Optic nerve edema as a consequence of respiratory disease

The authors describe a patient with bilateral papilledema, visual field abnormalities, poorly reactive pupils, meningeal enhancement on cranial MRI, and diffuse brain parenchymal hypervascularity. The opening pressure at the time of lumbar puncture was normal, and results of other CSF studies were normal. All abnormalities resolved with home oxygen therapy.     

D-dimer testing in the diagnosis of acute venous thromboembolism

Patients with acute VTE require clinical assessment and objective testing to be accurately diagnosed. Almost all patients with acute VTE have an elevated D-dimer level. An elevated D-dimer is associated with many illnesses, and therefore, is not specific for VTE. D-dimer tests can have a high sensitivity, however, which is useful because a normal test excludes the diagnosis of VTE. D-dimer testing is most appropriate in the assessment of outpatients because the prevalence of disease and the likelihood of comorbid conditions are lower than in inpatient populations, making a test of exclusion particularly valuable. Accuracy studies using conventional ELISA assays have confirmed that a test with a high sensitivity can be used to exclude a diagnosis of VTE, but conventional ELISA testing is not practical. Studies of more practical D-dimer testing indicate that, for patients with suspected DVT or PE, the need for serial testing or further investigation can be reduced if normal results are obtained using assays with a high sensitivity. There are, however, many sources of variation in the test characteristics of D-dimer assays. Therefore there is no reassurance that results from one manufacturer's test are applicable to other tests and different investigators may obtain varied results when using the same manufacturer's product. In addition, the results of D-dimer accuracy studies lack generalizability. This lack of generalizability has led to the recommendation that clinicians await the results of management studies before adopting the routine use of D-dimer assays in the diagnosis of VTE. Further, it may be reasonable to perform an accuracy study when planning to adopt a specific D-dimer assay from a published management trial, to be confident of its characteristics can be reproduced. In the management of patients with suspected DVT, rapid ELISA tests show promise as a practical D-dimer test, in that they have a sensitivity similar to that of the conventional ELISA assay. Two management studies have recently confirmed that a normal D-dimer result (using the SimpliRED whole-blood assay or the Instant IA rapid ELISA) in combination with a noninvasive test or a clinical model can reliably exclude DVT in outpatients. Use of a clinical model can reduce the need for VU, and the combination of a clinical model and D-dimer testing could further reduce the number of VU procedures required. As noted by Wells et al, who recently published a clinical model, however, a normal D-dimer result was most accurate in the patients with a low pretest likelihood (NPV = 99.5%) and least accurate in patients with a high pretest likelihood (NPV = 85.7%) Patients with a low pretest likelihood and a normal D-dimer are the largest proportion of outpatients referred for testing, and considerable resources may be saved if additional management studies confirm the usefulness of D-dimer testing in such patients. In patients with suspected PE, there is a lack of published management trials despite a number of accuracy studies indicating that D-dimer testing may be useful as a method of PE diagnosis exclusion. Recent results, however, from an accuracy study of patients with suspected PE who had D-dimer testing complement the findings of Wells et al in patients with suspected DVT. Using a standardized clinical model of PE in combination with a SimpliRED D-dimer assay, Ginsberg and colleagues found that the combination of a low pretest likelihood and a normal D-dimer had a negative predictive value of 99%, whereas the negative predictive value was only 78% in patients with a high pretest likelihood and a normal D-dimer. Similar to the findings in DVT, these results indicate that D-dimer testing is most useful in patients with a low pretest likelihood for PE and raise the possibility that such patients may not require lung scans. This finding is currently being evaluated in a prospective management trial.     

Bone age and linear skeletal growth of children with cerebral palsy

The aim of this study was to compare the linear growth of children with cerebral palsy (CP) with that of children without CP. The segmental lengths (humerus, ulna, femur, tibia, and spine), recumbent length, body weight, and bone age of 62 children with CP (age range 2.25 to 14 years, mean 7.13 years) were measured and compared with 68 children without CP (age range 1.50 to 12.67 years, mean 6.73 years). The results show that bone-age delay is common in children with CP (68% with a delay of more than 1 year). The linear growth of children with CP is similar to that of children without CP when bone age is used instead of chronological age. There is a strong correlation between segmental lengths and body height. Hence, this study favours using segmental lengths for estimating height in children with CP and using the comparison group as a reference for this purpose. Nutritional and non-nutritional factors on bone-age delay are discussed.     

Functional synapses are formed between human NTera2 (NT2N, hNT) neurons grown on astrocytes

The formation of functional synapses is a late milestone of neuronal differentiation. The establishment of functional synapses can be used to assess neuronal characteristics of different cell lines. In the present study, we examined the in vitro conditions that influence the ability of human neurons derived from the NT2 cell line (NT2N neurons) to establish synapses. The morphologic, immunologic, and electrophysiologic characteristics of these synapses was examined. In the absence of astrocytes, NT2N neurons rarely formed synapses and their action potentials were weak and uncommon. In contrast, when plated on primary astrocytes, NT2N neurons were able to form both glutamatergic excitatory (71%) and GABAergic inhibitory (29%) functional synapses whose properties (kinetics, ion selectivity, pharmacology, and ultrastructure) were similar to those of synapses of neurons in primary cultures. In addition, coculture of NT2N neurons with astrocytes modified the morphology of the neurons and extended their in vitro viability to more than 1 year. Because astrocyte-conditioned medium did not produce these effects, we infer that direct contact between NT2N neurons and astrocytes is required. These results suggest that NT2N neurons are similar to primary neurons in their synaptogenesis and their requirement for glial support for optimal survival and maturation. This system provides a model for further investigations into the neurobiology of synapses formed by human neurons.     

A comparison of the effect of clozapine with typical neuroleptics on cognitive function in neuroleptic-responsive schizophrenia

Clozapine has been reported to improve selected aspects of cognitive function in neuroleptic-resistant schizophrenia. In this study, we report the first direct comparison of the effect of clozapine and typical neuroleptic drugs on cognitive function in neuroleptic-responsive schizophrenia. Sixty-four patients with recent onset, neuroleptic-responsive schizophrenia or schizoaffective disorder were randomly assigned to either clozapine (n = 35) or typical neuroleptics (n = 29) and followed for 12 months. They were administered a comprehensive cognitive test battery at baseline and at 6 weeks, 6 months and 12 months after initiating drug treatment. Treatment with clozapine improved psychomotor speed and attention [Digit Symbol Substitution Test (DSST)] and verbal fluency [Category Instance Generation and Controlled Word Association Test (CWAT)] at 6 weeks. The improvement in these measures was maintained throughout the 12-month period. Treatment with typical neuroleptics produced no sustained improvement in any cognitive measure, except for a tendency to improve delayed recall memory (Verbal List Learning Test). The improvement in the DSST and CWAT was significantly greater with clozapine treatment compared to that with typical neuroleptics. These improvements were not related to improvement in psychopathology. These results suggest that clozapine is superior to typical neuroleptics in improving specific types of cognitive function in recent onset, neuroleptic-responsive schizophrenia.     

Reactive astrocytes express p53 in the spinal cord of transgenic mice expressing a human Cu/Zn SOD mutation

In a previous study, we reported increased NOS expression in the astrocytes in the spinal cord of SOD mutant transgenic mice that are used as ALS animal model. Recently, Messmer and Brune suggested that nitric oxide-induced apoptosis is intimately related with p53-dependent signaling pathway, and de la Monte et al. reported increased p53-immunoreactivity in the spinal cord of ALS patients. In the present study, we performed immunocytochemical studies to investigate the changes of p53-immunoreactivity in the brains of the mutant transgenic mice expressing a human Cu/Zn SOD mutation. Immunocytochemistry showed intensely stained p53-IR glial cells with the appearance of astrocytes in all levels of the spinal cord of the mutant transgenic mice, but no p53-IR glial cells were observed in the spinal cord of the control mice. P53-IR astrocytes were also detected in the brain stem of the mutant transgenic mice. In the medulla, they were observed in the medullary reticular formation, hypoglossal nucleus, vestibular nucleus, dorsal motor nucleus of the vagus and nucleus ambiguus. In the pons, their presences were noted in the pontine reticular formation, and trigeminal and facial nuclei. In the midbrain, astrocytes were detected in the mesencephalic reticular formation, red nucleus and periaqueductal gray matter. In the cerebellum, intensely stained p53-IR astrocytes were detected in the intracerebellar nuclei. In contrast to the mutant transgenic mice, no p53-IR astrocytes were detected in the brain stem and spinal cord of the control mice. Further multidisciplinary investigations involving p53-mediated cellular damage and pathogenesis of ALS are needed to clarify the importance of these results.     

Hemiballismus-hemichorea in older diabetic women: a clinical syndrome with MRI correlation

Eight older women from two different continents, all with nonketotic hyperglycemia, presented with hemiballismus-hemichorea (HB-HC) and high signal intensity in the contralateral striatum on T1-weighted MRI scans. Correction of underlying hyperglycemia and supportive care resulted in resolution within days to weeks. This characteristic clinicoradiologic picture suggests a clinical syndrome with benign outcome.     

The expression of alpha-, beta-, and gamma-synucleins in olfactory mucosa from patients with and without neurodegenerative diseases

A family of homologous proteins known as alpha-, beta-, and gamma-synuclein are abundantly expressed in brain, especially in the presynaptic terminal of neurons. Although the precise function of these proteins remains unknown, alpha-synuclein has been implicated in synaptic plasticity associated with avian song learning as well as in the pathogenesis of Parkinson's disease (PD), dementia with LBs (DLB), some forms of Alzheimer's disease (AD), and multiple system atrophy (MSA). Since olfactory dysfunction is a common feature of these disorders and the olfactory receptor neurons (ORNs) of the olfactory epithelium (OE) regenerate throughout the lifespan, we used antibodies specific for alpha-, beta-, and gamma-synucleins to examine the olfactory mucosa of patients with PD, DLB, AD, MSA, and controls without a neurological disorder. Although antibodies to alpha- and beta-synucleins detected abnormal dystrophic neurites in the OE of patients with neurodegenerative disorders, similar pathology was also seen in the OE of controls. More significantly, we show here for the first time that alpha-, beta-, and gamma-synucleins are differentially expressed in cells of the OE and respiratory epithelium and that alpha-synuclein is the most abundant synuclein in the olfactory mucosa, where it is prominently expressed in ORNs. Moreover, alpha- and gamma-synucleins also were prominent in the OE basal cells, which include the progenitor cells of the ORNs in the OE. Thus, our data on synuclein expression within the OE may signify that synuclein plays a role in the regeneration and plasticity of ORNs in the adult human OE.     

Physics and the quandaries of contemporary psychiatry: review and research

Although in physics, quantum mechanical principles have long replaced Newtonian ones, we continue to apply the latter in models of the mind and its diseases. This article discusses the possible theoretical application of quantum principles to mind-brain function. Empirically, this study tested which of these principles practicing psychiatrists found more applicable in clinical practice. Psychiatrists (N = 382) at universities around the United States were asked to answer a questionnaire that contained clinical scenarios reflecting mental, interpersonal, or therapeutic processes corresponding to quantum or classical physical principles. Respondents (N = 191) were significantly more likely to rate scenarios reflecting quantum principles as being consistent with their experience than they were those reflecting classical principles (p < .0005). This effect was significantly greater in more experienced psychiatrists. Quantum physics, a powerful tool in understanding properties of both micro- and macro-level phenomena, may have implications at the human level, invoking the roles of observer, interpersonal relationships, and resources such as resiliency and creativity.