Development of stress-induced gastric lesions involves central adenosine A1-receptor stimulation

When rats were exposed to immobilization stress for 1-12 h, gastric lesions did not occur at 1-6 h but did at 12 h of immobilization. Exogenous adenosine increased stress-induced gastric lesions, and dipyridamole, a blocker of adenosine uptake, potentiated the action of adenosine. The selective adenosine A1-receptor stimulants N6-cyclohexyl adenosine (CHA) and N6-(L-phenylisopropyl) adenosine (L-PIA) produced gastric lesions even in non-stressed state and markedly potentiated in dose- and time-dependent manner in stressed state. The stimulatory effect of N6-(D-phenylisopropyl) adenosine (D-PIA) on ulceration was weaker than that of CHA or L-PIA. Furthermore, intracerebral ventricular (i.c.v.) injection of adenosine or adenosine analogues produced the most rapid and most potent exacerbation of stress-induced gastric lesions relative to those induced with subcutaneous (s.c.) injection. The stress lesions enhanced by CHA were not affected by phentolamine, yohimbine, prazosin, naloxone and cholecystokinin (CCK8) but were inhibited by caffeine, clonidine, morphine and beta-endorphin. The inhibitory effect of clonidine was not antagonized by yohimbine or prazosin. The inhibition by morphine was selectively antagonized by exogenous CCK8 as well as naloxone. These results suggest that endogenous adenosine is tonically active in stress lesion formation which is modulated by opiate systems. Clonidine as well as caffeine may function as a purinoceptor antagonist, and it seems unlikely that the inhibitory effect of clonidine on stress ulcer is due to activation of alpha-adrenoceptors.     

A case of advanced rectal cancer responding to oral UFT and Leucovorin-based preoperative chemoradiation therapy

We report a case of a 44-year-old male with advanced lower rectal cancer that showed a significant effect after preoperative chemoradiation therapy. Preoperative radiation and chemotherapy included whole pelvis irradiation (30 Gy in total), oral UFT (500 mg/day), and Leucovorin (75 mg/day) was administered daily for 4 weeks. Consequently, the patient underwent a total pelvic exenteration with lymph node dissection (D 3). Histopathological findings showed: invasion to peritoneum(Ai); stage IIIa with n(-); and histological grading, Grade 2. Preoperative chemoradiation therapy appears to be effective for locally advanced lower rectal cancer.     

Antipsychotics improve Delta9-tetrahydrocannabinol-induced impairment of the prepulse inhibition of the startle reflex in mice

Recently, cannabinoid receptor agonists have been reported to impair prepulse inhibition (PPI) of the startle reflex. In the current study, we examined the effect of Delta9-tetrahydrocannabinol (THC), the principal psychoactive component of cannabis, on the PPI, and found that THC (10 mg/kg, i.p.) impaired the PPI concomitant with a decrease in the startle response. Antipsychotics such as haloperidol (0.3 mg/kg, i.p.) and risperidone (0.1 mg/kg, i.p.), which are potent dopamine D2 receptor antagonists, and SR141716 (10 mg/kg, i.p.), a CB1 cannabinoid receptor antagonist, reversed these THC-induced PPI deficits. Moreover, THC (10 mg/kg) increased dopamine (DA) release in the nucleus accumbens but not medial prefrontal cortex over a 50-100-min period (time of PPI test) after treatment, and SR141716 (10 mg/kg) reversed this increase in DA release induced by THC. These results suggest that dopaminergic hyperfunction in the nucleus accumbens may be involved in THC-induced PPI deficits.     

Drug-induced hypersensitivity syndrome due to cyanamide associated with multiple reactivation of human herpesviruses

Drug-induced hypersensitivity syndrome (DIHS), characterized by serious adverse systemic reactions in addition to skin rash, has unknown pathogenesis. Its association with human herpesvirus (HHV), mainly HHV-6, has been reported recently. A 46-year-old Japanese man is described in whom a generalized eruption developed about 1 month after taking cyanamide, a drug for alcoholism. This was associated with the following manifestations: high fever, lymphadenopathy, facial edema, marked leukocytosis with eosinophilia and atypical lymphocytes, lymphocytopenia, liver and renal dysfunction, and low IgG level. He was treated with 8 mg betamethasone daily and his condition improved, but he needed low-dose corticosteroid for almost 1 year because of several episodes of recurrence. HHV-6, HHV-7, herpes simplex virus (HSV), and cytomegalovirus (CMV) specific IgG titers showed more than a four-fold rise sequentially. Significant numbers of copies of HHV-6 and HHV-7 DNA were detected in the peripheral white blood cells by real-time polymerase chain reaction (PCR). HHV-6 and CMV DNA were detected in the serum by nested PCR. A patch test for cyanamide was positive. The diagnosis of DIHS due to cyanamide, which has never been reported as a causal drug of DIHS, accompanied by reactivation of not only HHV-6, but also HHV-7, CMV, and HSV, was made. Disturbance of the immune system was suggested by the persistent low level of IgG, and consecutive viral reactivation may have participated in the prolonged course in this case.     

Clinical outcomes and adverse events following transforaminal interbody fusion for lumbar degenerative spondylolisthesis in elderly patients

Transforaminal lumbar interbody fusion (TLIF) procedure is widely used, but the surgical indications for TLIF in elderly patients remain controversial because of potential risks such as inferior bone quality and higher rate of postoperative complications. Clinical efficacy and operative risk of TLIF in elderly patients are unclear. This study investigated the clinical effect and safety of TLIF for lumbar degenerative spondylolisthesis with radiculopathy or neurogenic claudication in patients aged 70 years or older. The clinical records were retrospectively reviewed of 35 consecutive patients aged 70-86 years (mean 74.8 years) who underwent one or two-level TLIF. The preoperative diagnosis included degenerative spondylolisthesis with segmental instability. Clinical outcomes were assessed by the Japanese Orthopaedic Association score, visual analogue scale, Oswestry Disability Index. Radiological fusion rate was also investigated. Clinical and radiological results were compared with those of 43 younger patients. Clinical outcome measures were significantly improved after operation in the elderly patients, but improvement rates were significantly lower than those of younger patients. Fusion rate was similar in both groups. Overall postoperative complications were increased in aged patients, although the prevalence of complications directly related to surgical technique was not significantly increased. Postoperative complications not related to the surgical procedure were factors affecting poor results. TLIF is acceptable for achieving clinical recovery and lumbar fusion with high radiographic fusion success even in elderly patients, although clinical benefits were limited compared with those of younger patients. Postoperative morbidity was mainly related to general or non-operative site complications.     

Gastro-pancreaticostomy using a tube stent as a less invasive palliative treatment for malignant obstructive pancreatitis

Surgical palliation of malignant obstructive pancreatitis poses a considerable burden to patients, especially those with extensive disease. We herein present a novel technique for performing gastro-pancreaticostomy using a tube stent as a less invasive palliative treatment for malignant obstructive pancreatitis. The main pancreatic duct was punctured via the wall of the pyloric antrum. After the insertion of a guidewire, a double pigtail-type tube stent with side holes was inserted into the main pancreatic duct through the wall of the pyloric antrum. This technique was useful as a means of accomplishing less invasive palliative treatment, and has the potential to improve the quality of life for patients with malignant obstructive pancreatitis.