Experimental isovolemic haemodilution-induced augmentation of carotid blood flow and oxygen transport through graded carotid stenoses.

The effect of haemodilution without volume expansion (isovolemic haemodilution) was assessed with respect to blood flow and oxygen transport across stenotic lesions of progressive severity in the dog carotid artery. As the mean haematocrit (Hct) was reduced from 40 +/- 1% (+/- SEM) to 32 +/- 0% (p less than 0.001), reductions in vascular resistance were significant across the 90% (p less than 0.001) and 95% (p less than 0.0003) relative carotid stenoses. Isovolemic haemodilution reduced fresh blood viscosity significantly by 27 +/- 3% (p less than 0.001) and 42 +/- 4% (p less than 0.001) at the low shear rates of 10 sec-1 and 1 sec-1 which are typical of low-flow states. Following a 20% reduction in Hct 30 to 35% increase (p less 0.001) in carotid blood flow occurred at non-critical degrees of stenosis while a mean 83% increase (p less than 0.001) occurred at the highly critical 95% relative stenosis. Oxygen transport after a 22% decrease in blood haemoglobin was significantly increased by 28% (p less than 0.01) at the 95% relative stenosis level. These data provide a physiologic rationale for the beneficial effects of haemodilution in acute cerebral ischaemia, cerebral vasospasm and cerebral revascularization or carotid endarterectomy.     

An in vivo study of the ontogeny of long-term potentiation (LTP) in the CA1 region and in the dentate gyrus of the rat hippocampal formation.

The influences of stimulus intensity, intratrain frequency, and number of trains were studied for their effects on the development of long-term potentiation (LTP) in the hippocampal formation. LTP was analyzed with full input-output curves for population spike (PS) amplitudes (PS-LTP) calculated from responses elicited in the CA1 region and in the dentate gyrus by monosynaptic activation. A standardized protocol employing a sequence of stimuli was devised to systematically compare LTP in the dentate gyrus to that in the CA1 region in rats of various ages ranging from postnatal day (PN) 6 to adults (PN 60). In adult animals, the degrees of LTP were comparable in the dentate gyrus and CA1 region for the 3 stimulus strengths studied (intensity just subthreshold for PS, intensity giving 1/4 maximal PS, and intensity giving 1/2 maximal PS). LTP developed at different rates in the two regions, reaching adult values about two weeks after birth in CA1 but about 3 weeks after birth in the dentate gyrus. We postulate that differences in the rate of development in CA1 and in the dentate gyrus are related to the later neurogenesis of dentate granule cells and also possibly to a later functional maturation of N-methyl-D-aspartate (NMDA) receptor-channel complexes on these cells.     

Toxoplasma encephalitis of immunocompetent and nude mice: immunohistochemical characterisation of Toxoplasma antigen, infiltrates and major histocompatibility complex gene products

The experimental infection of immunocompetent and immunodeficient athymic mice with an avirulent encephalitogenic Toxoplasma strain (DX strain) was employed to study the ensuing encephalitic process by use of histological and immunocytochemical methods. In the acute phase of the infection Toxoplasma cysts and tachyzoites were accompanied by an infiltrate composed of macrophages, CD4+ and CD8+ T cells. In the chronic stage a granulomatous encephalitis developed. In contrast to immunocompetent NMRI mice, athymic nude NMRI mice died 3 weeks post-infection because of a generalized toxoplasmosis with predominant involvement of the brain. A salient feature of murine Toxoplasma encephalitis was up-regulation of class I and II major histocompatibility complex (MHC) gene products. Class I antigen was widely expressed on microglial cells and astrocytes. Class II antigen was only expressed on microglial cells despite a considerable astrogliosis. Our results indicate a differential expression of MHC-determined antigens on brain cells in acute and chronic murine Toxoplasma encephalitis.     

Are haemostatic and fibrinolytic parameters predictors of preeclampsia in pregnancy-associated hypertension?

The plasma levels of several haemostatic and fibrinolytic parameters were measured before and after delivery in 61 hypertensive pregnant women of whom 22 developed preeclampsia, and compared to the results obtained in 42 normal pregnant women. In the two last weeks before delivery (D less than or equal to -15) tPA antigen, PAI-1 activity, vWF:Ag/FVIII:C ratio, ATIII activity and platelet count were found to be significantly different in the hypertensive pregnant women with and without preeclampsia. Combined all together, an association of three of these five parameters were found to be pathological (i.e.:tPA:Ag greater than or equal to 19 ng/ml, PAI-1 activity greater than or equal to 58 IU/ml, vWF:Ag/FVIII:C ratio greater than or equal to 2.6, ATIII activity less than or equal to 73%) in none of the hypertensive women without preeclampsia and in only 35% of the preeclamptic group. A positive correlation was demonstrated between vWF:Ag/FVIII:C ratio and tPA:antigen levels suggesting that both tPA and vWF:Ag could be considered as early indicators of a possible micro angiopathy occurring in preeclampsia. However, due to the high dispersion of the results, it appears that the investigated haemostatic and/or fibrinolytic criteria give only presumptive arguments before assigning risk for preeclampsia development among hypertensive pregnant women.     

The function of neutrophils in dermatoses]

A total of 102 patients were examined, 32 of these with true eczema, 38 with exudative mycosis of the soles, and 32 with eczema etiologically related to a fungal infection. Analysis of the immune and biochemical reactions in the examinees has shown a marked reduction of adenyl nucleotides in the leukocytic suspension and neutrophils of patients with a mycotic infection as against those with true eczema. The lowest creatine phosphate levels were detected in the leukocytic suspension and neutrophils of the patients suffering from eczema etiologically related to mycosis and exudative mycosis of the soles. These results give grounds to search for effective corrective therapy.     

X chromosome instability associated with familial Turner syndrome

A family with two members (two generations) exhibiting Turner syndrome is described. Cytogenetic studies on these individuals showed the presence of multiple X chromosome changes. Evidence is presented to show that the maternally inherited X chromosome is the chromosome involved in the structural alterations observed. The effect of a tendency of the maternal X chromosome to break at specific sites on the development of the Turner phenotype and abnormal karyology is discussed.     

Modulation of mild bleeding disorder during remissions and exacerbations of Graves' disease

A patient with Graves' disease had a symptomatic thrombocytopathy during periods of remission. When euthyroid, she noticed bruising, petechiae, and epistaxis. Hemostatic abnormalities included prolongation of the bleeding time by aspirin, reduced platelet retention (a second-phase defect), and abnormal thrombin-induced aggregation and serotonin release. When hyperthyroid, bleeding symptoms resolved, and platelet function returned to normal. These observations suggest that mild bleeding disorders may be influenced either directly or indirectly by thyroid hormone levels.     

Relation between electromyogram and torque of isometric reflex contractions in man

Human subjects maintained isometric plantar or dorsal flexions of the ankle in a matching task. H-reflexes of different sizes were superimposed on the steady activity. The peak-to-peak amplitude of the reflexes was measured on the electromyogram (EMG) of the soleus muscle. The size of the corresponding muscle contractions was determined on the isometric torque signal in relation to the maintained flexion force. The EMG-torque relation which was defined as the reflex muscle contraction as a function of the EMG reflex signal approximated a square root function for a given steady contraction level. It was not modulated by steady dorsal flexions, but it decreased continuously with stronger plantar steady torques. This dependence was caused by the silent period following the reflex discharge. Since the reflex discharge and the silent period were near in time to the duration of the contraction, the silent period had a direct effect on the reflex contraction amplitude.     

Plasma tumor necrosis factor and mortality in critically ill septic patients

Tumor necrosis factor (TNF) cachectin has been implicated as an important host mediator responsible for shock and multiple organ failure (MOF) observed during sepsis. Using a sensitive enzyme-linked immunosorbent assay, we measured plasma TNF levels in 43 septic patients suffering from a broad range of diseases. Measurements were taken on the day that sepsis was diagnosed. Eleven patients had detectable TNF plasma levels ranging from 10 to 100 pg/ml (TNF-positive group); in 32 patients circulating TNF could not be detected (TNF-negative group). The groups did not differ significantly as to age, underlying disease, percentage positive bacteremia and bacteriologic profile, sepsis score, and extent of MOF. Eight (73%) of 11 TNF-positive patients died from sepsis during ICU stay, vs. 11 (34%) of 32 TNF-negative patients (p less than .05). This study demonstrates that sepsis is accompanied by detectable circulating TNF in 25% of the cases, and for these patients mortality is twice that for comparable TNF-negative patients.