Albert L. Rubin

Hypertension is Not Adequately Controlled in Hemodialysis Patients

To examine the adequacy of hypertension control, we monitored the blood pressure (BP) of 53 hemodialysis patients who received treatment for hypertension. BP measurement using an ambulatory BP monitor began 1 hour before dialysis and continued every 30 to 60 minutes for 48 hours until the next dialysis. Diet, medications including antihypertensive drugs, and hemodialysis prescription were not changed during this study. Each patient had a mean of 68 BP measurements during the monitoring period. Mean (+/- SD) systolic and diastolic BP levels of all patients over 48 hours were 158.6 +/- 22.7 mm Hg and 88.7 +/- 16.6 mm Hg, respectively, without diurnal variations. In these, BP loads (the percentage of systolic BP exceeding 150 mm Hg and diastolic BP exceeding 90 mm Hg) were 58.4% and 39.4%, respectively, suggesting that hypertension was inadequately controlled for more than half of the study period. Eight patients (15%) maintained BP within normal ranges at all times. All patients lost weight (2.9 +/- 0.9 kg) at the end of dialysis by ultrafiltration. However, only 27 patients (51%) had a greater than 5% decrease in mean arterial BP post-dialysis, which returned to predialysis levels within 12 to 24 hours. Reduction of BP postdialysis was significantly more common among black patients (72%) than white patients (30%) (P less than 0.01). However, there was no difference in age, cause of kidney disease, amount of ultrafiltration, and BP loads between those whose BP decreased and those whose did not. BP monitoring was repeated in eight patients, 2 to 3 months after adjustment of their antihypertensive regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Tropocollagen: significance of protease-induced alterations.

Interaction properties of tropocollagen are markedly altered by treatment with pepsin. This treatment liberates terminal or near-terminal covalently bonded peptides whose amino acid composition is strikingly different from the composition of the pepsin-resistant triple-helix body of the macromolecule. Pepsin also converts most of the β-chains to α-chains. This fact indicates that the interchain link is also external to the body of the macromolecule and probably involves peptides. The role of these properties in bioregulative mechanisms is briefly discussed.

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

ObjectiveTo determine the relationship of hypolipidemia to cytokine concentrations and clinical outcomes in critically ill surgical patients. DesignConsecutive, prospective case series. SettingSurgical intensive care unit of an urban university hospital. PatientsSubjects 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. InterventionsBlood 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-&agr;, 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. ConclusionsLow 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.

Somatomedin and Growth after Renal Transplantation

Extract: Hormonal and metabolic factors which influence growth were studied in nine growth-retarded uremic children who received renal homografts. Post-transplant growth velocity based on bone age (GVBA) became normal in four (88–103%), accelerated in two (127–139%), and remained subnormal in three (18–50%). Serum somatomedin (SM), was very low in all children before transplant (0.39 ± 0.10 U/ml), but rose in each child after transplantation. Post-transplant somatomedin (0.84 ± 0.14 U/ml) was not significantly different from the somatomedin of eight healthy male control subjects matched for bone age (1.03 ± 0.16). Post-transplant GVBA was directly correlated (P < 0.05) with serum somatomedin and creatinine clearance (Ccr), but was not related to stimulated growth hormone response or to other variables of endocrine function. The data suggested that the growth failure in our patients with severe chronic uremia was due, at least in part, to lack of serum somatomedin. However, in four of five patients with persisting moderate azotemia (Ccr 11.8–42.5 ml/min/1.73 m2), subnormal growth continued despite relatively normalized serum somatomedin activity. Three of the four poorly growing azotemic patients had the highest average steroid dosages in the group (prednisolone > 9.1 mg/m2/24 hr).Speculation: If low serum somatomedin activity develops in the course of end stage renal disease in children, growth retardation may be the consequence. After renal transplantation normalization of serum somatomedin activity may be a necessary although not sufficient condition for the resumption of growth.

Hypercalcemia after renal transplantation

Hypercalcemia and hypophosphatemia after renal transplantation are described. Serum and urine calcium, phosphorus, creatinine and serum levels of parathyroid hormone (PTH) were followed in thirty-four patients who received transplants. Hypophosphatemia occurred in nearly all those with successfull transplants and correlated with the administration of oral hydroxide antacids. Clinical effects of phosphorus depletion included weakness, intention tremor, bone pain, pseudofractures and hypercalcemia. Treatment with oral phosphate reversed the abnormalities. The administration of aluminum phosphate gel did not induce hypophosphatemia. Hypercalcemia of 12 to 15 mg per cent necessitated subtotal parathyroidectomy in five patients, two of whom had oliguria and one polyuria due to hypercalcemia. The roles of parathyroid hyperplasia, phosphorus depletion, vitamin D therapy, steroid therapy and magnesium depletion in the evolution of post-transplant hypercalcemia are discussed.

Ototoxicity Induced by Furosemide

FUROSEMIDE is a diuretic that has achieved wide use because of its great potency as a saluretic agent and its low order of toxicity. We describe here transient ototoxic effects of high-dose furosem...

Retrievable, replaceable, macroencapsulated pancreatic islet xenografts : long-term engraftment without immunosuppression

Prevention of rejection and prolongation of graft survival are critical to achieving successful islet cell transplantation. Various techniques have been utilized to prolong graft survival. Recently, protection of pancreatic islets from host immune mechanisms by isolating the islets in artificial membranes has emerged as an attractive alternative to the use of immunosuppression. In this Rapid Communication, we describe a novel method for macroencapsulation of rat islets in hydrophilic macrobeads made with various combinations of agarose, collagen, and Gelfoam. Encapsulated xenotypic islets were placed intraperitoneally in mice in which diabetes was induced by streptozotocin. The encapsulated xenografts maintained normoglycemia > 170 days. Recipients mice had normal glucose tolerance tests, which indicates that the islets in the macrobeads were functioning as they would in an intact pancreas. Macrobeads retrieved up to 103 days after transplantation showed no evidence of tissue reaction or local inflammation. These retrieved macrobeads could also be retransplanted and replaced. Our studies indicate that the agarose-collagen/Gelfoam macrobeads we have developed serve both to protect islet xenografts from rejection and to provide a microenvironment in which the islets maintain and support their normal function in vivo. Because they may be retrieved after implantation and replaced, these macrobeads may be suitable for human clinical islet cell xenotransplantation.

Pruritus in Dialysis Patients Treated with Parenteral Lidocaine

Pruritus is one of the most disturbing and poorly understood symptoms in patients on chronic hemodialysis,1 2 3 4 its reported prevalence varying from 15 to 86 per cent. Except for a few case repor...

Three-Dimensional Culture of Mouse Renal Carcinoma Cells in Agarose Macrobeads Selects for a Subpopulation of Cells with Cancer Stem Cell or Cancer Progenitor Properties

The culture of tumor cell lines in three-dimensional scaffolds is considered to more closely replicate the in vivo tumor microenvironment than the standard method of two-dimensional cell culture. We hypothesized that our method of encapsulating and maintaining viable and functional pancreatic islets in agarose-agarose macrobeads (diameter 6-8 mm) might provide a novel method for the culture of tumor cell lines. In this report we describe and characterize tumor colonies that form within macrobeads seeded with mouse renal adenocarcinoma cells. Approximately 1% of seeded tumor cells survive in the macrobead and over several months form discrete elliptical colonies appearing as tumor cell niches with increasing metabolic activity in parallel to colony size. The tumor colonies demonstrate ongoing cell turnover as shown by BrdU incorporation and activated caspase-3 and TUNEL staining. Genes upregulated in the tumor colonies of the macrobead are likely adaptations to this novel environment, as well as an amplification of G(1)/S cell-cycle checkpoints. The data presented, including SCA-1 and Oct4 positivity and the upregulation of stem cell-like genes such as those associated with the Wnt pathway, support the notion that the macrobead selects for a subpopulation of cells with cancer stem cell or cancer progenitor properties.