PubMed Health⌕ Search

Biomedical subjects

A L Rubin

Publications and source records attributed to A L Rubin.

At least 19 recordsLinked to original sources
PubMed2001

Relationship of hypolipidemia to cytokine concentrations and outcomes in critically ill surgical patients.

OBJECTIVE: To determine the relationship of hypolipidemia to cytokine concentrations and clinical outcomes in critically ill surgical patients. DESIGN: Consecutive, prospective case series. SETTING: Surgical intensive care unit of an urban university hospital. PATIENTS: Subjects were 111 patients with a variety of critical illnesses, for whom serum lipid, lipoprotein, and cytokine concentrations were determined within 24 hrs of admission to a surgical intensive care unit. Controls were 32 healthy men and women for whom serum lipid, lipoprotein, and cytokine concentrations were determined. INTERVENTIONS: Blood samples were drawn on admission to the intensive care unit. Predetermined clinical outcomes including death, infection subsequent to intensive care unit admission, length of intensive care unit stay, and magnitude of organ dysfunction were monitored prospectively. MEASUREMENTS AND MAIN RESULTS: Measurements included total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoproteins A-I and B, phospholipid, triglyceride, interleukin-6, interleukin-10, soluble interleukin-2 receptor, tumor necrosis factor-alpha, and soluble tumor necrosis factor receptors p55 and p75. Mean serum lipid concentrations were extremely low: total cholesterol, 127 +/- 52 mg/dL; low-density lipoprotein cholesterol, 75 +/- 41 mg/dL; high-density lipoprotein cholesterol, 29 +/- 15 mg/dL. Total, low-density lipoprotein, and high-density lipoprotein cholesterol concentrations and apolipoprotein concentrations inversely correlated with interleukin-6, soluble interleukin-2 receptor, and interleukin-10 concentrations, whereas the triglyceride concentration correlated positively with tumor necrosis factor soluble receptors p55 and p75. Clinical outcomes were related to whether the admission cholesterol concentration was above (n = 56) or below (n = 55) the median concentration of 120 mg/dL. Each of the clinical end points occurred between 1.9- and 3.5-fold more frequently in the very low cholesterol (<120 mg/dL) group. Nine patients (8%) died during the hospitalization. Seven of the nine patients who died had total cholesterol concentrations below the median concentration of 120 mg/dL. CONCLUSIONS: Low cholesterol and lipoprotein concentrations found in critically ill surgical patients correlate with interleukin-6, soluble interleukin-2 receptor, and interleukin-10 concentrations and predict clinical outcomes.

APACHE↗
PubMed2001

Exercise-induced bronchospasm prevalence in collegiate cross-country runners.

PURPOSE: The purpose of this study was to determine the prevalence of exercise-induced bronchospasm (EIB) in collegiate cross-country runners using a protocol involving an intense exercise challenge conducted in the same environment in which the athletes train and compete. METHODS: One-hundred eighteen collegiate cross-country runners from the Los Angeles, California, metropolitan area participated in the study. All testing took place on a track at the time and location of a normal practice session. The baseline peak expiratory flow rate (PEFR) measurements (best of three) and preexercise heart rate were recorded, after which the athletes ran 2000 m on a track at 85% of maximum heart rate. The postexercise heart rate was recorded and then PEFR measurements at 2, 5, 10, and 30 min after exercise were recorded. The athletes completed a 16-item questionnaire regarding asthma symptoms and health history. Those athletes with a history of asthma and currently taking medications for the asthma were then excluded from statistical analysis of the questionnaire responses. A decrease in PEFR of 15% was considered positive for EIB. RESULTS: Of the 114 athletes not currently taking medications for asthma, at least 14% (16 athletes) were EIB positive. There was a poor correlation between reported symptoms of asthma and testing positive for EIB. CONCLUSION: This study demonstrates a high prevalence of EIB in collegiate cross-country runners (at least 14%) and that reported symptoms are a poor predictor of actual EIB.

Adolescent↗
PubMed1999

Glucose control and long-term survival in biobreeding/Worcester rats after intraperitoneal implantation of hydrophilic macrobeads containing porcine islets without immunosuppression.

BACKGROUND: We investigated the effectiveness of implanted macrobeads containing porcine islets as long-term therapy for type I diabetes mellitus in Biobreeding/Worcester (BB/Wor) rats, an animal model of spontaneous type I human diabetes. End points included acute control of glucose, weight gain, survival time, and the renal changes associated with diabetes. MATERIALS AND METHODS: Eighteen chronic spontaneously diabetic BB/Wor rats were each implanted with 56-150 porcine islet macrobeads secreting 1.3-5.2 U of insulin/24 hr in culture medium at 37 degrees C. Their clinical courses and selective histological observations were compared with those of animals maintained on Linplant insulin-release implants (6 rats) or protamine zinc insulin alone (10 rats). RESULTS: The rats that underwent porcine islet macrobead implantation (PIMI) survived for a mean of 171 days (range, 79-288) after implantation without exogenous insulin, immunosuppressive treatment, or lactated Ringer's therapy. All appeared healthy and maintained their body weights (mean 356+/-21 g) throughout this period, even though their nonfasting blood glucose levels fluctuated significantly, with the mean for the group being 245+/-102 mg/dl (range, 157-320 mg/dl). There was mild glucosuria in some animals. In comparison, the 10 BB/Wor rats maintained on exogenous protamine zinc insulin had a mean survival time of 53 days (range, 10-217), a "last entry" mean body weight of 283+/-23 g, and a mean nonfasting glucose level of 340+/-90 mg/dl. The six Linplant implant animals had a mean survival time of 164 days (range, 1-264 days), a "last entry" mean body weight of 374+/-21 g, and a mean nonfasting glucose level of 189+/-91 mg/dl (range, 135-219). Episodes of ketonuria, abrupt loss of body weight, dehydration, and symptomatic hypoglycemia were more common in both these groups than in the PIMI animals. Glucose tolerance tests comparing diabetic animals treated with porcine islet macrobead implants, exogenous insulin-treated diabetic BB/Wor rats, and normal nondiabetic Wistar-Furth rats showed that the responses of those with the macrobead implants were similar to those of the normal rats, while the exogenous insulin-treated diabetic BB/Wor rats had the expected abnormal responses. Light microscopic examination of the PIMI and Linplant animals' kidney sections appeared normal, whereas those of the exogenous insulin-injected BB rats showed moderate focal tubular atrophy and an increased mesangial matrix. Macrobeads retrieved from the peritoneal cavity at necropsy were found to secrete insulin, C-peptide, and glucagon, indicating that they were still functional after 199 or more days in the peritoneal cavity. CONCLUSIONS: Our results indicate that macrobeads containing porcine islets implanted intraperitoneally in natural insulin-dependent diabetic BB/Wor rats are capable of normalizing glucose control, permitting a normal life span, and preventing the renal changes normally associated with diabetes. Therefore, further short- and long-term studies of porcine islet macrobead implantation in chemically induced and naturally occurring diabetes in rodents, as well as larger animals including dogs, monkeys and possibly humans, are merited.

Animals↗
PubMed1998

Riedel's thyroiditis presenting with hypothyroidism and hypoparathyroidism: dramatic response to glucocorticoid and thyroxine therapy.

Riedel's thyroiditis is a rare fibro-inflammatory process originating in the thyroid gland with progressive extension and invasion of surrounding tissues. Patients frequently present with a stony hard thyroid mass suggestive of anaplastic carcinoma. We report a striking case of Riedel's thyroiditis associated with hypothyroidism, hypoparathyroidism and bilateral vocal cord paralysis. A dramatic response to high dose prednisone and levothyroxine therapy was seen, with recovery of parathyroid and vocal cord function. Our case suggests that early initiation of combination therapy may be important, particularly in the presence of severe disease.

Drug Therapy, Combination↗
PubMed1998

Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients.

Low serum albumin and low serum cholesterol levels are among the most consistent predictors of mortality in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Hypoalbuminemia is often interpreted as a marker of poor nutrition, but serum albumin and cholesterol levels can also be low as part of a cytokine-mediated acute-phase reaction to acute or chronic inflammation. Here we report the results from a 900-day prospective study designed to determine whether tumor necrosis factor-alfa (TNF-alpha) and interleukin-6 (IL-6) predict serum albumin and cholesterol levels and mortality in a group of 90 ambulatory, adult hemodialysis patients with no acute infection, hospitalization or surgery, and no known acquired immunodeficiency syndrome (AIDS), malignancy, or liver disease. Measurable levels of TNF-alpha and/or IL-6 were found in 89 of 90 patients. Significant relationships were found between TNF-alpha and IL-6 and the degree of hypoalbuminemia and dyslipoproteinemia. IL-6 was the strongest predictor of mortality in univariate and multivariate analysis, followed by age, albumin level, and body mass index (BMI). Although the cause of hypercytokinemia was not addressed in this study, the data support the view that hypoalbuminemia and hypocholesterolemia are negative acute-phase responses to inflammatory stimuli. These results suggest that efforts to identify the nature of the stimuli for cytokine production and to lower cytokine levels in hemodialysis patients might be effective in improving the survival of patients undergoing hemodialysis.

Adolescent↗
PubMed1997

Effect of nifedipine on renal allograft function and survival beyond one year.

We previously reported that a calcium channel blocker supplemented immunosuppression produced excellent patient and graft survival rates in cadaveric kidney transplantation. We report here the long term outcome of patients treated with nifedipine-supplemented triple immunosuppression as compared with those of historical controls who were treated similarly without nifedipine. Study subjects included 111 patients transplanted in 1990-1994, treated with nifedipine and triple immunosuppression and with functioning grafts for more than one year (Nifedipine group). The results of cyclosporine (CyA) dose, blood pressure (BP), serum creatinine (Cr), and actuarial graft survival rate (GSR) up to 5 years posttransplant in these patients were compared with those of 52 patients transplanted in 1985-1990, treated similarly without calcium channel blockers (Control group). Donor sources, gender ratio, age distribution, causes of end stage renal disease, incidence of hypertension prior to transplantation and incidence of rejection in the first year between the groups were comparable. Throughout the study period the Nifedipine group had significantly lower serum Cr (1.5 +/- 0.7 vs. 1.8 +/- 0.7 mg/dl) and higher GSR (93.8% vs. 88% at 5 years) than the Control group. BP was comparable despite higher CyA doses in the Nifedipine group (4.3 +/- 1.1 vs. 3.3 +/- 1.1 mg/kg/day). We conclude that nifedipine is beneficial in improving long-term graft function and survival in kidney transplant recipients by mitigating CyA associated renal injury.

Adult↗
PubMed1996

Long-term preservation of islets of Langerhans in hydrophilic macrobeads.

Several obstacles have hindered the successful transplantation of islets of Langerhans to human patients in efforts to cure type I diabetes mellitus. One problem is the necessity for short- and long-term storage of islets after isolation and before transplantation. Current long-term storage methods, such as incubation in a physiological medium and cryopreservation, are suboptimal, resulting in significant loss of viable islet mass or function. Better storage methods are needed. In this study we examined the long-term storage of rat islets in macrobeads composed of agarose and collagen. Islets isolated from Wistar-Furth rats were placed into macrobeads (1000 islets/macrobead) and maintained in culture for periods of up to 189 days at 37 degrees C. Insulin released from the cultured macrobeads remained constant for periods of at least 154 days. In one group, insulin release was 1050 mU/24 hr/4 beads on day 3 and 1040 mU/24 hr/4 beads on day 154. In another group, insuling release was 1305 Xenotransplantation of Wistar Furth islet macrobeads, stored for 10 to 112 days at 37 degrees C, degrees C into 42 B6AF/1 mice with streptozotocin-induced diabetes resulted in a return to euglycemia in the recipients within 24 hr. Thereafter, euglycemia was maintained for more than 100 days in 32/42 of the recipients, and removal of the macrobeads caused a return to hyperglycemia within 48 hr in all animals. In addition, a group of 7 mice receiving macrobeads containing 1000 islets stored for 84 days had normal glucose tolerance tests (compared with those of 7 nontreated, nontransplanted mice with streptozotocin-induced diabetes and 7 normal mice), demonstrating that the islets in the macrobeads were functioning as they would in an intact pancreas. Finally, 5 macrobeads transplanted after initial storage of 112 days, removed from the first recipient after 100 days or more, stored again for 4 days in vitro, and retransplanted into 5 other diabetic mice also restored and maintained euglycemia for at least 45 days. Our results indicate that collagen-agarose macrobeads are capable of preserving rat pancreatic islets for extended periods without loss of in vitro insulin release capability or ability to achieve and maintain euglycemia in vivo. As such they should be useful for human islet transplantation efforts.

Animals↗
PubMed1996

Low lipid concentrations in critical illness: implications for preventing and treating endotoxemia.

OBJECTIVES: To determine the prevalence and clinical significance of hypolipidemia found in critically ill patients, and whether the addition of a reconstituted lipoprotein preparation could inhibit the generation of tumor necrosis factor-alpha (TNF-alpha) in acute-phase blood taken from these patients. SETTING: Surgical intensive care unit (ICU) of a large urban university hospital. DESIGN: Prospective case series. PATIENTS: A total of 32 patients with a variety of critical illnesses had lipid and lipoprotein concentrations determined. Six patients and six age- and gender-matched control subjects had whole blood in vitro studies of the effect of lipoprotein on lipopolysaccharide mediated TNF-alpha production. INTERVENTIONS: Blood samples were drawn on admission to the ICU and over a subsequent 8-day period. MEASUREMENTS AND MAIN RESULTS: Mean serum lipid and lipoprotein values obtained from patients within 24 hrs of transfer to the surgical ICU were extremely low: mean total cholesterol was 117 mg/dL (3.03 mmol/L), low-density lipoprotein cholesterol 71 mg/dL (1.84 mmol/L), and high-density lipoprotein cholesterol 25 mg/dL (0.65 mmol/L). Only the mean triglyceride concentration of 105 mg/dL (1.19 mmol/L), and the mean lipoprotein(a) concentration of 25 mg/dL (0.25 g/L) were within the normal range. During the first 8 days following surgical ICU admission, there were trends toward increasing lipid and lipoprotein concentrations that were significant for triglycerides and apolipoprotein B. Survival did not correlate with the lipid or lipoprotein concentrations, but patients with infections had significantly lower (p = .008) high-density lipoprotein cholesterol concentrations compared with noninfected patients. Lipopolysaccharide-stimulated production of TNF-alpha in patient and control blood samples was completely suppressed by the addition of 2 mg/mL of a reconstituted high-density lipoprotein preparation. CONCLUSIONS: Patients who are critically ill from a variety of causes have extremely low cholesterol and lipoprotein concentrations. Correction of the hypolipidemia by a reconstituted high-density lipoprotein preparation offers a new strategy for the prevention and treatment of endotoxemia.

Adult↗
PubMed1995

Induction of pseudofoci and inhibition of density-mediated neoplastic transformation by PMA in NIH 3T3 cells after short-term exposures.

Depending on the precise conditions and cellular starting material, phorbol-13-myristate-12-acetate (PMA) can induce or suppress the transformation of NIH 3T3 cells. In sublines that do not undergo rapid transformation, exposure to PMA over the course of several weeks accelerated the process, while sublines that are primed for density-mediated transformation respond to PMA with a suppression of the process. This study examines the latter phenomenon. Within 1 h of exposure to 0.02 microgram/ml PMA, sparse cultures had undergone a morphological transition after which the cells appeared smaller and the processes thinner. These sublines exhibited a two- to sixfold increase in the saturation density achieved in 2% calf serum (CS). Phorbol ester analogs with hydrocarbon substitutions of 4 or more carbons at positions 12 and 13 of the phorbol nucleus had a similar effect as PMA on the saturation density. High concentrations of PMA (1 microgram/ml) induced the formation of cell aggregates (pseudofoci) that resembled transformed foci in their high local density, but unlike transformed foci, did not reinitiate focus formation if the cells were diluted and replated without PMA as secondary cultures. PMA inhibited the processes of neoplastic transformation and progression that occur readily in these NIH 3T3 sublines when they reach high cell density. I suggest that such changes occur because PMA abolishes the selection pressure at high densities that favors the transformation of some cells in heterogeneous populations. Induction of transformation by PMA (reported previously) occurs after much longer exposures in sublines that are relatively resistant to rapid density-mediated transformation.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1995

Reconstituted high-density lipoprotein neutralizes gram-negative bacterial lipopolysaccharides in human whole blood.

We have tested hypotheses relating lipoprotein structure to function as measured by the relative ability to neutralize endotoxin by comparing natural human lipoproteins, a chemically defined form of reconstituted high-density lipoprotein (R-HDL), and a lipid emulsion (Intralipid). The human whole-blood system was used as an in vitro model of lipopolysaccharide (LPS) binding protein and CD14-dependent activation of cytokine production. When lipoproteins were compared on the basis of protein content, R-HDL was most effective in reducing tumor necrosis factor alpha (TNF-alpha) production followed in order by very low density lipoprotein, low-density lipoprotein, Intralipid, and natural HDL. However, when these particles were compared by protein, phospholipid, cholesterol, or triglyceride content by stepwise linear regression analysis, only phospholipid was correlated to effectiveness (r2 = 0.873; P < 0.0001). Anti-CD14 monoclonal antibodies MY4 and 3C10 inhibited LPS binding protein and CD14-dependent activation of TNF-alpha production by LPS at LPS concentrations up to approximately 1.0 ng/ml. R-HDL (2 mg of protein per ml) blocked TNF-alpha production by LPS from both smooth- and rough-type gram-negative bacteria at concentrations up to 100 ng of LPS per ml but had little effect on heat-killed gram-positive Staphylococcus aureus and no effect on other LPS-independent stimuli tested. These results support our hypothesis that LPS is neutralized by binding to phospholipid on the surface of R-HDL and demonstrate that R-HDL is a potent inhibitor of the induction of TNF-alpha by LPS from both rough- and smooth-form gram-negative bacteria in whole human blood.

Antigens, CD↗
PubMed1994

Immunotherapy with anti-CD3 monoclonal antibodies and recombinant interleukin 2: stimulation of molecular programs of cytotoxic killer cells and induction of tumor regression.

Adoptive cellular immunotherapy, infusions of interleukin 2 (IL-2) in conjunction with in vitro-activated killer cells, has brought new hope to patients with cancer. The broad application of this strategy, however, is constrained by the need for repeated leukapheresis and by the labor-intensive process of in vitro activation of cells. Also, current protocols generally use nonphysiological and toxic concentrations of IL-2. Identification of an in vivo stimulant that renders T cells responsive to physiologic concentrations of IL-2 represents a potential improvement over existing approaches. We have determined whether in vivo administration of monoclonal antibodies (mAbs) directed at the T-cell surface protein CD3 induces T-cell responsiveness to IL-2, stimulates cytolytic molecular programs of natural killer cells and cytotoxic T cells, and induces tumor regression. These hypotheses were explored in a murine hepatic MCA-102 fibrosarcoma model. We report that in vivo administration of anti-CD3 mAbs plus IL-2 results in intrahepatic expression of mRNA-encoding perforin, cytotoxic T-cell-specific serine esterase, and tumor necrosis factor alpha. Anti-CD3 mAbs alone or IL-2 alone failed to induce or induced minimal expression of these molecular mediators of cytotoxicity. The anti-CD3 mAbs plus IL-2 regimen also resulted in a significantly smaller number of hepatic metastases and a significantly longer survival time of tumor-bearing mice, compared to treatment with anti-CD3 mAbs alone or IL-2 alone. Our findings suggest that a regimen of anti-CD3 mAbs plus IL-2 is a more effective antitumor regimen compared with anti-CD3 mAbs alone or IL-2 alone and advance an alternative immunotherapy strategy of potential value for the treatment of cancer in humans.

Animals↗
PubMed1994

Milk safety.

Explore the source record for details and available documents.

Animals↗
PubMed1994

Selective nature of phorbol 12-myristate 13-acetate-induced neoplastic transformation in NIH 3T3 cells.

The ability of phorbol 12-myristate 13-acetate (PMA) at 0.02 microgram/ml to induce neoplastic transformation in NIH 3T3 cells is highly dependent on the culture conditions. Optimal transformation, indicated by the saturation density and extent of focus formation in transferred cultures raised under standard conditions, was observed when the original cells were grown in 2% calf serum (CS) and exposed continually to PMA for at least 4 weeks before transfer into the assay. Transformation of stationary cultures in 10% CS occurred later and to a lesser degree than in 2% CS. The same cells subjected to thrice-weekly transfer in 2% or 10% CS at low cell density so that they were in a constant state of exponential growth exhibited no evidence of transformation in response to PMA. This strong condition-dependence of PMA-enhanced transformation is indicative of a selection process similar to that described for spontaneous transformation. In both cases, transformation is promoted by inhibiting multiplication and prevented by maximizing multiplication. Therefore, it has the earmarks of an epigenetic rather than a mutational process and requires phenotypic rather than genotypic variation to supply the states for selection. The concept of "progressive state selection," originally proposed to account for spontaneous transformation, can also account for PMA-enhanced transformation.

3T3 Cells↗
PubMed1994

Long term results of subtotal parathyroidectomy in patients with end-stage renal disease.

This is a retrospective, clinical study evaluating the long-term outcome of subtotal parathyroidectomy (PTX) in 60 patients with chronic renal failure and severe secondary hyperparathyroidism. Patients were 41 +/- 2 years old (mean +/- SE) at the time of PTX, and followed for 69 +/- 6 months since the procedure. At the time of PTX, three patients had chronic renal failure, 53 had been on chronic hemodialysis, and four had received successful kidney transplants. In more than 80 per cent of patients, symptoms of hyperparathyroidism (bone pain and muscle weakness) resolved within weeks, and biochemical signs (hypercalcemia, and high plasma alkaline phosphatase and parathyroid hormone concentrations) returned to normal ranges within a year. Subperiosteal resorption, bone fractures, and soft tissue calcification frequently improved. Osteosclerosis (rugger-jersey spine), cystic bone changes, osteopenia, and vascular calcifications were, however, often unchanged or progressive. Five patients (8%) who had either persistent or recurrent hyperparathyroidism required additional surgical procedures, and two had subsequent improvement. Twelve patients who had aluminum associated bone disease diagnosed later continued to progress with a high incidence of bone fractures and severe osteopenia. Cystic bone changes, especially of the carpal bones, in association with carpal tunnel syndrome, probably representing amyloid bone disease, also did not respond to PTX. In conclusion, PTX is an effective surgical procedure to reverse complications of hyperparathyroidism in patients with end-stage renal disease, provided that other causes of osteodystrophy, such as aluminum or amyloid-associated bone diseases, are adequately excluded. We feel that subtotal PTX, leaving a small remnant in place, is the procedure of choice.

Adolescent↗
PubMed1993

In vivo protection against endotoxin by plasma high density lipoprotein.

Overwhelming bacterial infection is accompanied by fever, hypotension, disseminated intravascular coagulation, and multiple organ failure leading to death in 30-80% of cases. These classical symptoms of septic shock are caused by potent cytokines that are produced in response to endotoxin released from Gram-negative bacteria. Treatments with antibodies and receptor antagonists to block endotoxin or cytokine mediators have given mixed results in clinical trials. High density lipoprotein (HDL) is a natural component of plasma that is known to neutralize endotoxin in vitro. We report here that raising the plasma HDL concentration protects mice against endotoxin in vivo. Transgenic mice with 2-fold-elevated plasma HDL levels had more endotoxin bound to HDL, lower plasma cytokine levels, and improved survival rates compared with low-HDL mice. Intravenous infusion of HDL also protected mice, but only when given as reconstituted HDL prepared from phospholipid and either HDL apoprotein or an 18-amino acid peptide synthesized to mimic the structure of apolipoprotein A-I of HDL. Intact plasma HDL was mildly toxic, and HDL apoprotein was ineffective. The effectiveness of the reconstituted peptide renders very unlikely any significant contribution to protection by trace proteins in apo-HDL. These data suggest a simple leaflet insertion model for binding and neutralization of lipopolysaccharide by phospholipid on the surface of HDL. Plasma HDL may normally act to protect against endotoxin; this protection may be augmented by administration of reconstituted HDL or reconstituted peptides.

Amino Acid Sequence↗