Prevention of hypertensive crisis with ATP during anesthesia for pheochromcytoma

In the anesthetic management of five patients undergoing excision of pheochromocytoma, adenosine triphosphate (ATP) was used for the purpose of regulating systemic arterial pressure during the period of tumor manipulation. ATP was administered at doses of 0.05–0.4mg/kg/min. Systemic arterial pressure showed a significant decrease from 162 ± 17/103 ± 11mmHg before manipulation to 136 ± 21/81 ± 10mmHg during the manipulation period. The plasma catecholamine levels showed significant increases in this period. Immediately after excision, the systemic arterial pressure was maintained at normal levels (118 ± 13/75 ± 16mmHg) by fluid replacement and discontinuation of ATP administration, subsequently becoming 129 ± 19/79 ± 16mmHg. The heart rate was very stable and tachycardia did not ocurr during the manipulation period. Only one arrhythmic episode ocurred in one patient. The systemic vascular resistance index was significantly lower during the manipulation period than before it. It was therefore considered that ATP was useful as an agent for controlling arterial pressue during the anesthesia for pheochromocytoma.(Murata K, Sodeyama O, Ikeda K et al.: Prevention of hypertensive crisis with ATP during anesthesia for pheochromocytoma. J Anesth 1: 162–167, 1987)     

Quantitative evaluation of regional pulmonary ventilation using PET and nitrogen-13 gas

A new quantitative method, "Simultaneous Exponential Equation method" (SEE), has been developed for the analysis of pulmonary ventilation studies using 13N-labeled nitrogen gas and positron emission computed tomography. This method uses Kety's model assuming insolubility of nitrogen gas in blood or tissues. Activity in poorly ventilated regions does not reach the equilibrium in the so-called equilibrium scan (EQ) performed following 3 or 4 min of washin. Therefore EQ images do not represent lung volume images nor do they provide the initial value of washout phase. Our method corrects for these transient phenomena observed during EQ scan and yields idealistic equilibrium state images (lung volume images) as well as more accurate regional ventilatory time constants than a modified Stewart-Hamilton (A/H) method and tomograms of high resolution.     

The Effects of Gold Kiwifruit Intake Timing with or without Pericarp on Postprandial Blood Glucose Level

The purpose of this study was to examine how gold kiwifruit pericarp (pericarp is defined as the skin of the fruit) consumption and the timing thereof affect the postprandial blood glucose profile. The study was conducted on twelve healthy volunteers (six men and six women). According to our results, the simultaneous intake of gold kiwifruit with bread and the prior intake of gold kiwifruit evidently suppressed the postprandial blood glucose elevation compared with exclusive bread intake. There was no significant difference in postprandial blood glucose changes between the ingestion of gold kiwifruit pericarp and pulp and that of gold kiwifruit pulp only. The highest postprandial blood glucose elevation was suppressed by 27.6% and the area under the blood glucose elevation curve by 29.3%, even with the exclusive ingestion of gold kiwifruit pulp. We predicted that the ingestion of both the pericarp and pulp of gold kiwifruit would reduce the postprandial blood glucose elevation to a greater extent than that of gold kiwifruit pulp only; however, there was no significant difference between the two. These results indicate that gold kiwifruit consumption significantly suppresses the postprandial blood glucose elevation regardless of pericarp presence or absence and the timing of ingestion.     

Enhancement of thermal damage in murine tumors by hydralazine-induced modification of blood flow and oxygen tension

We investigated changes in blood flow in normal muscle and in SCC-VII tumors treated by hyperthermia combined with hydralazine, to evaluate the enhancement of thermal tumor damage by hydralazine. We studied SCC-VII tumor-bearing C3H/He mice. Hydralazine was administered by intraperitoneal injection, and tumors were heated by a water bath. We measured blood flow using the laser Doppler method, and oxygen tension using polarography. The response of tumors to therapy was assessed using a growth delay analysis. In tumors, blood flow and O-2 tension significantly decreased with increasing doses of hydralazine. Compared to tumors treated by hydralazine alone or by hyperthermia alone, tumor blood flow was significantly decreased in the group treated by hyperthermia with hydralazine. In tumors treated by hyperthermia with hydralazine, blood flow was significantly decreased with increasing Hyd doses, heat durations, and temperatures. In normal muscle, no decrease in blood flow was induced by hyperthermia, hydralazine, or their combination. In tumors treated by hyperthermia (43 degrees C, 20 min) with hydralazine, a maximum additional growth delay was observed. Our results suggest that a decrease in tumor blood flow caused by hydralazine plays an important role in enhancement of the hyperthermic antitumor effect.     

Dynamic changes in glucose metabolism of living rat brain slices induced by hypoxia and neurotoxic chemical-loading revealed by positron autoradiography

Fresh rat brain slices were incubated with 2-deoxy-2-[18F]-fluoro-D-glucose ([18F]FDG) in oxygenated Krebs-Ringer solution at 36 degrees C, and serial two-dimensional time-resolved images of [18F]FDG uptake were obtained from these specimens on imaging plates. The fractional rate constant (= k3*) of [18F]FDG proportional to the cerebral glucose metabolic rate (CMRglc) was evaluated by applying the Gjedde-Patlak graphical method to the image data. With hypoxia loading (oxygen deprivation) or glucose metabolism inhibitors acting on oxidative phosphorylation, the k3* value increased dramatically suggesting enhanced glycolysis. After relieving hypoxia < or = 10-min, the k3* value returned to the pre-loading level. In contrast, with > or = 20-min hypoxia only partial or no recovery was observed, indicating that irreversible neuronal damage had been induced. However, after loading with tetrodotoxin (TTX), the k3* value also decreased but returned to the pre-loading level even after 70-min TTX-loading, reflecting a transient inhibition of neuronal activity. This technique provides a new means of quantifying dynamic changes in the regional CMRglc in living brain slices in response to various interventions such as hypoxia and neurotoxic chemical-loading as well as determining the viability and prognosis of brain tissues.     

Effects of protein meals on the urinary excretion of various plasma proteins in healthy subjects

To examine whether hemodynamic changes in response to acute protein loadings with different protein sources cause increases in urinary excretion of plasma proteins in healthy subjects, urinary excretions of various plasma proteins with various molecular radii and isoelectric points, namely albumin (Alb), IgG, IgG4, ceruloplasmin (CRL), and alpha2-macroglobulin (A2), were measured in healthy subjects after ingestion of a beef meal or of a tuna fish meal. Significant increases in urinary excretions of the negatively charged IgG4 and CRL and of the neutrally charged IgG were found in parallel with enhanced creatinine clearances after each protein ingestion. These renal responses returned to basal levels 9 h after the test. This finding suggests that in healthy subjects, the increase in glomerular filtration rate after acute protein loading caused selective enhancement of urinary excretions of plasma proteins with a molecular radius of approximately 55 A (the radius of IgG, IgG4, and CRL), irrespective of the charge barrier of the glomerulus. The increases in these three plasma proteins may be induced by leakage via the shunt pathway in the glomerulus, as proposed earlier (see text). In contrast, increases in urinary excretions of A2 and Alb were not found. The former finding may be explained by the possibility that A2 would not pass through this pathway, since the molecular radius of A2 (88 A) is larger than that of IgG, although the latter finding may be partially explained by preferential renal tubular reabsorption of Alb.     

Shock and acute organ dysfunction

Multiple trauma, hemorrhage, and sepsis may produce various kinds of shock, and such a host as shock could not be controlled and may easily fall into multiple organ dysfunction. Although those mechanisms on the pathogenesis of these sequential inflammatory responses have been clarified recently, the clinical outcome of such patients suffering from severe sepsis and multiple organ dysfunction is still very low. This inflammatory response against the insult shows a sequential manner; cardiovascular system failure, renal system failure, respiratory system failure, central nervous system failure, and finally, hepatic failure. However, the host response to the insult is a kind of defense against the invasion, and the clinical goal might be to stabilize hemodynamic system, metabolic system, and immunologic system. To achieve hemodynamic homeostasis, we use catecholamines and blood transfusion to improve the oxygen supply to important organs and enhance tissue repair. For metabolic homeostasis, early administration of hyperalimentation may be needed, either parenterally or enterally. Enteral feeding may also provided a route for bacterial translocation. To achieve immunologic homeostasis, prophylactic antibiotic administration and metabolic support may be required and should also protect against infection as a secondary invasion. This review explains these mechanisms in terms of the relationship between shock and organ dysfunction and the general features of clinical management.     

The occurrence of polymorphism of mannose 6-phosphate/insulin-like growth factor 2 receptor gene in laboratory and wild rats

Carcinogen-resistant inbred DRH rat strain was established from closed colony Donryu rats in the presence of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). Despite using 3'-Me-DAB during the stage of selection, the DRH rats developed normally and did not show any spontaneous tumor at over 1 year of age. In the present study, we examined the polymorphism in mannose 6-phosphate/insulin-like growth factor 2 receptor (M6p/Igf2r) gene and found that the DRH rat showed CCC (Proline)-type polymorphism in exon 48 and the Donryu rat had GCC (Alanine) sequence. Since the DRH rat was developed from the Donryu rat, we examined whether this polymorphism in exon 48 of M6p/Igf2r gene was due to mutation that occurred at the stage of selection in the presence of 3'-Me-DAB, using several other laboratory and wild rats. We detected the presence of polymorphism at the same site of the M6p/Igf2r gene among these rats. It is likely that the polymorphism in exon 48 of the M6p/Igf2r gene is present broadly in rats since ancient times and not due to the mutation during the course of selection unless this site is a hot spot for chemical carcinogens.