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Biomedical subjects

M Rothstein

Publications and source records attributed to M Rothstein.

At least 19 recordsLinked to original sources
PubMed2000

Laparoscopic nephrectomy in patients with end-stage renal disease and autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is often characterized by end-stage renal disease (ESRD) and problems including pain, hematuria, and infection. Open nephrectomy is curative; however, the morbidity of the procedure is considerable. Between 1995 and 1998, 11 laparoscopic nephrectomies were performed on nine symptomatic patients (five men and four women) with ESRD and ADPKD. Two patients underwent a staged bilateral laparoscopic nephrectomy. All patients presented with abdominal or flank pain and an abdominal mass. Other clinical problems included hypertension in eight patients, urinary tract infections in two patients, and gross hematuria in one patient. Seven patients were receiving long-term dialysis treatment, and two patients had undergone prior renal transplantation. Patients were evaluated for preoperative and postoperative pain, analgesic use, hospital course, and convalescence. The overall average operative time was 6.3 hours, with an average estimated blood loss of 153 mL. Eight nephrectomy specimens were removed by morcellation, and three specimens were removed intact through a 7- to 12-cm incision. The average hospital stay was 3 days, and the average time to normal activity was 5 weeks. With a mean follow-up of 31 months, all nine patients reported elimination of their preoperative pain based on a pain analogue score. Six major and two minor complications occurred, including blood transfusion, a vena cavotomy, splenic cyanosis, pulmonary embolism, clotted arteriovenous fistula, and brachial plexus injury. Incisional hernias occurred in two of the three patients who underwent open removal. One patient noted improvement, and two patients noted resolution of their hypertension postoperatively. Laparoscopic nephrectomy in patients with ADPKD and ESRD offers an effective alternative to open nephrectomy to manage renal-related pain. This procedure provides the benefits of minimal intraoperative blood loss, minimal postoperative pain, brief hospital stay, and rapid convalescence.

Aged↗
PubMed2000

A developmental trajectory in implicit memory is revealed by picture fragment completion.

Dissociations between performance on implicit and explicit tasks have often been taken as evidence that different neural structures subserve the two types of memory. One such dissociation involves developmental differences that emerge in explicit tasks, but which appear to be absent in implicit tasks. Such findings are consistent with the idea that implicit memory is subserved by a more primitive system that evolves earlier at both phylogenetic and ontogenetic levels. The present paper reviews previous studies that claimed to find evidence that implicit memory is fully developed in very young children. Issues of measurement error, ceiling effects, and insufficient power brought up questions about those studies with respect to the developmental issue. The present study compares performance on implicit (picture fragment completion) and explicit (free recall and recognition) memory tasks with groups ranging in age from 5-28 years. We find a reliable developmental trend in both implicit and explicit performance in which the former cannot be attributed to the operation of explicit memory processes. Thus, we conclude that implicit memory, like explicit memory, develops with age.

Adolescent↗
PubMed1999

Effect of recombinant human erythropoietin on endothelial cell apoptosis.

BACKGROUND: Recombinant human erythropoietin (rHuEPO) induces endothelial cell growth and angiogenesis in vitro. The mechanisms are unknown. Because an increase in endothelial cell survival could play a role in this process, we examined the effect of rHuEPO on lipopolysaccharide (LPS)-induced apoptosis in bovine pulmonary artery endothelial cells (BPAECs). METHODS: Four groups of cells were studied. The first group was preincubated in serum-free medium followed by treatment with LPS. The second group was preincubated with rHuEPO followed by LPS. The third group was treated with only rHuEPO. Control cells were cultured in the absence of rHuEPO and LPS. Apoptosis was determined by flow cytometric DNA analysis, propidium iodide staining, cellular DNA fragmentation by ELISA, and gel electrophoresis. RESULTS: LPS-treated cells showed an increase in hypodiploid DNA (36.4 +/- 6.1%) compared with controls (9.8 +/- 3.3%, P < 0.001). Preincubation with rHuEPO decreased this effect to 14.7 +/- 5.1% (P < 0.001). Apoptosis determined by propidium iodide was observed in 33 +/- 8% of LPS-treated cells, but in only 9 +/- 3% of cells preincubated with rHuEPO cells (P < 0.001). Similarly, DNA fragmentation was decreased in rHuEPO pretreated cells compared with LPS alone (0.155 OD +/- 0.02 vs. 0.538 +/- 0.09 OD, P < 0.001). DNA breakdown was observed in only LPS-treated cells. CONCLUSIONS: These results suggest that rHuEPO prevents LPS-induced apoptosis in endothelial cells. This protective effect could be an important factor in the action of rHuEPO on vascular endothelium.

Animals↗
PubMed1998

Tuberculosis infection and anergy in hemodialysis patients.

Patients on hemodialysis are at increased risk for developing active tuberculosis (TB) after primary infection. Although this increased risk is well documented, the prevalence of TB infection, as indicated by a positive tuberculin skin test (TST), is not well described. End-stage renal disease is also known to be a risk factor for skin test anergy, but the rate of anergy in hemodialysis patients is unclear. We sought to identify rates of anergy and TST positivity in patients at four hemodialysis units in St Louis, Missouri, from June 1996 through August 1996. Data obtained from patients and medical records included age, years on hemodialysis, medical history, and basic laboratory data. Patients without a history of TB or a positive TST had a TST with Tubersol, as well as candida and tetanus controls, placed by the Mantoux method. Tests were read 48 hours later. Of the patients enrolled at these units, 307 of 331 (93%) were evaluated. Patients had a mean age of 58 years (range, 19 to 91 years) and had been on hemodialysis for a mean of 3.7 years (range, 1 week to 18.7 years). Blacks made up 81% of the population. A history of a positive TST was obtained from 24 patients (8%), and an additional seven (2%) had a history of active TB. Of the 276 patients tested, 93 did not respond to either control antigen, but five of these patients had a positive TST, leaving 88 (32%) anergic. Anergy was related to age, immunosuppressive drug use, and the reagents used, but not to urea reduction ratio. Positive TSTs were found in 17 of 188 of nonanergic patients (9%) (6% of all tested patients). Overall, 48 of 307 patients (16%) had a positive TST or history of TB. TB or a positive TST was associated with liver disease and peptic ulcer disease, but not socioeconomic status. All 17 newly identified TST-positive patients received chest radiographs. No new cases of active TB were found. Only two of 17 of these patients (12%) were started on isoniazid (INH) prophylaxis. We identified high rates of TST positivity and anergy in the hemodialysis patients tested. Hemodialysis patients should receive regular TST screening, and INH prophylaxis needs to be more strongly encouraged. Studies are ongoing to define the rate of TST conversion over time.

Adult↗
PubMed1997

Picture naming by young children: norms for name agreement, familiarity, and visual complexity.

Researchers concerned with the development of cognitive functions are in need of standardized material that can be used with both adults and children. The present article provides normative measures for 400 line drawings viewed by 5- and 6-year-old children. The three variables obtained-name agreement, familiarity, and visual complexity-are important because of their potential effect on memory and other cognitive processes. The normative data collected in the present study indicate that young children are different from adults in both the name most frequently assigned and the number of alternative names provided. The alternative names given by the children are either coordinate names or names of objects that are visually similar to the pictured object. In addition, the failure (to name) rate is higher among young children compared to adults. Thus, we conclude that unequivocal interpretation of age-related differences in cognitive functions can be made only when age-appropriate pictorial stimuli are chosen.

Adult↗
PubMed1996

An ERP developmental study of repetition priming by auditory novel stimuli.

Event-related potentials were recorded from participants 5-7, 9-11, 14-16, and 22-28 years old during an auditory novelty oddball task. In this task, stimuli about which the participant is not instructed (i.e., novel or uncategorized) typically elicit a more frontally oriented P3 scalp topography (novelty P3). In contrast, stimuli to which the participant must respond (i.e., target or precategorized) elicit a P3 with a more posterior scalp topography. Repetition of identical novel stimuli led to a similar reduction in novelty P3 amplitude for all age groups. Moreover, with repetition the shift in scalp topography of the novelty P3 to a more parietally oriented distribution was similar in children and adults. A second component, the P3(2) (assumed to be an analog of the P3b), exhibited a repetition priming effect in both the adults and the youngest children. The fact that age-related differences induced by novel repetition were small and not systematic indicates that the processing of novel information is similar across a wide age range.

Acoustic Stimulation↗
PubMed1995

Vascular access thrombosis in new hemodialysis patients.

This study identifies factors that are associated with the risk of access thrombosis in 267 new hemodialysis patients. There are few longitudinal studies evaluating the risk of access thrombosis despite the need for long-term use of the access for maintenance hemodialysis. We used a prospective design following patients from 26 providers in Renal Network Council #12 (Iowa, Missouri, Kansas, and Nebraska) for 1 year who were starting hemodialysis. There were significant increases in access thrombosis relative risk (RR) associated with the placement of a polytetrafluoroethylene graft compared with patients with the arteriovenous fistula (RR 1.98; 95% confidence interval [CI] = 1.3, 3,01). The probability of remaining thrombosis free 90 days after first use was 90.1% (95% CI = 82.9, 94.4) for arteriovenous fistula patients, but only 71.6% (95% CI = 63.5, 78.2) for polytetrafluoroethylene graft patients. In arteriovenous fistula patients with more than 30 days maturity time the risk of thrombosis was significantly lower than in those with less maturity time (RR 0.40; 95% CI = 0.14, 0.84); however, there was no significant difference for maturity time among patients with a polytetrafluoroethylene graft. Reduced thrombosis risk also was observed in patients with dialyzer blood flow rates greater than 300 mL/min (RR 0.66; 95% CI = 0.44, 0.99). Total heparin dose and erythropoietin therapy were not associated with the risk of thrombosis. No differences in risk were found for age, renal diagnosis, or type of dialyzer.

Aged↗
PubMed1995

Recombinant human erythropoietin stimulates angiogenesis in vitro.

Endothelial cell migration and proliferation are the key steps in the angiogenic process, and both are stimulated by recombinant human erythropoietin (rHuEPO). In addition rHuEPO can increase endothelin-1 (ET-1) release by the endothelial cell. We designed the present study to address the question of whether rHuEPO stimulates angiogenesis. An in vitro quantitative assay for angiogenesis was used. This consisted of rat aortic rings embedded in a reconstituted basement membrane matrix and incubated with and without rHuEPO for eight days. We found that rHuEPO increased vessel outgrowth after four days of culture and this was continued for the next four days (rHuEPO vs. control: day 4, 12 +/- 2 vs. 4 +/- 1, P < 0.002 and day 8, 124 +/- 18 vs. 56 +/- 12 P < 0.006). Supernatant endothelin-1 (ET-1) levels, at 24 hours, were significantly higher than controls in the rings incubated with rHuEPO (107 +/- 13 vs. 43 +/- 10 pg/ml, P < 0.003). To investigate the role of ET-1 in rHuEPO-induced angiogenesis, rings were exposed to ET-1 alone (10(-8) M). We observed an increase in microvessel formation compared to control (day 4, 4 +/- 2 vs. 2 +/- 1, P < 0.006, and day 8, 67 +/- 12 vs. 51 +/- 10, P < 0.03). In addition, aortic rings were co-cultured with rHuEPO and anti-ET-1 IgG antibody. Stimulation of angiogenesis by rHuEPO was blunted by the ET-1 antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Endothelin-1 release by erythropoietin involves calcium signaling in endothelial cells.

We investigated the effects of recombinant human erythropoietin (rHuEPO) on intracellular calcium ([Ca2+]i) and whether these changes regulate both endothelin-1 (ET-1) protein release and ET-1 messenger RNA (mRNA) production in bovine pulmonary arterial endothelial cells (BPAEC). rHuEPO (3.3 U/ml) induced [Ca2+]i increases from a basal level of 54 +/- 12.2 (SE) to 147 +/- 21.1 nM (p < 0.001), in fura-2-loaded BPAEC. In the presence of nifedipine (10 microM), the increases in [Ca2+]i were significantly reduced. Furthermore, when extracellular calcium ([Ca2+]o) was reduced (200 microM), there was a significant reduction in [Ca2+]i increase after stimulation with rHuEPO. Incubation of BPAEC with rHuEPO for 4 h increased ET-1 levels in the culture supernatant from 44.7 +/- 5.3 to 85 +/- 7.6 pg/ml (p < 0.001). However, when the cells were treated with rHuEPO and nifedipine, the ET-1 levels were decreased, as compared to levels resulting from treatment with rHuEPO alone (41 +/- 6.1 vs. 85 +/- 7.6 pg/ml, p < 0.001, respectively). rHuEPO also induced a fourfold increase in the level of the preproET-1 mRNA as compared with control. PreproET-1 mRNA was diminished in the presence of nifedipine and rHuEPO and rHuEPO can increase [Ca2+]i in BPAEC, and this increase may be related to the stimulation of ET-1 synthesis and release.

Animals↗
PubMed1993

Recombinant human erythropoietin (rHuEPO) increases endothelin-1 release by endothelial cells.

Hypertension is a major complication of rHuEPO therapy in hemodialysis (HD) patients. We have previously reported that patients receiving rHuEPO intravenously (i.v.) had higher mean arterial pressure (MAP) and plasma endothelin-1 (ET-1) levels than those in which the hormone was administered subcutaneously (s.c.). To test whether the increased serum ET-1 levels associated with i.v. rHuEPO administration are the result of a direct effect of the hormone on ET-1 release by the endothelial cells (EC), we examined the effects of rHuEPO in vitro. Bovine pulmonary artery endothelial cells (BPAEC) were exposed to doses of rHuEPO of 0.8; 1.6; 3.3 and 6.6 U/ml. A 24 hour-time course showed maximal ET-1 production at 12 hours for all the doses tested. A significant increase in cell proliferation over controls was observed at 24 hours, for all rHuEPO doses, and no correlation was found between ET-1 values and cell proliferation. Inhibition of protein synthesis by cycloheximide (10 micrograms/ml) abolished the stimulation of ET-1 release by rHuEPO. Thrombin (4 U/ml) and angiotensin II (10(-7) M), two potent stimulators of ET-1 release, had additive effects to those of rHuEPO. Specific thrombin and angiotensin II antagonists blocked these additive effects, reducing ET-1 release to the level of rHuEPO stimulation alone. In summary, rHuEPO stimulates vascular EC in culture to increase ET-1 release through an increase in synthesis and in a time dependent fashion. The routes of stimulation seem to differ from other known ET-1 secretogoges. Our data also confirm a significant mitogenic effect of rHuEPO on the endothelial cell.

Cell Division↗
PubMed1993

Intravenous erythropoietin (rHuEPO) administration increases plasma endothelin and blood pressure in hemodialysis patients.

The correction of anemia in end stage renal disease with recombinant human erythropoietin (rHuEPO) is associated with hypertension in about a third of hemodialysis patients. In the present study, we investigated the role of endothelin (ET-1) on rHuEPO associated hypertension and the effect of the rHuEPO administration route on plasma ET-1 levels. We studied 50 stable chronic hemodialysis patients who were divided into three groups: 26 patients received rHuEPO intravenously (IV) and 21 subcutaneously (SC). The control group was nine patients who were treated with nandrolone decanoate (ND). Prehemodialysis ET-1 plasma levels were correlated with mean arterial pressure (MAP), hematocrit (Hct), time on dialysis, and rHuEPO doses. The antihypertensive therapeutic index (ATI) was used to determine the changes in blood pressure medication intake. We observed that the ET-1 levels were significantly higher in the IV group (19.3 +/- 2) than the SC (5.0 +/- 0.6) or ND groups (3.6 +/- 0.4 pg/mL) (P < 0.001, IV v SC or ND). After IV rHuEPO treatment, there were increases in both MAP (pre- v post-rHuEPO, P < .001) and in ATI (pre- v post-rHuEPO, P < .001). In the SC group, the increases in MAP and ATI were not significant. Only the IV group showed a significant correlation between MAP and ET-1 levels (r = .05, P = .02). To accomplish the same Hct, the IV group received higher rHuEPO doses than those of the SC (180 +/- 15 v 87 +/- 12 U/kg/week) (P < .001). No significant correlations were found between the plasma ET-1 levels and Hct, time on dialysis and rHuEPO doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Pneumocystis carinii pneumonia presenting as asthma: increased bronchial hyperresponsiveness in Pneumocystis carinii pneumonia.

Two male patients presented with clinical and laboratory findings consistent with typical bronchial asthma and subsequently developed Pneumocystis carinii pneumonia (PCP). Only on subsequent questioning did both admit to homosexuality and behavior associated with a high risk of HIV-infection. In order to determine how frequently reversible airway obstruction is seen in patients with PCP, we measured peak expiratory flow rates (PEFR) before and after bronchodilator administration in 37 of these patients. Initial PEFR measurements revealed a significant decrease in PEFR (< 80% predicted) in 84%, with 54% of these exhibiting a significant bronchodilator response (> or = 15% increase). For comparison, peak flow measurements were made in a control group of 31 HIV-infected patients without acute PCP, divided between those with asymptomatic HIV-infection, AIDS-related complex (ARC), and AIDS, (including patients with previous PCP). Only 23% of these individuals had low PEFR, and only 3% exhibited bronchodilator responses. In order to confirm the existence of bronchial hyperreactivity in patients with PCP, another 16 patients with PCP were tested by methacholine bronchial challenge and 50% were found to have positive responses. These findings suggest that both reversible airway obstruction and airway hyperreactivity are found in association with acute PCP and that as a result some patients with PCP may present with symptoms of asthma. It is important for physicians to have a high degree of suspicion to avoid missing a diagnosis of PCP in a patient presenting with apparent asthma.

AIDS-Related Complex↗
PubMed1990

Increased monocyte interleukin-1 activity and decreased vertebral bone density in patients with fasting idiopathic hypercalciuria.

Idiopathic hypercalciuria (IH) is a heterogeneous disorder frequently observed in patients with nephrolithiasis. At one extreme of its clinical spectrum is fasting hypercalciuria (FH), a condition characterized by increased bone resorption and turnover. In previous studies we have shown that monocytes from patients with high turnover osteoporosis and from women in early postmenopause elaborate increased amounts of interleukin-1 (IL-1), a cytokine that stimulates bone resorption in vitro and in vivo. Since IL-1 could also mediate the resorptive mechanism of FH and cause a clinically significant bone loss, we have studied the relationship of IH, vertebral mineral density, bone turnover, and monocyte IL-1 activity in 47 patients with absorptive hypercalciuria (AH), 23 with FH, and 38 nonhypercalciuric subjects with recurrent nephrolithiasis (controls). Vertebral mineral density, as measured by quantitative computer tomography, was decreased in each of the three patient groups, but was significantly lower in FH patients than in AH patients or control subjects. Twenty-four-hour total urinary hydroxyproline excretion was increased in FH patients compared to that in AH patients or controls, but blood levels of osteocalcin were not. Monocytes from FH subjects yielded significantly more IL-1 (alpha + beta) activity than those from AH patients or controls; levels of IL-1 activity in monocytes of AH and control patients were similar. In IH subjects, significant correlations were found between IL-1 and hydroxyproline (r = 0.70; P less than 0.0001), IL-1 and quantitative computer tomography values (r = -0.49; P less than 0.005), and IL-1 and urinary calcium (r = -0.36; P less than 0.05). Serum PTH levels were within normal limits in all subjects and were similar in the three study groups, 1,25-Dihydroxyvitamin D3 levels, although higher in IH patients than in controls, were not significantly different in FH and AH subjects. Increased IL-1 activity and decreased vertebral mineral density are features of a subset of patients with IH. Although a cause-effect relationship remains to be established, increased monocytic IL-1 activity, rather than elevated PTH or 1,25-dihydroxyvitamin D3 levels, could underlie the resorptive component of FH.

Adult↗