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The poor prognosis of ruptured intracranial aneurysms of the posterior circulation.

The first 48 hours after aneurysmal subarachnoid hemorrhage are critical in determining final outcome. However, most patients who die during this initial period are not included in hospital-based studies. We investigated the occurrence of subarachnoid hemorrhage in a population-based study to evaluate possible predictors of poor outcome. All patients diagnosed with aneurysmal subarachnoid hemorrhage between 1955 and 1984 were selected for analysis of mortality in the first 30 days using the medical record-linkage system employed for epidemiological studies in Rochester, Minnesota. One hundred and thirty-six patients were identified. The mean age of these 99 women and 37 men was 55 years. Rates for survival to 48 hours were 32% for the 19 patients with posterior circulation aneurysms, 77% for the 87 patients with anterior circulation aneurysms, and 70% for the 30 patients with a presumed aneurysm (p < 0.0001). Rates for survival to 30 days were 11%, 57%, and 53%, respectively, in these three patient groups (p < 0.0001). Clinical grade on admission to the hospital, the main variable predictive of death within 48 hours, was significantly worse in patients with posterior circulation aneurysms than in others (p < 0.0001). The prognosis of ruptured posterior circulation aneurysms is poor. The high early mortality explains why posterior circulation aneurysms are uncommon in most clinical series of patients with subarachnoid hemorrhage. The management of incidentally discovered intact posterior circulation aneurysms may be influenced by these findings.

Adolescent↗

Day-to-day fluctuation of schistosome circulating antigen levels in serum and urine of humans infected with Schistosoma mansoni in Burundi.

Day-to-day fluctuations of both circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) in serum and urine were examined simultaneously in a group of Schistosoma mansoni-infected individuals from Burundi and compared with each other and with fecal egg count fluctuations. Significant correlations were found between fecal egg counts and circulating antigens (CAA and CCA) and between circulating antigen levels in serum and urine samples. The cumulative percentage of positive results after three samplings was highest for urine CCA detection, followed by fecal egg counts, serum CCA, serum CAA, and urine CAA detection, respectively. It was demonstrated that circulating antigen levels in both serum and urine showed less fluctuation than fecal egg counts, except for urine CAA levels. The serum CAA detection assay in particular, although less sensitive in this low endemic area in Burundi, gave very constant measurements over a period of one week. Our results indicate that detection of circulating antigens in a single serum or urine sample provides a quantitatively more stable diagnosis of S. mansoni infection than fecal egg counts based on a single stool examination.

Adolescent↗

Mutated p53 in tumors, mutant p53 and p53-specific antibodies in the circulation in patients with gastric cancer.

The accumulation of mutated p53 in tumor cells results in the presence in the circulation of mutant p53 (p53m) and the production of p53-specific antibodies (p53Ab). We examined the relationships among these phenomena and analyzed their clinical implications in 62 patients with gastric cancer at various stages. Expression of p53 in tumors was studied by an immunohistochemical method and circulating p53m and p53Ab were quantitated with commercially available enzyme-linked immunosorbent assay kits. The detectable expression of p53 in tumors and circulating p53Ab was recognized in 28 (45.2%) and 7 (11.3%) of the 62 patients, respectively. The number of patients with higher levels of circulating p53m increased with the progression of the depth of cancer invasion. Patients with any positive findings for the three p53-related parameters had a poorer prognosis, and the difference was statistically significant in patients with p53Ab. When survival was analyzed in terms of the combination of the three p53-related parameters (detectable expression of p53 in tumor cells, high levels of p53m and p53Ab in the circulation), a significantly poorer prognosis was associated with an increase in the number of positive parameters. Analysis of p53 in tumor cells, together with analysis of circulating p53m and p53Ab, could improve the accuracy of prognosis in patients with gastric cancer.

Aged↗

Hapten concentrations in the circulation of animals actively immunized with hapten-protein conjugates.

Animals immunized with hapten-protein conjugates subsequently circulate high concentrations of hapten bound by antibody. The levels of hapten detected are capable of significantly reducing antibody titer in the sera immunized animals. In the case of steroid-protein conjugates, the main source of increased plasma steroid concentration is the immunizing conjugate, although a contribution from increased host secretion may also occur. The results for rabbits immunized with digoxin-BSA indicate that the appearance of circulating digoxin followed the appearance of circulating antibody to digoxin. Appearance of digoxin in circulation appears to coincide with the operation of the immune response and may be related to macrophage activity. Similar conclusions are drawn from results obtained for circulating morphine in the serum of a sheep immunized with morphine-BSA. Injected hapten-protein antigens are probably processed by macrophage to produce low molecular weight haptenic fragments which are maintained in circulation for prolonged periods in the form of antibody-hapten complexes.

Animals↗

Interactions of follicular factors and season in the regulation of circulating concentrations of gonadotrophins in mares.

Follicle growth and associated changes in circulating hormone concentrations were evaluated after follicle ablation in mares (n = 13) during four 13 day periods beginning at means of -98.5, -61.4, -26.0 and 10 days from the first ovulation and corresponding to mid-anovulatory, early-transitional, late-transitional and ovulatory periods, respectively. During each period, all follicles > 5 mm in diameter were ablated (day 0) followed by no subsequent ablations (all-follicle group) or the ablation of all follicles > 5 mm when a new follicle reached > 10 mm (0-follicle group). A follicular wave emerged at means of days 1.5-2.5 in all mares of the all-follicle group during each period. Follicle activity increased between the mid-anovulatory and the transitional periods, as indicated by increases in the diameter of the largest follicle and the number of follicles in the all-follicle groups; nonetheless, there were no differences in the FSH concentrations of the wave-stimulating surge throughout the study. Circulating total inhibin increased between day 3 and day 6 in the all-follicle groups but not in the 0-follicle groups, and was higher during the late-transitional and ovulatory periods than during earlier periods in the all-follicle groups. In the all-follicle groups, circulating FSH decreased between day 3 and day 6. In the 0-follicle groups, FSH did not decrease and was higher during the late-transitional and ovulatory periods than during the mid-anovulatory period. Circulating LH was higher during the late-transitional and ovulatory periods than during earlier periods and was not different between the all-follicle and 0-follicle groups. On the basis of temporal relationships, it was concluded that the follicles of a wave secreted inhibin during all periods and the follicular inhibin suppressed circulating FSH. An increase in circulating inhibin induced by the growth of follicles > 21 mm in diameter during the late-transitional and ovulatory periods counteracted a stimulatory effect on FSH mediated by season.

Animals↗

[Ischemic insult in the anterior and posterior cerebral circulation].

In the everyday practice among clinical and etiological classifications for ischemic stroke, the terms strokes in the anterior and posterior cerebral circulation are also in use. The aim of this study was to analyze the frequency of ischemic strokes in the anterior and posterior circulation, their age and sex distribution, risk factors and hospital mortality. In the study it was analyzed 1772 patients with acute ischemic stroke hospitalized at the Department of Neurology Tuzla, Bosnia and Herzegovina, between January 1st 1996 and December 31st 2000. The mean age was 65.5 years (+9.9), 942 (55%) were females. Ischemic strokes for all patients were confirmed with computed tomography, while other data were collected from the standard patients' history charts. Anterior circulation stroke (ACS) had 1408 patients (81.8%), the rest of 314 (18.2%) had posterior circulation stroke (PCS). In the both types females were slightly overrepresented: 784 (56%) in ACS, and 158 (50.5%) in PCS. Moreover, females were significantly older than males: 67 (+9.8) versus 64 (+10) years in ACS (p < 0.001), 67.5 (+10.3) versus 63.5 (+9.2) in PCS (p < 0.001). Hypertension was the major risk factor occurring in 67% patients with ACS and 71 with PCS; heart diseases 54% in the both types, and diabetes in 23% patients with ACS and 20% with PCS. The cortical ischemic lesion was verified in 46% patients with ACS, 41% with PCS; subcortical in 12.5% and 14.5%; and lacunar in 41.5% and 44.5%, respectively. Hospital mortality was 30% (430 patients) for ACS, and 32% (101 patients) for PCS. Hospital mortality was considerably higher among females: 33% versus 28% for ACS (p = 0.03), 38% versus 27% for PCS (p = 0.03). On the basis of our study we can conclude that ischemic strokes in the anterior cerebral circulation are 4/5 of all ischemic strokes at the Department of Neurology Tuzla. Both, anterior and posterior circulation strokes are more frequent in females, witches were in average older than males. The cortical lesion dominated in ACS, and lacunar in PCS. The distribution of risk factors (hypertension, heart diseases, and diabetes) is similar for ACS and PCS, and hospital mortality also; however, mortality rate is higher in females.

Aged↗

[Frequency and function decrease of circulating type 2 pre-dendritic cells (pDC2) and its clinical significance in liver cirrhotic patients with chronic HBV infection].

OBJECTIVE: To identify the frequency and interferon (IFN)-alpha-producing ability of circulating type 2 pre-dendritic cells (pDC2) and evaluate its role in liver cirrhotic patients with chronic HBV infection. METHODS: 27 liver cirrhotic patients were included in our study and 25 patients with chronic hepatitis B and 25 healthy individuals were enrolled as controls. The numbers of circulating pDC2 and lymphocytes including CD4+ T cells, CD8+ T cells, NK cells as well as B cells were analyzed by flow cytometry. The IFN-alpha-producing function of peripheral blood mononuclear cells (PBMCs) representing the circulating pDC2 was determined by ELISA assay after stimulated by ultraviolet-inactivated herpes simplex virus-1 (UV-HSV-1). RESULTS: The number of pDC2 were (7.21+/-2.38)*10(6)/L, (4.49+/-3.08) *10(6)/L and (2.89+/-1.17) *10(6)/L for healthy control, chronic hepatitis B and cirrhotic patients respectively. Both the number and IFN-alpha-producing function of circulating pDC2 in liver cirrhotic patients significantly lower than that in healthy subjects. There was a correlated simultaneous decrease numbers of circulating CD8+ T cells, NK cells in HBV-infected cirrhotic patients. Furthermore, cirrhotic patients with opportunistic infections have lower numbers of pDC2, CD8+ T cells and NK cells compared to those without opportunistic infections. CONCLUSIONS: Liver cirrhotic patients with chronic HBV infection have a significant decrease of circulating pDC2 level and IFN-alpha-producing function. The decreased number and function of pDC2, together with the lower number of CD8+ T cells and NK cells may result in the decline of host immune response, which may partially contribute to the disease progression of HBV infection and opportunistic infections.

Cell Count↗

[A study of association between age-related circulating endothelial progenitor cells and arterial elasticity].

OBJECTIVE: Reduced arterial elasticity is a hallmark of aging in healthy humans independently of diseases and endothelial-cell injury and dysfunction may be responsible for this fall in arterial elasticity. We hypothesized that circulating endothelial progenitor cells (EPCs) are involved in endothelial repair and that lack of EPCs contributes to impaired arterial elasticity. METHODS: A total of 56 healthy male volunteers were divided into young (n = 26) and elderly (n = 30) groups. Large and small artery elasticity indices were non-invasively assessed by using pulse wave analysis. Flow cytometer was used to count the number of circulating CD34(+) mononuclear cells (MNCs), which were isolated from peripheral blood by Ficoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture dishes. EPCs were characterized as adherent cells double positive staining for DiI-acLDL uptake and lectin binding with using fluorescent microscope. RESULTS: C(1) (large artery elasticity index) and C(2) (small artery elasticity index) were significantly reduced in the elderly group compared with those in the young group (11.73 +/- 1.45 vs 16.89 +/- 1.69 ml/mm Hg x 10, P < 0.001; 8.40 +/- 1.45 vs 10.58 +/- 1.18 ml/mm Hg x 100, P < 0.001 respectively). In parallel, the number of circulating EPCs was significantly reduced in the elderly group compared with the young group (0.13 +/- 0.02 vs 0.17 +/- 0.04%, P < 0.05). The number of circulating EPCs correlated with C(1) large and C(2) small artery elasticity indices (r = 0.47, P < 0.01; r = 0.4, P < 0.01). Fluorescent microscope was used to identify EPCs, which were double positive staining for DiI-acLDL uptake and lectin binding. CONCLUSION: The present findings suggested that the fall in circulating EPCs with subsequently impaired endothelial-cell repair and function might contribute to reduced arterial elasticity in humans with aging. The decrease in circulating EPCs could serve as a surrogate biologic measure of vascular function and human age.

Adult↗

Circulating angiotensin converting enzyme activity is correlated with muscle strength.

PURPOSE: The D-variant of the angiotensin-1 converting enzyme (ACE) gene is associated with higher circulating and tissue ACE activity. Some studies have suggested a similar association of genotype with muscle strength or the gain in strength in response to training. This study has assessed the relationship between circulating ACE activity, strength, and the response to training. METHODS: Eighty-one untrained men were tested for quadriceps muscle strength, and 44 of these performed an 8-wk program of dynamic strength training of the quadriceps muscle group. Venous blood was obtained for assessment of circulating ACE activity before and after the training program. ACE genotype was also determined. RESULTS: At baseline, circulating ACE activity was significantly correlated with isometric (r = 0.25-0.29, P < 0.02) and isokinetic (r = 0.38, P < 0.0005) quadriceps muscle strength. ACE genotype also seemed to be related to pretraining muscle strength. However, circulating ACE activity showed no significant association with the 9-14% mean increases of muscle strength in response to the training intervention. ACE genotype also showed no association with the training-induced change in muscle strength. Circulating ACE activity did not change significantly after the training program. CONCLUSIONS: The data support a role for ACE in the regulation of human skeletal muscle strength, but do not confirm a role in altering the response to short-term training.

Adolescent↗

[Preparation of 8-chloro-adenosine long circulation liposomes and its pharmacokinetics in rats].

AIM: To prepare 8-chloro-adenosine (8-Cl-A) long circulation liposomes with high entrapped efficiency and prolonged action-time of 8-Cl-A in vivo. METHODS: To prepare 8-Cl-A long circulation liposomes of nanometer size by improved multiple emulsion. The entrapped efficiency, size and size distribution of 8-Cl-A long circulation liposomes were determined, and its pharmacokinetics in rats was evaluated. RESULTS: The entrapped efficiency of 8-Cl-A long circulation liposomes was 62.70% and mean diameter of the liposomes was 79.9 nm. The pharmacokinetics studies indicated that 8-Cl-A long circulation liposomes showed higher drug concentration and larger AUC values than that of 8-Cl-A after iv to rats. CONCLUSION: 8-Cl-A long circulation liposomes could prolong the action-time of 8-Cl-A in vivo.

2-Chloroadenosine↗

Recombinant human C5a-induced bronchoconstriction in the guinea pig: inhibition by an H1 antagonist after depletion of circulating granulocytes and platelets.

Recombinant human C5a (rHuC5a) causes an intense bronchoconstriction very quickly after i.v. injection into the guinea pig. In addition, it causes a biphasic blood pressure response characterized by a small hypotensive phase followed by a larger transient hypertensive phase. The overall goal was to determine the role of circulating cells in the bronchoconstriction and changes in blood pressure induced by rHuC5a. Intravenous injection of rHuC5a causes a transient granulocytopenia and thrombocytopenia, suggesting that these cells may be important targets of C5a action. However, the magnitude of granulocytopenia does not directly correlate with the magnitude of the bronchoconstriction, suggesting no direct connection between the events. Our studies continued to determine if depletion of circulating granulocytes and/or platelets altered the magnitude of, or the participation of histamine in, C5a-induced bronchoconstriction in the guinea pig. Selective depletion of circulating granulocytes, circulating platelets or both with specific antisera did not alter the severity, time of onset or duration of the rHuC5a-induced bronchoconstriction. The rHuC5a-induced hypertensive blood pressure response was significantly reduced only in guinea pigs depleted of just granulocytes. After depletion of both circulating granulocytes and platelets, histamine plays an important role in mediating the rHuC5a-induced bronchoconstriction as evidenced by the effectiveness of an H1 antagonist in inhibiting the response. This is in contrast to the ineffectiveness of the same H1 antagonist in inhibiting rHuC5a-induced bronchoconstriction in guinea pigs with normal numbers of circulating granulocytes and platelets or guinea pigs depleted of granulocytes only or platelets only.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Detection of circulating antigen in schistosomiasis by dot-ELISA with monoclonal antibody].

Circulating antigen in sera from acute, chronic and late stages of schistosomiasis patients was detected by direct dot-ELISA with monoclonal antibody 3D8A against schistosome gut-associated cathodic antigen linked with peroxidase, the positive rates being 90.6%, 83.2% and 30.7%, respectively. No positive reactions were found with sera from patients of clonorchiasis, malaria and non-parasitic diseases. The positive rate and the circulating antigen level in EPG greater than 100 group of patients were found to be higher than those in EPG less than 100 group. Circulating antigen became negative one year after praziquantel treatment in 84.0% of patients who showed negative fecal examination, while the other patients remained positive with decreasing titers. The results indicated that the circulating antigen in sera from schistosomiasis patients of various stages can be detected by dot-ELISA with monoclonal antibody 3D8A against circulating schistosome gut-associated cathodic antigen. The authors concluded that the circulating antigen level was correlated with the intensity of infection and the efficacy of treatment.

Animals↗

[Measurement of portal systemic circulation by oral and per-rectal administration of I-123 iodoamphetamine].

In an earlier study, we measured the portal circulation noninvasively by Tc-99m pertechnetate per-rectal portal scintigraphy. This method makes it possible to see the portal circulation and to diagnose portal hypertension from the images of the liver and heart. However, the method mainly reflects circulation from the inferior mesenteric vein, the contribution of which to the portal circulation is less than that of the superior mesenteric vein. Here, we devised capsules of I-123 iodoamphetamine (IMP) that dissolve when the pH changes to evaluate the portal circulation arising from the superior mesenteric vein. I-123 IMP enclosed in an enteric-coated capsule was prepared and given orally, just before I-123 IMP was injected into the rectum. The per-rectal portal shunt index (RSI) and oral portal shunt index (OSI) were calculated from the count of radioactivity of the liver and lungs. The RSI and OSI of patients with cirrhosis were both higher than those of the patients with chronic hepatitis. In individual patients, the RSI was higher than the OSI. This noninvasive method seemed to be useful in evaluation of the portal systemic circulation in chronic liver diseases.

Administration, Oral↗

PO2 profiles and oxygen consumption in cat retina with an occluded retinal circulation.

If the retinal circulation is occluded, the retina is forced to rely on the choroidal circulation for its oxygen supply. We have measured intraretinal PO2 profiles before, during, and after such an occlusion in cat. Oxygen-sensitive microelectrodes were used to measure intraretinal PO2, and the retinal circulation was occluded by means of a glass probe placed on the retinal vessels at the optic disk. Both air and 100% O2 breathing conditions were investigated. With the retinal circulation occluded, intra-retinal PO2 fell to zero within 60% of the distance through the retina, measured from the choriocapillaris to the internal limiting membrane. With the circulation occluded, but with breathing of 100% O2, PO2 rose throughout the retina so that values within the inner retina were as high or higher than for air breathing with the retinal circulation present. This meant that the whole retina could be supplied with adequate oxygen by breathing with 100% O2 in cat. From these PO2 profiles, oxygen flux and consumption were calculated as a function of distance through the retina. These calculations showed that the outer 20% of the retina had a consumption of 5.45 +/- 2.46 (SD) ml.min-1.100 ml-1 compared with a mean value for the remaining retina of 1.47 +/- 2.66 ml.min-1.100 ml-1. This difference was statistically significant (P less than 0.001) which indicates that there are at least two regions in the retina with different oxygen consumption.

Animals↗

Relationship of the quality and quantity of circulating anti-BSA antibodies to the severity of glomerulonephritis in rats with chronic serum sickness.

Chronic serum sickness glomerulonephritis, induced in hyperimmunized rats by daily intravenous administration of bovine serum albumin, occurs in three stages, mild, moderate and severe, with abrupt onsets and distinctive features of kidney pathophysiology and immunopathology. We have studied the relationship between circulating anti-BSA antibodies and the severity of glomerulonephritis at each stage. The total amount of antibodies declined gradually during the course of disease, to low concentrations in the most severe stage of kidney inflammation. High levels of immune complexes were present in the circulation while precipitating antibodies were maintained, and rats remained in the mill stage of disease, exhibiting no abnormalities of kidney function and only mesangial immunopathology. The start of the moderate stage of chronic serum sickness, identified by proteinuria and the accumulation of immune deposits along the glomerular basement membrane, was associated with the disappearance of precipitating antibodies from circulation. With the onset of the severe stage of disease, marked by depressed glomerular filtration and sodium excretion, circulating antibodies of high affinity were no longer detected and circulating immune complex levels were only marginally elevated above normal. The experiments reported here demonstrate that, in chronic serum sickness glomerulonephritis of rats, transitions from one stage of kidney disease to another can be inferred from changes in the population of circulating antibodies. Kidney histopathology, therefore, can be predicted reliably from serological data alone.

Animals↗

A simple method for detecting HIV antibodies hidden in circulating immune complexes.

A method previously used for studying the specificity of antibody components of circulating immune complexes in different diseases has been applied to analyse circulating immune complexes in HIV-infected patients. Antibodies against HIV antigens hidden in circulating immune complexes were studied in 14 sera from 13 patients with asymptomatic HIV infection (group 1) and in 11 sera from seven patients with HIV symptoms (group 2). HIV antigen-coated wells from the Vironostika kit as well as core and envelope antigen-coated beads from the Abbott confirmatory kit were used as solid-phase antigen. Using the Vironostika plates, HIV antibodies were demonstrated in circulating immune complexes in three and five sera in groups 1 and 2, respectively. Anti-core antibodies hidden in circulating immune complexes were present in three out of eight and two out of nine sera, respectively, in groups 1 and 2, whereas anti-envelope antibodies were present in circulating immune complexes in one out of eight and six out of nine sera in the same groups. These findings demonstrate that not only core-anti-core but also envelope-anti-envelope immune complexes are present in the sera of HIV infected patients.

Acquired Immunodeficiency Syndrome↗

Circulating membrane vesicles in leukemic blood.

Ultramicroscopic membrane vesicles were found in the plasma of 17 patients with certain types of leukemia (acute promyelocytic leukemia, acute monocytic leukemia, acute myelomonocytic leukemia, and chronic myelogenous leukemia) and in guinea pigs with the L2C leukemia. Labeled vesicles were cleared from normal guinea pig plasma according to a two exponential function with a half-life for the second exponent of greater than 11 h. By immunofluorescence, vesicles shared antigens with the L2C leukemic cells. Attempts to elucidate the cellular origin of the circulating vesicles in human leukemias were less definitive. However, vesicles did not react with the platelet membrane antigen GP IIb/IIIa nor did the presence of circulating vesicles or vesicle-associated procoagulant activity correlate with the platelet count. In three patients studied serially, circulating vesicles paralleled disease activity. Vesicles were not detected in 16 other patients with leukemias including acute myelogenous leukemia and most lymphoid leukemias. Similarly, vesicles were not present in 29 normal plasmas or in 10 plasmas from patients with solid tumors or nonmalignant hematological disorders. In contrast to vesicles of similar appearance shed by a variety of solid and ascites tumor cells in vitro and in vivo, the vesicles circulating in leukemia patients and guinea pigs expressed variable and generally weak procoagulant activity and no tissue factor activity. Thus, although many of the patients with circulating vesicles expressed abnormal coagulation, we were not able to establish a close pathogenetic relationship between the procoagulant activity of circulating vesicles and clinical coagulopathies.

Animals↗

[Circulating immune complexes in primo-secondary and serological syphilis (author's transl)].

Some clinical features of syphilis suggest that immune complexes may be a pathogenetic factor in the syphilitic lesions. Recently, circulating immune complexes have been reported in six patients with secondary syphilis by Søling et al. In our study, the presence of circulating immune complexes was investigated in 42 patients with syphilis (primary, secondary, serological) by the method of C1q binding test. Elevated C1q binding activity was demonstrated in two-thirds of the patients with primo-secondary syphilis, with a significant difference between this group and the controls. Only two of the 21 patients with serological syphilis showed elevated C1q binding activity. Circulating immune complexes, often at moderates rates, appear very early and decrease rapidly during treatment. It was not possible to demonstrate a decline in serum complement in association with elevated C1q binding activity. During five Jarisch-Herxheimer reactions, no increase in circulating immune complexes has been noticed compared to pre-treatment values: this suggests that circulating immune complexes have no essential importance in this reaction. The characterization of the components of these circulating immune complexes by the previously described "radioimmunoprecipitation PEG assay" (RIPEGA) will enable us to state their specificity and to conceive their potential responsibility in some lesions of secondary syphilis, such as nephrotic syndrome.

Adult↗