder and abnormal platelet aggregation and secretion show reduced generation of inositol 1,4,5-trisphosphate, mobilization of intracellular Ca2+, and phosphorylation of pleckstrin in response to several G protein mediated agonists, suggesting a possible defect at the level of phospholipase C (PLC) activation (see accompanying report). A procedure was developed that allows quantitation of platelet PLC isozymes. After fractionation of platelet extracts by high-performance liquid chromatography, 7 out of 10 known PLC isoforms were detected by immunoblot analysis. The amount of these isoforms in normal platelets decreased in the order PLC- gamma 2 > PLC-beta 2 > PLC-beta 3 > PLC-beta 1 > PLC-gamma 1 > PLC- delta 1 > PLC-beta 4. Compared with normal platelets, platelets from the patient contained approximately one-third the amount of PLC-beta 2, whereas PLC-beta 4 was increased threefold. These results suggest that the impaired platelet function in the patient in response to multiple G protein mediated agonists is attributable to a deficiency of PLC-beta 2. They document for the first time a specific PLC isozyme deficiency in human platelets and provide an unique opportunity to understand the role of different PLC isozymes in normal platelet function.