Extended sigmoid-shaped free jejunal patch for reconstruction of the oral base and pharynx after total glossectomy with laryngectomy.

The procedure for reconstruction of the extensive defect after total glossectomy with total laryngectomy has not been standardised so far. We have devised a new method in which a free jejunal patch is extended to a sigmoid-shaped form specifically optimised for reconstruction of the defect that consists of the entire floor of the mouth and the antero-lateral walls of the pharyngoesophageal tract. After a jejunal segment of about 40 cm has been longitudinally opened in full length, the proximal quarter is folded parallel to the second quarter, which is then folded parallel to the third quarter in the opposite direction, to be laid out in a S-shaped form. Side-by-side sutures are then placed along each of the folded borders and corrective trimming is done to fit the defect. This widely extended patch replaces the whole oral base, whereas the remaining distal quarter of the patch replaces the antero-lateral walls of the hypopharynx and cervical esophagus. Because of the encouraging functional results with satisfactory restoration of oral alimentation, this procedure is considered to be ideal for the reconstruction of the defect which follows total glossectomy with total laryngectomy.

Urinary excretion of type IV collagen as a specific indicator of the progression of diabetic nephropathy.

AIMS AND METHODS: This study was carried out to clarify whether the urinary excretion of type IV collagen (u-IV collagen) detected by specific radioimmunoassay, can be used as an indicator for the progression of diabetic nephropathy. RESULTS: u-IV collagen was higher in diabetic subjects with microalbuminuria and overt proteinuria than those with normoalbuminuria, IgA nephropathy, membranoproliferative glomerulonephritis, membranous nephropathy, or control normal subjects. u-IV collagen was positively correlated with serum and urinary beta(2)-microglobulin and negatively with creatinine clearance only in diabetic patients, but not in patients with other glomerular diseases. The serum type IV collagen was not different between all the groups, and not correlated with its urinary excretion. In the advanced diabetic nephropathy, immunoreactive type IV collagen was detected in glomerular basement membrane (GBM), tubular basement membrane and Bowman's capsule much more than that in the normal kidney. CONCLUSION: These findings indicated increased production and degeneration of type IV collagen in diabetic nephropathy. It is suggested that augmented turnover of type IV collagen in GBM and tubular basement membrane results in increased concentrations of free u-IV collagen. Therefore, measurement of u-IV collagen may be a useful, specific indicator of the progression of diabetic nephropathy.

The effect of docarpamine, a dopamine pro-drug, on blood pressure and catecholamine levels in spontaneously hypertensive rats.

We studied the effects of bolus intravenous injection of the dopamine prodrug, docarpamine (200 microg/kg), on mean arterial pressure (MAP) and heart rate (HR) in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs). In WKY rats (n=18), MAP and HR increased 5 min after docarpamine and then returned to baseline levels within 15 min. In contrast, in SHRs (n=15), MAP and HR gradually decreased, reaching a nadir 20 min after injection. Five min after docarpamine, plasma dopamine and 3,4-dihydroxy phenyl acetic (DOPAC) levels increased in both WKY rats (n=5) and SHRs (n=5). The docarpamine-induced changes in MAP and HR in both rat strains (n=5/strain) were blocked by the D1-like antagonist, SCH23390. alpha-Adrenergic (n=4) and vasopressin V1 (n=3) receptor blockade also abrogated the effects of docarpamine in WKY rats. We conclude that docarpamine differentially affects MAP and HR in WKY and SHRs. In SHRs, the depressor and bradycardiac effects of docarpamine are mediated by D1-like receptors. In WKY rats, the pressor and tachycardiac responses are caused by an interaction among D1-like, alpha-adrenergic, and V1 receptors.

[Alpha-adrenoceptor antagonist (blocker)].

Alpha adrenergic receptors localized in blood vessels, heart, and kidneys as well as pre- and post-synaptic membrane are significantly important for controlling blood pressure. The treatment of alpha-adrenoceptor blocking drugs induce vasodilatation subsequently lowering blood pressure. Selective alpha-1 adrenoceptor blocking drugs (alpha-1 blockers) are recommended as a first line treatment of hypertension, because of their desirable effect on lipid and glucose metabolism. alpha-1 blockers decrease in total cholesterol and triglycerides, and increase in HDL-cholesterol. It is suggested that alpha-1 blockers improve insulin tolerance, cardiomegaly and atherosclerosis. Although they have many beneficial effect, we should consider adverse effects (orthostatic hypotension, flushing, etc.).

Dopaminergic activity and endorenal dopamine synthesis in non-insulin dependent diabetes mellitus.

In the present study we tried to clarify the differences of the cardiovascular and renal responses to feeding in relation to the peripheral dopamine system. In control subjects (C), ingestion of protein (100 g) induced an increase in Ccr accompanied by an increase in tubular sodium excretion (FENa+). Patients with non-insulin dependent diabetic (NIDDM), a protein-induced increase in Ccr was comparable to that in C, while FEN+ did not change following protein. Since an increase in urinary 3,4-dihydroxyphenylacetic acid was blunted in NIDDM, an impaired natriuretic response to high protein may be results from an insufficient synthesis of renal dopamine. Plasma dopamine and its metabolites in NIDDM following protein tended to be greater than in C. Protein induced a greater decrease in blood pressure (BP) in NIDDM, but no increase in pulse rate was observed. An ordinary diet containing 10 g of protein also induced a decrease in BP. A reflex tachycardia was observed in C and normotensive NIDDM but not in hypertensive one. In normotensive NIDDM, plasma dopamine and norepinephrine increased after the diet, while in hypertensive NIDDM there were no increases in catecholamines. From these results it is suggested that the relatively elevated peripheral dopaminergic activity and the blunted dopamine synthesis in the kidney may be responsible for the abnormal cardiovascular and renal responses to feeding in patients with NIDDM.

Dopamine deficiency--its potential contribution to chronic renal failure complicating hypertension.

Baseline dihydroxyphenylalanine (DOPA) and dopamine (DA), their respective sulfates as well as oral DOPA administration-induced changes were compared in age- and blood pressure-matched hypertensive patients without and with moderate chronic renal failure (CRF) and control subjects. The only common feature of both hypertensive groups was a defective DA generation from DOPA. Hypertensive patients with moderate CRF were distinct from those without, having increased basal concentrations of plasma DOPA and DA sulfates. After oral DOPA administration, plasma and urinary DOPA sulfate rose while renal DA sulfate clearance was decreased. Possible enzymatic defects contributing to CRF-induced increases of DOPA and DA sulfates and their potential role in perpetuating renal failure via glomerular hypertension are discussed.

Gene expression of aromatic L-amino acid decarboxylase mRNA in the kidney of normotensive and hypertensive rats.

Peripheral dopamine (DA) synthesis and release increase during hypertensive stage of spontaneously hypertensive rats (SHR). DA is generated from 3,4-dihydroxyphenylalanine by L-amino acid decarboxylase (AADC). We have studies urinary DA and DA metabolites and the gene expression of neuron and non-neuron specific AADC mRNA in the kidney of SHR. Compared to Wister-Kyoto rats (WKY), there was an increased urinary free DA and DOPAC excretions in 8 and 12 week-old SHR. At the age of 16 weeks, the difference in free DA excretion between SHR and WKY rats disappeared, although the urinary DOPAC excretion remained significantly higher in SHR, but urinary HVA excretion did not differ from WKY rats. The expression of the neuron specific AADC mRNA in the kidney of SHR and WKY rats was not detected, but the non-neuron specific AADC mRNA in the kidney of SHR and WKY rats was detected. The gene expression of the non-neuron specific AADC mRNA tended to decrease with age in SHR. The results suggest that a decrease in renal DA production with age may be caused by diminished expression of non-neuron specific AADC mRNA in kidney.

Postprandial changes in noradrenergic and dopaminergic activity in patients with essential hypertension.

In order to elucidate the role of noradrenergic and dopaminergic activity in the pathogenesis of postprandial hypotension, the effect of feeding of ordinary diet on blood pressure, pulse rate, plasma catecholamine and other circulating vasoactive substances such as insulin were examined in mild essential hypertensive patients (EH) and their age-matched control subjects (N). Mean blood pressure significantly decreased in both N and EH after feeding, and the decrease tended to be greater in EH than in N. Feeding induced a marked increase in plasma norepinephrine in both N and EH. Plasma dopamine significantly increased following feeding was observed in N, while the increase in plasma dopamine following feeding was blunted in EH. The ratio of norepinephrine to dopamine following in EH was significantly greater than that in N. From these results, it is suggested that the feeding-induced stimulation of noradrenergic activity may be a result from the decrease in blood pressure, and that the blunted response of dopaminergic activity in EH may reflect the enhanced conversion of dopamine to norepinephrine probably due to the enhanced activity of dopamine beta-hydroxylase in the sympathetic nerves.

Recent aspect of the role of peripheral dopamine and its receptors in the pathogenesis of hypertension.

Dopamine is an essential and indispensable catecholamine, which acts not only as a neurotransmitter in dopaminergic and noradrenergic sympathetic neurons but also as an autocrine/paracrine substance in non-neuronal tissues. The regulatory mechanism of dopamine synthesis in neuronal tissues seems to be different from that in non-neuronal tissues. Among receptors specifically bound to dopamine, five different receptors have already been cloned. Dopamine exhibits vasodilative and natriuretic effects by stimulating specific dopamine receptors located in renal tubular cells, blood vessels, etc. Physiological effects of dopamine appear to be protective against hypertension and sodium retention. Spontaneously hypertensive rats (SHR) are known to have an enhanced dopamine generation associated with the increased sympathetic nervous activity. A defect of renal D1-receptor-mediated coupling to adenylate cyclase has also been demonstrated in SHR. On the other hand, it has been reported that Dahl salt sensitive rats exhibit defective dopamine synthesis during high salt intake, which may be a definitive abnormality in this strain. The pathophysiological role of peripheral dopamine is essential hypertensive patients is still controversial. Considering the previous studies, it seems to be the case that essential hypertensive patients with increased sympathoadrenergic activity show enhanced dopaminergic discharge where dopamine may negatively modulate high blood pressure, and that stable essential hypertensive patients with salt-sensitivity and/or suppressed renin activity show insufficient dopamine synthesis in the kidney.

[The role of beta 2-adrenoceptor on the pathogenesis of insulin resistance in essential hypertension].

The role of beta 2-adrenoceptor on the pathogenesis of insulin resistance in essential hypertension (EH) was explored. After the measurement of blood pressure in 15 EH patients and 8 control subjects, EH patients were divided into two groups by the elevation of plasma NE (delta NE) 5 min after standing: 7 normoadrenergic EH (delta NE < 140 pg/ml) and 8 hyperadrenergic EH (delta NE > or = 140 pg/ml). On the morning after a 12-h overnight fast, regular insulin (0.1 U/kg) was injected intravenously, and glucose disappearance rate (GDR) was measured and used as an index of insulin sensitivity. On the following day, the test was reinvestigated following the administration of mabuterol, a beta 2 agonist. Plasma growth hormone (GH), cortisol, norepinephrine (NE) and epinephrine (Epi) were measured before and after the mabuterol administration. Although there were no significant differences of basal GDR among these three groups, mabuterol induced a considerable decrease in GDR in EH patients but not in control subjects. There was no significant difference in the decrease of GDR between normo- and hyperadrenergic EH. The decrease in GDR tended to correlate with the mean blood pressure at rest in EH but not in normal subjects. Plasma glucose and serum insulin in EH patients were increased more than in normal subjects. Plasma GH, cortisol and Epi were not elevated by mabuterol, but plasma NE increased in each group, significantly in hyperadrenergic EH. There was no correlationship between the increase in plasma NE and the decrease in GDR after mabuterol.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of idiopathic hyperaldosteronism with normal plasma aldosterone concentrations for 5 years after onset: a 12-year follow-up study].

We report a 54-year old man diagnosed as idiopathic hyperaldosteronism (IHA) at least 12 years after the onset. At the age of 42, he showed hypertension (162/100mmHg), hypokalemia, metabolic alkalosis, low plasma renin activity (PRA) and normal plasma aldosterone concentration (PAC) in a supine posture. Both PRA and PAC were elevated after a 2-hour ambulation following furosemide (60mg) injection. Since the accumulation of radioactivity following 131I-aldosterol injection with combined administration of dexamethasone was equally detected in both adrenal areas, he was diagnosed as low-renin essential hypertension (LREH). Blood pressure (BP) decreased to the normal range after treatment with nifedipine (40mg/day). At the age of 47, however, BP was hypertensive (164/106mmHg) serum potassium (K) level was normal. Although PAC was normal in a supine posture, it increased after a 2-hour ambulation following furosemide (60mg) injection. PRA after the stimulation was still suppressed despite the increase in PAC. At the age of 54, BP was 172/94mmHg. Serum K level was 3.4mEq/L. PRA was suppressed below 0.1 ng/ml/hr, while PAC was above the normal range (170pg/ml) in a supine posture. Serum cortisol and urinary excretion of 17-OHCS and 17-KS were within normal limits. PRA was still suppressed below 0.1 ng/ml/hr after a 2-hour ambulation following furosemide (60mg) injection, but PAC was markedly increased (330pg/ml). There was a diurnal rhythm of aldosterone, which was parallel to that of ACTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Dopaminergic abnormalities in hypertension associated with moderate renal insufficiency.

To evaluate the additive effect of moderate chronic renal failure to the abnormal dopamine generation and action observed in stable hypertension, we investigated 22 age-matched patients with a comparable degree of hypertension with and without chronic renal failure. Both groups were compared with each other and with an age-matched control group after a single oral dose of dihydroxyphenylalanine (DOPA) while cardiorenal responses and DOPA, dopamine, and their metabolites were measured. The hypertensive patients with chronic renal failure shared with their hypertensive counterparts without chronic renal failure an impaired DOPA decarboxylation to dopamine. However, patients with chronic renal failure had decreased hemodynamic and normal natriuretic responses compared with the hypernatriuresis of hypertensive patients with normal renal function; patients with chronic renal failure had elevated basal plasma concentrations of DOPA and dopamine sulfates as well as increased plasma and urinary DOPA sulfate but blunted urinary dopamine sulfate increases after DOPA administration; they presented augmented plasma atrial natriuretic factor concentrations. Thus, hypertensive patients with moderate chronic renal failure exhibit a decreased hemodynamic responsiveness to DOPA administration-induced dopamine elevation but with the natriuretic effect of dopamine maintained (possibly because of its permissive interaction with increased atrial natriuretic factor levels). Hypertensive patients with chronic renal failure have a heightened DOPA and dopamine sulfoconjugating propensity. Dopamine sulfate attenuates the biologic action of free dopamine. This may contribute (possibly via glomerular hypertension and hyperfiltration due to decreased postglomerular vasodilation) to progressive hypertensive renal damage, particularly in groups predisposed to dopamine deficiency, such as diabetics, blacks, and the elderly.