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[Xenogeneic splenic perfusion in the treatment of bronchial asthma patients].

Blood morphology, external respiratory function, central hemodynamics, cellular and humoral immunity, circulating immune complexes, average molecules and leucocytic index were examined in 40 patients with a severe and average severe course of infection-dependent bronchial asthma before and after xenosplenoperfusion. Positive clinical results were noted manifested in an increase of the immune reactivity, improvement of external respiratory function. The method should be used with care due to additional sensibilization of the patient and possible bronchospasm.

Adult↗

PEEP ventilation does not cause humorally mediated cardiac output depression in pigs.

OBJECTIVE: This study was designed to see if humorally mediated negative inotropism contributes to the cardiac output (CO) depression seen during positive end-expiratory pressure (PEEP) ventilation. DESIGN: 8 pairs of piglets were used and a combined blood circulation was established between the two animals in each pair. One animal was ventilated with a PEEP of 15 cmH20 (donor) and the other was ventilated without PEEP (recipient). MEASUREMENT AND RESULTS: CO and stroke volume deteriorated in the donors by 32% and 44%, respectively, while no change was seen in the recipients. CONCLUSION: As humorally mediated negative inotropism during PEEP ventilation has earlier been demonstrated in dogs, the results suggest that this mechanism might be species-dependent.

Analysis of Variance↗

[Restoration of the vital functions of animals resuscitated with the help of a donor following prolonged circulatory arrest].

Experiments were carried out on anesthetized dogs which had sustained a 15--20-minute circulatory arrest and were reanimated with the aid of donor circulation. In the I group of experiments the blood flow from the donor was directed to the heart of the revived dog, and in the II group--to the heart and the brain. Unlike other methods, donor reanimation, especially in the II variant of experiments, promoted a more rapid recovery of the vital functions of the organism and increased the number of survived animals. In spite of a complete apparent recovery of dogs after a prolonged circulatory arrest there were different changes in their brain depending both upon the duration of clinical death and the reanimation methods.

Animals↗

Myasthenia gravis and pregnancy.

Pregnancy is certainly an option open to patients with myasthenia gravis. Preconceptional counseling is the ideal, with the goal of discontinuing or reducing corticosteroid medications in patients requiring those agents. Alterations in physiology will require ongoing and careful assessment of the pregnant myasthenic or cholinergic crises. Antenatal testing for fetal well-being may be difficult to interpret. A small number of fetuses with fetal myasthenia gravis will be diagnosed by ultrasound. Attempts may be made to decrease the amount of circulating antibody crossing to the fetus. Interventions may include starting or increasing corticosteroid therapy, therapy with azathioprine, or plasmapheresis. Thymectomy is usually not performed during pregnancy. The intrapartum period will increase fatigue in the mother and may precipitate a myasthenic crisis. Epidural anesthesia is currently the agent of choice for decreasing pain and fatigue. An outlet forceps or vacuum delivery will shorten the second stage of labor in those patients who are unable to push repetitively. Cesarean delivery is preferably avoided in those patients at risk for pulmonary and thrombo-embolic complications. Narcotic and sedative medications may be used in the presence of careful and continuous assessment; they may increase respiratory and muscular symptoms. The postpartum period may be associated with an increase in exacerbations. Support services may help to eliminate or to reduce potent stressors during this time. Medication dosages may need to be adjusted as the mother's body returns to her prepregnant state. Transient, neonatal myasthenia is seen in up to 21% of maternal myasthenic cases, even in those patients with no detectable circulating antibody.

Adrenal Cortex Hormones↗

Should i.m. injections be avoided during cancer chemotherapy?

The intravascular transit of malignant tumor cells constitutes an important step in the formation of distant metastases. The development of tumors in extravascular tissues depends upon the exit of these cells from the circulation by crossing the barriers formed by endothelium and basement membrane and their growth in the extravascular environment. Cytostatic drugs may disturb the function of these barriers and some of them, as well as antiemetic drugs, are given as i.m. injections. Thus these both mechanically and chemically induced endothelial and extravascular tissue changes might facilitate tumor cell transit to extravascular tissues. These aspects are discussed in this case report of a young female patient with a mediastinal germ cell tumor. At 4 years after complete remission induced with chemotherapy and radiotherapy she developed recurrent germ cell tumor in the form of a s.c. gluteal abscess. This gluteal region is the most common site of i.m. injections during or after cancer chemotherapy.

Adult↗

Local versus central effect of halothane on carotid sinus baroreceptor function.

Depressive effect of halothane on carotid sinus baroreceptor function may be due to direct local action, in the CNS, or both. Paris of dogs were anesthetized with pentobarbital and ventilated with oxygen. The carotid sinus of the recipient dog was isolated and perfused with blood from the common carotid artery of the donor dog. Blood from the recipient sinus was returned through its external carotid to the donor common carotid. Thus, both carotid sinuses of the donor and the contralateral carotid sinus of the recipient dog received uninterrupted circulation. Carotid sinus nerve action potentials and lingual artery pressure of the isolated recipient sinus were recorded before and during steady state end-tidal halothane concentrations of 0, 0.5, 1.0, 1.5, 2.0, and 2.5% in oxygen, given randomly first to the donor dog (to evaluate direct local effect) and then to the recipient dog (to determine central effect). The dog not given halothane received pentobarbital. Plots of normalized nerve activity versus halothane concentrations showed approximately zero slope when the donor was given halothane but showed significant decrease in nerve activity when the recipient was given halothane. Halothane appears to have no direct local effect but causes depression of baroreceptor nerve activity, possibly via CNS inhibition of sympathetic efferents to the carotid sinus.

Action Potentials↗

Effects of acute L-arginine infusion on non-stress test in hypertensive pregnant women.

OBJECTIVE: The present report evaluates the effect of acute L-arginine administration on fetal heart variables by a computerized non-stress test (NST) analysis. METHODS: Fifteen pregnant women at 30-34 weeks of gestational age affected by mild to moderate gestational hypertension were enrolled in the study. The study was performed in the second and third days of hospitalization. Each woman received both active (Arg) or placebo treatment (Placebo), in a double-blind, randomized, cross-over design. Women received saline infusion for 40 min, then they were infused with either placebo (saline infusion prepared by Damor Pharmaceutics and labeled as Arg-B) or Arg (L-Arg 20 g/500 ml labeled as Arg-A). RESULTS: Multiple analysis of variance (MANOVA) indicated that both placebo and Arg infusion were unable to affect cardiac variables and fetal movements. As far as maternal blood pressure changes were concerned, MANOVA indicated that active treatment showed an acute hypotensive effect on both systolic (F=8.98, p<0.001) and diastolic values (F=15.78, p>0.001). Conversely, placebo infusion does not seems to have induced any change. Considering each time of infusion we observed that Arg treatment was able to lower systolic and diastolic blood pressure after the 40 min of infusion, with this effect persisting for 20 min. CONCLUSIONS: These data indicate that the acute, intravenous administration of high-dose L-arginine does not induce significant changes in fetal heart rate (FHR), whereas it lowers maternal blood pressure. Such conclusions are reinforced by the observation that saline administration in the same pregnant women was neutral for both FHR and maternal blood pressure values. According to previous studies, it seems conceivable that maternal L-arginine treatment enters the fetal circulation by crossing the placenta. The lack of changes in FHR, however, suggests that no significant hemodynamic changes were induced by the treatment. Contrary to what happens in the mother, this may possibly be due to a low, if any, conversion of L-arginine to nitric oxide in the fetus.

Adult↗

Regulation of acylcoenzyme A. Cholesterol acyltransferase and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity by lipoproteins in the intestine of parabiont rats.

Parabiont rats were used to study the regulation of intestinal cholesterol synthesis (3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase activity) and esterification (acylcoenzyme A/cholesterol acyltransferase [ACAT] activity) by lipoproteins and micellar cholesterol. The parabiont rat model offers a unique way to observe changes in cholesterol metabolism in the intestine, independently of luminal factors. In one group of six surgically joined pairs, one animal was fed rat chow and 0.1% propylthiouracil (PTU). Its joined mate was fed rat chow, 0.1% PTU, 5% lard, and 0.3% taurocholic acid. In another group of five pairs, one rat was fed rat chow, 0.1% PTU, 5% lard, 0.3% taurocholic acid, plus 1% cholesterol. Its joined mate was fed the same diet except the cholesterol was deleted. Serum cholesterol changes were equal between members of a given pair, attesting to their common circulation. The administration of PTU itself caused a significant elevation of serum cholesterol. When one parabiont ingested cholesterol, serum cholesterol concentrations increased significantly for both pair members compared with control pairs not ingesting cholesterol. Hepatic and intestinal HMG-CoA reductase activities were significantly decreased in rats fed the diet containing cholesterol. ACAT activities in both organs were markedly increased. This supports previous data that suggest that dietary or luminal cholesterol affects both HMG-CoA reductase and ACAT activity in the small intestine. Moreover, in rats that were hypercholesterolemic but not ingesting dietary cholesterol, hepatic and intestinal reductase activities were decreased and ACAT activities were increased compared with the control animals. Intestinal microsomal cholesterol content was increased only in rats fed cholesterol. No changes in intestinal microsomal cholesterol were observed in the other animals. The data suggest that intestinal HMG-CoA reductase and ACAT activities are regulated by plasma lipoproteins independently of luminal factors. This nonluminal regulatory effect occurs without a measurable contribution to the intestinal microsomal cholesterol pool.

Acyl Coenzyme A↗

Homohemodialysis: a technique of dialysis for the uremic animal.

As an alternative to kidney transplantation in conditions of renal failure, an in situ kidney of a healthy individual may be used. The present study utilizes the kidney of a healthy rabbit as a hemoperfusion unit for another, uremic, animal. The study comprised 17 experimental models, each of which consisted of 2 adult New Zealand rabbits. One animal of each model was rendered uremic by means of bilateral nephrectomy. The blood chemistry (urea, creatinine, sodium, potassium, pH and base deficit) was examined pre- and 4-hourly post-operatively. When after 48 hours post-nephrectomy, the blood chemistry had reached a level sufficient to endanger the animal's life, homohemodialysis was performed. The anticoagulated blood was circulated from the uremic animal to the normal one and then back to the uremic animal through the femoral vessels using a tube system. The blood chemistry was determined every 10 minutes and pH and base deficit every 30 minutes. All animals died or were sacrificed within 21 hours after shunting was started, and autopsy was done. Serum sodium was the first to normalize within the first 10 minutes post-shunting, followed by serum potassium and pH in 30 minutes. Blood urea and creatinine reached normal levels in 40 minutes and base deficit in 60 minutes post-shunting. The pathologic examination of specimens from the vital organs of both the normal and uremic animals showed different degrees of cellular damage probably due to hypotension or acute effects of the unbalanced animal homeostasis. The cellular damage was much less in the normal than in the uremic animals. In conclusion, homohemodialysis proved to be effective in normalizing the concentrations of the different substances retained in the blood of uremic animals within only 60 minutes of dialysis.

Animals↗

Recirculating and sessile B cell populations in normal and CBA/N mice.

Chromosomally distinguishable syngeneic mice were parabiosed and the resultant chimerism was followed for 6 weeks in the lymphoid organs, by culturing their cells with polyclonal mitogens, lipopolysaccharide (LPS) for B cells and phytohemagglutinin (PHA) for T cells. As expected of a recirculating population, the T cells equilibrated completely. The B cells in lymph nodes (LN) and Peyer's patches (PP) also equilibrated completely, suggesting that they too are recirculating. B cells in the spleen and blood, however, did not equilibrate over this period. After separation of parabiosed mice, the percentage of partner cells in both the recirculating T and B lymphocyte populations declined steadily, but it continued to rise in the LPS-responsive populations in spleen and peripheral blood suggesting that they were derived from precursor populations which were themselves chimeric. Injection of lymphocytes into CBA/Ca or CBA/N mice showed that LPS-responsive populations in LN and spleen localized differently. These results have been interpreted as demonstrating two major populations of LPS-responsive B lymphocytes in the mouse, one recirculating and the other sessile. The recirculating population appears to be the only LPS-responsive population in LN and PP. In the spleen, however, the recirculating cells constitute about a quarter of the LPS-responsive cells, while the rest are sessile cells. The relationship between these two populations has yet to be clarified. CBA/N mice are deficient in both populations but the sessile one appears to be more severely depleted.

Animals↗

The ontogeny of pulmonary alveolar macrophages in parabiotic mice.

A bilateral distribution of labeled blood monocytes was achieved by unilaterally labeling donor members of surgically parabiosed B6D2F1/J mice with tritiated thymidine (3HTdR). Labeled pulmonary alveolar macrophages (PAM) were found in lung lavage fluid of donors. By contrast, no labeled PAM were found in lung lavage fluid from unstimulated recipients, even 12 days after labeling. Contralateral 3HTdR flash labeling showed that in recipients 3%, or about 10(4), PAM were in S phase of the cell cycle. Contralateral intratracheal challenge of recipient members with either Corynebacterium parvum vaccine or with Salmonella typhimurium lipopolysaccharide induced the emigration of labeled blood monocytes of donor origin into recipient alveoli. These data show that in parabiotic mice, blood monocytes do not regularly enter the alveolar compartment. It may be concluded that monocytes are not needed on a daily basis to sustain PAM populations.

Animals↗

In vivo 3D MRI staining of mouse brain after subcutaneous application of MnCl2.

Follow-up T(1)-weighted 3D gradient-echo MRI (2.35 T) of murine brain in vivo (N = 5) at 120 microm isotropic resolution revealed spatially distinct signal increases 6-48 hr after subcutaneous application of MnCl(2) (20 mg/kg). The effects result from a shortening of the water proton T(1) relaxation time due to the presence of unchelated paramagnetic Mn(2+) ions, which access the brain by systemic circulation and crossing of the blood-brain barrier (BBB). A pronounced Mn(2+)-induced signal enhancement was first seen in structures without a BBB, such as the choroid plexus, pituitary gland, and pineal gland. Within 24 hr after administration, Mn(2+) contrast highlighted the olfactory bulb, inferior colliculi, cerebellum, and the CA3 subfield of the hippocampus. The affinity of Mn(2+) to various brain systems suggests the neuronal uptake of Mn(2+) ions from the extracellular space and subsequent axonal transport. Thus, at least part of the Mn(2+) contrast reflects a functional brain response of behaving animals, for example, in the olfactory system. In vivo MRI staining of the brain by systemic administration of MnCl(2) may contribute to phenotyping mutant mice with morphologic and functional alterations of the central nervous system.

Animals↗

Bacterial invasion and transcytosis in transfected human brain microvascular endothelial cells.

Most cases of neonatal bacterial meningitis develop as a result of a hematogenous spread, but it is not clear how circulating bacteria cross the blood-brain barrier. Attempts to answer these questions have been hampered by the lack of a reliable model of the human blood-brain barrier. Human brain microvascular endothelial cells (HBMEC) were isolated and transfected with a pBR322 based plasmid containing simian virus 40 large T antigen (SV40-LT). The transfected HBMEC exhibited similar brain endothelial cell characteristics as the primary HBMEC, i.e. gamma glutamyl transpeptidase and a high transendothelial electrical resistance. Escherischia coli and Citrobacter spp, two important Gram-negative bacilli causing neonatal meningitis, were found to transcytose across primary and transfected HBMEC, without affecting the integrity of the monolayer. In addition, E. coli and C. freundii invaded transfected HBMEC as shown previously with primary HBMEC. We conclude that E. coli and C. freundii are able to invade and transcytose HBMEC and these bacterial-HBMEC interactions are similar between primary and transfected HBMEC. Therefore, our transfected HBMEC should be useful for studying pathogenesis of CNS infections.

Blood-Brain Barrier↗

Vascular permeability factor/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis.

This Chapter has reviewed the literature concerning VPF/VEGF as a potent vascular permeabilizing cytokine. In accord with this important role, microvessels have been found to be hyperpermeable to plasma proteins and other circulating macromolecules at sites where VPF/VEGF and its receptors are overexpressed, i.e., in tumors, healing wounds, retinopathies, many important inflammatory conditions and in certain physiological processes, such as ovulation and corpus luteum formation. Moreover, microvascular hyperpermeability to plasma proteins was shown to have an important consequence: the laying down of a fibrin-rich extracellular matrix. This provisional matrix, in turn, favors and supports the ingrowth of fibroblasts and endothelial cells which, together, transform the provisional matrix into the mature stroma characteristic of tumors and healed wounds. Finally, we have considered the pathways by which these and other circulating macromolecules cross the endothelium of normal and VPF/VEGF-permeabilized microvessels. These pathways include VVOs and trans-endothelial openings that have been variously interpreted as inter-endothelial cell gaps or trans-endothelial cell pores. At least some trans-endothelial cell pores may arise from VVOs. In conclusion, these data provide new insights into the mechanisms of angiogenesis and stroma formation, insights which are potentially applicable to a wide variety of disease states and which may lead to identification of new targets for therapeutic intervention.

Animals↗

Magnetic resonance angiography (MRA) of the circle of Willis: a prospective comparison with conventional angiography in 54 subjects.

We prospectively correlated the findings of magnetic resonance angiography (MRA) with those of transfemoral four-vessel angiography in 54 patients to investigate the direction of flow within the circle of Willis. Our primary goal was to assess the direction of flow using the size of the vessel and signal intensity, without saturation techniques. Analysis of the circle of Willis, especially the communicating arteries, was performed double-blind by two groups of two radiologists. Three types of arteries were identified: high flow or cross-cerebral circulation, patent and nonvisualised arteries. Cerebral angiography was the standard for comparison between the two methods. MRA did not reveal any arteries invisible on angiography, thus providing a specificity of 100%. The sensitivity of MRA was 89.2% for the anterior and 81.3% for the posterior communicating arteries, and 100% for the anterior, middle and posterior cerebral arteries. MRA was shown to be a useful technique for the assessment of patency of the circle of Willis.

Adolescent↗

Perfusion of dominant left subclavian artery during thoracic aortic aneurysm operation.

A case of aneurysm of the descending thoracic aorta with dominant left vertebral artery and poor cross-collateral circulation is reported. We believe that in such a patient perfusion of the dominant left subclavian artery is a safe method to prevent vertebrobasilar ischemia during thoracic aortic aneurysm operation under normothermia.

Aorta, Thoracic↗