Search PubMed⌕ Search

Biomedical subjects

E G Maderazo

Publications and source records attributed to E G Maderazo.

At least 37 records · Page 2Linked to original sources
PubMed1988

Indomethacin-associated sepsis in very-low-birth-weight infants.

Indomethacin sodium promotes closure of the patent ductus arteriosus in premature infants. In addition to renal and gastrointestinal side effects, indomethacin may predispose to infection because of inhibition of polymorphonuclear leukocyte (PMN) function. We retrospectively assessed the incidence of sepsis in a group of 58 premature infants with patent ductus arteriosus who received either oral indomethacin, surgery, or usual medical management. A significant increase in the incidence of sepsis was observed in the indomethacin-treated group compared with patients treated with surgery or usual medical management (seven of 31 vs one of 27). All episodes of sepsis occurred within one week of therapy. Patients in the indomethacin group who developed sepsis were less mature, had more gastrointestinal symptoms, and were less likely to survive than nonseptic indomethacin-treated patients. Nine patients studied prospectively showed no difference in PMN chemotaxis and adherence before and after indomethacin administration. Neither adult nor neonatal cord PMN chemotaxis was inhibited following in vitro incubation with concentrations of indomethacin ranging from 1 to 1000 mg/L. Bactericidal activity of neonatal cord neutrophils was also unaffected by concentrations of indomethacin from 1 to 200 mg/L. These results suggest that oral indomethacin administration may predispose the very-low-birth-weight infant to the development of sepsis shortly after therapy is begun although the mechanism remains unclear.

Bacterial Infections↗
PubMed1988

The inhibitory effect of parenteral nutrition on recovery of neutrophil locomotory function in blunt trauma.

Twenty patients were investigated to determine whether total parenteral nutrition (TPN) influences the recovery of neutrophil (PMN) locomotory dysfunction in blunt trauma. Half were given TPN consisting of amino acids, glucose, electrolytes, and trace minerals, and half were given intravenous (I.V.) fluids consisting of 5% glucose in water or saline, electrolytes, and trace minerals. PMN locomotion was assayed using micropore filters. Analysis of the data by general linear modeling showed that PMN locomotion in TPN patients was significantly slower during the first 3 to 4 days postinjury. By sequential analysis, improved PMN function in the group not given TPN (NO TPN) occurred less than 95% of the time. TPN with amino acids and glucose may worsen and delay the recovery of PMN locomotory responses in blunt trauma, but the preference ratio of NO TPN:TPN for better PMN function was less than 95:5.

Adolescent↗
PubMed1988

High teicoplanin uptake by human neutrophils.

The cellular/extracellular (C/E) concentration ratio of teicoplanin in polymorphonuclear leukocytes (PMNs) increased rapidly with time (C/E 60 +/- 13 at 20 min). The C/E ratio was time- and concentration-dependent. At 20 min and an initial concentration of 75 +/- 16 micrograms/ml the cellular drug concentration was 4,700 +/- 1,300 micrograms/ml. The mechanism of drug uptake was by an active process and transported (cellular) drug retained its antimicrobial activity. Washing removed 42% of cellular drug. Teicoplanin inhibited PMN chemotaxis at very high concentrations and PMN microbicidal activity at lower concentrations.

Biological Transport, Active↗
PubMed1988

The influence of various factors on the accuracy of gallium-67 imaging for occult infection.

To examine whether the results and interpretation of gallium-67 citrate imaging may be adversely influenced by factors present in compromised patients, we reviewed our 1-year experience in 69 patients in intensive care units, renal transplants, and those on hemodialysis. Our results indicate that it is an inappropriate diagnostic procedure for acute pancreatitis since seven of nine had false-negative results. Using loglinear modeling and chi-square analysis we found that treatment with antiinflammatory steroids, severe liver disease, end-stage renal disease, and renal transplantation with immunosuppressive therapy did not interfere with gallium-67 uptake. Increased rate of true-negative results in patients with end-stage renal disease was due to a greater and earlier use of the test in the febrile transplant patient and in hemodialysis patients with infections not amenable to diagnosis with gallium-67 scan (transient bacteremia and bacteriuria). We conclude that gallium-67 imaging is a useful diagnostic tool that, with the exception of acute pancreatitis, has very few false-negative results.

Abdomen↗
PubMed1988

Late infections of total joint prostheses. A review and recommendations for prevention.

The incidence of late infection of total joint prostheses is 0.6%. Because this incidence has increased from 0.08% in 1978, the authors reviewed their experience and the literature in search of pathogenetic and preventative measures. The most common pathogen responsible for late prosthetic joint infections was staphylococcus (54%; both Staphylococcus aureus and Staphylococcus epidermidis), even when infection was of dental origin. The three most common origins of infection were skin and soft tissue (46%), dental (15%), and urinary (13%). Escherichia coli was the most common pathogen when the source was the urinary tract. Mortality and cost calculations indicate that chemoprophylaxis is justified for dental procedures and probably also for other surgical procedures in organs containing microflora. Prophylaxis must include antistaphylococcal drugs. The first generation cephalosporin antibiotics are recommended.

Adult↗
PubMed1988

Neutrophil heterogeneity in patients with blunt trauma.

To determine whether neutrophil (PMN) dysfunction observed in patients with blunt trauma could be explained by alterations in PMN functional subpopulations and to further study the origins of PMN heterogeneity, we studied PMN subpopulations in 18 patients with severe blunt trauma by using a micropore filter chemotactic assay and a mouse monoclonal antibody (31D8 Mab). A major PMN subpopulation binds 31D8 Mab avidly (31D8 "bright") and depolarizes and responds chemotactically to formyl peptide (fMLP) and C5a; a minor PMN subpopulation binds 31D8 Mab weakly (31D8 "dull") and fails to depolarize and responds poorly to fMLP and C5a. Fourteen patients with trauma had marked alteration of PMN 31D8 expression compared with healthy controls 52% +/- 20% versus 92% +/- 4% bright PMNs, respectively (p less than 0.01). These patients also had significantly decreased PMN chemotaxis and increased band counts compared with controls 30 +/- 10 micron versus 53 +/- 19 micron (p less than 0.01) and 34% +/- 14% versus 6% +/- 1% (p less than 0.01), respectively. Four patients with less-severe injuries had unaltered 31D8 PMN expression and normal PMN chemotaxis. In patients whose band counts exceeded 20%, there was a strong correlation between the number of bands and the percentage of 31D8 dull PMNs. PMNs that weakly express the 31D8 antigen appear to be less mature than PMNs that strongly express the antigen regardless of cell morphology (i.e., bands, multilobed cells). The data suggest that the decreased PMN chemotaxis and increased infection rate in patients with blunt trauma is caused partly by an increase in the number of poorly functioning 31D8 dull PMNs.

Adolescent↗
PubMed1987

Host defense during pregnancy: neutrophil chemotaxis and adherence.

Pregnancy is associated with impairment in several immunologic functions that effect the outcome of certain infectious and autoimmune diseases. Previous studies have indicated that pregnant women have decreased neutrophil motility, but results are discordant. We performed a longitudinal study of polymorphonuclear leukocyte chemotaxis using a micropore filter assay and polymorphonuclear leukocyte adherence using a nylon wool column assay in 58 women during pregnancy, delivery, and the postpartum period. Polymorphonuclear leukocyte chemotaxis was decreased significantly in pregnant women during the second (-20%) and third (-17%) trimesters and 1 to 3 months post partum (-18%), but not during the first trimester (-6%) compared with nonpregnant control subjects. The impairment in polymorphonuclear leukocyte chemotaxis appeared to be a cell-associated rather than a humoral defect. Polymorphonuclear leukocyte adherence was decreased significantly in pregnant women during the third trimester (-16%). These data may help explain the increased incidence of infection and amelioration of certain immunologically mediated illnesses during pregnancy.

Cell Adhesion↗
PubMed1987

Pentoxifylline enhancement of defective neutrophil function and host defense in neonatal mice.

Decreased neutrophil (PMN) chemotaxis is thought to contribute to the increased morbidity and mortality from infection in newborn infants. Pentoxifylline, a methylxanthine, has previously been shown to augment PMN chemotaxis in vitro. The authors therefore investigated the effects of pentoxifylline on 1) in vitro PMN chemotaxis, 2) in vivo leukocyte accumulation, and 3) protection against Staphylococcus aureus infection in newborn mice. Using a modified Boyden chamber system, they demonstrated that pentoxifylline significantly enhanced neonatal PMN chemotaxis in a dose-dependent manner. Additionally, pentoxifylline was found to increase PMN accumulation in vivo in a proteose peptone-induced peritonitis model. Finally, the survival rate in experimentally induced S aureus infection was 51% in neonatal mice given pentoxifylline, compared with 17% in a control (nonpentoxifylline) group (P less than 0.01). These data demonstrate pentoxifylline modulation of PMN migration and enhancement of host defense against bacterial infection.

Animals↗
PubMed1986

Inappropriate activation, deactivation, and probable autooxidative damage as a mechanism of neutrophil locomotory defect in trauma.

We studied 46 patients who suffered from serious blunt trauma to examine the possible mechanism of their acquired neutrophil (PMN) locomotory dysfunction. Concentrations of plasma C3adesArg were higher in patients than in controls (310 +/- 190 ng/ml vs. 90 +/- 28 ng/ml, respectively; P = 3 X 10(-5)). Both resting and phagocytosing PMNs from the patients produced higher quantities of H2O2 (0.31 +/- 0.29 and 5.2 +/- 3.4 nmol/10(6) PMNs per hr, respectively). These levels resemble the H2O2 production of normal PMNs preactivated with chemotactic factor (0.85 +/- 0.03 for normal and 8.2 +/- 1.6 nmol/10(6) PMNs per hr for preactivated PMNs). Concentrations of oxidized glutathione were not significantly higher in PMNs from patients compared with PMNs from controls (0.053 +/- 0.057 vs. 0.037 +/- 0.046 nmol/10(6) PMNs, respectively; P = .5). A higher percentage of PMNs from trauma patients than from controls were capped with concanavalin A (66% +/- 11% vs. 37% +/- 14%, respectively; P = 4 X 10(-5)), a result indicating microtubular dysfunction. These findings suggest that in trauma, activation of intravascular complement results in inappropriate chemotactic stimulation and subsequent deactivation and autoxidative damage of circulating PMNs.

Adolescent↗
PubMed1986

Treatment of the periodontal component of Papillon-Lefèvre syndrome.

A 9-year-old girl was treated for the periodontal component of Papillon-Lefèvre syndrome, an autosomal recessive disease characterized by palmarplantar hyperkeratosis and premature loss of teeth. Initially, the patient was found to have a polymorphonuclear leukocyte chemotactic dysfunction, defective leukocyte adherence, and deep periodontal pockets harboring presumptive periodontopathic bacteria. After unsuccessful treatment with combined mechanical therapy and 2 different antibiotics, all of the patient's erupted teeth were extracted in an attempt to minimize the chance of infection of teeth yet to erupt. At age 16 years, the now-erupted teeth have normal gingiva and crevice depths, radiographs show no evidence of periodontal pathology, no periodontopathic bacteria are detected in gingival crevices, and leukocyte function is normal.

Bacteria↗
PubMed1986

Polymorphonuclear leukocyte adherence and chemotaxis in stressed and healthy neonates.

Defects in polymorphonuclear neutrophil (PMN) adherence and chemotaxis in neonates are thought to be an important cause of their increased susceptibility to overwhelming bacterial infection. Few studies of these functions have been carried out in stressed neonates who are at even greater risk of infection. PMN adherence and chemotaxis were examined in 33 stressed neonates with acute lower respiratory illness, 13 healthy neonates, and 43 healthy adults using whole blood PMN adherence and chemotaxis assays. PMN chemotaxis was significantly decreased in stressed neonates (locomotion index of 38.4 +/- 9.7 micron) compared with that of healthy neonates (48.9 +/- 12.8 micron, p less than 0.01) or adults (61.6 +/- 11.9 micron, p less than 0.001). PMN chemotaxis was studied during illness and recovery in 13 of the 33 stressed neonates and showed significant improvement during recovery (41.6 +/- 9.9 and 53.2 +/- 11.9 micron, respectively, p = 0.012). PMN adherence was decreased in stressed neonates (1.4 +/- 1.6%) compared with that of adults (12.3 +/- 11.4%, p less than 0.01) but was similar to that of healthy neonates (1.1 +/- 1.4%). These findings suggest that further impairment of PMN chemotaxis in stressed neonates helps account for their increased susceptibility to overwhelming bacterial infection.

Adult↗
PubMed1986

Protective effects of ibuprofen and methylprednisolone on chemotactic factor-induced transcutaneous hypoxia.

We showed previously in vitro that ibuprofen, a nonsteroidal anti-inflammatory agent, at concentrations easily achievable in blood, inhibits polymorphonuclear leukocyte cell swelling and aggregation in response to chemotactic factor stimulation. To confirm this in vivo, we studied the ability of ibuprofen i.v. pretreatment to reverse the transcutaneous hypoxia induced by i.v. infusion of 1 nmol/kg of formyl-methionyl-leucyl-phenylalanine. This effect was compared with that of methylprednisolone. For ibuprofen and methylprednisolone, respectively, the maximum percentage of reversal of hypoxia was 85 and 106%; the dose required to produce 50% of maximum reversal was 2.7 and 4.6 mg/kg; and the serum drug concentration needed to achieve 50% of maximum reversal was 14 and 11 micrograms/ml. We conclude that ibuprofen could be a useful alternative to steroidal antiinflammatory agents for the prevention and treatment of complications of stimulated polymorphonuclear leukocytes.

Animals↗
PubMed1984

Inhibition of human polymorphonuclear leukocyte cell responses by ibuprofen.

The stimulation of cell swelling, cell aggregation, polymorphonuclear leukocyte locomotion, and lysosomal enzyme release in response to chemoattractant were all inhibited by ibuprofen, a nonsteroidal anti-inflammatory agent. The dosages needed to induce 50% inhibition (ID50) were 5.9, 7.6, 60, and 95 micrograms/mL, respectively. Aside from the differences in ID50, there was also a difference in the degree of maximum inhibition (Imax) of the complement C5a-stimulated responses observed, so that at achievable serum drug concentrations of 20-50 micrograms/mL, inhibition of 67-78% for cell swelling, 69-82% for cell aggregation, 20-35% for migration response, and 17-38% for lysosomal enzyme release were demonstrated. Also observed were a minor stimulatory effect on nitroblue tetrazolium reduction and an inhibitory effect on the ability to kill Staphylococcus aureus, but only at very high concentrations (approximately 2 mg/mL).

Blood Bactericidal Activity↗
PubMed1984

Granulocyte migration abnormality in patients suffering from seasonal allergic rhinitis: failure of treatment with cimetidine.

Granulocyte locomotory responses in 5 patients with symptomatic seasonal allergic rhinitis were lower compared with similar responses from 27 normal nonallergic controls. In a subsequent controlled, double-blind crossover study, neither cimetidine (histamine H2-receptor blocker) nor placebo improved these responses. In our in vitro study, histamine did not inhibit granulocyte responses to chemotactic attractant. These results indicate that defective granulocyte response in patients with seasonal allergic rhinitis may be due to factors other than or in addition to histamine.

Cell Movement↗
PubMed1983

Simplified micropore filter assay of neutrophil migration using whole blood.

A new method of micropore filter assay of neutrophil migration requiring only 0.1 ml of whole blood is described and compared with the standard separated polymorphonuclear neutrophil micropore filter assay. Whole blood was added to the upper compartment of a modified Boyden chemotactic chamber, and the neutrophils were allowed to migrate into a cellulose nitrate micropore filter. Acetic acid was used to remove erythrocytes and hemoglobin from the filter. Neutrophil chemotaxis was performed with cells from 19 neonates and 34 adults. The mean neonatal PMN migration was 40% of the adult value (48.1 +/- 12.6 vs 96.8 +/- 16.8 micron) with the whole blood assay and 39% of the adult value (44.7 +/- 10.1 vs 72.9 +/- 22.2 micron) with the separated polymorphonuclear neutrophil assay. The whole blood micropore filter assay, a simple and reliable method of determining neutrophil migration, is especially useful in studying patients when there are difficulties in obtaining large blood samples, such as with neonates and young children.

Cells, Cultured↗