Some dissociating factors in the analysis of structural and functional progressive damage in open-angle glaucoma.

AIM: To identify the presence, and origin, of any "dissociating factors" inherent to the techniques for evaluating progression that mask the relationship between structural and functional progression in open-angle glaucoma (OAG). METHODS: 23 patients (14 with OAG and 9 with ocular hypertension (OHT)) who had received serial Heidelberg Retina Tomograph (HRT II) and Humphrey Field Analyser (HFA) examinations for >or=5 years (mean 78.4 months (SD 9.5), range 60-101 months) were identified. Evidence of progressive disease was retrospectively evaluated in one eye of each patient using the Topographic Change Analysis (TCA) and Glaucoma Progression Analysis (GPA) for the HRT II and HFA, respectively. RESULTS: Six patients were stable by both techniques; four exhibited both structural and functional progression; seven exhibited structural progression, only, and six showed functional progression, only. Three types of dissociating factors were identified. TCA failed to identify progressive structural damage in the presence of advanced optic nerve head damage. GPA failed to identify progressive functional damage at stimulus locations, with sensitivities exhibiting test-retest variability beyond the maximum stimulus luminance of the perimeter, and where a perimetric learning effect was apparent. CONCLUSION: The three dissociating factors accounted for nine of the 13 patients who exhibited a lack of concordance between structural and functional progressive damage.

Reliability and validity of rigid lift and pelvic leveling device method in assessing functional leg length inequality.

Clinicians commonly include an assessment of leg length inequality (LLI) as a component of a musculoskeletal examination. Little research is available, however, documenting reliability and validity of clinical methods for assessing LLI. The purpose of this study was to determine the reliability and validity of assessing functional LLI using a pelvic leveling device. Subjects were 19 women and 13 men between the ages of 18 and 55 who reported having a diagnosed or suspected LLI. Clinical determination of LLI was made by placing rigid lifts under the suspected shorter lower extremity until the leveling device indicated that the iliac crests were level. This measurement was made twice by one investigator and once by a second investigator. Standing radiographic measurements of LLI using rigid lifts were used to establish validity of the clinical method. Intraclass correlation coefficients [ICC(2,1)] and absolute difference values were computed to assess reliability and validity. The mean absolute difference between the two clinical measurements of LLI by the same investigator was 0.29 cm (+/- 0.52), with an ICC = 0.84. The mean absolute difference between clinical measurements of LLI by the two investigators was 0.49 cm (+/- 0.46), with an ICC = 0.77. The ICC and mean absolute difference reflecting agreement between radiographic measurements and clinical measurements of LLI was 0.64 and 0.58 cm (+/- 0.58), respectively, for one investigator and 0.76 and 0.55 cm (+/- 0.37), respectively, for the second investigator. The intratester reliability, intertester reliability, and validity assessments included instances in which paired observations disagreed regarding which lower extremity was the shorter lower extremity. Factors that may be associated with the unacceptable reliability and validity of the clinical assessment method include asymmetric positioning of the ilia, body composition of the patient, and design of the clinical instrument. The authors discuss clinical implications related to assessment of LLI.

The niacin challenge test: clinical manifestation of altered transmembrane signal transduction in schizophrenia?

Several lines of evidence implicate altered phospholipid-dependent signal transduction (PDST) in the pathophysiology of schizophrenia. Niacin induces vasodilation through mechanisms requiring intact PDST. Thus, an altered response to a challenge dose of niacin may reflect disturbances in these signalling processes in this disorder. In the present study, niacin-induced vasodilation was estimated quantitatively in schizophrenic and comparison bipolar affective disorder and healthy subjects using thermocouple sensors to measure the change in skin temperature relative to core body and ambient room temperature. Twelve (42.9%) of 28 schizophrenic subjects did not vasodilate in response to a 200-mg niacin challenge dose, whereas only 1 of 18 (6%) bipolar disorder subjects and none of 28 controls showed impaired response (Fisher's Exact Test, p < .0001). These findings support the notion that the schizophrenic syndromes are biochemically heterogeneous and suggest the existence of a subgroup of schizophrenic subjects in whom phospholipid-dependent signalling responses may be impaired.

The niacin challenge test in schizophrenia: past, present and future.

Schizophrenia, a complex, heterogeneous illness, represents a diagnostic challenge in that defining the clinical subtypes of this illness remains equivocal. Moreover, a scarcity of research has focused on the integration of the biochemical and clinical aspects of schizophrenia. Therefore, there is a need to approach the subtyping of schizophrenia with attention to potential clinical manifestations of underlying biochemical disturbances. In an attempt to subtype schizophrenia, we review some of the clinical and biochemical evidence for alterations in phospholipid function in schizophrenia.

Phospholipases: in search of a genetic base of schizophrenia.

Evidence from a variety of clinical and biochemical sources indicates alterations in phospholipid synthesis and activity in schizophrenia. We review a recent study which suggests that a genetic variant near the promotor region of the gene for cytosolic phospholipase A2, the rate-limiting enzyme in the synthesis of prostaglandins from arachidonic acid (AA), is associated with schizophrenia. These findings are consistent with a extensive body of literature which suggests alterations in membrane phospholipids in schizophrenia.

Genetic variant near cytosolic phospholipase A2 associated with schizophrenia.

Two studies were undertaken to determine a possible genetic basis for alterations in phospholipid metabolism in schizophrenia. Initial results demonstrated an association in 65 schizophrenics compared with a matched normal control population. A follow-up haplotype relative risk study of 44 triads (mother, father, affected offspring), confirmed the results seen in the association study. Results suggest that a genetic variant near the promotor region of the gene for cytosolic phospholipase A2, the rate-limiting enzyme in the synthesis of prostaglandins from arachindonic acid, is associated with schizophrenia.

No evidence for association of dopamine D2 receptor variant (Ser311/Cys311) with major psychosis.

We investigated a variant of the dopamine D2 receptor gene (Ser311/Cys311 substitution) in Caucasian patients with schizophrenia (n = 273), delusional disorder (n = 62), bipolar I affective disorder (n = 63), and controls (n = 255). No evidence for association between the receptor variant and any of the diseases was found, even when patients with younger age-of-onset (< 25 years) were compared with controls. Furthermore, in a subgroup of schizophrenia patients whom we assessed for negative symptoms, those with the Cys allele did not differ from the remainder of the group. Also, the bipolar affective disorder patients with psychotic features did not show evidence for association with the receptor variant. Thus, our results do not provide evidence for an association between this D2 receptor variant and schizophrenia, or delusional disorder, or bipolar affective disorder.

Possible relevance of phospholipid abnormalities and genetic interactions in psychiatric disorders: the relationship between dyslexia and schizophrenia.

The fatty acids of cell membrane phospholipids are essential for normal membrane structures, for the functioning of membrane-bound and membrane-associated proteins and for normal cell-signalling responses. In dyslexia, there is evidence for reduced incorporation of docosahexaenoic acid and arachidonic acid into cell membranes, while in schizophrenia, there is evidence for an increased rate of docosahexaenoic acid and arachidonic acid loss from membranes because of enhanced phospholipase A2 activity. The presence of both defects will cause a much greater degree of abnormality than either one alone. It is hypothesized that unequivocal clinical schizophrenia may occur when both genes are present in the same individual. The dyslexia gene along will produce dyslexia while the schizophrenia gene alone may produce bipolar or schizoaffective disorders. These proposals could explain: 1. The reduced asymmetry of the brain, especially of the planum temporale in both schizophrenia and dyslexia; 2. The schizotypal personality characteristics of dyslexics; 3. The increased risks of dyslexia in families with a schizophrenic proband; 4. The increased risks of bipolar and schizoaffective disorders in families with a schizophrenic proband; 5. The earlier onset and possibly increased severity of both disorders in males since females have a lower requirement for arachidonic acid and docosahexaenoic acid; 6. The absence of selective pressure against schizophrenia since reproduction would be impaired only when the schizophrenic gene coexisted with a dyslexic gene. The schizophrenic gene alone might even lead to improved reproductive performance.

CNS signal transduction in the pathophysiology and pharmacotherapy of affective disorders and schizophrenia.

Until recently, research on the neurochemical basis of affective disorders (AD) and schizophrenia (SCZ) focused on detecting postulated disturbances in presynaptic neurotransmitter release and metabolism, or postsynaptic receptor function. New insights into the molecular mechanisms involved in the propagation of neurotransmitter signals across biological membranes and in the regulation of neuronal responses have allowed the development of novel hypotheses, which may explain the altered postsynaptic neuroreceptor responsivity thought to be integral to the pathophysiology of these disorders. In this review we evaluate evidence from both basic science and clinical research implicating disturbances in postreceptor signal transduction in the pathophysiology and pharmacotherapy of AD and SCZ. Specific findings regarding potential postreceptor sites of pathophysiology are highlighted in each of these disorders, together with the growing body of data on the possible postreceptor loci of psychotropic drug action, especially lithium and antidepressants.

The kappa opioid-related anticonvulsants U-50488H and U-54494A attenuate N-methyl-D-aspartate induced brain injury in the neonatal rat.

The neuroprotective effects of the kappa opioid-related anticonvulsants U-50488H and U-54494A were tested in a model of N-methyl-D-aspartate (NMDA)-induced brain injury in the neonatal rat. Seven-day-old rat pups were injected intracerebrally with 7.5 nmol NMDA. Five days later, the ensuing unilateral hemisphere weight reduction was measured and used to assess the severity of insult. Control animals (n = 85) exhibited a 21.7 +/- 0.5% hemisphere weight reduction. Animals treated with U-54494A in split doses before and after NMDA administration showed significant neuroprotection at 10, 15, and 20 mg/kg, with the maximum effect observed at 15 mg/kg (33.8% protection). Animals treated with U-50488H on a similar dosing schedule showed significant neuroprotection at all doses tested, with peak protection observed at 30 mg/kg (51.8% protection). Both compounds exhibited a neuroprotective effect when hemisphere cross-sectional area and hippocampal histology were assessed. Treatment with U-54494A after NMDA administration also afforded neuroprotection at various doses, as measured by hemisphere weight disparity, with peak protection occurring at a dose of 20 mg/kg (32.4% protection). These data show that both U-50488H and U-54494A afford neuroprotection against NMDA-induced neuronal injury in the neonatal rat brain.

Storytelling: a measure of anxiety in hospitalized children.

This study investigates the use of storytelling as a method of measuring children's anxiety during hospitalization. Sixty-seven hospitalized children were asked to create stories about pictures they were shown. The stories were categorized as negative or positive in tone and, hence, the children were categorized as anxious or not anxious. Children who told negative stories displayed significantly more negative behaviors and showed significantly higher anxiety levels and poorer adjustment to hospitalization as measured by observational methods. The most anxious children were male, black, and rural. Implications for practitioners who work with children in medical settings are discussed.

Children's health care: brief report. Nature experiences for hospitalized children.

Numerous projects conducted in various settings have supported the thesis that nature activities aid in the development of self-concept, self-confidence, and level of achievement. The nature activities described in this article were designed to cultivate the hospitalized children a sense of wonder about their world and to involve them in sensory experiences that would aid them in adjusting to their hospital experiences. As a unit, these experiments provide a comprehensive approach to therapy for the hospitalized child and add a positive dimension to the child life program.

Panic disorder and alcohol misuse.

The literature on the relationship of panic disorder to alcoholism is reviewed. Four cases of panic disorder are presented, illustrating instances in which the diagnosis of panic disorder was delayed or obscured by alcoholism. Professionals in alcoholism treatment should therefore be better able to recognize panic disorder. Also, since tricyclic antidepressants are very effective in the treatment of panic disorder, the opposition in the alcoholism field to the use of any medication is criticized.