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Biomedical subjects

A Greenberg

Publications and source records attributed to A Greenberg.

At least 37 records · Page 2Linked to original sources
PubMed2000

Tracheal constrictor drive above the apneic threshold in anesthetized dogs.

We have previously shown that raising arterial PCO(2) (Pa(CO(2))) by small increments in dogs ventilated below the apneic threshold (AT) results in almost complete tracheal constriction before the return of phrenic activity (Dickstein JA, Greenberg A, Kruger J, Robicsek A, Silverman J, Sommer L, Sommer D, Volgyesi G, Iscoe S, and Fisher JA. J Appl Physiol 81: 1844-1849, 1996). We hypothesized that, if increasing chemical drive above the AT mediates increasing constrictor drive to tracheal smooth muscle, then pulmonary slowly adapting receptor input should elicit more tracheal dilation below the AT than above. In six methohexital sodium-anesthetized, paralyzed, and ventilated dogs, we measured changes in tracheal diameter in response to step increases in tidal volume (VT) or respiratory frequency (f) below and above the AT at constant Pa(CO(2)) ( approximately 40 and 67 Torr, respectively). Increases in VT (400-1,200 ml) caused significantly more (P = 0.005) tracheal dilation below than above AT (7.0 +/- 2.2 vs. 2.8 +/- 1.0 mm, respectively). In contrast, increases in f (14-22 breaths/min) caused similar (P = 0.93) tracheal dilations below and above (1.0 +/- 1.3 and 1.0 +/- 0.8 mm, respectively) AT. The greater effectiveness of dilator stimuli below compared with above the AT is consistent with the hypothesis that drive to tracheal smooth muscle increases even after attainment of maximal constriction. Our results emphasize the importance of controlling PCO(2) with respect to the AT when tracheal smooth muscle tone is experimentally altered.

Animals↗
PubMed2000

Diuretic complications.

BACKGROUND: Diuretics are widely used and generally safe, but like any therapeutic agents, they may cause side effects. METHODS: A review of recent literature pertaining to diuretic usage was performed, with emphasis on specific reports of side effects. Reports of large-scale hypertension trials employing diuretics were also examined for descriptions of diuretic-related complications. RESULTS: All diuretics promote excretion of sodium. Depending upon the site and mode of action, some diuretics increase excretion of potassium, chloride, calcium, bicarbonate, or magnesium. Some can reduce renal excretion of electrolyte-free water, calcium, potassium, or protons. Consequently, electrolyte and acid-base disorders commonly accompany diuretic use. Except for the mildly natriuretic collecting duct agents, which are used mainly to limit potassium excretion, all diuretics can cause volume depletion with prerenal azotemia. Loop agents and distal convoluted tubule agents, such as the thiazides, produce hypokalemic, hypochloremic, metabolic alkalosis that responds to potassium chloride replacement. Carbonic anhydrase inhibitors produce less hypokalemia and volume depletion but commonly induce metabolic acidosis that is often symptomatic. The potassium-sparing agents also limit proton excretion, and spironolactone may produce metabolic acidosis. Hyperkalemia is a leading complication of the potassium-sparing agents, especially in patients with an underlying tendency for hyperkalemia. Thiazide diuretics, in particular, have been linked to glucose intolerance, which may be an effect of hypokalemia rather than the diuretic itself. Whether diuretic-induced hypokalemia increases cardiovascular risk is controversial. Loop agents and thiazides may lead to hyponatremia, which, in the case of thiazides, may cause permanent neurologic damage. Dose-related reversible or irreversible ototoxicity may complicate treatment with loop agents. Nephrocalcinosis, nephrolithiasis, hypomagnesemia, and hyperuricemia can potentially complicate treatment with some diuretic agents. Reported idiosyncratic reactions to diuretics include interstitial nephritis, noncardiogenic pulmonary edema, pancreatitis, and myalgias. CONCLUSIONS: Potential side effects of a diuretic can often be anticipated from its mode of action on the kidney. These complications may be mitigated with careful monitoring, dosage adjustment, and replacement of electrolyte losses. Other side effects are idiosyncratic and cannot be prevented.

Acid-Base Equilibrium↗
PubMed2000

Factors affecting system clotting in continuous renal replacement therapy: results of a randomized, controlled trial.

BACKGROUND: System clotting and the anticoagulation techniques employed to prevent it are important causes of morbidity in continuous renal replacement therapy (CRRT). Different means have been employed in attempts to prolong system lifespan while minimizing complications. SUBJECTS, MATERIALS AND METHODS: To determine whether augmenting blood flow and flush frequency could reduce clotting frequency, we compared system lifespan in a standard blood flow and saline flush group (125 ml/min and 100 ml once hourly, respectively) to an augmented blood flow and saline flush group (200-250 ml/min and 100 ml twice hourly). A total of 34 patients treated with continuous venovenous hemodialysis were randomized to receive either the standard or augmented regimens in a prospective trial conducted between August 1995 and March 1997. A total of 130 systems were studied. RESULTS: Based on intention-to-treat analysis, there was no difference in time to clot between the two groups. In a multivariate analysis of the outcome, red blood cell and platelet transfusion during CRRT were significantly associated with decreased clotting, and systemic heparin infusion significantly prolonged lifespan of CRRT systems. CONCLUSION: Increasing blood flow and flush frequency does not prevent clotting in CRRT. Since this intervention is more costly than standard treatment, its use cannot be justified.

Analysis of Variance↗
PubMed2000

Factors influencing function of temporary dialysis catheters.

AIM: To determine risk factors for failure of temporary dialysis catheters, we prospectively studied the outcome of 178 non-tunneled dual lumen catheters placed in 126 consecutive patients requiring treatment of acute renal failure (ARF) or end-stage renal disease (ESRD). METHODS: Internal jugular (IJ) or subclavian (SC) catheters were used in 122 instances and femoral catheters were employed in 56. RESULTS: IJ or SC catheters with tips in the right atrium or superior vena cava (n = 112) failed (defined as a blood flow < 250 ml/min) 17% of the time, compared with a 40% failure rate for catheters with more peripherally located tips (n = 10), p < 0.05, chi2 testing. In a multivariate analysis, use in ESRD and location peripheral to the SVC were risk factors for catheter failure. Use of one of three catheter brands was associated with a lower failure rate. Although mean venous pressures at 200 ml/min blood flow were higher in IJ or SC catheters that failed, the presence of a high venous pressure, number of catheter uses, IJ vs. SC placement, inpatient vs. outpatient status, and fresh venipuncture vs. placement over a guidewire passed through a previous catheter did not predict catheter malfunction. With femoral catheters, the only risk factor for failure was use in ESRD. CONCLUSION: Of the factors that can be influenced by placement technique, catheter tip location is most important. Whether one catheter brand is superior awaits further confirmation.

Catheterization↗
PubMed2000

Cefuroxime utilization evaluation: impact of physician education on prescribing patterns.

BACKGROUND: Cefuroxime is a second-generation cephalosporin antibiotic used widely for the treatment of various infections. OBJECTIVES: To assess the appropriateness of cefuroxime usage as well as the long-term impact of re-feeding the results to prescribing physicians. METHODS: Drug utilization evaluation involved three data-collecting periods, each comprising 6 weeks, during which all patients receiving cefuroxime were evaluated. Results of phase I were distributed to all physicians in a newsletter and departmental lectures; phase II was announced and conducted 6 months later. An identical phase III was unannounced and conducted one year after phase II. The study included all patients receiving cefuroxime during the three phases. The main outcome measure was appropriateness of initiation, and continuation beyond 3 days, of empirical treatment. Appropriateness was determined according to a prepared list of indications based on the literature and the hospital's protocols. RESULTS: Cefuroxime was initiated appropriately in 104 of 134 patients (78%) in phase I, in 85 of 100 (85%) in phase II, and in 93 of 100 (93%) in phase III (P < 0.001). Cefuroxime was continued appropriately after 3 days in 58/134 (43%), 57/100 (57%) and 70/100 (70%) respectively (P < 0.001). The total number of appropriate treatment days out of all treatment days increased from 516 of 635 (81%) in phase I, to 450 of 510 (88%) in phase II, to 485 of 509 (95%) in phase III (P < 0.001). The principal reason for cefuroxime usage was community-acquired respiratory tract infection. CONCLUSION: Drug utilization evaluation may provide valuable data on the usage of a particular drug. This information, once re-fed to physicians, may improve utilization of the particular drug. This positive effect may be prolonged beyond the immediate period of observation.

Cefuroxime↗
PubMed1999

Extraction and high-performance liquid chromatographic separation of selected pyrene and benzo[a]pyrene sulfates and glucuronides: preliminary application to the analysis of smokers' urine.

In the study of the complex mixture of urinary metabolites derived from polycyclic aromatic hydrocarbon compounds, it is desirable to simplify the analysis through separation of classes of compounds. We have developed a liquid chromatography (LC) method for the separation of selected sulfate and glucuronide conjugate isomers derived from hydroxybenzo[a]pyrenes (OH-BaP) and hydroxypyrenes. This LC method was utilized in the preliminary analysis of the urine of smokers by combining it with an extraction technique employing tetra-n-butyl-ammonium ion as a coupling agent to generate a 1:1 complex, extractable in chloroform at low pH prior to LC analysis.

Benzo(a)pyrene↗
PubMed1999

Nix and Nip3 form a subfamily of pro-apoptotic mitochondrial proteins.

We have identified Nix, a homolog of the E1B 19K/Bcl-2 binding and pro-apoptotic protein Nip3. Human and murine Nix have a 56 and 53% amino acid identity to human and murine Nip3, respectively. The carboxyl terminus of Nix, including a transmembrane domain, is highly homologous to Nip3 but it bears a longer and distinct asparagine/proline-rich N terminus. Human Nip3 maps to chromosome 14q11.2-q12, whereas Nix/BNip3L was found on 8q21. Nix encodes a 23. 8-kDa protein but it is expressed as a 48-kDa protein, suggesting that it homodimerizes similarly to Nip3. Following transfection, Nix protein undergoes progressive proteolysis to an 11-kDa C-terminal fragment, which is blocked by the proteasome inhibitor lactacystin. Nix colocalizes with the mitochondrial matrix protein HSP60, and removal of the putative transmembrane domain (TM) results in general cytoplasmic and nuclear expression. When transiently expressed, Nix and Nip3 but not TM deletion mutants rapidly activate apoptosis. Nix can overcome the suppressers Bcl-2 and Bcl-XL, although high levels of Bcl-XL expression will inhibit apoptosis. We propose that Nix and Nip3 form a new subfamily of pro-apoptotic mitochondrial proteins.

Amino Acid Sequence↗
PubMed1999

Effects of a chargrilled meat diet on expression of CYP3A, CYP1A, and P-glycoprotein levels in healthy volunteers.

BACKGROUND & AIMS: Carcinogenic heterocyclic amines and polycyclic aromatic hydrocarbons present in chargrilled meat are substrates for inducible CYP1A and CYP3A enzymes and for P-glycoprotein. We examined whether consumption of a chargrilled meat diet results in induction of these proteins. METHODS: Ten healthy adults were fed a diet enriched with chargrilled meat for 7 days. Duodenal biopsy specimens were obtained on days 1, 5, and 12 and analyzed for CYP1A, CYP3A, and P-glycoprotein messenger RNA (mRNA) and protein. On days 5 and 12, hepatic CYP3A4 and CYP1A2 activities were measured and colon biopsies were performed. The levels of polycyclic aromatic hydrocarbon DNA adducts in peripheral blood mononuclear cells were measured on days 1, 4, 11, and 26. RESULTS: There was no detectable induction of CYP3A4, CYP3A5, or P-glycoprotein mRNAs or protein in small intestine or colon and no induction of hepatic CYP3A4 enzyme activity. In contrast, the chargrilled meat diet resulted in unequivocal induction of CYP1A enzymes in the liver and small intestine of each subject. There was an inverse correlation between the level of peripheral polycyclic aromatic hydrocarbon DNA adducts measured on day 11 and both liver CYP1A2 activity (P = 0.027) and enterocyte CYP1A1 protein concentration (P = 0.046). CONCLUSIONS: Ingestion of chargrilled meat results in induction of CYP1A enzymes but not CYP3A4 or P-glycoprotein. This observation, combined with the correlation between adduct levels and CYP1A expression, supports an adaptive role for CYP1A but not CYP3A4 or P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Procedural results and late clinical outcomes following multivessel coronary stenting.

OBJECTIVES: To evaluate in-hospital and long-term clinical outcomes in a large consecutive series of patients undergoing percutaneous multivessel stent intervention. BACKGROUND: High restenosis and recurrent angina rates have limited the clinical outcomes of multivessel coronary angioplasty before stents were available to improve angioplasty results. METHODS: We evaluated in-hospital and long-term clinical outcomes (death, Q-wave myocardial infarction [MI], and repeat revascularization rates at one year) in 398 consecutive patients treated with coronary stents in two (94% of patients) or three native arteries, compared to 1,941 patients undergoing stenting procedure in a single coronary artery between January 1, 1994 and August 29, 1997. RESULTS: Overall procedural success was obtained in 96% of patients with two- or three-vessel stenting and in 970% of patients with single-vessel stent intervention (p = 0.36). Procedural complications were also similar (3.8% for multivessel versus 2.9% for single vessel, p = 0.14). During follow up, target lesion revascularization was 15% in multivessel and 16% in single-vessel interventions (p = 0.38), and repeat revascularization (calculated per treated patient) was also similar for both groups (20% vs. 21%, p = 0.73). There was no difference in death (1.4% vs. 0.7%, p = 0.26), and Q-wave MI (1.2% vs. 0%, p = 0.02) was lower following multivessel interventions. Overall cardiac event-free survival was similar for both groups (p = 0.52). CONCLUSIONS: Unlike previous conventional angioplasty experiences, multivessel stenting has (1) similar in-hospital procedural success and major complication rates and (2) similar long-term (one year) clinical outcomes compared with single-vessel stenting. Thus, stents may be a viable therapeutic strategy in carefully selected patients with multivessel coronary disease.

Angioplasty, Balloon, Coronary↗
PubMed1999

Effect of caudal block on the plasma adrenaline and noradrenaline concentrations in paediatric patients undergoing ilioinguinal herniorrhaphy.

This study compared the effect of two anaesthetic techniques on the catecholamine levels in children undergoing ilioinguinal herniorrhaphy. Forty male paediatric patients ASA class I were allocated randomly to one of two groups: the control group (n = 20) received general anaesthesia including intravenous fentanyl; and the caudal group (n = 20) received caudal anaesthesia with bupivacaine 0.25% 1 mL kg-1 combined with general anaesthesia but without opioids. Plasma adrenaline and noradrenaline concentrations were measured at induction, at the end of surgery and in the post-anaesthesia care unit (PACU). In the caudal group, there were significant decreases in the adrenaline and noradrenaline concentrations at the end of surgery and in the PACU compared with baseline concentrations. In the control group, there was a significant increase in PACU concentrations of adrenaline and noradrenaline compared with baseline concentrations. These findings suggest that the addition of a caudal block to general anaesthesia in children undergoing ilioinguinal herniorrhaphy decreases significantly the neurohormonal responses to surgery.

Anesthesia, Caudal↗
PubMed1998

Procedural results and long-term clinical outcomes following coronary stenting in perimyocardial infarction syndromes.

Initial experiences with coronary stents in acute coronary syndromes have suggested higher risk of ischemic complications and stent thrombosis. We evaluated in-hospital and 1-year clinical outcomes of coronary stent implantation in perimyocardial infarction (MI) syndromes. We studied 334 consecutive patients undergoing stent interventions in the first week after acute MI. Stenting was performed within 24 hours (n = 31), within 1 to 3 days (n = 95), and within 4 to 7 days (n = 208). Stents were used to improve angioplasty results and to treat dissections and abrupt/threatened closure. Postprocedure anticoagulation regimens were aspirin, ticlopidine, and low molecular weight heparin. Overall procedural success was achieved in 93% of patients. Major in-hospital complications included death (1.0%), recurrent Q-wave MI (0.6%), and emergent bypass surgery (3.0%). Stent thrombosis occurred in 0.6% of patients. At follow-up, cardiac event-free survival was 80%, mortality 2.2%, recurrent MI 3.5%, and target lesion revascularization 11%. We conclude that coronary stenting in periinfarction syndromes was effective in achieving sustained clinical benefit up to 1 year with low morbidity and mortality. Thus, stents seem to be a viable therapeutic strategy in patients sustaining perimyocardial infarction syndromes.

Aged↗
PubMed1998

Defects in regulation of apoptosis in caspase-2-deficient mice.

During embryonic development, a large number of cells die naturally to shape the new organism. Members of the caspase family of proteases are essential intracellular death effectors. Herein, we generated caspase-2-deficient mice to evaluate the requirement for this enzyme in various paradigms of apoptosis. Excess numbers of germ cells were endowed in ovaries of mutant mice and the oocytes were found to be resistant to cell death following exposure to chemotherapeutic drugs. Apoptosis mediated by granzyme B and perforin was defective in caspase-2-deficient B lymphoblasts. In contrast, cell death of motor neurons during development was accelerated in caspase-2-deficient mice. In addition, caspase-2-deficient sympathetic neurons underwent apoptosis more effectively than wild-type neurons when deprived of NGF. Thus, caspase-2 acts both as a positive and negative cell death effector, depending upon cell lineage and stage of development.

Amyotrophic Lateral Sclerosis↗
PubMed1998

Hyperkalemia in hospitalized patients: causes, adequacy of treatment, and results of an attempt to improve physician compliance with published therapy guidelines.

BACKGROUND: Hyperkalemia is a common, potentially life-threatening disorder. Electrocardiograms are considered to be sensitive indicators of the presence of hyperkalemia. Since the treatment of hyperkalemia involves relatively few maneuvers and because its success can be objectively scored, we investigated how physicians manage this disorder and how successful their prescribed therapy is. We also sought to determine whether treatment could be improved by providing the treating physicians with therapy guidelines on a real-time basis. METHODS: Consecutive patients with hyperkalemia were identified by review of laboratory records. During the observation-only phase of the study, demographic data, contributing causes, electrocardiogram findings, treatments used, compliance with prescribing guidelines, and patient outcome were recorded. During the subsequent notification phase of the study, treatment recommendations were sent to the patient's ward when the elevated potassium value was noted. The same outcome data were collected. RESULTS: There were 127 episodes of hyperkalemia during the observation-only phase and 115 during the notification phase. No patients died or had life-threatening cardiac arrhythmias. Electrocardiographic abnormalities consistent with hyperkalemia were observed in only 14% of episodes. Renal failure (77%), drugs (63%), and hyperglycemia (49%) contributed to most episodes. Treatments used were exchange resin (51%), insulin (46%), calcium (36%), bicarbonate (34%), and albuterol (4%). The agents were equally efficacious. The time to first treatment was shorter in patients with potassium levels of 6.5 mmol/L or more than in patients with lower values (2.1 +/- 2.2 vs 2.8 +/- 2.4 hours; P<.05). Treatment was better in the intensive care unit than on regular wards. Only 39% of episodes during the observation-only period met the predetermined criteria for monitoring and diagnosis, initial treatment, and follow-up. During the notification period, physician performance was no better; only 42% of episodes met all criteria. The laboratory transmitted a copy of the guidelines to the patient's ward only 38% of the time. In a separate analysis of these episodes, there was no improvement in treatment. Physicians who did not receive the notification fulfilled all treatment criteria more often than physicians who did (50% vs 30%; P<.05). CONCLUSIONS: Although treatment of hyperkalemia was frequently suboptimal, no serious arrhythmias and no deaths complicated management of 242 episodes of severe hyperkalemia. A narrowly targeted effort to improve physician management of a disorder with discrete treatment options did not improve therapy.

Adolescent↗
PubMed1998

Experimental induction and termination of acute psychological stress in human volunteers: effects on immunological, neuroendocrine, cardiovascular, and psychological parameters.

The present research investigated the effects of controlled experimental manipulations of stress on biological and psychological reactions. Fifty young adult male volunteers were exposed to a 12-min period of stress induced by the threat of an unavoidable, painful electric shock. A 12-min period without this threat preceded or followed the stress period. Blood was drawn during the 4th and the 12th minute of each period. Anticipatory threat led to significant elevations in the proportions and cytotoxic activity of natural killer (NK) lymphocytes, plasma epinephrine levels, pulse rate, and reported level of tension, and to a reduction in the CD4/CD8 ratios. The no-threat period induced a return to baseline values for epinephrine, pulse rate, and tension, and lower than baseline levels for cytotoxic activity of NK lymphocytes, within a similarly short time span. The findings underline the rapidity with which physiological changes may transpire in the course of a brief and acute period of psychological stress, and the rapidity of their reversal upon relief from the stressor.

Acute Disease↗
PubMed1998

Contributions of hypoxia and respiratory disturbance index to sympathetic activation and blood pressure in obstructive sleep apnea syndrome.

Hypertension is a common finding among obstructive sleep apnea (OSA) patients, and is thought to be caused by sympathetic hyperactivity. The present study compares the contributions of the respiratory disturbance index (RDI) as a reflection of sleep fragmentation, and the magnitude of oxygen desaturation, to sympathetic activation as indexed by urinary norepinephrine concentrations, as well as to morning and evening blood pressure in sleep apnea syndrome patients. Data (polysomnography, blood pressure [BP], and urine catecholamines) of 38 consecutive OSA patients (age, 46+/-14.5 years) were analyzed. Stepwise logistic regression analysis revealed that minimal oxygen saturation level (SaO2min) was a significant predictor of both morning and evening norepinephrine levels, and that 37% of morning systolic BP variance could be accounted for by a combination of age and norepinephrine, while 20% of the diastolic BP variance was accounted for by SaO2min alone. In contrast, RDI entered the prediction equation only when minimal oxygen saturation was rejected first. Our results indicate that the degree of nocturnal hypoxia is more closely associated with the level of sympathetic activation and with daytime level of blood pressure than with sleep fragmentation.

Adult↗
PubMed1998

Platelet activation in patients with antiphospholipid syndrome.

The binding of antiphospholipid antibodies to circulating platelets and the potential association with thrombocytopenia and platelet activation was investigated in 25 patients with primary antiphospholipid syndrome (APS). Fourteen patients had a platelet count above 150 x 10(9)/l, and 11 patients had mild to moderate thrombocytopenia of 50-150 x 10(9)/l. The presence of platelet autoantibodies was investigated by immunofluorescent binding. No correlation between the presence of autoantibodies on platelets and thrombocytopenia was found. The binding of antibodies in patients' serum and platelet eluates was investigated by performing enzyme-linked immunosorbent assays with phospholipids as antigens. In seven patients antibodies to negatively charged phospholipids were present in platelet eluates. Platelet activation was measured by flow cytometry using a fluorescein isothiocyanate (FITC) labeled monoclonal antibody to P-selectin (CD62). The binding of anti-P-selectin to patients' platelet surface P-selectin was not increased, compared with the binding to platelets obtained from normal donors. Platelet serotonin concentration in APS patients was significantly lower than that found in the platelets of normal controls. More studies are necessary to determine the exact role of antiphospholipid antibodies in the pathogenesis of thrombocytopenia, and to elucidate the cause of low serotonin levels in platelets of APS patients.

Adolescent↗