Current Clinical Trials with Authentic Recombinant Human Growth Hormone in Japan

ABSTRACT. Daily injections of methionine-free, recombinant hGH (rhGH), 8IU, were administered in six healthy volunteers. Non-esterified fatty acid levels increased significantly from 0.45 ± 0.06 to 1.08 ± 0.05 mEq/litre (mean ± SEM) at 4 hours after the first injection of rhGH (p < 0.001). Plasma IGF-1 levels increased significantly at 24 hours after each of the four daily injections of rhGH (basal, 0.80 ± 0.06 units/ml; 24 hours, 1.72 ± 0.21 units/ml; 48 hours, 3.22 ± 0.42 units/ml; 72 hours, 3.17 ± 0.49 units/ml; 96 hours, 3.63 ± 0.32 units/ml; p < 0.001). Eleven patients with hGH deficiency were treated with rhGH, 0.5 IU/kg/week for 3 months. Their heights increased by between 1.1 cm and 4.1 cm during the 3 months of treatment, which was calculated to be equivalent to 4.4–16.4 cm/year, with a mean height velocity of 8.6 ±1.1 cm/year. Anti-hGH antibody was observed in one patient treated with rhGH and had a titre of 10.     

Villous Adenoma in the Large Bowel Following Ureterosigmoidostomy: A Case Report and Review of the Pertinent Literature

This report presents a case of colonic adenoma which developedafter ureterosigmoidostomy. A 71-year-old man was initiallytreated by total cystectomy and ureterosigmoidostomy for transitionalcell carcinoma of the bladder in 1970. In 1983, a routine checkuprevealed urinary occult blood. A barium enema x-ray showed apolypoid lesion in the sigmoid colon. Colonoscopy confirmedthe presence of the polyp adjacent to the ureteral stoma. Thebiopsy findings were interpreted as villous adenoma with severeatypia. This tumor was removed endoscopically. This is the seventhcase report of neoplasia occurring in the sigmoid colon afterureterosigmoidostomy in Japan. Review of the pertinent literatureindicates that patients who have undergone this type of urinarydiversion have an increased risk of development of large bowelneoplasia. Adequate and regular surveillance of these patientshas been suggested in order to help in early detection.     

A Transarterial Approach of Electrical Ablation of Atrioventricular Junction in a Dog Model: Comparison of the Effects between High and Low Energy Shocks

To analyze the effectiveness of a transarterial catheter technique for electrical ablation of the atrioventricular junction, 30 mongrel dogs were studied by means of synchronized electrical shock between the catheter adjacent to the noncoronary cusp and a metal plate behind the dog's back using a standard cardioversion unit. These dogs were classified into two groups according to the energy delivered. The high energy group received more than 100 joules (group A) and the low energy group received from 20 to 60 joules (group B). Complete atrioventricular block was induced by a single shock in all dogs. In group A, ventricular premature beats appeared in all dogs; ventricular fibrillation and ventricular tachycardia appeared immediately in half (6/12) after electrical ablation. No ventricular dysrhythmias occurred in group B. Temporary right ventricular pacing was also performed in 10 out of 12 dogs in group A after electrical ablation. In contrast only one dog required pacing in group B. The cycle length of the subsidiary pacemaker rhythm was essentially identical in both groups. The QRS duration of the subsidiary pacemaker rhythm in group A was significantly longer in group B (P less than 0.01). The extent of myocardial damage induced by electrical ablation in group B was more localized than those in group A. However, the histological lesion representing the granulation tissue with necrosis and slight chronic inflammatory cell infiltration, was identical between both groups A and B. It was concluded that this technique of low energy electrical ablation of the atrioventricular junction adjacent to the noncoronary cusp via a transarterial approach was useful in producing an experimental model of chronic complete AV block.     

Double Ventricular Response by a Single Ventricular Extrastimulus to the Inner Loop of Reentry in a Patient Without Apparent Heart Disease

SHIMIZU, A., et al. : Double Ventricular Response by a Single Ventricular Extrastimulus to the Inner Loop of Reentry in a Patient Without Apparent Heart Disease. In a patient without apparent heart disease, a ventricular extrastimulus delivered from the left ventricular apex where the electrogram was recorded 30 ms after the onset of the QRS complex during VT advanced the second QRS complex, but not the first QRS complex. The morphology of the second QRS complex was the same as that of VT. The postpacing interval was the same as the cycle length of the VT. These findings indicated that the site of stimulation was at the inner loop of the reentry circuit of the VT. A ventricular extrastimulus with a shorter coupling interval advanced the first and second QRS complexes, indicating that the ventricle was activated by antidromic and orthodromic activation from the extrastimulus. Radiofrequency ablation at that site of stimulation terminated the VT and no further VT could be induced.     

Whole body oxygen consumption during extracorporeal hepatic resection: Usefulness of continuous monitoring of mixed venous oxygen saturation

Whole body oxygen consumption was measured using a thermodilution fibreoptic catheter in two patients undergoing extracorporeal hepatic resection. Each patient had virtually normal liver function before the operation. Anaesthesia was induced and maintained in a standard fashion and a venovenous bypass instituted. The anhepatic periods were 302 and 157 min. Upon removal of the liver, the oxygen consumption decreased by about 40% (50 mL/min), while the mixed venous oxygen saturation increased by about 15%. Following re-implantation, the oxygen consumption recovered and increased transiently above control values, while the mixed venous oxygen saturation changed in a reciprocal way. Monitoring whole body oxygen consumption instead of hepatic oxygen consumption seemed helpful in estimating restoration of blood flow and functions in the liver after reperfusion. It was also suggested that changes in oxygen consumption as well as those in cardiac output and haemoglobin concentration could be predicted easily by continuous monitoring of mixed venous oxygen saturation during the peri-anhepatic period.     

基于复杂网络分析高颖教授防治多发性硬化复发与残疾的用药规律

[目的] 旨在总结高颖教授防治多发性硬化复发与残疾的用药规律以及治疗思路。[方法] 针对复发与残疾具有一定疗效的中药处方,采用python、Gephi软件进行复杂网络分析,同时针对核心中药群进行聚类分析。[结果] 152个有效处方的复杂网络分析显示：共162个节点,3 883条边,平均节点度为47.94。其中核心节点为熟地黄、郁金、山茱萸、茯苓等。在矩阵列表中,共生成3 884组相互关联的配伍,其中权重最高为熟地黄与山茱萸。[结论] 核心方药为熟地黄、郁金、山茱萸、茯苓、豨莶草、知母、女贞子、萆薢、威灵仙、黄芩等,常用的配伍为熟地黄与山茱萸、熟地黄与茯苓、山茱萸与茯苓等,主要治法以补益肝肾为主,兼清热化湿、解毒通络,蕴涵动态变化、阴阳协调、攻补权衡的灵活辨治思路。     

Effects of uroguanylin on natriuresis in experimental nephrotic rats

Aim:   Uroguanylin, isolated from human and opossum urine, is a candidate intestinal natriuretic hormone that controls the sodium and water balance between the intestine and the kidneys. Levels of immunoreactive (ir)-uroguanylin in the plasma and urine are increased in rats and humans with nephrotic syndrome, which is physiologically characterized by sodium retention with massive proteinuria. The present study evaluates the effect of natriuresis induced by uroguanylin on nephrotic rats.
Methods:   Normal rats and rats rendered nephrotic by injections of puromycin aminonucleoside (PAN) were treated with uroguanylin (0.5 nmol/h, delivered by an osmotic pump) or with vehicle during the sodium retention phase. All rats consumed the same quantity of sodium.
Results:   Uroguanylin did not increase urinary excretion of sodium and water in normal rats, but significantly increased urinary sodium excretion during the sodium retention phase in nephrotic rats (untreated vs uroguanylin-treated nephrotic rats in mmol/mmol creatinine; 2.92 ± 0.65 vs 8.93 ± 2.53 on day 6, P  < 0.05; 3.55 ± 0.47 vs 10.37 ± 1.73 on day 7, P  < 0.01; 14.88 ± 2.32 vs 24.47 ± 2.86 on day 8, P  < 0.05). Plasma levels of ir-uroguanylin in uroguanylin-treated nephrotic rats on day 6 were significantly increased compared with those in uroguanylin-treated control and untreated nephrotic rats.
Conclusion:   Uroguanylin increased urinary sodium excretion in rats with PAN-induced nephrosis, and might be useful for treating sodium retention in patients with nephrotic syndrome.     

Mechanism of action and therapeutic indication of prosthetic mandibular advancement in obstructive sleep apnea syndrome

Abstract Prosthetic mandibular advancement (PMA) was applied to nine patients with obstructive sleep apnea syndrome (OSAS) and its therapeutic usefulness, mechanism of action, and clinical indication were discussed based on polysomnographic findings and serial examination of upper airway before and during PMA treatment. Apnea hypopnea index significantly decreased during PMA treatment compared with the value before treatment ( P < 0.01) and the rate of the treatment responder counted 78.1%. Cephalometric variables indicated forward and inferior advancement of mandible in our subjects. Magnetic resonance imaging of the upper airway during sleep revealed a marked improvement of velopharyngeal obstruction in most subjects. In addition, intraesophageal negative pressure during sleep decreased significantly. Our results confirmed the high therapeutic efficacy of PMA for OSAS and indicated forward advancement of the mandible and decrease of negative pressure loading on upper airway with PMA might suppress velopharyngeal collapse. Thus, PMA was regarded as one of the treatments of choice for OSAS occurring based on with velopharyngeal narrowing.     

Outbreak of acute glomerulonephritis in children: Observed association with the T1 subtype of group A streptococcal infection in Northern Kyushu,Japan

Group A streptococcal infection is associated with the occurrence of acute glomerulonephritis (AGN) and rheumatic fever (RF). A surveillance study in the Saga area, in northern Kyushu, Japan, showed a small variation in the reported number of group A streptococcal infections in the period 1988–94. However, of the AGN cases reported in this period, more than half were observed in 1992. In order to examine whether some change had occurred in the serotype distribution of Streptococcus pyogenes during the period, patients in the Saga area diagnosed as having group A streptococcal infection and patients with AGN or RF were analyzed. Serological T-typing of S. pyogenes was carried out for patients with group A streptococcal infections, and the association between the occurrence of AGN or RF and the distribution of each different T subtype was analyzed. M-typing of S. pyogenes was also carried out and the correlation between T and M types was examined. From 1988 to 1994, the annual number of patients with group A streptococcal infections in the Saga area showed a small variation, range 65–100 patients/year. Of the 42 patients with AGN and three with RF observed in this period, 27 with AGN (64%) and one with RF (33.3%) were detected in 1992. Only the T1 subtype increased in 1992; the other T subtypes showed little variation in incidence. The number of patients with the T1 subtype was significantly correlated with the occurrence of AGN by regression analysis (P < 0.01). Of the 170 subjects tested for both T and M subtypes, 44 of the 45 T1-typed subjects had the M1 protein. Our epidemiological study suggested that the T1 subtype of streptococcal infection was associated with an outbreak of AGN in 1992 in the Saga area.