Clinical effects of high oral dose of donepezil for patients with Alzheimer's disease in Japan

Background:  Donepezil 10 mg/day gained approval in Japan in August 2007 for the treatment of cognitive dysfunction in advanced Alzheimer's disease.
Methods:  We evaluated the efficacy and adverse effects of donepezil when the dose was increased to 10 mg/day in 61 Japanese patients with Alzheimer's disease. Cognitive function was evaluated using the Revised Hasegawa Dementia Scale and mini-mental state examination at the day before starting, and at 4, 8 and 24 weeks after starting donepezil 10 mg/day. The relationship with apolipoprotein E4 was also investigated.
Results:  The Revised Hasegawa Dementia Scale and mini-mental state examination scores were not statistically significantly different at any time after starting donepezil 10 mg/day. It can be anticipated that donepezil 10 mg/day will especially inhibit deterioration of cognitive function in advanced Alzheimer's disease. The incidence of adverse events was 11.5%, lower than the rate of 40% or higher recorded during previous clinical trials.
Conclusions:  The progression of cognitive dysfunction could be inhibited by increasing the dose of donepezil to 10 mg/day. It was suggested that longer-term treatment with 5 mg/day might lead to fewer adverse events when the dose is increased to 10 mg/day.     

Haplotype and genotype effects of the F7 gene on circulating factor VII,coagulation activation markers and incident coronary heart disease in UK men

Background: Evidence for the associations of single nucleotide polymorphisms (SNPs) in the F7 gene and factor (F)VII levels and with risk of coronary heart disease (CHD) is inconsistent. We examined whether F7 tagging SNPs (tSNPs) and haplotypes were associated with FVII levels, coagulation activation markers (CAMs) and CHD risk in two cohorts of UK men. Methods: Genotypes for eight SNPs and baseline levels of FVIIc, FVIIag and CAMs (including FVIIa) were determined in 2773 healthy men from the Second Northwick Park Heart Study (NPHS‐II). A second cohort, Whitehall II study (WH‐II, n = 4055), was used for replication analysis of FVIIc levels and CHD risk. Results: In NPHS‐II the minor alleles of three SNPs (rs555212, rs762635 and rs510317; haplotype H2) were associated with higher levels of FVIIag, FVIIc and FVIIa, whereas the minor allele for two SNPs (I/D323 and rs6046; haplotype H5) was associated with lower levels. Adjusted for classic risk factors, H2 carriers had a CHD hazard ratio of 1.34 [95% confidence interval (CI): 1.12–1.59; independent of FVIIc], whereas H5 carriers had a CHD risk of 1.29 (95% CI: 1.01–1.56; not independent of FVIIc) and significantly lower CAMs. Effects of haplotypes on FVIIc levels were replicated in WH‐II, as was the association of H5 with higher CHD risk [pooled‐estimate odds ratio (OR) 1.16 (1.00–1.36), P = 0.05], but surprisingly, H2 exhibited a reduced risk for CHD. Conclusion: tSNPs in the F7 gene strongly influence FVII levels. The haplotype associated with low FVIIc level, with particularly reduced functional activity, was consistently associated with increased risk for CHD, whereas the haplotype associated with high FVIIc level was not.     

Subclinical rhythmic electrographic discharge of adults (SREDA) in a case with spinocerebellar degeneration improved clinically by thyrotropin-releasing hormone

Herein, we report on a patient with spinocerebellar degeneration who exhibited subclinical rhythmic electrographic discharge of adults (SREDA). Thyrotropin-releasing hormone (TRH) improved the clinical symptoms and SREDA was observed only when administration of thyrotropin-releasing hormone was discontinued and the symptoms worsened. Furthermore, after resuming administration of taltirelin hydrate, a TRH analog, the improvement in motor function was accompanied by a decrease in delirium. It is plausible that taltirelin hydrate improved the distorted cerebral blood flow, which has been reported previously as the mechanism underlying SREDA, as a consequence of the functional improvement in neurotransmitter systems.     

Incidence of Haemophilus influenzae in the throats of healthy infants with different feeding methods

BACKGROUND: Haemophilus influenzae is the major cause of otitis media and lower respiratory tract infection in childhood. In the presence of human milk, which contains numerous host defense factors, Haemophilus influenzae may be inhibited in attaching to and colonizing pharyngeal cells. We investigated the incidence of H. influenzae in the throats of 162 healthy infants with different feeding methods: 70 breast-fed, 49 mixed-fed and 43 formula-fed infants. METHODS AND RESULTS: Haemophilus influenzae was identified using standard microbiological procedures and the API NH system. The incidence of H. influenzae in breast-fed infants, mixed-fed infants and formula-fed infants was 0, 0 and 7.0% respectively. CONCLUSION: The results suggest that the colonization of H. influenzae in the throat was inhibited by the presence of breast milk.     

Bacterial changes in neonatal intensive care unit

Organisms routinely cultured from throat swabs and infectious agents of sepsis and/or meningitis were reviewed. During the last 12 years, Klebsiella pneumoniae and Escherichia coli have been replaced by Staphylococcus aureus and Pseudomonas aeruginosa as the predominant isolates from throat swabs after admission. These change in the etiologic pattern of infectious agents of sepsis and/or meningitis, i.e., K. pneumoniae, E. coli, S. aureus, P. aeruginosa and staphylococcus epidermidis, were in agreement with the organisms isolated from the throat swabs after admission. The S. aureus isolated from throat swabs after admission showed a decrease in the bacterial activity of cloxacillin, cephazolin and cefotaxime since 1978.     

Prostate-specific antigen changes as a result of chlormadinone acetate administration to patients with benign prostatic hyperplasia: A retrospective multi-institutional study

BACKGROUND: Antiandrogens used to treat benign prostatic hyperplasia (BPH) may affect the diagnosis of prostate cancer by decreasing serum prostate-specific antigen (PSA) values. We conducted a retrospective survey of BPH patients treated with chlormadinone acetate (CMA) and analysed the effect of CMA on their PSA values. METHODS: A chart-based, retrospective, multi-institutional survey of clinically diagnosed patients with BPH who had been treated with CMA (Prostal; 50 mg/day) was conducted. The patients were divided into three groups according to their baseline PSA values: <4 ng/mL, Group I; >or=4 ng/mL and <10 ng/mL, Group II; and >or=10 ng/mL, Group III. The changes in the PSA values from baseline after 16, 26, and 52 weeks of CMA therapy were predicted using a nonlinear regression model analysis. RESULTS: Data from 192 of the 303 enrolled patients were analysed. The predicted percent changes from baseline among all patients after 16, 26, and 52 weeks of treatment were -49.6%, -49.8%, and -49.9%, respectively. The corresponding values were -42.4%, -43.7% and -43.8% in Group I; -57.4%, -58.4% and -58.5% in Group II; and -50.6%, -50.6% and -50.6% in Group III, respectively. CONCLUSION: The PSA values reached a nadir, approximately -50% of the baseline, after 16 weeks of CMA administration and remained at the same level thereafter. When CMA is used to treat BPH patients, the possibility of abnormal increases in PSA associated with prostate cancer must be considered; if prostate cancer is suspected, prompt testing, including a biopsy, should be performed.     

Clear cell adenocarcinoma of the endometrium is a biologically distinct entity from endometrioid adenocarcinoma

Clear cell adenocarcinoma (CCA) of the endometrium has a poor prognosis, although the biologic features of this rare tumor are not clear. In this study, we analyzed the expression of biologic markers relating to carcinogenesis, tumor growth, and progression. Thirteen cases of CCA were compared with cases of endometrioid adenocarcinoma (EMA) of the endometrium. Immunohistochemical staining for p53; Ki-67; cyclins A, D1, and E; E-cadherin; progesterone receptor (PR)-A and PR-B; P-glycoprotein; MLH1; and MSH2 was performed. Labeling indices of p53, Ki-67, and cyclins A, D1, and E in CCA were 46.4 +/- 24.3%, 52.1 +/- 20.5%, 37.9 +/- 21.4%, 12.3 +/- 27.9%, and 8.2 +/- 22.9%, respectively. E-cadherin was expressed in only 1 case (7.7%) of CCA, as compared to 39 cases (61.0%) of EMA. No CCAs were positive for PR-A and PR-B. P-glycoprotein was detected in seven cases (53.8%). Loss of either MLH1 or MSH2 expression occurred in eight cases (61.5%). High-level expression of p53, cyclin A, and P-glycoprotein, and low-level or no expression of cyclin E, E-cadherin, PR-A, and PR-B was observed in CCA compared with EMA. The mechanism of cell-cycle regulation in endometrial CCA is different from that in EMA and may influence its malignant potential. Endometrial CCA is a distinct entity from EMA.     

Lingual cyst in infancy: Importance of palpation for diagnosis

Two infants, 5 and 12 weeks of age, with lingual cysts were presented. Histological findings were compatible with a salivary retention cyst in one and a thyroglossal duct cyst in the other. Both infants were admitted to our hospital because of severe stridor that had developed from one to two weeks of age. Their lingual cysts were easily recognizable by simple palpation and were confirmed by non-invasive imaging techniques, such as ultrasound sonography, computed tomography and magnetic resonance imaging. Lingual cyst in infancy may be large enough to cause stridor and dyspnea, and occasionally result in sudden infant death, although once diagnosis is made a radical operation can be easily performed. Therefore, it is important that palpation in the oral cavity should be performed with all infants with persistent stridor as a part of a physical examination.     

Predictive Factors in Recurrent Spontaneous Aborters—A Multicenter Study

PROBLEM : Compare data from several centers relating to success rates in recurrent spontaneous miscarriage and assess the significance of indicators of subsequent pregnancy loss. METHOD : Data from 777 couples with unexplained recurrent spontaneous abortion from independent studies at seven centers were analyzed using logistic regression analysis. The following covariates were considered: age of patient, number of previous spontaneous abortions, length of previous abortions history, sub-fertility index (defined as the product of the number of spontaneous abortions and the abortion history), whether a patient was a primary or secondary aborter, and whether a patient had received leukocyte immunotherapy. RESULTS : There was a highly significant difference between the seven centers in success rates in the subsequent pregnancy and a highly significant association between success rate and each of the following covariates: the number of previous abortions, the length of the previous abortion history and the sub-fertility index. In particular, for each increase of 10 units in the value of the sub-fertility index, up to a value of 30, the odds in favor of a successful pregnancy decreased by a factor of 0.6, i.e., 40%. There was, however, little evidence of an association between the success rate in the subsequent pregnancy and age, parity, or immunization with cells from the husband. CONCLUSIONS : The sub-fertility index may be a useful measure of likelihood of success in a subsequent pregnancy.     

PSYCHOLOGICAL DISTRESS AMONG INFORMAL SUPPORTERS OF FRAIL OLDER PEOPLE AT HOME AND IN INSTITUTIONS

Objective. Investigate presence of psychiatric morbidity in informal carers using 30-item General Health Questionnaire (GHQ) and examine which factors best predict psychiatric morbidity. Design. Two-year longitudinal, panel survey of informal supporters of frail elderly subjects, using semi-structured interview schedules. Subjects were those defined as frail after screening stratified random sample of people aged 65 or over. Setting. Informal supporters of frail elderly subjects residing in private households or residential or nursing homes in four UK districts. Respondents. 623 informal supporters of subjects living at home, 129 regular visitors of those in long-term care. Measure. 30-item GHQ (cross-sectional analysis). Results. Stepwise multiple regression indicated main predictors of high GHQ scores in key supporters were: subjects had at least three problems of behaviour (b=1.56, 95% CI 1.25–1.94); supporters had to alter working hours (b=1.70, 95% CI 1.15–2.51); supporters were female (b=1.26, 95% CI 1.06–1.50). The following variables predicted low GHQ scores: supporters able to leave subject all day (b=0.71, 95% CI 0.64–0.80); subjects never wandered (b=0.78, 95% CI 0.62–0.99); supporters were ‘other relatives’ or friends of subject (b=0.74, 95% CI 0.59–0.91). For visitors, spouses were most likely to have high GHQ scores (b=2.46, 95% CI 1.32–4.57). Conclusions. Results suggest the need for greater collaboration between formal and informal care. Little work has been carried out to ascertain which interventions are most effective in alleviating carer stress: a series of randomized controlled trials to determine long-term effectiveness of various interventions for different groups of carers is required. © 1997 John Wiley & Sons, Ltd.