Biomedical subjects

S Arndt

Publications and source records attributed to S Arndt.

At least 19 recordsLinked to original sources

PubMed2001

Hippocampus and amygdala in schizophrenia: assessment of the relationship of neuroanatomy to psychopathology.

The hippocampus and amygdala are believed to be involved in the pathology of schizophrenia. In this study, we attempted to replicate the reported bilateral volume reduction of the hippocampus and amygdala and to study the relationship of the volumes of these structures to the symptoms of schizophrenia. The hippocampus-amygdala complex (HAC) was manually traced on 3-mm coronal T(1)-weighted MRIs, resampled into 1-mm coronal slices, from 20 male patients with schizophrenia and 20 age-matched male controls. The complex was divided into three parts: anterior one-third representing the amygdala and middle and posterior thirds representing the anterior and posterior halves of the hippocampus. Positive and negative symptoms and severity of hallucinations and thought disorder (conceptual disorganization) were quantified using the Brief Psychiatric Rating Scale (BPRS). None of the above structures, controlled for brain volume, differed significantly in patients compared with normal controls. When the relationship between volumes and symptoms was examined, the left HAC was found to inversely correlate with thought disorder and negative symptoms. Specifically, significant inverse correlations were found between (i) left amygdala and thought disorder, (ii) left hippocampus and negative symptoms, and (iii) left anterior and posterior hippocampus volumes and positive and negative symptoms, respectively. Our findings further support the role of the HAC in the pathophysiology of schizophrenia and suggest unique associations between individual structures and specific symptoms of the illness.

Adult↗

PubMed2001

Aberrant respiratory sensitivity to CO(2) as a trait of familial panic disorder.

BACKGROUND: According to three earlier studies, well individuals with a family history of panic disorder experience more anxiety following a single breath of 35% CO(2) than do those without such a family history. This study sought to determine whether a heightened sensitivity to CO(2) manifests specifically in respiratory changes. METHODS: Subjects were 18--35 years old and had no history of panic attacks and no current DSM-IV diagnosis other than simple or social phobia. Those at high risk for panic disorder (HR-P) (n = 46) had a first-degree relative with treated panic disorder. Low-risk control subjects (LR-C) (n = 39) had no first-degree relative with panic disorder. Respiratory measurements were taken continuously while subjects breathed room air through an attached mask for 3 min and, subsequently, while they breathed a 5% CO(2)/air mixture for an additional 3 min. RESULTS: HR-P subjects did not differ from control subjects by group means of the principal measure of respiratory response, changes in minute volume (MV) during CO(2) inhalation. However, these values assumed clearly different distributions in the two groups. Fifteen (32.6%) of the HR-P subjects showed a paradoxical decrease in MV while breathing CO(2) and six (13%) displayed a particularly rapid increase in MV. Only one (2.6%) of the control subjects had a negative MV slope and none had a high value [chi(2)(1) = 12.3, p <.001, p =.021, Fisher exact test, respectively]. Though the subjects with high MV increases also described greater increases in anxiety after breathing CO(2), a regression analysis indicated that the MV increase was the more important in discriminating high-risk from control subjects. CONCLUSIONS: These results suggest that respiratory sensitivity to CO(2) inhalation is operative in the familial transmission of panic disorder.

Adult↗

PubMed2001

Quinone-annonaceous acetogenins: synthesis and complex I inhibition studies of a new class of natural product hybrids.

The natural product hybrids quinone-mucocin and quinone- squamocin D were synthesized. In these hybrids, the butenolide unit of the annonaceous acetogenins mucocin and squamocin D is exchanged for the quinone moiety of the natural complex I substrate ubiquinone. For both syntheses, a modular, highly convergent approach was applied. Quinone-mucocin was constructed out of a tetrahydropyran (THP) component 1, a tetrahydrofuran (THF) unit 2, and a quinone precursor 3. A stereoselective, organometallic coupling reaction was chosen for the addition of the THP unit to the rest of the molecule. In the final step, the oxidation to the free quinone was achieved by using cerium(IV) ammonium nitrate (CAN) as the oxidizing agent. Quinone-squamocin D was assembled in a similar manner, from the chiral side chain bromide 16, the central bis-THF core 17, and the quinone precursor 18. Inhibition of complex I (isolated from bovine heart mitochondria) by the quinone acetogenins and several smaller building blocks was examined; quinone mucocin and quinone-squamocin D act as strong inhibitors of complex I. These results and the data from the smaller substructures indicate that other substructures of the acetogenins besides the butenolide group, such as the polyether component and the lipophilic left-hand side chain, are necessary for the strong binding of the acetogenins to complex I.

Animals↗

PubMed2001

Population-based association analyses of the HOPA12bp polymorphism for schizophrenia and hypothyroidism.

HOPA is an Xq13 chromosome gene that codes for a RXR nuclear receptor co-activator. In a prior study of the genetic basis of schizophrenia, we showed that exonic polymorphisms in HOPA were associated with increased risk of schizophrenia and hypothyroidism in a large cohort of probands from New York. In an attempt to replicate these findings, we examined this relationship in a cohort of 173 schizophrenic probands (128 males and 45 females providing 218 alleles) from Iowa. Consistent with the prior findings, we found an increased rate of the HOPA12bP exonic polymorphism in schizophrenic probands compared with random newborn controls (9 of 218 alleles vs. 33 of 2,049 alleles, P < 0.02). Furthermore, retrospective review of the medical records showed that two of the nine probands possessing the HOPA12bp allele in whom thyroid function was assessed were hypothyroid compared with 6 of 164 probands possessing the normal HOPAwild allele(s) (P < 0.06). We conclude that the HOPA12bp polymorphism shows a nominally significant association with schizophrenia and a nominal trend for association with hypothyroidism in our study and that further studies are required to define the features of this syndrome and the molecular mechanisms of disease pathogenesis.

Amino Acid Sequence↗

PubMed2001

Clozapine use in patients with schizophrenia and the risk of diabetes, hyperlipidemia, and hypertension: a claims-based approach.

BACKGROUND: Numerous case reports have linked clozapine to the development of diabetes mellitus and hyperlipidemia in patients with schizophrenia. However, investigators have been unable to clearly demonstrate this association when compared with a control group receiving conventional antipsychotics. METHODS: Medical and pharmacy claims from the Iowa Medicaid program were used to compare incidence rates for diabetes, hyperlipidemia, and hypertension in 552 patients receiving clozapine and 2461 patients receiving conventional antipsychotics (eg, haloperidol, chlorpromazine hydrochloride), with the use of a retrospective cohort design. Logistic regression was used to compare incidence rates adjusting for age, sex, and duration of available follow-up. RESULTS: No significant differences in overall incidence rates for diabetes, hyperlipidemia, or hypertension were observed in patients receiving clozapine vs conventional antipsychotics. However, among younger patients (aged 20-34 years), clozapine administration was associated with a significantly increased relative risk of diabetes (2.5 [95% confidence interval, 1.2-5.4]) and hyperlipidemia (2.4 [95% confidence interval, 1.1-5.2]), but not hypertension (0.9 [95% confidence interval, 0.4-2.0]). CONCLUSIONS: These data suggest that clozapine may not be an independent cause of diabetes or hyperlipidemia, but instead acts as an effect modifier in susceptible populations by increasing weight or affecting insulin secretion and resistance. This finding requires confirmation in other settings and patient populations and with the other atypical antipsychotics (risperidone, olanzapine, and quetiapine fumarate). The potential long-term medical and economic implications of the early induction of diabetes and hyperlipidemia in patients with schizophrenia warrant further study.

Adult↗

PubMed2001

Anatomic and functional variability: the effects of filter size in group fMRI data analysis.

In the analysis of group fMRI scans, an optimal spatial filter should be large enough to accurately blend functionally homologous anatomic regions, yet small enough not to blur the functionally distinct regions. Hanning filters varying from 0.0 to 18.0 mm were evaluated in a group analysis of six healthy controls performing a simple finger-tapping paradigm. Test-retest reliability and Talairach-based measurements of the sensorimotor region were used to explore the optimal filter size. Two distinct regions of functional activation were noted in the sensorimotor cortex in group images (n = 6) at both time 1 and time 2. These regions merge once the filter size exceeds approximately 6.0 mm. The original hypothesis that these represented a motor and sensory activation was rejected on the basis of structural and functional variability. A discussion of the inherent difficulties in choosing an appropriate filter size is presented.

Adult↗

PubMed2001

Cytogenetic-clinicopathologic correlations in rhabdomyosarcoma: a report of five cases.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children younger than the age of 15 years. Histologically, RMS can be subdivided into two major subtypes; embryonal (E-RMS) and alveolar (A-RMS) rhabdomyosarcoma, with E-RMS being the more common. Although cytogenetic and molecular genetic findings have been reported extensively for RMS, clinicopathologic-genetic correlations among these tumors have not been reported in detail. In this report, we correlate the cytogenetic findings, including fluorescence in situ hybridization and spectral karyotyping, with pathologic findings and outcome for five RMS, including two A-RMS, one E-RMS, one botryoid RMS, and one anaplastic nonclassified RMS (N-RMS). The findings in A-RMS and E-RMS generally were consistent with previous reports; however, gain of chromosome 7 in A-RMS and gain of chromosome 9 segments in E-RMS observed here have seldom been reported in the literature. Importantly, the botryoid RMS had a cytogenetic profile similar to other types of E-RMS. An add(11)(q21) observed in this tumor, together with a t(8;11)(q12 approximately 13;q21) reported previously, indicates that 11q21 rearrangements may be nonrandomly related to botryoid RMS. In addition, the N-RMS expressed a cytogenetic pattern similar to that observed in E-RMS, thus providing genetic evidence that anaplastic N-RMS is a variant of E-RMS. Finally, these cases provide cogent evidence for the diagnostic and prognostic significance of the pathologic-genetic classification of RMS.

Adolescent↗

PubMed2001

Generating random series with known values of Kendall's tau.

Kendall's tau(a) offers statistical advantages to the more common Pearson's correlation and both are common in biomedical research. While generating random X-Y pairs from a known population value of Pearson's correlation is straightforward, the process for generating random sequences for a known value of Kendall's tau(a) is more complicated. Algorithms are presented that yield random numbers from a population with a known expected tau(a). They begin with a small set of values that have a known tau. These values are 'grown' to produce an arbitrarily large population that has the same expectation as the smaller set. Two examples are given. One example simulated samples from a population where tau(a) equaled 0.33 and confidence intervals are produced. A second example illustrates how the algorithm can be used to provide statistical power estimates for research studies using Kendall's tau(a).

Algorithms↗

PubMed2001

Unilateral vs. bilateral ultrasound in the monitoring of cerebral microemboli.

We used bilateral transcranial Doppler to monitor the number of microembolic events (ME) in the left and right middle cerebral arteries of 29 patients during cardiac surgery that required extracorporeal circulation. Based on a previously published study, we hypothesized that the commonly used method of doubling unilateral ME counts to obtain an estimated bihemispheric load would result in significant errors of estimation. In our sample, estimated bihemispheric counts were inaccurate by an average of 18% (range 0--80%). Despite this large range of error, calculation of Cronbach's alpha revealed that actual error due to unreliability (4%) was small relative to the large variation in ME counts across subjects in this patient series. These findings suggest that unilateral monitoring is sufficient when the goal is to characterize a given subject's ME load within the context of the other subjects in the sample. However, when precise ME counts are required, bilateral monitoring is essential.

Cardiac Surgical Procedures↗

PubMed2001

Effects of olanzapine on cerebellar functional connectivity in schizophrenia measured by fMRI during a simple motor task.

BACKGROUND: According to current theories, schizophrenia results from altered connectivity in brain circuits for fundamental cognitive operations. Consequently, the poorly understood mechanisms of neuroleptic treatment may be explainable by altered functional interactions within such networks. The 'cognitive dysmetria' model hypothesizes that one key structure in these circuits is the cerebellum. To investigate the effects of olanzapine on cerebellar functional connectivity (CFC), a seed-voxel correlation analysis (SVCA) was used in a functional magnetic resonance imaging (fMRI) study of a simple finger-tapping task. METHODS: fMRI scans were obtained from six schizophrenic patients under both drug-free and olanzapine-treated conditions and from a matched control group of six healthy subjects at corresponding time points. SVCAs were performed for anatomically and functionally standardized seed voxels in the anterior cerebellum. SVCA results were then processed by three different randomization analyses. RESULTS: The analyses revealed that olanzapine caused widespread changes of CFC, including prominent changes in prefrontal cortex and mediodorsal thalamus. Significant changes in motor structures were found after subtractions within both groups and may thus indicate repetition effects rather than drug effects. Olanzapine 'normalized' the patients' CFC patterns for the right, but not for the left cerebellum. CONCLUSION: Even for a simple motor task, olanzapine affects functional interactions between the cerebellum and many non-motor brain regions, including elements of the 'cognitive dysmetria' circuit. Altogether, our findings suggest that olanzapine has a stronger differential effect on neural activity in prefrontal cortex and thalamus than in motor structures.

Adult↗

PubMed2001

Caregiver report of hallucinations and paranoid delusions in elders aged 70 or older.

This study examined the demographic, medical, and psychiatric correlates of hallucinations and paranoid delusions reported by proxy informants for 822 elders aged 70 or older. This sample comprised people who were deemed unable to complete a direct interview in a large nationwide study of aging. Marital status, trouble with vision, and cognitive impairment were associated with report of both paranoid delusions and hallucinations. Depressive symptoms and stroke were associated with hallucinations only. These results suggest that inadequate external stimulation in the elderly leads to psychotic experiences.

Aged↗

PubMed2001

Bupropion SR vs. methylphenidate vs. placebo for attention deficit hyperactivity disorder in adults.

Despite the increasing recognition of attention-deficit hyperactivity disorder (ADHD) in adults, there are few controlled trials demonstrating the effectiveness of pharmacological treatments, particularly with nonstimulants. One controlled trial found bupropion SR more effective than placebo in the treatment of ADHD adults. We conducted a controlled study to contrast the effectiveness of bupropion SR and methylphenidate to placebo in ADHD adults. A randomized, double-blind, parallel design was used in this study. Following a 7-day placebo lead-in, 30 ADHD (DSM-IV) subjects (18-60 years old) were randomized to bupropion, methylphenidate, or placebo for 7 weeks. Methylphenidate was titrated over 1 week to a maximum dose of 0.9 mg/kg/d divided into 3 doses while bupropion was titrated over 2 weeks to a maximum dose of 200 mg A.M. and 100 mg P.M. Response rates based on Clinical Global Impression improvement ratings in patients receiving bupropion, methylphenidate, and placebo were 64, 50, and 27%, respectively. The difference in response rates between active treatment and placebo was not statistically significant (p = 0.14). Neuropsychological testing demonstrated trends favoring drug treatment on measures of immediate recall and verbal fluency. While bupropion SR may be a viable clinical alternative for adults with ADHD, further investigation is needed.

Adrenergic Agents↗

PubMed2001

Bioavailable testosterone as a correlate of cognition, psychological status, quality of life, and sexual function in aging males: implications for testosterone replacement therapy.

Andropause is a syndrome described in aging males, is composed of a constellation of physical, sexual, and emotional symptoms, and is thought to be related to declining concentrations of serum testosterone. Numerous studies of testosterone replacement therapy in elderly hypogonadal males have documented the physical benefits of such treatment, but have failed to assess cognition, psychological functioning, and quality of life. Male outpatients greater or equal to 55 years of age completed cognitive, psychological, sexual, and quality of life assessments. A serum sample was provided for bioavailable testosterone assay. The associations between bioavailable testosterone concentrations and neuropsychological testing were assessed using Spearman rank correlation. Overall, bioavailable testosterone was not an important determinant of cognitive, psychological, or sexual functioning or of quality of life. The implications for future studies involving testosterone replacement therapy are discussed.

Aged↗

PubMed2001

Lithium and suicidal behavior in major affective disorder: a case-control study.

OBJECTIVE: A number of studies have suggested that lithium may be particularly effective in reducing suicide risks among patients with major affective disorders. The design of many of these studies left them open to biases associated with treatment compliance, however. METHOD: Subjects were drawn from a naturalistic, long-term follow-up of patients with major affective disorders. Fifteen who committed suicide while receiving somatotherapy where matched to non-suicidal patients who were similarly receiving somatotherapy at the same point in follow-up. The same procedure was followed for 41 patients who made a serious suicide attempt during follow-up. RESULTS: Six (40.0%) of the patients who committed suicide, and eight (53.3%) of their controls, were thought to have been taking lithium in the preceding week. Among attempters and their controls, nine (22.0%) and eight (19.5%), respectively, were taking lithium. CONCLUSION: These results do not support previous suggestions that lithium has uniquely antisuicidal properties. Other existing datasets should be explored with this design to establish whether lithium does, or does not, offer special protection against suicide.

Adult↗

PubMed2001

The effect of remission of poststroke depression on activities of daily living in a double-blind randomized treatment study.

Poststroke depression has been associated with impaired recovery of activities of daily living (ADL) during the first 2 years after stroke. This study examined the effect of remission of poststroke depression on recovery in ADL in a double-blind randomized treatment study. Based on a semistructured psychiatric exam and DSM-IV diagnostic criteria, a consecutive series of 23 patients who met criteria for major depression (N = 16) or minor depression (N = 7) were selected and randomly assigned to either active treatment (nortriptyline) or placebo. Functional physical (i.e., ADL) impairment was assessed using the Johns Hopkins Functioning Inventory (JHFI). Patients whose depressive disorder remitted at follow-up had significantly greater recovery in ADL functions compared with patients whose depression did not remit. There were no differences in demographic variables, lesion characteristics, and neurological symptoms between the two groups, which would explain the significantly greater improvement among the remitted patients. Because both major and minor depression patients who remitted showed greater improvement in ADL than nonremitted patients some of whom were treated with active and some with placebo medication, nonpharmacotherapeutic mechanisms related to recovery from depression appear to mediate this enhanced recovery.

Activities of Daily Living↗

PubMed2000

The impact of substance abuse on the course of bipolar disorder.

BACKGROUND: Substance abuse occurs at high rates in bipolar disorder. The reasons for this co-occurrence are unknown. Alcohol use disorders have been associated with both earlier and later age of onset of bipolar disorder, in part based on the temporal associations of the two conditions. Both drug and alcohol use disorders are associated with impaired outcome of bipolar illness. This influence may involve both direct effects of alcohol or drugs on the initiation of affective symptoms and indirect effects on treatment compliance. To extend these previous findings we examined the temporal associations of substance abuse and affective symptoms in patients with new onset bipolar disorder. METHODS: Associations between affective symptoms and alcohol and cannabis use disorder symptoms were evaluated using regression and time-series correlative methods in 50 new-onset bipolar patients. RESULTS: The duration of alcohol abuse during follow-up was associated with the time patients experienced depression. The duration of cannabis abuse was associated with the duration of mania. Several subgroups could be identified with different temporal relationships among these disorders. CONCLUSIONS: Although the relationships among substance use and bipolar disorders are complex, systematic study of the courses of the disorders might clarify how these conditions interact longitudinally. As the numbers of subjects in specific subgroups are relatively small in this study, these results should be considered preliminary.

Acute Disease↗

PubMed2000

Cerebellar hypoactivity in frequent marijuana users.

It is uncertain whether frequent marijuana use adversely affects human brain function. Using PET, regional cerebral blood flow was compared in frequent marijuana users and comparable, non-using controls after at least 26 h of monitored abstention by all subjects. Marijuana users showed substantially lower brain blood flow than controls in a large region of posterior cerebellum, indicating altered brain function in frequent marijuana users. A cerebellar locus of some chronic and acute effects of marijuana is plausible, e.g. the cerebellum has been linked to an internal timing system, and alterations of time sense are common following marijuana smoking.

Adult↗

PubMed2000

Effects of frequent marijuana use on brain tissue volume and composition.

To investigate CNS effects of frequent marijuana use, brain tissue volume and composition were measured using magnetic resonance imaging (MRI) in 18 current, frequent, young adult marijuana users and 13 comparable, non-using controls. Automated image analysis techniques were used to measure global and regional brain volumes, including, for most regions, separate measures of gray and white matter. The marijuana users showed no evidence of cerebral atrophy or global or regional changes in tissue volumes. Volumes of ventricular CSF were not higher in marijuana users than controls, but were, in fact, lower. There were no clinically significant abnormalities in any subject's MRI. Sex differences were detected in several global volume measures.

Adult↗