Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2

Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.     

Aortico-right ventricular tunnel: prenatal diagnosis leading to neonatal survival

In the 36th week of gestation a large aortico-right ventricular tunnel with an otherwise structurally normal heart was diagnosed by fetal echocardiography. This report describes for the first time the impact of the timely prenatal diagnosis of an aortico-right ventricular tunnel followed by successful management in early infancy.     

Ultra-Widefield Indocyanine Green Angiography Reveals Patterns of Choroidal Venous Insufficiency Influencing Pachychoroid Disease

PurposeTo compare patterns of choroidal venous drainage in eyes with pachychoroid disease to those of healthy subjects using ultra-widefield indocyanine green angiography (UWF ICGA).MethodsPatients with pachychoroid disease and healthy controls were recruited at two referral centers. UWF ICGA images were used to evaluate the proportion of the postequatorial fundus drained by major vortex vein systems in each quadrant and to study the incidence and topography of choroidal vascular hyperpermeability (CVH) and intervortex venous anastomoses. Widefield swept-source optical coherence tomography (SS-OCT) was used to evaluate choroidal thickness at the posterior pole in eyes with pachychoroid disease.ResultsFifty-two pachychoroid eyes and 26 healthy eyes were evaluated. Eyes with pachychoroid disease showed a significant within-subject variance in the proportion of the postequatorial fundus drained by each vortex vein system (range, 4.1%–48.1%; P < 0.0001) that was not seen in controls (range, 17.3%–31.7%; P = 0.11). CVH was present in all pachychoroid disease eyes and three of 26 controls. Intervortex venous anastomoses were present in 46 of 52 pachychoroid disease eyes and nine of 26 control eyes. Vortex vein systems with large drainage areas showed greater density of CVH spots. SS-OCT demonstrated asymmetric choroidal drainage in the macula of 59% of pachychoroid eyes. CVH and intervortex venous anastomoses were more prominent in areas showing maximal choroidal thickness.ConclusionsIn eyes with pachychoroid disease, imbalanced choroidal venous drainage with congestion of specific vortex vein systems may contribute to a state of choroidal venous insufficiency characterized by regional choroidal thickening, CVH and remodeling of venous drainage routes.     

Decrease of benzodiazepine receptors in frontal cortex of alcoholics

We hypothesize that chronic alcohol abuse results in a loss of neurons and their associated synaptic receptors. This encephalopathy may be a precursor of brain atrophy and end-stage dementia. Autopsies were performed on normal brains of 27 alcoholics (mean age 62.5) and 30 nonalcoholic matched controls (mean age 64.4) free of other brain and liver diseases. None had recently received benzodiazepine medications. Gross brain atrophy was slight and equal in both groups. Benzodiazepine receptor densities and affinities in homogenates of frontal cortex were determined using [3H]flunitrazepam. Bmax specific binding was reduced by 20% in alcoholics compared with nonalcoholic controls of comparable age and with similar death-autopsy time intervals. The affinity was slightly less in the alcoholics. Wet tissue brain protein concentrations and their yields of 50,000-g pellet proteins were similar. Aging, death-autopsy time intervals, pneumonia and chronic obstructive pulmonary disease (diseases usually associated with hypoxia) had no significant effect on brain proteins, receptor densities, or affinities. We conclude that chronic alcoholism is associated with a loss of benzodiazepine receptor densities. Alcohol abuse may affect the results of post-mortem neurochemical investigations of other diseases.     

Neue Ergebnisse zur Frage des Muskel Tonus

Ohne Zusammenfassung     

ACCUMULATION OF ANTIBODIES IN THE CENTRAL NERVOUS SYSTEM

1. Antibodies can be extracted from the brain and spinal cord of rabbits actively or passively immunized with typhoid bacilli. 2. The titers of the antibodies in the extracts of brain and cord depend upon the titer of the blood serum. In actively immunized rabbits the following numerical relationships exist between the titers of the serum and of these organ extracts: The ratio of the titer of the serum is to the titers of extract of brain and of the spinal cord about as 100 is to 0.8; the titer of the serum is to the titer of the cerebrospinal fluid as 100 is to 0.3. In passively immunized rabbits the titer of the serum is to the titer of brain and spinal-cord extract as 100 is to 0.7. 3. The antibodies recovered from the brain are not due to the presence of blood in it for perfusion of the brain does not reduce its antibody content appreciably. 4. Antibodies penetrate into the spinal fluid from the blood even in the absence of inflammation of the meninges. When the penetration is completed the following numerical relationship exists between the titer of the serum and that of the cerebrospinal fluid: 100 to 0.25. 5. The penetration into the cerebrospinal fluid of antibodies injected intravenously proceeds at a slow rate, being completed only several hours after the immune serum has been injected. The penetration of antibodies into the tissue of the brain occurs at a very rapid rate. It is completed within 15 minutes. 6. It is very unlikely that when the immune serum is injected intravenously the antibodies reach the brain tissue by way of the cerebrospinal fluid, for (1) the antibody titer of the cerebrospinal fluid is lower than that of the brain extract, and (2) antibodies penetrate faster into the tissue of the brain than into the cerebrospinal fluid.     

Hippocampal cavities are not associated with cognitive impairment in transient global amnesia

Background: Hippocampal sulcal cavities (HSC) have been speculated to contribute to a higher vulnerability of memory pathways and might be a possible etiological factor in transient global amnesia (TGA). Therefore, we evaluated the influence of HSC on cognitive long‐term outcome in TGA‐patients. Methods: Fourteen otherwise healthy patients with the clinical syndrome of TGA in their history underwent a high‐resolution magnetic resolution imaging and a comprehensive neuropsychological test battery. The neuropsychological control group consisted of 15 healthy subjects and was balanced for age, sex and other risk factors as well as intellectual and social status. Results: Magnetic resolution imaging and neuropsychological testing have been performed 1128 days (median) after the TGA. HSC have been detected in nine of the 14 patients and have been bilateral in eight of them. There were no differences in cognitive performance in patients with and without HSC as well as compared to healthy subjects. Even in patients with greater lesion load, only a slight visuospatial deficit was found. Conclusions: Although an increased incidence of HSCs is detected in TGA patients, cavities are not obligatorily in TGA. Moreover, even patients with hippocampal cavities achieve a full neuropsychological recovery independent of the frequency and size of the hippocampal lesions.     

The Emotion Word Fluency Test (EWFT): Initial psychometric,validation, and physiological evidence in young adults

Introduction: The clinical assessment of affective functioning has been slow to incorporate findings from affective neuroscience. Of particular interest in the current study is the assessment of affective word production. Method: In a series of four studies, we examined test–retest and interrater reliability for the Emotion Word Fluency Test (EWFT), basic construct validity with existing verbal fluency measures, physiological responses across verbal fluency tasks, and a novel scoring method to examine qualitative aspects of participant response sets. Results: Results demonstrated interrater and test–retest reliability values that were comparable to those of other commonly used verbal fluency tests. Construct validity was demonstrated by relations between the EWFT and other verbal fluency tests as well as through physiological evidence that performance on the EWFT is related to greater sympathetic activity than traditional verbal fluency tasks. Lastly, some of the novel scoring metrics related to two self-report measures of emotional functioning. Conclusions: Taken together, our findings provide initial support for the use of the EWFT as a measure of emotion word generation ability in young adults. This measure may prove to be useful in the assessment of affective language production in patient populations.     

Migraine and the hypothalamus

Migraine is a complex brain disorder where several neuronal pathways and neurotransmitters are involved in the pathophysiology. To search for a specific anatomical or physiological defect in migraine may be futile, but the hypothalamus, with its widespread connections with other parts of the central nervous system and its paramount control of the hypophysis and the autonomic nervous system, is a suspected locus in quo. Several lines of evidence support involvement of this small brain structure in migraine. However, whether it plays a major or minor role is unclear. The most convincing support for a pivotal role so far is the activation of the hypothalamus shown by positron emission tomography (PET) scanning during spontaneous migraine attacks. A well-known theory is that the joint effect of several triggers may cause temporary hypothalamic dysfunction, resulting in a migraine attack. If PET scanning had consistently confirmed hypothalamic activation prior to migraine headache, this hypothesis would have been supported. However, such evidence has not been provided, and the role of the hypothalamus in migraine remains puzzling. This review summarizes and discusses some of the clues.