Intramuscular ziprasidone treatment of acute psychotic agitation in elderly patients with schizophrenia.

OBJECTIVE: Intramuscular (i.m.) ziprasidone treatment has been shown to be effective and well tolerated in reducing the symptoms of acute psychosis in adults. Few data are available as to safety in the elderly. The growing utilization of health services by elderly psychiatric patients warrants an evaluation in this population. METHOD: Consecutive elderly patients (60 years of and older) admitted to a psychogeriatric ward in a large, university-affiliated tertiary psychiatric center were treated by i.m. ziprasidone for acute psychotic agitation. Patients received three days of flexible-dose i.m. ziprasidone. After an initial dose of 10-20 mg, a subsequent dose of 10-20 mg could be given after 12 hours if needed (maximum daily dose: 40 mg). RESULTS: All treatment emergent side effects and adverse events along with the investigators' assessments of severity were systematically recorded as the primary outcome. The Brief Psychiatric Rating Scale (BPRS) and the Behavioral Activity Rating Scale (BARS) were the secondary outcomes. Twenty-one patients, six male and 15 female, mean age 71.4 +/- 1.3 years (range: 60-81 years) were enrolled. All had completed the three days i.m. ziprasidone treatment. There was one adverse event in a patient with untreated benign prostatic hypertrophy who developed urinary retention. Two side effects of mild severity that resolved spontaneously were observed: blurred vision and sedation. The BPRS decreased by 26.8 points after three days of treatment (p = 0.001). The BARS score, reflecting agitation, decreased significantly after each injection, reaching maximal decrease of 2.14 points at completion of study (p = 0.001). CONCLUSION: Intramuscular ziprasidone in this series of elderly patients suggests acceptable safety and efficacy in the management of acute psychotic agitation among elderly patients with schizophrenia.     

Primary gastrointestinal lymphomas in Turkey: a retrospective analysis of clinical features and results of treatment.

Thirty-three patients with primary gastrointestinal lymphoma (GIL) followed at Ankara University Medical School have been evaluated. The most frequent locations of the disease are the small intestine (48.4%) and the stomach (39.3%). The intermediate and high grade lymphomas constitute 84.8% of the cases. The mean age of the patients with small intestinal lymphoma is 28.7 years and 47.1 years for those with gastric lymphoma. The patients treated with surgery and chemotherapy (S+CT) have a longer survival than those treated with chemotherapy (CT) alone. In conclusion: 1) Small intestinal lymphoma occurs more frequently than gastric lymphoma in our study. 2) The median age of the Turkish patients with primary GIL is approximately 10 years less than those in the Western countries. 3) The therapeutic results of S+CT are superior to those of CT in the early stages of the disease.     

Inter-NICU variation in rates and management of thrombocytopenia among very low birth-weight infants.

OBJECTIVES: To investigate variation among neonatal intensive care units (NICUs) in prevalence and management of thrombocytopenia in infants <1500 g. STUDY DESIGN: In total 1283 infants &<1500 g admitted to six NICUs over 21 months were prospectively analyzed. Illness severity was measured by the Score for Neonatal Acute Physiology (SNAP). Platelet counts in the first 12 hours after birth and on day 3 of life were abstracted from the infants' medical records. Thrombocytopenia was determined from the lowest platelet count in each of these time periods. RESULTS: There was variability in rates of thrombocytopenia among NICUs, even after controlling for risk factors (e.g., SNAP, small for gestational (SGA) age and maternal hypertension). One site had a high prevalence of thrombocytopenia, but the lowest percentage of infants with thrombocytopenia who received platelet transfusions. After controlling for SNAP, GA, SGA, Apgar score and incidence of thrombocytopenia, the odds of receiving platelets at this site, relative to the site with the highest transfusion rate, was 0.10 (95% CI 0.02 to 0.43). CONCLUSIONS: This multicenter study finds a 10-fold variation among NICU in the administration of platelets to their thrombocytopenic infants that cannot be explained by presence of thrombocytopenia or illness severity.     

'Hemorrhagic' and microvascular phenomena within the arterial wall.

OBJECTIVE: To study microvasculature and hemorrhage within the arterial wall. DESIGN: Human autopsy specimens of the arch of the aorta, the carotid, brachiocephalic, subclavian and coronary arteries perfused with liquid casting material and maintained at physiological pressure until the material had set. MAIN RESULTS: Evidence of dense microvasculature and other phenomena which have the morphological appearance of 'hemorrhage' within the arterial wall, coupled with calcified matter and other impressions made on the cast by atherosclerotic plaques. CONCLUSIONS: The findings lend support to suggestions in the literature that neovascularization may play a role in the pathogenesis of coronary atherosclerosis and its sequelae, that hemorrhage into the intima may be due to rupture of capillaries which are derived from the coronary lumen, and that an increase in microvasculature occurs in the immediate vicinity of localized atherosclerotic lesions.     

Congenital toxoplasmosis—prenatal aspects of Toxoplasma gondii infection

Toxoplasma gondii (T. gondii) is the cause of toxoplasmosis. Primary infection in an immunocompetent person is usually asymptomatic. Serological surveys demonstrate that world-wide exposure to T. gondii is high (30% in US and 50–80% in Europe). Vertical transmission from a recently infected pregnant woman to her fetus may lead to congenital toxoplasmosis. The risk of such transmission increases as primary maternal infection occurs later in pregnancy. However, consequences for the fetus are more severe with transmission closer to conception. The timing of maternal primary infection is, therefore, critically linked to the clinical manifestations of the infection. Fetal infection may result in natural abortion. Often, no apparent symptoms are observed at birth and complications develop only later in life. The laboratory methods of assessing fetal risk of T. gondii infection are serology and direct tests.Screening programs for women at childbearing age or of the newborn, as well as education of the public regarding infection prevention, proved to be cost-effective and reduce the rate of infection.The impact of antiparasytic therapy on vertical transmission from mother to fetus is still controversial. However, specific therapy is recommended to be initiated as soon as infection is diagnosed.     

Effect of the glucocorticoid receptor antagonist RU 38486 on muscle protein breakdown in sepsis

The role of glucocorticoids in muscle catabolism during sepsis was tested with the glucocorticoid receptor antagonist RU 38486. Sepsis was induced in male Sprague-Dawley rats (40 to 60 gm) by cecal ligation and puncture (CLP). Other animals underwent sham operation. Two hours before CLP or sham operation, rats received RU 38486 (5 mg/kg) or a corresponding volume of vehicle by gavage. Sixteen hours after CLP or sham operation, protein synthesis rate was determined by measuring incorporation of 14C-phenylalanine into protein in incubated extensor digitorum longus muscles. Total and myofibrillar protein breakdown rates were determined by measuring net release of tyrosine and 3-methylhistidine, respectively. The protein synthesis rate was approximately 30% lower in rats with sepsis than in sham operated rats and was not affected by treatment with RU 38486. The total protein breakdown rate was increased by approximately 70% and myofibrillar protein degradation was increased more than fivefold in muscle from rats with sepsis. Treatment with RU 38486 resulted in a 28% reduction of total and a 44% reduction of myofibrillar protein breakdown in rats with sepsis but did not affect proteolysis in muscle from sham-operated animals. The results support a role of glucocorticoids in accelerated muscle proteolysis during sepsis. It is not clear whether glucocorticoids are the only required mediator or they interact with other substances to induce muscle protein breakdown during sepsis.     

De novo amplification within a "silent" human cholinesterase gene in a family subjected to prolonged exposure to organophosphorous insecticides

A 100-fold DNA amplification in the CHE gene, coding for serum butyrylcholinesterase (BtChoEase), was found in a farmer expressing the "silent" CHE phenotype. Individuals homozygous for this gene display a defective serum BtChoEase and are particularly vulnerable to poisoning by agricultural organophosphorous insecticides, to which all members of this family had long been exposed. DNA blot hybridization with regional BtChoEase cDNA probes suggested that the amplification was most intense in regions encoding central sequences within BtChoEase cDNA, whereas distal sequences were amplified to a much lower extent. This is in agreement with the "onion skin" model, based on amplification of genes in cultured cells and primary tumors. The amplification was absent in the grandparents but present at the same extent in one of their sons and in a grandson, with similar DNA blot hybridization patterns. In situ hybridization experiments localized the amplified sequences to the long arm of chromosome 3, close to the site where we previously mapped the CHE gene. Altogether, these observations suggest that the initial amplification event occurred early in embryogenesis, spermatogenesis, or oogenesis, where the CHE gene is intensely active and where cholinergic functioning was indicated to be physiologically necessary. Our findings demonstrate a de novo amplification in apparently healthy individuals within an autosomal gene producing a target protein to an inhibitor. Its occurrence in two generations from a family under prolonged exposure to parathion indicates that organophosphorous poisons may be implicated in previously unforeseen long-term ecological effects.     

Multicontrast MRI of remyelination in the central nervous system

Although magnetic resonance imaging (MRI) represents the most sensitive tool for the detection of white matter abnormalities in patients with multiple sclerosis (MS), the heterogeneity of MS placques severely hampers the elucidation of specific pathophysiological processes. In order to identify putative MRI markers for de- and remyelination, we employed the cuprizone mouse model which leads to a selective and reversible demyelination of the corpus callosum with little or no axonal damage. Apart from histopathology, animals were studied with high-resolution three-dimensional MRI in vivo using multiple contrasts. While individual MRI findings significantly correlated with electron microscopy, the differentiation of regions with normal, demyelinated or remyelinated white matter by one contrast alone was less specific than by histology or electron microscopy. However, an accurate MRI prediction of the in vivo myelin status was achieved by a discriminant function analysis using a combination of T1, T2 and magnetization transfer contrast. With a correct assignment of 95% of all animals examined, the procedure will allow for the survey of new therapeutic approaches aiming at improved remyelination.     

Exploring the potential association among sleep disturbances,cognitive impairments,and immune activation in 22q11.2 deletion syndrome

22q11.2 deletion syndrome (22q11.DS) is a neurogenetic disorder caused by a microdeletion in chromosome 22. Its phenotype includes high rates of psychiatric disorders, immune system abnormalities, and cognitive impairments. We assessed the quality of sleep in 22q11.2DS and its potential link to inflammatory markers and cognitive deficits. Thirty‐three 22q11.2DS individuals and 24 healthy controls were studied. Sleep parameters were assessed by the Pittsburgh sleep quality index (PSQI) questionnaire and correlated with serum cytokine levels and cognitive functioning, measured using the Penn computerized neurocognitive battery (CNB). The 22q11.2DS individuals had significantly worse sleep quality scores than the controls, unrelated to the psychiatric or physical comorbidities common to 22q11.2DS. Interleukin 6 levels were correlated with the overall score of the PSQI questionnaire for nonpsychotic 22q11.2DS participants only. Several domains of the CNB were associated with poorer sleep quality, suggesting that cognitive impairments in 22q11.2DS may be at least partially explained by poor sleep quality. Our findings confirm sleep impairments in individuals with 22q11.2DS, which might negatively affect their cognitive functioning, and corroborate a potential role of immunological pathways in the 22q11.2DS neuro‐phenotype.