Microvascular disturbances in the colonic mucosa in antibiotic-associated haemorrhagic colitis: Involvement of platelet aggregation

An ultrastructural study of the colonic mucosa was performed in four patients with antibiotic-associated haemorrhagic colitis and new findings are reported. Colonoscopy was performed and biopsy specimens were obtained within 24 h of the onset of bloody diarrhoea. Colonoscopy demonstrated diffuse oedematous and haemorrhagic mucosa with erosions and white coat. Light microscopy revealed mucosal haemorrhage and inflammatory cell infiltration. Ultrastructurally, platelet aggregation was frequently present in the lumina of colonic mucosal capillaries, causing engorgement of red blood cells in adjacent microvessels. Mild to severe damage was observed in capillary endothelial cells, including discontinuity of basement membranes, gaps between endothelial cells and the destruction of capillaries. There was no evidence of microvascular spasm. In conclusion, our findings suggest that antibiotics directly or indirectly cause microcirculatory disturbances, which result in tissue damage and haemorrhage, in the colonic mucosa.     

Erectile dysfunction in hemodialysis patients with diabetes mellitus: Association with age and hemoglobin A1c levels

Abstract Aim: Erectile dysfunction (ED) is common in patients with diabetes mellitus (DM) as well as those undergoing hemodialysis (HD). The purpose of this study is to investigate the frequency and severity of ED in HD patients with DM and those without DM. In addition, we examined the relationship between erectile function and several risk factors, including presence of DM and hemoglobin A1c levels in HD patients. Methods: This study involved 180 patients on HD, including 66 HD patients with DM (DM‐HD) and 114 patients without DM (non‐DM‐HD). We evaluated erectile function using an abridged five‐item version of the international index of erectile function (IIEF‐5). Logistic regression analysis was used to investigate the relationship between presence of ED and several risk factors. Results: The total score of IIEF‐5 in DM‐HD patients (9.5 ± 4.2) was significantly lower than in non‐DM‐HD patients (13.5 ± 5.7). The prevalence of severe ED was 42.4% and 18.4% in DM‐HD patients and non‐DM‐HD patients, respectively. Age, cardiovascular disease history, and DM were identified as independent risk factors for the presence of ED. Furthermore, age and elevated hemoglobin A1c levels were identified as independent risk factors for the presence of severe ED. Conclusion: DM‐HD patients are more likely to have ED, and particularly severe forms of ED, than non‐DM‐HD patients. DM and elevated hemoglobin A1c levels were associated with the presence of ED or severe ED, respectively. Aging was identified as an independent factor in both ED and severe ED.     

E1AF expression is associated with extra‐prostatic growth and matrix metalloproteinase‐7 expression in prostate cancer

E1AF is associated with malignant aggressiveness via regulation of matrix metalloproteinases (MMPs), which play pivotal roles in invasion through the degradation of extracellular matrix of tissues surrounding tumors. However, the clinical significance of E1AF and MMPs in patients with prostate cancer is not fully understood. We reviewed 50 tissue samples from patients with T2‐3N0M0 prostate cancer who had undergone radical operation. Expression levels of E1AF, MMP‐1, ‐3, ‐7, ‐9 and ‐14 were determined semiquantitatively by immunohistochemistry. The mean ± SD percentage of E1AF‐stained cancer cells was 8.56 ± 5.22, and it was significantly higher (p < 0.001) than the E1AF‐immunostaining index of normal cells (1.17 ± 0.61). E1AF immunostaining index in pT3 (12.74 ± 4.80) was significantly higher (p < 0.001) than that in pT2 (5.78 ± 3.31). Although E1AF expression correlated with that of MMP‐7 and MMP‐9 (r = 0.47, p < 0.001 and r = 0.41, p = 0.004, respectively), multivariate analysis showed that E1AF correlated with only MMP‐7 expression (OR = 5.81, 95% CI = 1.27–26.59, p = 0.023). Our results demonstrated that increased expression of E1AF is involved in tumor aggression of prostate cancer. This finding may be influenced by regulation of MMP‐7. We speculate that E1AF is a possible target in treatment and prevention of tumor growth in prostate cancer.     

Subchronic Oral Toxicity of Glyoxal via Drinking Water in Rats

Subchronic Oral Toxicity of Glyoxal via Drinking Water in Rats.Ueno, H., Segawa, T., Hasegawa, T., Nakamuro, K., Maeda, H.,Hiramatsu, Y., Okada, S., and Sayato, Y. (1991). Fundam. Appl.Toxicol. 16, 763–772. The subchronic oral toxicity ofglyoxal via drinking water and the effect on in vivo proteinsynthesis in tissues following a single treatment with thissubstance were assessed in Sprague–Dawley male rats. Animalsreceived drinking water containing glyoxal levels of 2000, 4000,and 6000 mg/liter ad libitum for 30, 60, and 90 days in PhaseI. In Phase II, the high-dose and control-1 groups fed the dietad libitum, and a diet-limited control-2 group given the sameamount of diet as consumed by the high-dose group were maintainedfor 90 and 180 days. The study designs included observationsof clinical signs, body weights, major organ weights, grossand histopathological examinations, serum clinical chemistry,and biochemical examinations such as glyoxalase activity andglutathione content in selected tissues. Body weight gain andorgan weights significantly decreased with dosage. Althoughconsumption of food and water was also depressed in the exposedgroup, the reduction of body weight gain was greater in thehigh-dose group than in the diet-limited control 2 group. Histopathologicalexaminations revealed only a slight papillary change in thekidneys from the high-dose group at both 90 and 180 days terminationsin Phase II. The induction of both glyoxalase I and II was observedin liver and erythrocytes at 30-day termination of the exposedgroups. Serum enzyme and protein levels were significantly reducedby the mid- and/or high-dose exposures. With a single oral high-dosetreatment of glyoxal, a great decline in the incorporation ofL-[³H]leucine was shown particularly in the liver, and thisprobably led in part to a reduction in the serum protein levelsin rats following subchronic exposure to glyoxal. These dataindicated an overall low degree of systemic toxicity to ratsexposed subchronically to glyoxal via drinking water.     

Inhibitory Activity of Camptothecin Derivatives Against Acetylcholinesterase in Dogs and Their Binding Activity to Acetylcholine Receptors in Rats

Abstract— A camptothecin derivative, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), shows a potent antitumour activity in experimental tumour models and in clinical trials. However, CPT-11 induced early diarrhoea and vomiting at high dose levels in clinical studies and showed an acetylcholine-like action on the guinea-pig ileum and trachea. In the present study, we investigated the activities of camptothecin derivatives in inhibiting acetylcholinesterase (AChE) and in binding to muscarinic acetylcholine receptors (AChR). CPT-11 inhibited AChE and binding of the specific ligand to AChR with respective 50% inhibition concentrations of 0·2 and 5 μm . These inhibitions were induced by camptothecin derivatives having an amino group at the C-10 position (or the C-4 position of hexacyclic derivatives), but were not or were only slightly induced by the others. Early defecation and vomiting in dogs were observed after intravenous injection of DU-6596 and DU-6888, two hexacyclic derivatives having the aminomethyl group at the C-4 position, and of CPT-11. DU-6174, however, which has a hydroxy group at this position, induced no early defecation and little vomiting. Plasma concentrations of CPT-11, DU-6596 and DU-6888 after intravenous treatment at doses causing such early adverse effects were maintained for 1 h or longer at levels sufficient to inhibit AChE. These results suggest that the inhibition of AChE by camptothecin derivatives with an amino group at the C-10 position (or the C-4 position) relates to the early defecation or diarrhoea and vomiting.     

Prognosis and clinical features of intractable epilepsy: A prospective study

Abstract  Of the epileptic patients who were treated for ≥ 5 years until the end of 1990 and had more than four seizures in 1990, 63 patients had been treated without interruption until the end of 1995. We analyzed their clinical courses from 1990 to 1995 prospectively. More than half the subjects were diagnosed with temporal lobe epilepsy. Twenty cases had presumed etiology, and 32 had neuropsychiatric complications. Of the subjects whose seizures were not controlled with conventional antiepileptic drugs (AED), 11 cases demonstrated significant improvement when new AED; that is, lamotrigine, vigabatrin, clobazam, topiramate, tiagabine or CGP33101 were added. However, 10 patients did not respond to new AED. Presumed etiology, neuropsychiatric complications, multiple epileptic foci in EEG and abnormalities on head CT or MRI were characteristics of the patients whose seizures were resistant to new AED.     

Arrhythmias in Centenarians

Background: Many studies have shown an increase in the prevalence of arrhythmias with advancing age. However, little is known about arrhythmias in centenarians. Method and Results: Thirty-two Japanese centenarians aged 100–106 years (14 males, 18 females) were studied. All of them had 12-lead EGGs, and 22 also had 24-hour ambulatory monitoring. As controls, 89 healthy Japanese elderly from the same geographic area underwent 12-lead ECG. Their mean age was 75 ± 6 years with a range of 63–93 years, and there were 28 males and 61 females. Twenty-three of them also had Holter ECGs. On the 12-lead ECG, the heart rate was slightly, but significantly, higher in the centenarians (76.8 ± 12.7 beats/min) than that in the elderly subjects (74.9 ± 5.9 beats/min, P < 0.005). PQ and QT_C were significantly longer in the centenarians (174 ± 29 and 439 ± 33 msec, respectively) compared with the elderly subjects (158 ± 23 and 417 ± 31 msec, P < 0.005 and P < 0.001, respectively). Supraventricular premature beats (SVPBs) were observed in 31% of the centenarians and in 4% of the elderly subjects (P < 0.001). First- and second-degree AV block was recorded in 25% of the centenarians and 1% of the elderly subjects (P < 0.001). Right bundle branch block was found in 19% of the centenarians and 7% of the elderly subjects (P < 0.05). There were no differences in the frequency of ventricular premature beats (VPBs) or QRS voltage. On the Holter ECG, there were no significant differences in average heart rate, maximum heart rate, minimum heart rate, or the longest RR interval. A subgroup of centenarians had frequent SVPBs. However, none of them had > 1,000 VPBs/day as opposed to four elderly subjects (P < 0.01). Atrial fibrillation was not observed in any records of the centenarians despite the presence of frequent SVPBs. Conclusion: These data suggest that conduction disturbances of the AV nodal—His-Purkinje system and frequent SVPBs are common in centenarians, whereas very frequent VPBs and atrial fibrillation seem less common.     

骨髓前列腺特异抗原诊断前列腺癌骨转移

目的：探讨检测骨髓前列腺特异抗原（PSA）筛选前列腺癌骨转移的价值。方法：选择20例前列腺癌患者,按同位素骨扫描结果,分为无骨转移的阴性组（8例）和有骨转移的阳性组（12例）,20例良性前列腺增生症患者为对照组,分别检测骨髓及血清中PSA值,并测定骨髓PSA与血清PSA的比值。 结果：有骨转移组和无骨转移组骨髓PSA值差异有显著性（P<0.05）,以骨髓/血清PSA比值为0.70作为筛选骨转移阳性的参考值时,预测前列腺癌骨转移的敏感性为78%,特异性为86%,准确率为73%。 结论：骨髓PSA与前列腺癌骨转移有关,可作为前列腺癌骨转移的肿瘤标记物,骨髓/血清PSA比值0.70可作为骨转移的筛检指标之一。     

CASE REPORT: Haemorrhagic colitis associated with royal jelly intake

The case report of a 53-year-old woman with abdominal pain and bloody diarrhoea is described. Prior to the onset of symptoms the patient had taken royal jelly for 25 days. Colonoscopy revealed that the mucosa was haemorrhagic and oedematous throughout the 20 cm long sigmoid colon. Histopathologically, mucosal haemorrhage, oedema, and infiltration of inflammatory cells were observed. Transmission electron microscopic examination revealed platelet aggregation in 30% of capillaries in the mucosal lesions. The drug-induced lymphocyte stimulation test was slightly positive for royal jelly (847 c.p.m., SI= 147%) compared with the control (576 c.p.m.). The patient's signs and symptoms disappeared within a few days after the initiation of conservative therapy, and the colonic lesions disappeared after 2 weeks of this therapy. This is the first reported case of haemorrhagic colitis associated with royal jelly intake.