How to manage difficulties with colonoscope insertion

Unsuccessful insertion of a colonoscope is usually as a result of bending or looping of the scope. Looping of the colonoscope increases when too much air is insufflated or the scope is inserted with undue force, resulting in increased pain and risk of perforation. Successful insertion therefore requires careful handling of the scope to keep it straight, careful regulation of air levels, shortening of the colon length by gathering of the colon folds and rapid correction of any looping that should occur. This can be complicated in cases with an unusually long colon or with adhesion. The use of a colonoscope with variable rigidity or a small‐caliber colonoscope is recommended to increase the rate of successful insertion to relieve pain and to prevent accidents.     

Clinical evaluation of double stenting for duodenal and biliary obstructions caused by pancreatic head carcinoma using covered self‐expandable metallic stents

Five patients with non‐resectable pancreatic head carcinoma complicated by duodenal and biliary obstructions were successfully treated by double stenting with covered self‐expandable metallic stents (EMS). Diamond (Boston Scientific, Natick City, MA, USA) stents covered with a polyurethane membrane were used to treat biliary obstructions, whereas covered Ultraflex (Boston Scientific) stents for esophageal stenting were used to treat duodenal obstructions. That is, Diamond stents were initially placed in the biliary tract percutaneously in one patient and endoscopically in the remaining four patients. Subsequently, covered Ultraflex stents were placed in the duodenum. Double stenting with EMS was successfully performed in all five patients without inducing early technical complications. All patients were able to take a liquid diet orally at a mean 1.6 days after the double stenting procedure and were able to eat solid foods thereafter. Sludge‐induced biliary obstructions were detected in two patients 3 and 6 months after the placement of EMS. However, recurrent biliary obstruction was not noted in the remaining three patients. The EMS left in the duodenum were not obstructed during the observation period. The survival period of the patients ranged from 86 to 363 days (mean 172 days). There have not been any reports evaluating the usefulness of double stenting using covered EMS for duodenal and biliary obstructions. Because favorable results were obtained by double stenting in our patients, stenting for duodenal and biliary obstructions caused by non‐resectable pancreatic head carcinoma may become a useful treatment modality substituting for bypass surgery.     

Effects of asbestos on the cell cycle of PHA-stimulated human peripheral blood lymphocytes

It is well known that persons exposed to asbestos display systemic immunological alterations: impaired lymphocyte response to PHA, the appearance of autoantibodies and elevation of the serum immunoglobulin level. The authors intend in this report to determine whether asbestos fibres (crocidolite, chrysotile and amosite) have any effect on the cell cycle of human lymphocytes after PHA stimulation. Peripheral blood mononuclear (PBM) cells were incubated with 10 micrograms/ml PHA for 2 days. After PHA stimulation, a decrease in the percentage of cells in the G0 phase and an increase in that of cells in the G1A, G1B and S phases was observed. When asbestos fibres or titanium dioxide (TiO2) was added to the culture dish at the beginning of the experiment, the progression of the cell cycle was inhibited only by asbestos fibres, in which case the percentage of cells in the G0 phase was significantly increased, while those of cells in the G1B and S phases were significantly decreased. The experiment for determining the critical period for inhibition of blastogenic response revealed that no inhibition was demonstrable when crocidolite fibre was added at 24 hr after PHA stimulation. Although the mechanisms of asbestos-fibre-mediated suppression remain to be clarified, these results showed that asbestos fibres act at an early stage (G0 phase) of the cell cycle and suppress the PHA stimulation of PBM cells.     

Phosphorylation of neuronal nitric oxide synthase at Ser847 by CaM-KII in the hippocampus of rat brain after transient forebrain ischemia.

The authors previously demonstrated that Ca2+/calmodulin (CaM)-dependent protein kinase IIalpha (CaM-KIIalpha) can phosphorylate neuronal nitric oxide synthase (nNOS) at Ser847 and attenuate NOS activity in neuronal cells. In the present study, they established that forebrain ischemia causes an increase in the phosphorylation of nNOS at Ser847 in the hippocampus. This nNOS phosphorylation appeared to be catalyzed by CaM-KII: (1) it correlated with the autophosphorylation of CaM-KIIalpha; (2) it was blocked by the CaM-KII inhibitor, KN-93; and (3) nNOS and CaM-KIIalpha were found to coexist in the hippocampus. Examination of the spatial relation between nNOS and CaM-KIIalpha in the brain revealed coexistence in the hippocampus but not in the cortex during reperfusion, with a concomitant increase in autophosphorylation of CaM-KIIalpha. The phosphorylation of nNOS at Ser847 probably takes place in nonpyramidal hippocampal neurons, which increased after 30 minutes of reperfusion in the hippocampus, whereas no significant increase was detected in the cortex. An intraventricular injection of KN-93 significantly decreased the phosphorylation of nNOS in the hippocampus. These results point to CaM-KII as a protein kinase, which by its colocalization may attenuate the activity of nNOS through its Ser847 phosphorylation, and may thus contribute to promotion of tolerance to postischemic damage in hippocampal neurons.     

Preclinical biodistribution and safety study of reduced expression in immortalized cells/Dickkopf-3-encoding adenoviral vector for prostate cancer gene therapy

The biodistribution and safety of adenoviral vectors encoding the human REIC/Dkk-3 tumor suppressor gene (Ad-REIC) were examined in this preclinical study for in?situ prostate cancer gene therapy. First, the in vitro apoptotic effects of Ad-REIC in normal and cancer cells derived from the prostate and liver were examined. Significant apoptotic effects were observed at 100 MOI (multiplicity of infection) in prostate cancer cells (LNCaP, PC3) and hepatoma cells (HEP3B and HEPG2); however, no effects were seen in normal cells. To analyze the safety of intraprostatic Ad-REIC administration, the biodistribution and histology after Ad-REIC injection were evaluated in various organs of normal male C57BL6 mice. In a supporting study, vector dissemination following intravenous injection of Ad-REIC into tail veins was determined. To evaluate whether Ad-REIC was present in the collected tissue specimens, human REIC gene detection was performed using DNA-PCR. Intraprostatic treatment administered at lower doses showed vector biodistribution into the colon, urinary bladder and prostate. At higher doses, vector dissemination was observed in tissues more distant from the prostate, including the lung, thymus, heart, liver and adrenal gland. After intravenous injection of Ad-REIC, dissemination was observed in the liver and spleen. These results indicate that the biodistribution of Ad-REIC is determined by the dose and route of administration. Although acute inflammatory effects were observed in the prostate after intraprostatic administration at higher doses, no abnormal histological findings were noted in the other tissues, including those of intravenously treated mice. Regarding the safety of Ad-REIC administration, no deaths and no signs of toxicity or unusual behavior were observed in the mice in any treatment group. Based on these preclinical experiments, adenovirus-mediated in situ REIC/Dkk-3 gene therapy is considered to be safe for use as a treatment for human prostate cancer.     

Association between genetic polymorphisms of glutathione S-transferase P1 and N-acetyltransferase 2 and susceptibility to squamous-cell carcinoma of the esophagus

We examined the effect of genetic polymorphisms of phase-II enzymes, glutathione S-transferase P1 (GSTP1) and N-acetyltransferase2 (NAT2) on susceptibility to esophageal squamous-cell carcinoma. To determine the genotypes of the 2 polymorphisms, PCR-based analysis was performed on samples from 66 Japanese patients who had been histologically diagnosed as having esophageal squamous-cell carcinoma, and 164 healthy Japanese controls. The frequency of the AA genotype of GSTP1 was significantly higher in esophageal-cancer patients than in the controls according to logistic-regression analysis (92% of the patients and 68% of the controls; odds ratio (OR), 8.0; p = 0.0013). Also, more patients had the slow and intermediate acetylator genotypes of NAT2 than the controls (15% and 38% vs. 10% and 32% respectively; OR of the slow acetylator genotype, 4.2; p = 0.032; OR of the slow plus intermediate acetylator genotypes, 2.9; p = 0.015). Polymorphisms of GSTP1 and NAT2 may serve as genetic biomarkers for predicting susceptibility to esophageal squamous-cell carcinoma. Int. J. Cancer (Pred. Oncol.) 79:517–520, 1998.© 1998 Wiley-Liss, Inc.     

Effects of phototherapy in patients with delayed sleep phase syndrome

Phototherapy was given to six patients with delayed sleep phase syndrome (DSPS). Polysomnography (PSG) and core body temperature were examined before and after phototherapy. Phototherapy was administered to each patient for 5 days, and this treatment not only advanced the delayed sleep phase but also delayed the time of minimum body temperature in all patients. On the PSG, decreases in total sleep time and amounts of stages 2 and REM were observed after phototherapy. These results suggest that phototherapy is effective even in the short term in advancing delays in sleep phase and time of minimum body temperature in DSPS patients.     

Differential control of H-reflex amplitude in different weight-bearing conditions in young and elderly subjects

Objective

This study measured the modulation of conditioned (femoral nerve, paired-stimuli) and unconditioned soleus H-reflexes in young and elderly subjects when changing weight-bearing (WB) requirements and body position.

Methods

Conditioned and unconditioned H-reflexes were examined in 14 elderly subjects and 11 young subjects during six different WB conditions: (1) lying supine with no WB, (2) supine position inclined by 30° with 50% WB, (3) standing with 50%, (4) 75%, (5) 100% and (6) 125% WB.

Results

The elderly subjects had consistently higher background soleus EMG activity across the WB conditions compared to the young. Femoral nerve conditioning caused facilitation of the H-reflex that changed across WB conditions in the young subjects, but not in the elderly subjects. Finally, elderly subjects had less depression with paired-stimulation (PRD) across WB conditions, which was not observed in the young subjects.

Conclusions

The elderly may have more direct activation of motoneurons from descending pathways, coupled with less segmental spinal control of inhibitory interneurons, as evidenced by the increased background soleus activity, H/M-max ratios and the lack of modulatory control observed when conditioning the H-reflex.

Significance

There was an age-specific response from descending and segmental pathways during conditions that involved either different WB requirements or changes in body position.     

Infusion of neuropeptide Y into CA3 region of hippocampus produces antidepressant-like effect via Y1 receptor

A couple of papers indicate that patients with depression show a decrease in serum neuropeptide Y (NPY). To study the role of NPY in depression, we examined the effects of infusion of NPY into the hippocampus of learned helplessness (LH) rats (an animal model of depression). Infusion of NPY into the cerebral ventricle of LH rats showed antidepressant-like effects. Infusion of NPY into the CA3 region, but not the dentate gyrus (DG), produced antidepressant-like effects in the LH paradigm. Infusion of NPY did not affect locomotor activity or aversive learning ability. Coadministration of BIBO3304 (a Y1 receptor antagonist) with NPY to the CA3 region blocked the antidepressant-like effects of NPY, whereas coadministration of NPY with BIIE0246 (a Y2 receptor antagonist) to the CA3 region failed to block antidepressant-like effects. Furthermore, infusions of [Leu(31) Pro(34)]PYY (a Y1 and Y5 receptor agonist) alone and BIIE0246 alone into the CA3 region produced the antidepressant-like effects in LH rats. These results suggest that infusion of NPY into the CA3 region of hippocampus of LH rats produces antidepressant-like activity through Y1 receptors and attenuating effects through Y2 receptors.