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We investigated the effect of bromide on gamma-aminobutyric acid (GABA)-activated currents in cultured cerebral neurons of the rat, employing whole-cell voltage- and current-clamp techniques. Application of 100 microM GABA elicited currents whose reversal potential was 0 mV with equal concentrations of chloride in both pipette and bath solutions and more negative than -60 mV with 159 mM chloride extracellularly and 4 mM chloride inside. Bicuculline blocked the currents. These findings showed that the currents were composed of chloride flux through GABAA receptor-coupled channels. Reversal potential revealed a permeability ratio of bromide with respect to chloride (PBr/PCl) of 1.51. When 100 microM GABA was applied with the extracellular solution containing 140 mM bromide and 19 mM chloride, the currents were enhanced 2.00- and 1.91-fold at the holding potentials of -20 mV and 0 mV, respectively. Extracellular solutions containing various concentrations of bromide substituted for the same amount of chloride were applied with 100 microM GABA. The therapeutic concentration of 10 mM and 20 mM bromide enhanced the currents 1.28- and 1.36-fold of the control currents at the holding potential of -20 mV, respectively. Under current-clamp recording, a larger hyperpolarization was obtained by the application of GABA with a 140 mM bromide-containing solution. These findings suggest that bromide potentiated GABA-activated currents at the therapeutic concentrations ranging from 10 mM to 20 mM, causing the larger GABA-induced hyperpolarization. It is postulated that the antiepileptic effect of bromide might occur through the potentiation of inhibitory postsynaptic potentials elicited by GABA.

In order to evaluate the quality-of-life (QOL) of epilepsy surgery patients, we surveyed patients' degree of life satisfaction and their families' degree of satisfaction with patient's status in a range of domains both pre- and post-operatively. Of 100 patient-family sets of surveys that were mailed out, 93 were completed and returned from patients and 91 from their families. All patients surveyed had temporal lobe epilepsy and had been followed for longer than 2 years after resective surgery. Patients and their families rated overall QOL as having markedly improved following surgery. However, they rated social domains of QOL, including role activities, financial status, and social and family relationships as having improved relatively little. Despite freedom from seizures, a few patients' families were dissatisfied with the patients' post-operative status, primarily for psychosocial reasons. Patients operated on at a later age reported little gains in life satisfaction following surgery. This study supports the conclusion that surgical intervention should occur before patients are subjected to the psychological conflicts and social handicaps associated with chronic intractable epilepsy.

Discrepancies in the findings of studies sponsored by the Department of Veterans Affairs (VA) in the United States and the Medical Research Council (MRC) in the United Kingdom concerning the efficacy of valproate (VPA) in controlling simple or complex partial seizures, particularly those without secondarily generalized seizures, were reviewed. It was noted that the two studies differed with respect to their subjects' pretreatment seizure frequency. The frequency of complex partial seizures before treatment was obviously greater in the VA study, where carbamazepine (CBZ) provided better seizure control than VPA. Based on other comparative and non-comparative studies as well as the author's over 20 years of experience in the use of VPA in a tertiary epilepsy clinic, it is suggested that although VPA may be effective in controlling both the secondarily generalized seizures of symptomatic localization-related epilepsies and the generalized tonic-clonic seizures of idiopathic and, if not always, symptomatic generalized epilepsies, the efficacy of VPA in controlling simple or complex partial seizures is likely limited to patients with infrequent seizures.

Long-term investigation of a male case of Landau-Kleffner syndrome with auditory, verbal and non-verbal agnosia was performed clinico-electroencephalographically and neuropsychologically. Atypical absences and secondarily generalized tonic-clonic seizures were observed. The spike-wave index of slow wave sleep from all-night EEG recordings was 96% in this case. It was impossible to differentiate this case from epilepsy with "continuous spikes and waves during slow wave sleep (CSWS)" except the presence of auditory agnosia. Auditory agnosia of this case disappeared after antiepileptic therapy. It is suggested that Landau-Kleffner syndrome showing CSWS may have a good prognosis about agnosia from that of this case and others previously reported.

We investigated the localizing and lateralizing value of principal seizure manifestations in temporal lobe epilepsies (signal symptoms, oroalimentary automatisms, somatomotor manifestations, unilateral dystonic posturing, ictal speech, motionless stare) of 223 complex partial seizures in 50 patients. All the patients had invasive long-term monitoring with the combined implantation of intracerebral electrodes in and subdural electrodes on the bilateral temporal lobes. Postoperative freedom from seizures was ascertained for longer than one year. We found that 35 patients had amygdalohippocampal seizures and 15 had lateral temporal seizures. The value of the manifestations was established in relation to the site and side of seizure origin and to the progression of seizure discharges within the unilateral temporal lobe or to the contralateral cerebral hemisphere. Several signs among the manifestations were found to be reliable in predicting the site or side of the temporal lobe seizure focus. We emphasized the importance of investigating sequential changes of seizure manifestations in relation to ictal EEG findings by means of simultaneous recording.

1. In addition to 4 types of drop attacks previously described by Ikeno et al., we could ascertain the falls of the myoclonic-tonic type in genuine drop attacks. The genuine drop attacks were seen in Lennox-Gastaut syndrome, epilepsy with myoclonic-astatic seizures and other symptomatic generalized epilepsies, and never in partial epilepsies. 2. None of the patients with partial epilepsy revealed genuine drop attacks as defined. Their drop attacks were slower (i.e. the falls were completed in more than 1 sec.). 3. In the 15 patients with Lennox-Gastaut syndrome, the drop attacks disappeared in 8 patients, and decreased in severity and frequency in 3 patients. Namely, the intractability of drop attacks in two-thirds of the children decreased as the patients grew older. This finding must be taken into consideration when patients with drop attacks are considered for surgical treatment of their epilepsy.

Twenty-four spontaneously occurring convulsive seizures were documented by closed-circuit TV (CCTV)-EEG monitoring in 3 cats subjected to unilateral amygdaloid overkindling for < or = 2 years. Electroclinical manifestations suggested that the seizures originated in the kindled amygdala (AM) (10 seizures in 3 cats), contralateral AM (7 seizures in 3 cats), or ipsilateral frontal cortex (7 seizures in 1 cat). All seizures of AM origin except one occurred during sleep 23 h to 20 days after the last stimulation-induced kindled seizure and culminated in secondarily generalized seizures. The seizures of frontal cortical origin occurred during waking within 1 h of a kindled seizure and remained partial in nature. In seizures of AM origin, ictal patterns at the primary and secondary sites were mirror images of each other, but latency of onset of each seizure stage in seizures of secondary site AM origin was longer than that in seizures of primary site AM origin in 2 of the 3 animals. We conclude that the secondary epileptogenic functional alterations capable of producing clinical seizures do occur in AM-overkindled cats, but the seizures are not entirely independent of the primary kindled site.

The genes encoding three different human somatostatin receptor subtypes, designated SSTR1, SSTR2, and SSTR3, were mapped to chromosomes 14, 17, and 22, respectively, by analyzing their segregation in a panel of reduced human-hamster somatic cell hybrids. These assignments were confirmed independently using fluorescence in situ hybridization to metaphase chromosomes and the genes were further localized to 14q13, 17q24, and 22q13.1, respectively. Highly informative simple tandem repeat DNA polymorphisms were identified in SSTR1 and SSTR2.

To determine whether recombinant human erythropoietin (rHuEPO) has direct effect on mean arterial pressure or renal function, rHuEPO was infused intrarenally at a rate of 100 U min-1 for 30 min in anesthetized rabbits without renal failure. Intrarenal infusion of rHuEPO resulted in no change in mean arterial pressure, renal blood flow, or renal vascular resistance as compared with vehicle control. rHuEPO also produced no significant change in glomerular filtration rate, filtration fraction, or arterial hematocrit. However, urine volume, urinary excretion of sodium and potassium, and fractional sodium excretion were significantly reduced by intrarenal infusion of rHuEPO. These observations demonstrate that rHuEPO has no direct effects on mean arterial pressure or renal hemodynamics, whereas rHuEPO stimulates net tubular sodium reabsorption possibly by direct tubular action, and reduces urine volume and urinary excretion of sodium and potassium in anesthetized rabbits without renal failure.

Semiology of postictal aphasia as well as its generating mechanism involving both the epileptogenic zone and language area has not yet been sufficiently elucidated. Therefore, postictal aphasias were studied in 3 patients with localization-related epilepsy. Postictal motor aphasia was observed in a patient (patient 1) with frontal lobe epilepsy whose recovery of language function progressed from loss of language function, to Broca's aphasia, and eventually to poor spontaneous speech. Postictal sensory aphasia was observed in 2 patients (patient 2 and 3) with temporal lobe epilepsy whose recovery of language function progressed from loss of language function, to jargon, and eventually to circumlocutory anomic speech. Both patient 2 and 3 did not show fluent speech. Seizure manifestations, EEG, IMP-SPECT and MRI indicated that epileptogenic zones were in the left frontal lobe including Broca's area in patient 1, the mesial part of the left temporal lobe in patient 2, and the middle and posterior part of the left temporal lobe including Wernicke's area in patient 3. A postictal verbal dichotic listening test showed the reduction of correct responses by right ear in the patient 3. Postictal auditory verbal learning tests showed the impairment of verbal memorization in patient 2 and 3. The impairment of verbal memorization was particularly marked in patient 2. These results suggest that 1) the characteristics of postictal motor and sensory aphasia are clearly elucidated by analyzing the sequence of recovery from postictal language dysfunction, 2) postictal aphasia is generated by the epileptogenic zone involving the language area or the ictal discharges propagating to the language area, and 3) not only the disturbance of language function, but also the impairment of verbal memorization seems to participate in the disturbance of repeating and understanding sentences in the patient with postictal sensory aphasia.

Twenty-nine children with childhood epilepsy characterized by frequent grand mal (generalized tonic-clonic) seizures in spite of maximal doses of antiepileptic drugs and by an early onset of seizures (before 1 year of age) were followed up for more than 5 years. The children were divided into 3 groups: severe myoclonic epilepsy in infancy (SME), no SME, and intractable childhood epilepsy with generalized tonic-clonic seizures (GTC). In all the 3 groups, the grand mal seizures persisted, whereas the other types of seizures tended to disappear as the patients aged, and the prognosis for mental development was poor. In the majority of cases in all the 3 groups, the waking grand mal seizures altered to sleep grand mal seizures with aging. Two pairs of monozygotic twins with SME suggested that genetic factors play a role in this epileptic syndrome. Intractable childhood epilepsy with GTC is distinguished by the absence of other types of generalized seizures. It cannot be regarded as an epileptic syndrome, but its pathogenesis and treatment require further studies.

We present the results of pre- and postoperative neuropsychological evaluations of 58 patients with temporal lobe epilepsy who underwent a chronic intracranial EEG monitoring and a subsequent standard anterior temporal lobectomy. Wada's test provided valuable information on the speech dominant side and on the focus localization. Some warning signs as well as verbal automatisms indicated the effect for focus localization and lateralization. The results of interictal neuropsychological tests suggested that each subgroup of TLE performed differently. A postoperative neuropsychological performance has improved in many tests that may be explained by the diminished epileptic bombardment resulting from the resection.

The omission of invasive long-term monitoring before surgical resection in patients with epilepsy should be permitted only for those in whom the epileptogenic focus is presumed to localize unilaterally in the mesial aspect of the temporal lobe. The localization may well be confirmed through noninvasive measures. Retrospective analyses of data obtained from noninvasive investigations (scalp-recorded and sphenoidal EEGs, neuroimages, and electroclinical seizure manifestations) were carried out in 58 patients. The localization of their epileptogenic focus was subsequently confirmed by the implantation of both intracerebral and subdural electrodes; the focus had an amygdalohippocampal origin in 41 patients and a lateral temporal origin in 17 patients. From the comparison of noninvasive findings between these two groups, we propose the following indispensable conditions for omitting an invasive evaluation: 1. Appearance of focal epileptic discharges unilaterally in the sphenoidal lead observed during the simple phase of partial seizures, or unilateral discharges with predominancy in the sphenoidal lead during the early phase of complex partial seizures. 2. Interictal spikes on scalp-recorded EEGs localizing unilaterally in the anterior region of the temporal lobe, and if bilaterally independent, presenting with unilateral predominancy in a ratio of greater than 4:1. 3. Presence of autonomic signs in the initial phase of signal symptoms. 4. Neuroimaging findings in the mesial temporal region: elongated T2 on MRI and hippocampal atrophy, or a tumorous lesion. The lateralization conforms to interictal and ictal paroxysmal EEG findings. There were 8 patients with seizure of amygdalohippocampal origin who satisfied all the indispensable condition, but not a single patient with seizures of lateral temporal origin.(ABSTRACT TRUNCATED AT 250 WORDS)

We investigated the effect of zonisamide, a new antiepileptic drug, on voltage-dependent Ca2+ currents in cultured neurons of rat cerebral cortex. Whole-cell voltage-clamp recordings demonstrated at least two distinct voltage-dependent Ca2+ currents: (1) a low-threshold, rapidly inactivating component, T-type Ca2+ current, which is sensitive to 100 microM Ni2+, and (2) a high-threshold, slowly inactivating (long-lasting) component, L-type Ca2+ current. Zonisamide, a new anticonvulsant effective against maximal electroshock (MES) seizures in mice reduced T-type Ca2+ current in a dose-dependent manner. The mean percentage of reduction was 59.5 +/- 7.2% at 500 microM, but zonisamide had no effect on L-type Ca2+ current. A methylated analog of zonisamide, which is ineffective against MES seizures in mice, was tested at a concentration of 500 microM, and reduced neither T-type nor L-type Ca2+ current. These findings suggest that the effects of zonisamide against MES seizures might occur through the reduction of T-type Ca2+ current. Because drugs that are effective against MES seizures are thought to prevent seizure discharge spread, T-type Ca2+ channels could underlie a cellular mechanism of spreading activity in epileptic seizures.

The effects of recombinant human erythropoietin (rHuEPO) on mean arterial pressure (MAP) and renal hemodynamics were studied in anesthetized rabbits without renal failure. Intrarenal infusion of rHuEPO at a rate of 100 U/min for 30 min resulted in no change in MAP, renal blood flow, or renal vascular resistance. rHuEPO also produced no significant change in glomerular filtration rate filtration fraction, or arterial hematocrit. These results demonstrate that rHuEPO has no direct effects on MAP or renal hemodynamics in anesthetized rabbits without renal failure.

1. The guidelines for clinical evaluation of antiepileptic drugs (AEDs), proposed by the International League Against Epilepsy in 1989, were scrutinized through our clinical experiences with zonisamide. 2. Seizure type, seizure frequency, number of concomitant AEDs, and type of epilepsy were found to be essential factors in quantitatively determining the efficacy of a new drug. 3. The majority of patients selected according to the guidelines consist inevitably of those with complex partial seizures with or without secondary generalization. Consequently, the efficacy of new AEDs is evaluated mainly in patients with partial seizures, and it is difficult to evaluate their efficacy in those with refractory generalized seizures, either convulsive or nonconvulsive. 4. In order to avoid such predilection, patients with various types of generalized seizures who are taking one or two conventional AEDs should account for 30 to 40% of the total patient population selected for clinical drug trials.

A longitudinal study was conducted in 89 children with partial seizures who had rolandic discharges on their interictal EEGs. The clinical characteristics and seizure prognosis were compared in children without an organic background (idiopathic) and in children with an organic background (symptomatic). Since rolandic discharges and sylvian seizures were found in the symptomatic children and their seizure outcome was favorable, it is likely that they are symptomatologically close to benign childhood epilepsy with centrotemporal spikes. Some of the symptomatic patients may have had complex partial seizures, although rolandic discharges were the principal EEG finding. Their seizure prognosis was as unfavorable as that of the patients with other symptomatic partial epilepsies. The rolandic discharges disappear in an age-related manner in idiopathic patients, but tend to persist in the symptomatic ones. The presence of rolandic discharges was not considered a hallmark of a benign outcome. Instead, the presence of sylvian seizures heralds a benign outcome of partial epilepsies regardless of whether they are idiopathic or symptomatic.

Dapsone (4,4'-diaminodiphenyl sulfone; DDS), an established anti-leprosy drug, showed anticonvulsive effects in the amygdaloid kindling model of epilepsy. Single doses of the drug in rats (6.25-12.5 mg/kg, i.p.) suppressed the kindled seizures in a dose-dependent manner without overt behavioral toxicity. With repeated oral administration in cats, relatively higher initial doses (13-23 mg/kg) were required to obtain seizure suppression, and neurotoxic signs occurred within a few days with serum drug levels of approximately 20 micrograms/ml. Although dapsone showed anticonvulsive effects in both animal species, the effective serum levels overlapped the toxic levels reported in the clinical treatment of leprosy. In the majority of the cats, however, seizure suppression was maintained even after the discontinuation of dapsone with lower serum levels than those observed at the beginning of the seizure suppression. Therefore, dapsone would be useful as an antiepileptic drug only when long-term anticonvulsive efficacy is demonstrated using smaller doses comparable to those used in the treatment of leprosy.

A 27-year-old man had a 5-year history of a peculiar state characterized by clouded consciousness provoked by ingestion of alcohol. The episode was identified electroclinically as nonconvulsive status epilepticus and was activated by ingestion of alcohol. Single-photon emission computed tomography (SPECT) examination during the nonconvulsive status epilepticus showed increased regional cerebral perfusion in the right frontal region. This finding, along with the EEG expressions, supports a cortical origin of the nonconvulsive status epilepticus and a diagnosis of complex partial status epilepticus (CPSE). To our knowledge, this is the first report of a documented case of CPSE during intoxication provoked by alcohol ingestion and also of a SPECT examination during CPSE.

1. The seizure manifestations of patients with hemiplegia were reminiscent of partial seizures. The motor manifestations were notably asymmetrical and impairment of consciousness was mild. Nevertheless, tonic seizures, identified by electroclinical correlation were found in 49 patients (88%) although they were predominantly unilateral or asymmetrical. 2. Unclassified seizures characterized by ictal automatisms, which mimic complex partial seizures was observed in 5 patients (9%). 3. Late epileptic seizures of the HHE syndrome were regarded as psychomotor seizures by Gastaut et al. In the present study, however, complex partial seizures were found in only 3 at 28 patients with HHE syndrome (11%) whereas tonic seizures in 23 of these patients (82%). One possible reason for this discrepancy is bias in the selected patient population, because those with transient hemiplegia were not included, and infrequently occurring partial seizures might have been missed. Further study is therefore needed to determine whether the HHE syndrome is associated with complex partial seizures or predominantly unilateral tonic seizures.

We reported 3 cases with subacute sclerosing panencephalitis (SSPE) showing recurrent and involuntary motor phenomena. Their electroclinical correlates were analyzed using CCTV-EEG. Clinically, they slanted their trunks and/or heads, and dropped their upper limbs momentarily only when their antigravity muscles were suitably contracting (sitting, standing, or stretching out their arms). Electrographically, the motor phenomena corresponded with the occurrence of periodic synchronous discharges (PSD) (in one-to-one manner). EMG potentials associated with the muscle contraction subsided at the very moment. These motor phenomena observed in patients with SSPE were discussed in relation to asterexis.

Verbal dichotic listening test was conducted before and after anterior temporal lobectomy on 25 patients who underwent the operation because of their medication-resistant epileptic seizures. Their speech dominance by Wada test was all left sided. 1. Preoperatively, patients having the epileptogenic focus in the right temporal lobe (R-TLE) and those having the focus in the left (L-TLE) were, as expected, all right-ear dominant. The mean number of correct responses was fewer in L-TLE than in R-TLE group. 2. Postoperatively, no detrimental effects for recognition of verbal auditory stimuli by the ear contralateral to the focus was observed both in L-TLE and in R-TLE group. 3. Postoperatively, the ear-dominance shifted: to the left in patients with L-TLE, and to the right more conspicuously in patients with R-TLE compared to the preoperative scores. In other words, the recognition ability by the ears ipsilateral to the side of focus, or of resected temporal lobe, was ameliorated. Summarizing, the unilateral anterior temporal lobectomy did not cause "lesion effect" but yielded improvement of verbal auditory recognition by ears ipsilateral to the epileptogenic focus. Diminished epileptic bombardment resulted in by the resection surgery may be a possible explanation.

To properly establish the surgical treatment of epilepsy in the comprehensive care program, we planned a surgical strategy mainly for a temporal lobe epilepsy and have performed 60 temporal lobectomies. The surgical candidates were selected from 142 patients who met the initial criteria, and passed the initial evaluation for surgical intervention. Forty-five patients had long-term intracranial EEG recording, and circumscribed organic lesions were disclosed in 27 patients by neuroimaging techniques. The outcome of 23 patients who were followed for 2 years postoperatively was complete freedom from complex partial seizures in 17 patients (74%) and an increase in full employment from 2 to 10 patients. Despite the possible surgical complications, including detrimental effects on the higher cerebral functions, it is essential that the surgical treatment of epilepsy should be established as a part of the comprehensive care program. Our experiences and analyses of the state of the art in surgical intervention also suggest that surgical indications for more intractable patients whose social adjustment is less hopeful should be established and the surgical care system for these patients should also be planned. Furthermore, some patients may be free from recurrent seizures postoperatively, but still have difficulties in social rehabilitation. The problems for such patients remain unsolved.

Temporal lobe epilepsy with amygdalohippocampal seizures may have episodes of severe convulsions in childhood more frequently and the onset age is significantly lower compared to epilepsy with lateral temporal seizures. To the contrary, tumorous lesions are found more frequently in epilepsy with lateral temporal seizures. In view of the presumed known etiologies in relation to the localization of epileptogenic foci, the Classification of Epileptic Syndrome (1989), subdividing temporal lobe epilepsies into 2 groups, was found to be useful.

We studied 40 patients with temporal lobe epilepsies who had long-term intracranial EEG recordings and temporal lobectomies. They were divided into 3 groups on the basis of the anatomical site of seizure origin. An electrode implantation technique combined intracerebral depth electrodes with subdural strip electrodes. The seizures were of amygdalo-hippocampal origin in 18 patients, lateral temporal in 13 patients, and temporo-basal in 9 patients. The clinical and EEG features were reviewed retrospectively with regard to 3 factors in each patient: localization of interictal spikes in the scalp-recorded EEG, signal symptoms (auras), and presumed etiologies. Epilepsy with amygdalo-hippocampal and lateral temporal seizures was found to be distinguishable by the electroclinical features. It seems practical to classify these 2 subtypes of temporal lobe epilepsies as in the 1989 Classification of Epilepsies and Epileptic Syndromes. Temporal lobe epilepsies thus defined can be regarded as epileptic syndromes rather than a cluster of seizure manifestations.

Clinical features of a pair of monozygotic male twins, both with severe myoclonic epilepsy in infancy (SME), are described. They were almost completely concordant with respect to seizure onset, clinical seizure symptomatology, interictal, and ictal EEG expressions and seizure prognosis. The existence of such twins suggests the possibility that a genetic factor is determinant in the etiology of this particular epileptic syndrome.

The development of a rational approach and prognostication of epilepsy is based on a special profile of seizure events or the suggested diagnosis of a specific disorder. Although classifications based on neurobiological knowledge would be highly desirable, the present state of inadequate information makes such task difficult. Current classification schemes are, therefore, based on clinical signs and symptoms which are readily identifiable. The significant progress of epileptology has brought us to the stage where one can delineate a number of epileptic syndromes, provide a precise definition, and orient individual syndromes. With further accumulation of both clinical experience and new knowledge in neurosciences, the proposed classification will develop to more appropriate schemes.

Urinary excretion of thromboxane B2 (TXB2), a stable metabolite of TXA2, was measured by radioimmunoassay in 58 normal subjects (17 males and 41 females) aged from 19 to 98 years. The basal level of urinary TXB2 in normal subjects was 100 +/- 6.7 ng/day (mean +/- SEM). In young males, contamination of urine specimens with seminal fluid, which is known to contain large amounts of prostaglandin E, did not change the level of urinary TXB2. Urinary excretion of TXB2 was significantly higher in male subjects than in female (124 +/- 12.6 vs 90 +/- 7.4 ng/day, p less than 0.05). There was no significant age-related difference in 24-h urinary excretion of TXB2 in normal subjects. However, when urinary excretion of TXB2 was expressed as a function of urinary creatinine excretion, it was significantly higher in the elderly (60-93 years old) than in the younger subjects (19-59 years old)(141 +/- 15.7 vs 99 +/- 7.7 ng/g creatinine, p less than 0.02). Renal TXA2 may have a pathophysiological role in the functional impairment of the kidney in elderly people.

Plasma renin activity in the renal veins (V) or infrarenal inferior vena cavae (IVC) of 20 patients with unilateral renovascular hypertension (RVH) was measured to determine how renal vein renin ratio (RVRR) compares with renin index (V-IVC/IVC) as a predictor of curability of RVH. Although there was no significant difference between them in predicting curability, 3 out of 4 patients with hypersecretion of renin (V-IVC/IVC greater than or equal to 0.48) in the stenosed side with contralateral suppression (V-IVC/IVC less than or equal to 0) on the normal side were cured. In addition, 7 out of 11 patients with contralateral suppression irrespective of values of renin index in the stenosed side were also cured. On the other hand, only one out of 6 patients who had neither hypersecretion nor contralateral suppression was cured. These results reconfirm that significant renin secretion with or without contralateral suppression, or only contralateral suppression of renin is highly suggestive of curable RVH.

The present study was performed to investigate the roles of renal kallikrein and prostaglandin (PG) E in the mechanism of the exaggerated fractional Na excretion in hypertensive patients with advanced renal disease by means of the determination of urinary excretion of kallikrein and PGE, and fractional Na excretion in 20 healthy volunteers and 41 patients with chronic glomerulonephritis (14 normotensive patients; 9 borderline hypertensive patients; 18 sustained hypertensive patients). Urinary excretion of kallikrein and PGE was significantly decreased in patients with sustained hypertension as compared with healthy volunteers, while not decreased in those with normotensive or borderline hypertensive patients. Four times higher values for the fractional Na excretion and four or five times higher values for the urinary excretion of PGE corrected for creatinine clearance, were found in patients with borderline or sustained hypertension. There was a significant positive correlation (r = 0.6777) between the two. These results suggest that PGE in the renal tubular compartment may be involved in the mechanism of the exaggerated fractional Na excretion in patients with advanced renal disease. The urinary excretion rate of kallikrein corrected by creatinine clearance was three times greater in patients with borderline hypertension, but no significantly increase in those with sustained hypertension compared with that in healthy volunteers. There was no significant correlation between the fractional Na excretion and urinary kallikrein excretion corrected for creatinine clearance.

To assess the pathophysiological role of renal prostaglandin E (PGE) in renin subgroups of essential hypertension, urinary excretion of PGE before (24 hours urine) and after the administration of furosemide (1 mg/kg, iv) and 2 hours upright posture was estimated in 66 essential hypertensives, classified into high, normal and low renin subgroups. In each renin subgroup, the administration of furosemide and 2 hours upright posture induced marked increases in urinary excretion of PGE and sodium, and in plasma renin activity. However, there were no significant differences in basal values of urinary excretion of PGE among the 3 subgroups, nor in the values after the administration of furosemide and 2 hours upright posture. The present data do not support the hypothesis that the difference in renin level in essential hypertensives is dependent on the synthesis of renal PGE.

To assess the role of inactive renin in hypertensive patients, active, inactive and total renin concentrations (ARC, IRC and TRC) were measured in 37 patients with hypertension of various etiologies. Inactive renin was activated by trypsin and renin concentration was measured using an excess of sheep substrate. Mean values of ARC, IRC, TRC and active renin ratio (AR ratio = ARC/TRC) were higher in 6 cases of renovascular hypertension, and lower in 6 cases of primary aldosteronism and 1 case of idiopathic hyperaldosteronism, when compared with 59 cases of normal subjects. Between ARC and IRC, a slightly positive correlation was observed. Moreover, between ARC and TRC as well as between ARC and AR ratio, close positive correlations were observed. Exceptionally, in a case of juxtaglomerular cell tumor, AR ratio was low in spite of the extremely high value of ARC. Our data suggest that the increase in circulating active renin is due to both the enhancement of the release of renin from the kidney and the increase in the activation of inactive renin, and vice versa.