Effect of dimethadione administered intravenously on pancreatic secretion in dogs

Abstract In order to detect both pancreatic excretion of dimethadione (DMO), a weak organic acid, and the effect of pancreatic DMO on secretin-stimulated pancreatic secretion, DMO was given intravenously to dogs with pancreatic fistulae at a dose of 50, 100 and 200 mg/kg. DMO was promptly excreted into pancreatic juice; the concentration decreased exponentially as it did in plasma at the highest dose of the compound. At equilibrium of DMO between pancreatic juice and plasma, the DMO concentration in the juice depended directly on that in plasma; the juice/plasma concentration ratios for DMO exceeded 1.0, ranging from 1.7 to 2.1. Pancreatic DMO caused a small but significant decrease in the water, bicarbonate and sodium secretion at non-equilibrium, and in the bicarbonate secretion at equilibrium. A decrease in the bicarbonate secretion may result largely from the buffer action of bicarbonate on protons provided by the undissociated form of DMO. The sum of both bicarbonate and chloride concentrations in pancreatic juice decreased with the increased DMO concentration in the juice, implying that DMO may compete with the secretion of bicarbonate and/or chloride across the apical membrane of the duct cell. Pancreatic DMO can act as a non-specific inhibitor of pancreatic water and electrolyte secretions.     

Importance of mechanical damage to urinary red blood cells by the glomerular basement membrane

The reasons for morphological changes of urinary red blood cells (RBC) in patients with glomerulonephritis are still controversial. In order to evaluate the importance of mechanical damage by the glomerular basement membrane (GBM), we examined urinary RBC taken from the patients with two different diseases which have characteristic GBM changes. Urinary RBC taken from 20 patients with Alport syndrome and nine with thin GBM disease were examined using a scanning electron microscope. Nineteen out of the 20 patients (95.0%) with Alport syndrome showed ‘glomerular type’, while five of the nine patients (55.6%) with thin GBM disease showed ‘glomerular type’. These results suggest that more complicated GBM abnormalities cause more severe RBC distortion. Therefore, we conclude that mechanical damage by the GBM may be the major factor in dysmorphism of urinary RBC.     

Drug eruption due to intravesical instillations of both epirubicin and mitomycin C

We present the first patient to develop drug eruption due to intravesical instillations of both epirubicin and mitomycin C. A 58-year-old-man underwent transurethral resection (TUR) for superficial bladder carcinoma followed by instillations of intravesical chemotherapy. Immediately after TUR, the first instillation of epirubicin was performed. Two days after the first instillation, the patient developed generalized erythema of the face, trunk, upper and lower limbs. Two days after the second instillation, the patient developed severe generalized erythema and was diagnosed as having drug eruption due to intravesical instillations of epirubicin by the dermatologist. Instead of epirubicin, mitomycin C was instilled 2 weeks postoperatively. Two days after the first instillation of mitomycin C, the patient again developed severe generalized erythema and was diagnosed as having drug eruption due to intravesical instillation of mitomycin C. Drug eruption after the first instillation of epirubicin might have been due to drug toxicity of the agent. However, drug eruptions after the second instillation of epirubicin and the first instillation of mitomycin C might have been due to allergic reactions to the drugs. The patient has not received any further intravesical chemotherapy and has not demonstrated any such a drug eruption again.     

Effects of nifedipine on hepatic venous pressure gradient and portal vein blood flow in patients with cirrhosis

Abstract We investigated the effects of nifedipine on splanchnic haemodynamics in 13 patients with cirrhosis and portal hypertension, and in 10 control subjects using hepatic venous catheterization and pulsed Doppler ultrasound. There were no significant changes in systemic or splanchnic haemodynamics in control patients. In contrast, systemic vascodilatation, evidenced by significant decreases in mean arterial pressure and systemic vascular resistance, was observed in patients 20 min after sublingual application of 10 mg nifedipine. Moreover, hepatic venous pressure gradient and portal vein blood flow significantly increased after nifedipine administration. There was a significant correlation between the percentage increases in portal vein blood flow and in hepatic venous pressure gradient. However, no correlation was found between the percentage change in cardiac output and that in portal vein blood flow. Thus the increase in portal vein blood flow appears to be related to splanchnic arterial vasodilatation by nifedipine. Consequently, nifedipine has deleterious effects on portal haemodynamics in patients with cirrhosis. As nifedipine may potentially increase the risk of variceal haemorrhage in patients with less advanced varices, this drug should be used with caution in patients with chronic liver disease.     

Enhancement of J–ST-Segment Elevation by the Glucose and Insulin Test in Brugada Syndrome

NOGAMI, A., et al. : Enhancement of J–ST-Segment Elevation by the Glucose and Insulin Test in Brugada Syndrome. The effects of glucose and insulin on J–ST-segment elevation were evaluated in seven men   (mean age 45 ± 10 years)   with Brugada syndrome. Six patients had been reanimated from VF and one patient had experienced syncope. The effects of intravenous (1) pilsicainide 50 mg, (2) glucose 50 g, and (3) glucose 50 g plus regular insulin 10 IU on the precordial ECG leads were examined. Pilsicainide significantly enhanced J-ST elevation in all patients and induced VF in 1 patient. A significant accentuation of the abnormal J-ST configuration was observed in all patients at a mean of   51 ± 40   minutes after glucose and insulin infusion. Changes in blood glucose and serum potassium concentration were   111 ± 158 mg/dL   and   −0.30 ± 0.48 mEq/L   , respectively. These changes were not directly related to the ECG changes. Glucose infusion without insulin caused a subtle increase in J-ST elevation. In conclusion, the administration of glucose and insulin safely unmasked or accentuation the J–ST-segment elevation in Brugada syndrome. Blood glucose and insulin concentrations may be factors modulating the circadian or day-to-day ECG variations in this syndrome. (PACE 2003; 26[Pt. II]:332–337)     

Laparoscopic cholecystectomy in the elderly: Analysis of pre-operative risk factors and postoperative complications

A retrospective study was conducted of two groups of patients over (group 1, n= 57) and under (group 2, n= 655) the age of 70 years who underwent laparoscopic cholecystectomy (LC). The pre-operative physical status and systemic complications, operation time, postoperative complications, postoperative hospital stay and other clinical features of the two groups were compared. The incidence of pre-operative complications in group 1 was significantly higher than that in group 2 (P < 0.05). Postoperatively no severe complication was found in any patient. Group 1 showed significantly prolonged operation time and postoperative hospital stay compared with group 2 (P < 0.05). The difference between the groups in the intra-operative treatment time and postoperative treatment is attributed to the greater prevalence of common bile duct stone in group 1 as there was little difference between the groups in the postoperative recovery after exclusion of these patients. No pulmonary complications, which are associated with LC, were observed; the postprocedure pain was slight and the period of bedrest was short. If complications associated with pneumoperitoneum can be prevented, this surgery is an excellent measure to improve the quality of life of even elderly patients with cholecystolithiasis.     

A Structure-Relationship Study of the Uptake of Aliphatic Polyamine Compounds by Rat Intestinal Brush-border Membrane Vesicles

The effects of lipophilicity, ion-diffusion potential and membrane surface potential on the uptake of various aliphatic polyamine compounds by rat intestinal brush-border membrane vesicles (BBMV) have been investigated. A valinomycin-induced potassium-diffusion potential (inside-negative) stimulated the initial uptake of diamine compounds, and good correlation was observed between lipophilicity and the amount of diffusion-potential-dependent transport of the diamines. In contrast, because of their much lower lipophilicity, tri- and tetraamine compounds were not affected by the diffusion potential. Tetracaine, which can make the membrane surface potential more positive, inhibited the transport rate of 1,9-nonanediamine, spermidine and spermine by the BBMV. These data suggest that the transport mechanism of diamines is similar to that of monoamine compounds in respect to its dependence on ion-diffusion potential and on the membrane surface potential. The extent of the effect of ion-diffusion potential on the rate of transport of the diamines was closely related to the lipophilicity of the diamine. In contrast, only the surface potential contributed to the transport mechanism of lower lipophilic tri- and tetraamine compounds.     

Enantioselective Pharmacokinetics of Homochlorcyclizine: Disposition of (+)- and (–)-Homochlorcyclizine after Intravenous and Oral Administration of Racemic Homochlorcyclizine to Rats

Abstract— Concentrations of homochlorcyclizine enantiomers in blood, urine, and tissues of the liver, lung, kidney, brain, heart, spleen, intestine and stomach of rats after drug administration were determined by high-performance liquid chromatography on a chiral stationary phase. After intravenous administration (10 mg kg^?1), homochlorcyclizine was rapidly distributed in many tissues, with the highest concentration in lung. No differences were found between enantiomers in blood concentrations. After oral administration (50 mg kg^?1), the concentrations of the (+)-isomer in nearly all tissues were higher than those of the (–)-isomer. The AUC_0-x values of the (+)- and (–)-isomers differed significantly. The absorption of racemic homochlorcyclizine from rat small intestine was not enantioselective. These results suggested that the different concentrations between enantiomers after oral administration were not caused by enantioselective absorption or distribution but rather by preferential first-pass metabolism of the (–)-isomer in the liver. The enantioselectivity of metabolism was also demonstrated by in-vitro experiments.     

Long-term sequential changes of antibody to p40tax in HTLV-I carrier mothers and children

Antibody to p40^tax (anti-p40^tax) in serum specimens obtained sequentially from a human T cell lymphotropic virus type I carrier population of mothers and children were assayed. The prevalences of anti-p40^tax at the initial sampling were 88% (7/8) in children and 55% (16/29) in mothers. Two of the seven positive children lost their anti-p40^tax during the investigation period, resulting in a final prevalence of 63% (5/8) in children. However, anti-p40^tax status was constant in all the 22 mothers with multiple serum samples (15 remained positive and seven remained negative). A decline in the absorbance value of EIA for anti-p40^tax was observed in seven of the 15 anti-p40^tax positive mothers. This decline may result in the disappearance of anti-p40^tax in some of them.