Prediction of psychosis onset in Alzheimer disease: The role of cognitive impairment, depressive symptoms, and further evidence for psychosis subtypes.

BACKGROUND: Psychotic symptoms in Alzheimer disease (AD+P) identify a heritable phenotype associated with more rapid cognitive decline. The authors have proposed that AD+P is itself a composite of a misidentification and a paranoid subtype with increased cognitive impairment restricted to the misidentification type. Most prior studies of the clinical correlates of AD+P have been limited, however, by the inclusion of prevalent cases. METHODS: Subjects with possible or probable AD or mild cognitive impairment (MCI) without psychosis at study entry were assessed at the time of initial presentation and then annually. Psychotic symptoms were assessed using the CERAD Behavioral Rating Scale. Survival analyses used Cox proportional hazard models with time-dependent covariates to examine the predictors of psychosis onset. RESULTS: A total of 288 subjects completed at least one follow-up examination. Mean duration of follow-up was 22.1 months. The incidence of psychosis was 0.19 per person-year. Cognitive impairment was associated with onset of psychosis, largely as a result of its association with onset of the misidentification, but not the paranoid, subtype. Including psychotropic medication use in the model revealed an association of antidepressant use with the onset of psychosis. This latter association appeared to arise from an underlying association between depression and the risk of psychosis onset rather than from antidepressant treatment. CONCLUSION: These findings are consistent with the hypothesis that the misidentification and the paranoid subtypes each define a more biologically homogeneous group than AD+P as a whole. Further exploration of the relationship between depressive symptoms and psychosis in patients with AD is warranted.     

Ultrasound Examination and Localization of the Sciatic Nerve: A Volunteer Study

Background: Few studies have examined the use of ultrasound for sciatic nerve localization. The authors evaluated the usefulness of low-frequency ultrasound in identifying the sciatic nerve at three locations in the lower extremity and in guiding needle advancement to target before nerve stimulation.

Methods: In this prospective observational study, 15 volunteers underwent sciatic nerve examination using a curved ultrasound probe in the range of 2-5 MHz and a Philips-ATL 5000 unit (ATL Ultrasound, Bothell, WA) in the gluteal, infragluteal, and proximal thigh regions. Thereafter, an insulated block needle was advanced inline with the ultrasound beam to reach the nerve target, which was further confirmed by electrical stimulation. The quality of sciatic nerve images, ease of needle to nerve contact, threshold stimulating current, and resultant motor response were recorded.

Results: The sciatic nerve was successfully identified in the transverse view as a solitary predominantly hyperechoic structure on ultrasound in all of the three regions examined. The target nerve was visualized easily in 87% and localized within two needle attempts in all patients. Nerve stimulation was successful in 100% after two attempts with a threshold current of 0.42 +/- 0.12 (mean +/- SD) eliciting foot plantarflexion or dorsiflexion.     

Penicillium piceum infection: diagnosis and successful treatment in chronic granulomatous disease.

Infections due to Penicillium species other than P.marneffei are rare. We identified a boy with X-linked chronic granulomatous disease (X-CGD) with a pulmonary nodule and adjacent rib osteomyelitis caused by Penicillium piceum. The only sign of infection was an elevated sedimentation rate. P. piceum was isolated by fine needle aspirate and from excised infected tissues. Surgical removal and one year of voriconazole treatment were very well tolerated and led to complete recovery. Microbiological, microscopic and molecular studies support the fungal diagnosis. P. piceum should be considered as a relevant pathogen in immunocompromised patients.     

Investigation of the phenylalanine hydroxylase gene and tardive dyskinesia.

Phenylketonuria (PKU), an inborn error of phenylalanine metabolism, has been shown to be a risk factor for tardive dyskinesia (TD). In male psychiatric patients there was a significant relationship between TD and measures of plasma phenylalanine following ingestion of a standardized phenylalanine dose that was indicative of higher brain availability of phenylalanine in patients with TD. In addition, a medical food formulation consisting of branched chain amino acids, which compete with phenylalanine for transport across the blood-brain barrier, has been demonstrated to be an efficacious treatment for TD. Cumulatively these findings suggested that TD was related to phenylalanine metabolism and thus that sequence variants in the gene for phenylalanine hydroxylase (PAH), the rate-limiting enzyme in the catabolism of phenylalanine, could be associated with TD susceptibility. Genetic screening of PAH in a group of 123 psychiatric patients revealed ten sequence polymorphisms and two mutations, but none appeared to be a significant risk factor for TD.     

Mode of Delivery and the Survival of Macrosomic Infants in the United States, 1995–1999

ABSTRACT: Background: Although increases in perinatal mortality risk associated with fetal macrosomia are well documented, the optimal route of delivery for fetuses with suspected macrosomia remains controversial. The objective of this investigation was to assess the risk of neonatal death among macrosomic infants delivered vaginally compared with those delivered by cesarean section. Methods: Data were derived from the U.S. 1995–1999 Linked Live Birth‐Infant Death Cohort files and term (37–44 wk), single live births to United States resident mothers selected. A proportional hazards model was used to analyze the risk of neonatal death associated with cesarean delivery among 3 categories of macrosomic infants (infants weighing 4,000–4,499 g; 4,500–4,999 g; and 5,000+ g). Results: After controlling for maternal characteristics and complications, the adjusted hazard ratio for neonatal death associated with cesarean delivery among the 3 categories of macrosomic infants was 1.40, 1.30, and 0.85. Conclusions: Although cesarean delivery may reduce the risk of death for the heaviest infants (5,000+ g), the relative benefit of this intervention for macrosomic infants weighing 4,000–4,999 g remains debatable. Thus, policies in support of prophylactic cesarean delivery for suspected fetal macrosomia may need to be reevaluated. (BIRTH 33:4 December 2006)     

Phase I trial of doxorubicin-containing low temperature sensitive liposomes in spontaneous canine tumors.

PURPOSE: To determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic characteristics of doxorubicin encapsulated in a low temperature sensitive liposome (LTSL) when given concurrently with local hyperthermia to canine solid tumors. EXPERIMENTAL DESIGN: Privately owned dogs with solid tumors (carcinomas or sarcomas) were treated. The tumors did not involve bone and were located at sites amenable to local hyperthermia. LTSL-doxorubicin was given (0.7-1.0 mg/kg i.v.) over 30 minutes during local tumor hyperthermia in a standard phase I dose escalation study. Three treatments, given 3 weeks apart, were scheduled. Toxicity was monitored for an additional month. Pharmacokinetics were evaluated during the first treatment cycle. RESULTS: Twenty-one patients were enrolled: 18 with sarcomas and 3 with carcinomas. Grade 4 neutropenia and acute death secondary to liver failure, possibly drug related, were the dose-limiting toxicities. The maximum tolerated dose was 0.93 mg/kg. Other toxicities, with the possible exception of renal damage, were consistent with those observed following free doxorubicin administration. Of the 20 dogs that received > or = 2 doses of LTSL-doxorubicin, 12 had stable disease, and 6 had a partial response to treatment. Pharmacokinetic variables were more similar to those of free doxorubicin than the marketed liposomal product. Tumor drug concentrations at a dose of 1.0 mg/kg averaged 9.12 +/- 6.17 ng/mg tissue. CONCLUSION: LTSL-doxorubicin offers a novel approach to improving drug delivery to solid tumors. It was well tolerated and resulted in favorable response profiles in these patients. Additional evaluation in human patients is warranted.