Biological effects of endotoxin.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
J E Doran
Publications and source records attributed to J E Doran.
Current status of fibronectin in transfusion medicine: focus on clinical studies.
It has long been hypothesized that fibronectin (Fn) is essential to the function of the reticuloendothelial system (RES) and that the reversal of Fn deficiency in critically ill patients would result in a clinical benefit to these patients. Fn administration to deficient patients was postulated to improve the function of the RES, decrease the incidence of organ failure, sepsis and ultimately mortality. Over the past 15 years, several clinical studies have been performed to test these hypotheses. The initial anecdotal studies using cryoprecipitate (a plasma fraction enriched in Fn) revealed promising results but were neither controlled nor blinded. Further controlled studies were published utilizing both cryoprecipitate and purified Fn. Unfortunately, the great majority of authors found no beneficial effects of Fn administration in critically ill patients, in relation to incidence of organ failure, sepsis, or mortality. These results do not support the use of Fn in this setting. Fn utilization in wound healing has shown promising results in case reports. Although its role in wound healing is not yet fully delineated, initial reports with corneal wounds show a beneficial influence of Fn administration. Further studies are needed to determine the exact function(s) of Fn in a healing wound. Efficacy must still be shown in controlled clinical trials; dosing and administration regimens need to be elucidated.
Clinical Trials as Topic↗
Serum concentrations of immunoglobulins and of antibody isotypes in bone marrow transplant recipients treated with high doses of polyspecific immunoglobulin or with cytomegalovirus hyperimmune globulin.
The kinetics of immunoglobulins (Ig) and antibodies were followed in 10 bone marrow transplant recipients who received either high doses (0.5 g/kg body weight) of polyspecific intravenous Ig (HD-IVIG) weekly or cytomegalovirus hyper-Ig (CMV-IVIG, 0.1 g/kg body weight) every 3 weeks. In the HD-IVIG group, the mean total IgG concentration more than tripled and similar significant increases were seen for IgG1 and IgG2. IgG antibodies to CMV showed a marked increase in the HD-IVIG and a less pronounced rise in the CMV-IVIG group. IgM antibodies to CMV were present initially or became detectable in five patients, unrelated to the IVIG preparation. HD-IVIG induced a significant increase of IgG antibodies to streptococcal group A carbohydrate (A-CHO) and to smooth strain lipopolysaccharides (LPS) but not of antibodies against lipid-A. When the Ig treatment was discontinued, levels of total IgG and of IgG antibody to CMV decreased with an apparent half-life of 30 days. Both IVIG preparations were well tolerated and had no negative feedback on total Ig and on specific antibody production or other antimicrobial defence mechanisms. In patient nos. 4 and 10 who developed severe graft-versus-host-disease, transient serum Ig peaks including several Ig isotypes appeared after day 14. In patient no. 10 this peak contained an IgG antibody to H. influenzae type b (Hib), and IgM antibodies to CMV, Hib, A-CHO and LPS. This study clearly shows that serum concentrations of Ig isotypes, subtypes and specific antibodies, depend on at least four factors: total amount and composition of Ig infused, consumption, catabolism and endogenous production.
Adult↗
Effects of high-dose aprotinin on blood loss, platelet function, fibrinolysis, complement, and renal function after cardiopulmonary bypass.
The use of aprotinin to reduce blood loss after cardiopulmonary bypass is under debate. Concern has been raised about the renal effects of aprotinin. We administered a mean aprotinin dose of 4.2 x 10(6) kallikrein-inhibiting units to 13 patients with coronary disease undergoing cardiopulmonary bypass for 74 +/- 5 minutes (mean +/- standard error of the mean); 13 comparable patients having cardiopulmonary bypass served as control subjects, and all were studied postoperatively for 24 hours. Aprotinin reduced postoperative blood loss by 50% (p = 0.0082). Two of the 13 patients who received aprotinin needed one red cell unit each versus a total of 18 units in eight of 13 control patients (p = 0.0096). Blood pressure, hemoglobin value and serum protein concentration were higher after operation in the aprotinin group (p less than 0.05 to p less than 0.01). Platelet counts did not differ, but plasma thromboxane was lower in aprotinin recipients (p less than 0.001). In control patients fibrinogen degradation products (D dimer) doubled, and alpha 2-antiplasmin activity was halved during and after cardiopulmonary bypass (p less than 0.01 to p less than 0.001), whereas aprotinin patients showed no changes. The complement breakdown products C4a, C3a, and C3dg as well as C9 neoantigen increased from prebypass baseline in both groups (p less than 0.001); the increment of C3a and C3dg was greater in the aprotinin than in the control patients (p less than 0.001). Serum electrolytes, osmolality, and creatinine remained normal in both groups of patients. Creatinine clearance was normal or above normal and virtually identical in both groups. Osmolar clearance and fractional sodium excretion were higher in the aprotinin group than in the control group shortly after cardiopulmonary bypass (p less than 0.05 to p less than 0.01); renal function was unremarkable the next morning. No adverse clinical effects attributable to aprotinin were seen. In summary, aprotinin offers advantages for cardiopulmonary bypass.
Antithrombin III↗
Ontogeny of the humoral response to group A streptococcal carbohydrate: class and IgG subclass composition of antibodies in children.
We determined isotypes of natural antibodies to streptococcal group A carbohydrate (A-CHO) in sera from 101 children between 1 and 16 years of age, using a calibrated enzyme-linked immunosorbent assay system. Anti-A-CHO IgM could be detected in all but one sera. Median levels increased with age and were highest between 8 and 12 years. IgG antibodies were present at low concentrations up to the age of 4 years, and consisted predominantly of the IgG1 subclass. Between 4 and 8 years, concentrations of anti-A-CHO IgG markedly increased and median levels continued to increase through age 12-16. Anti-A-CHO IgG1 levels closely followed the pattern of IgG antibody concentrations. The number of IgG2 antibody positive sera was low in young children, as expected. In the 8-12 year age group and later, anti-A-CHO IgG2 was present in more than half of the samples, and in children between 12 and 16, medians of IgG2 and IgG1 antibodies were similar. Sera containing anti-A-CHO IgG3 were rare in children up to 4 years of age, but in the group of 4-8-year-old children, this subclass was detectable in 36% and later in up to 77% of the sera. Thus, the IgG response to A-CHO showed a clear maturation during childhood, involving the subclasses IgG1, IgG2 and IgG3. There were no significant differences in A-CHO levels between boys and girls.
Adolescent↗
[Personal computer-assisted "acceptable hemoglobin concentration". An example of preoperative autologous blood donation].
At rest, the actual cardiac output (CO) exceeds the CO required to cover the oxygen consumption VO2, provided the hemoglobin level and the non-Hb parameters impacting on cellular oxygen supply (e.g. paO2, pH and body temperature) are normal. The size of this hemodynamic buffer as a function of Hb levels and the non-Hb parameters can be quantified for any clinically conceivable combination including VO2. As Hb levels decrease, the patient's condition is progressively destabilized in the sense that the gradual vanishing of the buffer makes him increasingly sensitive to abnormalities of the non-Hb parameters, such as hypermetabolism, arterial hypoxemia, and alkalosis. This concept is used to illustrate the course of patients participating in an autologous blood predeposit program.
Anesthesia, General↗
The influence of fibronectin administration on the incidence of sepsis and septic mortality in severely injured patients. The Medical College of Georgia Fibronectin Research Group.
Eighty-five trauma patients between the ages of 18 and 55, with American College of Surgeon's (ACOS) trauma scores greater than or equal to 7 were entered into a double-blind, randomized, placebo-controlled study to assess the efficacy of prophylactic fibronectin (Fn) administration on clinical course, sepsis development, and septic mortality. Patients were randomized on admission to receive purified human virus-inactivated Fn or placebo control (human serum albumin, HSA). Fn or HSA was administered on a daily basis if and when the patient was Fn deficient (less than 75% normal). When a Fn deficiency was not evident, the patient received saline. Seventy one patients developed Fn deficiencies during their initial clinical course: 36 received Fn, 35 received HSA. Fourteen patients did not develop a Fn deficiency after trauma and thus received only saline. Analysis of admission data demonstrated no significant differences between the three groups with respect to extent of injury (injury severity score, ACOS trauma score) or physiologic assessments of organ function (serum creatinine, bilirubin, lactic acid). On day 1 after trauma, Fn levels were shown to correlate with other plasma proteins and cellular components (range of r values, 0.24 to 0.75; all p less than 0.05), but not with organ function parameters. Eighteen of 85 patients became septic as judged by clinical criteria. Ten of these patients had received Fn (10 of 36), five had received HSA (5 of 35), and three had received only saline (3 of 14) before the development of sepsis (differences not significant). When septic, nine of 17 patients developed Fn deficiencies. Six patients received Fn while septic, three received albumin, and eight received saline. Seven patients died: 5 of 6 Fn patients, 1 saline, and 1 HSA recipient. Our data suggest that exogenous Fn repletion in states of deficiency does not alter clinical course, the development of sepsis, or septic mortality.
Adolescent↗
Is there a generally valid, minimum acceptable hemoglobin level?
The different versions of autologous blood transfusion have rekindled interest in a generally valid 'minimum acceptable hemoglobin concentration' of patients around or below 10 g Hb/dl. The adequate Hb concentration capable of covering the oxygen demands of the body depends on several variables measurable at the bedside: oxygen consumption VO2, arterial oxygen tension paO2, body temperature, arterial and mixed venous pH, and cardiac output CO as the most important compensatory variable in anemia. Because of the strain imposed on the myocardium and the coronary circulation, anemia should not raise CO to more than twice the resting value, i.e. less than 10 l/min. Similarly, the mixed venous pO2, as an indicator of tissue oxygenation, should not fall below 35 mm Hg. With these two restrictions, we studied the relationships of the above-mentioned parameters in a computer-supported model. Under otherwise similar conditions, pvO2 falls with an increase in VO2, a decrease in paO2, a decrease in the temperature, an increase in pH, and a decrease in CO. A resting and slightly acidotic patient without other impediments of his cellular oxygen supply--e.g. the patient on chronic hemodialysis--tolerates a Hb level of 6-7 g/dl with a pvO2 barely exceeding 35 mm Hg and a CO approximately 50% above baseline. By contrast, the hypermetabolic and hypoxemic intensive care patient needs Hb levels in the low normal range, i.e. 12-13 g/dl, especially if he is also alkalotic. A generally valid 'minimum acceptable hemoglobin level' does not exist; the adequate Hb concentration is an individual characteristic needing careful attention.(ABSTRACT TRUNCATED AT 250 WORDS)
Anemia↗
[Serum immunoglobulin concentrations in patients following bone marrow transplantation and preventive administration of high-dose nonspecific or normal-dose CMV-specific immunoglobulin].
Ten consecutive bone marrow transplant recipients were assigned alternatively to receive either a high dose polyspecific intravenous immunglobulin (HDIVIG) 0.5 g/kg weekly X 14, or a conventional dose of a CMV specific intravenous immunglobulin (CMVIG) 0.1 g/kg every three weeks. Before and after each application we determined the levels of total IgG, IgG subclasses, IgG 1, IgG 2, IgG 3, IgG 4, total IgA and IgM and of specific IgG and IgM antibody concentrations against endotoxin, lipid A, streptococcus A, hemophilus, EBV and CMV. In the HDIVIG, total IgG rose from 11 (median, range 2-11) g/l to 25 (22-32) g/l by day 89, in the CMVIG group, IgG dropped from 11 (10-15) g/l to 9 (6-12) g/l. In the same period the mean levels of IgG subclasses expressed as % of normal plasma pool increased in the HDIVIG group in all subclasses, not in the CMVIG group. The differences were significant, however, only for IgG 1 and IgG 2. IgG-antibodies against CMV, EBV, endotoxin, streptococcus and hemophilus did increase significantly in the HDIVIG group, but not in the CMVIG group. No increase was seen in both groups in lipid A antibodies and in specific IgM antibodies. Each application of CMVIG induced a transient increase of anti-CMV antibodies. We conclude that HDIVIG induces reproducibly an increase of specific and non-specific IgG antibodies. No attempt was made to assess clinical outcome. However, these results provide a rational basis for further therapeutic studies.
Adult↗
Complement and humoral immune parameters in bone marrow transplant recipients: effects of intravenous immunoglobulin administration.
Explore the source record for details and available documents.
Adult↗
[How great is the risk of cancer and recurrence following benign breast biopsy?].
Four hundred and thirty-eight patients with biopsy-proven benign breast disease were followed annually in a prospective manner for 4-17 years, to analyze breast cancer risk, correlations with cancer development and recurrence during follow-up. Twelve breast cancers developed in 12 patients during follow-up, giving a 2.6 fold increased cancer risk over the reference population. No association was found between patients who developed cancer and those who did not with respect to the initial histologic feature (p = 0.9), the age at entry by decades (p = 0.4) and relative to menopause (p = 0.3), the presence of cysts (p = 0.5) or calcification (p = 0.2) in the biopsy specimen, a family history of breast cancer (p = 0.7) or the follow-up time (p = 0.9). Benign breast disease does not inevitably lead to recurrence. Moreover, 47% of the 438 patients never had any recurrence and were free of symptoms during follow-up, and 84% never required a further operation. We conclude that an aggressive approach to benign breast disease is not justified, for any type of lesion as defined in this report.
Adenofibroma↗
[The mobile cecum syndrome: appendectomy and cecopexy or only appendectomy?].
1159 patients underwent appendectomy via a McBurney incision from 1972 to 1983 at our institution. 115 patients (10%) had a mobile cecum syndrome (CMS) as defined by Nicole, without evidence of appendicitis or other pathologic findings at operation. 102 patients were followed up to 15 years after the operation. 82% of the 102 patients were free of symptoms at assessment. 36 patients underwent appendectomy and 63 appendectomy and cecopexy. The two cohorts were comparable with respect to sex, age at operation, duration of right lower abdominal pain, operative findings and length of follow-up. There was no significant difference in the postoperative result of patients with appendectomy alone and those with appendectomy and cecopexy. Moreover, we were not able to identify patients who may benefit from an additional cecopexy, on the basis of patient related factors or intraoperative findings.
Adolescent↗
Long-term follow-up of patients with biopsy-proven benign breast disease.
Three hundred sixty-five patients with biopsy-proven benign breast disease were followed annually in a prospective manner for 4-15 years to analyze breast cancer development, recurrence, and efficacy of management during follow-up. Eleven breast cancers developed in 11 patients during follow-up, giving a 2.6-fold increased cancer risk over the reference population. No association was found between patients who developed cancer and those who did not with respect to the initial histologic feature (p = 0.62), the age at entry by decades (p = 0.40), and relative to menopause (p = 0.54), the presence of cysts (p = 0.87), or calcification (p = 0.74) in the biopsy specimen, a family history of breast cancer (p = 0.80), or the number of observation years (p = 0.27). We conclude that an aggressive approach to benign breast disease is not justified for any type of lesion as defined in this report. Benign breast disease does not inevitably lead to recurrence. Moreover, 41% of our patients never had any recurrence and were free of symptoms during follow-up; 67% never had a mammogram and 82% never required a further operation. There was no association with initial histologic feature in patients who had clinical examination only and those who had mammogram, biopsy, or both during follow-up (p = 0.93). Mammograms were mainly used to clarify a clinical recurrence than as a screening tool, regardless of histologic feature (p = 0.76). Mammograms were mainly used in premenopausal patients (p less than 0.001) having lumps (p less than 0.001), namely, the most difficult patients for radiologic interpretation. This may be one important reason for the rather low sensitivity (75%) and specificity (40%) of mammography in this report. In conclusion, clinical examination is the outstanding investigational tool to follow patients with biopsy-proven benign breast disease, especially in young premenopausal patients.
Age Factors↗
[Shock mediators and their antagonists as future therapeutic perspectives].
Explore the source record for details and available documents.
Arachidonic Acid↗
[Long-term results following surgery of varicose veins].
In a long-term follow-up after operation for primary varicose vein disease, patients were revisited 5, 10 and 15 years after their operation, in an attempt to define the goal of the treatment and the result. The results were analyzed as well as those factors which had a significant influence on the findings at assessment. The long-term results were good with respect to the patient's self-judgement and relative to improvement of trophic disturbances, especially of venous ulceration, however recurrent superficial varicose veins increase significantly with increasing follow-up time. The outstanding role of incompetent communicating veins is discussed with respect to trophic disturbances and recurrent varicose veins.
Adult↗
Humoral immune function in pediatric patients treated with autologous bone marrow transplantation for B cell non-Hodgkin's lymphoma. The influence of ex vivo marrow decontamination with anti-Y 29/55 monoclonal antibody and complement.
Elimination of neoplastic B cell populations from autologous bone marrow grafts also removes normal B lymphocytes. This is potentially hazardous for the reconstitution of the immune system in patients undergoing high-dose chemotherapy and total body irradiation followed by autologous marrow rescue. Five pediatric patients with B cell non-Hodgkin's lymphoma in first remission undergoing such a regimen were studied. They received bone marrow pretreated with anti-Y 29/55 monoclonal antibody and complement. B and T lymphocyte subpopulations reached normal levels within 6 months after autologous bone marrow transplantation (ABMT), and serum immunoglobulin levels became normal within 4 to 9 months. Vaccination with diphtheria and tetanus toxoid, trivalent poliomyelitis vaccine of the Salk type, and pneumococcal capsular antigens (38 to 54 months after transplantation) gave rise to specific antibody production. ABO isoagglutinins could be demonstrated in all patients. The response pattern was similar to that of patients who received unmanipulated autologous bone marrow. It is concluded that ex vivo anti-Y 29/55 depletion of the marrow graft does not induce relevant disturbances of humoral immune functions.
Adolescent↗
Role of the reticuloendothelial system in the pathogenesis of organ damage.
Macrophages ingest foreign materials, effete and damaged tissues, and bacterial products. They also secrete biologically active products which promote and regulate host inflammatory responses. The balance between these macrophage activities may lead to the development of an effective and self-limiting inflammatory response or one that results in tissue damage and potentially in organ failure.
Humans↗
Plasma fibronectin in abdominal sepsis and shock: therapeutic and prognostic value.
Explore the source record for details and available documents.
Fibronectins↗