Search PubMed⌕ Search

Biomedical subjects

A Schwartz

Publications and source records attributed to A Schwartz.

At least 55 records · Page 3Linked to original sources

Workshop II: "neuroprotection"--the Lugano consensus.

Consensus could be reached that there is overwhelming evidence of preclinical neuroprotection. However, the evidence of neuroprotection/neurorescue under clinical conditions is limited. Lessons from clinical trials designed to show neuroprotection (selegiline, amantadine, dopamine agonists) demonstrate that with the drugs available neuroprotection/neurorescue has to start as early as possible. A PET-controlled clinical trial with ropinirole shows that there seems to be a good chance for neuroprotection in the early phase of Parkinson's disease in patients treated from the very beginning of the disease while there is no such benefit in patients with a late start of a neuroprotective therapeutic strategy. Also long-term neuroprotection cannot be reached. Complicating factors to demonstrate clinical neuroprotection are discussed.

Clinical Trials as Topic↗

Traumatic brachiocephalic pseudoaneurysm presenting with delayed stroke: case report.

We report a traumatic pseudoaneurysm of the internal carotid artery bifurcation and subclavian artery with recurrent strokes events in a 19-year-old man. He was admitted with an acute left hemiparesis. His history revealed a similar episode 1 year and a major car accident 3 years previously. Contrast enhanced MR angiography confirmed colour Doppler sonographic findings of a carotid and subclavian artery pseudoaneurysm presumably resulting from seat-belt trauma. The pseudoaneurysm, containing thrombus, was thought to be the source of artery-to-artery embolism.

Accidents, Traffic↗

Functional plasticity in primate somatosensory thalamus following chronic lesion of the ventral lateral spinal cord.

The long-term consequences of thoracic spinothalamic tract lesion on the physiological properties of neurons in the ventral posterior lateral nucleus of the thalamus in monkeys were assessed. Neurons responding to both compressive and phasic brush stimuli (multireceptive neurons), but not brush-specific (low-threshold) neurons, in the partially deafferented thalamus showed increased spontaneous activity, increased responses evoked by cutaneous stimuli and larger mean receptive field size than the same types of cells in the thalamus with intact innervation. The spike train properties of both the spontaneous and evoked discharges of cells were also altered so that there was an increased incidence of spike-bursts in cells of deafferented thalamus. These changes were widespread in the thalamus, and included cells in both the fully innervated forelimb representation and the partially denervated hindlimb representation ipsilateral to the lesion. The spontaneous and evoked spike trains in the ipsilateral thalamus also show increased frequency of both spike-burst and non-burst events compared to the intact thalamus. These results indicate that chronic spinothalamic tract lesion produces widespread changes in the physiological properties of a discrete cell population of the thalamus.The findings in this study indicate that the thalamic processing of somatosensory information conveyed by the lemniscal system is altered by transection of the spinothalamic tract. This change in sensory processing in the thalamus would result in altered cortical processing of innocuous somatosensory inputs following deafferentation and so possibly contribute to the generation of the central pain syndrome.

Action Potentials↗

Circulating levels of IL-1beta, a prothrombotic cytokine, are elevated in unstable angina versus stable angina.

BACKGROUND: Multiple studies support a role for inflammation in the pathogenesis of coronary atherosclerosis and unstable cardiac syndromes. However, of the known proinflammatory cytokines, only elevated plasma levels of interleukin-6 have been linked to unstable angina. We sought to examine the plasma levels of other major proinflammatory cytokines in similar clinical settings and to determine the extent of the relationship between inflammation and unstable coronary syndromes by measuring the levels of various proinflammatory cytokines in patients with stable and unstable angina. METHODS: We measured plasma levels of interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) in 97 patients: 67 with stable angina, 24 with unstable angina, and 15 healthy controls. RESULTS: Mean levels of IL-1beta were significantly higher in patients with unstable angina as compared to patients with stable angina (p =.009). Levels of IL-6 were significantly higher than control patients for both stable angina and unstable angina patients (p =.031 and.006, respectively). No significant differences were found in the levels of TNF-alpha. CONCLUSIONS: Our results suggest that both IL-1beta and IL-6 contribute to the pathogenesis of unstable angina, and that the profile of circulating plasma levels of proinflammatory cytokines differs in unstable angina from that in stable angina. Abbreviated Abstract. Multiple studies support a role for inflammation in the pathogenesis of coronary atherosclerosis and unstable cardiac syndromes. We measured plasma levels of interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) in patients with stable and unstable coronary syndromes. Levels of IL-1beta and IL-6 were found to be elevated in patients with unstable coronary syndromes. No significant differences were found in the levels of TNF-alpha. Our results suggest that both IL-1beta and IL-6 contribute to the pathogenesis of unstable angina.

Adult↗

Pharmacokinetics of methotrexate in cerebrospinal fluid and serum after osmotic blood-brain barrier disruption in patients with brain lymphoma.

OBJECTIVE: To evaluate the pharmacokinetics of methotrexate in ventricular cerebrospinal fluid and serum after osmotic blood-brain barrier disruption and intra-arterial administration compared with intravenous or simple intra-arterial infusion in patients with primary central nervous system lymphoma. METHODS: Serum and ventricular cerebrospinal fluid were sampled after methotrexate administration in 12 patients. Blood-brain barrier disruption was induced on 2 sequential days by mannitol (25%) infusion delivered to the vertebral or internal carotid artery territories followed by intra-arterial methotrexate (dose, 1.4 g/m2; 47 treatments). Sixteen treatments were given without barrier disruption by intravenous (3.5 g/m2; nine treatments) or intra-arterial (2.8 g/m2; seven treatments) infusion. RESULTS: Ventricular cerebrospinal fluid-methotrexate peak levels after blood-brain barrier disruption of the vertebral and the internal carotid arteries territories were 19.3 +/- 2.9 and 8.5 +/- 0.7 micromol/L (P < .001), and the area under the curve from time 0 to infinity was 178.0 +/- 21.3 and 110.0 +/- 12.4 [micromol/L x h, respectively (P < .01). No significant differences were observed in serum levels. After intra-arterial infusion was performed without disruption, the serum peak level was higher than that achieved by intravenous treatment (518.2 +/- 67.7 versus 180.6 +/- 31.8 micromol/L; P < .001). No differences were observed in cerebrospinal fluid concentrations, which dropped below 1 micromol/L at 6 hours. The cerebrospinal fluid/serum ratio [AUC(%)] of methotrexate after blood-brain barrier disruption was three to four times greater than that by systemic administration. CONCLUSION: Enhanced methotrexate delivery to the central nervous system can be attained by intra-arterial administration combined with osmotic disruption of the blood-brain barrier compared with simple intra-arterial or intravenous administration.

Adult↗

Evidence-based morning report for inpatient pediatrics rotations.

The authors describe a patient-centered method for teaching evidence-based medicine that is part of the inpatient morning report for pediatrics residents at the University of Illinois at Chicago. With library support, residents search for evidence to answer their own questions about patients, and present it at morning report

Chicago↗

Bilateral accessory iliac horns: pathognomonic findings in Nail-patella syndrome. Scintigraphic evidence on bone scan.

Nail-patella syndrome is a rare hereditary (autosomal dominant) disorder, also called hereditary osteo-onychodysplasia and Fong's syndrome. Its incidence is 4.5 per million population in the United States. Patients have a characteristic tetrad of pathologic symptoms including fingernail dysplasia, hypoplastic or absent patellas, radial head dislocation, and iliac horns. Soft-tissue changes and renal dysplasia have also been associated with the syndrome. Iliac horns are bilateral accessory outgrowths consisting of cortex and medulla continuous with the iliac bone. They are located at the site of attachment of the gluteus medius muscles and project posterolaterally. These smooth bony outgrowths are asymptomatic, frequently palpable, and, because they have no effect on gait, they need not be treated. Iliac horns are the pathognomonic feature of Nail-patella syndrome; that is, they occur in approximately 80% of cases and are observed only in this condition. Four patients (two female, two male) with Nail-patella syndrome have been examined in the authors' department: three family members, including a 37-year-old woman, her 18-year-old son, and her 15-year-old daughter, and an unrelated 26-year-old man. All patients, regardless of age or sex, had similar pelvic findings on their bone scans. Although whole-body scans were obtained in all patients, significant scintigraphic findings were observed only in the pelvis in all the patients examined. This is most likely the result of the mild nature of the related deformities, which do not yield scintigraphically detectable osteoblastic changes. A representative image showing these independent ossification on a Tc-99m MDP bone scan is presented. A conventional pelvic radiographic image of the same patient's pelvis is presented for comparison.

Adolescent↗

Two-dimensional gel analysis of haemolymph proteins from Plasmodium-melanizing and -non-melanizing strains of Anopheles gambiae.

Haemolymph polypeptides from Plasmodium-refractory and -susceptible mosquitoes were compared by one- and two-dimensional gel electrophoresis. The refractory strain of Anopheles gambiae kills malaria parasites by a humoral melanization mechanism whereas the parasites develop normally in susceptible mosquitoes. The two strains respond in a similar manner to carboxy-methyl-Sephadex beads that have been injected into the thoracic haemocoel, i.e. beads are strongly melanized in refractory but not susceptible mosquitoes. Protein profiles were compared between strains following cold shock (naïve control), saline injection and Sephadex bead injection. Using the susceptible naïve control as the standard, eight constitutively expressed polypeptides were specific to naïve susceptible mosquitoes while twelve other spots were reduced, enhanced or specific to refractory mosquitoes. Several of the strain-specific spots probably comprise related pairs (one in each strain) which vary only in isoelectric focusing point. Nine spots were induced by sham injection or by an injection of beads or saline, but none was reproducibly different between the strains. Amino acid sequence analysis of one of the refractory strain-specific spots identified it as AgSp14D1, an A. gambiae infection-responsive serine protease that is most similar to the Drosophila gene easter and Manduca prophenoloxidase activating enzyme. This gene maps to polytene chromosome division 14, which has been implicated in the melanization phenotype by quantitative trait loci mapping.

Animals↗

Controlled ovarian hyperstimulation--a state of endothelial activation.

PROBLEM: To aim of the study was to investigate whether controlled ovarian hyperstimulation (COH) causes endothelial activation and whether there is a correlation between endothelial activation and serum sex-steroid levels. METHOD OF STUDY: The study population consisted of 14 consecutive patients undergoing our routine IVF long gonadotropin-releasing hormone-analog protocol. Blood was drawn three times during the COH cycle: (1) day when adequate suppression was obtained (Day-S); (2) on the day of or the day prior to hCG administration (Day-hCG); and (3) on the day of ovum pick-up (Day-OPU). The levels of sex steroids and plasma soluble endothelial (E)-selectin were compared among the time points. Soluble E-selectin was measured with a commercial sandwich enzyme-linked immunosorbent assay. RESULTS: Soluble E-selectin levels were significantly higher on Day-OPU than Day-S and Day-hCG, whereas no difference was observed between Day-hCG and Day-S. No significant correlations were found between soluble E-selectin level and patient age, number of gonadotropin ampoules used, number of oocytes retrieved, or serum estradiol, progesterone and human chorionic gonadotropin levels. CONCLUSIONS: Human chorionic gonadotropin administration leads to endothelial activation regardless of the degree of ovarian response. Further studies are required to elucidate the relationship between COH and endothelial activation. These findings may lead to new strategies for predicting and preventing complications of COH, such as severe ovarian hyperstimulation syndrome.

Adult↗

Replacement of an NH(3) by an iminoether in transplatin makes an antitumor drug from an inactive compound.

To investigate the modifications of antitumor activity and DNA binding mode of transplatin after replacement of one nonleaving group NH(3) by an iminoether group, trans-[PtCl(2)(Z-HN=C(OMe)Me)(NH(3)] and trans-[PtCl(2)(E-HN=C(OMe)Me)(NH(3)] complexes (differing in the Z or E configuration of iminoether, and abbreviated mixed Z and mixed E, respectively), have been synthesized. In a panel of human tumor cell lines, both mixed Z and mixed E show a cytotoxic potency higher than that of transplatin, the mean IC(50) values being 103, 37, and 215 microM, respectively. In vivo mixed Z is more active and less toxic than mixed E in murine P388 leukemia and retains its efficacy against SK-OV-3 human cancer cell xenograft in nude mice. In the reaction with naked DNA, mixed Z forms monofunctional adducts that do not evolve into intrastrand cross-links but close slowly into interstrand cross-links between complementary guanine and cytosine residues. The monofunctional mixed Z adducts are removed by thiourea and glutathione. The interstrand cross-links behave as hinge joints, increasing the flexibility of DNA double helix. The mixed Z, transplatin, and cisplatin interstrand cross-links, as well as mixed Z monofunctional adducts are not specifically recognized by HMG1 protein, which was confirmed to be able to specifically recognize cisplatin d(GpG) intrastrand cross-links. These data demonstrate that the DNA interaction properties of the antitumor-active mixed Z are very similar to those of transplatin, thus suggesting that clinical inactivity of transplatin could not depend upon its peculiar DNA binding mode.

Animals↗

Cost-effectiveness of universal compared with voluntary screening for human immunodeficiency virus among pregnant women in Chicago.

OBJECTIVES: To determine and compare the cost-effectiveness of implementing 3 screening strategies to detect human immunodeficiency virus (HIV) infection among pregnant women in Chicago, Illinois: no screening, voluntary screening, and universal screening. METHODS: A decision-analysis model was developed, using standard cost-effectiveness analysis from a societal perspective. Reference case estimates were derived from a surveillance project conducted by the Illinois Department of Public Health and studies were published in the medical literature. Costs included direct and indirect medical costs associated with identification of pregnant women infected with HIV and identification, prevention, and treatment of perinatally HIV-infected newborns. Specifically, for each screening option, the cost per pregnant woman screened, the resulting number of pediatric HIV infections, and the number of newborn life-years were calculated. All costs were adjusted to the 1997 dollar value and discounted at 3%. Sensitivity analyses were determined for all variables included in the decision model. RESULTS: The estimated prevalence of HIV infection among pregnant women in Chicago is .41%. For every 100,000 pregnant women, it is estimated that 104.6 children would be infected with HIV if no screening strategy were implemented and 44.8 children would be infected if voluntary HIV testing (assuming a 92.7% acceptance rate) were available. In comparison, if universal HIV testing was performed, the number of children infected with HIV would decrease to 40 cases. Sensitivity analysis across a maternal HIV prevalence rate of.01% to 2.2% found that universal screening would be cost-saving in communities where the seroprevalence is.21%. In Chicago, it would take an estimated 5. 2 months of screening pregnant women to avert 1 case of pediatric HIV. Taking into consideration the lifetime costs of treating a child with HIV infection, universal HIV testing of 100,000 pregnant women would result in a cost-savings of $3.69 million when compared with no screening, and $269,445 when compared with voluntary screening. We estimated that it would cost $11.1 million to screen 100,000 pregnant women in Chicago. The cost-savings produced with increased screening are the direct result of reduced cases of newborns infected with HIV. A 2-way sensitivity analysis was performed to examine how costs vary as a function of the voluntary rates for HIV-positive and HIV-negative women. When screening falls below 50% for HIV-positive mothers, universal screening becomes cheaper than voluntary screening even if no HIV-negative mothers were screened. CONCLUSION: Reference case analyses showed that universal HIV screening of pregnant women in Chicago would both decrease the number of HIV-infected newborns and save money in comparison to voluntary or no testing strategies. Sensitivity analysis was robust across all variables for the conclusion that universal screening was more effective than voluntary screening. For many communities that have HIV prevalence rates for mothers of >.21%, universal screening would also save money in comparison to voluntary screening. For communities with prevalence rates <.21%, the benefits of universal screening may outweigh the costs for screening as we found that desirable incremental cost-effectiveness ratios were found for prevalence rates as low as.0075%.

AIDS Serodiagnosis↗

In vivo assessment of the window of barrier opening after osmotic blood-brain barrier disruption in humans.

OBJECT: Osmotic blood-brain barrier (BBB) disruption induced by intraarterial infusion of mannitol is used in conjunction with chemotherapy to treat human brain tumors. The time course to barrier closure, or the so-called therapeutic window, has been examined in animals but little information is available in humans. The authors, therefore assessed the time course to barrier closure after osmotic BBB disruption in humans. METHODS: Disruption of the BBB was demonstrated using 99mTc-glucoheptonate (TcGH) single-photon emission computerized tomography (SPECT) scanning in 12 patients who were treated monthly with combination chemotherapy in conjunction with BBB disruption. The primary diagnosis was primary central nervous system lymphoma in seven patients and primitive neuroectodermal tumors in five. The TcGH (20 mCi) was injected at 1- to 480-minute intervals after osmotic BBB disruption, and patients underwent SPECT scanning after 4 hours. A total of 38 studies was performed. Good-to-excellent BBB disruption was obtained in 29 procedures and poor-to-moderate disruption was seen in the other nine studies. The TcGH indices correlated with the degree of BBB disruption as measured postprocedure on contrast-enhanced CT scans (r = 0.852). Mean baseline TcGH indices were 1.02+/-0.07. For the group of patients with good-to-excellent disruptions the mean indices at 1 minute postdisruption measured 2.19+/-0.18. After 40 minutes no significant change was noted (mean index 2.13+/-0.2). Then the indices declined more steeply and at 120 minutes after the disruption the index was 1.36+/-0.02. A very slow decline was noted between 120 and 240 minutes after mannitol infusion. At 240 minutes the barrier was still open for all good-to-excellent disruptions (index 1.33+/-0.08) but at 480 minutes the mean indices had returned to the baseline level. CONCLUSIONS: Results of these in vivo human studies indicate that the time course to closure of the disrupted BBB for low-molecular-weight complexes is longer than previously estimated. The barrier is widely open during the first 40 minutes after osmotic BBB disruption and returns to baseline levels only after 6 to 8 hours following the induction of good or excellent disruption. These findings have important clinical implications for the design of therapeutic protocols.

Adult↗

Laparoscopic cholecystectomy for an abnormal hepato-iminodiacetic acid scan: a worthwhile procedure.

Patients with symptoms similar to symptomatic cholelithiasis but with no sonographic evidence of gallstones can be difficult to manage. Cholecystokinin (CCK)-stimulated hepatobiliary scans can be helpful in determining whether the biliary tract is the potential source of the symptoms. We retrospectively reviewed the medical records of 69 patients at our institution who underwent CCK-stimulated hepatobiliary scans over a 2-year period. Twenty-nine of 69 patients had an abnormal gallbladder ejection fraction (defined as 35% or less). All 29 patients had no sonographic evidence of cholelithiasis. Seventeen of the 29 underwent cholecystectomy. There were no complications or deaths within the operative group. Fifteen of the pathologic specimens had evidence of chronic cholecystitis, one was cytomegalovirus cholecystitis, and one showed only cholesterolosis. There was no other intraperitoneal pathology to explain the abdominal symptoms. At an average follow-up of 11 months, eight patients (47%) in the operative group had complete resolution of their symptoms, six (35%) had significant improvement, two (12%) were unchanged, and one (6%) was worse. Twelve of 29 patients did not have a cholecystectomy. At an average follow-up of 11 months, four (33%) of these patients had improvement and eight (66%) reported no change or worsening of their symptoms. In the operative group, 53 per cent had reproduction of their symptoms with CCK stimulation, and in the nonoperative group, 33 per cent reported symptoms. Average gallbladder ejection fraction was 10 per cent (range, 0-32) in the operative group and 23 per cent (range, 0-35) in the nonoperative group. Liver function tests were similar in each group. CCK-stimulated hepatobiliary scans were helpful in defining biliary tract disease in patients without gallstones. These patients may benefit from cholecystectomy with minimal risk of morbidity and mortality.

Adult↗