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Biomedical subjects

S Reddy

Publications and source records attributed to S Reddy.

At least 19 recordsLinked to original sources
PubMed2000

RNA CUG repeats sequester CUGBP1 and alter protein levels and activity of CUGBP1.

An RNA CUG triplet repeat binding protein, CUGBP1, regulates splicing and translation of various RNAs. Expansion of RNA CUG repeats in the 3'-untranslated repeat of the mutant myotonin protein kinase (DMPK) mRNA in myotonic dystrophy (DM) is associated with alterations in binding activity of CUGBP1. To investigate whether CUGBP1 is directly affected by expansion of CUG repeats in DM tissues, we examined the intracellular status of CUGBP1 in DM patients as well as in cultured cells over expressing RNA CUG repeats. The analysis of RNA-protein complexes showed that, in control tissues, the majority of CUGBP1 is free of RNA, whereas in DM patients the majority of CUGBP1 is associated with RNA containing CUG repeats. Similarly to DM patients, overexpression of RNA CUG repeats in cultured cells results in the re-allocation of CUGBP1 from a free state to the RNA.protein complexes containing CUG repeats. CUG repeat-dependent translocation of CUGBP1 into RNA-protein complexes is associated with increased levels of CUGBP1 protein and its binding activity. Experiments with cyclohexamide-dependent block of protein synthesis showed that the half-life of CUGBP1 is increased in cells expressing CUG repeats. Alteration of CUGBP1 in DM is accompanied by alteration in translation of a transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta), which has been previously described to be a target of CUGBP1. Analysis of C/EBPbeta isoforms in DM patients with altered levels of CUGBP1 showed that translation of a dominant negative isoform, LIP, is induced by CUGBP1. Results of this paper demonstrate that the expansion of CUG repeats in DM affects RNA-binding proteins and leads to alteration in RNA processing.

Animals↗
PubMed2000

Skeletal muscle sodium channel gating in mice deficient in myotonic dystrophy protein kinase.

Myotonic dystrophy, a progressive autosomal dominant disorder, is associated with an expansion of a CTG repeat tract located in the 3'-untranslated region of a serine/threonine protein kinase, DMPK. DMPK modulates skeletal muscle Na channels in vitro, and thus we hypothesized that mice deficient in DMPK would have altered muscle Na channel gating. We measured macroscopic and single channel Na currents from cell-attached patches of skeletal myocytes from mice heterozygous (DMPK(+/-)) and homozygous (DMPK(-/-)) for DMPK loss. In DMPK(-/-) myocytes, Na current amplitude was reduced because of reduced channel number. Single channel recordings revealed Na channel reopenings, similar to the gating abnormality of human myotonic muscular dystrophy (DM), which resulted in a plateau of Na current. The gating abnormality deteriorated with increasing age. In DMPK(+/-) muscle there was reduced Na current amplitude and increased Na channel reopenings identical to those in DMPK(-/-) muscle. Thus, these mouse models of complete and partial DMPK deficiency reproduce the Na channel abnormality of the human disease, providing direct evidence that DMPK deficiency underlies the Na channel abnormality in DM.

Aging↗
PubMed2000

Inactivation of creatine kinase by S-glutathionylation of the active-site cysteine residue.

Protein S-thiolation, the formation of mixed disulphides of cysteine residues in proteins with low-molecular-mass thiols, occurs under conditions associated with oxidative stress and can lead to modification of protein function. In the present study, we examined the site of S-thiolation of the enzyme creatine kinase (CK), an important source of ATP in myocytes. Inactivation of this enzyme is thought to play a critical role in cardiac injury during oxidative stress, such as during reperfusion injury. Reaction of rabbit CK M isoenzyme with GSSG, used to model protein S-thiolation, was found to result in enzyme inactivation that could be reversed by GSH or dithiothreitol. Measurement of GSH that is released during the thiolation reaction indicated that the maximum extent of CK thiolation was approx. 1 mol of GSH/mol of protein, suggesting thiolation on one reactive cysteine residue. Accordingly, matrix-assisted laser-desorption ionization MS confirmed that the molecular mass of CK was increased, consistent with addition of one GSH molecule/molecule of CK. Using trypsin digestion, HPLC and MS analysis, the active-site cysteine residue (Cys(283)) was identified as the site of thiolation. Reversal of thiolation was shown to be rapid when GSH is abundant, rendering dethiolation of CK thermodynamically favoured within the cell. We conclude that S-glutathionylation of CK could be one mechanism to explain temporary reversible loss in activity of CK during ischaemic injury. The maintainance of GSH levels represents an important mechanism for regeneration of active CK from S-glutathionylated CK.

Amino Acid Sequence↗
PubMed2000

Crk-associated substrate p130(Cas) interacts with nephrocystin and both proteins localize to cell-cell contacts of polarized epithelial cells.

Crk-associated substrate (p130(Cas), Cas) is a docking protein first recognized as having elevated phosphotyrosine content in mammalian cells transformed by v-Src and v-Crk oncoproteins. Subsequent studies have implicated Cas in the control of normal cell behavior through its roles in integrin-mediated signal transduction and organization of the actin cytoskeleton at sites of cell adhesion. In this study, we sought to gain new insight into normal Cas function by identifying previously unrecognized interacting proteins. A yeast two-hybrid screen using the C-terminal region of Cas as a bait identified the Src homology 3 (SH3) domain of the mouse "nephrocystin" protein-orthologous to a human protein whose loss of function leads to the cystic kidney disease familial juvenile nephronophthisis. The putative full-length mouse and partial canine nephrocystin sequences were deduced from cDNA clones. Additional studies using epitope-tagged mouse nephrocystin indicated that nephrocystin and Cas can interact in mammalian cells and revealed that both proteins prominently localize at or near sites of cell-cell contact in polarized Madin-Darby canine kidney epithelial cells. Our findings provide novel insight into the normal cellular activities regulated by both Cas and nephrocystin, and raise the possibility that these proteins have a related function in polarized epithelial cells.

Adaptor Proteins, Signal Transducing↗
PubMed2000

A foodborne outbreak of gastroenteritis associated with Norwalk-like viruses: first molecular traceback to deli sandwiches contaminated during preparation.

In March 1998, an outbreak of acute gastroenteritis occurred among students at a Texas university. Overall, 125 ill students sought medical care. Case-control studies revealed that illness was significantly associated with eating foods from the university's main cafeteria deli bar on 9 and 10 March. Stool specimens from 9 (50%) of 18 ill students and samples of deli ham showed evidence of Norwalk-like viruses (NLVs) by reverse-transcriptase (RT) polymerase chain reaction (PCR) assay. A food handler who prepared sandwiches for lunch on 9 March reported that her infant had been sick with watery diarrhea since just before the outbreak. A stool sample from the infant was positive for NLV by RT-PCR, and the sequence of the amplified product was identical to that of amplified product from deli ham and students' stool specimens. This is the first time RT-PCR and sequence analysis have successfully confirmed viral contamination of a food item likely to have been contaminated by a food handler.

Adolescent↗
PubMed2000

Evaluating clinical skills of radiation oncology residents: parts I and II.

UNLABELLED: The purposes of this article are to: (1) underscore both the importance and the difficulty of assessing clinical skills at the graduate level, (2) review both old and new assessment methods of clinical skills in an attempt to familiarize educators with current views on evaluation modalities, and (3) assess the state of clinical-skills assessment specifically in radiation oncology. A series of articles published in The Lancet in 1995, entitled "Examining the Examiner," was used as a starting point. We then conducted an extensive literature search (using MEDLINE) to find publications that examined different examination methods, old and new, that apply to the education of radiation oncology residents. Concepts critical to understanding any discussion of clinical skills evaluation methods are also reviewed. RESULTS: Part I of the article provides an introduction critical to understanding the objectives of clinical-skills evaluation. Also, three older, well-established methods of clinical skills evaluation (ward evaluation, oral examination, and multiple-choice questions) are assessed. In Part II, the objective structured clinical examination (OSCE), the standardized patient (SP), and the patient management problem (PMP), all born of recent innovations in the field, are discussed. Part II concludes with a review of how the issues presented in both parts are relevant to the assessment of the radiation oncology resident. All evaluation methods that can be applied to the education of radiation oncology residents have perceived advantages and shortcomings. With the proper administration of many of these (save, perhaps, the PMP), any perceived difficulties in evaluating the clinical skills of radiation oncology residents may be addressed and diminished. Suggestions offered that are worthy of further discussion, debate, and study include establishment of a standardized "ward" examination, a formative oral examination to accompany the ACR In-Training examination, and the possible revision of the American Board of Radiology oral examination. An in-depth appraisal on the feasibility of using newer evaluation methods (OSCE, SP, etc.) is also needed. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 1-12 (2000).

Algorithms↗
PubMed2000

Isolation and characterization of the human secretogranin II gene promoter.

The goal of this study was to isolate and functionally characterize the human secretogranin II (SgII) gene promoter. SgII is a member of the granin family of proteins which are selectively expressed in neurosecretory cells. The human SgII promoter contains a consensus TATA box and cyclic AMP response element (CRE) 35 and 74 bp upstream of the transcription start site, respectively, elements also found in the mouse and rat SgII gene promoters. Transfection studies showed that 869 bp of the human SgII promoter were sufficient to confer cell type-specific expression of an SgII promoter-luciferase reporter gene in neurosecretory PC-12, GH and BE(2)-M17 cells. The activity of the human SgII promoter was also compared in three N-type, human neuroblastoma cell lines [BE(2)-M17, SMS-KAN and SH-SY5Y], which differ markedly in the level of SgII expression. SgII promoter activities in the neuroblastoma cell lines correlated not only with the levels of SgII but also the levels of the cyclic AMP response element-binding protein CREB which were highest in BE(2)-M17 cells and lowest in SH-SY5Y cells. To establish that the activity of the human SgII promoter in these neuroblastoma cell lines is dependent on the level of CREB, rat CREB was overexpressed in SH-SY5Y cells. SgII promoter activity was up to 8-fold higher in SH-SY5Y cells overexpressing CREB. These results suggest that SgII expression is a marker for neuronal differentiation in human neuroblastoma cell lines and is dependent on the level of CREB expression.

Animals↗
PubMed2000

The urokinase plasminogen activator receptor (UPAR) is preferentially induced by nerve growth factor in PC12 pheochromocytoma cells and is required for NGF-driven differentiation.

Nerve growth factor (NGF)-driven differentiation of PC12 pheochromocytoma cells is a well studied model used both to identify molecular, biochemical, and physiological correlates of neurotrophin-driven neuronal differentiation and to determine the causal nature of specific events in this differentiation process. Although epidermal growth factor (EGF) elicits many of the same early biochemical and molecular changes in PC12 cells observed in response to NGF, EGF does not induce molecular or morphological differentiation of PC12 cells. The identification of genes whose expression is differentially regulated by NGF versus EGF in PC12 cells has, therefore, been considered a source of potential insight into the molecular specificity of neurotrophin-driven neuronal differentiation. A "second generation" representational difference analysis procedure now identifies the urokinase plasminogen activator receptor (UPAR) as a gene that is much more extensively induced by NGF than by EGF in PC12 cells. Both an antisense oligonucleotide for the UPAR mRNA and an antibody directed against UPAR protein block NGF-induced morphological and biochemical differentiation of PC12 cells; NGF-induced UPAR expression is required for subsequent NGF-driven differentiation.

Animals↗
PubMed2000

Incidence and significance of pneumomediastinum after laparoscopic esophageal surgery.

BACKGROUND: Pneumomediastinum can be a sign of esophageal perforation. During laparoscopic esophageal surgery, the mediastinum is exposed to carbon dioxide gas under pressure that can cause pneumomediastinum. METHODS: Forty-five patients undergoing laparoscopic esophageal procedures had erect, inspiratory, single-view chest radiographs (CXR) performed in the recovery room (RR). Patients with extraabdominal gas underwent daily erect, inspiratory, single-view CXR until resorption of the gas or discharge from the hospital. Insufflation time and pressure were recorded, and morbidity was evaluated. Results are expressed as mean +/- SEM. RESULTS: Twenty-five men (56%)and 20 women (44%) aged 33.0 +/- 2.9 years underwent 10 Heller myotomies (22.2%), 27 Nissen fundoplications (60.0%), six Toupet fundoplications (13.3%), and two paraesophageal hernia repairs (4.4%). Twenty-four patients (53.3%) had normal CXR in RR, and 21 (46.7%) had extraabdominal gas. Eighteen (85.7%) of the 21 had pneumomediastinum, three (14.3%) had pneumothorax, and 12 (57.1%) had subcutaneous emphysema in RR. Sixteen of these 21 remained hospitalized and had repeat CXR on postoperative day 1. Of these 16, five (31.3%) had normal CXR, 11 (68.8%) had pneumomediastinum, and seven (43.8%) had subcutaneous emphysema. There were no esophageal perforations and no chest tube insertions, and there was no morbidity related to pneumomediastinum. CONCLUSION: Pneumomediastinum is observed frequently following laparoscopic esophageal operations and often persists past 24 h. After these operations, pneumomediastinum is not necessarily indicative of esophageal perforation. In this group, it caused no clinically significant events that altered the course of the patients.

Adolescent↗
PubMed2000

Molecular heterogeneity of protein kinase C expression in human ventricle.

OBJECTIVE: Although activation of protein kinase C (PKC) modulates the function of normal cardiac myocytes and likely plays a role in the pathogenesis of cardiomyopathic disease states, the molecular basis of PKC expression in human ventricle has not been examined in detail. METHODS: We have performed Western analysis and immunohistochemistry on explanted human cardiac tissue from nondiseased and diseased specimens using isoform-specific antibodies directed against all known PKC isozymes. RESULTS: In homogenates from left and right ventricle, all isoforms except PKC-gamma and theta were detected by immunoblotting, with confirmation using a second antibody directed against a different epitope when possible. For PKC-betaII, delta, and epsilon, data indicated that these isoforms were variably phosphorylated in vivo, resulting in multiple bands during immunoblotting. Because of potential antibody cross-reactivity, reverse transcriptase polymerase chain reaction (RT-PCR) was performed which confirmed expression of PKC-alpha, betaI, and zeta. Immunohistochemistry demonstrated that all isoforms detected in ventricular homogenate by Western analysis could be localized to cardiac myocytes. From a methodologic standpoint, significant degradation of PKC isoforms could be demonstrated when samples were either frozen or allowed to remain at room temperature, compared to immediate subcellular fractionation. CONCLUSIONS: These findings indicate that the PKC expression in human ventricular myocytes is remarkably diverse, with multiple conventional, novel, and atypical isoforms present, and highlight the importance of sample preparation in comparative studies of PKC isoform expression.

Adolescent↗
PubMed2000

Emergency reinstitution of cardiopulmonary bypass following cardiac surgery: outcome justifies the cost.

OBJECTIVE: Crash back on bypass (crash-BOB) is occasionally required in the resuscitation of patients developing life-threatening complications following cardiac surgery. This study aims to determine the incidence, aetiology and cost-effectiveness of such intervention. METHODS: Retrospective review of all crash-BOB patients over 5.5 years at one hospital. RESULTS: The incidence of crash-BOB was 0.8% and occurred at a mean of 7 h post-operatively (range 1 h-20 days). Pre-operative Parsonnet scores were similar to the overall population of patients undergoing surgery in our institution (mean score 10; range 0-45). The original cardiac operations were coronary revascularization (39), valve surgery (12) and others (4). Indications for crash-BOB were cardiac arrest (23), bleeding (20), hypotension (7), ischaemia (1) and others (4). Of the 55 patients, 20 died on the operating table. Of the remaining 35, a further 12 died in hospital. Overall survival was therefore 42%. Where crash-BOB was for bleeding, 17 of 20 patients (85%) survived to leave theatre, of whom 11 patients (55%) left hospital alive. In the 35 non-bleeders, only 18 (51%) survived crash-BOB and 12 (34%) left hospital alive. Sixteen patients required a second period of aortic cross-clamping of whom 13 (81%) survived to leave theatre, and 11 (69%) left hospital alive. Conversely, of nine patients in whom no specific diagnosis was found during crash-BOB, only two (22%) survived the procedure and none survived to hospital discharge. Multiple logistic regression identified pre-operative Parsonnet score (P=0.045) and the need for aortic cross-clamping to deal with an identified surgical problem (P=0.03) as significant predictors of hospital survival. Indication for crash-BOB (bleeder/non-bleeder) failed to reach significance (P=0.08). Age, sex, intra-aortic balloon pump use at the primary procedure, and time following the primary procedure to crash-BOB were not identified as predictors of hospital survival. Of the 23 hospital survivors, three patients suffered a stroke post-operatively and made a good functional recovery prior to discharge. Two patients developed sternal wound dehiscence requiring surgical rewiring. At follow-up (mean 3 years, range 1-6 years), 19 patients were in NYHA class I and four were in class II. Crash-BOB patients required an average of 8 extra intensive care days and 2 extra ward days. The total cost of these resources was pound164900 (including theatre time, cardiopulmonary bypass and intra-aortic balloon pump use). This was equivalent to pound7170 per life saved. CONCLUSIONS: Crash-BOB occurred in 0.8% of cases and was associated with a survival to discharge of 42%, and a justifiable cost of only pound7170 per life saved. Establishing an accurate diagnosis for the cause of clinical deterioration resulting in crash-BOB intervention was important, and the need for a further period of aortic cross-clamping did not preclude a favourable outcome.

Aged↗
PubMed2000

Temporal relationship between immune cell influx and the expression of inducible nitric oxide synthase, interleukin-4 and interferon-gamma in pancreatic islets of NOD mice following adoptive transfer of diabetic spleen cells.

Beta cell destruction in NOD mice can be accelerated by adoptive transfer of diabetic spleen cells into irradiated adult NOD mice. Here mice receiving diabetic spleen cells were examined at days 0, 7, 14, 21 and at onset of diabetes for the resulting insulitis and the number of intra-islet CD4 and CD8 cells and macrophages. The progression of insulitis and the number of intra-islet CD4 and CD8 cells and macrophages were correlated with the expression and co-localization of inducible nitric oxide synthase, interferon-gamma and interleukin-4 by dual-label light and confocal immunofluorescence microscopy. Diabetes developed in 7/8 mice by 27 days following cell transfer. The insulitis score increased slightly by day 7 but rose sharply at day 14 (p = 0.001) and was maintained until diabetes. The mean number of intra-islet CD4 and CD8 cells and macrophages showed a similar trend to the insulitis scores and were present in almost equal numbers within the islets. Immunolabelling for inducible nitric oxide synthase was observed at day 7 in only some cells of a few islets but increased sharply from day 14. It was restricted to islets with insulitis and was co-localized in selective macrophages. Weak intra-islet interleukin-4 labelling was observed at days 7 and 14 but became more pronounced at day 21 and at onset of diabetes, being present in selective CD4 cells. Intra-islet labelling for interferon-gamma was first observed at day 21, but became more intense at onset of diabetes and was co-localized in a proportion of macrophages. Both cytokines were expressed in islets with advanced insulitis. Interferon-gamma staining was also observed within endothelial cells located in the exocrine pancreas. We conclude that transfer of diabetic spleen cells results in a rapid influx of CD4 and CD8 cells and macrophages within the pancreas of recipient mice. During the period of heightened insulitis, selective immune cells begin to express inducible nitric oxide synthase and the opposing cytokines, interferon-gamma and interleukin-4. Expression of these molecules becomes more pronounced immediately prior to and during the onset of diabetes.

Adoptive Transfer↗
PubMed2000

Progressive atrioventricular conduction block in a mouse myotonic dystrophy model.

INTRODUCTION: Myotonic dystrophy is caused by expansion of a CTG trinucleotide repeat on human chromosome 19, and leads to progressive skeletal myopathy and atrioventricular conduction disturbances. A murine model of myotonic dystrophy has been designed by targeted disruption of the myotonic dystrophy protein kinase (DMPK) gene. The DMPK-deficient mice display abnormalities in A-V conduction characteristics, similar to the human cardiac phenotype. The purpose of this study was to determine whether age-related progression of A-V block occurs in a mouse model of DMPK-deficiency. METHODS AND RESULTS: Surface ECGs and intracardiac electrophysiology (EP) studies were performed in 60 immature and 90 adult homozygous (DMPK-/-), heterozygous (DMPK+/-), and wild-type (WT) DMPK+/+ control mice. Complete studies were obtained on 141 of 150 mice. The RR, PR, QRS, and QT intervals were measured on ECG. Sinus node recovery time, AV refractory periods, paced AV Wenckebach and 2:1 block cycle lengths, atrial and ventricular effective refractory periods were compared between genotypes and age groups. There were no differences in ECG intervals or EP findings in the young mutant mice, but progressive PR prolongation in older mice. The A-V conduction defects are also sensitive to DMPK gene dosage. Adult DMPK-/- mice develop 1 degrees, 2 degrees and 3 degrees A-V block, whereas DMPK+/- mice develop only 1 degrees heart block. CONCLUSION: These data demonstrate that both age and DMPK dose are important factors regulating cardiac conduction in myotonic dystrophy. This mouse model of DM is remarkably similar to the human phenotype, with age-related progression in atrioventricular conduction defects.

Aging↗
PubMed2000

Heterozygous loss of Six5 in mice is sufficient to cause ocular cataracts.

Myotonic dystrophy (DM) is an autosomal dominant disorder characterized by skeletal muscle wasting, myotonia, cardiac arrhythmia, hyperinsulinaemia, mental retardation and ocular cataracts. The genetic defect in DM is a CTG repeat expansion located in the 3' untranslated region of DMPK and 5' of a homeodomain-encoding gene, SIX5 (formerly DMAHP; refs 2-5). There are three mechanisms by which CTG expansion can result in DM. First, repeat expansion may alter the processing or transport of the mutant DMPK mRNA and consequently reduce DMPK levels. Second, CTG expansion may establish a region of heterochromatin 3' of the repeat sequence and decrease SIX5 transcription. Third, toxic effects of the repeat expansion may be intrinsic to the repeated elements at the level of DNA or RNA (refs 10,11). Previous studies have demonstrated that a dose-dependent loss of Dm15 (the mouse DMPK homologue) in mice produces a partial DM phenotype characterized by decreased development of skeletal muscle force and cardiac conduction disorders. To test the role of Six5 loss in DM, we have analysed a strain of mice in which Six5 was deleted. Our results demonstrate that the rate and severity of cataract formation is inversely related to Six5 dosage and is temporally progressive. Six5+/- and Six5-/- mice show increased steady-state levels of the Na+/K+-ATPase alpha-1 subunit and decreased Dm15 mRNA levels. Thus, altered ion homeostasis within the lens may contribute to cataract formation. As ocular cataracts are a characteristic feature of DM, these results demonstrate that decreased SIX5 transcription is important in the aetiology of DM. Our data support the hypothesis that DM is a contiguous gene syndrome associated with the partial loss of both DMPK and SIX5.

Animals↗
PubMed2000

The added diagnostic value of automated QT-dispersion measurements and automated ST-segment deviations in the electrocardiographic diagnosis of acute cardiac ischemia.

The purpose of this study was to determine the added value of automated QT dispersion and ST-segment measurements to physician interpretation of 12-lead electrocardiograms (ECGs) in patients with chest pain. To date, poor reproducibility of manual measurements and lack of shown added value have limited the clinical use of QT dispersion. Twelve-lead ECGs (n = 1,161) from the Milwaukee Prehospital Chest Pain Database were independently classified by 2 physicians into 3 groups (acute myocardial infarction (AMI), acute cardiac ischemia (ACI), or nonischemic), and their consensus was obtained. QT-end and QT-peak dispersions were measured by a computerized system. The computer also identified ST-segment deviations. Sensitivity, specificity, and positive predictive values (PPVs) and negative predictive values (NPV) for AMI and ACI were evaluated independently and in combinations. For AMI, physicians' consensus classification was remarkably good (sensitivity, 48%, specificity, 99%). Independent classification by QT-end and QT-peak dispersions or ST deviations was not superior to the physicians' consensus. Optimal classification occurred by combining automated QT-end dispersion and ST deviations with physicians' consensus. This combination increased sensitivity for the diagnoses of AMI by 35% (65% vs 48%, P < .001) and ACI by 55% (62% vs 40%, P < .001) compared with physicians' consensus, while maintaining comparable specificity. This study supports a potential clinical role for automated QT dispersion when combined with other diagnostic methods for detecting AMI and ACI.

Adolescent↗
PubMed2000

Characteristics of HIV-1-infected patients with CD4:CD8 lymphocyte ratio normalization on antiretroviral therapy.

Antiretroviral therapy for human immunodeficiency virus (HIV)-infection results in normalization of CD4:CD8 T-lymphocyte ratio in about 6% of cases. The T-cell ratio normalization on therapy was associated with a baseline CD4 of over 350 cells per microliter and a T-cell ratio of over 0.5 (for each, p < 0.01), but not with the current level of viral load suppression or compliance with clinic appointments (for each, p > 0.05). The patients with T-cell ratio normalization had a baseline median CD4 count of 428 cells per microliter (range, 353-883 cells per microliter) and a median T-cell ratio of 0.75 (range, 0.54-0.87). We could not address the effect of baseline viral load on T-cell ratio normalization, but there was no association with age, gender, race, HIV risk factor, or the length of antiretroviral therapy.

Adult↗
PubMed2000

Anterior ischemic optic neuropathy: a complication after systemic inflammatory response syndrome.

BACKGROUND: Patients are surviving previously fatal injuries. Unique morbidities are occurring in these survivors. Anterior ischemic optic neuropathy represents a previously unrecognized cause of blindness in the trauma victim. We hypothesize that this phenomenon is caused by unique characteristics of optic edema/ pressure or decreased blood flow associated with massive resuscitation. METHODS: Between November of 1991 and August of 1998, there were 18,199 admissions to our trauma center. Of this group, 350 patients required massive volume resuscitation (>20 liters infused over first 24 hours). Patients having closed head injuries, facial fractures or direct orbital trauma were excluded from study. The following variables were studied: demographics, injury severity (Injury Severity Score, highest lactate, worst base deficit, and lowest pH) crystalloid and transfusion requirements, ventilator requirements (PEEP) RESULTS: Of the 350 patients with massive resuscitation, 9 patients were diagnosed with anterior ischemic optic neuropathy (2.6%). Of these, seven patients required celiotomy (78%). Six of the seven celiotomy patients had damage control celiotomies and abdominal compartment syndrome (86%). One patient had a repair of a subclavian artery; one had a complex acetabular repair. Blindness was unilateral in five patients and bilateral in four. All nine patients had evidence of global hypoperfusion, systemic inflammatory response, massive resuscitation, and high ventilatory support; one patient required cardiopulmonary resuscitation. CONCLUSION: Prone positioning is known to be associated with an increased intraocular pressure. We postulate that the combination of massive resuscitation and prone positioning will increase the incidence of anterior ischemic optic neuropathy. As such, we recommend that prone positioning for adult respiratory distress syndrome be reserved for only those patients at risk of death.

Adolescent↗