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Evaluation of arteriovenous crossing sheathotomy for branch retinal vein occlusion by fluorescein videoangiography and image analysis.

PURPOSE: We quantitatively evaluated the effects of arteriovenous (A/V) crossing sheathotomy on retinal circulation in patients with branch retinal vein occlusion (BRVO) accompanied by macular edema. DESIGN: Interventional case series. METHODS: In 18 consecutive patients (18 eyes) with BRVO accompanied by macular edema who underwent A/V crossing sheathotomy between August 1999 and April 2002, changes in retinal circulation after the surgery were evaluated by fluorescein videoangiography with a scanning laser ophthalmoscope and by image analysis using dye dilution technique. At a venule distal to the responsible A/V crossing site and a normal venule, the circulation time (T50) from the beginning of filling to 50% filling of the peak intensity was calculated. The time difference (DeltaT50) between T50 at the point on the affected venule and that at the point on the normal venule, which represents the filling delay at the venule distal to the A/V crossing site, was compared between before and early after the surgery. RESULTS: The preoperative DeltaT50 was 1.36 +/- 1.15 seconds (mean +/- SD), and the postoperative DeltaT50 was 0.72 +/- 0.77 seconds (P =.035, paired t test). In 11 of the 18 eyes, DeltaT50 decreased by 20% or more after the surgery. In the other 7 eyes, DeltaT50 was unchanged or slightly increased after the surgery. CONCLUSIONS: Although a randomized controlled study is needed to confirm the effectiveness of A/V crossing sheathotomy on visual function, this technique could be effective for improving the delay in perfusion in the affected venule.

Aged↗

Isoproterenol and propranolol: ability to cross the blood-brain barrier and effects on cerebral circulation in man.

Using the "double indicator" technique the ability of 3H-isoproterenol and 14C-propranolol to cross the blood-brain barrier was studied in man. In 3 subjects extraction of isoproterenol was 3.8% in a single passage and the PS product was 2.0 ml/100g/min. In 4 patients extraction of propranolol was 63% and PS was 46.7 ml/100/min. Regional cerebral blood flow (rCBF) was studied in man with the 133Xe-intraarterial injection method. Intracarotid isoproterenol (3 migrogram/min., 6 patients) caused a significant reduction in rCBF, but after correction for a concomitant decrease in arterial PCO2 the alteration was no longer significant (59.8 -51.7/57.4 ml/100g/min.). Intracarotid propranolol (0.15 mg/kg, 11 patients) caused no significant change in rCBF, but after correction for arterial PCO2 change the lateration although on 4% was just significant, p less than 0.05. (56.3 -55.8/54.1 ml/100g/min). After propranolol the rCBF changes caused by alterations in the arterial PCO2 were normal and the focal flow increase during hand work could not be changed by simultaneous intracarotid propranolol.

Adult↗

Demonstration of a cell wall antigen cross-reacting with cryptococcal polysaccharide in experimental disseminated trichosporonosis.

Patients with disseminated infections caused by Trichosporon beigelii have a circulating antigen that cross-reacts with the polysaccharide capsule of Cryptococcus neoformans. We studied the localization of this antigen by immunoelectron microscopy in a rabbit model of experimental disseminated trichosporonosis. Deparaffinized lung sections were examined by using a murine monoclonal anti-cryptococcal polysaccharide antibody and colloidal gold particles coated with goat antibody to murine immunoglobulin G. Antigen that cross-reacted with the monoclonal antibody was observed in the T. beigelii cell wall and in a fibrillar matrix extending from the cell wall.

Animals↗

Cross-linked bispecific monoclonal antibody heteropolymers facilitate the clearance of human IgM from the circulation of squirrel monkeys.

We have previously demonstrated that cross-linked bispecific monoclonal antibodies (mAb) heteropolymers (HP), specific for primate erythrocyte (E) complement receptor type 1 (CR1) and target antigen (Ag), facilitate the binding of these target Ag to human and non-human primate E. Once bound in vitro to rhesus monkey E, upon re-infusion these HP/Ag complexes are recognized in vivo by cells of the reticuloendothelial system (RES) and removed from the circulation without loss of the E. We now show, in squirrel monkeys, that an HP specific for E CR1 and human IgM (anti-CR1 x anti-IgM) can be used to facilitate in vivo E binding and clearance from the circulation of a previously injected and circulating model protein pathogen, human IgM. Approximately 70-80% of 125I-labeled human IgM is cleared from the circulation of each of five squirrel monkeys via the HP system. We observe, in experiments analogous to previous studies on immune complex (IC) clearance, that subsequent to HP/Ag clearance there is a decrease in the number of CR1 epitopes per E which is manifested when we use both monoclonal and polyclonal anti-CR1 probes. Our results indicate that the primary organs responsible for uptake of the complexes are the liver and spleen. This work strongly suggests that the HP/Ag complexes, bound to E, function as IC prototypes and are recognized and processed as such in vivo. Thus, the HP-E system may eventually serve as a viable immunotherapy for the clearance of blood-borne pathogens from the circulation.

Animals↗

Fibrin sealant improves surgical results of type A acute aortic dissections.

From January 1984 to July 1990, 63 patients were operated on for type A acute aortic dissection. Forty-two patients (aged 22 to 80 years) had isolated replacement of the ascending aorta with the following techniques: group 1 (n = 10) had replacement of the ascending aorta with an intraluminal sutureless graft, group 2 (n = 14) had a Dacron prosthesis sutured to the aorta, and in group 3 (n = 18) the proximal and distal aortic stumps were glued together and reinforced at the suture sites with fibrin sealant before implantation of the Dacron prosthesis. There were no significant differences between the three groups with respect to age, sex, or preoperative clinical and anatomical data. Three (30%) intraoperative deaths occurred in group 1, 4 (29%) in group 2, and none in group 3. Cross-clamp and extracorporeal circulation time were significantly lower in group 1 when compared with groups 2 and 3. Perioperative blood loss during the first 24 hours was significantly lower in group 3 (372 +/- 155 mL) when compared with group 1 (755 +/- 210 mL; p less than 0.05) or group 2 (1,055 +/- 370 mL; p less than 0.01). Total hospital mortality was 7 (70%) in group 1, 6 (43%) in group 2, and 1 (5.5%) in group 3. All patients were reviewed: one late death occurred in group 2 and none in the other groups. All survivors were in good clinical condition. In conclusion, intraluminal sutureless grafts allowed shorter cross-clamp and extracorporeal circulation time but did not improve surgical results for treatment of type A acute aortic dissections.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Apoptosis in fetal nucleated erythrocytes circulating in maternal blood.

The purpose of this study was to determine if apoptosis occurs in fetal cells that have crossed into the maternal circulation, which would potentially explain the difference between the number of intact fetal cells and the amount of fetal DNA detectable in maternal plasma. We flow-sorted fetal nucleated erythrocytes (FNRBCs) using antibody to the gamma chain of fetal haemoglobin and confirmed them to be fetal in origin by FISH analysis using chromosome-specific probes. Fetal cells were then analysed microscopically for the presence of terminal UdTP nuclear end labelling (TUNEL) staining. Apoptotic change was observed in 42.7% of fetal NRBCs (106/246) and 3.5% of maternal cells (29/818). Results of this study indicate that a significant number of fetal cells in maternal blood are undergoing apoptosis at the time of sampling. Apoptosis may be one mechanism by which fetal cells are cleared by the maternal circulation.

Adult↗

Circulating angiotensin converting enzyme levels are increased in concentric, but not eccentric, left ventricular hypertrophy in elderly men.

OBJECTIVE: To study the cross-sectional relationship between circulating angiotensin converting enzyme (ACE) activity and echocardiographically determined left ventricular geometry in a study of 380 70-year-old men participating in a health-survey reexamination and 50 patients with hypertension. METHODS: Two-dimensional guided M-mode and Doppler echocardiography. Fluorometric assay of serum ACE activity. RESULTS: The serum ACE activity was higher in the elderly men with left ventricular concentric hypertrophy than it was in men with normal geometry and left ventricular eccentric hypertrophy (32, 27, and 26 U/l, respectively, P < 0.01 for both comparisons before and after adjustment for the 24 h mean arterial pressure, body mass index, and use of antihypertensive medication). The serum ACE activity correlated with the thickness of the left ventricular interventricular septum (r = 0.12, P = 0.0095), the left ventricular relative wall thickness (r = 0.13, P = 0.0053 ), and the total peripheral resistance (r = 0.16, P = 0.0034), but not with the left ventricular mass (r = -0.039, P = 0.45) of these elderly men. The serum ACE activity in the hypertensive patients also correlated with the left ventricular interventricular septum thickness (r = 0.34, P = 0.020) independently of the 24 h mean arterial blood pressure, age, sex, body mass index, and insulin sensitivity. CONCLUSION: Levels of serum ACE activity are associated with left ventricular geometry.

Adult↗

Circulating immune complexes in Behçet's syndrome: purification, characterization and cross-reactivity studies.

The C1q-binding assay was performed on 30 sera from patients with Behçet's syndrome and circulating immune complexes were found in 46%. Circulating immune complexes were isolated and purified from the sera of two patients by immunoadsorption on a column of polymethylmetacrylate beads coated with C1q and then labelled with 125I. In double immunodiffusion these purified immune complexes were found to contain IgG, C1q, C1s and C3. Anti-IgG activity was not detectable in the purified immune complexes while specific cross-reactivity was found in a solid-phase radioimmunoassay with the majority of the sera of behçet's syndrome.

Antigen-Antibody Complex↗

Adjunctive growth hormone during ovarian hyperstimulation increases levels of insulin-like growth factor binding proteins in follicular fluid: a randomized, placebo-controlled, cross-over study.

GH increases circulating insulin-like growth factor I (IGF-I), which can promote the growth and differentiated function of ovarian granulosa and theca cells. Reported studies of GH as an adjunct to menotropin stimulation in women, largely those with ovarian dysfunction, have not consistently shown a benefit of GH, despite increases in serum and follicular fluid IGF-I. We hypothesized that changes in intrafollicular IGF-binding proteins (IGFBPs), which can antagonize IGF actions on granulosa cells, may underlie the inconsistent effects of GH. In the present study of GH, administered in double-blind, placebo-controlled, cross-over fashion to regularly cycling women undergoing in vitro fertilization, we found that follicular fluid levels of IGFBP-1, -3, and -4 and serum levels of IGFBP-3, as well as follicular fluid and serum IGF-I, were significantly increased in the GH-treated cycles, when compared with the placebo cycle of the same patient. We suggest that the net increase in intrafollicular IGFBPs in GH cycles may mitigate the potential beneficial effect of increased IGF-I.

Adult↗

The metabolic syndrome is associated with elevated circulating C-reactive protein in healthy reference range, a systemic low-grade inflammatory state.

OBJECTIVE: To elucidate the underlying mechanisms between C-reactive protein (CRP) and cardiovascular disease, we examined the association of circulating CRP in healthy reference range (< or =1.0 mg/dl) measured by high-sensitive CRP assay with the metabolic syndrome (MS). DESIGN: Cross-sectional study of circulating CRP in adult men. SUBJECTS: A total of 3692 Japanese men aged 34-69 y. MEASUREMENTS: Serum CRP, total cholesterol, triglycerides, LDL-cholesterol, fasting glucose, fasting insulin, uric acid, systolic blood pressure, diastolic blood pressure, and body mass index (BMI). RESULTS: There was a statistically significant positive correlation between CRP and BMI (r=0.25), total cholesterol (r=0.096), triglycerides (r=0.22), LDL-cholesterol (r=0.12), fasting glucose (r=0.088), fasting insulin (r=0.17), uric acid (r=0.13), systolic blood pressure (r=0.12), and diastolic blood pressure (r=0.11), and a significant negative correlation of CRP with HDL-cholesterol (r=0.24). After adjusting for age, smoking, and all other components of MS, obesity, hypertriglyceridemia, hyper-LDL-cholesterolemia, diabetes, hyperinsulinemia, and hyperuricemia were significantly associated with both mildly (> or =0.06 mg/dl) and moderately (> or =0.11 mg/dl) elevated CRP. Compared with men who had no such components of the MS, those who had one, two, three, four, and five or more components were, respectively, 1.48, 1.84, 1.92, 3.42, and 4.17 times more likely to have mildly elevated CRP levels (trend P<0.001). As for moderately elevated CRP, the same association was observed. CONCLUSIONS: These results indicate that a variety of components of the MS are associated with elevated CRP levels in a systemic low-grade inflammatory state.

Adult↗

Elevated circulating concentrations of platelet activating factor in preeclampsia.

OBJECTIVE: The aim of this study was to determine whether any association exists between preeclampsia and circulating platelet activating factor levels. STUDY DESIGN: We performed a cross-sectional observational study of circulating platelet activating factor concentrations in nonpregnant women, normotensive pregnant women in the third trimester, women with preeclampsia in the third trimester, and normotensive men. Platelet activating factor concentrations were measured with a commercially available platelet activating factor-specific radioimmunoassay (NEN Life Science Products, Inc, Boston, Mass). The primary outcome measure was the difference in mean platelet activating factor concentrations among the 4 study groups. Preeclampsia was determined according to the criteria of The American College of Obstetricians and Gynecologists. Data were analyzed with the Student t test, the chi(2) test, the Fisher exact test, analysis of variance, and the Tukey test for pairwise multiple comparisons, with significance established at P <.05. RESULTS: The mean (+/-SD) circulating concentration of platelet activating factor was significantly higher in the group with preeclampsia (338.1 +/- 26.9 ng/mL) than in either the normotensive pregnant group (217.9 +/- 25.9 ng/mL; P <.05) or the nonpregnant female group (237.9 +/- 20.9 ng/mL; P <.05). The 2 pregnant groups were similar with respect to selected demographic characteristics and gestational age at time of collection. There were no significant differences in the mean platelet activating factor concentrations between the group with preeclampsia and the normotensive male group or between the normotensive pregnant female group and the nonpregnant female group. CONCLUSION: Circulating platelet activating factor concentrations were increased in women with pregnancies complicated by preeclampsia with respect to those in normotensive pregnant women and normotensive nonpregnant women. Platelet activating factor may therefore serve as a marker for the risk of preeclampsia.

Adolescent↗

[Aortic arch replacement and elephant trunk method for thoracic aneurysm].

A 73-year-old female with ischemic heart disease and thoracic aneurysm from the ascending aorta to the descending aorta underwent coronary bypass and aortic arch replacement combined with the elephant trunk method with the aid of extracorporeal circulation and selective cerebral perfusion. The graft provided with four limbs for arch replacement was inverted in advance. The ascending aorta was cross-clamped following extracorporeal circulation. The anastmosis of the left internal thoracic artery to LAD was continuously performed by 8/0 prolene. As the elephant trunk 11 cm in length of the inverted graft was inserted into descending aorta after the arch and descending aorta were opened. The inverted end of the graft was sutured to the aorta beyond the origin of the left subclavian artery. The inverted end of graft with four limbs was then withdrawn. Brachiocephalic vessels were reconstructed during rewarming. The patient recovered well without any cerebral complications. Aortogram made after operation showing proximal aortic replacement and a segment dangling in the distal aneurysm surrounded with thrombus.

Aged↗

Monoclonal antibody assay for free urinary pyridinium cross-links.

The pyridinium cross-links of collagen, pyridinoline (Pyd) and deoxypyridinoline (Dpd), provide structural integrity and rigidity to collagen fibrils in bone. During bone degradation (resorption), the cross-links are released into the circulation and eventually excreted in urine. Pyridinium cross-link measurements in urine have been shown to be sensitive and specific indicators of resorption by both established HPLC and newer enzyme immunoassay (EIA) techniques. We have developed a monoclonal antibody that preferentially binds to the non-peptide-bound free forms of Pyd & Dpd. We have incorporated the antibody conjugated to alkaline phosphatase in a competitive EIA by using Pyd-coated microtiter strip wells. After a 3-h incubation of sample and antibody-enzyme conjugate, color is developed for 1 h with p-nitrophenyl phosphate as the substrate. The intraassay (n = 52) CVs were 3.0-7.6%, and interassay (n = 8) CVs were 6.1-7.4%. Comparisons of the assay (y) with HPLC (x) and a polyclonal antibody-based EIA (x') gave regression equations of y = 0.46x + 4, r = 0.96, and y = 0.56x' + 8, r = 0.96. The EIA detected increased Pyd & Dpd concentrations in urine from postmenopausal women and patients with osteoporosis, hyperthyroidism, hyperparathyroidism, and Paget disease of bone. EIA concentrations also reflected the reduction in Pyd&Dpd excretion resulting from estrogen replacement in surgically menopausal women. Measurement of pyridinium cross-links with this simple EIA appears to provide an accurate index of the rate of resorption and may be useful for metabolic bone disease assessment and monitoring the effects of antiresorptive therapy.

Adult↗

A potential inverse association between insulin-like growth factor I and hypertension in a cross-sectional study.

PURPOSE: Elevated circulating insulin-like growth factor I (IGF-I) levels increasingly are being implicated as a potential risk factor for the development of some cancers; however, relatively few epidemiologic studies have focused on potential relationships between circulating IGF-I levels and cardiovascular risk factors or cardiovascular disease. Hence, our objective is to examine relationships between IGF-I levels; body mass index (BMI); fasting insulin level; IGF binding protein 1 (IGFBP-1), IGFBP-2, and IGFBP-3 levels; and an array of traditional cardiovascular risk factors. METHODS: Our analysis included 715 men and women aged 30 to 62 years who participated in the Västerbotten Intervention Project cohort. IGF-I and IGFBP-1, -2, and -3 were measured in stored plasma samples. Cardiovascular risk factors of interest included glucose level (fasting and 2-hour postload), lipid levels (total cholesterol, high-density lipoprotein cholesterol, and triglycerides), blood pressure (systolic and diastolic), and hypertension status. All presented results were adjusted for age, sex, and laboratory batch. RESULTS: IGF-I quartile was associated inversely with 2-hour glucose level and diastolic blood pressure. There was a stepwise inverse graded association between increasing IGF-I quartile and hypertension, with an odds ratio of 0.51 (95% confidence interval, 0.29-0.90) for hypertension comparing the fourth IGF-I quartile with the first. Further adjusting for BMI and IGFBP-3 level simultaneously strengthened the inverse association, with an odds ratio of 0.42 (95% confidence interval, 0.22-0.80) for hypertension comparing the fourth with the first IGF-I quartile. CONCLUSIONS: Contrary to positive associations between IGF-I levels and some cancers, our results suggest that IGF-I level may be related inversely to prevalent hypertension, a risk factor for cardiovascular disease.

Adult↗

Increasing organ blood flow during cardiopulmonary bypass in pigs: comparison of dopamine and perfusion pressure.

OBJECTIVE: To determine whether low-dose dopamine infusion (5 micrograms/kg/min) during cardiopulmonary bypass selectively increases perfusion to the kidney, splanchnic organs, and brain at low (45 mm Hg) as well as high (90 mm Hg) perfusion pressures. DESIGN: Randomized crossover trial. SETTING: Animal research laboratory in a university medical center. SUBJECTS: Ten female Yorkshire pigs (weight 29.9 +/- 1.2 kg). INTERVENTION: Anesthetized pigs were placed on normothermic cardiopulmonary bypass at a 100-mL/kg/min flow rate. After baseline measurements, the animal was subjected, in random sequence, to 15-min periods of low perfusion pressure (45 mm Hg), low perfusion pressure with dopamine (5 micrograms/kg/min), high perfusion pressure (90 mm Hg), and high perfusion pressure with dopamine. Regional perfusion (radioactive microspheres) was measured in tissue samples (2 to 10 g) from the renal cortex (outer two-third and inner one-third segments), stomach, duodenum, jejunum, ileum, colon, pancreas, and cerebral hemispheres. MEASUREMENTS AND MAIN RESULTS: Systemic perfusion pressure was altered by adjusting pump flow rate (r2 = .61; p < .05). In the kidney, cortical perfusion pressure increased from 178 +/- 16 mL/min/100 g at the low perfusion pressure to 399 +/- 23 mL/min/100 g at the high perfusion pressure (p < .05). Perfusion pressure augmentation increased the ratio of outer/inner renal cortical blood flow from 0.9 +/- 0.1 to 1.2 +/- 0.1 (p < .05). At each perfusion pressure, low-dose dopamine had no beneficial effect on renal perfusion or flow distribution. Similar results were found in the splanchnic organs, where regional perfusion was altered by perfusion pressure but not by dopamine. In contrast, neither changing perfusion pressure nor adding low-dose dopamine altered blood flow to the cerebral cortex. CONCLUSIONS: These data indicate that the lower autoregulatory limits of perfusion to the kidneys and splanchnic organs differ from those limits to the brain during normothermic bypass. Selective vasodilation from low-dose dopamine was not found in renal, splanchnic, or cerebral vascular beds. Increasing the perfusion pressure by pump flow, rather than by the addition of low-dose dopamine, enhanced renal and splanchnic but not cerebral blood flows during cardiopulmonary bypass.

Animals↗

Responses of plasma "estradiol" and plasma LH to ovariectomy, ovariectomy plus adrenalectomy, and estrogen injection at various ages.

Plasma LH and "estradiol" were measured by radioimmunoassay in female rats 5, 10, 15, 20, 25, 30, 40, and 80 days of age, and the changes in these hormone levels 24 h after ovariectomy, ovariectomy plus adrenalectomy, and estrogen injection were determined. Plasma "estradiol" was high at 5 days of age; it increased further to a peak at 15 days of age, and declined thereafter to the low levels seen in adult rats. At each age, plasma "estradiol" declined about 50% 24 h after ovariectomy, whereas it fell to undetectable levels 24 h after ovariectomy plus adrenalectomy at 20 and 80 days of age. Plasma LH did not increase 24 h following ovariectomy at 5 days of age, but it did at all ages thereafter. The peak increase occurred 24 h after ovariectomy at 15 days of age, and the increment was progressively smaller at older ages. Ovariectomy plus adrenalectomy did not cause a significantly greater increase in plasma LH than ovariectomy alone. Injection of estradiol caused a decrease in plasms LH at all ages except in the animals ovariectomized at 5 days of age. The greatest decrease was seen in animals ovariectomized at 15 days of age, with a progressively smaller negative feedback response as age increased. In addition to providing systematic data on changes in the negative feedback effect of estradiol at various ages, the results indicate that, especially in immature animals, there is a circulating substance which cross-reacts with antibodies to estradiol but which does not appear to be a biologically-active estrogen. It does not come from the ovaries and disappears from the circulation if the adrenals as well as the ovaries are removed.

Adrenal Glands↗