Pharmacokinetics of carboplatin and etoposide in a haemodialysis patient with Merkel-cell carcinoma

We present a Merkel-cell carcinoma patient with chronic renal failure requiring haemodialysis and evaluate the pharmacokinetics of carboplatin and etoposide during haemodialysis. The area under the concentration-time curve of carboplatin was increased by prolonging the interval between administration and haemodialysis. However, that of etoposide was not changed. Carboplatin showed good membrane permeability in haemodialysis, while etoposide showed no permeability. In conclusion, the pharmacokinetics of carboplatin could be controlled by haemodialysis and the interval between chemotherapy and haemodialysis. However, the pharmacokinetics of etoposide were not affected.     

The value and limitation of resting 201Tl reinjection after stress-redistribution imaging for the assessment of myocardial viability: comparison with wall motion improvement by revascularization]

Clinical value and limitation of resting reinjection of small dose of thallium (37 MBq) for the assessment of myocardial viability were evaluated. The results were compared with the degree of wall motion improvement by revascularization to infarcted myocardium supplied by chronic total vessels in 12 patients with old myocardial infarction. Thallium uptake was visually scored and judged as normal, reversible defect (Group 1), new fill in after reinjection (Group 2A), and no fill in even after reinjection (Group 2B). Among 53 segments with initial perfusion abnormality, 21 segments reverted to almost normal, while 32 segments remained abnormal on redistribution images. New fill in after reinjection was observed in 11 segments of 32 segments showing persisting defect on stress and delayed image (37%). Wall motion score index of Group 2A improved significantly higher than Group 2B (p less than 0.01) and almost equal to Group 1, suggesting the utility of reinjection for the assessment of tissue viability which may be underestimated by conventional imaging. But significant wall motion improvement (greater than or equal to 0.6 mean SD/chords) was observed in 6 segments (29%) of 21 segments showing neither redistribution nor fill in after reinjection. These data indicate that small dose of thallium reinjection may enhance detection of viable but jeopardized myocardium, although some underestimation of viability remained to be resolved.     

Successful Norwood operation for single left ventricle associated with severe subaortic stenosis, coarctation of aorta and hypoplastic aorta]

A 4 month-old boy who had double-inlet left ventricle, severe subaortic stenosis, hypoplastic ascending aorta and coarctation of the aorta revealed severe respiratory failure. An urgent Norwood operation was done. The procedure consisted of enlargement of the ascending aorta and main pulmonary artery and a systemic-pulmonary shunt using 5 mm PTFE tube. Postoperative course was uneventful.     

Electrogastrographic activity in patients who received proximal gastrectomy plus jejunal interposition or total gastrectomy plus jejunal interposition.

Electrogastrograms (EGGs) were recorded in patients both before and after receiving proximal gastrectomy plus jejunal interposition (PGJI) or just after receiving total gastrectomy plus jejunal interposition (TGJI). Intraluminal pressure was also recorded in some postoperative patients. The EGG 3 cpm component (2.5-4.9 cpm) remained after PGJI, but subsequently decreased with a significant reduction in the preoperative to postoperative ratio of the 3 cpm components (P<0.05). The mean frequency of the 3 cpm components increased significantly after PGJI (P<0.05) and its instability factor increased. The EGG 10 cpm components became relatively dominant compared to other frequency components in 2 out of 8 of patients having PGJI but the mean amplitude of 10 cpm decreased. In TGJI patients, only the 10 cpm component was conspicuous in EGG as in the case of total gastrectomy and Roux en Y anastomosis procedures. The spectral frequencies of intraluminal pressure in the interposed jejunum were similar to the EGG of 10 cpm components both in the case of PGJI and TGJI patients. In conclusion, surface EGG could record the electrical activities of the interposed jejunum more easily in patients having had TGJI than in PGJI.     

Radical correction of paracardiac type IIb of total anomalous pulmonary venous connection using pedicled flaps of right atrium and atrial septum

Surgical results of total anomalous pulmonary venous connection (TAPVC) has been improved in recent years, however, late development of pulmonary venous obstruction was our concern in its total correction in early infancy. In the cardiac type of TAPVC, in which the pulmonary veins were connected to the right lateral wall, prosthetic patch is conventionally used in diversion of pulmonary venous flow into left atrium. It seemed favorable to repair this subset without using prosthesis. A 3-month-old female with TAPVCIIb according to Darling's classification underwent total correction on September 22th, 1988. Two pedicled flaps were developed using the right atrial wall and the atrial septum to create a pulmonary venous channel to divert arterial blood into left atrium and absorbable sutures were used throughout. Right atrium was entered through a vertical incision in its body and all the pulmonary veins were found in a recess in the lateral wall of the right atrium. Atrial septal defect in the cranial aspect of the fossa ovalis was enlarged by cutting the primum tissue along the right limbus and its caudal margin so as to form a pedicled flap attached to the left limbic tissue. Then the flap was sutured along the limbus to create a roof of the fossa ovalis. The second flap was made in the middle of the lateral atrial wall and was used to create a tunnel from the recess to the atrial septal defect. The defect in the right atrial wall was closed directly and no prosthetic patch was used. Postoperative course was uneventful and echocardiogram showed wide pulmonary venous channel draining into the left atrium.     

Preferential consumption of heparin cofactor II in disseminated intravascular coagulation associated with acute promyelocytic leukemia.

We measured plasma heparin cofactor II (HC II) activity in patients with disseminated intravascular coagulation (DIC) due to various underlying diseases together with the levels of antithrombin III (AT III), pseudocholinesterase (a marker of hepatic synthesis), and various haemostatic molecular markers. Both HC II and AT III were decreased in DIC secondary to all the underlying diseases studied, except acute promyelocytic leukemia (APL), when compared with healthy subjects. The lowest HC II and AT III levels was observed in coagulopathy secondary to liver disease, the HC II level in sepsis was the second lowest. In DIC due to APL, the decrease in HC II was not accompanied by a decrease in AT III. Thus, we divided all 124 samples tested into APL and non-APL groups. The HC II level correlated positively with fibrinogen and plasminogen in both the APL and non-APL groups. In the APL group, the HC II level had a significant negative correlation with the thrombin-AT III complex (TAT), fibrinogen/fibrin degradation products, and D-dimer levels as well as the prothrombin time, while AT III showed no correlations with any of the haemostatic parameters. These results suggest that HC II may be consumed preferentially by thrombin in APL patients with DIC, and thus may spare the consumption of AT III. Accordingly, HC II seems to be a superior indicator of DIC than AT III in APL patients. Moreover, replacement therapy with HC II instead of AT III may be useful to treat DIC associated with APL. In the non-APL group, the HC II levels were positively correlated with the levels of AT III and pseudocholinesterase activity. This indicates that plasma HC II levels are closely related not only to consumption coagulopathy but also to hepatic synthetic activity, as is the case for plasma AT III.     

Pharmacologic preconditioning effects: Prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver

Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver.     

Tape-stripping method in man: comparison of evaporimetric methods

BACKGROUND/PURPOSE: If the occlusion time of a closed chamber evaporimeter on the skin is too long, saturation might occur. We previously compared an open chamber and a closed chamber device on healthy volunteers. Comparable data on stripped skin with higher evaporation rates are not available. This study compares the sensitivity and correlation of open and closed chamber devices in a tape-stripping human model. The amount of tape removed SC was also quantified with a protein assay method. METHODS: Ten healthy volunteers (six male and four female; seven Caucasians and three Asian; mean age 38+/-16) were enrolled. In a randomized manner, one forearm was measured by an open chamber device and the opposite by a closed chamber device. After recording baseline measurements, 20 strippings were taken on each test site with tape disks. Transepidermal water loss (TEWL) was measured at the end of 10 and 20 tape strippings at each test site. Stratum corneum (SC) aggregates in the strips was assayed. RESULTS: The mean values obtained from two devices were similar after 10 trips and 20 strips. There was no statistically significant difference. The closed chamber device showed a slightly higher (but not significant) inter-individual coefficient of variation. SC aggregates in the strips were similar and without a statistically significant difference. CONCLUSION: The study suggests that both devices might yield similar TEWL values on stripped human skin in vivo.     

Mechanism of toxic action of fluoride in dental fluorosis: whether trimeric G proteins participate in the disturbance of intracellular transport of secretory ameloblast exposed to fluoride

In enamel fluorosis model rats treated with sodium fluoride, secretory ameloblasts of incisor tooth germs exhibited disruption of intracellular trafficking. We examined whether heterotrimeric G proteins participated in the disruption of vesicular trafficking of the secretory ameloblast exposed to fluoride, using immunoblotting and pertussis toxin (IAP)-induced adenosyl diphosphate (ADP)-ribosylation for membrane fractions of the cell. Immunoblotting of crude membranes, post supernatants of the ameloblast, with anti-G_i3/o and anti-G_s antibodies showed that G_i3 or G_o proteins existed in the secretory ameloblast, but G_s protein did not. Immunoblotting of the subcellular membrane fractions indicated that the G_i3 or G_o proteins were located in the Golgi membrane, but were not in the rough endoplasmic reticulum (rER) membrane. Autoradiograph of IAP-induced ADP-ribosylation, however, showed the existence of IAP-sensitive G proteins both in rER and Golgi membranes. Fluoride treatment decreased the G proteins bound to both membranes. These findings indicate that different G proteins, both of which are IAP-sensitive, are present in the rER and Golgi apparatus, and suggest that these G proteins participate in the disturbance of intracellular transport of the secretory ameloblast exposed to fluoride. Received: 24 June 1998 / Accepted: 8 September 1998