APOE2 allele increased in tardive dyskinesia.

Ninety-seven inpatients with tardive dyskinesia (average AIMS score = 13), the majority of whom were schizophrenic, were studied. Forty patients were Caucasian, and 57 were African-American. The APOE genotypes of these patients were compared to previously published genotypes of controls and with previously published studies of APOE genotypes in patients with schizophrenia. There were no significant differences in APOE allele frequencies comparing the African-American tardive dyskinesia population and the African-American control groups. In contrast, significant (< 0.05) P values were obtained comparing the Caucasian tardive dyskinesia population to the Caucasian controls, when comparing allele frequencies and genotypic frequencies. This study suggests that Caucasians bearing an APOE2 allele are at increased risk of developing tardive dyskinesia, whereas African-Americans are not. APOE genotype-specific risks of both tardive dyskinesia and Alzheimer's disease that vary across populations could be due to recruitment of patients or controls or could be due to modifying effects of differing genetic or environmental backgrounds. The mechanism by which the APOE2 allele increases risk of tardive dyskinesia is not known. Further information about the mechanisms of increased risk of tardive dyskinesia could result in stratification of prescribing practices weighing the costs of medications against the relative risk of side effects.     

Intensity-dependent regional cerebral blood flow during 1-Hz repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers studied with H215O positron emission tomography: I. Effects of primary motor cortex rTMS.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) affects the excitability of the motor cortex and is thought to influence activity in other brain areas as well. We combined the administration of varying intensities of 1-Hz rTMS of the motor cortex with simultaneous positron emission tomography (PET) to delineate local and distant effects on brain activity. METHODS: Ten healthy subjects received 1-Hz rTMS to the optimal position over motor cortex (M1) for producing a twitch in the right hand at 80, 90, 100, 110, and 120% of the twitch threshold, while regional cerebral blood flow (rCBF) was measured using H(2)(15)O and PET. Repetitive transcranial magnetic stimulation (rTMS) was delivered in 75-pulse trains at each intensity every 10 min through a figure-eight coil. The regional relationship of stimulation intensity to normalized rCBF was assessed statistically. RESULTS: Intensity-dependent rCBF increases were produced under the M1 stimulation site in ipsilateral primary auditory cortex, contralateral cerebellum, and bilateral putamen, insula, and red nucleus. Intensity-dependent reductions in rCBF occurred in contralateral frontal and parietal cortices and bilateral anterior cingulate gyrus and occipital cortex. CONCLUSIONS: This study demonstrates that 1-Hz rTMS delivered to the primary motor cortex (M1) produces intensity-dependent increases in brain activity locally and has associated effects in distant sites with known connections to M1.     

Fine structure of nuclear division and microgametogony ofEimeria nieschulzi Dieben, 1924

Nuclear division and microgametogony ofEimeria nieschulzi were studied by transmission electron microscopy. All nuclear divisions occurred in close proximity to the gamont surface with four centrioles situated between the nuclear envelope and the gamont plasmalemma. During early nuclear divisions, each nucleus had a rod or hourglass-shaped nucleolus, indicating that the nucleolus probably pinched in two during nuclear division. Nuclear divisions occurred by nearly centrally located intranuclear spindles. Two centrioles were associated with each centrocone. Spindle microtubules, which originated from each centrocone, either traversed to the other centrocone or terminated at kinetochores. Four to 6 chromosome-like structures were present in each dividing nucleus. The formation of 50 to 100 biflagellate microgametes occurred at the margin of the microgamont by a process similar to that described for other coccidian species. Microgametes were limited by a single membrane with a prominent glycocalyx, 13 nm thick.Based on a thesis submitted by G.J. Sibert to the Graduate School of the University of Montana in partial fulfillment of the requirements for the Master of Science degree     

Neurobiology of Bipolar Illness: Implications for Future Study and Therapeutics

Many findings implicating prefrontal cortical and limbic areas of the brain and endocrine systems in the neuropathology and pathophysiology of bipolar illness have greatly increased our understanding of the neurobiology of the illness. New imaging techniques such as PET, MRI, SPECT, and MRS have detailed more evidence of specific regional alterations in the brains of bipolar patients than was thought possible just 20 years ago. These methods are beginning to be used to help predict response to treatment. Examining the mechanisms of action of mood stabilizers (such as lithium, carbamazepine, and valproate) has provided clues to potential underlying neurobiological abnormalities in the illness. Recent studies of postmortem brain tissue have begun to confirm prefrontal cortical and limbic neurochemical and microstructural alterations in patients with bipolar illness compared with controls. It is postulated that it is the balance between primary pathological versus secondary adaptive alterations in gene expression in the illness and their enhancement or dampening by pharmacotherapy, that may determine the episodic course of mood fluctuations and remissions. Further examination of the pathophysiology and neurobiology of bipolar illness should lead to both more effective treatments and, potentially, secondary and even primary episode prevention.     

Non-immune therapy of IgA glomerulonephritis

Summary: The involvement of the IgA immune system and complement components in IgA glomerulonephritis (IgAGN) has prompted the use of immunosuppressive drugs in therapy, but none has so far been shown to alter the natural course of the disease. Because most patients with IgAGN present during the chronic phase of their illness, at the time when the initiating immune events may no longer be active, nonimmune therapy which targets the common pathway of progressive renal injury is likely to be more useful. There is increasing evidence that angiotensin-converting enzyme inhibitors (ACEI) reduce proteinuria and renal injury in patients with IgAGN, and this effect may be observed in both normotensive and hypertensive patients. Yet to be determined is whether this effect is specific for ACEI and whatever other effective antihypertensive drugs may achieve a similar result. Fish oil has recently been shown to retard the progression of renal failure in patients with aggressive IgAGN, but a narrow therapeutic window appears to exist for this form of treatment. Antiplatelet agents on their own appear to be ineffective but in combination with anticoagulation (low dose warfarin) have been shown to have an antiproteinuric effect and may preserve renal function in patients with progressive disease. Future directions of non-immune therapy of IgAGN include evaluation of the renoprotective effect of angiotensin II receptor antagonists, free-radical scavengers and antilipid drugs. More work should also be done to identify factors which put the patients at risk of developing progressive disease and which predict therapeutic response, as has been done recently with the identification of the deletion polymorphism of the angiotensin-converting enzyme gene as a marker of progressive disease and therapeutic response to ACEI in patients with IgAGN.     

Imaging of the pelvis and hip

Imaging is basic in the orthopedic evaluation of hip disorders. For optimal evaluation of these images, the orthopedic surgeon must not only correlate normal anatomy and pathology with radiographic findings, but must also be familiar with the newer modalities of CT, magnetic resonance imaging and ultrasound and the role and place of these studies in the evaluation of musculoskeletal disorders. This article correlates normal anatomy of the hip with these modalities and discusses the details of these techniques, particularly CT and MRI, that are pertinent to the orthopedic surgeon.