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Biomedical subjects

S Kolla

Publications and source records attributed to S Kolla.

15 recordsLinked to original sources
PubMed1999

Extracorporeal life support in pulmonary failure after trauma.

OBJECTIVE: To present a series of 30 adult trauma patients who received extracorporeal life support (ECLS) for pulmonary failure and to retrospectively review variables related to their outcome. METHODS: In a Level I trauma center between 1989 and 1997, ECLS with continuous heparin anticoagulation was instituted in 30 injured patients older than 15 years. Indication was for an estimated mortality risk greater than 80%, defined by a PaO2: FIO2 ratio less than 100 on 100% FIO2, despite pressure-mode inverse ratio ventilation, optimal positive end-expiratory pressure, reasonable diuresis, transfusion, and prone positioning. Retrospective analysis included demographic information (age, gender, Injury Severity Score, injury mechanism), pulmonary physiologic and gas-exchange values (pre-ECLS ventilator days [VENT days], PaO2:FIO2 ratio, mixed venous oxygen saturation [SvO2], and blood gas), pre-ECLS cardiopulmonary resuscitation, complications of ECLS (bleeding, circuit problems, leukopenia, infection, pneumothorax, acute renal failure, and pressors on ECLS), and survival. RESULTS: The subjects were 26.3+/-2.1 years old (range, 15-59 years), 50% male, and had blunt injury in 83.3%. Pulmonary recovery sufficient to wean the patient from ECLS occurred in 17 patients (56.7%), and 50% survived to discharge. Fewer VENT days and more normal SvO2 were associated with survival. The presence of acute renal failure and the need for venoarterial support (venoarterial bypass) were more common in the patients who died. Bleeding complications (requiring intervention or additional transfusion) occurred in 58.6% of patients and were not associated with mortality. Early use of ECLS (VENT days < or = 5) was associated with an odds ratio of 7.2 for survival. Fewer VENT days was independently associated with survival in a logistic regression model (p = 0.029). Age, Injury Severity Score, and PaO2:FIO2 ratio were not related to outcome. CONCLUSION: ECLS has been safely used in adult trauma patients with multiple injuries and severe pulmonary failure. In our series, early implementation of ECLS was associated with improved survival. Although this may represent selection bias for less intractable forms of acute respiratory distress syndrome, it is our experience that early institution of ECLS may lead to improved oxygen delivery, diminished ventilator-induced lung injury, and improved survival.

Adolescent↗
PubMed1998

Matrices of paired substitutions show the effects of tRNA D/T loop sequence on Drosophila RNase P and 3'-tRNase processing.

Drosophila RNase P and 3'-tRNase endonucleolytically process the 5' and 3' ends of tRNA precursors. We examined the processing kinetics of normal substrates and the inhibitory effect of the tRNA product on both processing reactions. The product is not a good RNase P inhibitor, with a KI approximately 7 times greater than the substrate KM of approximately 200 nM and is a better inhibitor of 3'-tRNase, with a KI approximately two times the KM of approximately 80 nM. We generated matrices of substitutions at positions G18/U55 and G19/C56 (two contiguous universally conserved D/T loop base pairs) in Drosophila tRNAHis precursors. More than half the variants display a significant reduction in their ability to be processed by RNase P and 3'-tRNase. Minimal substrates with deleted D and anticodon stems could be processed by RNase P and 3'-tRNase much like full-length substrates, indicating that D/T loop contacts and D arm/enzyme contacts are not required by either enzyme. Selected tRNAs that were poor substrates for one or both enzymes were further analyzed using Michaelis-Menten kinetics and by structure probing. Processing reductions arise principally due to an increase in KM with relatively little change in Vmax, consistent with the remote location of the sequence and structure changes from the processing site for both enzymes. Local changes in variant tRNA susceptibility to RNase T1 and RNase A did not coincide with processing disabilities.

Animals↗
PubMed1998

An approach to the treatment of severe adult respiratory failure.

OBJECTIVES: The purpose of this article is to evaluate outcome in adult patients with severe respiratory failure managed with an approach using (1) limitation of end inspiratory pressure, (2) inverse ratio ventilation, (3) titration of PEEP by SvO2, (4) intermittent prone positioning, (5) limitation of FiO2, (6) diuresis, (7) transfusion, and (8) extracorporeal life support (ECLS) if patients failed to respond. PATIENTS AND METHODS: This study was designed as a retrospective review in the intensive care unit of a tertiary referral hospital. One-hundred forty-one consecutive patients with hypoxic (n = 135) or hypercarbic (n = 6) respiratory failure referred for consideration of ECLS between 1990 and 1996. Overall, initial PaO2/FiO2 (P/F) ratio was 75+/-5 (median = 66). RESULTS: Lung recovery occurred in 67% of patients and 62% survived. Forty-one patients improved without ECLS (83% survived); 100 did not and were supported with ECLS (54% survived). Survival was greater in patients cannulated within 12 hours of arrival (59%) compared with those cannulated after 12 hours (40%, P < .05). Multiple logistic regression identified age, duration of mechanical ventilation before transfer, four or more dysfunctional organs, and the requirement for ECLS as independent predictors of mortality. CONCLUSIONS: An approach that emphasizes lung protection and early implementation of extracorporeal life support is associated with high rates of survival in patients with severe respiratory failure.

Adolescent↗
PubMed1997

CCAAT displacement protein (CDP/cut) recognizes a silencer element within the lactoferrin gene promoter.

Expression of neutrophil secondary granule protein (SGP) genes is coordinately regulated at the transcriptional level, and is disrupted in specific granule deficiency and leukemia. We analyzed the regulation of SGP gene expression by luciferase reporter gene assays using the lactoferrin (LF) promoter. Reporter plasmids were transiently transfected into non-LF-expressing hematopoietic cell lines. Luciferase activity was detected from reporter plasmids containing base-pair (bp) -387 to bp -726 of the LF promoter, but not in a -916-bp plasmid. Transfection of a -916-bp plasmid into a LF-expressing cell line resulted in abrogation of the silencing effect. Sequence analysis of this region revealed three eight-bp repetitive elements, the deletion of which restored wild-type levels of luciferase activity to the -916-bp reporter plasmid. Electrophoretic mobility shift assay and UV cross-linking analysis identified a protein of approximately 180 kD that binds to this region in non-LF-expressing cells but not in LF-expressing cells. This protein was identified to be the CCAAT displacement protein (CDP/cut). CDP/cut has been shown to downregulate expression of gp91-phox, a gene expressed relatively early in the myeloid lineage. Our observations suggest that the binding of CDP/cut to the LF silencer element serves to suppress basal promoter activity of the LF gene in non-LF-expressing cells. Furthermore, overexpression of CDP/cut in cultured myeloid stem cells blocks LF expression upon granulocyte colony-stimulating factor-induced neutrophil maturation without blocking phenotypic maturation. This block in LF expression may be due, in part, to the persistence of CDP/cut binding to the LF silencer element.

Base Sequence↗
PubMed1997

Extracorporeal life support for 100 adult patients with severe respiratory failure.

OBJECTIVE: The authors retrospectively reviewed their experience with extracorporeal life support (ECLS) in 100 adult patients with severe respiratory failure (ARF) to define techniques, characterize its efficacy and utilization, and determine predictors of outcome. SUMMARY BACKGROUND DATA: Extracorporeal life support maintains gas exchange during ARF, providing diseased lungs an optimal environment in which to heal. Extracorporeal life support has been successful in the treatment of respiratory failure in infants and children. In 1990, the authors instituted a standardized protocol for treatment of severe ARF in adults, which included ECLS when less invasive methods failed. METHODS: From January 1990 to July 1996, the authors used ECLS for 100 adults with severe acute hypoxemic respiratory failure (n = 94): paO2/FiO2 ratio of 55.7+/-15.9, transpulmonary shunt (Qs/Qt) of 52+/-22%, or acute hypercarbic respiratory failure (n = 6): paCO2 84.0+/-31.5 mmHg, despite and after maximal conventional ventilation. The technique included venovenous percutaneous access, lung "rest," transport on ECLS, minimal anticoagulation, hemofiltration, and optimal systemic oxygen delivery. RESULTS: Overall hospital survival was 54%. The duration of ECLS was 271.9+/-248.6 hours. Primary diagnoses included pneumonia (49 cases, 53% survived), adult respiratory distress syndrome (45 cases, 51 % survived), and airway support (6 cases, 83% survived). Multivariate logistic regression modeling identified the following pre-ECLS variables significant independent predictors of outcome: 1) pre-ECLS days of mechanical ventilation (p = 0.0003), 2) pre-ECLS paO2/FiO2 ratio (p = 0.002), and 3) age (years) (p = 0.005). Modeling of variables during ECLS showed that no mechanical complications were independent predictors of outcome, and the only patient-related complications associated with outcome were the presence of renal failure (p < 0.0001) and significant surgical site bleeding (p = 0.0005). CONCLUSIONS: Extracorporeal life support provides life support for ARF in adults, allowing time for injured lungs to recover. In 100 patients selected for high mortality risk despite and after optimal conventional treatment, 54% survived. Extracorporeal life support is extraordinary but reasonable treatment in severe adult respiratory failure. Predictors of survival exist that may be useful for patient prognostication and design of future prospective studies.

Adolescent↗
PubMed1997

Prolonged extracorporeal life support (ECLS) for varicella pneumonia.

OBJECTIVE: To review the institutional experience of a national tertiary referral center for extracorporeal life support (ECLS) in severe varicella pneumonia. DATA SOURCES: Hospital records and ECLS flow sheets. STUDY SELECTION: All pediatric (nonneonatal) and adult patients who were treated for varicella pneumonia with ECLS at the University of Michigan Medical Center between 1986 and 1995. DATA EXTRACTION: Diagnosis of varicella pneumonia was made by history of recent exposure to chickenpox, progressive dyspnea, fever, a characteristic diffuse, vesicular rash, and a supporting chest roentgenogram. Indications for ECLS included a shunt fraction of > 30% or PaO2/FlO2 ratio of < 80 despite maximal conventional therapy, which included aggressive diuresis, blood transfusions to optimize oxygen-carrying capacity, pressure-controlled/inverse-ratio ventilation, and intermittent prone positioning. DATA SYNTHESIS: Between 1986 and 1995, 191 patients were referred for ECLS. Among these patients, there were 51 (27%) cases of viral pneumonia, of which nine cases were due to acute varicella-zoster infection. Intravenous acyclovir was administered to eight of the nine patients. Of the nine patients, two patients improved using conventional ventilator management, and seven patients underwent ECLS. Overall survival on ECLS was 71% (5/7). The mean (+/-SD) alveolar-arterial oxygen gradient and PaO2/FlO2 ratio were 533 +/- 101 torr (71.3 +/- 13.5 kPa) and 67 +/- 24, respectively. The median duration of mechanical ventilation before ECLS and the subsequent duration of ECLS were 4 and 12.8 days, respectively. One of the deaths was from progressive right heart failure secondary to pulmonary hypertension and the other death was from overwhelming Pseudomonas sepsis. CONCLUSIONS: Early recognition of imminent pulmonary failure and rapid institution of ECLS are critical in the successful management of severe, life-threatening varicella pneumonia.

Acyclovir↗
PubMed1995

Sequence and structure requirements for Drosophila tRNA 5'- and 3'-end processing.

Eukaryotic tRNAs are processed at their 5'- and 3'- ends by endonucleases RNase P and 3'-tRNase, respectively. We have prepared substrates for both enzymes, separated the activities from a Drosophila extract, and designed variant tRNAs to assess the effects of sequence and structure on processing. Mutations affect these reactions in similar ways; thus, RNase P and 3'-tRNase probably require similar substrate structures to maintain the catalytic fit. RNase P is more sensitive to substrate substitutions than 3'-tRNase. In three of the four stems, one substitution prevents both processing reactions while the opposite one has less effect; anticodon stem substitutions hardly affect processing, and double substitution intended to restore base pairing also restore processing to the wild type rate. Structure probing suggests that tRNA misfolding sometimes coincides with reduced processing. In other cases, processing inhibition probably results from specific unfavorable stem appositions leading to local helix deformation. A single T loop substitution disrupts the tertiary D-T loop interaction and reduces processing. We have thus begun mapping tRNA processing determinants on the global, local, and tertiary structure levels.

Animals↗
PubMed1994

A dual block to cell cycle progression in HL60 cells exposed to analogues of vitamin D3.

The physiologically active form of vitamin D3, 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3), induces differentiation of several types of myeloid leukaemia cells. The acquisition of monocyte-like phenotype is accompanied by slower progression through the cell cycle, and G1 block has been reported to be the basis of this effect. It is shown here that human promyelocytic leukaemia HL60 cells treated with analogues of vitamin D3 which are potent inducers of monocytic differentiation have an additional cell cycle block. Exposure to 10(-7) M 1,25(OH)2D3 or 1,25-(OH)2-16-ene-D3 resulted in monocytic differentiation and the expected G1 block evident at approximately 48 h in a rapidly differentiating variant of HL60 cells (HL60-G), and at 96 h in the more slowly differentiating HL60-240 cells. In addition, a G2+M block was noted at approximately 72 h in HL60-G and HL60-240 cells. Exposure to vitamin D3 analogues also markedly increased the number of dikaryons, suggesting that cytokinesis was impaired more than karyokinesis. Treatment with a third analogue 25-hydroxy-16,23-diene-D3 produced little differentiation and had minimal effects on the cell cycle parameters. These findings indicate that vitamin D3 analogues regulate cell proliferation by control of the transition of G1 and G2+M phases, reminiscent of the cdc2/CDK2 type of cell cycle control.

Antineoplastic Agents↗
PubMed1992

Cardiac growth after pediatric heart transplantation.

BACKGROUND: To assess whether normal cardiac growth occurs after heart transplantation in the pediatric age group, we performed a study of 13 infants and children who underwent orthotopic heart transplantation at Stanford. METHODS AND RESULTS: The echocardiographic data from a population of 93 normal children were analyzed to determine estimates of the fifth, 25th, 50th, 75th, and 95th percentiles of the normal pediatric population. Growth curves for each of the cardiac dimensions were stratified into six classes representing each of the percentile bands, and dimensions for the 13 patients were tracked between early postoperative (early) and point of maximal follow-up (late). Results were compared by Student's paired t test to determine whether normal growth was occurring. The mean age at transplant was 5.0 +/- 1.3 years (mean +/- SEM) (range, 0.4-12.8 years), duration of follow-up was 3.1 +/- 0.4 years (1.3-5.8 years), and change in body surface area was 0.24 +/- 0.03 m2 (0.12-0.50 m2). Both right ventricular (RV) and left ventricular (LV) chamber dimensions were within the normal range at both early and late time points and grew normally as assessed by a lack of class changes. Early wall thickness measurements were above the 95th percentile in seven of 13 patients (LV), 12 of 13 patients (septum), and four of 13 patients (RV). Wall thickness measurements remained above normal, and there were no significant class changes at late follow-up. Histological examination in five patients showed markedly increased septal myocyte width, indicating myocyte hypertrophy. Atrial and great vessel anastomotic sites showed no evidence of obstruction by Doppler and catheterization studies. CONCLUSIONS: These data demonstrate that normal cardiac chamber dimensional growth occurs at greater than 3 years' follow-up after pediatric heart transplantation. Significant LV and septal (and to a lesser extent RV) hypertrophy persists and may have implications for long-term allograft growth and function.

Body Surface Area↗
PubMed1989

Analysis of bivariate flow karyotypes.

Bivariate flow karyotype analysis is performed using data from chromosomes stained with two fluorescent dyes, typically chromomycin A3 and Hoechst-33258, and measured in a flow cytometer or cell sorter (Carrano et al.: Proceedings of the National Academy of Sciences of the United States of America 76:1382-1384, 1979; Gray et al.: Proceedings of the National Academy of Sciences of the United States of America 72:1231-1234, 1975; Langlois et al.: Proceedings of the National Academy of Sciences of the United States of America 79:7876-7880, 1982). In the resulting bivariate histogram, most chromosome types appear as individual peaks. In sorting of chromosomes to purify a specific chromosomal type, its corresponding peak in the bivariate histogram is delineated by a rectangular region which surrounds it. All events (objects) that fall within this region trigger the sorting process. In most cases, peaks for different chromosomal types overlap to some extent, and in addition there is always an underlying background due to chromosome fragments and clumps. Thus the sorted population will not be pure; it may include more than one chromosome type and will include debris. To determine the purity of a sort, i.e., the percentage of the sorted material that is of the actual chromosomal type desired, two methods of mathematical analysis have been developed. In the more general method, the bivariate data within an analysis region that includes the sort region, are fit with a series of bivariate Gaussian functions, one for each peak. In a simplified method, the data within the analysis region are transformed into a univariate distribution of either chromomycin A3 or Hoechst-33258 fluorescence. The peaks in these univariate distributions are fit with univariate Gaussian functions. In both methods the purity is determined mathematically. The results of both methods agree well with independent methods of analysis.

Animals↗
PubMedDate not supplied

Extracorporeal life support for cardiovascular support in adults.

The authors retrospectively reviewed their institution's experience with extracorporeal life support (ECLS) for adult cardiovascular failure to determine efficacy and further indications for its use. From 1985 to 1996, venoarterial ECLS was used in 27 adult patients. Indications for ECLS included post cardiotomy cardiac failure, primary myocardial failure, bridge to transplant, and emergency cardiopulmonary resuscitation. The average age was 38.7 +/- 2.7 years and duration of support was 164.0 +/- 26.8 hr. Overall cardiovascular recovery from ECLS was 44%, and hospital survival was 30%. Late deaths were due to multisystem organ failure. Best results were obtained in patients whose processes were reversible during a short duration of ECLS (< 91.6 +/- 33.3 hr. The worst results were obtained in post cardiotomy patients who underwent prolonged support with ECLS. Evaluation of physiologic parameters during the first 30-48 hr of support showed marked improvements from values before ECLS. Because of its relative ease of deployment and its rapid correction of acute physiologic derangements, ECLS can be used as a temporary means of support to determine extent and reversibility of organ dysfunction. Longer term support should include consideration of other mechanical assist devices. The authors no longer consider bridge to transplant an indication for ECLS due to relative donor unavailability.

Adolescent↗
PubMedDate not supplied

Characteristics of an albumin dialysate hemodiafiltration system for the clearance of unconjugated bilirubin.

Extraction of protein bound liver failure toxins, such as unconjugated bilirubin, short chain fatty acids, and aromatic amino acids has been reported using hemodiafiltration with albumin in the dialysate, but the characteristics of such a system have not been described. Therefore, bilirubin clearance using albumin dialysate hemodiafiltration was evaluated in the setting of different dialysate albumin concentrations, varying temperature and pH. An in vitro continuous hemodiafiltration circuit was used with single pass countercurrent dialysis. Unconjugated bilirubin was added to bovine blood and filtered across a polyalkyl sulfone (PAS) hemofilter using matched filtration and dialysate flow rates. The serial bilirubin content was measured and first order clearance kinetics verified. The clearance rate constants were calculated for three dialysate groups of different albumin concentration at constant temperature and pH (group 1: 10 g/dl albumin, n = 5; 2 g/dl albumin, n = 5; normal saline, n = 5), and three groups of different temperature and pH at constant albumin dialysate concentration (group 2: pH = 7.0, temperature = 20 degrees C, n = 5; pH = 7.5, temperature = 20 degrees C, n = 5; pH = 7.0, temperature = 40 degrees C, n = 5). Comparisons were made with ANOVA and Tukey post hoc analysis. When albumin was used in the dialysate, the 2 g/dl group cleared bilirubin 3.1 times faster than saline alone (p = 0.001), and the 10 g/dl group was superior to both (p = 0.001). There were no measurable differences between the 2 g/dl groups at the various temperatures tested (p = 0.08), but the clearance was less at a pH of 7.5 (p = 0.015). The clearance of unconjugated bilirubin is greatly enhanced with the use of albumin containing dialysates when compared to traditional crystalloid hemodiafiltration, is greater at lower pH, and seems to be unaffected by temperature.

Albumins↗
PubMedDate not supplied

Total respiratory support with tidal flow extracorporeal circulation in adult sheep.

A novel pressure gated tidal flow extracorporeal circulation (TF ECC) device was developed, and it was hypothesized that it could provide total respiratory support in apneic adult sheep without adverse hemodynamic or cardiac effects. The circuit consisted of a single lumen cannula, computer driven tubing occluders gated by circuit pressure, a nonocclusive peristaltic blood pump, a spiral coiled membrane lung, and a heat exchanger. Six paralyzed, anesthetized adult sheep were instrumented and TF ECC was instituted via cannulation of the right atrium. Total respiratory support was provided by the circuit during an apneic period of 6 hours. Echocardiography was performed with the animal instrumented (baseline) and after 2 hours of TF ECC. Circuit blood tidal volume was 172.6 +/- 18.0 cc, resulting in a TF ECC flow of 71.1 +/- 10.1 cc/kg/min. At the end of the study period, PaCO2 was 35.5 +/- 7.6 mmHg, paO2) was 91.2 +/- 30.6 mmHg, and pulmonary artery oxygen saturation (SPAO2) was 95 +/- 5%. Hemodynamic stability was maintained with no significant differences at baseline and after 6 hours in mean arterial pressure, mean pulmonary artery pressure, or heart rate noted. Echocardiographic evaluation showed preserved fractional shortening of the left ventricular (LV) septal-lateral dimension (baseline 32.4 +/- 11.4%; 2 hours 34.8 +/- 8.4%). This study demonstrates TF ECC provides total respiratory support without adverse hemodynamic effects, and preserved LV function.

Animals↗