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Biomedical subjects

A Greenberg

Publications and source records attributed to A Greenberg.

At least 55 records · Page 3Linked to original sources
PubMed1998

Hyperkalemia: treatment options.

Although extracellular potassium accounts for only 1% to 2% of total body potassium, its concentration, [K+], is critical because it affects the depolarization of electrically excitable tissues such as heart and skeletal muscle. Renal failure is a predisposing factor in three-quarters of cases of hyperkalemia. Drugs contribute to the development of hyperkalemia in half of the cases, and most cases are multifactorial. Because hyperkalemia can lead to fatal arrhythmias, it deserves respect as a genuine electrolyte emergency. Nonetheless, recent data highlight the poor correlation of the EKG with [K+]. When present, however, EKG changes should be rapidly antagonized by infusion of calcium salts. Additional measures include shifting potassium from the extracellular to the intracellular compartment, removing potassium from the body, and eliminating risk factors for recurrence. Insulin is the most reliable agent for promoting transcellular shift of potassium. Albuterol can be used alone or to augment the effect of insulin. Alkalinization with bicarbonate, although formerly recommended as a mainstay of therapy, is not efficacious. Hemodialysis rapidly and reliably removes potassium and lowers [K+]. Exchange resins are also useful in removing potassium. Precise data on the quantity of potassium removed with current hemodialysis techniques or with resin are lacking. Although effective, rapid, and convenient means of treating hyperkalemia are available, physicians frequently fail to use them effectively.

Adrenergic beta-Agonists↗
PubMed1997

Activation of caspase-2 in apoptosis.

Members of the CED-3/interleukin-1beta-converting enzyme (ICE) protease (caspase) family are synthesized as proforms, which are proteolytically cleaved and activated during apoptosis. We report here that caspase-2 (ICH-1/NEDD-2), a member of the ICE family, is activated during apoptosis by another ICE member, a caspase-3 (CPP32)-like protease(s). When cells are induced to undergo apoptosis, endogenous caspase-2 is first cleaved into three fragments of 32-33 kDa and 14 kDa, which are then further processed into 18- and 12-kDa active subunits. Up to 50 microM N-acetyl-Asp-Glu-Val-Asp-aldehyde (DEVD-CHO), a caspase-3-preferred peptide inhibitor, inhibits caspase-2 activation and DNA fragmentation in vivo, but does not prevent loss of mitochondrial function, while higher concentrations of DEVD-CHO (>50 microM) inhibit both. In comparison, although the activity of caspase-3 is very sensitive to the inhibition of DEVD-CHO (<50 nM), inhibition of caspase-3 activation as marked by processing of the proform requires more than 100 microM DEVD-CHO. Our results suggest that the first cleavage of caspase-2 is accomplished by a caspase-3-like activity, and other ICE-like proteases less sensitive to DEVD-CHO may be responsible for activation of caspase-3 and loss of mitochondrial function.

Apoptosis↗
PubMed1997

Focal segmental glomerulosclerosis associated with nephrotic syndrome in cholesterol atheroembolism: clinicopathological correlations.

To better characterize the heavy proteinuria occasionally described in cholesterol atheroembolic renal disease (CAE), we reviewed the clinical features and histological findings of 24 patients found at renal biopsy to have CAE. Twelve (50%) had a typical clinical presentation soon after an invasive vascular procedure. Eight (33%) underwent biopsies to evaluate proteinuria and four (17%) with insidiously developing renal failure to exclude rapidly progressive glomerulonephritis. All had usual and similar risk factors for CAE; 71% were male, 96% had peripheral vascular disease, 79% had recently undergone an invasive vascular procedure, 74% were hypercholesterolemic, and all were hypertensive. Proteinuria was higher and serum creatinine lower in the proteinuria group. In the nine (38%) nephrotic patients, serum creatinine measurements were lower (2.7 +/- 1.2 v 5.6 +/- 2.4 mg/dL), duration of renal disease to biopsy longer, and time from biopsy to dialysis greater (23.5 +/- 14.8 v 0.03 +/- 0.098 mo, P < 0.05 for all). Focal segmental glomerulosclerosis (FSGS) was observed in 15 (63%) of the biopsy specimens. Although FSGS itself did not occur more commonly in nephrotic patients, these patients did have a higher fraction of segmentally sclerosed glomeruli (0.158 +/- 0.097 v 0.026 +/- 0.050, P < 0.01). A variant of FSGS, the cellular lesion with epithelial cell prominence and capillary loop collapse, was observed in 7 of 9 (78%) patients with nephrotic-range proteinuria, but in only 3 of 12 (25%) patients with lesser degrees of protein excretion (P < 0.05). The cellular lesion was accompanied by higher mean proteinuria, 7.6 +/- 4.3 versus 2.1 +/- 2.4 g/24 hr (P < 0.01). In a larger group of patients with a similar age range as the CAE group who were identified by search of a computerized biopsy database, membranous nephropathy was the only other form of idiopathic glomerulonephritis that occurred with CAE. One of 82 (1.2%) patients with membranous nephropathy also had CAE, compared with 20 of 102 (19.6%) with FSGS (P < 0.0002, chi2). Thus, the finding of FSGS with CAE was not coincidence. Mean follow-up was 20 +/- 26 months (range, 0 to 103 months). Six patients (25%) were followed-up at least 3 years after renal biopsy. These findings indicate that extended survival in CAE is not rare and that heavy proteinuria occurs as part of a chronic disorder with distinctive histological features. Cholesterol atheroembolism with FSGS should be considered in the differential diagnosis of nephrotic syndrome in elderly patients with advanced atherosclerosis.

Aged↗
PubMed1997

Acute renal failure in recipients of organ transplantation and nontransplantation patients: comparison of characteristics and mortality.

Mortality from acute renal failure in critically ill patients remains in excess of 50% despite decades of improvement in supportive care. It is not known whether replacement of other failing organs by non-renal organ transplantation affects mortality in acute renal failure. We retrospectively reviewed the course of 169 patients with acute renal failure managed at a single university medical center over a 1-year period. Measures of disease severity (need for renal replacement therapy, mechanical ventilation or parenteral nutrition, presence of oliguria and APACHE II scores) and final outcome were compared in 97 patients with acute renal failure who did not receive transplants and 72 patients with acute renal failure who underwent non-renal solid organ transplants. Overall mortality was 50.3% and directly correlated with APACHE II score. Compared to nontransplant patients, transplant recipients were younger. more frequently male, and less often oliguric; but the groups were similar in mean APACHE II scores and need for renal replacement therapy, prolonged mechanical ventilation, and parenteral nutrition. Overall, mortality was significantly lower for transplant patients compared to nontransplant patients (34.7% vs. 61.9%, p < 0.05). In nonoliguric acute renal failure and renal failure not requiring renal replacement therapy, mortality was low and similar in both transplant and nontransplant patients. Compared to nontrasplant patients with similar risk factors and similar APACHE II scores, mortality was significantly lower for transplant patients who were oliguric, or who required renal replacement therapy, mechanical ventilation, or parenteral nutrition. Organ transplantation is associated with a survival advantage in acute renal failure when compared to the outcome of critically ill nontransplant patients. The relation between APACHE II scores and survival is altered by transplantation.

APACHE↗
PubMed1997

The role of strontium-89 systemic radiotherapy in the management of osseous metastases from prostate cancer.

Strontium-89 systemic radiotherapy can play a significant role in the palliation of symptomatic osseous metastases from prostate cancer. Given as a single injection, strontium's affinity for osteoblastic activity draws it to all sites of osseous involvement simultaneously. The metastases are bathed with beta-particles whose short range in tissues spares the surrounding normal structures. This article will review the rationale, physiology, and patient selection criteria for its use. Approximately 80% of patients will respond to treatment as documented by the authors experience and by a review of the literature.

Adult↗
PubMed1996

Hypernatremia in hospitalized patients.

OBJECTIVE: To determine the incidence, clinical characteristics, and outcome for general medical-surgical hospital patients with hypernatremia. DESIGN: A prospective cohort study. SETTING: A 942-bed urban university hospital. PATIENTS: All patients who developed a serum sodium concentration of 150 mmol/L or greater during a 3-month observation period. MEASUREMENTS: Daily fluid balance, mental status, and serum and urine electrolytes and osmolality. RESULTS: 103 patients were identified. Eighteen patients were hypernatremic on hospital admission, and 85 developed hypernatremia during hospitalization. Patients who developed hypernatremia during hospitalization were younger than patients who developed hypernatremia before hospital admission (mean age +/- SD, 58.9 +/- 19.2 years compared with 76.6 +/- 16.6 years; P < 0.01) but did not differ in age from the patients of the general hospitalized population. Eighty-nine percent of patients who developed hypernatremia during hospitalization had urine concentrating defects, primarily as the result of the use of diuretics or of solute diuresis, whereas only 50% of patients who were hypernatremic on admission could be shown to have concentrating defects (P < 0.01). Fifty-five percent of all hypernatremic patients had increased insensible water losses, and 35% had increased enteral water losses. Eighty-six percent of patients with hospital-acquired hypernatremia lacked free access to water, 74% had enteral water intake of less than 1 L/d, and 94% received less than 1 L of intravenous electrolyte-free water per day during the development of hypernatremia. No supplemental electrolyte-free water was prescribed during the first 24 hours of hypernatremia in 49% of patients. The duration of hypernatremia was shorter in patients who were hypernatremic on admission (median duration, 3 days) than in patients with hospital-acquired hypernatremia (median duration, 5 days; P < 0.05). Mortality was 41% for all patients, but hypernatremia was judged to have contributed to mortality in only 16% of patients. CONCLUSIONS: Although the development of hypernatremia before hospital admission occurs primarily in geriatric patients, hospital-acquired hypernatremia was more common in our cohort and had an age distribution similar to that of the general hospitalized population. Hospital-acquired hypernatremia was primarily iatrogenic, resulting from inadequate and inappropriate prescription of fluids to patients with predictably increased water losses and impaired thirst or restricted free water intake or both. Treatment of hypernatremia is often inadequate or delayed. Efforts to manage hypernatremia better and altogether avoid hospital-acquired hypernatremia should focus on both physician education and the development of hospital systems to prevent errors in fluid prescription.

Adult↗
PubMed1996

Topically applied recombinant tissue plasminogen activator for the treatment of venous ulcers. Preliminary report.

BACKGROUND: Increasing evidence suggests that fibrin deposition is an important pathogenic component of venous ulceration and that fibrin removal could accelerate ulcer healing. OBJECTIVE: We sought to determine whether topical application of recombinant tissue plasminogen activator (tPA) compounded in 1% hyaluronate acid (HA) can be used safely in venous ulcers and whether it can accelerate healing. METHODS: Twelve patients were randomized in a double-blind fashion in three sequential groups of four subjects each, so as to receive daily topical application of either placebo (HA alone, one patient) or tPA/HA (three patients) at escalating doses of 0.25, 0.5, and 1.0 mg/ml of tPA for 4 weeks. RESULTS: No safety problems occurred, and we found a close direct correlation between mean ulcer reepithelialization, fibrin removal, and the dose of topically applied tPA (r = 0.991). CONCLUSION: In this first study to examine its usefulness, topically applied tPA appears to be a safe and promising agent for treating venous ulcers.

Administration, Cutaneous↗
PubMed1996

PCO2 affects tracheal tone during apnea in anesthetized dogs.

We hypothesized that CO2, like hypoxia and withdrawal of pulmonary slowly adapting receptor input, would cause tracheal constriction during neural apnea (absence of phrenic activity). In seven anesthetized paralyzed dogs ventilated to neural apnea, we increased arterial PCO2 (PaCO2) in steps by adding CO2 to the inspirate while keeping ventilation constant. Increases in PaCO2 caused tracheal constriction during neural apnea in all dogs; 69 +/- 26 (SD)% of the change in tracheal diameter occurred during neural apnea. Average sensitivity of tracheal diameter to CO2 was 0.44 mm/Torr PaCO2. Our data suggest that central chemoreceptor inputs to brain stem neurons controlling smooth muscle of the extrathoracic airway bypass central mechanisms generating inspiration.

Animals↗
PubMed1996

Pregnancy outcomes in a prospective matched control study of pregnancy and renal disease.

OBJECTIVE: Assessment and comparison of pregnancy outcomes in women with renal disease and women with high risk pregnancies due to medical illness without renal disease. DESIGN: A prospective, matched controlled study. SETTING: The High Risk Obstetrical Clinics of Magee Women's Hospital, a primary and referral center where approximately 9,500 deliveries occur per year. PATIENTS: Two groups of pregnant women, all identified in the first trimester. The study group included 43 pregnancies in 40 women with renal disease as defined by: 1) known renal disease antedating pregnancy, 2) prepregnant proteinuria > or = 150 mg/24 hours, or 3) first trimester serum creatinine > or = 0.8 mg/dl or proteinuria > or = 300 mg/24 hours. The 43 controls included women with medical problems other than renal disease that placed them at high obstetrical risk. Control women were matched to study women for parity, advanced maternal age, race, and insulin-dependent diabetes mellitus. MEASUREMENTS: For all patients, blood pressure was recorded once at approximately 10, 20, and 30 weeks gestation. For study patients, serum creatinine, 24-hour urinary protein, and creatinine clearance were obtained at least once in each trimester. Pregnancy outcomes were recorded as favorable if gestation was > or = 36 weeks and without evidence of intrauterine growth retardation. Adverse pregnancy outcomes included prematurity, intrauterine growth retardation, intrauterine fetal death, spontaneous abortion, or neonatal death. RESULTS: Forty-two percent of study and control patients were diabetic. First trimester renal function was normal (creatinine < 0.8 mg/dl) in 12 study patients, mildly impaired in 24 (creatinine 0.8-1.4 mg/dl) and moderately impaired in 5 (creatinine > or = 1.4 mg/dl). Compared with controls, first and third trimester hypertension was more prevalent in the study patients (p = 0.003, p = 0.012); overall mean blood pressure was also higher in study patients (92 +/- 11 mmHg vs 85 +/- 8 mmHg, p = 0.002). The mean gestational age was shorter in the study patients (33.4 +/- 6.9 weeks vs 37.2 +/- 4 weeks, p = 0.001). Overall pregnancy loss was more common in the study patients (14/43 vs 3/43, p = 0.003) with spontaneous abortion contributing half of those pregnancy losses (7/14). Hypertension in any trimester was associated with adverse pregnancy outcome in study but not control patients. In the subset of study patients, adverse fetal outcome was directly associated with degree of renal dysfunction and proteinuria. CONCLUSIONS: Pregnancy outcome in women with renal disease was significantly worse than in the control group and showed no improvement over retrospective reports from the 1970's and 1980's. Specifically, fetal deaths were more common in women with renal disease and were predicted by proteinuria and the degree of renal dysfunction. The uncommonly low number of spontaneous abortions in the control group may have contributed to the worse fetal outcome in the study patients compared with controls. Women with diabetes mellitus and hypertension are at particularly high risk for relatively poor pregnancy outcome. These higher risks should be discussed when counseling women with renal disease who contemplate pregnancy.

Adult↗
PubMed1995

An assessment of a urinary biomarker for total human environmental exposure to benzo[a]pyrene.

Urinary banzo[a]pyrene (BaP) metabolite levels were compared to human environmental exposure to BaP through inhalation and dietary ingestion to assess the predictive validity of the exposure biomarker. These measurements were made for 14 adult volunteers over 14 consecutive days, once during summer/fall, again during winter periods. Based on personal air monitoring, median potential inhalation doses of 11.0 and 2.3 ng/day were estimated for the winter and summer/fall studies, respectively. A median potential ingested dose of 176 ng/day, estimated from "duplicate plate" sampling, exceeded inhalation by 6- and 122-fold for the winter and summer/fall studies, respectively. "Total" urinary BaP metabolites were measured using a published "reverse metabolism" (BaP) method of analysis. Median rates of urinary BaP metabolite elimination for the winter and summer/fall studies were 121 and 129 ng/day, respectively. The changes in inhaled and ingested potential doses were regressed on the change in urinary metabolite elimination from week 1 to week 2 to test the predictive validity of the biomarker measurement. The regression was statistically significant (r = 0.620, p = 0.015, n = 25) when body weight was included and two extreme values were removed. Consistent with the exposure measurements showing diet as the dominant route of exposure, most of the variation in urinary metabolite elimination was explained by the ingested dose. It is concluded that the measurement of urinary BaP by "reverse metabolism" is qualitative and of marginal predictive validity as an exposure biomarker due to the method's low recoveries and the large unexplained variance.

Adult↗
PubMed1995

Interindividual differences in the concentration of 1-hydroxypyrene-glucuronide in urine and polycyclic aromatic hydrocarbon-DNA adducts in peripheral white blood cells after charbroiled beef consumption.

Biological markers of internal dose and macromolecular dose from PAHs provide a potential means of assessing environmental exposure to PAHs through inhalation, ingestion and percutaneous absorption. In this study we examined the time course and interindividual variation of 1-hydroxypyrene-glucuronide (1-OHP-gluc) excretion in urine and PAH-DNA adduct formation in peripheral white blood cells (WBCs) after charbroiled (CB) beef consumption. As a marker of internal dose, 1-OHP-gluc was measured in human urine using immunoaffinity chromatography and synchronous fluorescence spectroscopy. PAH-DNA adducts were measured in WBCs by enzyme-linked immunosorbent assay (ELISA) in order to assess macromolecular dose. Ten healthy non-smoking males consumed identical amounts of CB beef on five consecutive days. Multiple blood and urine samples were collected before, during, and after the feeding period. The morning after the first day of CB beef consumption, individual urinary concentrations of 1-OHP-gluc increased 10- to 80-fold (range: 2.0-16.6 pmol/ml urine) above pre-feed baseline concentrations (0.23 +/- 0.11 pmol/ml) in the 10 subjects. 1-OHP-gluc concentration decreased to near baseline levels by 24-72 h after CB beef consumption ended. In contrast, PAH-DNA adducts in WBCs increased markedly in only four of 10 subjects during or after CB beef consumption. Significant interindividual variation was observed for both urinary 1-OHP-gluc concentration (P < 0.001 by Kruskal-Wallis) and PAH-DNA adduct levels (P < 0.005) during the feeding period. The mean urinary 1-OHP-gluc concentration for each subject during and immediately after (days 2-8) the feeding period was significantly correlated with their mean PAH-DNA adduct level in WBCs during the same time period (Spearman r = 0.79, P < 0.01). Evidence of segregation of the subjects into separate response groups based on level of urinary 1-OHP-gluc was observed, suggesting that discrete determinants may regulate the absorption, metabolism and/or excretion of ingested pyrene.

Adult↗
PubMed1995

Clinical similarity and biological diversity in the response to alprazolam in patients with panic disorder and generalized anxiety disorder.

Thirty-six patients with panic disorder (PD) and 35 patients with generalized anxiety disorder (GAD) participated in an open alprazolam treatment phase that preceded controlled withdrawal from alprazolam. Clinical ratings, blood pressure and heart rate were obtained along with plasma measurements of cortisol, ACTH, growth hormone and catecholamines. A similar clinical response profile was evident in both groups with rapid onset of improvement within the first week. The two diagnostic groups differed in their biological response to alprazolam. PD patients had a significant reduction in blood pressure, plasma cortisol and a trend toward significant reduction in plasma epinephrine, which were not seen in the GAD patients. GAD patients showed a significant reduction in plasma norepinephrine. These findings provide further evidence that PD and GAD are biologically distinct syndromes.

Adrenocorticotropic Hormone↗
PubMed1994

Assessment of renal function during pregnancy using a random urine protein to creatinine ratio and Cockcroft-Gault formula.

The current standard for assessment of renal function in pregnant women is a 24-hour urine collection to determine creatinine clearance and proteinuria. It is easier to use the random urine protein to creatinine (P:C) ratio and the Cockcroft-Gault (CG) formula to estimate protein excretion and glomerular filtration rate, but the reliability of these formulae in combination for assessing renal function in pregnant women with renal disease is unknown. We compared the results of the P:C ratio with the 24-hour urinary protein excretion and the results of the CG clearance estimate with the 24-hour urine creatinine clearance in 34 pregnant women with underlying renal disease. Comparisons were made once in each trimester and postpartum. Prepregnancy weights were used in the CG formula: (140 - age x weight [kg] x 0.85)/72 x serum creatinine (mg/dL). Twenty-six first trimester, 33 second trimester, 21 third trimester, and 15 postpartum comparisons were made for creatinine clearance and 16 first trimester, 29 second trimester, 15 third trimester, and 15 postpartum comparisons were made for protein excretion. Measured creatinine clearance for the three trimesters combined (105 +/- 40 mL/min [mean +/- SD]) correlated significantly with CG clearances (113 +/- 52 mL/min; r = 0.87). The mean P:C values (2.03 +/- 3.15) for the three trimesters combined correlated significantly with 24-hour urine protein (2.25 +/- 4.21 g; r = 0.92). Our study demonstrates excellent correlations between the CG formula using prepregnancy weights and 24-hour creatinine clearance and between the P:C and 24-hour urinary protein in this population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Assessment of carcinogenic risk from personal exposure to benzo(a)pyrene in the Total Human Environmental Exposure Study (THEES).

The Total Human Environmental Exposure Study (THEES) was an investigation of multimedia exposure to the ubiquitous environmental carcinogen, benzo(a)pyrene (BaP). The three-phase study was conducted in Phillipsburg, New Jersey and involved the participation of 14-15 individuals (8-10 homes) during each 14-day monitoring period. Microenvironmental sampling of air, food, water and soil indicated that environmental exposure to BaP was primarily through air and food. Exposure and risk estimates were, therefore, based on the results of personal monitoring of breathing zone air and prepared food samples. Based on a comparison of the range and magnitude of inhalation and dietary BaP exposures, food ingestion was clearly the predominant exposure to pathway. The relative contributions of other potential sources of community exposure to BaP (e.g., soil and drinking water ingestion) were also assessed. The excess cancer risk estimates for food ingestion were consistently greater than those for personal air, reflecting both the predominantly higher BaP exposures through the diet and the higher carcinogenic potency value for oral exposure. Overall, the total lifetime risk from personal exposure to BaP for nonsmokers in the community was estimated at 10(-5). In identifying risk reduction options, it is important to account for the observation that personal activities, lifestyle, and diet strongly influenced individual exposures to BaP.

Air Pollutants↗
PubMed1993

Regulation of alveolar macrophage transforming growth factor-beta secretion by corticosteroids in bleomycin-induced pulmonary inflammation in the rat.

In a model of pulmonary inflammation and fibrosis induced by the antineoplastic antibiotic, bleomycin, we previously demonstrated that TGF-beta was markedly elevated within 7 d of bleomycin administration. At the time of maximal TGF-beta production, TGF-beta 1 was localized by immunohistochemistry to be present almost exclusively in alveolar macrophages. In this study, we have demonstrated that alveolar macrophages stimulated by bleomycin-induced injury secrete large quantities of biologically active TGF-beta 1 when explanted into tissue culture. However, alveolar macrophages from normal saline-treated rats secrete small quantities of biologically inactive TGF-beta. In contrast, splenic macrophages secrete large quantities of inactive TGF-beta and are unaffected by the intratracheal bleomycin treatment. High doses of the corticosteroid methylprednisolone given intramuscularly before and concomitantly with bleomycin administration prevented the influx of alveolar macrophages into the lungs, diminishing both the number of macrophages present in the alveoli and the total lung content of TGF-beta. However, the rate of secretion of TGF-beta by alveolar macrophages recovered from the alveoli was unchanged after corticosteroid treatment. When activated alveolar macrophages were cultured in the presence of several concentrations of dexamethasone that completely suppressed IL-1 secretion, little effect on TGF-beta secretion was observed. The findings in this study demonstrate that during bleomycin-induced injury, alveolar macrophages not only secrete large quantities of active TGF-beta 1, but are a predominant source of the enhanced TGF-beta response seen in this model. Furthermore, the alveolar macrophage secretion of TGF-beta is not inhibited by the presence of high concentrations of corticosteroids.

Animals↗