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M Yamaura

Publications and source records attributed to M Yamaura.

At least 19 recordsLinked to original sources

Effect of atropine on QT prolongation and torsade de pointes induced by intracoronary acetylcholine in the long QT syndrome.

We recently reported a marked QT prolongation and torsade de pointes (TDP) induced by an intracoronary acetylcholine (ACh) administration in patients with long QT syndrome, but the mechanism was not determined. In the present study, the effect of atropine on the ACh-induced QT prolongation and TDP was studied in long QT syndrome. Nine patients with congenital long QT syndrome were studied. ACh at doses of 20, 50, and 100 microg were injected in a stepwise manner into the left main coronary artery, and the changes in the QT interval were measured. In 4 of the 9 patients, ACh administration at a dose of 100 microg was repeated after an intravenous atropine administration at a dose of 0.5 mg. The QT intervals were measured using 12-lead electrocardiograms, and the data were compared before and after atropine administration. The coronary angiograms were normal and coronary spasm was not induced by ACh in all patients. The intracoronary administration of ACh at a dose of 100 microg significantly prolonged the corrected QT interval (QTc), from 511 +/- 26 to 629 +/- 40 ms (p <0.05). In 5 of the 9 patients, TDP was induced and was spontaneously terminated within 10 seconds (n = 4) or required direct-current shock (n = 1). After atropine administration, intracoronary ACh at the same dose resulted in no QT prolongation, and the QTc interval remained unchanged (525 +/- 29 vs 520 +/- 21 ms before and after atropine), and no TDP was induced. These findings indicate that the muscarinic receptor is involved in ACh-induced QT prolongation and TDP, both of which were prevented by the atropine administration.

Acetylcholine

Elevated serum lipoprotein(a) is a risk factor for left atrial thrombus in patients with chronic atrial fibrillation: a transesophageal echocardiographic study.

BACKGROUND: Patients with chronic atrial fibrillation have an increased risk of thromboembolism. Apoprotein(a) has a structural homology with plasminogen, suggesting that lipoprotein(a) [Lp(a)] may produce thrombogenic effects by modulating the fibrinolytic system. However, the role of Lp(a) level in the formation of left atrial thrombus has not been studied. We sought to evaluate whether Lp(a) is a risk factor for left atrial thrombus in patients with chronic atrial fibrillation. METHODS AND RESULTS: The consecutive series of 150 patients (mean age 67 +/- 8 years) with chronic atrial fibrillation underwent transesophageal echocardiography. Left atrial thrombus was diagnosed by transesophageal echocardiography. Clinical, biochemical, and echocardiographic variables were prospectively collected. Univariate analysis showed that patients with left atrial thrombus (n = 29, 19%) had higher frequency of spontaneous echo contrast (93% vs 55%, P <.0001) than patients without left atrial thrombus (n = 121). Patients with left atrial thrombus also had a significantly higher serum concentration of Lp(a) (34.5 +/- 24.1 vs 17.9 +/- 13.5 mg/dL, P <.0001), a larger left atrium (5.4 +/- 0.9 vs 4.8 +/- 0.7 cm, P <.001), and a lower left atrial appendage peak flow velocity (11.1 +/- 5.4 vs 23.5 +/- 14.6 cm/s, P <.0001). Multivariate regression analysis showed that the Lp(a) concentration (P <.0001) was a significant positive predictor and the left atrial appendage peak flow velocity (P =.0125) was a significant negative predictor of left atrial thrombus. Left atrial thrombus was present in 16 (48%) of 33 patients with Lp(a) level >/=30 mg/dL. CONCLUSIONS: Elevated serum levels of Lp(a) are strongly associated with left atrial thrombus. These findings suggest that Lp(a) level may be a novel risk factor for left atrial thrombus in patients with chronic atrial fibrillation.

Aged

Effects of the ATP-sensitive K channel opener nicorandil on the QT interval and the effective refractory period in patients with congenital long QT syndrome. Investigator Group for K-Channel Openers and Arrhythmias.

Congenital or idiopathic long QT syndrome is characterized by a frequently lethal ventricular arrhythmia called torsades de pointes (TdP) as well as a prolonged QT interval. The long QT interval related to an abnormal gene of the Na+ channel has been shown to be shortened by mexiletine. However, the action of K+ channel openers on the QT interval associated with abnormal genes of the K channel has yet to be studied. Seven patients of five families with long QT syndrome were included in this study, of whom six had syncope and six had documented TdP. Either long QT interval or sudden cardiac death had been observed in family members of all seven patients. At 1 to 3 weeks after admission, when TdP or frequent ventricular arrhythmia had subsided, nicorandil, an ATP-sensitive K channel opener, was administered orally at a dose of 15 mg/day in five patients and at 30 mg/day in the remaining two patients, and the effects were assessed on the third day after drug administration. In four patients, the effective refractory period was measured in the right ventricle before and after administration of K channel opener administration. The QT interval (QTc) prior to administration of the K channel opener was 0.60 +/- 0.09 ms (mean +/- SD) (0.61 +/- 0.10 second(1/2)), which was shortened to 0.54 +/- 0.05 ms (0.55 +/- 0.06 second(1/2)) on the third day of drug administration (P < .05 for both): 10.4 +/- 8.0% (8.6 +/- 5.5%). The QT interval at varying preceding R-R intervals on Holter electrocardiograms showed a shift toward the right as a result of the drug administration. The effective refractory period showed a significant prolongation, 256 +/- 26 ms versus 280 +/- 22 ms before and after drug administration, respectively (P <.05). Intravenous administration of nicorandil resulted in no significant change in heart rate or blood pressure, while QTc showed a tendency to shorten, but nonsignificantly (P = .08). However, a hump on the monophasic action potential was abolished, especially at the long preceding R-R interval induced by premature stimulation of the ventricle. It is concluded that nicorandil shortens the QT interval slightly when administered orally, whereas the effective refractory period shows a slight prolongation. The physiologic and clinical significance of these effects needs to be studied further.

Administration, Oral

Comparison of arrhythmogenicity of atrial pacing at several right atrial pacing sites: evaluation of canine atrial electrograms during atrial pacing and arrhythmogenicity for atrial fibrillation.

The changes in the duration of atrial electrograms and the appearance of AF during atrial pacing were compared among five atrial pacing sites in dogs to clarify the arrhythmogenicity of atrial pacing at different atrial pacing sites. In seven mongrel dogs (15-20 kg), the right atrial surface was exposed by right thoracotomy. Atrial electrograms were recorded via bipolar electrodes with an interelectrode distance of 1.2 mm at four right atrial sites: (1) the high right atrium (HRA), (2) the mid-right atrium (MRA), (3) the low right atrium (LRA), and (4) the center of the pectinate muscle (PM). The duration of the atrial electrograms at these four recording sites were measured during atrial pacing with fixed cycle lengths of 200, 150, and 120 ms delivered at five atrial sites: (1) the HRA, (2) the inferior vena cava (IVC), (3) the right atrial appendage (RAA), (4) Bachman's bundle (BB), and (5) the atrial septum (AS). In each dog, the atrial pacing with the 120-ms cycle length was performed five times at each pacing site to evaluate the inducibility of AF. When AF was induced, the atrial recording site which first showed a fragmented atrial electrogram was considered the initiation site of the AF. AF was induced during 9 of 35 episodes of atrial pacing at the HRA site, 11 of 35 at the IVC site, 5 of 35 at the RAA site, 3 of 35 at the BB site, and none at the AS site. The initiation site of AF was in the HRA site in 11 of 28 episodes of induced AF, in the MRA site in 9 of 28, and in the LRA site in 8 of 28. At each recording site, the shorter the paced cycle length, the longer the duration of the atrial electrogram regardless of the pacing site. During the atrial pacing with the 200-ms cycle length, the HRA pacing resulted in the shortest duration of the atrial electrogram at each recording site in comparison with the other pacing sites. However, during atrial pacing at the two shorter paced cycle lengths, the duration of the atrial electrogram was shorter during the pacing at the BB or AS sites in comparison with the other three pacing sites, i.e., the HRA, IVC, and RAA sites. These results were the same for all atrial recording sites, but the prolongation of the atrial electrogram was most prominent at the HRA and MRA recording sites, which are most likely initiation sites of the induced AF. In the canine atria, (1) the initiation sites of AF were likely to be the HRA, MRA, or LRA sites in comparison with the PM site; and (2) the atrial pacing at the BB or AS sites was considered less arrhythmogenic for AF than the pacing at the HRA, LRA, or RAA sites.

Animals

Reentrant ventricular tachycardia. Interpretations of electrophysiologic findings and its applications.

Monomorphic sustained ventricular tachycardia (MSVT) was revisited in relation to the electrophysiologic findings and their relation to the drug efficacy. Old myocardial infarction is less common cause of MSVT in Japan, and the majority (about 2/3) of MSVT is unrelated to coronary artery disease but, the mechanism shared a common mechanism: reentry with an excitable gap as others. The reentrant mechanism was supported from the inducibility, the terminability of VT by electrical stimulation, and by the ability to entrain with rapid pacing. In MSVT associated with underlying heart diseases, diseased myocardium showed low amplitude and fragmented electrograms and the area was considered to participate as the central common pathway of reentrant circuit. The area of slow pathway showed a decremental conduction or all-or-nothing conductive property. The width of the excitable gap seemed to be determined by the maximal conductive frequency but not by the duration of action potential: effective refractory period. As to the drug efficacy, there was no baseline characteristics in predicting the efficacy. However, the significant narrowing of the width of the excitable gap was associated with the drug efficacy and VT became non-inducible after addition of the same drug. The response pattern of the excitable gap to specific drug including class III, was not predictable. Further electropharmacological studies will be warranted.

Anti-Arrhythmia Agents

Electrophysiologic effects of intravenous MS-551, a novel class III antiarrhythmic agent, on human atrium and ventricle.

The effects of intravenous MS-551, a new class III antiarrhythmic drug, on atrium and ventricle were evaluated in 6 patients with ventricular tachyarrhythmias (4 males and 2 females; mean age 45 +/- 21 years) in an electrophysiologic study. Two patients had sustained ventricular tachycardia (VT) and 4 patients had ventricular fibrillation (VF). Electrophysiologic study was performed before and after the administration of MS-551 (loading infusion 0.3 mg/kg for 5 min + 0.01 mg/kg/min). The QT and QTc intervals were significantly prolonged by MS-551 from 359 +/- 52 to 411 +/- 63 msec (p = 0.01) and from 410 +/- 36 to 452 +/- 47 (p = 0.0172), respectively. No effect was observed on the sinus cycle length, QRS duration, or AH and HV intervals in sinus rhythm. The effective refractory periods of the right atrium (AERP) were significantly prolonged at paced cycle lengths of 600 (from 222 +/- 19 to 250 +/- 23 msec, p = 0.0009), 400 (from 207 +/- 15 to 228 +/- 15, p < 0.0001) and 300 (from 193 +/- 10 to 205 +/- 8 msec, p = 0.0127) msec. Similarly, the right ventricular ERP (VERP) were significantly prolonged at paced cycle lengths of 600 (from 240 +/- 23 to 268 +/- 23 msec, p < 0.0001), 400 (from 225 +/- 22 to 250 +/- 24 msec, p = 0.0007), and 300 msec (from 213 +/- 14 to 228 +/- 18 msec, p = 0.0071). MS-551 prolonged AERP and VERP in a "reverse" use-dependent manner without changing the conduction time in patients with ventricular tachyarrhythmias. MS-551 prevented the induction of VT in 1 patient and VF in only 1 patient in this electrophysiologic study. Further evaluation of the therapeutic potential of MS-551 using higher dosages is necessary.

Adolescent

Comparison of electrophysiologic effects of intravenous E-4031 and MS-551, novel class III antiarrhythmic agents, in patients with ventricular tachyarrhythmias.

Electrophysiologic effects of intravenous E-4031 and MS-551, novel class III antiarrhythmic agents, were evaluated in 5 and 6 patient with ventricular tachyarrhythmia, respectively. Six patients had sustained ventricular tachycardia (VT) and 5 had ventricular fibrillation (VF). Electrophysiologic study was performed before and after administration of E-4031 and MS-551 [E-4031; loading infusion 9 micrograms/kg for 5 min + 0.15 microgram/kg/min, MS-551; loading infusion 0.3 mg/kg for 5 min + 0.01 mg/kg/min]. The QT intervals were significantly prolonged after administration of E-4031 and MS-551 from 409 +/- 37 to 455 +/- 49 msec (11%), and from 359 +/- 52 to 411 +/- 63 msec (14%), respectively. The QTc intervals were significantly prolonged from 457 +/- 17 to 494 +/- 24 msec (8%), and from 410 +/- 36 to 452 +/- 47 (10%), respectively. There were no significant differences in the QT and QTc intervals between these two agents. The right ventricular effective refractory period (VERP) with E-4031 was prolonged at 600 (from 244 +/- 27 to 270 +/- 31 msec, 11 +/- 2%), 400 (from 222 +/- 23 to 242 +/- 24 msec, 9 +/- 3%), and 300 msec (from 206 +/- 19 to 218 +/- 25 msec, 6 +/- 4%), and those with MS-551 were prolonged at 600 (from 240 +/- 23 to 268 +/- 23 msec, 12 +/- 2%), 400 (from 225 +/- 22 to 250 +/- 24 msec, 11 +/- 4%), and 300 msec (from 213 +/- 14 to 228 +/- 18 msec, 7 +/- 4%). Both E-4031 and MS-551 prolonged VERP in a "reverse" use-dependent manner without changing the conduction velocity. E-4031 prevented the induction of VT in one patient. MS-551 prevented the induction of VT and VF in one patient each. Further evaluation of these selective class III agents may be needed to determine if higher doses are required to achieve the pharmacological effects in patients with ventricular tachyarrhythmias.

Adult

A comparison of electrophysiologic properties between responders and non-responders to DL-sotalol among patients with ventricular tachyarrhythmia. Importance of the lack of a reverse use-dependent effect on ventricular refractoriness to responders.

This study was undertaken to determine whether dl-sotalol can prevent ventricular tachyarrhythmia inducibility that can be predicted from electrophysiologic parameters. The effects of dl-sotalol in 16 patients (ventricular tachycardia (VT) in 11 and fibrillation (VF) in 5) were determined in electrophysiologic studies before and after dl-sotalol (320 mg/day). In 9 of 16 patients (56%) after dl-sotalol, ventricular tachyarrhythmia could not be induced by the entire stimulation protocol (responders). There were significant differences in QT interval (462 +/- 52 vs. 415 +/- 34 msec; p < 0.05) and ventricular effective refractory period (VERP) at 600, 400 and 300 msec (302 +/- 28 vs. 262 +/- 20 msec; p < 0.001, 280 +/- 23 vs. 240 +/- 21 msec; p < 0.001, 256 +/- 24 vs. 222 +/- 12 msec; p < 0.005, respectively) between responders and non-responders. The percentile increases in VERP (% VERP) at 600, 400, and 300 msec in responders were 25%, 26%, and 27%, whereas those in non-responders was 9%, 7%, and 7%, respectively. Isoproterenol administered to responders did not fully reverse the dl-sotalol-induced prolongation of VERP (delta VERP) at 600, 400, and 300 msec, which remained significantly prolonged compared to the baseline (281 +/- 18 vs. 241 +/- 16 msec; p < 0.01, 258 +/- 20 vs. 223 +/- 21 msec; p < 0.01, 247 +/- 22 vs. 202 +/- 16 msec; p < 0.01, respectively). % VERP did not exhibit significant differences at 600 (16%), 400 (15%), and 300 (20%) msec, indicating the lack of a reverse use-dependency. The results suggest that delta VERP in responders did not show reverse use-dependency, and that the phenomenon may account for the efficacy of dl-sotalol.

Action Potentials

Methotrexate maintains bone mass by preventing both a decrease in bone formation and an increase in bone resorption in adjuvant-induced arthritic rats.

We examined the effects of low doses methotrexate (MTX) and indomethacin (IND) on bone mass and turnover in normal male Sprague-Dawley rats and those with adjuvant-induced arthritis. Normal and the adjuvant (heat-killed mycobacterium)-injected rats, 6 weeks of age, were given MTX at daily doses of 0.05, 0.1, or 0.2 mg/kg body weight (BW) or IND at a daily dose of 1.0 mg/kg BW. Rats were killed at the start, or at 14 and 28 days. In normal rats, the administration of these agents did not change the lumbar and femoral BMD values, nor did the serum osteocalcin or urinary deoxypyridinoline (D-Pyr) levels. Lumbar trabecular osteoclast number (Oc.N/BS) and osteoclast surface (Oc.S/BS) were decreased in the rats given IND. In the arthritic rats, the administration of MTX did not prevent an early increase of paw edema in the adjuvant-injected limb, but late inflammatory edema was alleviated in the non-injected limb. However, MTX administration at a dose of 0.1-0.2 mg/kg BW maintained an age-dependent increase in the lumbar and femoral BMD values. While serum osteocalcin levels were decreased and urinary D-Pyr values were increased in the arthritic control rats, these bone markers remained at the levels of the normal rats. Decreases in mineral apposition rate (MAR) and bone formation rate (BFR/BS) and increases in the trabecular Oc.N/BS and Oc.S/BS values were prevented by MTX. While IND almost completely prevented inflammatory paw edema, it did not improve the parameters of bone formation. An increase in osteoclasts was prevented and the osteopenia in the lumbar and the femoral bone was only partially prevented by IND. These data suggest that MTX improves bone mass and turnover in the arthritic rat, in which several cytokines that affect bone cells are involved. An increase in bone resorption may be due to prostaglandins, but bone formation defect was suggested to be due to other cytokines such as IL-1, IL-6, and TNF-alpha in this model.

Animals

Local bone turnover in the metaphysis of the proximal tibia and the lumbar vertebra during the early periods after ovariectomy in rats.

To clarify the local changes in bone formation and resorption during the early period after ovariectomy (OVX), 200 SD rats, 4 months of age, underwent OVX or sham surgeries and seven to nine rats from each group were terminated at 1, 3, 7, 11, 15, 19, 23, 28, 35, 63, and 91 days postsurgery after tetracycline labeling. Serum intact osteocalcin levels were measured. Undecalcified sections of the 5th lumbar body (L5) and the right proximal tibia were measured for trabecular bone area, the labeled perimeters and the interlabeling distances after Villanueva's staining. On the 4th lumbar body (L4) and the left proximal tibia, undecalcified sections were measured for the trabecular osteoclast by tartrate-resistant acid phosphatase staining. The uterine horns were atrophied on the 3rd postovariectomy day (day 3). Serum osteocalcin levels increased on day 7 and reached the highest value on day 23. In either L5 or the metaphysis of the proximal tibia, trabecular bone volume (BV/TV) significantly decreased on day 15. The trabecular bone loss on day 28 was approximately 50% in the tibia and 15% in the L5. In either the lumbar or the tibia, osteoclast numbers significantly increased at day 3, and peaked between days 15 and 23. In the tibia, however, the bone formation rates (BFR/BS) were significantly reduced on the 3rd and 7th post-surgical days compared with the start value for both the OVX and sham groups. The BFR/BS values in L5 did not decrease during the first 7 days in either group. The BFR/BS values were then increased for both L5 and the tibia after day 7. These data clearly demonstrated that the local bone turnover 7 days post-OVX was identical in the proximal tibia and the lumbar vertebra. In the proximal tibia, however, it may be suggested that the increased bone resorption and reduced formation within 7 days after OVX due to the combined effects of both an estrogen deficiency and the surgical intervention would possibly play a critical role in the greater magnitude of the trabecular bone loss.

Animals

The effect of 17 beta-estradiol treatment on the mass and the turnover of bone in ovariectomized rats taking a mild dose of thyroxin.

We performed the dosing experiment to establish whether estrogen administration has any beneficial effects on the mass and the turnover of bone in ovariectomized rats taking a mild dose of thyroxin. Thirty-five Wistar rats, 28 weeks of age, received ovariectomies (OVX) or sham operations and were divided into five groups. Group 1 was the sham group, Groups 2-5 were ovariectomized. Group 2 was the OVX-control, Group 3 treated with thyroxin 30 micrograms/kg/day (T4), Group 4, 17 beta-estradiol 0.3 mg/kg/week (E2), and Group 5, the combination of T4 and E2. The duration of the experiment was 12 weeks. At the end of the experiment, serum chemistries were measured. Bone minerals in the femur were determined with single photon absorptiometry and bone turnover was assessed histomorphometrically. Alkaline-phosphatase increased in Group 3 (OVX-T4), but it reduced in Groups 4 (OVX-E2) and 5 (OVX-T4 + E2). Bone minerals decreased in Groups 2 (OVX) and 3. In Group 4, it was preserved at the same level as in Group 1. Group 5 showed a significant increase of bone mass compared with Group 1. Eroded surface and osteoid surface increased in Groups 2 and 3 and they were reduced in Groups 4 and 5. Bone volume and mineral apposition rate were at a maximum in Group 5. This study demonstrated that 17 beta-estradiol was capable of preventing the bone mass decrease by regulating the turnover in ovariectomized rats taking a mild dose of thyroxin. Osteoblast function appeared to be stimulated in combination with 17 beta-estradiol and thyroxin.

Animals

[Diagnostic value of glass microfibre-based basophil histamine release test in food allergic children. Comparison with specific IgE antibody and skin scratch test].

We evaluated the diagnostic value of the glass microfibre-based histamine release test (HRT), which allows measurements to be performed using small amounts of whole blood, in 50 children with food allergy case histories. The patients were evaluated by radioallergosorbent tests (RAST), skin scratch tests (ST) and food challenge tests. Of the 50 patients, 39 had a confirmed clinical diagnosis of food allergy from food challenge tests and case histories, and were affected by a total of 60 positive allergens (egg 37, milk 11, soy beans 4, wheat 5, rice 3). The concordance, sensitivity, and specificity of HRT with the clinical diagnosis were 85.3%, 66.7% and 92.1%, those of RAST were 59.4%, 90.0% and 48.2%, and those of ST were 84.7%, 71.8% and 88.7%, respectively. The positive predictive values of HRT, RAST and ST were 75.5%, 38.8% and 66.7%. The false positive ratio of HRT (24.5%) was the lowest among all the tests. There was a significant correlation between HRT and RAST (r = 0.513, p < 0.001). However, the concordance of HRT with respect to RAST was 56.0%. The concordance and specificity of HRT in relation to the clinical diagnosis were higher than RAST and the same as ST. The sensitivity of RAST was higher than that of HRT. From these results, we concluded that RAST is good for the screening of allergens and that HRT is a useful diagnostic method for the confirmation of a clinical allergy.

Basophils

Reduced mechanical competence of bone by ovariectomy and its preservation with 24R,25-dihydroxyvitamin D3 administration in beagles.

To examine changes in mechanical competence of bone caused by ovariectomy, and to assess the effect of 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) administration on mass and structure, we conducted mechanical tests on canine lumbar vertebrae and femur 31 months after surgery. Beagles weighing 9-10 kg were ovariectomized (OVX) or sham operated (n = 3, group 1). OVX dogs were divided into three groups. Group 2 (n = 3) received only the agent vehicle, groups 3 (n = 4) and 4 (n = 4) received daily 24R,25(OH)2D3 doses of 2 and 10 mcg/kg, respectively from 1 month after surgery. In group 4, the dose level was increased up to 100 mcg/kg by the 17 month. Then, L3 and L4 vertebrae and left femur were excised from each animal. Torsional tests at the femoral diaphysis were conducted. On the L3 specimen, the circumferential shell was removed to obtain a cancellous core specimen. The shell was left intact on the L4 specimen. In compression tests, the loading was stopped just after maximal strength was reached for minimum specimen collapse, from which 7-mcm thick, undecalcified, midcross sections parallel to the base of the specimen were obtained. Neither femoral morphology, bone mineral contents (BMCs) nor structural stiffness indicated a significant difference among groups. Though L3 and L4 BMCs were reduced in group 2, in group 3 and 4 they were significantly larger than in group 2. Compression tests on lumbar vertebral specimens showed a significant decrease in mechanical parameters in group 2. On the cancellous core specimen of L3, the mean structural stiffness in group 2 was 31.8% of that in group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3

[Assessment of the amount of drug deposited in the lungs of asthmatic children using disodium cromoglycate as the marker].

Disodium cromoglycate (DSCG) is easily absorbed from the airways and lungs, and is excreted unchanged in the urine and bile. Therefore it is possible to estimate the dose of DSCG deposited in the airways and lungs based upon urinary excretion. The urinary concentration of DSCG was measured by the HPLC method in 78 asthmatic children aged 0 to 16 years after they had inhaled 20 mg nebulizer solutions with facemasks. Jet-type nebulizers were used. The mean urinary excretion of DSCG in the patients aged 0, 1, 2 and 3 years from 4-hour urinary collection represented 0.204%, 0.231%, 0.593%, 0.790%, respectively, of the dose administered. In the patients aged 3, 4, 5-6, 7-9 and 10-16 years, from 24-hour urinary collection, the figures were 0.625%, 0.895, 0.855, 1.176%, 1.070%, respectively. The mean dose deposited in the airways and lungs of the age groups 0-1, 2, 3, 4-6, 7-9, and 10-16 years represented approximately 0.5%, 1.4%, 1.4-1.8%, 2.0%, 2.7%, 2.4%, respectively, of the dose administered. Although there was a wide range in the total amount of DSCG deposited in the airways and lungs of asthmatic children, these data seem to provide a useful guide to standardizing the dosing in inhalation therapy.

Administration, Inhalation

The displacement of the femoral head by rotational acetabular osteotomy. A radiographic study of 97 subluxated hips.

To determine the limits of medial and inferior displacement of the subluxated femoral head by rotational acetabular osteotomy, we studied the acetabular coverage and position of the femoral head radiographically before and after surgery in 97 hips. The median age of the patients at the time of surgery was 33 (18-54) years. The position of the femoral head was represented by its center and medial and upper borders. The average increase and decrease in the CE and the AC angle were 39 degrees and 27 degrees, respectively. The average medial displacement of the head was 8 (-12 to +19) mm measured from its center, and 7 (-10 to +21) mm measured from its medial border. The average inferior displacement was 5 (-6 to +19) mm from its center and 4 (-10 to +15) mm from the upper border. These results indicate that concentric reduction by rotational acetabular osteotomy is limited and that medial displacement of the subluxated femoral head is within similar ranges obtained by other conventional pelvic osteotomies.

Acetabulum

Molecular cloning and nucleotide sequence of the cDNA for human liver glutamate dehydrogenase precursor.

Two cDNA clones (lambda GDHh1 and lambda GDHn61) for glutamate dehydrogenase (GDH) were isolated from a human liver cDNA library in lambda gt11. The clone, lambda GDHh1, was isolated from the library using a synthetic 45mer oligodeoxy-ribonucleotide, the sequence of which was derived from the known amino acid sequence near the NH2-terminus of human liver GDH. Subsequently, lambda GDHn61 was isolated from the same library using lambda GDHh1 as a probe. The inserts of both clones contained an overlapping cDNA sequence for human liver GDH, consisting of a 5'-untranslated region of 70 bp, an open reading frame of 1677 bp, a 3'-untranslated region of 1262 bp and a 15 base poly(A) tract. The predicted amino acid sequence revealed that the human liver GDH precursor consisted of a total of 558 amino acid residues including the NH2-terminal presequence of 53 amino acids. The sequence deduced for the mature enzyme showed 94% homology to the previously reported amino acid sequence of human liver GDH.

Amino Acid Sequence