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Biomedical subjects

G Schulman

Publications and source records attributed to G Schulman.

At least 55 records · Page 3Linked to original sources
PubMed1993

The effects of recombinant human growth hormone and intradialytic parenteral nutrition in malnourished hemodialysis patients.

Malnutrition in hemodialysis patients is associated with increased morbidity and mortality. The use of intradialytic parenteral nutrition (IDPN) to improve nutritional parameters has been shown to be of limited benefit in most studies. We studied the use of recombinant human growth hormone (rHuGH) in potentiating the effects of IDPN in seven hemodialysis patients dialyzed with a Kt/V of 1.03 +/- 0.11 (mean +/- SEM), but with evidence of malnutrition: albumin, 3.2 +/- 0.18 g/dL; transferrin, 215 +/- 30 mg/dL; insulin-like growth factor-1 (IGF-1), 115 +/- 19 ng/mL, protein catabolic rate (PCR), 0.70 +/- 0.05 g/kg/d; and weight, 12.3% +/- 4.0% below ideal body weight. During 6 weeks of IDPN, resulting in an additional 18 +/- 4 kcal and 0.69 +/- 0.03 g of protein/kg body weight per dialysis session, albumin concentration increased to 3.5 +/- 0.14 g/dL (compared with baseline, P = NS), transferrin increased to 279 +/- 36 mg/dL (P < 0.002), IGF-1 increased to 152 +/- 32 ng/mL (P = NS), and PCR increased to 0.81 +/- 0.04 g/kg/d (P = NS). During the next 6 weeks, IDPN administration was continued and rHuGH, at a dose of 5 mg subcutaneously during each dialysis, was added to the regimen. This resulted in an increase in albumin concentration to 3.8 +/- 0.08 g/dL (P < or = 0.04 compared with end of IDPN phase), an increase in transferrin to 298 +/- 41 mg/dL (P = NS compared with end of IDPN phase), and an increase in IGF-1 to 212 +/- 45 ng/mL (P = 0.05 compared with end of IDPN phase).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Rapidly progressive acute renal failure due to acyclovir: case report and review of the literature.

Acyclovir nephrotoxicity has been described since the inception of the drug's use more than a decade ago. Acute renal failure mediated by this compound is characterized by abrupt elevations in serum creatinine and a gradual return to baseline renal function on discontinuation of the drug. Drug crystal formation in collecting tubules resulting in an intraparenchymal form of obstructive nephropathy has been suggested as the mechanism for acyclovir nephrotoxicity. The patient we present developed rapidly progressive acute renal failure with concomitant mental status changes in the setting of treatment with high-dose parenteral acyclovir. Acyclovir therapy was discontinued and an open renal biopsy was obtained to further evaluate our patient's diminishing renal function. Pathologic examination of the biopsy specimen revealed loss of proximal tubule brush border and dilated proximal and distal tubules with flattening of lining cells and focal nuclear loss. No crystals were noted. These changes were consistent with acute tubular necrosis with regeneration. Over the next 4 days our patient's renal and neurologic levels recovered to their prehospitalization statuses. It appears that our patient was affected by acyclovir-mediated nephrotoxicity that manifested on biopsy by acute tubular necrosis and the absence of crystalluria or crystal deposition. Intravenous acyclovir treatment can therefore produce rapidly progressive acute neurologic and renal toxicity that is usually reversible. The pathologic changes of acute tubular necrosis must now be included as part of the spectrum of renal damage associated with acyclovir therapy.

Acute Kidney Injury↗
PubMed1993

Heparin-associated thrombocytopenia and thrombosis (HATT) presenting with livedo reticularis.

BACKGROUND: Heparin-associated thrombocytopenia and thrombosis (HATT) is an infrequently encountered syndrome characterized by ischemic necrosis of soft tissue and vital organs following anticoagulation with heparin. The syndrome is thought to be due to heparin-dependent platelet aggregation and thrombosis, which is mediated by pathologic immunoglobulins. CASE REPORT: A 60-year-old man developed truncal livedo reticularis and ischemic necrosis of the left foot associated with thrombocytopenia, disseminated intravascular coagulopathy (DIC), and microangiopathic hemolytic anemia during intravenous heparin therapy. Skin biopsy from an area of livedo reticularis revealed fibrin thrombi in dermal blood vessels, which is characteristic of HATT. The diagnosis of HATT promoted discontinuation of heparin and a resulting rapid resolution of the livedo reticularis and hematologic abnormalities. No other potential causes of DIC were identified, and, other than stopping heparin, no specific therapy was employed. CONCLUSIONS: Periodic monitoring of platelets should be performed on all patients receiving treatment with heparin, as early detection of heparin-induced thrombocytopenia followed by discontinuation of the drug may prevent life threatening thrombotic complications. HATT should be included in the differential diagnosis of patients with livedo reticularis that occurs during heparin therapy.

Biopsy↗
PubMed1993

Demonstration of nuclear translocation of the mineralocorticoid receptor (MR) using an anti-MR antibody and confocal laser scanning microscopy.

Using a synthetic peptide that corresponds to a unique region of the N-terminal domain of the human mineralocorticoid receptor (MR), amino acids 87-96, we have generated a polyclonal antibody, human (h) MRsN. This sequence shares no homology with the corresponding sequences of the glucocorticoid receptor or other steroid/thyroid hormone receptor superfamily members. Antibody hMRsN cross-reacts with MR from human, rat, and mouse cells and recognizes denatured MR from either crude preparations or partially purified rat kidney cytosol, rat colon, or recombinant hMR overexpressed in baculovirus-infected Sf9 cells. Immunoprecipitation of the native MR from either partially purified or crude preparations of rat kidney cytosol with hMRsN, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver stain, demonstrated a major protein band with a mol wt of 116 kilodaltons. In addition, using confocal laser scanning microscopy and digital image analysis, the immunocytochemical localization of the recombinant hMR over-expressed in Sf9 cells 24 h post-transfection was determined. In the absence of ligand, the MR was detected solely in the cytoplasm, after a 30-min exposure to 100 nM aldosterone the MR was perinuclear, and after 60 min, the MR was predominantly nuclear. To ascertain that this phenomenon was not unique to insect cells, aldosterone induced MR nuclear translocation in mouse macrophage cells was also demonstrated immunocytochemically, clearly indicating a role for nuclear translocation in MR function.

Amino Acid Sequence↗
PubMed1993

Bradykinin generation by dialysis membranes: possible role in anaphylactic reaction.

Several recent reports have described a high incidence of anaphylactic reactions in patients being dialyzed with high-flux membranes while simultaneously using angiotensin-converting enzyme inhibitors. Many of these reports implicate polyacrylonitrile (PAN) as the membrane commonly involved in these reactions. To elucidate potential mechanisms of these anaphylactic reactions, whether dialysis membranes can activate the Hageman factor-dependent (contact) pathways as assessed by the in vitro generation of activated Hageman factor (Hfa), as well as the formation of kallikrein and subsequent bradykinin generation was examined. Both cuprophane (CUP) and PAN membranes were able to activate Hageman factor and convert prekallikrein to kallikrein as measured by an ELISA against kallikrein-C1-inactivator complexes. Subsequently, the active kallikrein was able to cleave bradykinin from its endogenous substrate, high-molecular-weight kininogen. However, it was found that the PAN membrane consistently led to an earlier and significantly higher formation of Hfa and kallikrein when compared with CUP. Importantly, there was also a pronounced but transient generation of bradykinin by the PAN membrane, in contrast to slower bradykinin formation by CUP, with both normal and uremic blood. It was proposed that the early and vigorous bradykinin generation induced by the contact of blood with PAN could explain, in part, the pathogenesis of the reported anaphylactoid reactions.

Acrylic Resins↗
PubMed1993

A review of the concept of biocompatibility.

The consequences of blood-membrane interactions are numerous. The perturbations created in the cellular components and humoral pathways are being actively pursued. These changes interact with and may be modified by other aspects of the hemodialysis treatment. They are capable of producing adverse events in the hemodialysis patient. Events range from acute life-threatening reactions, through chronic changes which may interfere with the immune response, impact upon the patients' nutritional status and cause residual renal function to deteriorate.

Biocompatible Materials↗
PubMed1992

Modulators of the glucocorticoid receptor also regulate mineralocorticoid receptor function.

Modulators are proposed to be novel ether aminophosphoglycerides that stabilize unoccupied and occupied glucocorticoid receptor steroid binding and inhibit glucocorticoid receptor complex activation. Two isoforms, modulator 1 and modulator 2, have been purified from rat liver cytosol [Bodine, P.V., & Litwack, G. (1990) J. Biol. Chem. 265, 9544-9554]. Since the mineralocorticoid receptor is relatively resistant to activation, modulator's effect on rat distal colon mineralocorticoid receptor function was examined. Warming of unoccupied receptor decreased residual specific [3H]aldosterone binding by 86 +/- 2%. Both modulator isoforms completely prevented this destabilization with Km's of 2 +/- 1 microM modulator 1 and 24 +/- 5 microM modulator 2. Warming of occupied mineralocorticoid receptors decreased [3H]aldosterone binding by 56 +/- 3%. Modulator only partially stabilized occupied receptor binding with Km's of 10 +/- 2 microM modulator 1 and 68 +/- 8 microM modulator 2. Modulator inhibited receptor activation with Km's of 3 +/- 1 microM modulator 1 and 33 +/- 10 microM modulator 2. Double-reciprocal analysis showed linear kinetics, and mixing modulator isoforms together had additive effects on unoccupied and occupied receptor steroid binding stabilization and activation inhibition. Colon cytosol contained a low molecular weight, heat-stable factor(s) which inhibited receptor activation and stabilized occupied receptor steroid binding. Molybdate completely stabilized unoccupied mineralocorticoid receptor steroid binding and inhibited activation with half-maximal effects at 3-4 mM but only stabilized occupied receptor binding by approximately 40%. These data indicate that (i) apparent physiologic concentrations of modulator stabilize mineralocorticoid receptor steroid binding and inhibit receptor activation, (ii) an aldosterone-responsive tissue contains a modulator-like activity, and (iii) molybdate mimics the effects of modulator.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1992

Glucocorticoids inhibit colonic aldosterone-induced conductive Na+ absorption in adrenalectomized rat.

Low-dose glucocorticoids induce only electroneutral Na absorption in rat colon. High-dose dexamethasone induces both electroneutral and electrogenic Na absorption. Aldosterone induces only electrogenic Na absorption and inhibits basal electroneutral transport in distal colon. To define the interrelationship between glucocorticoid-mediated and aldosterone-mediated Na absorption, adrenalectomized rats were treated with aldosterone and either glucocorticoid-receptor-specific doses of dexamethasone or the specific glucocorticoid RU26988. In combination the steroids did not increase Na and Cl absorption in proximal and distal colon and transmural potential difference (PD) and K secretion in distal colon as much as aldosterone alone. Na absorption was not inhibited by spironolactone or amiloride (10(-4) M). Transport in both segments was by Na-H exchange as demonstrated by marked inhibition by amiloride (10(-3) M) and the Na-H antiport inhibitor 5-(N-ethyl-N-isopropyl)amiloride. Thus glucocorticoids not only decreased Na absorption but also produced a marked qualitative change in the mode of Na absorption in aldosterone-treated rats. Acute dexamethasone infusion in rats pretreated with aldosterone decreased Na absorption and transmural PD within 30 min, suggesting inhibition of electrogenic Na absorption at a step distal to synthesis of aldosterone-induced proteins. These findings suggest that upregulation of one Na absorptive mechanism downregulates the other. This may explain why in intact unstressed rats there is little or no conductive Na absorption, despite sufficient endogenous steroid to occupy the aldosterone receptor. It may also explain why in proximal colon of intact rats, despite the presence of aldosterone receptors, even prolonged aldosterone exposure does not induce significant conductive Na absorption.

Absorption↗
PubMed1992

Characterization of in vitro translated human mineralocorticoid receptor. Structure and activation.

The structures of the unactivated and activated mineralocorticoid receptors have been difficult to characterize because of receptor lability and steroid dissociation. Therefore, human mineralocorticoid receptor mRNA was translated in rabbit reticulocyte lysate in the presence and absence of [35S]methionine to compare the structure of [3H]aldosterone-bound and [35S]labeled receptor. In vitro synthesized receptor was able to specifically bind [3H]aldosterone. Unactivated [3H]aldosterone-bound and 60% of unactivated [35S]labeled receptor eluted from DEAE-cellulose with 250 mM salt and had a Rs of 72A. Forty percent of unactivated [35S]labeled receptor eluted from DEAE-cellulose with 100 mM salt and had a Rs of 54A. SDSPAGE showed intact hMR was present in both DEAE-cellulose eluates as three bands between M(r) 110,000-120,000. However, the low salt eluate contained less intact receptor and more lower MW bands. Neither [3H]aldosterone-bound nor [35S]labeled receptor was activated by incubation at 25 degrees C as readily as glucocorticoid receptor studied under identical conditions. Activated [3H]aldosterone-bound receptor eluted from DEAE-cellulose at 100 mM salt and had a Rs of 37A. After activation, 60% of [35S]labeled receptor eluted from DEAE-cellulose with 100 mM salt and had a Rs of 91A. SDS-PAGE of the high and low salt DEAE-cellulose eluates showed that 50% of intact receptor eluted in the low salt peak after activation. These data indicate that: 1. Some in vitro synthesized mineralocorticoid receptor assembles into the heteromeric unactivated form; 2. The remaining intact receptor remains monomeric and unable to bind steroid; 3. Activation causes dissociation of intact receptor from a larger complex; and 4. Activated receptor tends to aggregate.

Aldosterone↗
PubMed1991

Complement activation retards resolution of acute ischemic renal failure in the rat.

We investigated the role of complement activation on the resolution of acute ischemic renal failure in the rat. Acute renal failure was induced by clamping of the renal arteries of Sprague-Dawley rats for 45 minutes (Day 0). On subsequent days, groups of rats with acute renal failure were exposed to daily zymosan infusion (an activator of the complement system), or to blood incubated with cuprophane (CUP) or polyacrylonitrile (PAN) dialysis membranes. We serially measured the change in BUN daily, glomerular filtration rate and 24-hour proteinuria on Day 3 and Day 5 following ischemia. On Day 6, the animals were sacrificed and their kidneys examined histologically. Zymosan and cuprophane exposed rats had a significant delay in the recovery of renal failure, reduced glomerular filtration rate, and histologically had more neutrophil infiltration than control or PAN exposed animals. To investigate the potential pathophysiology of these observations, we assessed the response of zymosan-exposed rats to infusion of deferoxamine (DFO), a potent inhibitor of hydroxyl radical formation (OH.). Infusion of DFO prior to zymosan significantly improved recovery of renal function. We also measured urinary thromboxane B2 levels in these groups of rats. While the groups of rats exposed to zymosan had the highest levels of thromboxane B2, these levels were not different between the groups exposed to zymosan alone, or to zymosan and DFO. These observations suggest a role for hydroxyl radicals in the prolongation of renal failure in this model. Taken together, these findings may have implications for the dialytic intervention in patients with acute renal failure.

Acute Kidney Injury↗
PubMed1991

Low-dose glucocorticoids maintain Na-H exchange in distal colon of adrenalectomized rats.

With in vivo perfusion we demonstrated that physiological doses of glucocorticoids restore Na and Cl absorption in adrenalectomized rat colon. The absorption is spironolactone and amiloride resistant and is inhibited by the Na-H inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA), suggesting that glucocorticoids modulate Na-H antiport. The present in vitro study examines pathways mediated by glucocorticoids in adrenalectomized rat distal colon and rectum. In vivo administration of 2.5 micrograms/100 g body wt dexamethasone did not alter serosal-to-mucosal flux or tissue electrical parameters but restored mucosal-to-serosal flux and net Na and Cl absorption within 2-3 h of administration to levels found in intact rat colon. Transport was not inhibited by 10(-5) M amiloride but was eliminated by 10(-5) M EIPA. After 26 h of dexamethasone, an amiloride-resistant short-circuit current was stimulated, accompanied by increased residual ion flux in rectum, but not distal colon, suggesting that a delayed or secondary effect of glucocorticoids is stimulation of electrogenic anion secretion. Thus adrenalectomy reduces net ion flux in distal colon by its effect on electroneutral mucosal-to-serosal NaCl flux. Small doses of glucocorticoids completely ameliorate this effect via stimulation of the Na-H antiport. Glucocorticoids maintain basal electroneutral NaCl absorption in distal rat colon.

Adrenalectomy↗
PubMed1991

Psyche and skin.

In this short communication, I intend to present a specific psycho-dynamic theory which explains some of the psychodynamics associated with eczemas and perhaps to some other skin lesions. It provides a framework for understanding and treating such lesions with pure psychodynamic methods, i.e., by psychoanalysis or analytic psychotherapy. These ideas were first presented in 1968 by Ester Bick, a Polish psychoanalyst living in London. Her theory of the role of the primal object for the baby, as the provider of necessary psychological containment, a kind of psychological skin, has proven to be of great value for psychoanalysts and psychotherapists treating adults and children with skin problems. When this "skin function" of the caretaking object fails, real skin lesions may follow. When the person finds in treatment an object who has this containing function, his/her skin heals.

Humans↗
PubMed1989

Kinetics and efficacy of deferoxamine in iron-overloaded hemodialysis patients.

We evaluated the kinetics and efficacy of deferoxamine (DFO) therapy in iron-overloaded hemodialysis patients. Concentrations of DFO and its chelated product, feroxamine (Fx), were assessed following single-dose DFO administration in twelve patients, and during chronic therapy over one year's time in eight, similarly iron-overloaded dialysis patients. A functional assay which relies on measurements of iron and iron binding capacity for the determination of Fx and DFO, respectively, was corroborated with liquid chromatographic techniques. Half-life measurements were also corroborated with tracer doses of 14C-DFO and 59Fe-feroxamine. Intradialytic DFO half-life (2.3 +/- 1.1 h) was considerably less than interdialytic half-life (26 +/- 1 hr). Unbound DFO was found to persist throughout the interdialytic period. Calculation of the percent saturation of the DFO dose indicated that only 30% of a given dose is chelated. The amount of iron removed dialytically was approximately 13.1 +/- 2.7 mg per dialysis session. Chronic DFO administration was also shown to enhance gastrointestinal iron excretion threefold. However, ferritin levels decreased by only 25% after one year of thrice-weekly DFO therapy. We conclude that DFO therapy for iron-overloaded hemodialysis patients is optimized by its administration interdialytically, and results in slow removal of iron, via both dialytic and gastrointestinal routes.

Adult↗
PubMed1989

Low-dose glucocorticoids stimulate electroneutral NaCl absorption in rat colon.

Glucocorticoids, not aldosterone, may regulate basal colonic NaCl transport. Aldosterone induces spironolactone-inhibitable, amiloride-inhibitable conductive Na absorption but basal transport is electroneutral and amiloride and spironolactone resistant. We examined in vivo the Na absorptive pathway induced by glucocorticoid receptor specific doses of glucocorticoid using various amiloride analogues. Doses of dexamethasone sufficient to co-occupy aldosterone receptors produced amiloride-sensitive Na absorption in proximal and distal colon. Low doses of dexamethasone or the specific glucocorticoid RU26988 markedly stimulated Na absorption but did so by an amiloride-resistant mechanism. The Na-H antiport inhibitor, 5-N-ethyl-N-isopropylamiloride (NENIA) eliminated glucocorticoid-induced Na and Cl absorption without changing transmural potential difference (PD) in proximal and distal colon (Ki = 0.7 x 10(-7) M). NENIA had no effect on aldosterone-induced transport. NENIA (10(-5) M) almost eliminated Na absorption in adrenal intact animals if infused early in the experimental protocol. With time, NENIA resistance developed, corresponding with the previously documented rise in endogenous aldosterone. Thus glucocorticoids induce an electroneutral Na absorptive pathway that may be the luminal Na-H antiport, suggesting that glucocorticoids regulate adrenal-dependent electroneutral Na absorption in rat colon.

Adrenalectomy↗
PubMed1987

Iron overload and mobilization in long-term hemodialysis patients.

Iron overload from repeated transfusions of RBCs in long-term hemodialysis patients is a problem of increasing clinical significance. We report on the prevalence of and diagnostic criteria for identification of hemodialysis patients with iron overload. In 150 unselected hemodialysis patients, 62 (41%) had ferritin levels greater than 2,000 ng/mL (normal = 10 to 360 ng/mL). In 16 of these patients, accurate transfusion histories were obtained and ferritin levels correlated with calculated transfusional iron burden (r = 0.553, P less than .05). These patients could be divided into two distinct groups on the basis of their response to a single dose (2 g, IV) of deferoxamine: "high" responders had twice the level of feroxamine (the chelated product of deferoxamine and iron) of the "low" responders (P less than .001). High responders also had significantly higher prevalence of the "hemochromatosis" alleles A3, B7, and B14 than a large group of dialysis patients awaiting transplantation (71% v 37%, P less than .001). In two patients with iron overload and clinically significant bone disease, bone histology revealed prominent iron staining at the calcification front. We conclude that transfusional iron overload is a significant clinical problem in long-term hemodialysis patients, that may also be associated with bone pathology.

Adult↗
PubMed1987

Severe metabolic alkalosis complicating regional citrate hemodialysis.

Regional citrate hemodialysis has been effectively used as an alternative to heparin anticoagulation during dialysis of patients at increased risk for bleeding. Few complications have been noted; however, we report the occurrence of severe metabolic alkalosis in two patients requiring high infusion rates of citrate during hemodialysis while being mechanically ventilated. Careful monitoring of acid-base status is mandatory in this setting, and reduction of citrate dose may be advisable.

Aged↗
PubMed1986

Characterization of the rat colonic aldosterone receptor and its activation process.

Aldosterone increases sodium absorption, short circuit current, and transmural potential difference in rat colon. We studied the rat colonic aldosterone receptor using the synthetic glucocorticoid, 11 beta, 17 beta-dihydroxy-17 alpha-propynylandrosta-1,4,6-triene-3-one, to prevent binding to the glucocorticoid receptor. Specific aldosterone binding was found in proximal and distal colon. Heating to 25 degrees C decreased binding within 15 min, but the protease inhibitor, phenylmethylsulfonyl fluoride, stabilized binding. Binding was highest in terminal distal colon. Competitive binding assay showed aldosterone specificity compared to other competitors was greater at 30 than at 4 degrees C, suggesting temperature-sensitive changes in receptor specificity. Scatchard analysis revealed a straight line with a KD of 2.5 nM at 0 degrees C and 4.1 nM at 30 degrees C. Bmax was higher in distal than in proximal colon (30 degrees C, 156 +/- 33 versus 65 +/- 9 fmol/mg protein) and increased by 36% in proximal and 180% in distal colon at 30 degrees C compared to 0 degrees C. DEAE-cellulose chromatography of unactivated receptor demonstrated a single peak eluting at 200-250 mM KCl. Heat, ATP, and gel filtration did not activate the receptor, whereas increasing cytosolic salt concentration to 300 mM KCl, raising the pH to 8, or adding EGTA and EDTA caused increased DNA-cellulose binding and a new peak eluting at 30-80 mM KCl on DEAE-cellulose chromatography. There is a specific aldosterone receptor in colon with increasing number of binding sites from proximal to most distal segments paralleling aldosterone's physiological effects. Absence of receptor activation with heat, gel filtration, or ATP suggests differences between activation of the aldosterone receptor and other steroid hormone receptors.

Aldosterone↗