PubMed Health⌕ Search

Biomedical subjects

S S Kaplan

Publications and source records attributed to S S Kaplan.

At least 19 recordsLinked to original sources
PubMed1997

Comparative pharmacokinetics and renal effects of cyclosporin A and cyclosporin G in renal allograft recipients.

Cyclosporin G (CSG) has produced less nephrotoxicity than cyclosporin A (CSA) at equivalent doses in animal models. Conflicting results have been reported concerning differences in the pharmacokinetics of CSA and CSG in preclinical studies, and no data exist regarding the effect of steady-state oral administration of CSG on renal function in transplant patients or CSG-induced release of endothelin and nitric oxide (NO) in vivo. The objective of the study was to examine steady-state pharmacokinetic profiles of adult renal allograft recipients receiving CSA and CSG in relation to concentrations of endothelin-1 and NO2/NO3 in urine and plasma, creatinine clearance (Clcr), and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) 9 months after transplantation. Concentrations of CSA and CSG were measured in whole blood over a 12-hour dose interval by both a monoclonal and polyclonal fluorescence polarization radioimmunoassay for CSA. A metabolite fraction was defined as the numerical difference between the levels obtained at each time point by both assays. Patient groups were defined as follows: group 1: initial CSA (n = 6); group 2: initial CSG (n = 7); group 3: five of the seven patients in group 2 taking CSG subsequently undergoing conversion to CSA; group 4: the same five patients in group 3 restudied 1 month after 1:1 dosage conversion to CSA; and group 5: CSA groups 1 and 4 combined (n = 11). In group 1, the metabolite fraction accounted for 32% to 54% of the total measurable drug concentration at each time point, whereas in group 2, the metabolite fraction accounted for at most 10% to 15% of the total drug levels measurable by polyclonal fluorescence polarization radioimmunoassay. Although there were no significant differences in any of the mean pharmacokinetic parameters between groups using monoclonal fluorescence polarization radioimmunoassay, the normalized area under the concentration-time curve (NAUC) value was less in four of five patients after conversion from CSG to CSA, with a more variable and delayed time to reach peak concentration (tmax) but equivalent apparent oral clearance (Clpa) values. Clcr was found to change significantly with time in groups 1 and 5 but not in group 2, with CSA producing a more profound and sustained decrease than CSG. Endothelin-1 and NO2/NO3 levels in plasma and urine remained relatively constant after administration of both CSA and CSG, and there were no significant differences between groups 3 and 4 regarding mean endothelin-1 and NO2/NO3 concentrations in plasma, urinary release of endothelin-1 and NO2/NO3, and mean AUC of endothelin-1 and AUC of NO2/NO3. However, monoclonal NAUC correlated significantly with total urinary endothelin-1 within CSA groups 1 and 5 but not within CSG group 2. Metabolite NAUC correlated significantly with total urinary NAG within CSA group 1. Although limited by the small number of patients, this study suggests that 1) CSG may produce less of a reduction in Clcr over time after oral administration at steady state than does CSA, and 2) this beneficial effect of CSG may be in part due to decreased intrarenal release of endothelin-1, as urinary excretion of endothelin-1 seemed to correlate better with CSA than with CSG exposure.

Acetylglucosaminidase↗
PubMed1997

Biologic response modulation by tumor necrosis factor alpha (TNF alpha) in a phase Ib trial in cancer patients.

During a phase I study of recombinant human tumor necrosis factor (TNF) in cancer patients, serial immune studies were performed and analyzed for effects of TNF. The TNF (specific activity 9.6 x 10(6) U/mg protein, < 5.0 endotoxin units/mg protein) was given over 2 h intravenously on days 1, 8-12, 29-33, 50-54, and 71-75 at doses of 40, 80, 160, 200, and 240 micrograms/m2. Immunologic testing was performed before therapy three times and subsequently on days 2, 8, 10, 12, 29, 33, 50, 54, 71, 75, and off-study two times. Immune parameters evaluated included cytotoxicity [natural killer (NK), spontaneous lymphokine activated killer cells (LAK), LAK, and monocyte], cytokine production [spontaneous and stimulated interferon (IFN)-gamma and interleukin (IL)-2], superoxide production [resting and stimulated polymorphonuclear (PMN) and mononuclear cells (MNC)], and phenotype of peripheral blood lymphocyte subsets (CD3, CD4, CD8, CD16, CD56, CD19). Data were analyzed for long-term effects, the effect after 1 day of treatment (day 1), and for weekly effect (change from day 1 to day 5 of a given treatment week). Significant decreases were seen in the spontaneous cytotoxicity of peripheral blood NK cells and IL-2-inducible LAK cells, whereas increases in spontaneous peripheral blood LAK activity were seen with TNF treatment. Consistent increases in superoxide production of resting PMN and MNC were demonstrated, with late increases in superoxide production by opsonized, zymosan-treated PMN. No spontaneous IFN-gamma or IL-2 were noted in sera with treatment, but production of IL-2 by MNCs rose with TNF treatment. During 5 days of TNF treatment, the percentages of circulating CD8+ and CD56+ cells decreased, whereas that of CD4+ and CD19+ cells increased significantly and consistently, as determined by a multivariate analysis. Significant changes in several independently measured parameters were observed, including a dose-related diminished production of IFN-gamma by MNC stimulated by phytohemagglutinin and increased in vitro-generated LAK activity. Because there was no clinical response in this trial, no association of immunologic change with clinical response can be made. No biologically optimal dose of TNF was evident. The data suggest that TNF may act as a trigger cytokine, initiating a broad immune/inflammatory response.

Dose-Response Relationship, Immunologic↗
PubMed1996

Biomaterial-neutrophil interactions: dysregulation of oxidative functions of fresh neutrophils induced by prior neutrophil-biomaterial interaction.

Biomaterial-associated infection results in increased morbidity and mortality, and may occur because of nonproductive premature activation of neutrophils resulting in impaired phagocyte function at the biomaterial surface in the event of bacterial challenge. To further explore the effects of this premature activation, we evaluated the supernatants of biomaterial associated neutrophils to determine whether soluble mediators were released, and the likely role of these mediators. We show that these supernatants contain a chemoattractant and thereby induce chemotaxis by fresh neutrophils. No evidence of enhanced oxidative free radical production by either unstimulated neutrophils or a primed response to other mediators occurs when neutrophils were incubated with these supernatants. We also examined the effect of adding fresh neutrophils to a biomaterial surface containing a previous inoculum of neutrophils, and observed that the fresh cells did not become stimulated to release reactive oxygen intermediates (ROI) and also exhibited impaired killing of staphylococci. These studies suggest that not only does the biomaterial surface activate the initial wave of neutrophils but that subsequent waves of neutrophils exhibit an impaired host-defense function. These results are consistent with the known impairment of host defense in the presence of biomaterials, and provide evidence for a long-term down-regulation of neutrophil function at biomaterial surfaces.

Biocompatible Materials↗
PubMed1996

Inflammatory cytokine and nitric oxide responses in pediatric sepsis and organ failure.

OBJECTIVE: To examine the relationship of circulating proinflammatory and anti-inflammatory cytokine concentrations to nitric oxide and organ failure in pediatric sepsis. DESIGN: Prospective study. SETTING: Pediatric intensive care unit (ICU), children's Hospital of Pittsburgh, University of Pittsburgh. PATIENTS: Nineteen patients with a diagnosis of sepsis admitted to the pediatric ICU. Twelve uninfected critically iII patients served as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma interleukin (IL)-10, IL-6, and nitrite/nitrate concentrations were measured and compared with an index of organ failure daily for 3 days after presentation with the sepsis syndrome. Children with increased plasma IL-6 concentrations (n = 6) had increased plasma nitrite/nitrate concentrations (p < 0.01 on each day), increased organ failure scores (p < .05 on days 1 and 3), and the highest plasma IL-10 concentrations (p < .05 on days 1 and 3, p = .054 on day 2) when compared with children with sepsis and undetectable IL-6 concentrations. Children with sepsis and detectable IL-6 concentrations, and children with undetectable IL-6 concentrations, both had increased nitrite/nitrate concentrations (p < .005 on days 1 through 3) and increased IL-10 concentrations (p < .05 on days 1 and 2) compared with controls. Children with increased IL-6 concentrations had higher organ failure on each day (p < .01), and children with undetectable IL-6 concentrations had higher organ failure on days 1 and 2 only (p < .005) when compared with controls. Organ failure improved over time in the children with undetectable IL-6 concentrations (p < .005). CONCLUSIONS: Increased plasma nitrite/nitrates and increased organ failure scores occurred in the children with sepsis who had an exaggerated proinflammatory state, despite a pronounced anti-inflammatory response. When the anti-inflammatory response predominated and the proinflammatory state was dampened, organ failure status improved.

Adolescent↗
PubMed1996

Effect of nitric oxide on staphylococcal killing and interactive effect with superoxide.

The role of reactive nitrogen intermediates (RNI) such as nitric oxide (.NO) in host defense against pyogenic microorganisms is unclear, and the actual interactive effect of RNI and reactive oxidative intermediates (ROI) for microbial killing has not been determined. Since, in nature, ROI and RNI might be generated together within any local infection, we evaluated the separate and interactive effects of .NO and O2- on staphylococcal survival by using a simplified system devoid of eukaryotic cells. These studies showed that prolonged exposure of staphylococci to .NO does not result in early loss of viability but instead is associated with a dose-related delayed loss of viability. This effect is abrogated by the presence of hemoglobin, providing further evidence that the effect is RNI associated. Superoxide-mediated killing also is dose related, but in contrast to RNI-mediated killing, it is rapid and occurs within 2 h of exposure. We further show that the interaction of .NO and O(2)- results in decreased O(2)--mediated staphylococcal killing at early time points. .NO, however, appears to enhance or stabilize microbial killing over prolonged periods of incubation. This study did not produce evidence of early synergism of ROI and RNI, but it does suggest that .NO may contribute to host defense, especially when ROI-mediated killing is compromised.

Dose-Response Relationship, Drug↗
PubMed1996

Nitric oxide production in critically ill patients.

OBJECTIVE: To measure serum nitrite and nitrate levels in critically ill children as indicators of endogenous nitric oxide (NO) production. HYPOTHESIS: Endogenous NO production is increased in children with conditions characterised by immune stimulation. DESIGN: Prospective descriptive study in a multidisciplinary paediatric intensive care unit. PATIENTS: 137 consecutive critically ill children with a variety of clinical conditions. INTERVENTIONS: Using a rapid microtitre plate technique, daily serum nitrite and nitrate levels were measured from serum samples that remained in the clinical laboratory after daily routine phlebotomy. Clinical and laboratory information was also gathered daily for each patient. RESULTS: The maximum serum nitrite plus nitrate levels (microM) reached by children with infection (41.8 (SD 18.1)), sepsis syndrome (85.1 (39.9)), shock without sepsis (36.4 (19.1)), transplantation alone (61.0 (43.4)), transplantation with sepsis (200.7 (150.5)), or rejection (161.7 (70.4)), were higher than in controls (18.1 (9.3)). In the absence of exogenous NO donors, levels greater than 80 microM were reached only in children with the sepsis syndrome, organ transplantation, or acute rejection. CONCLUSIONS: Increased endogenous NO production occurs in children with clinical conditions associated with immune stimulation. Further investigation is warranted to determine the value of this simple and rapid test as a clinically useful diagnostic tool and therapeutic monitor in the evaluation of children at risk for the sepsis syndrome or acute allograft rejection.

Child↗
PubMed1995

US-guided core biopsy of the breast with a coaxial system.

From July 1993 through June 1994, the authors performed 42 ultrasound (US)-guided core biopsies with use of a coaxial technique in which a 14- or 15-gauge core biopsy needle was passed through a 12-gauge introducer needle. This technique proved to be effective in all 42 biopsies. Use of the coaxial technique decreased the procedure time necessary for US-guided core biopsy and may be less traumatic than the standard core biopsy technique.

Adult↗
PubMed1994

Mechanisms of biomaterial-induced superoxide release by neutrophils.

Biomaterial-centered infection is an important cause of the failure of prosthetic implants and organs. Because neutrophils mediate host defense against infection, the effect of biomaterials on neutrophil superoxide release and the mechanism of that effect were investigated using three materials commonly employed in surgical practice. The graft materials were expanded polytetrafluorethylene (PTFE), polyurethane and woven dacron. Polystyrene, a commonly used laboratory support vessel, was also studied. Both polystyrene and polyurethane were activating, but serum inhibitable, whereas PTFE was nonactivating, and woven dacron was not activating unless serum was present. The signaling mechanisms used by these materials demonstrated time and material dependency. Pertussis toxin inhibition of G protein-dependent activation had little or no effect on biomaterial induced activation, whereas FMLP-induced activation of the same biomaterial-associated cells was inhibited. Protein kinase C inhibition with staurosporine greatly inhibited polystyrene-induced activation, but had only a partial effect with polyurethane and even less effect with the activation associated with serum-treated woven dacron. These studies demonstrated that biomaterial contact-induced neutrophil activation differed from that described for cells in suspension, and showed that activation mechanisms on one material cannot be extrapolated to mechanisms on other materials.

Alkaloids↗
PubMed1994

Incidentally discovered arteriovenous malformation of the anterior fossa dura.

Dural arteriovenous malformations (AVMs) are rare vascular abnormalities that most frequently involve the cavernous, transverse or sigmoid sinus. Anterior cranial fossa dural AVMs are uncommon. We report the clinical, radiological and surgical features of an incidentally discovered anterior fossa dural AVM. The literature regarding the anatomy and clinical presentation of this lesion is reviewed.

Aged↗
PubMed1994

Biomaterial-host interactions: consequences, determined by implant retrieval analysis.

Prosthetic biomaterials have had a profound impact on reconstructive surgery but complete biocompatability remains illusive. This review considers the retrieval analysis of four common prosthetic structures: the hip, the knee, heart valves, and blood vessels. We show that despite a fine record of early success, deterioration due to mechanical failure or deleterious host responses to the implant may compromise long term function. The eventual retrieval and detailed analysis of implanted structures provides an invaluable opportunity to determine the characteristics of implant success or failure and to provoke the development of still better materials.

Biocompatible Materials↗
PubMed1993

Extracranial vertebral artery pseudoaneurysm presenting as subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: True aneurysms of the extracranial vertebral artery are rare. The usual pathogenesis of aneurysms in this location is either penetrating or blunt trauma with resultant pseudoaneurysm formation. We report a postpartum patient with a presumed traumatic pseudoaneurysm of the extracranial vertebral artery presenting with subarachnoid hemorrhage. CASE DESCRIPTION: A 41-year-old woman had three episodes of neck stiffness 1 month after an uncomplicated vaginal delivery. The last episode, 3 days before admission, was accompanied by intense neck and head pain and paresthesias that extended into the left arm, thumb, and forefinger. RESULTS: Lumbar puncture showed subarachnoid hemorrhage. Angiography revealed a left vertebral artery dissection from C6-7 to C3 with pseudoaneurysm at C5-6. Computed tomography demonstrated impingement of the C6 root at the foramen by this lesion. The lesion was successfully treated by balloon occlusion of the vertebral artery. CONCLUSION: We present a patient with an extracranial vertebral pseudoaneurysm with subarachnoid hemorrhage and cervical root impingement. To our knowledge, this is the first case of such a lesion presenting as subarachnoid hemorrhage. The lesion was successfully treated using endovascular techniques.

Adult↗
PubMed1993

Flow cytometric study of the expression of neutral endopeptidase (CD10/CALLA) on the surface of newborn granulocytes.

The susceptibility of newborn infants to bacterial infections is well documented. Neutrophils play an important role in defense against bacterial infection, the most common kind of infection in the newborn period. Many studies of lymphocyte surface characteristics during that period of life are available, but there are no reports on the surface immunophenotype of the granulocytes at birth. Because some of their membrane associated antigens have been identified as enzymes (CALLA/CD10), neutral endopeptidase, and (CD13) amino peptidase that could play a role in the biological functions of neutrophils, a study of the membrane phenotype appeared potentially important. Using flow cytometry, we studied the expression of a panel of the antigens expressed on mature neutrophils including CD10, CD13, and CD33 in 28 full-term babies and 19 adults. A significantly (p < 0.001) lower expression of CD10, CD13, and CD33 was found in full-term babies compared with 19 adults. These data raise two points: first, that because CD10 is detected only on segmented granulocytes, the low level of CD10 observed in neonates is consistent with a degree of immaturity of the neutrophil membrane, and second, that the deficiency of endopeptidase may impair neutrophil interactions with peptide effectors and thus play a role in the increased susceptibility to bacterial infections exhibited in newborns.

Adult↗
PubMed1993

A new procedure for cell lineage determination in acute leukemias. Myeloperoxidase mRNA detection.

Determination of cell lineage in acute leukemias is essential for diagnosis and treatment. Detection of myeloperoxidase (MPO) mRNA establishes myeloid lineage of leukemic blasts that may be too primitive to be identified as myeloblasts based on morphology, cytochemistry, or immunophenotype. A highly specific and sensitive new procedure for MPO mRNA detection has been developed using HL-60 cells. It involves a microprocedure for total cellular RNA extraction, reverse transcription, and specific amplification of target sequences in the resulting MPO cDNA, by the polymerase chain reaction. Specific primers are designed to amplify an 89-base pair (bp) sequence from the signal peptide, 179 and 318-bp sequences from the start and end, respectively, of the heavy-chain sequence, and a 255-bp sequence overlapping the proregion and light chain. The correct-size amplification products, detected electrophoretically, demonstrate MPO mRNA expression in the leukemic cells analyzed. The sensitivity of this new procedure was evaluated on serial concentrations of HL-60 cells and was found to be 10-10(4) cells depending on the MPO cDNA amplified sequence. No amplification products were obtained using peripheral blood lymphocytes as a negative cellular control. The specificity of the procedure is demonstrated by Southern blotting and hybridization with 32P-labeled oligonucleotide probes specific for each of the amplified sequences. An additional advantage of this procedure is availability of results in 8-24 h, compared with 1-2 weeks for conventional RNA methods.

Base Sequence↗
PubMed1992

TNF and IL-1 generation by human monocytes in response to biomaterials.

The biocompatibility of surgically implanted materials may be compromised as a consequence of inflammatory reactions associated with phagocyte activation. Two important mediators of the inflammatory response are Interleukin-1 (IL-1) and tumor necrosis factor (TNF), both of which exert a wide range of biologic effects on many cells. This study was designed to evaluate the release of these cytokines by human monocytes (HM) brought into contact with four biomaterials utilized in clinical practice: polyurethane, expanded polytetrafluorethylene (ePTFE), Dacron velour, and woven Dacron. In vitro cultures for the generation of IL-1 and TNF by HM in the presence of the above biomaterials were established by exposing cells to each biomaterial in the presence and absence of lipopolysaccharide (LPS) with harvest of supernatants after 6 or 18 h. These studies showed that in the absence of LPS, IL-1 was released only by Dacron velour and woven Dacron associated monocytes while TNF was secreted in response to all of the materials. When LPS was present, however, monocytes associated with all of the materials released IL-1; and TNF release was greatly augmented. Further, the quantity of released cytokine was directly related to the duration of the association time. This study demonstrated that HM in association with various biomaterials were activated to produce both TNF and IL-1 and that the addition of nanogram quantities of LPS, such as would be produced if infection were present, greatly increased the amount of cytokines released.

Adult↗
PubMed1992

Biomaterial-induced alterations of neutrophil superoxide production.

Because periprosthetic infection remains a vexing problem for patients receiving implanted devices, we evaluated the effect of several materials on neutrophil free radical production. Human peripheral blood neutrophils were incubated with several sterile, lipopolysaccharide (LPS)-free biomaterials used in surgically implantable prosthetic devices: polyurethane, woven dacron, and velcro. Free radical formation as the superoxide (O2-) anion was evaluated by cytochrome c reduction in neutrophils that were exposed to the materials and then removed and in neutrophils allowed to remain in association with the materials. Neutrophils exposed to polyurethane or woven dacron for 30 or 60 min and then removed consistently exhibited an enhanced release of O2- after simulation via receptor engagement with formyl methionyl-leucyl-phenylalanine. Enhanced reactivity to stimulation via protein kinase C with phorbol myristate acetate, however, was not consistently observed. The cells evaluated for O2- release during continuous association with the biomaterials showed enhanced metabolic activity during short periods of association (especially with polyurethane and woven dacron). Although O2- release by neutrophils in association with these materials decreased with longer periods of incubation, it was not obliterated. These studies, therefore, show that several commonly used biomaterials activate neutrophils soon after exposure and that this activated state diminishes with prolonged exposure but nevertheless remains measurable. The diminishing level of activity with prolonged exposure, however, suggests that ultimately a depletion of reactivity may occur and may result in increased susceptibility to periprosthetic infection.

Biocompatible Materials↗
PubMed1992

Neutrophil function in chronic neutrophilic leukemia: defective respiratory burst in response to phorbol esters.

Functional analyses were performed on neutrophils isolated from 6 patients from two institutions who displayed features of chronic neutrophilic leukemia (CNL). These neutrophils demonstrated a consistent deficiency (44 +/- 8% of control values) in superoxide anion (O2-) production in response to the phorbol ester, phorbol myristate acetate (PMA). O2- production in response to chemotactic peptides was near normal (82.3 +/- 10.7% of control values). Bacterial killing was normal in the two patients studied, and chemotaxis was diminished in response to zymosan-activated plasma and to high concentrations of chemotactic peptides in the patients studied. Cytosolic C kinase activity was decreased in one of the two patients studied. These results suggest that a deficient O2- release in response to PMA is a hallmark of neutrophils in CNL and may provide a diagnostic indicator of this condition.

Aged↗
PubMed1992

Delivery of passivating proteins to sutures during passage through the vessel wall reduces subsequent platelet deposition by blocking fibrinogen adsorption.

Intraluminal vascular suture material, which attracts fewer than the expected number of platelets compared with the same biomaterial exposed to blood in vitro, differs from the untreated biomaterial in that it has been passed once through the vessel wall. The mechanism by which this apparently trivial maneuver reduces platelet deposition was investigated. Polypropylene suture (7-0 Prolene) was passed through human arteries (fetal and adult), and platelet deposition to the suture was measured in a standardized perfusion chamber. Single vessel passage of the sutures reduced platelet deposition by 68 +/- 23%, which contrasts sharply with the power of prostaglandin E1 (1 microM PGE1 is sufficient to abolish platelet shape change and aggregation), which inhibited only 11% of platelet deposition to the sutures. Aspirin treatment of the vessel (to prevent PGI2 formation) or endothelial stripping (to remove the ability to produce nitric oxide) had no effect on the degree of inhibition. Passage of the suture through a vessel analogue (expanded polytetrafluoroethylene) did not inhibit platelet deposition. 125I-fibrinogen adsorption to the suture after vessel passage was reduced to a degree similar to that of platelet deposition. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of proteins eluted from vessel-passed sutures revealed bands at 66, 47, and 16 kd. Western blotting indicated the presence of large amounts of albumin and hemoglobin, a moderate amount of haptoglobin, and only trace amounts of fibrinogen. When sutures were exposed to each of these proteins in vitro before perfusion, albumin and hemoglobin were found to reproduce the effect of vessel passage alone on platelet deposition. We conclude that albumin and hemoglobin adsorb to sutures during their passage through the vessel subendothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗