Intestinal Absorption of Stable Cyclic Glycylphenylalanine: Comparison with the Linear Form*

The absorption, especially the stability and transportability, of the cyclic peptide cyclic glycylphenylalanine (cyclo(Gly-Phe)) and the linear peptides glycylphenylalanine, glycyl-d -phenylalanine and phenylalanylglycine have been studied in rat small intestine. Linear peptides were degraded on the mucosal side and only glycyl-d -phenylalanine appeared on the serosal side. However, cyclo(Gly-Phe) was stable on the mucosal side and appeared on the serosal side. Furthermore, the absorption clearance of cyclo(Gly-Phe) was higher than that of glycyl-d -phenylalanine. In the presence of the peptidase inhibitor bestatin, the degradation of linear peptides was reduced and linear peptides appeared on the serosal side, but only phenylalanylglycine, which is transported by the oligopeptide transporter, was absorbed faster than cyclo(Gly-Phe). The absorption clearance of cyclo(Gly-Phe) was reduced as its concentration was increased from 125 μm to 500 μm . Furthermore, the absorption clearance of cyclo(Gly-Phe) at 125 μm was reduced at 4°C or in the presence of glycylsarcosine and cephalexin, which are transported by the oligopeptide transporter. These results indicated that cyclo(Gly-Phe) was stable enough to be absorbed and was transported in part by the oligopeptide transporter rather than completely by passive diffusion.     

A case of tetrasomy 9p

A case of mosaic 9p tetrasomy (46,XX/47,XX, + dic[9] [q21]) is reported. Clinical manifestations of the patient were generalized hypotonia, severe mental retardation and characteristic dysmorphic features of 9p tetrasomy. A brief review of the literature is also included.     

Long-term prognosis and prognostic factors of liver cirrhosis in the 1980s

Abstract The prognosis of 174 patients with cirrhosis during the 1980s (1981–89) was analysed. The estimated survival rates were 87.3% in 3 years and 68.5% in 5 years. During the follow-up period, 58 patients died: 20 of hepatocellular carcinoma (37.7%); 11 of hepatic failure (20.8%); eight of gastrointestinal bleeding (15.1%); and 14 of other causes (26.4%). Multivariate analysis revealed that serum albumin, indocyanine green retention rate at 15 min and white blood cell count were significantly associated with prognosis. The results were also compared to our previous study covering the 1970s (1971–80). The estimated survival rate was significantly improved compared to that during the 1970s (54.3% in 5 years, P < 0.001). In the 1980s, hepatic failure mortality significantly decreased ( P < 0.01), and non-liver-related mortality significantly increased ( P < 0.05). In summary, the prognosis of cirrhosis has improved in recent years, and changes of death cause and prognostic factors were observed. It was concluded that to evaluate the severity and prognosis of cirrhosis, new indices and appropriate classification were necessary.     

Spread of subarachnoid hyperbaric amethocaine in pregnant women

In order to examine how the gestational period influences thespread of spinal anaesthesia, we have measured the extent ofspinal block produced by hyperbaric amethocaine 8 mg in 90 women.The patients were allocated to one of five groups accordingto the gestational period: non-pregnant group (n = 17), firsttrimester group (6–12 weeks, n = 14), second trimestergroup (13–24 weeks, n = 26), third trimester group (25–36weeks, n = 15) and term group (37–41 weeks, n = 18). Maximumcephalad spread of analgesia was significantly higher in thesecond trimester (median T3 (range T9–C6)), third trimester(T3 (T4–C7)) and term groups (T2.5 (T4–C8)) thanin the non-pregnant (T4 (T8–T2)) and first trimester groups(T4 (T11–C7)). We found that not only term pregnancy butalso second and third trimester pregnancies enhanced the spreadof spinal anaesthesia, and that first trimester pregnancy didnot affect the spread of spinal anaesthesia.     

The Efficacy and Diagnostic Significance of Sodium Thiosulphate Solution Spraying After Iodine Dyeing of the Esophagus

Abstract: Spraying with Sodium Thiosulphate Solution (STSS, Detoxol®) is reported to be useful in reducing the side effects of Iodine dyeing on the esophagus. In order to determine the optimal concentration of STSS and its efficacy, STSS was administered in the following concentrations. Group A: 10% (Original Solution), Group: B 5%. Group C, 2.5%. Group D: 1.7% and Group E: saline with no STSS, and a questionnaire was conducted to assess the side effects. The results showed that the higher the concentration, the less frequent and short lasting the side effects were. The effects of STSS on diagnostic efficacy was also evaluated. After spraying with STSS, the 2.5% solution removed iodine gradually but there were differences in discoloration among the various degrees of inflammation. When iodine dyeing was repeated, clear images with a good contrast were obtained. Excess iodine was neutralized and details of the surface and vascular pattern were more readily observed. Spraying with STSS seemed to increase the diagnostic ability of the procedure.     

Immunoreactivity to M2 proteins in antimitochondrial antibody-negative patients with primary biliary cirrhosis

Abstract Although antimitochondrial auto-antibodies are characteristically present in the serum of patients with primary biliary cirrhosis (PBC), there is a discrepancy between the positivity for antimitochondrial antibody (AMA) and that for anti-M2 auto-antibody. In an attempt to explain the discrepancy, this study investigates the relationship between the AMA titre, determined by indirect immunofluorescence, and immunoreactivity to four inner mitochondrial membrance proteins (M2 proteins) with molecular weights of 70, 50, 47, and 40 kDa in 129 patients with PBC. Antimitochondrial antibody positivity was identified in 114 (88%) of 129 patients with clinically and histologically confirmed PBC. There were no significant differences between the AMA-negative and AMA-positive groups in clinical characteristics or histologically determined disease stage. Immunoblot analysis showed that all patients had anti-M2 auto-antibodies to one or more of the four M2 proteins. Nine (60%) of the 15 AMA-negative patients had antibodies to only one M2 protein (either 70 or 47 kDa). In contrast, 34 (53%) of the 64 patients with high AMA titres ( 1: 320) had antibodies to all four M2 proteins. There was a significant rank correlation between the AMA titre and the number of antibodies to M2 proteins ( P < 0.01). These findings indicate that the AMA titre is not influenced by the immunogenicity of M2 protein but by the number of M2 proteins that elicit an antibody response and that decreased immunoreactivity to M2 proteins may induce AMA negativity in PBC serum samples.     

Differential Response of QTU Interval to Exercise, Isoproterenol, and Atrial Pacing in Patients with Congenital Long QT Syndrome

Sympathetic stimulation is well known to contribute to the genesis of QTU prolongation and ventricular lachyarrhythmias in patients with congenital long QT syndrome. In this study, we performed exercise treadmill testing, isoproterenol infusion (1–2 μg/min), and right atrial pacing (cycle length 500 msec) in 11 patients with congenital long QT (LQT) syndrome (LQT group) and in 12 age- and sex-matched controls (control group). The responses of the corrected QT (QT_c; Bazett's method) interval and the TU wave complex tvere evaluated. The QT_c interval was prolonged from 482 ± 63 msec^1/2 to 548 ± 28 msec^1/2 by exercise in the LQT group (n = 11; P < 0.005), and this was associated with fusion of the T waves with enlarged U waves, whereas the QT_c interval did not increase with exercise in the control group (n = 12; 402 ± 19 msec^1/2 vs 409 ± 22 msec^1/2). The QT_c interval was also prolonged from 466 ± 50 msec^1/2 to 556 ± 33 msec^1/2 by isoproterenol in the LQT group (n = 7; P < 0.005) in association with morphological changes of the TU wave complex like those seen with exercise, whereas it was only slightly increased from 399 ± 10 msec^1/2 to 436 ± 13 msec^1/2 by isoproterenol in the control group (n = 77; P < 0.001). However, the QT_c interval did not increase with atrial pacing in the LQT group (n = 8; 476 ± 57 msec^1/2 vs 486 ± 59 msec^1/2), whereas it was slightly increased from 400 ± 21 msec^1/2 to 426 ± 18 msec^1/2 by atrial paring in (he control group (n = 8; P < 0.005). These results suggest that sympathetic stimulation plays an important role in the QTU prolongation and marked TU wave complex abnormalities in patients with congenital long QT syndrome.     

Cutting Balloon Angioplasty for a Restenosis Lesion at the Distal Anastomosis of a Saphenous Vein Graft

We successfully performed cutting balloon angioplasty for a restenotic lesion involving the distal saphenous vein graft (SVG) anastomosis that had developed within 1 month after conventional balloon angioplasty. We considered that cutting balloon angioplasty, which has been considered to produce less vascular injury, could be a viable choice for the treatment of a lesion at the distal anastomosis of an SVG.     

Diastolic Mitral Regurgitation in Patients with First-Degree Atrioventricular Block

Diastolic mitral regurgitation has been observed in patients with DDD pacemakers when the atrioventricular (AV) delay was prolonged. However, diastolic mitral regurgitation associated with first-degree AV block has not been fully studied. We examined transmitral blood flow in 24 patients with first-degree AV block and normal cardiac function (ages 35.3 ± 17.4 years), and in nine patients with DDD pacemakers and normal cardiac function (ages 73.1 ± 8.1 years), using pulsed Doppler echocardiography. Diastolic mitral regurgitation was observed in 19 of 24 patients with first-degree AV block. Although PQ interval was shortened from 0.32 ± 0.06 to 0.20 ± 0.05 seconds (P < 0.01) after 1 mg atropine sulfate IV, the interval between P wave (ECG) and the beginning of diastolic mitral regurgitation did not change, while the duration of diastolic mitral regurgitation was shortened from 0.15 ± 0.03 to 0.05 ± 0.03 seconds (P < 0.01). There was a significant correlation between changes in PQ interval and changes in the duration of diastolic mitral regurgifation (r = 0.92, P < 0.001). Although cardiac output (3.9 ± 0.05 L/min) and pulmonary capillary wedge pressure (5.1 ± 1.5 mmHg) were normal in all patients with pacemakers, diastolic mitral regurgitation was observed when the AV delay was prolonged. The critical PQ interval for the appearance of diastolic mitral regurgitation was 0.23 ± 0.01 seconds. In patients with prolonged PQ intervals, delayed ventricular contraction following atrial contraction may be associated with mitral regurgitation in the presence of a reversed AV pressure gradient. The results of this study suggest that diastolic mitral regurgitation occurs not only in patients with DDD pacemakers, but also with AAIR pacemakers when the PQ interval is prolonged. The occurrence of diastolic mitral regurgitation is associated with the pacing mode or the setting of AV delay.     

Deficiency of endogenous prostanoids in gastric and duodenal ulcer diseases

The levels of prostaglandin E₂ (PGE₂), 6-keto-prostaglandin F₁α (PGF₁α) and thromboxane B₂ (TXB₂) in endoscopic biopsy specimens from the gastric and duodenal mucosa of healthy volunteers and ulcer patients were measured by radio-immunoassay. The PGE₂ and PGF₁α levels in the mucosa of the corpus of the stomach were lower and the TXB₂ level was higher in 10 patients with gastric ulcer in the corpus than in the 16 healthy subjects. The PGE₂ level in the antral mucosa of 14 patients with gastric ulcer in the antrum was lower than in the controls. In 18 patients with duodenal ulcer, PGE₂ deficiency was more widespread in the entire gastric and duodenal mucosa while the reduced PGF₁α level was limited in the gastric corpus. Lower levels of PGE₂ in patients with antral or duodenal ulcer and of PGE₂ and PGF₁α in patients with corpus ulcer in the anatomical mucosal area including the ulcer site may predispose the mucosa to ulceration.