University of Texas Medical Branch

About: University of Texas Medical Branch is a education organization based out in Galveston, Texas, United States. It is known for research contribution in the topics: Population & Virus. The organization has 22033 authors who have published 38268 publications receiving 1517502 citations. The organization is also known as: The University of Texas Medical Branch at Galveston & UTMB.

Application of genome-wide expression analysis to human health and disease

Abstract: The application of genome-wide expression analysis to a large-scale, multicentered program in critically ill patients poses a number of theoretical and technical challenges. We describe here an analytical and organizational approach to a systematic evaluation of the variance associated with genome-wide expression analysis specifically tailored to study human disease. We analyzed sources of variance in genome-wide expression analyses performed with commercial oligonucleotide arrays. In addition, variance in gene expression in human blood leukocytes caused by repeated sampling in the same subject, among different healthy subjects, among different leukocyte subpopulations, and the effect of traumatic injury, were also explored. We report that analytical variance caused by sample processing was acceptably small. Blood leukocyte gene expression in the same individual over a 24-h period was remarkably constant. In contrast, genome-wide expression varied significantly among different subjects and leukocyte subpopulations. Expectedly, traumatic injury induced dramatic changes in apparent gene expression that were greater in magnitude than the analytical noise and interindividual variance. We demonstrate that the development of a nation-wide program for gene expression analysis with careful attention to analytical details can reduce the variance in the clinical setting to a level where patterns of gene expression are informative among different healthy human subjects, and can be studied with confidence in human disease.

The Association Between Fluid Administration and Outcome Following Major Burn: A Multicenter Study

Abstract: Fluid resuscitation remains the cornerstone of early burn management. Adequate fluid administration is critical to the prevention of burn shock and other complications of thermal injury. Eighty years after Frank Underhill’s observations on the critical importance of fluid resuscitation on survival following major burn,1 a perfect formula for predicting fluid requirements remains elusive despite decades of research and debate.2–6 In addition, controversy persists over the best method to determine fluid volume necessary to prevent the complications of hypovolemic shock.7–13 The Parkland formula has been used to estimate appropriate volumes of fluid resuscitation for over 40 years. Based on a number of studies in animal models, Baxter and Shires determined that adequate fluid resuscitation can be achieved in the majority of patients by using 3.7 to 4.3 mL/kg/% TBSA of crystalloid solution.3,14 However, more recent evidence suggests that the Parkland formula does not accurately predict fluid requirements, particularly in patients with larger burns, and that patients today are receiving more fluid per-percent TBSA than in the past.8,15–18 Cancio et al reported that the Parkland formula underestimated fluid requirements in 84% of patients.15 Friedrich et al compared the volume of fluid resuscitation delivered in the first 24 hours after injury to 10 patients in the 1970s with age and % TBSA-matched patients in the year 2000 and found the patients in 2000 received over twice the volume of resuscitation.17 In a multicenter survey, Engrav et al found that 58% of patients with large burns received more than 4.3 mL/kg/% TBSA.16 Pruitt has labeled this trend toward larger volumes of fluid administered “fluid creep.”19 Concerns over administered fluid volumes are predicated on the belief that fluid volume can be critical to the development of organ failure, infections, and death. The potential sequelae of underresuscitation involve complications of inadequate perfusion, including hypovolemic shock, renal failure, and the conversion of partial thickness wounds to full thickness wounds. There has similarly been increasing emphasis on the potentially deleterious effects of massive volumes of fluid resuscitation, including extremity, orbital and abdominal compartment syndromes, acute respiratory distress syndrome (ARDS), prolonged periods of ventilator dependence, and increased mortality.18,20–22 As awareness of the potential negative sequelae of large fluid volume administration increases, the need to better define the factors that can impact fluid requirements and the need to understand the effects of larger fluid volumes have similarly increased. Baxter initially identified 3 risk factors for fluid requirements above volumes predicted by the formula: excessively deep burns with muscle necrosis, inhalation injury, and delay in resuscitation.5,23 Several other patient and clinical variables may also impact fluid requirements.8,10,11,13 The Inflammation and Host Response to Injury is a collaborative program supported by the National Institute of General Medical Sciences designed to better define the proteomic and genomic response to injury. In the context of this large cohort study, we set out: 1) to evaluate the relationship between injury characteristics and volume of resuscitation, and 2) to examine the relationship between volumes of fluid resuscitation and adverse outcomes.

Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus.

Abstract: To determine if a hypersensitive-type lung pathology might occur when mice were given an inactivated MERS-CoV vaccine and challenged with infectious virus as was seen with SARS-CoV vaccines, we prepared and vaccinated mice with an inactivated MERS-CoV vaccine. Neutralizing antibody was induced by vaccine with and without adjuvant and lung virus was reduced in vaccinated mice after challenge. Lung mononuclear infiltrates occurred in all groups after virus challenge but with increased infiltrates that contained eosinophils and increases in the eosinophil promoting IL-5 and IL-13 cytokines only in the vaccine groups. Inactivated MERS-CoV vaccine appears to carry a hypersensitive-type lung pathology risk from MERS-CoV infection that is similar to that found with inactivated SARS-CoV vaccines from SARS-CoV infection.

Progressive loss of pancreatic function in chronic pancreatitis is delayed by main pancreatic duct decompression. A longitudinal prospective analysis of the modified puestow procedure.

Abstract: OBJECTIVE: This study evaluated the effect of operative drainage of the main pancreatic duct (MPD) on functional derangements associated with chronic pancreatitis (CP). SUMMARY BACKGROUND DATA: The author previously reported delayed functional impairment in an evaluation of the impact of operative drainage in patients with CP. The author now reports on a prospective study of 143 patients with this diagnosis. METHODS: Each patient underwent 1) ERCP, 2) the Bentiromide PABA, 3) 72-hour fecal fat test, 4) oral glucose tolerance test (OGTT) and 5) fat meal (LIPOMUL)--stimulated pancreatic polypeptide release (PP). All patients were stratified as mild/moderate (M/M) or severe CP on the basis of a 5-point system that was developed by the author. Patients were studied at 16-month intervals. RESULTS: All 143 patients underwent initial and follow-up evaluations in a mean follow-up of 47.3 months; 83 of 143 patients had M/M grade at initial evaluation. Eighty-seven patients underwent (MPD) decompression to relieve abdominal pain. In a separate prospective 17 patients with a diagnosis of CP, a grade of M/M and non-disabling abdominal pain were randomized to operative or non-operative treatment; 9 of these randomized patients were operated upon and 8 were not. No patient improved their grade during follow-up; 47 of 83 M/M patients had operative drainage and 36 did not. This grade was preserved in 41 of 47 (87%) operated patients but in only 8 of the 36 non-operated patients (22%). In the randomized trial, seven of nine operated patients retained their functional status in follow-up, whereas only two of eight patients (25%) randomized to non-operation preserved their functional grade. CONCLUSIONS: These data in this large study as well as among a previous randomized sample, support a policy of early operative drainage before the development of irreversible functional impairment in patients with chronic pancreatitis and associated dilation of the main pancreatic duct.