Adverse effects of anticholinergic activity on cognitive functions in Alzheimer's disease

Background:  Elderly patients with Alzheimer's disease (AD) take more medicines, other than those for anti-dementia agents, than healthy people and are sensitive to anticholinergic medications. There are only a few reports, however, on the relationship between cognitive function and anticholinergic activity in AD patients, which is caused by taking prescribed medication.
Methods:  We measured serum anticholinergic activity (SAA) in 76 AD patients referred to a Psychogeriatric Unit and separated them into SAA positive group ( n = 26, SAA (+) group) and SAA negative group ( n = 50, SAA (−) group). The difference in demographic data and cognitive functions were compared between the two groups.
Results and Conclusions:  The total scores of the Mini-Mental State Examination (MMSE), the score of MMSE domain of registration and recall were significantly lower ( P < 0.05) and the Functional Assessment Staging (FAST) score, the number of different kinds of prescribed psychotropic medications (the number of prescribed psychotropic medications) were significantly higher ( P < 0.05) in the SAA (+) group than in the SAA (−). These results suggest that a higher number of psychotropic medications prescribed leads to a tendency for SAA to be positive and that anticholinergic activity accelerates Alzheimer's pathology and decreases cognitive function, especially memory in AD patients. We should more prudently prescribe psychotropic medications to AD patients, because the prescribed psychotropic medications are one of the important causes of decline in cognitive function of AD patients by way of anticholinergic activity.     

Electrophysiological Features of Atrial Tachycardia Arising from the Atrioventricular Annulus

MATSUOKA, K., et al. : Electrophysiological Features of Atrial Tachycardia Arising from the Atrioven-tricular Annulus. Atrial tachycardia (AT) arises from various sites in the atrium and the mechanisms are nonuniform. McGuire et al. reported that the cells around the atrioventricular annuli resembled nodal cells in their cellular electrophysiology. The purpose of this study was to delineate the electrophysiological features of AT arising from the atrioventricular (AV) annulus (AVAT). The study included five patients with six AVATs that were abolished by the radiofrequency energy delivery. The location of the AV annuli was defined by using the AV ratio of the local electrograms and the amplitude of the ventricular electrograms, in addition to the anatomic findings under fluoroscopic guidance. The tachycardia cycle lengths were  403 ± 117 ms  . An AV ratio of the electrograms at the successful ablation sites was  0.4 ± 0.4  at the tricuspid annulus and  1.5 ± 0.3  at the mitral annulus. Small doses (  mean 3.2 ± 1.8 mg  ) of adenosine triphosphate could terminate all the tachycardia episodes for five of the ATs without the development of AV nodal conduction block. The successful ablation sites were located at the right mid-septum in 1 AT, right posteroseptum in 2 ATs, right posterolateral region in 1 AT, and left anteroseptum in 2 ATs. These findings suggest that the cells with nodal-type action potentials around both annuli might play an important role in the genesis of AVAT.     

Electrophysiologic Evaluation of Asymptomatic Patients with the Wolff-Parkinson-White Pattern

In the past 4 years, 34 asymptomatic patients with the Wolff-Parkinson-White (WPW) pattern underwent electrophysiologic study. The effective refractory period (ERP) of antegrade conduction over the accessory pathway was 288 +/- 29 msec. In three asymptomatic patients (9%), the antegrade ERP of the accessory pathway was shorter than 250 msec. The antegrade ERP of the accessory pathway became shorter than 250 msec in an additional 12 of 22 (55%) patients after isoproterenol administration. Nineteen (56%) of the asymptomatic patients showed the absence of retrograde conduction over the accessory pathway even after isoproterenol administration. The rate of induction of orthodromic reciprocating tachycardia in the asymptomatic WPW patients was 15% (5/34), which was significantly lower than that in the symptomatic patients. These data suggest that in the asymptomatic patients, the absence of retrograde conduction over the accessory pathway is the reason they remained asymptomatic, free of reciprocating tachycardia. However, even in the asymptomatic patients, some had the accessory pathway in which antegrade ERP was shorter than 250 msec. They may result in rapid ventricular conduction over the accessory pathway when atrial fibrillation develops.     

Sufficient prophylactic efficacy with minor adverse effects by intravesical instillation of low-dose bacillus Calmette-Guérin for superficial bladder cancer recurrence

BACKGROUND: Intravesical instillation of bacillus Calmette-Guérin (BCG) is the most efficient strategy for prophylaxis of superficial bladder cancer recurrence. Adverse effects of BCG are major obstacles, but the reduction of BCG dose could minimize these effects. The efficacy and adverse effects of half-dose (40 mg) BCG, Tokyo 172 strain, were prospectively evaluated. METHODS: A total of 93 patients with superficial bladder cancer (pTa or pT1) were sequentially assigned to receive either 40 or 80 mg of BCG after transurethral resection. BCG was administered weekly for 6 weeks postoperatively. Eighty patients observed longer than 12 months after BCG therapy (41, 40 mg group; 39, 80 mg group) were analyzed. RESULTS: BCG therapy course was completed in 71 patients. Tumor recurrence was recognized in 11 of 40 patients in the 40 mg group and in 5 of 31 patients in the 80 mg group. There was no significant difference in tumor recurrence rate between the two groups (P = 0.547). BCG therapy was withdrawn in 1 patient in the 40 mg group and in 8 patients in the 80 mg-group because of BCG-related adverse effects. The morbidity of BCG-related toxicity was significantly higher in the 80 mg group. CONCLUSION: Half-dose of BCG Tokyo 172 strain had a similar efficacy and its toxicity was significantly lower compared to the standard dose. Thus, half-dose of this strain might be suitable, at least for initial BCG therapy, for the prophylaxis of bladder cancer recurrence. Further study would be necessary to clarify the efficacy of low-dose instillation in high-risk patients.     

Intraoperative transesophageal echocardiography for inferior vena caval tumor thrombus in renal cell carcinoma

BACKGROUND: We investigated the advantages of intraoperative transesophageal echocardiography (TEE) during inferior vena caval tumor thrombectomy in renal cell carcinoma (RCC). METHODS: Five patients with RCC that extended into the inferior vena cava (IVC) underwent radical nephrectomy. To remove the tumor thrombus in the IVC, an inflated Fogarty balloon catheter was used to pull the thrombus below the level of the hepatic veins with real-time TEE monitoring. RESULTS: In all cases, TEE monitoring during surgery provided an accurate and excellent view of the IVC thrombus. TEE was particularly helpful for the thrombectomy to minimize hepatic mobilization by using occlusion balloon catheter in two patients whose thrombus extended to the intrahepatic IVC. CONCLUSIONS: Intraoperative real-time TEE monitoring is a safe, minimally invasive technique that can provide accurate information regarding the presence and extent of IVC involvement, guidance for placement of a vena caval clamp, confirmation of complete removal of the IVC thrombus and intervention using catheters to assist in thrombectomy.     

Experimental Study About Removal of the Implanted Tined Polyurethane Ventricular Lead by Radiofrequency Waves Through the Lead

Polyurethane pacemaker leads are widely used nowadays. However, only a few studies have been done to investigate the fixation mechanism of polyurethane leads. To elucidate how pacemaker leads are fixed at the early phase after implantation, polyurethane-insulated tined ventricular leads were implanted in seven mongrel dogs. One to 4 months later, tips of the leads were anchored among the trabeculae and the distal part of the leads were encapsulated by whitish fibrous tissue. It was found that not organized thrombi, but cell reaction with various stages of inflammatory cells was responsible for forming the fibrous tissue. We attempted to remove the lead by delivering radiofrequency wave through the lead. However, no lead could be removed.     

FK506 promotes liver regeneration by suppressing natural killer cell activity

We examined the mechanism of promotion of liver regeneration by tacrolimus hydrate (FK506), a potent immunosuppressant, after partial hepatectomy. The administration of FK506 significantly increased the bromodeoxyuridine (BrdU) labelling index at 36 and 48 h after 70% hepatectomy compared with the placebo group. Using the same model, we examined the effect of FK506 on the expression of hepatocyte growth factor (HGF) and transforming growth factor-β1 (TGF-β1) and found no changes in HGF and TGF-β1 mRNA expression in the liver or in the HGF protein concentration in plasma. We found that pretreatment with FK506 markedly reduced the activity and number of liver-resident natural killer (NK) cells at the time of partial hepatectomy. Our observations suggest that the promotion of liver regeneration by FK506 may be attributable to a reduction in the number of liver-resident NK cells and to inhibition of their activity.     

Sucrose permeability as a meas of detecting diseases of the upper digestive tract

The healthy gastric epithelium will not allow easy permeation of a disaccharide-sized molecule such as sucrose. However, during gastric damage, intact sucrose can pass the gastric epithelium and ultimately appear in the urine. We examined the relationship between total urinary sucrose excretion and various diseases. We used 149 patients (105 had upper gastrointestinal disease, 12 had gastric cancer and 32 were normal). Subjects were given a solution containing 100g sucrose in 450 c.c. water. All urine was collected for 7.5 h. The urinary sucrose concentration was determined by anion exchange high-performance liquid chromatography. Total urinary sucrose excretion was significantly higher in patients with gastric ulcer and those with gastric cancer than in endoscopically normal controls. In the 34 patients with gastric ulcer, the total sucrose excretion was closely correlated with ulcer size. Ulcer location did not affect urinary sucrose excretion. A strong correlation was also observed between sucrose excretion and lesion size in the 12 patients with gastric cancer. The sucrose permeability test may be a relatively sensitive method to detect gastric disease.     

Familial occurrence of congenital bile duct cysts

Congenital bile duct cysts are now a well-documented anomaly of the biliary tree, and have become more common in Japan. Familial occurrence of congenital bile duct cysts, however, is extremely rare, with only six reported cases in the literature. We report a familial pattern of congenital bile duct cysts in a mother and her daughter. A 33-year-old female was admitted for evaluation of right upper quadrant abdominal pain and fever 6 days after an uneventful delivery of her second child. A com- puted tomography (CT) and ultrasound scan (US) revealed an obstructed biliary tract. Percutaneous transhepatic biliary drainage was then performed, and a cholangiogram revealed a Scholtz type B choledochocele without an anomalous connection of the pancreaticobiliary ducts. Endoscopic US demonstrated that the choledochocele was associated with a stone in the cyst. A pylorus-preserving pancreatoduodenal resection was performed, and a histological study revealed that the choledochocele was lined by biliary mucosa without evidence of malignancy. The newborn infant had an abdominal tumour. An US and CT revealed a congenital bile duct cyst. An operation was performed and the intraoperative cholangiogram showed an Alonso-Lej type I congenital bile duct cyst with an anomalous connection of the pancreaticobiliary ducts. Whether congenital bile duct cysts are hereditary remains to be elucidated.     

p75NGFR Immunostaining for the Detection of Perineural Invasion by Cutaneous Squamous Cell Carcinoma

BACKGROUND: Perineural invasion (PNI) in cutaneous squamous cell carcinoma (CSCC) may portend a poor prognosis for patients. p75NGFR (nerve growth factor receptor) is part of a membrane receptor complex that binds nerve growth factor. Its use for detecting PNI in CSCC in comparison with S-100 immunohistochemical staining has not been explored. OBJECTIVE : To determine whether detection of PNI may be improved by staining with p75NGFR compared with hematoxylin and eosin (H&E) and S-100. METHODS: Thirty-four cases of CSCC were retrospectively evaluated for the presence of PNI using standard H&E, as well as S-100 and p75NGFR immunohistochemical stains. Staining intensity was correlated to the presence or absence of PNI and tumor differentiation. RESULTS: The results showed a positive correlation between staining intensity and the presence of PNI detected by p75NGFR (p=.04). Using p75NGFR allowed for the detection of seven cases of PNI not detected by H&E alone. Five of these cases were detected by S-100, with two cases seen by p75NGFR only. Six cases of PNI were detected using S-100 not seen on H&E, with one case also not seen using p75NGFR. CONCLUSION: p75NGFR immunostaining increased detection of PNI compared with H&E. p75NGFR could serve as an alternative to S-100 in the detection of PNI or as part of an immunostaining panel for PNI detection.