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PubMed2005

Aneurysms of the posterior circulation: detection and treatment planning using volume-rendered three-dimensional helical computerized tomography angiography.

OBJECT: The aim of this study was to determine whether computerized tomography (CT) angiography could be used to identify and characterize aneurysms of the posterior circulation and guide optimal treatment selection, and how data obtained using this method compared with intraoperative findings. METHODS: Patients suspected of harboring brain aneurysms underwent CT angiography and digital subtraction (DS) angiography; the results were prospectively interpreted by blinded independent evaluators. All patients with posterior circulation aneurysms were consecutively enrolled in the study. After treatment, neurosurgeons and endovascular therapists evaluated the ability of CT and DS angiography to demonstrate features of the lesions important for triage between treatment options (Wilcoxon signed-rank test) and to allow for coil or clip preselection and complete treatment planning (McNemar test of proportions), while using intraoperative findings as the basis of truth. In 242 patients overall, CT angiography detected 38 aneurysms and two aneurysmal blisters in 32 patients. The sensitivity of CT angiography in revealing posterior circulation aneurysms was 100% compared with DS angiography, with no false-positive results. Furthermore, CT angiography was sufficient as the sole study at triage for 65% of the posterior circulation aneurysms (26 of 40 lesions; p < 0.001), including 62% of the complex lesions (p < 0.001), and permitted coil or clip preselection in 74% of treated cases (20 of 27 cases; p < 0.002). Results of CT angiography revealed information about mural calcification and intraluminal thrombus not available on DS angiography, which affected patient care. CONCLUSIONS: In this study population, CT angiography was comparable to DS angiography in the detection and characterization of aneurysms of the posterior circulation. Computerized tomography angiography was used successfully to triage patients between endovascular and neurosurgical treatment options in a significant proportion of cases and permitted treatment planning in more than 70% of treated cases.

Adult↗
PubMed1991

Red cell mechanics: what changes are needed to adversely affect in vivo circulation.

The ability of red cells to deform is essential to allow their circulation. However the degree of rheological abnormality which can be tolerated before flow is impaired is not so clear. Red cell rheology has been characterised in a number of physiological, pathological and genetic conditions, and some inferences can be drawn. In vivo aging causes a small loss of cell deformability attributable to increased membrane and internal viscosity; volume and surface area are also lost. These changes cannot be sufficient to cause cellular removal, since the cells sampled had continued to circulate. In sickle cell disease, the oxygenated blood contains dense cells that are more severely abnormal than dense, aged cells from normal individuals. Melanesian ovalocytes have comparable rigidity to dense SS cells, but this condition has no marked circulatory pathology. Thus circulatory problems in SS disease probably stem from deoxygenation-induced sickling which causes extreme loss of deformability, rather than from the abnormal cells in oxygenated blood. In falciparum malaria, immature parasites cause appreciable loss of deformability but continue to circulate. Maturation of the parasites causes much greater rheological changes, including attachment to vascular endothelium, and the cells cease to circulate. In summary, quite marked changes in cell mechanics can occur without loss of ability to circulate. It thus seems that slight rheological alterations reported in some clinical studies are unlikely to cause appreciable flow disruption.

Biomechanical Phenomena↗
PubMed2004

Monitoring the circulating levels of the HER2/neu oncoprotein in breast cancer.

The HER2/neu oncoprotein is a major target for the development of new cancer therapies and is similar to the estrogen receptor, which guides hormone therapy. The HER2/neu status is used to guide therapy decisions in patients with HER2/neu-overexpressing breast cancer tumors. The HER2/neu oncogene, or c-erbB-2, encodes a transmembrane receptor protein that is expressed on normal epithelial cells and can be overexpressed in breast cancer cells. Studies have shown that the extracellular domain (ECD) of the HER2/neu oncoprotein is released from the cell and can be measured in the circulation of women with breast cancer. Enzyme-linked immunosorbent assay methods used to measure the circulating HER2/neu ECD have shown that the prevalence of elevated ECD levels is approximately 18.1% in women with primary breast cancer and approximately 45.6% in women with metastatic breast cancer (MBC). Many studies have monitored the circulating ECD levels after surgery and indicate that increasing ECD levels can indicate recurrence of breast cancer earlier than clinical diagnosis. Studies in women with MBC showed that serial changes in circulating HER2/neu ECD levels paralleled the clinical course of disease, regardless of the treatment regimen. Several studies identified a subgroup of patients with MBC who had HER2/neu-negative disease by tissue testing but developed elevated ECD levels with MBC. In contrast to tissue testing, which is a one-time event, monitoring the circulating levels of the HER2/neu ECD in patients with breast cancer provides a real-time assessment of the HER2/neu status and provides important information for managing the therapy of patients with MBC.

Adult↗
PubMed1998

Measurement of circulating immunoreactive alpha-atrial natriuretic peptide in human plasma: validation and clinical application.

Recent evidence suggests that plasma alpha-atrial natriuretic peptide (alpha-ANP) may serve as a useful biochemical marker of severe heart failure, as circulating levels become ighly elevated. In the present study, a specific radioimmunoassay (RIA) protocol was adapted and optimised for rapid quantitative measurement of circulating alpha-ANP levels in plasma taken from clinically normal subjects and heart transplant recipients with no evidence of heart failure or heart transplant rejection. The plasma concentration of immunoreactive alpha-ANP in heart transplant recipients (115 +/- 10 pg/ml, n = 14) was significantly higher (p < 0.01) than in normal subjects (14 +/- 5 pg/ml, n = 20). Comparison of circulating plasma immunoreactive alpha-ANP levels obtained by the adapted assay to levels obtained by a standard RIA protocol revealed a significant correlation (r = 0.998, y = 1.004 x -2.94, n = 40). The adapted assay is simple, precise, and with a shorter incubation time that would enable results to be available within one working day. These results show that circulating biological active a-ANP levels are elevated in healthy heart transplant recipients with no evidence of heart failure; thus extending previous reports concerning the elevation in circulating alpha-ANP levels from patients with a wide range of heart disorders. The adapted RIA protocol would facilitate rapid detection and quantification of alpha-ANP in experimental research and routine clinical investigations.

Atrial Natriuretic Factor↗
PubMed1999

Application of immunodiagnostic assays: detection of antibodies and circulating antigens in human schistosomiasis and correlation with clinical findings.

In an initial cross-sectional survey, serum, urine, and stool samples were collected from 370 participants representing about 10% of the population (n = 4,438) in Behbeet village, 50 km south of Cairo, Egypt, an area well known to be endemic solely for Schistosoma haematobium. Diagnosis was approached in two parallel ways. The first approach, which simulated actual conditions in many endemic areas in Egypt, was based on physical examination and urine and stool microscopic analysis. The second approach was based on two advanced immunodiagnostic assay systems. One system detected antibodies to species-specific microsomal antigens, the other detected circulating schistosomal antigens. Microsomal antigens from S. haematobium and S. mansoni were used to detect antibodies in the Falcon assay screening test (FAST)-ELISA and the enzyme-linked immunoelectrotransfer blot (EITB). Circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) were quantified in serum and urine samples in a sandwich ELISA using monoclonal antibodies. Parasitologically, the prevalence of S. haematobium was 7.01% in females and 25.82% in males, giving an overall prevalence of 15.8%. The combination of urine CCA and serum CAA for detecting circulating antigens and the combination of the S. haematobium adult worm microsomal antigens (HAMA) FAST-ELISA and the HAMA EITB for detecting antibodies significantly improved the sensitivity of detecting S. haematobium circulating antigens and antibodies. Also, including a medical examination as an integral part of field studies and correlating immunodiagnostic results with other clinical and investigational data allowed us to calculate an accurate estimation of S. haematobium prevalence in this area of low endemicity.

Adolescent↗
PubMedDate not supplied

Preeclampsia: the endothelium, circulating factor(s) and vascular endothelial growth factor.

It has been proposed that endothelial cell activation is the primary event in the multisystem disorder of preeclampsia. Evidence for endothelial involvement in this condition abounds. The best-characterized morphologic abnormality of this syndrome, glomerular endotheliosis, involves endothelial cells. Also associated with preeclampsia is a loss of endothelial cell integrity, with the consequent increase in vascular permeability, and an increase in the circulating levels of the endothelial cell markers, fibronectin, von Willebrand factor, tissue plasminogen activator, and plasminogen activator inhibitor-1. It is now well documented that endothelial activation contributes to the coagulation abnormalities observed in this disease. There is much evidence that the endothelial alterations in preeclampsia result from one or more circulating factors. The incubation of cultured endothelial cells with serum or plasma samples, taken from normal pregnant women and women with preeclampsia, results in marked alterations in cell behavior and metabolic processes. More recently, experiments employing myographic techniques have demonstrated convincingly the effects of a circulating factor(s) on the function of endothelial cells of resistance arteries. Vascular endothelial growth factor (VEGF) possesses many of the characteristics required of a candidate circulating factor. It contains a hydrophobic secretory signal sequence, exerts in vitro effects specific to vascular endothelial cell, and promotes endothelial expression of procoagulant activity. Circulating VEGF concentrations are elevated in women with preeclampsia, and VEGF increases microvascular endothelial cell prostacyclin production in a dose-dependent manner, analogous to the acute effects of plasma from patients with preeclampsia. Similarly, in myographic studies, when myometrial resistance arteries are incubated with VEGF, there are dose-dependent alterations in endothelium-dependent behavior, mirroring those found after incubation with plasma from patients with preeclampsia.

Endothelial Growth Factors↗
PubMedDate not supplied

Allergen-specific IgE in circulating immune complexes in patients with inhalant allergy undergoing specific immunotherapy.

Specific immunotherapy (SIT) has been used worldwide since it was introduced near the beginning of this century. Although this mode of therapy has been known for over 80 years, its mechanism of action is still not definitely clear. The problem of the presence of allergen-specific IgE in IgE-containing circulating immune complexes of patients with inhalant allergy has been mentioned in the literature. However, there are no data concerning specific immunotherapy. The aim of our study was to evaluate the influence of SIT in patients with inhalant allergy on allergen-specific IgE in serum and in IgE circulating immune complexes. A total of 112 subjects with allergic rhinitis (57 with grass pollen allergy and 55 sensitive to house dust mites Dermatophagoides pteronyssinus) were included in the study. SIT was administered to 29 patients suffering from pollinosis and 27 patients sensitive to house dust mites. The remaining patients were treated with an H2-receptor antagonist only. The decrease of allergen-specific IgE concentration in IgE circulating immune complexes was parallel to the analogous changes in the serum only in the patients with pollinosis. Immunotherapy of house dust mite-sensitive patients caused a much slower decrease of allergen-specific IgE in circulating immune complexes than in serum. The binding index of allergen-specific IgE in circulating immune complexes increased during the course of the treatment. No significant associations were found between the immunological indices studied and clinical score of the disease activity.

Adolescent↗
PubMed1999

Elimination of cholesterol as cholestenoic acid in human lung by sterol 27-hydroxylase: evidence that most of this steroid in the circulation is of pulmonary origin.

Human alveolar macrophages have exceptionally high capacity to convert cholesterol into 27-hydroxycholesterol and cholestenoic acid by the sterol 27-hydroxylase mechanism. It is shown here that the human lung has a higher content of 27-hydroxycholesterol relative to cholesterol than any other organ. In order to evaluate the importance of the sterol 27-hydroxylase mechanism for cholesterol homeostasis in the lung, the production of cholestenoic acid by human lung was investigated. Removal of one lung reduced the level of cholestenoic acid in the circulation by 48 +/- 4% (P < 0.005). The levels of cholestenoic acid in the pulmonary artery and in the pulmonary vein showed significant differences (P < 0.002) with higher levels in the pulmonary vein (108 +/- 16 and 104 +/- 16 ng/mL, respectively). This corresponds to a net flux of cholestenoic acid from the lung of about 14 mg/day, which is more than 80% of the reported removal of this oxysterol and its metabolites from the circulation by the liver per day. Bypassing the lung for 60 min led to a reduction in circulating cholestenoic acid (30%) that fits with a pulmonary origin when taking into account the half-life of cholestenoic acid. The level of circulating cholestenoic acid was found to be less in patients with different lung diseases. It is evident that most of the cholestenoic acid in the circulation is of pulmonary origin. The present results suggest that the sterol 27-hydroxylase in the lung is responsible for at least half of the total flux of 27-oxygenated cholesterol metabolites to the liver and that this enzyme system may be of importance for cholesterol homeostasis in the lung.

Cardiopulmonary Bypass↗
PubMed1999

The changes in circulating hepatocyte growth factor after partial hepatectomy in the baboon.

There is no established model of regenerative liver resection in the baboon, and no study comparing the circulating hepatocyte growth factor (HGF) response with the DNA synthetic response after liver resection. A mean 20% partial hepatectomy (PH) was performed in 19 baboons and a sham operation comprising liver mobilisation only was performed in 20 baboons. Blood HGF levels were measured up to 5 days after either procedure, using the human HGF enzyme-linked immunosorbent assay (ELISA) kit (Otsuka, Japan). The white cell count (WCC), aspartate transaminase (AST) and bilirubin were also measured. Liver regeneration, reflected by an increase in DNA synthesis, was determined from serial liver biopsies in 23 baboons, using a tritiated thymidine assay of liver thymidine kinase (TK). Liver resection and WCC had a significant influence on circulating HGF levels. There was a linear relationship between WCC and circulating HGF levels, which was independent of PH. For a constant value of WCC, resection produced a peaking of HGF over time, with the maximal levels occurring between 2 and 3 days, compared with the linear response in HGF in sham-operated baboons. Liver damage, as reflected by AST levels, was found to have no significant influence on circulating HGF levels. The 20% PH produced a significant increase in liver TK, with maximum levels evident between 2 and 4 days. Accordingly in this baboon model of PH the increase in biologically active, circulating HGF preceded the increase in liver DNA synthesis over 5 days. This observation supports the role of HGF in hepatocyte proliferation and as an initiator of liver regeneration, and suggests that further investigation into the potential endocrine action of HGF could be studied in this established liver regenerative primate model.

Animals↗
PubMed1999

Methods to avoid adverse effect of circulating antigen on biodistribution of 125I-labeled antiTac dsFv: preinjection of intact antibody versus clearance of antigen with adivin-biotin system.

UNLABELLED: The presence of circulating antigen may adversely affect the biodistribution of a radiolabeled antibody. The alpha subunit of the interleukin-2 receptor (IL-2Ralpha) is a cell-surface receptor that is overexpressed in various hematologic malignancies and in benign disorders. This receptor is cleaved from the cell surface and can be found in high concentrations in serum. Radiolabeled antiTac antibodies are being evaluated to target this receptor. Previous studies have shown that circulating soluble IL-2Ralpha (slL-2Ralpha) adversely affected the biodistribution of radiolabeled antiTac disulfide-stabilized (ds)Fv. In this study, we compared blocking and clearing sIL-2Ralpha to see which better minimized its interference with the biodistribution of radiolabeled antiTac dsFv. METHODS: Two models of sIL-2Ralpha were used: one consisted of mice given intravenous sIL-2Ralpha and the other consisted of mice bearing SP2/Tac tumor xenografts (IL-2Ralpha positive), which shed sIL-2Ralpha. We biotinylated humanized antiTac monoclonal antibody (bt-HuTac) and radiolabeled it with 125I. We then compared its biodistribution with that of humanized antiTac monoclonal antibody IgG (HuTac). We examined the biodistribution of an injected dose of 125I-labeled antiTac dsFv after a preinjection of HuTac to block the sIL-2Ralpha epitope and after a preinjection of bt-HuTac, followed by an avidin chase. RESULT: The 125I-labeled bt-HuTac cleared from the serum at a rate similar to that of HuTac. The avidin chase effectively cleared >92% of circulating 125I-labeled bt-HuTac within 20 min and was also effective in clearing sIL-2Ralpha. In comparison, HuTac prolonged the retention of 125I-labeled sIL-2Ralpha in the circulation, and the avidin chase decreased 125I-labeled sIL-2Ralpha to <18% of control. Although the two-step antigen-clearing system effectively cleared the antigen from the circulation and improved the biodistribution of 125I-labeled dsFv, the HuTac preinjection method had a similar but longer lasting beneficial effect on 125I-labeled dsFv biodistribution. CONCLUSION: Preinjection of either HuTac or bt-HuTac with avidin chase improved the biodistribution of subsequently administered 125I-labeled antiTac dsFv by preventing the dsFv from binding to the sIL-2Ralpha, but the HuTac blocking method is simpler and longer lasting.

Animals↗
PubMed1999

Is dialysis membrane type responsible for increased circulating adhesion molecules during chronic hemodialysis?

BACKGROUND: Patients with chronic renal failure under maintenance hemodialysis (HD) present with numerous adverse effects including immunologic alterations. Serious abnormalities of neutrophil function have been reported to be associated with disturbed cell adhesiveness. These adhesion processes are mediated by cytokines and different adhesion molecules. PATIENTS AND METHODS: In this study, serum concentrations of the intercellular adhesion molecule ICAM-1, vascular cell adhesion molecule VCAM-1 and endothelial leukocyte adhesion molecule E-selectin were investigated during employment of different dialysis membranes (cuprophane: n = 23, cellulose: 8, polysulfone: 26, acrylonitrile: 7). These adhesion parameters from 64 patients before and after a hemodialysis session were investigated parallel to the serum levels of circulating cytokines and their inhibitors. RESULTS: Circulating ICAM-1 levels were not elevated in low-flux membranes and most of the high-flux HD membranes, except for one high-flux polysulfone membrane. cVCAM-1 levels were significantly elevated both in low- and high-flux dialysis membranes, whereas cE-selectin was not increased. cICAM-1 levels were not different before and after hemodialysis in the entire study group. In contrast, cVCAM-1 and cE-selectin levels increased significantly during HD in the entire study group (both p < 0.001). Serum levels did not correlate with the duration of end-stage renal failure and hemodialysis. Levels of circulating cytokine antagonists/inhibitors (Il-lra, Il-2R, TNFsRp55/75) were significantly increased in all patients before and after HD, whereas the serum concentrations of the corresponding circulating cytokines (I1-1beta, Il-1, TNF-alpha) were within normal ranges. CONCLUSION: Increased levels of cVCAM-1 which suggest an important role for immunological alterations in HD and cytokine-independent changes during HD sessions in all membranes without alterations of cICAM-1 in most membranes and unchanged cE-selectin indicate that processes such as uremia are responsible for these effects rather than membrane characteristics. The level of circulating adhesion molecules does not serve as an appropriate marker of membrane biocompatibility.

Acrylonitrile↗
PubMed2000

Circulating HER2 extracellular domain and resistance to chemotherapy in advanced breast cancer.

To test the hypothesis of an association between HER2 and chemotherapy resistance, we performed a prospective assessment of the predictive value of the circulating HER2 extracellular domain (ECD) in patients with advanced breast carcinoma in the setting of a multicenter Phase II trial using paclitaxel and doxorubicin. Serum samples were collected from 58 patients with metastatic breast carcinoma before first-line chemotherapy for advanced disease, and the levels of circulating HER2 ECD were measured using an enzyme immunoassay. Immunohistochemistry with anti-HER2 monoclonal antibody CB11 was used to assess the overexpression of HER2 in the primary tumors. When 450 fmol/ml was used as a cutoff, 24 cases (41%) had elevated HER2 ECD levels. Elevated levels of circulating HER2 ECD were associated with the expression of HER2 in the primary tumor tissue and with the metastatic tumor burden (evaluated with the marker CA 15-3; P = 0.032 and P = 0.002, respectively) but not with variables such as menopausal status, stage at diagnosis, previous adjuvant therapy, or the number of metastatic sites. The levels of circulating HER2 ECD correlated inversely with the response to treatment. The probability of obtaining a complete response to chemotherapy was significantly lower (P = 0.021) in patients with elevated HER2 ECD levels (0%; 95% confidence interval, 0-13%) compared with patients with nonelevated HER2 (26%; 95% confidence interval, 12-45%). In addition, the duration of clinical response was significantly shorter in patients with elevated HER2 ECD, compared with the cases with nonelevated HER2 (7.5 versus 11 months; P = 0.035). In conclusion, elevated levels of circulating HER2 ECD in patients with metastatic breast cancer correlate with reduced efficacy of a paclitaxel-doxorubicin chemotherapy combination. We suggest that the poor response rate associated with HER2 expression in advanced breast cancer may not be reversed by aggressive chemotherapy alone.

Antibodies, Monoclonal↗
PubMed2000

Identification of novel circulating human embryonic blood stem cells.

Using murine models, primitive hematopoietic cells capable of repopulation have been shown to reside in various anatomic locations, including the aortic gonad mesonephros, fetal liver, and bone marrow. These sites are thought to be seeded by stem cells migrating through fetal circulation and would serve as ideal targets for in utero cellular therapy. In humans, however, it is unknown whether similar stem cells exist. Here, we identify circulating hematopoeitic cells present during human in utero development that are capable of multilineage repopulation in immunodeficient NOD/SCID (nonobese diabetic/severe combined immunodeficient) mice. Using limiting dilution analysis, the frequency of these fetal stem cells was found to be 1 in 3.2 x 10(5), illustrating a 3- and 22-fold enrichment compared with full-term human cord blood and circulating adult mobilized-peripheral blood, respectively. Comparison of in vivo differentiation and proliferative capacity demonstrated that circulating fetal stem cells are intrinsically distinct from hematopoietic stem cells found later in human development and those derived from the fetal liver or fetal bone marrow compartment at equivalent gestation. Taken together, these studies demonstrate the existence of unique circulating stem cells in early human embryonic development that provide a novel and previously unexplored source of pluripotent stem cell targets for cellular and gene-based fetal therapies. (Blood. 2000;96:1740-1747)

ADP-ribosyl Cyclase↗
PubMed2000

[Circulation of the poliovirus in endemic zones with children vaccinated by the oral polio vaccine].

Strategies aiming to eradicate the poliovirus and poliomyelitis seek primarily to eliminate wild strains associated with the disease, by means of world wide vaccination campaigns using the oral attenuated vaccine (OPV). OPV contains attenuated viral strains which retain their replicating capacity in the digestive tract and thus induce the development of an antiviral local intestinal immunity and limit the circulation of the virus. In such a context, poliomyelitis surveillance laboratories should study above all cases of acute flaccid paralysis (AFP), highlighting the circulation of wild strains, identifying regional reservoirs and guiding vaccination strategies. Alongside circulation, there appear to be important genetic and phenotypic shifts in vaccinating strains, since the OPV is capable of preserving a reservoir of pathogenic stains and thereby impairing vaccination efficacy and the eradication of the virus. Furthermore, non-polio enteroviruses should be considered as a source of emerging pathogenic strains. These questions are being studied by the Pasteur Institute with the objective of determining the effects of OPV campaigns on the circulation of the poliovirus. We have studied the poliovirus vaccine and the circulation of wild strains in urban and peripheral urban areas in African countries known to be endemic for poliomyelitis (Central African Republic, Madagascar, Côte d'Ivoire). The study population consisted of children who had already been vaccinated and new-borns in the course of vaccination. We also evaluated the diffusion of the vaccine strains in their immediate environment. Genetic interchanges were taken into account. For children who received the 3-4 OPV doses, asymptomatic virus excretion was insignificant (0.4-2.4%). The rate of virus excretion in the surrounding environment of children in the course of being vaccinated was relatively low (1.76-5.3%). Our study also detected variant and recombinant strains.

Central African Republic↗
PubMed2001

Oxysterols in the circulation of patients with the Smith-Lemli-Opitz syndrome: abnormal levels of 24S- and 27-hydroxycholesterol.

Infants with the cholesterol synthesis defect Smith- Lemli-Opitz syndrome (SLO) have reduced activity of the enzyme 7-dehydrocholesterol-7-reductase and accumulate 7-dehydrocholesterol, with the highest concentration in the brain. As a result of the generally reduced content of cholesterol, plasma levels of oxysterols would be expected to be reduced. 24S-hydroxycholesterol is almost exclusively formed in the brain, whereas 27-hydroxycholesterol is mainly formed from extrahepatic and extracerebral cholesterol. In accordance with the expectations, sterol-correlated plasma levels of 24S-hydroxycholesterol were reduced in infants with SLO (by about 50%). In contrast, the sterol-correlated levels of 27-hydroxycholesterol in the circulation were markedly increased. No side-chain oxidized metabolites of 7-dehydrocholesterol were detected in the circulation. Recombinant human CYP27 had markedly lower 27-hydroxylase activity toward 7-dehydrocholesterol than towards cholesterol. HEK293 cells expressing 24S-hydroxylase active toward cholesterol had no significant activity towards 7-dehydrocholesterol. The plasma levels of 3 beta,7 alpha-dihydroxy-5-cholestenoic in the patients acid were reduced, suggesting a generally reduced metabolism of 27-oxygenated steroids. It is concluded that the accumulation of 7-dehydrocholesterol in the brains of patients with SLO reduces formation of 24S-hydroxycholesterol. The condition is associated with markedly increased circulating levels of 27-hydroxycholesterol, most probably due to reduced metabolism of this oxysterol. We discuss the possibility that the circulating levels of 24S-hydroxycholesterol may be used as a marker for the severity of the disease.--Björkhem, I., L. Starck, U. Andersson, D. Lütjohann, S. von Bahr, I. Pikuleva, A. Babiker, and U. Diczfaulsy. Oxysterols in the circulation of patients with the Smith-Lemli-Opitz syndrome: abnormal levels of 24S- and 27-hydroxycholesterol. J. Lipid Res. 2001. 42: 366--371.

Adolescent↗
PubMed1978

Retinal oxygenation via the choroidal circulation.

The possibility of supplying normal amounts of oxygen to the inner layers of the retina by diffusion from the choroid in the presence of retinal arterial obstruction was studied in cats and rhesus monkeys. While the animals were under general anesthesia, an oxygen electrode was placed in the vitreous cavity immediately adjacent to the retina, and a retinal artery blocker probe was used to occlude various segments of the retina blood supply. The inspired oxygen concentration was alternated between 20% and 100%. The choroidal circulation was intermittently occluded by elevating the intraocular pressure. In all animals it was possible to return the oxygen tension of the innermost retina to normal concentrations or above while the retinal arterial circulation alone was occluded, by having the animal breathe 100% oxygen at one atmosphere pressure. This could not be done when the intraocular pressure was elevated to 85 mm Hg, occluding the choroidal as well as the retinal circulation. The electroretinogram and the visually evoked response were recorded in cats while the retinal circulation was occluded and the inspired oxygen concentration changed from 20% to 100% at one atmosphere pressure. The electroretinogram and the visually evoked response were extinguished by occluding the retinal circulation while the animal was breathing 20% oxygen, and these responses were returned to normal by changing to a 100% inspired oxygen concentration.

Animals↗
PubMed1997

Myocardial Revascularization in Patients 70 Years of Age and Older Without the Use of Extracorporeal Circulation.

Myocardial revascularization in elderly patients (i.e., over 70 years of age) is associated with higher incidence of morbidity and mortality compared with younger patients. We herein report our experience on myocardial revascularization in the elderly comparing the results between 2 groups; one operated on with the aid of cardiopulmonary bypass and the other group in whom extracorporeal circulation was not used. The records of 265 elderly patients ( at or above 70 yrs) undergoing myocardial revascularization were prospectively analyzed between January 1994 and December 1995. Mean age was 74 Â+/- 6 years (range 70-95 yrs), with 83 (31.3%) females and 182 (68.7%) males. The following were the preoperative diagnoses: chronic ischemia and angina (186 patients), reoperation (28 patients), unstable angina (26 patients), failed angioplasty (13 patients), post-thrombolytic therapy (7 patients), cardiogenic shock (2 patients), evolving myocardial infarction (2 patients), and aortic dissection (1 patient). Extracorporeal circulation was used in 204 (76.9%) patients (Group I) and no extracorporeal circulation was used in 61 (23.1%) patients (Group II). The overall mortality was 6.4%, with 7.8% (16/204) in Group I and 1.6% (1/61) in Group II. Hospital stay was 11.4 days in Group I and 7.1 in Group II. Transfusion requirements were 1.4 and 0.6 units for Groups I and II, respectively. The use of extracorporeal circulation in the elderly is a major cause of morbidity and mortality following myocardial revascularization. Whenever possible, myocardial revascularization in the elderly should be performed without the use of extracorporeal circulation.

Journal Article↗
PubMed2001

Early changes of bone histology and circulating markers of bone turnover after parathyroidectomy in hemodialysis patients with severe hyperparathyroidism.

AIMS: There have so far been no reports on the changes in bone histology in the early period after parathyroidectomy and autografting (PTX-AG). We investigated the effects of PTX-AG on bone histology during the initial 12 weeks after undergoing these surgical procedures. MATERIALS AND METHODS: We performed bone histomorphometry 3 times (before as well as 4 and 12 weeks after PTX-AG) in 6 patients and 2 times (before and 4 weeks after PTX-AG) in 3 hemodialysis patients. In addition, the circulating parameters of bone metabolism were also assessed before and after PTX-AG in all 9 patients. The changes in the histomorphometric (static) parameters between pre-surgery and 4 weeks after surgery and those between 4 weeks and 12 weeks after surgery were assessed by the t-test while changes in the circulating parameters of bone metabolism were analyzed by Friedman's test. RESULTS: Bone formation parameters including carboxy terminal propeptide of human type I procollagen (PICP), alkaline phosphatase (ALP) and intact osteocalcin (i-OC) were all extremely high before surgery. These parameters initially increased after PTX-AG and thereafter gradually declined. In contrast, the circulating bone resorption parameters including tartrate-resistant acid phosphatase (TRAP) and deoxypyridinoline (Dpyr) were also extremely high at baseline but markedly declined after operation. Osteoid-related parameters including osteoid volume (OV/BV), osteoid surface (OS/BS), and osteoid thickness (O.Th) all initially increased at 4 weeks after PTX-AG. In contrast, osteoblast surface (Ob.S/BS), osteoclast surface (Oc.S/BS), eroded surface (ES/BS), and fibrosis volume (Fb.V/TV) all decreased at 4 weeks after surgery, while Ob.S/BS decreased further at 12 weeks in cases 1-6. Although bone mineralization was ongoing at 4 weeks after surgery, both the mineral apposition rate (MAR) and bone formation rate (BFR) remained below the mean for normal individuals. CONCLUSIONS: The circulating bone formation parameters and osteoid-related parameters showed an initial increase after PTX-AG. The concomitant decline in the circulating bone resorption parameters reflected the reduction in bone resorption. BFR decreased, but bone mineralization did not stop after PTX-AG.

Acid Phosphatase↗