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Biomedical subjects

J A Ramirez

Publications and source records attributed to J A Ramirez.

At least 19 recordsLinked to original sources

Diabetic vitreopapillary traction and macular oedema.

PURPOSE: To describe an association between optic disc traction and diabetic macular oedema (DME) unresponsive to laser treatment. METHODS: A retrospective review of all patients with DME who attended our clinic between September 2001 and November 2003 was undertaken. The patients had undergone ophthalmic history and examination, fluorescein angiography, and optical coherence tomography (OCT) of the macular area and optic nerve head (ONH). A total of 10 nonvitrectomized eyes that were found to have an elevation of the ONH secondary to vitreopapillary traction were included in the analysis. Eyes with additional traction at the posterior pole were excluded. RESULTS: Out of the 10 eyes (seven patients, aged 47-79 years) with vitreo-papillary traction, nine had previously undergone argon laser photocoagulation(s) for DME. In seven eyes (seven patients), OCT verified the vitreopapillary traction as the sole traction, whereas in the fellow eyes of three patients vitreomacular traction was evident as well. In the seven eyes with only vitreopapillary traction, OCT demonstrated parapapillary serous retinal detachment in two eyes and a diffuse DME in all eyes (mean foveal thickness, 396+/-144 microm). Maximal thickness of the papillo-macular bundle site was adjoining the elevated ONH in three eyes, and was maximal at the central macula in the other four eyes. Ultrasonography (n=5) revealed an incomplete detachment of the posterior hyaloid in each, adherent only at the ONH. CONCLUSIONS: Diffuse DME unresponsive to laser treatment may be associated with vitreopapillary traction. Further studies should indicate whether these two phenomena could suggest a cause and effect in such eyes.

Aged↗

Direct coronary stenting versus stenting with balloon pre-dilation: immediate and follow-up results of a multicentre, prospective, randomized study. The DISCO trial. DIrect Stenting of COronary Arteries.

AIMS: To assess the safety of direct coronary stenting, its influence on costs, duration of the procedure, radiation exposure, clinical outcome and angiographic restenosis. METHODS AND RESULTS: We randomized 416 patients (446 lesions) to direct stent implant or stent implant following balloon pre-dilation. Patients >75 years old, heavily calcified lesions, bifurcations, total occlusions, left main lesions and very tortuous vessels were excluded. Direct stenting was successful in 217/224 lesions (96.8%). No single loss or embolization of the stent occurred. All stents in the group with pre-dilation were effectively deployed. The immediate post-procedure angiographic results were similar with both techniques. Fluoroscopy and procedural time were significantly lower in direct stenting (6.4+/-0.3 and 21+/-0.9 min) than in pre-dilated stenting (9.1+/-0.4 and 27.5+/-1.1 min) (P>0.001). Major adverse cardiac events during hospitalization were one in direct and four in pre-dilated stenting (P=0.05) but there were no significant differences at follow-ups at 1, 6 and 12 months between the two groups. Angiographic reevaluation at 6 months was performed in 94% of the cases. Restenosis rate was 16.5% in direct stenting and 14.3% in pre-dilated stenting (P=ns). CONCLUSIONS: Direct stenting is as safe as pre-dilated stenting in selected coronary lesions. Acute angiographic results are similar but procedural costs, duration of the procedure and radiation exposure are lower in direct stenting. Overall success rate, mid-term clinical outcome and restenosis are similar with both techniques.

Adult↗

Hyperhomocysteinemia in stable pediatric, adolescents, and young adult renal transplant recipients.

BACKGROUND: High total plasma homocysteine (tHcy) levels are accompanied by an increased risk for premature development of atherosclerosis and atherothrombosis. Adult renal transplant recipients have elevated tHcy levels. Corresponding data in pediatric, adolescent, and young adult renal transplant recipients are scarce. We investigated whether tHcy levels were elevated in stable renal transplant recipients who received kidney grafts before age 18. METHODS: This cross-sectional study was conducted during routine posttransplantation follow-up. Fasting tHcy levels, serum creatinine, and lipoprotein profile were measured in 38 clinically stable renal transplant recipients with different degrees of renal function. No patient was receiving B vitamin or folic acid supplementation. Estimated glomerular filtration rate (GFR) was assessed according to Schwartz's formula. All patients followed a triple-drug immunosuppressive regimen, with the exception of three patients (deflazacort and azathioprine). Forty-one apparently healthy subjects constituted the control group. tHcy levels were determined by fluorescence polarization immunoassay in an IMx analyzer. RESULTS: Mean tHcy levels in transplant recipients were significantly higher than in controls (16.8+/-8.7 micromol/L and 9.5+/-2.3 micromol/L, respectively; P<0.01). A significant positive correlation between tHcy and serum creatinine levels was observed for both transplant recipients (rS=0.70, P<0.01) and controls (rS=0.54, P<0.01). In transplant recipients, tHcy correlated negatively with estimated GFR (rS=[minus]0.47, P<0.05). Fasting tHcy levels in excess of 14.6 micromol/L (>95th percentile in controls) were present in 19 (50%) patients; 14 of these patients had an estimated GFR<60 ml/min per 1.73 m2. When the renal transplant recipients were analyzed by renal function, mean tHcy was significantly higher in patients with an estimated GFR<60 ml/min per 1.73 m2 compared with patients with an estimated GFR> or =60 ml/min per 1.73 m2 (20.5+/-9.9 vs. 13.2+/-5.8 micromol/L, P<0.01). Both groups were significantly different from controls (P<0.01). No relationship was found between tHcy level and either cumulative cyclosporine or cumulative methylprednisone doses. No differences were observed in tHcy levels or lipoprotein profile between patients who were receiving deflazacort and those on methylprednisone. CONCLUSIONS: Hyperhomocysteinemia in renal transplant recipients is a common condition. Testing for fasting tHcy level might be a useful tool to identify patients at increased risk for development of vascular disease.

Adolescent↗

Early switch from intravenous to oral antibiotics in hospitalized patients with bacteremic community-acquired Streptococcus pneumoniae pneumonia.

BACKGROUND: The identification of Streptococcus pneumoniae bacteremia in hospitalized patients with community-acquired pneumonia is considered by some investigators to be an exclusion criterion for early switch from intravenous to oral therapy. OBJECTIVE: To determine whether the switch from intravenous to oral therapy in such patients, once the bx;1patient reaches clinical stability, is associated with poor clinical outcome. METHODS: The medical records of 400 patients with community-acquired pneumonia hospitalized at the Veterans Affairs Medical Center of Louisville (Louisville, Ky) were reviewed to identify patients with bacteremic S pneumoniae. Four criteria were used to define when a patient reached clinical stability and should be considered a candidate for switch therapy: (1) cough and shortness of breath are improving, (2) patient is afebrile for at least 8 hours, (3) white blood cell count is normalizing, and (4) oral intake and gastrointestinal tract absorption are adequate. RESULTS: A total of 36 bacteremic patients were identified. No clinical failures occurred in 18 patients who reached clinical stability and were switched to oral therapy or in 7 patients who reached clinical stability and continued intravenous therapy. Clinical failures (5 deaths) occurred in the group of 11 patients who did not reach clinical stability. CONCLUSION: Once a hospitalized patient with community-acquired pneumonia reaches clinical stability, it is safe to switch from intravenous to oral antibiotics even if bacteremia caused by S pneumoniae was initially documented.

Administration, Oral↗

Accuracy of intravascular ultrasound for diameter measurement of phantom arteries.

BACKGROUND: Uniplanar quantitative angiography (QA) is the standard method for measuring vessel diameter during surgical and endovascular procedures. Intravascular ultrasound (IVUS), a relatively new technology, is another means of obtaining this measurement. This study was designed to validate the accuracy of these two modalities by comparing each to direct caliper measurement, the gold standard, using phantom femoral artery segments (PAS). MATERIALS AND METHODS: PAS diameter was measured with a 12.5-MHz mechanically rotating IVUS catheter (Boston Scientific Corp.) and QA (OEC Corp.) was compared to the direct caliper measurement (Mitutoyo Corp.) at 60 different locations within PAS. At each location minimal lumen diameter and perpendicular lumen diameter were measured and their mean was calculated. The intraclass correlation coefficients (ICCC) between direct caliper measurement and IVUS and uniplanar and biplanar angiography were calculated. Fisher's Z transformation was used to compare the correlation coefficients. RESULTS: The ICCC for IVUS was 0.89. The ICCCs for uniplanar and biplanar angiography were 0.73 and 0.82, respectively. IVUS correlated more closely with direct caliper measurement than uniplanar and biplanar angiography (P = 0.00008, 0.02) Biplanar angiography correlated more closely with direct caliper measurement than uniplanar angiography (P = 0.04). CONCLUSIONS: IVUS more accurately measures lumen diameter than uniplanar or biplanar angiography. Diameter measurement with biplanar angiography is more accurate than uniplanar angiography.

Angiography↗

Ambulatory blood pressure monitoring after recovery from hemolytic uremic syndrome.

The outcome of acute renal failure due to diarrhea-associated hemolytic uremic syndrome (D+ HUS) is generally predicted to be good. However, there are only a few long-term observations with detailed reports on long-term sequelae. Specifically, adequate long-term blood pressure (BP) evaluations are scarce. The present study evaluated BP in pediatric patients after childhood D+ HUS. The study group comprised 28 patients (20 males) aged 6-23.5 years (median 10.1 years). All patients had a history of D+ HUS at a median age of 1.1 years (range 0.5-6 years). Based on the duration of oliguria and/or anuria, the primary disease was classified as mild (n=6), moderate (n=6), or severe (n=16). The BP in these patients was studied at a median time of 8.4 years (range 2.3-22.9 years) after manifestation of D+ HUS by means of office BP measurements and 24-h ambulatory BP monitoring (ABPM) using a Spacelabs 90207 oscillometric monitor. Measurements were compared with normal values of published standards for healthy children and adolescents. Conventional office BP measurements were above the 95th percentile in 1 patient. By ABPM, 2 patients were diagnosed to have mean systolic daytime and nighttime values in the hypertensive range, and systolic and diastolic hypertension was confirmed in the first patient. All these patients had a severe form of D+ HUS in the past. By applying ABPM, BP anomalies were detected in 5 additional patients. Elevated systolic BP loads were found in 4 patients, and daytime systolic and diastolic hypertension in the other 1. At the time of the study, 2 of them were classified as "recovered." The late outcome of D+ HUS may be worse than anticipated. BP anomalies as long-term sequelae of D+ HUS could be identified by ABPM but not by office BP measurements. These findings may represent an isolated sign of residual renal disturbance.

Adolescent↗

Analysis of nonpenetrating clips versus sutures for arterial venous graft anastomosis.

The use of nonpenetrating clips (NPC) for vascular anastomosis is quickly becoming accepted. Studies attest to decreased anastomotic time, comparable patency rates, and decreased blood loss. Few human studies on the use of NPC have been done to date. The purpose of this study was to evaluate primary patency rates, operative time, and complications associated with NPC compared to those with standard sutures for arterial venous graft (AVG). We retrospectively reviewed the clinical course of 82 patients with a mean age of 45 years (range, 22 to 87) from February 1996 to July 1999. All patients underwent upper extremity AVG construction. The procedures were performed at a single institution, by a single, well-experienced surgeon who has extensive experience with NPC. Primary patency rates, operative time, and complications were analyzed. Overall thrombotic incidence of AVG when NPC were used (27/48, 56%) was similar to that of sutures (17/34, 50%). Thrombotic incidence within the first year was similar as well (23/48, 48% and 13/34, 38%). The mean time to primary thrombosis was similar in both groups (6.9 and 6.8 months). The operative time required to construct an AVG with NPC (83 min) was significantly less than that with sutures (96 min) (p = 0.015). There was no significant difference in incidence of graft infection or pseudoaneurysm formation. NPC for AVG reduced operative time and resulted in primary patency and complication rates similar to those associated with use of sutures. The mean time to primary thrombosis was similar for both groups. Our findings suggest an intimal hyperplastic response of a similar nature resulting in thrombosis of both NPC and sutured AVGs.

Adult↗

Characterization of Chlamydia pneumoniae persistence in HEp-2 cells treated with gamma interferon.

Infection with Chlamydia pneumoniae has been implicated as a potential risk factor for atherosclerosis. This study demonstrated the effects of gamma interferon (IFN-gamma)-mediated indoleamine 2,3-dioxygenase activity on C. pneumoniae persistence in HEp-2 cells, inclusion morphology, and ultrastructure. C. pneumoniae replication showed a dose-dependent decrease when treated with increasing concentrations of IFN-gamma and a phenotypic switch resulting in a decrease in typical inclusions with an increase in smaller, less-dense atypical inclusions. Ultrastructural analysis of IFN-gamma-treated C. pneumoniae revealed atypical inclusions containing large reticulatate-like aberrant bodies with no evidence of redifferentiation into elementary bodies.

Chlamydophila pneumoniae↗

Erythrocytic glutathione and plasma cysteine status of human immunodeficient patients.

Both deficient and normal blood levels of glutathione (GSH) and cysteine (Cys) have been reported in HIV patients, a discrepancy that has been attributed to different methodologies. The goal of this study was to apply our analytical method to this problem. Blood samples from HIV patients and healthy subjects were collected, immediately stabilized, and quantified using high performance liquid chromatography with dual electrochemical detection. The results showed that the erythrocytic GSH levels were the same in healthy subjects and in HIV patients regardless of their CD4 lymphocyte level. Only those with the lowest CD4 level plus opportunistic infections had supranormal [corrected] GSH concentrations (P < 0.001). GSH plus glutathione disulfide (GSSG) levels also were normal in patients. However, the Cys contents were higher in patients than in controls (P < 0.05). These findings demonstrated that HIV patients have normal erythrocytic GSH concentrations and supranormal Cys levels.

Adult↗

Managing antiinfective therapy of community-acquired pneumonia in the hospital setting: focus on switch therapy.

Targeting patients for early switch from intravenous to oral antibiotic therapy and early hospital discharge is an important strategy in the management of community-acquired pneumonia (CAP). This strategy can reduce costs due to drug administration and length of hospital stay. We show that switch therapy can be implemented safely when four criteria are met: cough and respiratory distress improve, fever abates for at least 8 hours, white blood cell count is returning to normal, and patient can take drugs orally In prospective clinical studies conducted at our institution, the clinical cure rate with switch therapy was 99%, and mean length of hospital stay was reduced by more than 2 days. Early switch, coupled with hospital discharge, may be possible in nearly half of all CAP patients. Universal use of switch therapy in the United States could result in the total reduction of about 440,000 hospital days annually and an overall savings of $400 million.

Administration, Oral↗

Conversion from azathioprine [correction of azathioprina] to mycophenolate mofetil in pediatric renal transplant recipients with chronic rejection.

BACKGROUND: Chronic rejection is the leading cause of graft failure. Both nonimmunological and immunological mechanisms contribute to this pathology. METHODS: We studied changes in kidney function, mixed lymphocyte culture, cell-mediated lympholysis, serum HLA class I antigens, cytotoxic antibodies, and lymphocyte population before and after 6 months of follow-up in 22 pediatric renal transplanted patients. The immunosuppressive protocol used was: cyclosporine, azathioprine, and corticosteroids. Eight patients demonstrated chronic graft rejection (by biopsy), group I; and eight patients had no clinical evidence of chronic and/or acute rejection, group II. Substitution of mycophenolate mofetil (MMF) (600 mg/m2 bid for azathioprine was done in patients of groups I and II. Another six patients with chronic rejection, did not receive MMF, group III. RESULTS: Creatinine clearance increased in group I (44+/-5 vs. 51.1+/- ml/min/1.73 m2, P<0.03) but it decreased in group III (30+/-3 vs. 25+/-2, P<0.01). Urinary protein excretion decreased only in group I (0.3+/-0.03 to 0.06+/-0.03 g/24 hr, P<0.03). During MMF therapy antidonor mixed lymphocyte culture decreased 62 and 70% (P<0.05) in group I and II. Cell-mediated lympholysis against lymphocyte of the donor decreased 65% (P<0.05) in group I. Cell-mediated lympholysis toward control cells decreased 54% (P<0.01) in group II. Serum HLA class I antigens, only decreased from 0.7+/-0.1 to 0.5+/-0.1 microl/ml, P<0.05, in group I. CD19+ decreased from 7.9+/-1.1 to 5.6+/-0.8%, P<0.05, and 7.8+/-1.2 to 5.5+/-0.9%, P<0.05, in groups I and II, respectively. CD16+ increased from 5.7+/-1.1 to 8.6+/-1.3 (P<0.05) only in group I. CONCLUSIONS: Our data suggest that substituting MMF for azathioprine therapy leads to an improvement in the immunosuppression and renal function in children with on-going chronic rejection.

Adolescent↗

Interactions of Chlamydia pneumoniae with human endothelial cells.

In order to fulfill the "biological plausibility" criterion of a role for infection with Chlamydia pneumoniae in the pathogenesis of human atherosclerosis, detailed studies on the interaction of this organism with the cell types involved are necessary. This article summarizes the current knowledge on the interaction of C. pneumoniae with human endothelial cells. In vitro, C. pneumoniae can infect human endothelial cells and induce the expression of many molecules that are important mediators of atherogenesis including cytokines, adhesion molecules, chemokines, and molecules with procoagulant activity.

Arteriosclerosis↗

Clinical efficacy of intravenous followed by oral azithromycin monotherapy in hospitalized patients with community-acquired pneumonia. The Azithromycin Intravenous Clinical Trials Group.

The purpose of this study was to evaluate intravenous (i.v.) azithromycin followed by oral azithromycin as a monotherapeutic regimen for community-acquired pneumonia (CAP). Two trials of i.v. azithromycin used as initial monotherapy in hospitalized CAP patients are summarized. Clinical efficacy is reported from an open-label randomized trial of azithromycin compared to cefuroxime with or without erythromycin. Bacteriologic and clinical efficacy results are also presented from a noncomparative trial of i.v. azithromycin that was designed to give additional clinical experience with a larger number of pathogens. Azithromycin was administered to 414 patients: 202 and 212 in the comparative and noncomparative trials, respectively. The comparator regimen was used as treatment for 201 patients; 105 were treated with cefuroxime alone and 96 were given cefuroxime plus erythromycin. In the comparative trial, clinical outcome data were available for 268 evaluable patients with confirmed CAP at the 10- to 14-day visit, with 106 (77%) of the azithromycin patients cured or improved and 97 (74%) of the comparator patients cured or improved. Mean i.v. treatment duration and mean total treatment duration (i.v. and oral) for the clinically evaluable patients were significantly (P < 0.05) shorter for the azithromycin group (3.6 days for the i.v. group and 8.6 days for the i.v. and oral group) than for the evaluable patients given cefuroxime plus erythromycin (4.0 days for the i.v. group and 10.3 days for the i.v. and oral group). The present comparative study demonstrates that initial therapy with i.v. azithromycin for hospitalized patients with CAP is associated with fewer side effects and is equal in efficacy to a 1993 American Thoracic Society-suggested regimen of cefuroxime plus erythromycin when the erythromycin is deemed necessary by clinicians.

Administration, Oral↗

Inhibition of Chlamydia pneumoniae replication in human aortic smooth muscle cells by gamma interferon-induced indoleamine 2, 3-dioxygenase activity.

Infection with Chlamydia pneumoniae, a human respiratory pathogen, has been implicated as a potential risk factor in atherosclerosis, possibly because the pathogen can exist in a persistent form similar to that described for Chlamydia trachomatis. The present study investigated whether gamma interferon (IFN-gamma) can induce indoleamine 2,3-dioxygenase (IDO) activity in aortic smooth muscle cells, leading to a marked inhibition of C. pneumoniae growth. Our data indicate a stimulation of IDO mRNA expression and dose-dependent enzymatic activity following IFN-gamma treatment. IDO-mediated increase in tryptophan catabolism resulted in a dose-dependent marked inhibition of C. pneumoniae replication.

Aorta↗

Requirement for NF-kappaB in transcriptional activation of monocyte chemotactic protein 1 by Chlamydia pneumoniae in human endothelial cells.

Infection with Chlamydia pneumoniae, a causative agent of acute and chronic respiratory diseases, has recently been implicated as a potential risk factor in atherosclerosis. Atherosclerotic lesions are characterized by monocyte infiltration, which may be regulated by the chemokine monocyte chemotactic protein 1 (MCP-1). We have previously shown that C. pneumoniae infection stimulates MCP-1 production in human endothelial cells, an event which may be specific to this species of Chlamydia, since Chlamydia trachomatis infection fails to induce this response. To examine the underlying mechanisms by which C. pneumoniae infection induces MCP-1 production in endothelial cells, the present study investigated the role of transcription factor NF-kappaB in MCP-1 mRNA expression. Human umbilical vein endothelial cells (HUVEC) were infected with the coronary isolate C. pneumoniae A-03 or with C. trachomatis L2, and MCP-1 mRNA expression was assessed after different periods of infection by reverse transcription-PCR. Expression of MCP-1 mRNA in C. pneumoniae-infected HUVEC was significantly elevated as early as 1 h postinfection and increased dramatically by 12 and 24 h compared to baseline controls. Nuclear translocation of NF-kappaB occurred by 30 min of infection, as determined by electrophoretic mobility shift assays and immunofluorescence staining. Treatment of C. pneumoniae-infected HUVEC with parthenolide, a specific inhibitor of NF-kappaB activation, suppressed MCP-1 mRNA expression. In contrast, infection with C. trachomatis L2 did not induce MCP-1 mRNA in infected HUVEC and failed to activate NF-kappaB. Results from this study demonstrate a requirement for NF-kappaB activation in stimulation of MCP-1 gene expression by C. pneumoniae in human endothelial cells. Furthermore, the data suggest that, within the genus Chlamydia, functionally distinct signaling pathways leading to NF-kappaB activation are utilized by C. pneumoniae in endothelial cells during infection.

Arteriosclerosis↗

Antiviral effect of brassinosteroids against herpes virus and arenaviruses.

A natural brassinosteroid and a series of synthetic derivatives were found to be good inhibitors of herpes simplex virus type 1 (HSV-1) and arenavirus replication in cell culture. The synthetic compounds tested were analogues of the 24(S) ethylbrassinone. Compounds (22 R,23 R,24S)-2alpha, 3alpha,5alpha,22,23-pentahydroxy-stigmastan-6-one and (22R,23R,24S)-3beta-bromo-5alpha,22,23-trihydroxy stigmastan-6-one were cytotoxic at concentrations of 20-40 microM. (22S,23S,24S)-2alpha,3alpha,22,23-tetrahydroxy-5alpha, stigmastan-6-one, (22R,23R,24S)-3beta-acetoxy-22,23-dihydroxy-5alpha-choles tan-6-one, (22S,23S,24S)-3beta-bromo-22,23-dihydroxy-5alpha-cholestan-6 -one and (22S,23S,24S)-3beta-bromo-5alpha,22,23-trihydroxy-stigmastan -6-one were the most active of the series against HSV-1, with selectivity index (SI) values (CC50/EC50) ranging from 10.6 to 16.5. The majority of the compounds were potent inhibitors of arenaviruses, (22S,23S,24S)-3beta-bromo-5alpha,22,23-trihydroxy-stigmastan -6-one being the most active, with SI values of 307.8 and 692.5 for Tacaribe and Junin viruses, respectively. The antiviral activity of brassinosteroid derivatives was not because of direct inactivation; time-of-addition experiments suggested that a late step in HSV-1 multiplication was affected, whereas arenaviruses remained susceptible to the compounds throughout the replicative cycle.

Animals↗

A randomized, double-blind, placebo-controlled trial of the effects of prophylactic theophylline on renal function in term neonates with perinatal asphyxia.

BACKGROUND: The kidney is the most damaged organ in asphyxiated full-term infants. Experiments in rabbits and rats have shown that renal adenosine acts as a vasoconstrictive metabolite in the kidney after hypoxemia and/or ischemia, contributing to the fall in glomerular filtration rate (GFR) and filtration fraction. Vasoconstriction produced by adenosine can be inhibited by the nonspecific adenosine receptor antagonist, theophylline. Gouyon and Guignard performed studies in newborn and adult rabbits subjected to normocapnic hypoxemia. Their results clearly showed that the hypoxemia-induced drop in GFR could be avoided by the administration of low doses of theophylline. OBJECTIVE: This study was designed to determine whether theophylline could prevent and/or ameliorate renal dysfunction in term neonates with perinatal asphyxia. SETTING: Buenos Aires, Argentina. STUDY DESIGN: We randomized 51 severe asphyxiated term infants to receive intravenously a single dose of either theophylline (8 mg/kg; study group: n = 24) or placebo (control group: n = 27) during the first 60 minutes of life. The 24-hour fluid intake and the urine volumes formed were recorded during the first 5 days of life. Daily volume balances (water output/input ratio and weights) were determined. Severe renal dysfunction was defined as serum creatinine elevated above 1.50 mg/dL, for at least 2 consecutive days after a fluid challenge, or rising levels of serum creatinine (.3 mg/dL/day). The GFR was estimated during the second to third days of life by endogenous creatinine clearance (mL/minute/1.73 m2) and using Schwartz's formula: GFR (mL/minute/1.73 m2) =.45 x length (cm)/plasma creatinine (mg/100 mL) during the first 5 days of life. Tubular performance was assessed as the concentration of beta2-microglobulin (beta2M) determined by enzyme immunoassay, on the first voided urine 12 hours after theophylline administration. The statistical analysis for the evaluation of the differences between the groups was performed with Student's t and chi(2) tests as appropriate. RESULTS: During the first day of life, the 24-hour fluid balance was significantly more positive in the infants receiving placebo compared with the infants receiving theophyline. Over the next few days, the change in fluid balance favored the theophyline group. Significantly higher mean plasma values were recorded in the placebo group from the second to the fifth days of life. Severe renal dysfunction was present in 4 of 24 (17%) infants of the theophylline group and in 15 of 27 (55%) infants of the control group (relative risk:.30; 95% confidence interval:.12-.78). Mean endogenous creatinine clearance of the theophylline group was significantly increased compared with the creatinine clearance in infants receiving placebo (21.84 +/- 7.96 vs 6.42 +/- 4.16). The GFR (estimated by Schwartz's formula) was markedly decreased in the placebo group. Urinary beta2M concentrations were significantly reduced in the theophylline group (5.01 +/- 2.3 mg/L vs 11.5 +/- 7.1 mg/L). Moreover, 9 (33%) patients of the theophylline group versus 20 (63%) infants of the control group had urinary beta2M above the normal limit (<.018). There was no difference in the severity of the asphyxia between infants belonging to the theophylline and control groups in regards of Portman's score. Except for renal involvement, a similar frequency of multiorganic dysfunction, including neurologic impairment, was observed in both groups. The theophylline group achieved an average serum level of 12.7 microg/mL (range: 7.5-18.9 microg/mL) at 36 to 48 hours of live versus traces (an average serum level of .87 microg/mg) in the placebo group. CONCLUSIONS: Our data suggest that prophylactic theophylline, given early after birth, has beneficial effects on reducing the renal dysfunction in asphyxiated full-term infants. (ABSTRACT TRUNCATED)

Asphyxia Neonatorum↗