Insulin sensitivity and the effects of insulin on renal sodium handling and pressor systems in essential hypertensive patients.

Insulin resistance and hyperinsulinemia are linked with essential hypertension. To clarify insulin sensitivity in Japanese essential hypertensive patients and the role of insulin resistance in these patients, a euglycemic hyperinsulinemic glucose clamp was applied in 17 essential hypertensive patients and 12 normotensive subjects. The mean glucose infusion rate was used as an indicator of insulin sensitivity (M value). This study revealed a significantly lower M value in essential hypertensive patients than in normotensive subjects. Increased plasma norepinephrine, renin activity, and aldosterone levels were observed after hyperinsulinemia for 120 minutes after glucose clamp in normotensive subjects and essential hypertensive patients. Urinary sodium excretion and fractional excretion of sodium were decreased in essential hypertensive patients as well as normotensive subjects during glucose clamp compared with the period before glucose clamp. No difference in the percent change was observed between essential hypertensive patients and normotensive subjects. These results indicate that selective insulin resistance with respect to glucose metabolism exists in essential hypertensive patients and that insulin action on renal sodium handling and pressor systems was maintained in these patients.

Role of interleukin-6 in the progression of mesangial proliferative glomerulonephritis.

Mesangial proliferative glomerulonephritis (mesPGN) is histologically characterized by proliferation of mesangial cells (MC), suggesting the involvement of a growth factor for MC in the pathogenesis of mesPGN. We have previously shown that interleukin-6 (IL-6) induces proliferation of cultured rat mesangial cells, and urine samples from patients with IgA nephropathy contain high level of IL-6 activity. We have also demonstrated that transgenic mice carrying a human IL-6 genomic gene showed severe mesangial proliferation and matrix enlargement. Urinary samples of patients with lupus nephritis as well as IgA nephropathy contain significant IL-6 activity. Over a ten month follow-up, a positive correlation between the urinary IL-6 and pathological score was observed. Hence, measurement of urinary IL-6 can be used as a good indicator for monitoring IgA nephropathy and lupus nephritis. Using RT-PCR methods, IL-6 mRNA was detected in the glomeruli of renal biopsy specimens obtained from patients with IgA nephropathy and lupus nephritis.

Does insulin resistance participate in an impaired glucose tolerance in primary aldosteronism?

It has been reported that glucose intolerance is occasionally found in primary aldosteronism. In this study, we measured insulin sensitivity by the euglycaemic hyperinsulinaemic glucose clamp technique and ability to release insulin by 75 g oral glucose tolerance test (OGTT) in primary aldosteronism. Seven patients with primary aldosteronism (PA) (53.7 +/- 3.4 years; mean +/- SEM) and eight normotensive subjects (NS) (57.5 +/- 2.6 years) were employed in this study. The two-hour euglycemic hyperinsulinaemic glucose clamp technique was performed in seven PA before adrenalectomy, six PA after adrenalectomy and eight NS. The 75 g OGTT was also done in five PA before and after adrenalectomy and eight NS. The mean rate of glucose infusion to maintain euglycemia for the last 30 minutes of the clamp technique was used as an indicator of insulin sensitivity (M-value). The total blood glucose levels during 75 g OGTT (area under the curves) (sigma blood glucose) were significantly higher in PA than those in NS, and the total insulin levels during 75 g OGTT (area under the curves) (sigma IRI) were significantly lower in PA than those in NS. After adrenalectomy in PA, blood glucose levels were significantly decreased and IRI were significantly increased compared with the normal range. There was a significant positive correlation (P < 0.05, r = 0.71) between serum potassium levels and IRI in PA which were determined before and after adrenalectomy. In PA, M-values (240.7 +/- 14.6 mg/m2/min) were significantly higher than those in NS (199.0 +/- 12.3 mg/m2/min).(ABSTRACT TRUNCATED AT 250 WORDS)

[Plasma levels of antithrombin III, thrombin-antithrombin III complex, alpha 2 plasmin inhibitor and plasmin alpha 2 plasmin inhibitor complex in normal and sick newborn infants].

Both bleeding and thrombosis are commonly seen in newborn infants because of their imbalance of coagulation and fibrinolysis system. In order to clarify some aspects of the hemostatic characteristics during neonatal period, we measured the levels of antithrombin-III (AT-III), thrombin AT-III complex (TAT), alpha 2-plasmin inhibitor (alpha 2PI) and plasmin alpha 2PI complex (PIC) in 137 normal and sick newborn infants. The results were as follows 1) AT-III levels in normal neonates were significantly low as compared with them in normal adults, and further lower levels were found in sick neonates. 2) TAT levels in sick neonates were significantly higher than those in either normal neonates and adults. In sick neonates, the incidence of abnormally high TAT values increased with DIC score points. 3) No significant difference of alpha 2PI level was seen between normal term neonates and adults. However, alpha 2PI levels in sick neonates were significantly low as compared with them in normal term neonates and adults. 4) PIC levels in either normal and sick infants were significantly higher than those in adults, but there was no significant difference in PIC levels between normal and sick newborn infants.

[Benefits and problems of home infusion therapy].

A survey was performed to clarify the benefits and problems of home infusion therapy because 8 years had passed since this type of treatment was officially approved in Japan. Questionnaires were sent to hemophiliacs and the physicians in charge of hemophiliacs in the Kyushu district. The main results obtained from analysis of responses concerning 197 patients were as follows. 1) Out of 197, 140 patients were on home therapy programs. 2) The number of bleeding episodes was increased in 6.8%, decreased in 51.1% and unchanged in 42.1% of patients after the start of home infusion therapy programs. 3) The severity of bleeding symptoms was reduced in 92.9% of patients after the start of these programs. 4) After the start of home infusion therapy programs, the amount of blood products administered increased in 24.4%, decreased in 20.6% and was unchanged in 55.0%. 5) Complications such as abdominal pain, headache, ulticaria, itching, shivering, fever and discomfort were reported from 19 hemophiliacs. Only one of them visited the hospital due to severe abdominal pain which appeared immediately after home infusion of blood product. 6) It was indicated that better education or re-education of home infusion therapy is necessary for hemophiliacs and/or their families who are on home infusion therapy programs, because half of them had not received proper education concerning home infusion.

[Successful treatment of an infant with fulminant hepatitis by factor VII concentrate].

A 2-month-old boy was admitted to our hospital because of poor sucking and jaundice. There were no abnormalities during the whole period of pregnancy and at birth. His mother was a HBeAb positive HBsAg carrier, but prophylactic maneuver such as anti-HB immunoglobulin and HB vaccine was not performed on him at birth. Physical examination on admission revealed mild disturbance of consciousness. The laboratory findings showed marked increments of serum bilirubin, GOT, GPT, and NH3, and prolongation of prothrombin time, activated partial thromboplastin time and hepaplastin test. Thus, he was diagnosed as fulminant hepatitis and treated with exchange transfusion once or twice a day. Biochemical data improved gradually, but hypocoagulable states remained unchanged. At that time we decided to use Factor VII concentrate, because we found that, among several coagulation factors, factor VII activity decreased most rapidly after exchange transfusion. The alternate therapy of exchange transfusion and Factor VII concentrate improved his coagulation abnormality without any side effects. Our experience suggests that the combination therapy of exchange transfusion and Factor VII concentrate may be useful for management of fulminant hepatitis, particularly for uncontrollable coagulopathy.

[A report of successful surgical management of right coronary artery to right atrium fistula forming giant aneurysms at the posterior wall of the right atrium].

A 52-year-old woman was diagnosed by echocardiography to have a fistula of the right coronary artery (RCA) and the right atrium (RA). Aortography demonstrated a remarkably dilated and undulating fistulous tract originating from the region corresponding to the orifice of the normal RCA. The fistulous tract detoured to the posterior wall of the RA, and forming 2 aneurysms there, opened to the RA. A RCA of normal size originating midway of the fistulous tract was also observed. The patient was operated on under cardio-pulmonary bypass. Aortocoronary saphenous vein graft to the RCA having normal diameter was performed, and the RCA was ligated in the proximal side of the anastomosis. The orifice of the fistulous tract from the aorta was closed with a patch and the entrances into the RA were also closed by pledgetted mattress sutures. The post operative course was uneventful and the patient is now doing well without any complaints.

Slow continuous hemodialysis--new therapy for acute renal failure in critically ill patients--Part 2. Animal experiments and clinical implication.

Five acutely uremic dogs were treated for 9 hours by means of slow continuous hemodialysis using our newly developed machine. The blood concentrations of urea nitrogen (BUN) and creatinine were determined every hour and were compared to those calculated from a mathematical pool model. In order to assess the accuracy of volume control, the body weight of dogs was monitored continuously by scale bed, under simultaneous 200 ml/hour infusion and ultrafiltration. Arterial and swan-ganz catheter were inserted to measure hemodynamic changes during hemodialysis. The efficacy of solute elimination was coincidental with the predicted value. The error of volume control was within +/- 5% of set rate. Hemodynamic parameters were not significantly influenced in spite of a large amount of volume exchange. In conclusion, it was demonstrated that slow continuous hemodialysis could be a better alternative to peritoneal dialysis, continuous hemofiltration or conventional hemodialysis in order to treat acute renal failure in critically ill patients, in terms of solute removal, volume control and the effects on hemodynamics.

[Cohort study on cariostatic effect of 100ppmF- fluoride mouthrinsing].

The cariostatic effect of fluoride mouthrinsing with dilute fluoride solution in the school dental health programs was examined. The subjects were 138 children (75 of boys and 63 of girls) who carried out fluoride mouthrinsing with solution of 100 ppmF- for 6 years and 105 children (65 of boys and 40 of girls) who had no fluoride mouthrinsing were analysed by cohort study from 1983 to 1989. The cariostatic effect was evaluated by DMFT index and DMF rate for each tooth type in each erupted school grade. The increment of DMFT index was less than that of the control group. There was a clear cariostatic effect with the advance in the school grade. DMF rate for each tooth type of 1 in 2nd grade and 2 in 3rd grade students showed a statistically significant difference. Both that of upper and lower first molars in 1st and 2nd grade also showed the same result as that of upper incisors. In conclusion, a high cariostatic effect was obtained by introducing the use of fluoride mouthrinsing with a solution of 100ppmF- to the school dental health program, and the observation of DMF rate for each tooth type classified with each erupted school grade was a useful method to evaluate the cariostatic effect of fluoride mouthrinsing.

Effects of hyperinsulinaemia on renal function and the pressor system in insulin-resistant obese adolescents.

1. In the present study, using the euglycaemic hyperinsulinaemic glucose clamp technique, we investigated the effects of hyperinsulinaemia on sodium-water metabolism and the pressor system in obesity, both of which have been reported to be closely associated with insulin resistance and/or hyperinsulinaemia. 2. Sixteen obese young subjects and 24 non-obese young subjects who were all normotensives, participated in this study. The 2 h euglycaemic hyperinsulinaemic glucose clamp was performed in a fasting state. The mean glucose infusion rate needed to maintain a fasting blood sugar level (FBS) during the last 30 min of the clamp was used as an indicator of insulin sensitivity (M-value). Before and after the clamp, the following parameters were measured: creatinine clearance (Ccr); urinary excretion of sodium (UNaV); fractional excretion of sodium (FENa); plasma renin activity (PRA); plasma aldosterone concentration (PAC) and plasma noradrenaline concentration (PNA). 3. The M-value was significantly lower in obese subjects compared with non-obese subjects, although FBS and fasting immunoreactive insulin levels were similar in both groups. UNaV and FENa fell only in obese subjects during the clamp, while Ccr showed no significant change in either group. PNA and PRA increased significantly and PAC tended to increase in both groups. 4. These results suggest that obese subjects have insulin resistance with respect to glucose metabolism, but that urinary sodium excretion and the pressor system remain insulin-sensitive; the sensitivity of the sodium retaining action to hyperinsulinaemia was actually higher in obese subjects than in non-obese subjects. Therefore, if compensatory endogenous hyperinsulinaemia was raised by insulin resistance, these two factors may lead to chronic sodium retention and pressor system stimulation and, in turn, to hypertension in obesity.

Effects of hyperinsulinemia under the euglycemic condition on calcium and phosphate metabolism in non-obese normotensive subjects.

The effect of acute insulin infusion on the metabolism of calcium (Ca) and phosphate (P) was examined in 17 healthy subjects. They were hospitalized and kept on a constant diet for 5 days, and an euglycemic hyperinsulinemic glucose clamp was applied. Synthetic human insulin was infused at the rate of 40 mU/m2/min for 2 hr, and glucose was also infused to maintain basal glucose levels of each subject. The control study was performed in 8 of the 17 subjects, into whom 10% xylitol was infused for 2 hr at the rate of 100 ml/hr. The plasma insulin concentrations were 7.94 +/- 0.35 and 62.3 +/- 14.3 mU/liter before and after the glucose clamp technique, but serum free Ca ion was increased significantly (p < 0.05), and serum P and serum parathyroid hormone (PTH) were decreased significantly (p < 0.001). Creatinine clearance did not change during the glucose clamp technique. Urinary excretion of Ca (UCaV) was significantly higher after the glucose clamp than the control study. Fractional excretion of Ca (FECa) was increased significantly (p < 0.05), and urinary excretion of P (UPV) and fractional excretion of P (FEP) were decreased significantly (p < 0.05) under the hyperinsulinemic condition. The results suggested that, under the conditions of euglycemic hyperinsulinemia by glucose clamp technique, insulin increased the serum free Ca ion, and as a result, PTH was suppressed. Decreased PTH might induce calciuresis and enhance tubular P reabsorption under hyperinsulinemia. Insulin increased serum free Ca ion might relate to the vasodilating action of insulin by its decrease of intracellular free Ca ion in vascular smooth muscle.