Effect of histamine and substance P on the rabbit and human iris sphincter muscle

Background and methods: In an attempt to clarify the functional action of histamine and substance P on atropine-resistant miosis, we isolated rabbit and human iris sphincter muscles and investigated their mechanical properties using the isometric tension recording method. Results: Substance P dose-dependently contracted the rabbit iris sphincter, but had no effect on the human iris sphincter. In the rabbit iris sphincter, histamine reduced the amplitude of twitch contraction evoked by field stimulation but had no effect on carbachol-induced contraction. Thioperamide, but not mepyramine or cimetidine, partially antagonized the histamine-induced reduction in the amplitude of twitch contractions. In the human iris sphincter, on the other hand, histamine dose-dependently provoked contraction and the amplitude of histamine-induced contraction was affected neither by atropine nor by indomethacin. Conclusions: These results provide evidence that histamine has strong contractile effect on the human iris sphincter muscle; the rabbit iris sphincter muscle, however, apparently lacks functional histamine receptors. In rabbits, exogenously applied histamine only activates H₃ receptors located on the cholinergic nerve terminal, hence the excitatory neuro-effector transmission is suppressed. Thus, histamine may have an important roles in atropine-resistant miosis in humans, but not in rabbits.     

Haematological improvement by long-term administration of recombinant human granulocyte-colony stimulating factor and recombinant human erythropoietin in a patient with severe aplastic anaemia

A 6-year-old girl with post-hepatitic severe aplastic anaemia was referred to our hospital. Haematological examination showed a haemoglobin level of 5.2 g/dl, platelet count of 8,000/l, and white blood cell count of 130/l with 17% neutrophils. She was treated with recombinant human granulocytecolony stimulating factor (15 g/kg/day i.v.) and cyclosporin A (6 mg/kg/day p.o.). The absolute neutrophil count gradually increased, but Hb and platelets were not improved. The intravenous administration of recombinant human erythropoietin (100 U/kg three times a week) was started, and the reticulocyte count reached 20000/l on day 12. The platelets increased to 81000/l after 16 months of combined administration of recombinant human granulocyte-colony stimulating factor, recombinant human erythropoietin and cyclosporin A. After 20 months of combined administration, the haematological results were: Hb, 13.1 g/dl; platelets 80000/l: WBC, 9500/l with 40% neutrophils. After recombinant human granulocyte-colony stimulating factor treatment, the myeloid elements of the bone marrow and the number of granulocyte-macrophage colony forming units increased. Bone marrow erythropoiesis and erythroid colonies also increased after recombinant human erythropoietin administration. The clinical course suggested a beneficial effect of haemopoietic growth factors and cyclosporin A in post-hepatitic aplastic anaemia.     

Handlebar hernia with intra-abdominal extraluminal air presenting as a novel form of traumatic abdominal wall hernia: Report of a case

An 18-year-old male was admitted to our Emergency Department with a traumatic abdominal wall hernia (TAWH) of the left lower quadrant (LLQ) after suffering hypogastric blunt injury and urogenital lacerations in a motorcycle accident. Upright chest X-ray showed a small amount of right infradiaphragmatic free air, and a computed tomographic (CT) scan demonstrated an abdominal wall hernia. At surgery, no impairment was found in the digestive tract, and an abdominal herniorrhaphy was performed. It is suggested that the free air had passed through a connection between the scrotal laceration and the contralateral abdominal defect via the subcutaneous space and was palpated as emphysema. This is a new type of TAWH, which suggests that blunt abdominal trauma may result in negative pressure in the subcutaneous and peritoneal cavity, and this could reflect the pathophysiology of TAWH.     

Unilateral middle cerebral artery stenosis in an adult with Down's syndrome--case report

A 29-year-old male with Down's syndrome presented with severe headache and vomiting. Computed tomography demonstrated subarachnoid hemorrhage. Left carotid angiography showed severe stenosis of the middle cerebral artery 2 cm distal to its origin, as well as abnormal hyper-vascularization near the stenosis site similar to that seen in moyamoya disease. Right carotid angiography showed no abnormalities. However, slight stenosis of the distal part of the bilateral vertebral arteries was noted. There was no aneurysm. We judged that the subarachnoid hemorrhage had been caused by rupture of the moyamoya-like vessel. Some patients with Down's syndrome have anatomical vascular abnormality and vascular fragility. The cerebral vascular abnormality found in this case may be part of the systemic vascular abnormalities associated with Down's syndrome. The vascular changes in some adult patients with Down's syndrome may be a sign of premature aging, and long-term studies with periodic vascular examination of patients with Down's syndrome need to be performed.     

Use of YAG laser combined with mucosal suturing for the treatment of polypoid vocal cord]

To improve low-pitched voices in cases with polypoid vocal cords, YAG laser irradiation combined with a mucosal suturing technique was attempted in 9 female cases with severe polypoid changes in their vocal cords. A YAG laser beam (5 to 10 W) was used to irradiate the upper surface of the polypoid vocal cord. The polypoid content of the cord was gradually coagulated, and the free edge of the cord appeared to slide up toward the burned area. The polypoid content was then removed and squeezed through an open wound made in the burned area using a conventional method. Bleeding was successfully controlled using the laser. After the excessive mucosal margin was trimmed and the contour of the vocal cord was adjusted, the wound was closed by 7-0 monofilament absorbable suture. Suturing was relatively easy because the mucosal edge was also coagulated. Postoperative evaluations of voice quality revealed an improvement in the GRBAS scale of voice quality as well as an elevation in voice pitch and an upwards shift in the voice range in all cases.     

Dysadherin overexpression in pancreatic ductal adenocarcinoma reflects tumor aggressiveness: relationship to e-cadherin expression.

PURPOSE: The E-cadherin-mediated cell adhesion system is frequently inactivated by multiple mechanisms and is involved in tumor progression in many types of cancer. Recently, we reported the cloning and characterization of dysadherin and showed that it downregulated E-cadherin and promoted metastasis. The aim of this study was to investigate the clinical significance of dysadherin expression and the relationship between dysadherin expression and E-cadherin expression in pancreatic ductal adenocarcinoma. PATIENTS AND METHODS: We examined dysadherin and E-cadherin expression in 125 surgically resected pancreatic ductal adenocarcinoma patients using immunohistochemistry. RESULTS: Dysadherin was expressed at the cell membrane of cancer cells, but not in nontumor duct and acinar cells. Its expression was stronger in infiltrative and poorly differentiated nests compared with well-differentiated nests. Although the correlation between the expression of dysadherin and E-cadherin was not significant, a group of patients showed reduced E-cadherin expression with dysadherin overexpression. Increased dysadherin expression was significantly correlated with distant metastasis (P =.047), high tumor grade (P =.006), positive tumor margins (P =.024), and infiltrative type of growth pattern (P =.014). A survival advantage was observed in patients with 0% to 20% dysadherin-positive cells compared with patients with 51% to 100% dysadherin-positive cells, independent of tumor-node-metastasis classification, and World Health Organization tumor grade (P =.019). A combination of increased dysadherin expression and reduced E-cadherin expression (< 90%) further worsened the prognosis. CONCLUSION: In pancreatic ductal adenocarcinoma, dysadherin expression seems to reflect tumor aggressiveness and to be a positive marker of poor prognosis when considered both alone and in combination with downregulation of E-cadherin.     

Radiation tolerance of the cochlear nerve at the γ-knife in rabbits

Since the first treatment of acoustic neurinoma using the γ-knife by Leksell, a series of cases have been reported with good control rates. However, the most frequent complication is delayed hearing loss which occurs in more than 50% of patients. The purpose of this study was to define a safe dose by analyzing the radiosurgical dose-response relationship and histological effects on the normal cochlear nerve in rabbit. The rabbits had computed tomography (CT)-guided stereotactic radiosurgery on their cochlear nerves in the internal auditory canal with a 4 mm collimator focusing of a γ-unit. Maximum doses of 10, 20, 30, 40, 60, 80, 100, 200 and 500 Gy were administered. After the radiosurgery, auditory brain stem responses (ABR) and the behavior of the rabbits were evaluated periodically. At the conclusion, histological investigations were performed. No physiological or histological findings were observed from doses of 30 Gy or below during the 12 month period after the radiosurgery. A dose of 100 Gy caused a severe ABR threshold elevation, vestibular dysfunction and facial palsy. Necrosis and demyelination of nerves were observed pathologically. In this study, we determined that the safe dose to the normal cochlear nerve during radiosurgery was under 40 Gy in rabbits, and complications seemed to vary due to individual differences in radiation tolerance.     

Inhibitory Effect of Macrolides on Interleukin-8 Secretion From Cultured Human Nasal Epithelial Cells

The mechanism of macrolide therapy in chronic sinusitis patients is unclear. The authors studied the effect of macrolides on interleukin (IL)-8 secretion from cultured human nasal epithelial cells. Epithelial cells harvested from the nasal polyps of patients with chronic sinusitis were primary-cultured, and secreted IL-8 in culture media was measured by enzyme immunoassay. The cells secreted considerable amounts of IL-8 constitutively and in response to lipopolysaccharide. The secretion was significantly inhibited by 10^?5 M of erythromycin, clarithromycin, roxithromycin, and josamycin. 10^?6 M erythromycin still showed the inhibitory effect, whereas the same concentration of josamycin did not. These results indicate that macrolide antibiotics may act as an immunomodulator to reduce IL-8 in inflammatory sites and, at least partially, account for the clinically discrepant effects between 14- and 16-membered ring macrolides in long-term low-dose therapy for chronic sinusitis.