Influence of the FDA Talk Paper upon the use of atypical antipsychotics for psychotic symptoms in older patients with dementia in Japan

Background: Atypical antipsychotic medications have often been used in the treatment of behavioral and psychological symptoms of dementia (BPSD). Recently, the US Food and Drug Administration (FDA) issued new safety information concerning atypical antipsychotic drugs, indicating that their use may increase the risk of cardiovascular adverse events among elderly adults with BPSD. Based on this information, the Japanese Ministry of Health, Labor and Welfare issued a similar warning against the use of atypical antipsychotic drugs licensed in Japan. We then sought to determine whether or not the use of typical antipsychotics should be recommended to replace atypical antipsychotics. In this paper, we discuss the influence of these warnings on the withholding of use of risperidone exemplified in seven case histories. Methods: Seven inpatients who exhibited BPSD received risperidone monotherapy in our hospital. In response to the FDA notice, the atypical antipsychotics used to treat these patients were replaced with typical antipsychotic agents. Results: During the period of risperidone administration, all patients exhibited clinical improvement compared with their baseline results and showed no adverse events. Two of our seven patients developed psychotic exacerbation and exhibited extrapyramidal symptoms coinciding with the replacement of risperidone with conventional antipsychotics. Conclusion: To the best of our knowledge, this is the first clinical report on the influence of the FDA alert on the use of atypical antipsychotics for psychotic symptoms in older patients with dementia in Japan. In two of our seven BPSD cases, there was no benefit from taking conventional antipsychotics. Our results lead to the conclusion that the use of typical antipsychotics should not be recommended to replace atypical antipsychotics. Although close attention should be paid to the FDA alert, clinicians must take into consideration the balance of benefits and risks when evaluating the appropriate use of antipsychotics in older patients with dementia.     

Motor activity rhythm in dementia with delirium

Abstract Using an actigraph, the activity patterns in 13 demented patients with delirium were examined. We analyzed the data of the eight patients, wearing the actigraphs for more than 10 days. They were classified into four types:type A, nocturnal delirium type; type B, wandering type; type C, hypobulia type; and type D, lying down type. The day to day activity variation was most prominent in type A and seemingly the least in type B. The dominant period of activity rhythm was nearly 24 h in all cases. Additional 12-h period was observed in type C. Actigraphs might become useful in making therapeutic decisions regarding demented patients with delirium.     

CORRELATION BETWEEN FUNCTION OF THE PITUITARY-THYROID AXIS AND METABOLISM OF CATECHOLAMINES BY THE FETUS AT DELIVERY

The relationship between the pituitary-thyroid axis and the metabolism of catecholamines has been studied in 33 maternal, arterial and venous cord blood specimens obtained at the time of normal vaginal delivery, following uncomplicated pregnancies. Ten fetal cord blood samples were collected at the time of elective caesarean section. Levels of noradrenaline and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in all these samples, using the high performance liquid chromatography (HPLC)-electrochemical detection method, and TSH was measured by radioimmunoassay. In cord arterial blood samples at vaginal delivery the levels of plasma noradrenaline and serum TSH were significantly increased, but those of DOPAC, which reflects central dopaminergic activity, were unchanged when compared to samples obtained at elective caesarean section. Within the same samples there was a significant correlation between the levels of plasma noradrenaline and those of serum TSH. Noradrenaline is believed to have a stimulatory and dopamine an inhibitory influence on TSH secretion. The fetal thyroid gland seems to respond adequately to the stimulus of TSH at term. The present study suggests that catecholamines, especially noradrenaline, may regulate secretion of TSH from the pituitary gland in the fetus at delivery and that elevation of TSH probably induces a subsequent rapid increase in thyroid hormones in the neonate.     

Plasmocytosis circumorificialis successfully treated with topical fusidic acid ointment

Plasmocytosis circumorificialis is a benign chronic inflammatory disease, which causes erythema, erosions, ulcers, nodules and related changes in and around the openings of the human body, and is histopathologically characterized by dense infiltration of the dermis by plasma cells. We recently encountered a 49-year-old man in whom this disease affected the lower lip. On initial examination in our department, a well-demarcated region of erosion (10 mm × 5 mm), accompanied in part by formation of a crust, was noted on the left side of his lower lip. Histopathologically, the mucosal epithelium exhibited erosions, and dense plasma cell infiltration, without signs of atypia, was noted in the upper through middle layers of the lamina propria. On the basis of these findings, plasmocytosis circumorificialis was diagnosed. Because the patient had experienced repeated cycles of remission and relapse, despite topical treatment with various drugs (e.g. topical antibiotics and steroids), prior to referral to our department, we administered topical 2% fusidate sodium or Fucidin (Leo Pharmaceutical, Ballerup, Denmark) ointment. His eruption healed approximately 3 weeks after the start of this treatment. We report this case and discuss the findings reported in Japan on the development of plasmocytosis circumorificialis of the lips.     

Biallelic DNA rearrangements and deletions within the BCL-6 gene in B-cell non-Hodgkin's lymphoma

Summary. Chromosomal translocations involving band 3q27 are recently described common specific cytogenetic abnormalities in B-cell neoplasms, and the BCL-6 gene, identified on 3q27, was shown to be disrupted and over-expressed in lymphoma cells having these chromosomal translocations. In the present study we found rearrangements within the BCL-6 gene in seven out of 3 5 cases with B-cell non-Hodgkin's lymphoma (NHL). Further analysis revealed that three of these patients with BCL-6 abnormality had multiple rearranged bands hybridized with probes from a single restriction fragment within the major translocation cluster (MTC). suggesting that independent DNA rearrangements would occur on both alleles. Additionally, Southern blot analysis indicated that three patients carry deletions encompassing the area containing the first exon of the BCL-6 gene. Our results suggest that biallelic DNA rearrangements and deletions would occasionally occur in NHL patients with BCL-6 abnormality.     

Antiperoxidative Activity of Neolignans from Magnolia obovata

Honokiol and magnolol, neolignans in Magnolia obovata, have been evaluated as antioxidants. Microsomal lipid peroxidation induced by Fe(III)-ADP/NADPH and mitochondrial lipid peroxidation induced by Fe(III)-ADP/NADH were inhibited by these compounds. These neolignans protected mitochondrial respiratory chain enzyme activity against NADPH-induced peroxidative stress and protected red cells against oxidative haemolysis. The anti-oxidative activity of honokiol was more potent than that of magnolol. Neolignans in M. obovata were shown to be effective in protecting biological systems and functions against oxidative stress.     

Usefulness and Limitations of Endoscopic Ultrasonography in Diagnosis of Adenomyomatosis of the Gallbladder

Abstract: Although endoscopic ultrasonography (EUS) is commonly used to examine lesions in the gallbladder, its ability to accurately diagnose adenomyomatosis (ADM) has not been evaluated. We compared the accuracy of EUS and various other imaging techniques in the diagnosis of ADM. Thirty-one patients undergoing cholecystectomy after elevated lesions were found in the gallbladder by various imaging techniques were studied retrospectively. Based on histopathologic examination, the sensitivity and specificity of EUS were evaluated in ADM. The sensitivity of abdominal ultrasonography, CT and ERCP in ADM were also evaluated. Of the 11 patients diagnosed with ADM by EUS, 9 cases were confirmed histologically (81.8%). Of the 11 patients with histologic diagnosis of ADM, 9 were accurately diagnosed preoperatively by EUS (81.8%). EUS proved more reliable for diagnosis of ADM than the other imaging techniques. Important diagnostic features include preservation of the three-layered structure of the gallbladder, wall-thickening exceeding 3 mm, and 2 or more Rokitansky-Aschoff sinuses occurring within a 1 cm area of the gallbladder.     

A female infant successfully treated by ganciclovir for congenital cytomegalovirus infection

An 11 month old female infant, diagnosed as having congenital cytomegalovirus (CMV) infection and suffering from pneumonia and intractable diarrhea, was treated with 9-(1,3-dihydroxy-2-propoxymethyl) guanine (DHPG), intravenously for 8 weeks. Watery diarrhea ceased and pneumonia associated with massive endotracheal aspirates was reduced. No leukopenia, thrombocytopenia or other side effects were observed during the therapy. The clinical findings suggest that DHPG might be an effective and safe agent for the treatment of both intestinal and lower respiratory CMV infection in young infants.     

Utility of Intraoperative Fetal Heart Rate Monitoring for Cerebral Arteriovenous Malformation Surgery during Pregnancy

We report two methods of intraoperative fetal heart rate (FHR) monitoring in cases of cerebral arteriovenous malformation surgery during pregnancy. In one case in her third trimester, cardiotocography was used. In another case in her second trimester, ultrasound sonography was used, with a transesophageal echo probe attached to her lower abdomen. Especially, the transesophageal echo probe was useful because of the advantages of being flexible and easy to attach to the mother''s lower abdomen comparing with the usual doppler ultrasound probe. In both cases, the surgery was successfully performed and FHR was monitored safely and stably. The use of intraoperative FHR monitoring provides information about the influence of induced maternal hypotension and unexpected bleeding on fetus during surgery. These monitoring techniques would be especially emphasized in cerebrovascular surgery for the safe management of both mother and fetus.