Positive effect of physicians-in-training on patient care.
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Clinical Competence↗
Biomedical subjects
J Mattana
Publications and source records attributed to J Mattana.
Effect of time of day of dialysis shift on serum biochemical parameters in patients on chronic hemodialysis.
It is unknown whether predialysis serum biochemical parameters may differ among chronic hemodialysis patients depending on the shift during which they are dialyzed. We studied 115 patients on chronic hemodialysis in our institution for 3 consecutive months and compared clinical and biochemical parameters based on the shift during which they were dialyzed. Predialysis serum potassium was found to be progressively higher for patients dialyzed on later as compared with earlier dialysis shifts, and phosphate was significantly higher for patients dialyzed during the evening shift as well. Regression analysis suggested that higher of potassium and phosphate levels were related to the time of day these sessions and not to patient age, amount of dialysis given or diet. By contrast, serum albumin, creatinine, sodium, and chloride levels were found to differ depending on dialysis shift, though these differences appeared to be accounted for by patient age. We concluded that the time of day of the beginning of the dialysis shift appears to mildly influence the levels of serum predialysis biochemical parameters which are important in monitoring patients on chronic hemodialysis, in particular potassium and phosphate. Further insight into the mechanism of this observed effect might improve our ability to interpret and treat derangements of these serum biochemical parameters in patients on chronic hemodialysis.
Case-Control Studies↗
Effects of prostaglandin E2 on mesangial cell migration.
Mesangial cell migration is a feature of certain renal diseases such as mesangiocapillary glomerulonephritis, a disorder which responds to treatment with cyclo-oxygenase inhibitors. We undertook the present study to determine whether prostaglandin E2 (PGE2) might have a direct effect on mesangial cell migration. PGE2 (10(-8) M) treated cells migrated a mean percent area of 16.8 +/- 0.5 during 24 h when compared to control cells which migrated only a mean percent area of 10.3 +/- 0.8 (p < 0.001). At 48 h, PGE2-treated cells migrated a mean percent area of 21.7 +/- 1.1 when compared to control cells which migrated only a mean percent area of 14.7 +/- 1.4 (p < 0.01). Meclofenamate (10(-5) M), a cyclo-oxygenase inhibitor, significantly (p < 0.02) inhibited migration of mesangial cells (at 48 h controls 13.4 +/- 0.5 vs. meclofenamate-treated cells 3.2 +/- 0.8). Since meclofenamate attenuates basal production of PGE2 by mesangial cells, inhibition of migration by mesangial cells by meclofenamate indicates that the basal production of PGE2 by mesangial cells also significantly contributes to the migration of mesangial cells. 3-Isobutyl-1-methylxanthine (IBMX, 10(-3) M), a phosphodiesterase inhibitor, also significantly (p < 0.001) enhanced migration of mesangial cells (controls 13.4 +/- 0.5 vs. IBMX-treated cells 20.8 +/- 0.5). These results suggest that mesangial cell migration is directly enhanced by PGE2. The present study provides a rationale for the use of cyclo-oxygenase therapy in patients with mesangiocapillary glomerulonephritis.
1-Methyl-3-isobutylxanthine↗
Effects of macrophage supernatants on mesangial cell migration and hillock formation.
There is considerable evidence suggesting a role for the macrophage (M phi) in the development of glomerulosclerosis (GS) and atherosclerosis, lesions which appear to be analogous. Migration of mesangial cells (MC), which are modified smooth muscle cells, may play a role in the pathogenesis of glomerular injury, and smooth muscle migration may play a role in the pathogenesis of atherosclerosis as well. We undertook the present study to determine the effects of M phi supernatants (M phi SN) on MC migration and formation of MC hillocks, which are considered an in vitro model of GS. By means of a migration assay using wounded cultures of confluent, growth-arrested MC, MC migration was found to be significantly enhanced by incubation with M phi SN at 24 hr (migration score: M phi SN, 24.3 +/- 1.3; control, 11.6 +/- 1.0, P < 0.001) as well as 48 hr incubation (migration score: M phi SN, 34.0 +/- 1.4; control, 15.4 +/- 1.4, P < 0.001). Enhanced MC migration following prolonged incubation with M phi SN was also shown using phase contrast microscopy and scanning electron microscopy. MC hillock formation was enhanced by M phi SN in a concentration-related manner as was hillock size. These data demonstrate that M phi SN can directly enhance MC migration and hillock formation, processes that may in part account for the observed role for the M phi in the development of mesangial expansion and GS as well as atherosclerosis.
Animals↗
Repetitive mechanical strain suppresses macrophage uptake of immunoglobulin G complexes and enhances cyclic adenosine monophosphate synthesis.
Uptake of immunoglobulin G (IgG) complexes by macrophages (M phi) may play an important role in disease states characterized by increased levels of circulating immune complexes. In sites such as the glomerular mesangium M phi may be subjected to repetitive mechanical strain, although in vitro studies of M phi endocytosis are typically carried out with cells grown on rigid surfaces. We undertook the present study to determine whether repetitive mechanical strain could modulate M phi endocytosis of IgG complexes. IgG complex uptake was significantly diminished in M phi that were subjected to repetitive mechanical strain using parameters corresponding to peak and minimal intraglomerular pressures compared with control, and uptake varied according to the amount of mechanical strain applied. There was no significant difference in surface binding of IgG between M phi subjected to strain and those not. Mechanical strain did not significantly influence the rate of IgG complex degradation. Inhibition of nitric oxide synthase and guanylate cyclase activity did not alter the effect of mechanical strain, although this effect was potentiated by 3-isobutyl-1-methylxanthine (IBMX). Angiotensin II, which has been shown to reduce adenosine 3',5'-cyclic monophosphate (cAMP) production in M phi, significantly attenuated the suppressive effect of mechanical strain on IgG complex uptake as well as another inhibitor of cAMP generation, indomethacin. Enzyme immunoassay demonstrated significantly enhanced levels of cAMP in M phi that were subjected to mechanical strain compared with control, an effect that was potentiated by IBMX and attenuated by angiotensin II and indomethacin. These results demonstrate that repetitive mechanical strain significantly reduces IgG complex uptake by M phi, most likely by enhancing cAMP synthesis. Such an effect might play a significant role in macromolecule handling by M phi in sites in which they are subjected to repetitive mechanical deformation such as the glomerular mesangium.
1-Methyl-3-isobutylxanthine↗
Heparin attenuates the effect of mitogenic vasoconstrictors on mesangial cell proliferation and handling of immunoglobulin G complexes.
Angiotensin II (ANG II) and endothelin-1 (ET-1) may both play significant roles in causing mesangial expansion and glomerulosclerosis after renal injury by enhancing mesangial cell (MC) proliferation and by increasing MC uptake of macromolecules. Heparin has been demonstrated to significantly ameliorate the development of glomerulosclerosis in animal models of progressive renal injury, although the mechanism is unknown. We undertook the present study to examine in an in vitro system the mechanism by which heparin might modulate the effects of ANG II and ET-1 on MC proliferation and MC uptake of immunoglobulin G (IgG) complexes. Heparin was found to suppress MC uptake of IgG complexes in a concentration-related manner. Whereas ANG II significantly enhanced (P < .01) uptake of IgG complexes, this increase was significantly antagonized (P < .01) by coincubation of MC with heparin at therapeutic concentration (1 U/ml). ET-1 also was found to significantly increase MC uptake of IgG complexes (P < .02), and this increase also was significantly antagonized by coincubation with heparin (P < .02). Heparin was found to inhibit surface binding of IgG to MC in a concentration-related manner (55% reduction at 1 U/ml). MC [3H]thymidine incorporation was significantly enhanced by both ANG II (P < .01) and ET-1 (P < .001) and these mitogenic effects were significantly attenuated by coincubation of cells with heparin (P < .01 and P < .001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin II↗
Urosepsis from an atypical pathogen in a patient with babesiosis.
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Aged↗
Housestaff and faculty perceptions of patients' "teaching value".
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Aged↗
Macrophage Fc receptor activity modulates mesangial cell proliferation and matrix synthesis.
Substantial in vivo evidence exists to implicate the macrophage (M phi) in modulating mesangial expansion and glomerulosclerosis (GS) following renal injury. We studied in an in vitro system how M phi activation via Fc-receptor-mediated endocytosis, such as occurs in immune complex-mediated disease states, may influence the effect of M phi secretory products (MSP) on mesangial cell (MC) proliferation and matrix synthesis. MSP from M phi incubated with immunoglobulin G (IgG) complexes caused significantly greater (P < 0.001) enhancement of MC [3H]thymidine incorporation compared with MSP from unstimulated M phi or from M phi activated via nonspecific endocytosis (P < 0.001). MSP from M phi incubated with IgG complexes plus the inhibitor of endocytosis cytochalasin B showed an attenuated effect on MC proliferation (P < 0.02). MSP were also found to enhance MC matrix synthesis (P < 0.001). These data demonstrate that MSP can play a direct role in mesangial expansion by increasing both MC proliferation and matrix synthesis. Surface binding alone of IgG complexes may not be sufficient to activate M phi and enhance their mitogenic effect on MC as endocytosis appears to be required. These findings lend in vitro support to a potential role for the M phi in the process of mesangial expansion and GS following renal injury.
Cell Division↗
Opioids modulate migration, spreading and adherence of mesangial cells.
Glomerular mesangial cells are considered to be modified smooth muscle cells and seem to play a role in the maintenance of glomerular hemodynamics. The present study was carried out to determine the effect of opioids on adhesiveness, spreading and migration of mesangial cells. Morphine enhanced spreading of mesangial cells at early time periods (5 mini, control 8 +/- 2% vs. morphine 15 +/- 1%, p < 0.05; 15 min, control 21 +/- 5% vs. morphine 38 +/- 2%, p < 0.05) as well as at later time periods when compared to control cells (at 2 h, control 23 +/- 1% vs. morphine 49 +/- 1%, p < 0.001; at 3 h, control 28 +/- 3% vs. morphine 63 +/- 2%, p < 0.05). beta-Endorphin also enhanced (p < 0.001) spreading of mesangial cells (at 2 h, control 23 +/- 1% vs. beta-endorphin 48 +/- 3%; at 3 h, control 28 +/- 3% vs. beta-endorphin 65 +/- 1%). Morphine decreased adhesion of mesangial cells to the plastic substrate at 24 h as well at 48 h when compared to the control cells. Naloxone attenuated the effect of morphine on adhesion to the substrate. Morphine enhanced (p < 0.05) migration (percentage of denuded area covered by mesangial cells when compared to control cells (control 26.07 +/- 1.08% vs. morphine 37.5 +/- 2.94%; n = 9). Since the morphine-induced decreased adhesiveness could be attenuated by naloxone, this effect of morphine on mesangial cells appears to be mediated by opioid receptors.
Animals↗
Cocaine interacts with macrophages to modulate mesangial cell proliferation.
Human immunodeficiency virus infection is associated with the development of focal segmental glomerulosclerosis (FSGS). The majority of these patients with renal disease, however, are also cocaine abusers, but it is unknown what role cocaine may play in the development of focal segmental glomerulosclerosis. We undertook the present study to determine in vitro whether cocaine can modulate mesangial cell (MC) proliferation, a process believed to be a precursor to the development of glomerulosclerosis, either directly or indirectly via interaction with macrophages (M phi). Cocaine alone was not found to alter significantly either MC number or MC [3H]thymidine incorporation. However, when MC were incubated with secretory products collected from M phi preincubated with standard medium or medium containing cocaine, MC proliferation was found to be significantly enhanced with secretory products from M phi preincubated with cocaine in both serum-free (P < .001) and serum-stimulated conditions (P < .001). The effect of cocaine was found to be concentration-related. Pretreatment of macrophage secretory products from cocaine-treated M phi with neutralizing antibodies to transforming growth factor-beta significantly augmented the mitogenic effect of cocaine macrophage secretory products, and neutralizing antibodies to interleukin-6 significantly attenuated this effect. Direct incubation of MC with transforming growth factor-beta and interleukin-6 caused significant suppression and augmentation of MC proliferation, respectively. These data suggest that cocaine can modulate MC proliferation via interaction with M phi and that interleukin-6 and transforming growth factor-beta participate in this modulating effect. These results support a potential role for cocaine in the development of focal segmental glomerulosclerosis in patients with human immunodeficiency virus infection.
Animals↗
High-dose epinephrine in cardiopulmonary resuscitation.
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Cardiopulmonary Resuscitation↗
Prevalence and determinants of acute renal failure following cardiopulmonary resuscitation.
BACKGROUND: The purpose of this study was to determine the prevalence and determinants of acute renal failure in patients following cardiac arrest. METHODS: This was a cross-sectional study of 420 consecutive admissions with a diagnosis of cardiac arrest admitted to the Long Island Jewish Medical Center, New Hyde Park, NY, the Long Island Campus for the Albert Einstein College of Medicine, Bronx, NY, over a 2-year period. Fifty-six patients who initially survived cardiopulmonary resuscitation following cardiac arrest and had serial biochemical and renal function data available were studied. The events during cardiopulmonary resuscitation and clinical and biochemical data were compared and contrasted among patients who developed acute renal failure following cardiopulmonary resuscitation (group 1, n = 16) and those who did not (group 2, n = 40). RESULTS: Patients who developed acute renal failure following cardiopulmonary resuscitation (group 1) had longer duration of resuscitation (12.0 +/- 2.1 minutes vs 6.7 +/- 0.9 minutes for group 2) and received larger dosages of epinephrine during cardiopulmonary resuscitation (1.81 +/- 0.36 mg vs 0.90 +/- 0.18 mg for group 2). Patients in group 1 had a significantly higher frequency of congestive heart failure (43.8% vs 12.5% for group 2), coronary artery disease (87.5% vs 37.5% for group 2), and preexisting compromised renal function (50% vs 12.5% for group 2). Patients in group 1 had significantly worsened long-term survival compared with group 2 patients (6.3% vs 47.5% for group 2). CONCLUSIONS: We conclude that acute renal failure occurs commonly in the postcardiac arrest period. Administration of the vasoconstrictor epinephrine, congestive heart failure, coronary artery disease, and preexisting renal insufficiency may be significant risk factors for the development of postcardiac arrest acute renal failure. The development of acute renal failure following cardiopulmonary resuscitation predicts a lesser likelihood of survival to discharge from the hospital.
Acute Kidney Injury↗
Macrophage supernatants have both stimulatory and suppressive effects on mesangial cell proliferation.
Macrophages may modulate mesangial expansion following renal injury via secretory products. We undertook the present study to determine the effects of macrophage supernatants on mesangial cell proliferation. Macrophage supernatants collected in serum-free media after 24 hours caused significantly enhanced mesangial cell proliferation in long-term culture at concentrations up to 50% but caused suppression at higher concentrations (control, 122,000 +/- 14,000 cells/well; 50% supernatant, 188,000 +/- 15,100 cells/well, P < 0.02 compared to control, n = 4; 80% supernatant, 52,000 +/- 3,500 cells/well, P < 0.01 compared to control, n = 4). In short-term culture [3H]thymidine incorporation, a measure of DNA synthesis, was significantly enhanced compared to control at supernatant concentrations up to 30% (30% supernatant, 4,120 +/- 310 cpm/well; control, 3,210 +/- 97 cpm/well, P < 0.5, n = 4), but uptake was reduced at high concentration (80% supernatant, 2,900 +/- 74 cpm/well; control, 3,210 +/- 97 cpm/well, P < 0.05, n = 4). When macrophage supernatants were collected after 48 hours incubation and incubated with mesangial cells, mesangial cell thymidine uptake was significantly suppressed compared to control (48-hour supernatant, 4,060 +/- 260 cpm/well; control, 5,890 +/- 270 cpm/well, P < 0.01, n = 4) and compared to 24-hour supernatants, which enhanced uptake (24-hour supernatant, 8,080 +/- 340 cpm/well; control, 5,890 +/- 270 cpm/well, P < 0.01, n = 4). Our results suggest that macrophage supernatants can directly enhance mesangial cell proliferation in vitro in both short-term and long-term culture, though this effect is lost at high concentrations of supernatant. These data lend support to the potential role of the macrophage in mediating mesangial expansion following renal injury.
Animals↗
Mesangial cell proliferation is directly enhanced by sera from patients with renal insufficiency.
We undertook the present study to determine whether there is a direct effect of sera from patients with renal insufficiency on mesangial cell proliferation. Growth-arrested mesangial cells were incubated with sera from patients with varying degrees of renal insufficiency and then pulsed with [3H]thymidine. Thymidine uptake was progressively greater with more advanced renal failure and was linearly correlated with (creatinine)-1. This data suggests that serum from patients with loss of renal function contains mitogens capable of directly enhancing mesangial cell proliferation.
Animals↗
Naloxone-responsive encephalopathy in end-stage renal disease.
We report the case of a 61-year-old diabetic woman with end-stage renal disease who was on hemodialysis and who developed an encephalopathy and episodes of hypotension and hypoventilation, all of which showed rapid and dramatic responses on multiple occasions to the administration of the opiate antagonist naloxone. Improvement in encephalopathy was confirmed by electroencephalography. The patient had received no exogenous opiates and had a normal beta-endorphin level. She subsequently developed myoclonus and was treated for possible aluminum overload that was of borderline magnitude. We conclude that this patient had an encephalopathy that responded to opiate receptor blockade. Because of cerebrovascular disease, episodes of diminished blood pressure due to a state of increased opiate receptor stimulation may have unmasked this underlying encephalopathy. These effects may have been secondary to increased opiate-binding sites or to elevated central nervous system levels of endogenous opiates.
Brain Diseases↗
L-arginine and progressive glomerulosclerosis.
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Animals↗
Effects of atrial natriuretic peptide and cGMP on uptake of IgG complexes by macrophages.
Macromolecular handling by macrophages and glomerular mesangial cells may be important in the development of renal injury. We undertook the present study to determine whether atrial natriuretic peptide (ANP), a particulate guanylate cyclase stimulator, plays a direct role in uptake of immunoglobulin G (IgG) complexes by macrophages. Macrophages incubated with ANP at 10(-5) and 10(-6) M showed significantly suppressed uptake of IgG complexes compared with control. Macrophage uptake of IgG complexes was also significantly suppressed by the soluble guanylate cyclase stimulator sodium nitroprusside. Dibutyryl guanosine 3',5'-cyclic monophosphate and dibutyryl adenosine 3',5'-cyclic monophosphate both significantly suppressed IgG complex uptake as well. ANP was found to significantly enhance macrophage guanosine 3',5'-cyclic monophosphate (cGMP) levels compared with control cells, and this effect was antagonized by angiotensin II. Angiotensin II significantly enhanced uptake of IgG complexes and suppressed macrophage adenosine 3',5'-cyclic monophosphate synthesis, and both effects were antagonized by coincubation with ANP. These results suggest that ANP modulates uptake of IgG complexes by macrophages and that this effect may be mediated via cGMP.
Angiotensin II↗