Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast

It is well known that sex steroids play important roles in the development of invasive ductal carcinoma (IDC) of the human breast. However, biological significance of sex steroids remains largely unclear in ductal carcinoma in situ (DCIS), regarded as a precursor lesion of IDC, which is partly due to the fact that the intratumoral concentration of sex steroids has not been examined in DCIS. Therefore, in this study, we first examined the intratumoral concentrations of estradiol and 5alpha-dihydrotestosterone (DHT) using liquid chromatography/electrospray tandem mass spectrometry in DCIS. Intratumoral concentrations of both estradiol and DHT were threefold higher in DCIS than non-neoplastic breast tissues and estrogen-producing enzymes (aromatase, steroid sulfatase, and 17beta-hydroxysteroid dehydrogenase type 1 (17betaHSD1)), and androgen-producing enzymes (17betaHSD5 and 5alpha-reductase type 1 (5alphaRed1)) were abundantly expressed in DCIS by real-time PCR and immunohistochemical analyses. The intratumoral concentration of DHT was significantly lower in IDC than DCIS, while the expression of aromatase mRNA in carcinoma cells and intratumoral stromal cells was significantly higher in IDC than those in DCIS. Immunohistochemistry for sex steroid-producing enzymes in DCIS demonstrated that 5alphaRed1 immunoreactivity was positively correlated with Ki-67 labeling index and histological grade and was also associated with an increased risk of recurrence in patients with DCIS examined. Results of our study suggest that intratumoral concentrations of estradiol and DHT are increased in DCIS, which is possibly due to intratumoral production of these steroids. Therefore, estradiol and DHT may play important roles in the development of DCIS of the human breast.     

Histopathologic changes in serum bile acid fractions in pressure ulcer patients

BACKGROUND/AIMS: Bile acids are synthesized in the liver and released into the intestinal tract to aid in digestion and absorption by increasing permeability via alteration of the cell membrane. Bedridden elderly patients typically have pressure ulcers that may be due to both physical local pressure as well as skin cell changes induced by the physiologic effects of bile acids. METHODOLOGY: This study investigated 31 elderly bedridden patients with pressure ulcers (mean age, 81.7 years) and 19 healthy elderly (mean age, 79.7 years). Five serum bile acid fractions were summed to determine total bile acid, and transaminase and cholesterol levels were also measured. RESULTS: Total cholesterol levels were significantly lower (p<0.05) in pressure ulcer patients and transaminase levels were not significantly different between the two groups. The primary bile acids were generally higher and the secondary and tertiary bile acids lower in pressure ulcer patients. In particular, the secondary bile acid deoxycholic acid was significantly higher in all pressure ulcer patients. When analyzed by grade of pressure ulcer, the primary bile acids were significantly lower in pressure ulcer patients. CONCLUSIONS: Secondary bile acid fraction deoxycholic acid measurements may indicate bedridden patients at higher risk for pressure ulcers.     

Diffuse hepatic calcification as a sequela to shock liver

A 31-yr-old Japanese woman who was on chronic hemodialysis for 3 yr died of intractable congestive heart failure. Three years before death, the patient was in a state of shock for 48 h due to ventricular tachycardia and gastrointestinal bleeding, which was followed by marked elevation of serum transaminase. Four months later, abdominal plain radiography demonstrated diffuse hepatic calcification. At autopsy, microscopic examination of the liver revealed parenchymal necrosis and tiny calcifications in the central to midzonal area of the lobule. Calcification in the degenerative area of the hepatic lobule occurred subsequent to parenchymal ischemia after overt shock that lasted for 2 days. Although a definitive explanation for the calcification was not obtained, it may be related to the disturbances of intracellular Ca2+ homeostasis as a result of ischemic liver injury or it may be related to an elevated calcium-phosphorus product in the uremic state.     

Long-term trend in serum (1,3)-β-D-glucan level in a man with chronic disseminated candidiasis treated with corticosteroids

Chronic disseminated candidiasis (CDC) is a type of invasive candidiasis. CDC commonly appears in the neutrophil recovery phase after chemotherapy in patients with hematologic malignancies, and immune reconstitution inflammatory syndrome (IRIS) is thought to play a major role in CDC development. This report describes the case of a 33-year-old man with CDC as a complication of acute myeloid leukemia. We describe the clinical course, body temperature, therapy, and (1,3)-β-D-glucan (BDG) levels over the course of 22 months. He was initially treated with antifungals, but corticosteroids were added because of a persistently elevated body temperature, which we attributed to IRIS. After starting corticosteroids, his clinical condition improved, but his BDG levels became markedly elevated. We hypothesize that the suppression of the excessive immune response by corticosteroids lead to granuloma collapse, fungal release, and hematogenous dissemination, resulting in elevated BDG levels. The patient's condition gradually improved over the course of follow-up.     

Early effects of lafutidine or rabeprazole on intragastric acidity: which drug is more suitable for on-demand use?

Background Medication for the relief of heartburn should have the rapid onset of action required for on-demand use. We studied the inhibition of gastric acid secretion by lafutidine and rabeprazole, given in single doses to fasting and postprandial subjects.Methods A total of 22 healthy male, Helicobacter pylori-negative volunteers participated in this randomized, two-way crossover study. They were randomly assigned to receive a single oral dose of 10mg lafutidine or 20mg rabeprazole after fasting overnight (12 subjects, fasting study) or after eating a test meal (noodles, 364kcal; protein, 10.1g; fat, 16g; carbohydrates, 44.9g; NaCl, 1.1g; 10 subjects, postprandial study). Intragastric pH was monitored continuously for 6h after treatment. The other drug was given after a washout period of at least 7 days, and intragastric pH was similarly monitored.Results In the fasting study, lafutidine sustained pH at >3 and >4 during the second, third, fourth, fifth, and sixth hours of the study for significantly longer than rabeprazole. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole. In the postprandial study, lafutidine sustained pH >3 and >4 for longer periods than rabeprazole during the third, fourth, fifth, and sixth hours of the study. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole.Conclusions Lafutidine 10mg produces a prompter rise in intragastric pH than rabeprazole 20mg in fasting and postprandial Helicobacter pylori-negative male subjects.