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Biomedical subjects

Anthony Sebastian

Publications and source records attributed to Anthony Sebastian.

18 recordsLinked to original sources
PubMed2006

Assessing relative risks of infection and rejection: a meta-analysis using an immune function assay.

BACKGROUND: Long-term use of immunosuppressants is associated with significant morbidity and mortality in transplant recipients. A simple whole blood assay that has U.S. Food and Drug Administration clearance directly assesses the net state of immune function of allograft recipients for better individualization of therapy. A meta-analysis of 504 solid organ transplant recipients (heart, kidney, kidney-pancreas, liver and small bowel) from 10 U.S. centers was performed using the Cylex ImmuKnow assay. METHODS: Blood samples were taken from recipients at various times posttransplant and compared with clinical course (stable, rejection, infection). In this analysis, 39 biopsy-proven cellular rejections and 66 diagnosed infections occurred. Odds ratios of infection or rejection were calculated based on measured immune response values. RESULTS: A recipient with an immune response value of 25 ng/ml adenosine triphosphate (ATP) was 12 times (95% confidence of 4 to 36) more likely to develop an infection than a recipient with a stronger immune response. Similarly, a recipient with an immune response of 700 ng/ml ATP was 30 times (95% confidence of 8 to 112) more likely to develop a cellular rejection than a recipient with a lower immune response value. Of note is the intersection of odds ratio curves for infection and rejection in the moderate immune response zone (280 ng/ml ATP). This intersection of risk curves provides an immunological target of immune function for solid organ recipients. CONCLUSION: These data show that the Cylex ImmuKnow assay has a high negative predictive value and provides a target immunological response zone for minimizing risk and managing patients to stability.

Graft Rejection↗
PubMed2006

Relationship and interaction between sodium and potassium.

Compared with the Stone Age diet, the modern human diet is both excessive in NaCl and deficient in fruits and vegetables which are rich in K+ and HCO3- -yielding organates like citrate. With the modern diet, the K+/Na+ ratio and the HCO3-/Cl- ratio have both become reversed. Yet, the biologic machinery that evolved to process these dietary electrolytes remains largely unchanged, genetically fixed in Paleolithic time. Thus, the electrolytic mix of the modern diet is profoundly mismatched to its processing machinery. Dietary potassium modulates both the pressor and hypercalciuric effects of the modern dietary excess of NaCl. A marginally deficient dietary intake of potassium amplifies both of these effects, and both effects are dose-dependently attenuated and may be abolished either with dietary potassium or supplemental KHCO3. The pathogenic effects of a dietary deficiency of potassium amplify, and are amplified by, those of a dietary excess of NaCl and in some instances a dietary deficiency of bicarbonate precursors. Thus, in those ingesting the modern diet, it may not be possible to discern which of these dietary electrolytic dislocations is most determining of salt-sensitive blood pressure and hypercalciuria, and the hypertension, kidney stones, and osteoporosis they may engender. Obviously abnormal plasma electrolyte concentrations rarely characterize these dietary electrolytic dislocations, and when either dietary potassium or supplemental KHCO3 corrects the pressor and hypercalciuric effects of these dislocations, the plasma concentrations of sodium, potassium, bicarbonate and chloride change little and remain well within the normal range.

Acid-Base Imbalance↗
PubMed2006

Compatible ABO mismatch and liver transplantation: a single center's experience.

OBJECTIVES: The current shortage of suitable donor organs and clinical urgency can lead to implanting grafts from ABO-mismatched donors. One-year graft survival rates for patients in this scenario have been reported as ranging between 25% and 75% less than those for ABO-identical or ABOcompatible grafts. We review and compare our experiences with transplanting ABO-identical and ABO-compatible mismatched livers. MATERIALS AND METHODS: Considering orthotopic liver transplantation (OLTx), 520 were performed at our institution between November 1992 and May 2003, 55 of which were ABO-compatible mismatched transplants. We retrospectively reviewed the data and compared patient and graft survival rates. RESULTS: Overall 1-month and 1-, 5-, and 10-year patient survival rates among identical (group 1) and mismatched (group 2) groups were 97% and 91%, 90%, and 88.5%, and 79%, and 74%, 66%, and 65%, respectively. No significant difference existed between the 2 groups (P>.05). Similarly, 1-month, and 1-, 5-, and 10-year graft survival rates among groups 1 and 2 were 96% and 87%, 89% and 83%, 78% and 71% and 66% and 59%, respectively; these were not significant either (P>.05). All of the patients in the mismatched group had a high status according to the United Network for Organ Sharing (UNOS). Only 1 person received an incompatible mismatched graft (B to A), which subsequently developed primary nonfunction. CONCLUSIONS: ABO-compatible mismatch OLTx is unavoidable given the current state of organ shortage. Our results suggest that this type of OLTx can be performed with minimal risk among patients who require urgent transplantation and have high rankings according to the UNOS and the model for end-stage liver disease (MELD) system.

ABO Blood-Group System↗
PubMed2005

Multiplex cytokine profiling of initial therapeutic response in patients with chronic hepatitis C virus infection.

Currently available prognostic tools are inadequate to discern the molecular basis of the heterogenic response in hepatitis C virus (HCV)-infected patients treated with the current standard of therapy. The expression and biological function of immune mediators have been shown to be critical in all phases of the immune response to HCV infection and likely therefore influence host response. Herein, a biometric multiplex serum cytokine assay was utilized to characterize the immunomodulatory effects of host response in 10 HCV patients. Serum levels of 17 cytokines were compared before and after 1 month of treatment and against controls. Overall serum cytokine levels were significantly higher in patients (P < 0.05) than controls. Additionally, viral titers decreased in all patients after 1 month of therapy, as did overall serum cytokine levels in the cohort (P < 0.05). To assess relationships between changes in cytokine levels and changes in viral titer, the cohort was divided into three statistically distinct subgroups based on changes in viral titers. Specific sets of cytokines decreased in each group: decreases in CCL4, interleukin (IL)-2, CXCL8, and IL-1beta correlated with the greatest drops in viral titer, decreases in IL-5, granulocyte colony stimulating factor (G-CSF), and CCL4 correlated with moderate drops in viral titer, and only CCL2 correlated with the lowest drops in viral titer. Interestingly, decreases in CCL4 levels correlated with decreases in viral titers in all patients. CCL4 controls leukocyte influx and thus propagates inflammation. In conclusion, these data raise the possibility that characteristic changes in host response modulate the therapeutic response, demonstrating the prognostic power of serum cytokine profiling in chronic HCV.

Adult↗
PubMed2005

Origins and evolution of the Western diet: health implications for the 21st century.

There is growing awareness that the profound changes in the environment (eg, in diet and other lifestyle conditions) that began with the introduction of agriculture and animal husbandry approximately 10000 y ago occurred too recently on an evolutionary time scale for the human genome to adjust. In conjunction with this discordance between our ancient, genetically determined biology and the nutritional, cultural, and activity patterns of contemporary Western populations, many of the so-called diseases of civilization have emerged. In particular, food staples and food-processing procedures introduced during the Neolithic and Industrial Periods have fundamentally altered 7 crucial nutritional characteristics of ancestral hominin diets: 1) glycemic load, 2) fatty acid composition, 3) macronutrient composition, 4) micronutrient density, 5) acid-base balance, 6) sodium-potassium ratio, and 7) fiber content. The evolutionary collision of our ancient genome with the nutritional qualities of recently introduced foods may underlie many of the chronic diseases of Western civilization.

Acid-Base Equilibrium↗
PubMed2004

Long-term persistence of the urine calcium-lowering effect of potassium bicarbonate in postmenopausal women.

Potassium bicarbonate (KBC) potently reduces urine calcium excretion in adult humans, including patients with hypertension or calcium urolithiasis, and postmenopausal women. In the latter, who have substantial risk of calcium deficiency, it remains unknown whether the observed short-term urine calcium-lowering effect of KBC persists over years. We studied 170 postmenopausal women randomized to KBC 30, 60, or 90 mmol/d (KBC treatment), or placebo, for up to 36 months. Each received a multivitamin with 400 IU vitamin D, and calcium carbonate as needed to produce a total dietary calcium intake of at least 30 mmol daily. Daily urine calcium excretion (UCaV) did not differ among groups at baseline (all-groups mean +/- SD, 155 +/- 83 mg/d). From 1-36 months of KBC treatment, adjusting UCaV for creatinine (Cr) excretion, each dose of KBC reduced UCaV (P < 0.01) with a dose-dependent trend (P = 0.05). The reduced UCaV/Cr persisted throughout the KBC treatment period (up to 36 months) in all KBC, and the greatest reductions occurred in the subjects with greatest baseline UCaV/Cr (Delta UCaV/Cr vs. baseline UCaV/Cr; P < 0.001). Twenty-eight percent of the subjects had high baseline calciuria (UCaV/Cr > 200 mg Ca/1000 mg Cr). With baseline UCaV/Cr of 250 mg/1000 mg Cr, KBC 60 mmol decreased UCaV/Cr by 55.8 mg/1000 mg Cr, a potential daily calcium retention that over a 36-month period would accumulate up to 55,845 mg of calcium, nearly 5% of bone calcium content. KBC treatment induced a dose-dependent decrease in UCaV/Cr that persisted up to 36 months, with the greatest decreases occurring in those women with the greatest baseline UCaV, nearly a third of whom had high baseline calciuria. Thus, one can preselect postmenopausal women most likely to have the urine calcium-lowering effect of KBC and predict their potential bone calcium increase.

Adult↗
PubMed2004

Peri and postoperative pulmonary complications among cirrhotic individuals.

Surgical intervention among cirrhotic individuals carries a high risk for peri-and postoperative complications. We review the literature regarding the frequency and consequences of pulmonary complications in cases of cirrhosis. The experience with hepato-pulmonary syndrome and porto-pulmonary hypertension in liver transplant recipients is also presented.

Humans↗
PubMed2003

Experience with liver dialysis in acetaminophen induced fulminant hepatic failure: a preliminary report.

BACKGROUND/AIMS: Our aim was to assess the efficacy of the liver dialysis unit (LDU) in the treatment of patients with acetaminophen-induced fulminant hepatic failure. METHODS: Seventeen patients with acetaminophen-induced fulminant hepatic failure between January 1996 and December 2001 were retrospectively studied. A liver dialysis unit became available in our Unit in July 2000, and as of December 2001, four of these 17 patients had undergone treatment with liver dialysis. RESULTS: Mean age was 29 years (range: 14-47) and 76% were women. Four of 17 patients underwent a total of 12 (range: 1-4) LDU sessions. Ammonia level tended to be lower following the LDU and all four patients recovered without a need for orthotopic liver transplantation (OLT). Prior to July 2000, eight of 13 patients survived with supportive therapy, three expired and two underwent OLT. No major bleeding episodes were observed during the LDU course. A significant difference was found between the three cases who died and the cases that survived with respect to the grade of encephalopathy (p<0.001). There was significant difference in the admission serum creatinine among survivors (p<0.05). CONCLUSION: In conclusion, the Liver Dialysis Unit treatment appeared to benefit patients with acetaminophen-induced fulminant hepatic failure by reverse of the encephalopathy and spontaneous recovery of the damaged liver in selected patients.

Acetaminophen↗
PubMed2002

Estimation of the net acid load of the diet of ancestral preagricultural Homo sapiens and their hominid ancestors.

BACKGROUND: Natural selection has had < 1% of hominid evolutionary time to eliminate the inevitable maladaptations consequent to the profound transformation of the human diet resulting from the inventions of agriculture and animal husbandry. OBJECTIVE: The objective was to estimate the net systemic load of acid (net endogenous acid production; NEAP) from retrojected ancestral preagricultural diets and to compare it with that of contemporary diets, which are characterized by an imbalance of nutrient precursors of hydrogen and bicarbonate ions that induces a lifelong, low-grade, pathogenically significant systemic metabolic acidosis. DESIGN: Using established computational methods, we computed NEAP for a large number of retrojected ancestral preagricultural diets and compared them with computed and measured values for typical American diets. RESULTS: The mean (+/- SD) NEAP for 159 retrojected preagricultural diets was -88 +/- 82 mEq/d; 87% were net base-producing. The computational model predicted NEAP for the average American diet (as recorded in the third National Health and Nutrition Examination Survey) as 48 mEq/d, within a few percentage points of published measured values for free-living Americans; the model, therefore, was not biased toward generating negative NEAP values. The historical shift from negative to positive NEAP was accounted for by the displacement of high-bicarbonate-yielding plant foods in the ancestral diet by cereal grains and energy-dense, nutrient-poor foods in the contemporary diet-neither of which are net base-producing. CONCLUSIONS: The findings suggest that diet-induced metabolic acidosis and its sequelae in humans eating contemporary diets reflect a mismatch between the nutrient composition of the diet and genetically determined nutritional requirements for optimal systemic acid-base status.

Acid-Base Equilibrium↗
PubMed2002

Potassium citrate prevents increased urine calcium excretion and bone resorption induced by a high sodium chloride diet.

The amount of sodium chloride in the diet of industrialized nations far exceeds physiological requirements. The impact of abundant dietary salt on skeletal health has yet to be established, but is potentially detrimental through increased urinary calcium losses. We examined the effect of increased dietary sodium chloride on urine calcium excretion and bone turnover markers in postmenopausal women and, further, whether potassium citrate attenuates the effects of increased dietary salt. Postmenopausal women (n = 60) were adapted to a low-salt (87 mmol/d sodium) diet for 3 wk, then randomized to a high-salt (225 mmol/d sodium) diet plus potassium citrate (90 mmol/d) or a high-salt diet plus placebo for 4 wk. Urine calcium, urine N-telopeptide, urine cAMP, serum osteocalcin, and fasting serum PTH were measured at the end of the low- and high-salt diets. On the high salt plus placebo diet, urine calcium increased 42 +/- 12 mg/d (mean +/- SEM), but decreased 8 +/- 14 mg/d in the high salt plus potassium citrate group (P = 0.008, potassium citrate vs. placebo, unpaired t test). N-telopeptide increased 6.4 +/- 1.4 nanomoles bone collagen equivalents per millimole creatinine in the high salt plus placebo group and 2.0 +/- 1.7 nanomoles bone collagen equivalents per millimole creatinine in the high salt plus potassium citrate group (P < 0.05, potassium citrate vs. placebo, unpaired t test). Osteocalcin, PTH, and cAMP were not significantly altered. The addition of oral potassium citrate to a high-salt diet prevented the increased excretion of urine calcium and the bone resorption marker caused by a high salt intake. Increased intake of dietary sources of potassium alkaline salts, namely fruit and vegetables, may be beneficial for postmenopausal women at risk for osteoporosis, particularly those consuming a diet generous in sodium chloride.

Aged↗
PubMed2002

Unusual presentation of hepatic vascular tumors as fulminant hepatic failure.

Epithelioid hemangioendothelioma and angiosarcoma of the liver are rare neoplasms of vascular origin. They can present with nonspecific symptoms such as malaise and weight loss, as well as with liver-related symptoms such as abdominal pain, tender hepatomegaly and jaundice. Portal hypertension and rarely liver failure can occur. We hereby report two cases of fulminant hepatic failure that were eventually diagnosed with epithelioid hemangioendothelioma and angiosarcoma of the liver.

Journal Article↗
PubMedDate not supplied

Endothelial biomedicine: its status as an interdisciplinary field, its progress as a basic science, and its translational bench-to-bedside gap.

The endothelium, a layer of endothelial cells lining the luminal surface of all blood vessels, functions as a highly metabolically active organ spatially distributed throughout the body. Despite enormous advances in our understanding of endothelial cell biology, little awareness of this organ reaches clinical practice. The present study aims to document the extent and scope of the bench-to-bedside gap in endothelial biomedicine, and to offer hypotheses to explain the gaping chasm. A PubMed search using keywords "endothelial cells" and "endothelium" yielded over 90,000 publications, increasing exponentially over the past decade. A Scirus search without date restriction returned journal results for the endothelium not greatly fewer than for the epithelium. A survey of representative vascular biology meetings revealed a high percentage of talks related to the endothelium. The number of grants awarded by the National Institutes of Health for studies in endothelial cell biology continues to steadily increase. At the bedside, however, few clinicians give consideration to the health of the endothelium. A survey of the major medical textbooks revealed a paucity of index entries for "endothelial cells" or "endothelium." The endothelium does not offer itself for inspection, palpation, percussion, and/or auscultation. No convenient blood tests measure endothelial function. The authors propose to explain the bench-to-bedside gap in endothelial biomedicine as a function of (1) historical constraints, (2) the unseen and diffuse nature of the cell layer, (3) the complexity of the system, and (4) its adaptability. Until the bench-to-bedside gap closes, the enormous potential of the endothelium as a diagnostic, preventive, and therapeutic target will remain largely untapped.

Animals↗