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J S Solomkin

Publications and source records attributed to J S Solomkin.

At least 73 records · Page 4Linked to original sources
PubMed1985

Surgical infection stratification system for intra-abdominal infection. Multicenter trial.

One hundred eighty-seven patients treated for established intra-abdominal infection in five medical centers were studied using the surgical infection stratification system. This system combines an anatomic category with a numerical estimate (acute physiology score [APS]) of deviation from normal of 33 routine laboratory tests or physical findings. Overall mortality was 24% and the rate of treatment "success" with a single operation and single course of antibiotics was 48%. Eighty percent of deaths occurred with infection present. Multivariate analysis disclosed that APS, malnutrition, and age were most noteworthy for predicting survival or death. Intra-abdominal infection carries substantial mortality and morbidity despite advances in understanding the underlying pathophysiologic condition. Additional clinical studies are needed. Uniform reporting criteria, including the use of an objective severity scoring system, are suggested for future reports concerning intra-abdominal infection.

Abdomen↗
PubMed1985

Regulation of neutrophil superoxide production in sepsis.

Neutrophil superoxide production has been recognized as an important pathway for microbicidal activity and regulation of the local inflammatory environment. To investigate neutrophil superoxide production in sepsis, we studied 22 patients with intra-abdominal infections, and correlated superoxide production with chemotactic response and granular enzyme content. Our results showed that neutrophils from infected patients had specific loss of chemotactic response to C5a, and were deficient in the granular enzymes, lysozyme, and beta-glucuronidase. Superoxide production in response to opsonized zymosan was intact, but response to the chemoattractant N-formyl-methionyl-leucyl-phenylalanine was markedly depressed. This could be reversed in vitro by the addition of cytochalasin B. These results suggest that down regulation of exocytosis of superoxide to nonphagocytic stimuli occurs during sepsis, possibly protecting the host from tissue injury due to oxide radical release. Superoxide response to phagocytic stimulation was intact.

Abdomen↗
PubMed1985

Determination of C3b receptors on normal and patient polymorphonuclear neutrophils with C3b-coated fluorescent microspheres.

A method, devised in the authors' laboratories, for the determination of C3b receptors on normal and patient neutrophils using C3b-coated fluorescent microspheres, was applied to the quantitation of C3b receptors on the neutrophils of several patients suffering from burns and trauma and a patient with pancreatitis. From three to 11 days in the clinical course the relative number of C3b receptors was, or rose to, two to ten times the number of receptors present at later times in the clinical course and, in most of the cases studied, the increase in C3b receptor number coincided with enhanced neutrophil bactericidal function. The rise in C3b receptor number was ascribed to up-regulation by C3a and C5a des Arg from complement activation and also, in the cases where sepsis occurred, to the presence of bacterial chemotactic peptides. Preliminary experiments with zymosan-activated serum and the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine confirmed this explanation.

Blood Bactericidal Activity↗
PubMed1985

Regulation of monocyte function by complement activation products.

Normal human monocytes, obtained at a mean purity of 60% by Percoll density gradient centrifugation, were found to be chemotactically deactivated to C5a by exposure to low, and biologically significant, concentrations of zymosan-activated serum (ZAS), while retaining their full response to FMLP. C5a was found to be 40X more potent than its metabolite C5adesArg in reducing chemotaxis to activated pooled serum. Conversely, exposure of monocytes to varying concentrations of N-formyl-methionyl-leucyl-phenylalanine (FMLP) decreased chemotaxis to that attractant, though had no effect on chemotaxis to activated serum. Monocytes were also found to actively absorb C5a from solutions of ZAS, rich in C5a. Our data support the concept that monocytes are specifically regulated by C5a and C5adesArg.

Blood↗
PubMed1985

Suppressed neutrophil oxidative activity in sepsis: a receptor-mediated regulatory response.

We have reported that neutrophils from patients with intraabdominal sepsis show suppressed superoxide production in response to soluble chemoattractants. To determine whether this could be a result of altered receptor function, neutrophil function studies and characterization of receptors were performed upon 22 patients recently operated upon for intraabdominal sepsis. Patient cells showed an absence of subagarose migratory response to activation serum (C5) but intact FMLP response. Superoxide production to FMLP was 5.3 +/- 0.1 nmole FcC compared to 11.2 +/- 0.1 nmole for laboratory normals. Addition of cytochalasin B reversed this. Scatchard analyses of patients' cells showed affinity of 55.5 +/- 0.6 as compared to 36.5 +/- 1.8 for controls. The number of receptors of cell was approximately 55,000 for both controls and patients. Internalization studies revealed significant increase in tritiated-FMLP uptake at room temperature. These results support the hypothesis that superoxide suppression is due to enhanced clearance of stimulant by enhanced internalization of the receptor-ligand complex.

Abdomen↗
PubMed1985

Complement activation and clearance in acute illness and injury: evidence for C5a as a cell-directed mediator of the adult respiratory distress syndrome in man.

The appearance of the adult respiratory distress syndrome (ARDS) during the course of acute illness is believed to result, in part, from intrapulmonary neutrophil sequestration and degranulation induced by circulating inflammatory mediators. To evaluate the role of complement-neutrophil interactions in the pathogenesis of ARDS in man, 34 patients suffering from intra-abdominal sepsis (seven), multisystem trauma (15), or acute pancreatitis (12) were serially studied with regard to neutrophil migratory responses to C5a and F-Met-Leu-Phe, lysosomal content of beta-glucuronidase and lysozyme, and simultaneously obtained plasma levels of immunoreactive C3adesArg and C5adesArg. Nineteen patients developed ARDS. In these patients, plasma C3adesArg levels obtained within 72 hours of admission to the hospital were elevated to 305 +/- 35 ng/ml compared with 145 +/- 16 ng/ml for patients who did not develop ARDS (p less than 0.0005). C5adesArg levels were not elevated in either group. In vitro studies showed that neutrophils from normal persons were able to clear all of the C5a/C5adesArg generated in up to 5% zymosan-activated serum, while no clearance of C3adesArg was identified. Patient migratory responses could be divided into three groups based on their initial (less than 72 hour) samples: (1) hyperresponsive to both N = formyl-methionyl-leucyl-phenylalanine (FMLP) and C5a, (2) specifically deactivated to C5a, and (3) deactivated to both C5a and FMLP. Patients in the latter two groups developed ARDS. Enzyme content of neutrophils from patients who developed ARDS showed a substantial fall in beta-glucuronidase and lysozyme levels. The finding of elevated plasma C3a levels and deactivation of migratory response to C5a support the contention that complement activation had occurred in these patients and that their neutrophils had been exposed to C5a/C5adesArg in vivo. The finding of nonspecific migratory dysfunction associated with lysozymal enzyme loss, a circumstance not reproducible in vitro by C5a exposure, suggests that other stimuli produced degranulation of neutrophils made hyperresponsive by prior exposure to C5a.

Chemotaxis, Leukocyte↗
PubMed1984

A proposed classification of intra-abdominal infections. Stratification of etiology and risk for future therapeutic trials.

Serious studies of ultra-abdominal infections have yielded a mortality that ranges from 3.5% (a composite of antibiotic studies evaluating 1,275 patients) to more than 60% in studies of multiple-organ failure. In reviewing these studies, it is apparent that under the umbrella of "serious intra-abdominal infection," different diseases, processes, and patients are being studied. We define a binomial classification incorporating both an anatomic and a functional approach to intra-abdominal infection. There are ten etiologic classifications of intra-abdominal infections combined with an acute physiologic score (APS), measuring severity of illness, in three gradations. In the patient with undifferentiated intra-abdominal sepsis, the patient will be in class I, II, III, or IV, with a score, A, B, or C, added. Each of the groups V-X, defining a specific infectious category, can also use the APS, which has been verified in patients in intensive care and in those with intra-abdominal infection. It is anticipated that using this approach will provide a technique to evaluate patient groups uniformly in which drug or technical approaches to the management of intra-abdominal infections are being studied. The patients being studied will be more clearly defined, and studies will be comparable from one center to another.

Bacterial Infections↗
PubMed1984

Neutrophil dysfunction in sepsis. III. Degranulation as a mechanism for nonspecific deactivation.

Prominent and global abnormalities in chemotactic, oxidative, and microbicidal activity have been identified in neutrophils from patients with severe sepsis. To evaluate the possible contribution of degranulation as the basis for the observed abnormalities, 12 patients with intrabdominal infection were serially studied and neutrophil chemotaxis, enzyme content, and receptors for FMLP were evaluated. There was a significant correlation between chemotactic response to both activated serum and FMLP with the granular enzymes beta-glucuronidase and lysozyme. For FMLP-directed migration, r = 0.73, P less than 0.001 for lysozyme, and r = 0.59, P less than 0.001 for beta-glucuronidase. There was a similarly significant correlation between loss of lysozyme and an increase in FMLP receptors, previously shown to be a marker for degranulation. These data support the concept that in vivo degranulation, possibly due to effects of circulating chemoattractants on adherent neutrophils, is responsible for the enzymatic and chemotactic loss seen in cells from septic patients. This hypothesis also provides a mechanism to explain the respiratory distress syndrome if degranulation were to occur in the pulmonary capillary bed.

Bacterial Infections↗
PubMed1984

Antibiotic trials in intra-abdominal infections. A critical evaluation of study design and outcome reporting.

The introduction of several new antibiotics, including cephalosporins and ureido-penicillins, has been a stimulus for clinical trials with these agents for intra-abdominal infection. Despite marked differences in antibacterial spectra, substantial differences in treatment results have not been documented. We reviewed published trials of antibiotic therapy for intra-abdominal infection to determine factors in study design that might impair identification of clinically important differences between regimens. Sixteen articles were identified that provided sufficient numbers of cases and data for analysis. Eight were prospective comparative trials, the remainder "single-armed" studies. The mortality rate was 3.5%, and the overall success rate was 84% for aminoglycoside plus clindamycin (range 52%-96%), 89% (range 83%-93%) for aminoglycoside plus metronidazole, and 93% (range 61%-95%) for cephalosporin-based regimens. Several defects in study design were identified. (1) Exclusionary criteria employed generally prevented enrollment of seriously ill patients or infections associated with high failure rates: Patients were excluded if even mild renal impairment was present or if antibiotic therapy had been recently administered, thereby excluding patients with postoperative or recurrent infections. Several studies allowed entry of contaminated but not infected patients. (2) Criteria used for reporting infectious diagnosis, premorbid health status, severity of infection, and outcome were nonuniform, and few studies provided such information. (3) Despite the small number of treatment failures, data reported did not allow determination of the basis for failure. For example, only four studies provided information on the operations performed upon treatment failures. Whether treatment failures were due to inadequate antibiotic therapy could therefore not be determined. Enrollment of a variety of low mortality infections precluded demonstration of any differences in regimens. Use of stratified randomization, stratifying for site of infection and severity of infection, and inclusion of greater numbers of patients would increase the likelihood of identifying differences between regimens. Such study design would likely require a multicenter trial to enroll sufficient numbers of cases for statistical analysis.

Abdomen↗
PubMed1984

Regulation of neutrophil migratory function in burn injury by complement activation products.

Polymorphonuclear neutrophils were isolated from patients with burn injury and random mobility, chemotaxis in response to C5adesArg (as agarose-activated control serum) and to N-formyl-methionyl-leucyl-phenylalanine (F-Met-Leu-Phe) were assessed. For a group of eight patients identified as not experiencing systemic infection, all three neutrophil migratory functions were observed to fall below control levels, beginning 4 to 6 days following burn injury, and to return to control levels after 21 to 30 days of hospitalization. Over this time the chemotactic differential (distance chemotactic migration-distance random migration) for F-Met-Leu-Phe remained positive, while the chemotactic differential for activated serum became nil after postburn day 4. This temporal, specific loss of a chemotactic response to activated serum was associated with rises in immunoreactive plasma C3a and C5a. This pattern of loss of chemotactic function was associated with a selective loss of C5a but not F-Met-Leu-Phe binding activity. These results demonstrate that burn injury can alter neutrophil migratory functions generally, and specifically depress chemotactic responsiveness to activated serum. The mechanism of the latter phenomenon appears to be related to desensitization of circulating neutrophils to C5a due to complement activation.

Adolescent↗
PubMed1984

Complement-induced expression of cryptic receptors on the neutrophil surface: a mechanism for regulation of acute inflammation in trauma.

We explored the hypothesis that identified changes in neutrophil function in patients with acute injury result from in vivo exposure to C5a. To evaluate this hypothesis, we performed a battery of tests on 26 trauma patients (14 with blunt injury, 12 with penetrating injury). Measured were plasma levels of the complement activation products C3a and C5a; neutrophil chemotaxis to C5a and N-formyl-methionyl-leucyl-phenylalanine (FMLP); neutrophil receptors for FMLP and C3b; and superoxide response to FMLP and serum-opsonized zymosan. Patient responses measured within 48 hours of admission were divided into two groups based on neutrophil migratory response to C5a. Patients unresponsive to C5a (but responsive to FMLP) showed elevated plasma C3a levels (248 +/- 6 ng/ml) compared with patients with normal C5a migratory response (104 +/- 8 ng/ml). FMLP receptor number was markedly increased in the chemotactically deactivated group (group I: 155,680 +/- 100; group II: 51,200 +/- 200) and receptor affinity was diminished. Binding activity of C3b increased in the C5a-unresponsive cells to 126% that of controls versus 94% for normally responsive patient cells. Superoxide production was found to be significantly increased in patient cells with increased receptor numbers. These results support the concept that a subgroup of trauma patients manifest plasma and neutrophil changes compatible with complement activation. The neutrophil changes identified demonstrate a state of cellular activation. The clinical significance of these results may reside in a risk of pulmonary microvascular injury if activated cells are marginated and then subsequently stimulated.

Chemotaxis, Leukocyte↗
PubMed1982

Indications for therapy for fungemia in postoperative patients.

We reviewed the clinical courses of 63 surgical patients who had experienced one or more days of fungemia, to determine the clinical setting for such infections and to define indications for systemic therapy. Fifty-one patients experienced fungemia as a late complication of intraperitoneal infection. Candida was identified as part of a polymicrobial flora in 70%. If untreated, the mortality was 83% (30 of 36). No untreated patients with fungemia for more than one day survived. Adequate therapy with amphotericin B (total dose, greater than 3 mg/kg) improved survival to 67% (ten of 15). Autopsies performed in 20 cases revealed visceral Candida microabscesses in seven, with the gastrointestinal tract (12) and intraabdominal abscess (five) as the most common sources of fungi. These data support the concept of Candida as an important participant in polymicrobial infection and recommend therapy with amphotericin B for patients with intraperitoneal infection experiencing fungemia.

Abdomen↗
PubMed1982

Candida infections in surgical patients. Dose requirements and toxicity of amphotericin B.

The natural history of candidiasis in general surgical patients has been poorly documented, and the toxicity of amphotericin B is widely heralded. For these reasons therapy for candidiasis is frequently withheld in situations where antimicrobial treatment seems indicated on clinical grounds. The clinical courses of 47 general surgical patients who received amphotericin therapy for presumed Candida infection were reviewed. Nineteen patients had had solid tumors, but 12 were either localized or resected tumors. Only nine patients had received prior cancer themotherapy. Twenty-one patients were treated for fungemic disease, 10 for Candida in peritonitis fluid, and 16 for apparent colonization associated with fever and organ failure syndromes. Pre-existing renal or other organ failure was the primary determinant of survival with 4/22 survivors (18%) in patients with renal failure compared with 17/25 (78%) survivors in patients without such organ failure. In patients with serum creatinine values less than 2.5 mg/dl, amphotericin therapy was associated with a transient 30% fall in creatinine clearance and a proportionate rise in serum creatinine. Dose response curves were determined and revealed substantial sterilization of cultures in both fungemic and nonfungemic patients receiving greater than or equal to 6 mg/kg. This was confirmed by autopsy material. We suggest that in this acutely ill patient popoulation uncontrolled infection is the primary determinant of organ failure. Short-term limited dosing with amphotericin B (6-8 mg/kg total dose) in conjunction with appraisal of clinical response is adequate therapy for most presumed Candida infections. Long-term high dose therapy, such as that recommended in immuodepressed patients, is not a routine necessity.

Acute Kidney Injury↗
PubMed1981

Neutrophils dysfunction during the course of intra-abdominal infection.

Twenty-four patients with intra-peritoneal infections were studied sequentially to evaluate neutrophil chemotaxis, spontaneous migration, and chemiluminescence. In six patients, infection was due to spontaneous disease processes and 18 others, infection was a sequel of intra-abdominal operation. In the patients studied prior to drainage, operation chemotaxis, spontaneous migration and chemiluminescence were all significantly depressed. Operation resulted in a further depression of these functions, and recovery of neutrophil migratory responses was delayed for two weeks. During the period of functional depression, 16 patients developed recurrent infections (nine episodes of intra-abdominal abscess, and 12 episodes of extra-abdominal infection). These infection were associated with a fall-off in neutrophil migratory and chemiluminescence responses prior to clinical evidence of infection. This study suggests that the delayed recovery of neutrophil function may be related to the recurrent infection seen in this patient population. Further, monitoring of neutrophil function in patients recovering from intra-abdominal infection may provide early evidence of recurrent infection.

Abdomen↗
PubMed1981

Neutrophil dysfunction in sepsis. II. Evidence for the role of complement activation products in cellular deactivation.

Abnormalities in chemotactic and bactericidal activity have been identified in patients suffering from burn injury, trauma, and infection. Such abnormalities may lead to bacteremia or nosocomial infection. The mechanism for these abnormalities is unclear. We studied the role of chemotactic deactivation by complement component C5a in 47 patients with intra-abdominal infection and with disordered neutrophil function. Plasma C5a levels in such patients were elevated (102.1 +/- 8.3 versus 52.6 +/- 3.4 ng/ml for control subjects, P less than 0.01). There was a linear relationship between C5a and chemotaxis (r = 0.56, P less than 0.01). Examination of patients' neutrophils showed changes consistent with nonspecific deactivation. There were parallel losses of chemotaxis to N-formyl methionyl-leucyl-phenylalanine (FMLP) and activated serum (C5a) (r = 0.74, P less than 0.001), chemotaxis and intracellular beta-glucuronidase (r = 0.82, P less than 0.001), and C5a and FMLP chemotaxis and (r = 0.56, P less than 0.01). Receptor assays revealed specific loss of C5a binding but intact FMLP binding. Exposure of normal neutrophils to plasma from patients with depressed chemotaxis caused similar loss of C5a receptors and loss of FMLP and activated serum-induced chemotaxis at high plasma concentrations and selective loss of activated serum response at lower concentrations. These data support the concept that a major factor leading to neutrophil dysfunction during intra-abdominal infection is nonspecific chemotactic deactivation of neutrophils after in vivo exposure to high levels of chemoattractants such as C5a.

Adolescent↗