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M J Shapiro

Publications and source records attributed to M J Shapiro.

At least 37 records · Page 2Linked to original sources
PubMed1999

Nuclear magnetic resonance chromatography: applications of pulse field gradient diffusion NMR to mixture analysis and ligand-receptor interactions.

Pulse field gradient (PFG) diffusion NMR spectroscopy is a non-invasive method for the spectroscopic separation and identification of compounds of interest from a mixture. Because it relies on differences in translational diffusion rates to resolve NMR signals from individual components, pulse field gradient NMR is a unique method for analyzing complex mixtures and for detecting intermolecular interactions. A number of multidimensional pulse field gradient NMR experiments have been developed to alleviate the overlap of NMR signals arising from a complex mixture and facilitate component identification. The applications of pulse field gradient NMR for mixture analysis and for the direct identification of high affinity ligands are reviewed.

Base Sequence↗
PubMed1999

Aqueous and vitreous penetration of levofloxacin after oral administration.

OBJECTIVE: To investigate the penetration of levofloxacin, an optical S-(-)isomer of ofloxacin, into the aqueous and vitreous humor after oral administration. DESIGN: Randomized, clinical trial comparing tissue levels of levofloxacin after one or two doses 12 hours apart. PARTICIPANTS: Forty-five patients undergoing initial vitrectomy between February 1997 and June 1997 at the UIC Eye Center. METHODS: Aqueous, vitreous, and serum samples were obtained and later analyzed from 45 patients after oral administration of 1 500-mg tablet (group 1, 22 patients) or 2 500-mg tablets (group 2, 23 patients) 12 hours apart before surgery. MAIN OUTCOME MEASURES: Aqueous, vitreous, and serum concentrations of levofloxacin (micrograms/milliliter). RESULTS: Group 1 achieved mean aqueous, vitreous, and serum levels of 0.59 +/- 0.48 microg/ml, 0.32 +/- 0.34 microg/ml, and 4.34 +/- 3.59 microg/ml, respectively. Group 2 achieved mean aqueous, vitreous, and serum levels of 1.90 +/- 0.97 microg/ml, 2.39 +/- 0.70 microg/ml, and 8.02 +/- 3.14 microg/ml. CONCLUSIONS: Mean inhibitory aqueous and vitreous MIC90 levels were achieved against a majority of ocular pathogens, including Staphylococcus aureus and Staphylococcus epidermidis, Streptococcus pneumoniae (vitreous), Bacillus cereus (vitreous), Haemophilus influenzae, Moraxella catarrhalis, and most gram-negative aerobic organisms except Pseudomonas aeruginosa after two doses given 12 hours apart. Mean MIC90 levels were obtained in the vitreous for a majority of pathogens responsible for traumatic, postoperative, or bleb-related endophthalmitis.

Administration, Oral↗
PubMed1999

Affinity NMR: decoding DNA binding.

We have shown that affinity NMR can be used to edit a NMR spectrum so that ligands that have affinity to DNA can be observed in the presence of other nonbinding molecules. Diffusion encoded spectroscopy (DECODES) can be used to identify the binding ligands. We were able to identify Hoechst 33342 as binding to the Drew-Dickerson dodecamer d(CGCGAATTCGCG)2 in the presence of the nonbinding molecules adenine, adenosine, and thiamine. Affinity NMR appears to be readily applicable to DNA systems for the following reasons. (1) The relaxation rate of the DNA oligonucleotides is favorable, thus the signal intensity loss due to relaxation is not severe. (2) A comparison of the patterns of the DNA cross-peaks upon binding in the two-dimensional total correlation spectroscopy and correlation spectroscopy spectrum are easily performed, and the ligand signals in the two-dimensional DECODES spectrum can be readily identified. (3) The aromatic part of the DNA spectrum is devoid of 2D cross-peaks in these correlation spectra, greatly facilitating the interpretation of the bound ligand in the DECODES spectrum.

Adenine↗
PubMed1999

Overuse of splenic scoring and computed tomographic scans.

BACKGROUND: As the most commonly injured abdominal organ in blunt trauma, the management of splenic injury has undergone evolution. The risk of blood transfusions administered in an attempt to save the spleen has lowered the threshold for operation and also expanded the limits for nonoperative management. An in-depth analysis was carried out of risk factors on patients requiring immediate surgery and those who fail non-operative management based on organ injury scaling grading by computed tomographic (CT) scan and operation. The application of nonoperative management in the elderly population and the use of follow-up CT scanning and sonography in the outpatient setting was also examined. METHODS: Between January of 1991 and June of 1996, 226 consecutive blunt splenic trauma, injured patients at a Level I trauma center were evaluated. All subsequent CT scans and sonograms in the inpatient and outpatient setting were analyzed. The Student's t test, Pearson chi2 analysis with Yates correction, and analysis of variance were used to compare between and among groups. RESULTS: There were 153 men (67.7%), an average age of 34.8 years, an average Injury Severity Score of 24.4, and 28 deaths (12%). There was a significant difference with respect to Injury Severity Score, Glasgow Coma Scale score, Revised Trauma Score, units of packed red blood cells transfused, length of stay, intensive care unit length of stay, mean splenic injury grade, and cost between patients observed initially and those operated on initially. There was no significant difference in age between the two groups. Of 170 patients, 37 patients (22%) who had an initial CT scan underwent immediate exploratory laparotomy. The remaining 133 patients (78%) had nonoperative management; however, 15 patients (11%) failed the period of observation. Five in this group had a laparotomy secondary to other causes and another six were operated on within 24 hours of their injury for their splenic injury. Thus, only four of the nonoperative management patients (3%) actually failed nonoperative splenic management after 24 hours of injury. There were 100 second CT scans obtained. Three of these patients, who had developed hemodynamic instability, required operation for a bleeding spleen. The subsequent CT scan was confirmatory in these three patients who resided in the intensive care unit. All other CT scans and sonograms for clinically unremarkable patients failed to yield any alteration in care based on the scans. CONCLUSION: Blunt splenic injured patients can be safely observed; however, there are certain risk factors in those requiring immediate surgery and those failing nonoperative management. The CT scan underestimates injury, possibly related to a progression of bleeding found at the time of operation. No outpatient studies altered the course of management. Age also did not influence outcome. Thus, in the dedicated trauma center, nonoperative management of blunt splenic injury patients does not lead to undue morbidity or mortality. Once discharged, follow-up radiographs in asymptomatic patients are not necessary.

Adolescent↗
PubMed1999

Outcome of vitreoretinal surgery and penetrating keratoplasty using temporary keratoprosthesis.

PURPOSE: The use of a temporary keratoprosthesis has allowed earlier surgical intervention in eyes with coexisting vitreoretinal and corneal disease. We analyzed our experience with this type of surgery. METHODS: We retrospectively reviewed charts of patients in whom a temporary keratoprosthesis was used between 1987 and 1998. Analysis was focused on ocular history, indications for surgery, visual acuity (VA), intraocular pressure, anatomic results, and complications. RESULTS: A temporary keratoprosthesis was used in 31 eyes, 22 (71.0%) of which were for trauma-related indications. In 6 (19.4%) of the operated eyes, the fellow eye also had severely reduced VA. Retinal detachments were present in 30 (96.8%) eyes; most had evident proliferative vitreoretinopathy. Twelve (38.7%) eyes had vitreous hemorrhage, and 20 (64.5%) had corneal scars. Improvement in VA was seen initially in 45.1% of patients, and 51.6% maintained equal or better VA at their final visit as compared with before surgery. The common documented reasons for poor final VA were recurrent retinal detachments deemed inoperable (32.3%), phthisis (22.6%), and optic atrophy or macular scar (16.1%). Corneal grafts remained clear in 41.9%. Nine patients had further surgery. The most significant complication was one case of sympathetic ophthalmia. CONCLUSIONS: Combined vitreoretinal and corneal surgery using temporary keratoprostheses has been used in our institution to treat eyes with extreme abnormalities. Outcomes were less favorable than some reported in the literature, probably because of the severity of disease for which temporary keratoprostheses were reserved. Although results are probably better than the natural course of the disease, patients should be informed of realistic expectations for improvement and potential complications when offered this option.

Adolescent↗
PubMed1999

Frightening dreams and spells: a case of ventricular asystole from Lyme disease.

We present a case of a 20-year-old woman who presented with a febrile illness, frightening dreams and repeated short episodes of apparent seizure activity. Third degree heart block and ventricular asystole were noted on the monitor when the patient experienced a spell during conscious sedation for a lumbar puncture. The combination of heart block and a predominantly lymphocytic cerebrospinal fluid led to the diagnosis of Lyme disease. Lyme titres were strongly positive and subsequently confirmed by Western Blot analysis. Cardiac aetiologies and specifically heart block associated with Lyme disease should be considered in patients from endemic areas presenting with fever and unexplained spells or seizure-like activity.

Adult↗
PubMed1999

Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin.

Because of the role of thrombin and platelets in myocardial infarction and other pathological processes, identifying and blocking the receptors by which thrombin activates platelets has been an important goal. Three protease-activated receptors (PARs) for thrombin -- PAR1, PAR3, and PAR4 -- are now known. PAR1 functions in human platelets, and the recent observation that a PAR4-activating peptide activates human platelets suggests that PAR4 also acts in these cells. Whether PAR1 and PAR4 account for activation of human platelets by thrombin, or whether PAR3 or still other receptors contribute, is unknown. We have examined the roles of PAR1, PAR3, and PAR4 in platelets. PAR1 and PAR4 mRNA and protein were detected in human platelets. Activation of either receptor was sufficient to trigger platelet secretion and aggregation. Inhibition of PAR1 alone by antagonist, blocking antibody, or desensitization blocked platelet activation by 1 nM thrombin but only modestly attenuated platelet activation by 30 nM thrombin. Inhibition of PAR4 alone using a blocking antibody had little effect at either thrombin concentration. Strikingly, simultaneous inhibition of both PAR1 and PAR4 virtually ablated platelet secretion and aggregation, even at 30 nM thrombin. These observations suggest that PAR1 and PAR4 account for most, if not all, thrombin signaling in platelets and that antagonists that block these receptors might be useful antithrombotic agents.

Adenosine Triphosphate↗
PubMed1999

Enhanced emergency department referral improves primary care access.

OBJECTIVE: People who use the emergency department (ED) as their main source of medical care cite access barriers to primary care as the reason. The purpose of this study was to test an intervention designed to refer regular ED users to primary care. STUDY DESIGN: A prospective randomized clinical trial. PATIENTS AND METHODS: Adults who stated the ED is their regular source of care and have no primary care (n = 189) were randomized to 2 groups: the intervention being studied or usual care. The study took place over 3 months at a northeastern urban hospital. RESULTS: Subjects in the intervention group were more than twice as likely to keep the primary care appointment compared with the usual care group, and most also received some measure of preventive care. There was no significant difference in ED utilization by these patients in the 12-month period following study entry. CONCLUSION: Making an appointment with detailed instructions during a visit to the ED markedly improves show rates at follow-up appointments with a primary care provider and allowed for opportunity to provide important preventive services.

Adult↗
PubMed1998

Separate signals for agonist-independent and agonist-triggered trafficking of protease-activated receptor 1.

Protease-activated receptor 1 (PAR1), a G protein-coupled, protease-activated receptor for the serine protease thrombin, is activated when thrombin cleaves its amino-terminal exodomain. This irreversible mechanism of activation may have necessitated an unusual pattern of receptor trafficking. Unactivated PAR1 cycles tonically between the cell surface and an intracellular pool, providing an intracellular store of uncleaved receptors and allowing repopulation of the surface with uncleaved receptors after thrombin exposure without new receptor synthesis. Activated PAR1 internalizes rapidly and is degraded in lysosomes. We report characterization of a PAR1 mutant that trafficked like the wild-type receptor when activated but did not internalize and recycle in the absence of agonist. This complements a previous study in which a mutant with normal tonic internalization but defective agonist-triggered internalization was described. These observations suggest that the trafficking behaviors of unactivated and activated PAR1 are specified by distinct signals within the receptor and imply that PAR1 internalization in the presence or absence of agonist may be mediated by distinct molecular machinery. PAR1 mutants that did not internalize in the absence of agonist were also shown to localize exclusively to the cell surface and to be defective in their ability to repopulate the cell surface with uncleaved receptors after thrombin exposure. These observations suggest that tonic internalization is necessary for maintenance of the intracellular PAR1 pool.

Amino Acid Sequence↗
PubMed1998

NMR methods in combinatorial chemistry.

The use of NMR spectroscopy in combinatorial chemistry has provided a versatile tool for monitoring combinatorial chemistry reactions and for assessing ligand-receptor interactions. The application of magic angle spinning NMR is widespread and has allowed structure determination to be performed on compounds attached to solid supports. A variety of two-dimensional NMR techniques have been applied to enhance the usability of the magic angle spinning NMR data. New developments for solution NMR analysis include high performance liquid chromatography, NMR, mass spectroscopy and flow NMR. NMR based methods currently being investigated may prove valuable as compound screening tools.

Chemistry, Organic↗
PubMed1998

Effectiveness of helicopter versus ground ambulance services for interfacility transport.

BACKGROUND: Helicopters provide rapid interfacility transport, but the effect on patients is largely unknown. METHODS: Patients requested to be transported between facilities by helicopter were followed prospectively to determine survival, disability, health status, and health care utilization. A total of 1,234 patients were transported by the primary aeromedical company; 153 patients were transported by ground and 25 patients were transported by other aeromedical services because of weather or unavailability of aircraft. RESULTS: There were no differences at 30 days for survivors in disability, health status, or health care utilization. Nineteen percent of helicopter-transported patients died compared with 15% of those transported by ground (p=0.21). CONCLUSION: The patients transported by helicopter did not have improved outcomes compared with patients transported by ground. These data argue against a large advantage of helicopters for interfacility transport. A randomized trial is needed to address these issues conclusively.

Adult↗
PubMed1998

Intraocular penetration of gentamicin after once-daily aminoglycoside dosing.

BACKGROUND: Intraocular concentrations-particularly intravitreal concentrations-after systemic administration of gentamicin are poor. Once-daily aminoglycoside dosing of intravenous gentamicin achieves peak serum levels up to five times higher than conventional dosing. Whether these increased serum levels of gentamicin improve the aqueous or vitreous concentrations in humans has not been determined. The authors sought to determine if the intraocular penetration of gentamicin would be improved using this method. METHODS: Patients undergoing vitrectomy procedures were administered intravenous gentamicin in a dose of 7 mg/kg approximately 1 hour before surgery. An adjustment in dosing was made for anyone more than 20% over his or her ideal body weight. Aqueous, vitreous, and serum samples were collected before any intraocular surgical manipulation. The samples were analyzed by fluorescence polarization immunoassay (TDx system). RESULTS: The average single gentamicin dose was 498 mg (range, 360-700 mg). The aqueous, vitreous, and serum levels averaged 1.14 microg/mL, 0.41 microg/mL, and 22.07 microg/mL, respectively. No correlation between serum level concentrations and time of administration was found for the aqueous and vitreous levels in this study. CONCLUSION: Although the average peak serum level of gentamicin was five times higher than previously reported, the vitreous levels averaged only 1.5 times higher. The blood-retinal barrier is difficult to penetrate even when higher serum levels are achieved. Due to its poor ocular penetration, gentamicin may not be among the best drugs for prophylaxis of penetrating eye injuries, surgical prophylaxis, or treatment of endophthalmitis.

Anti-Bacterial Agents↗
PubMed1997

Effects of cytokine antagonists on the hepatic acute-phase response.

Endotoxin-induced hepatic acute-phase protein synthesis has been thought to be primarily regulated through cytokines such as interleukin-1 (IL-1) and interleukin-6 (IL-6). Previously, it was found that a 23-kDa murine acute-phase protein, the lipopolysaccharide (LPS)-induced protein (LIP), was synthesized following treatment of hepatocytes in vitro with LPS. Since this protein was also induced by IL-1 and IL-6, the present studies were undertaken to determine if the effect of endotoxin was mediated through these cytokines. Primary cultures of murine hepatocytes were treated with LPS, IL-1, IL-6, or an LPS-stimulated macrophage supernatant in the presence or absence of the IL-1 receptor antagonist (IL-1 RA) and/or an anti-IL-6 antibody. The cells were then radiolabeled with [35S]methionine. LIP was detected by electrophoresis and autoradiography of the secreted proteins. In vitro, IL-1 RA completely inhibited the stimulation of LIP synthesis elicited by IL-1 and the macrophage supernatant, but did not affect LPS-stimulated synthesis of this protein. The anti-IL-6 antibody inhibited IL-6-triggered synthesis of LIP, but had no effect on LPS-stimulated synthesis. Hepatocytes isolated from mice treated in vivo with both IL-1 RA and LPS synthesized LIP to the same degree as hepatocytes isolated from mice treated with LPS alone. LPS-stimulated synthesis of LIP in vitro does not require IL-1 or IL-6 as an obligatory intermediate. These results are consistent with the hypothesis that endotoxin can directly stimulate hepatocyte acute-phase protein synthesis in the absence of cytokines.

Acute-Phase Proteins↗
PubMed1997

Do internists and emergency physicians agree on the appropriateness of emergency department visits?

The purpose of this study was to determine the levels of agreement between three methods of assessing appropriateness of emergency department (ED) visits. In particular, we tested the agreement between internists and emergency physicians reviewing the ED nurses' triage notes, containing information that might be available by telephone to an internist. For 892 adult patient ED visits reviewed, we found only moderate agreement (kappa = 0.47) between these groups. In cases of disagreement, emergency physicians were 10.3 times more likely than internists to classify those with minor discharge diagnoses as appropriate for ED care. As managed care grows, the determination of ED appropriateness may depend on open discussions between physician groups, as well as on access to timely care in office settings.

Adult↗
PubMed1997

Delta-opiate DPDPE in magnetically oriented phospholipid micelles: binding and arrangement of aromatic pharmacophores.

D-Penicillamine(2,5)-enkephalin (DPDPE) is a potent opioid peptide that exhibits a high selectivity for the delta-opiate receptors. This zwitterionic peptide has been shown, by pulsed-field gradient 1H NMR diffusion studies, to have significant affinity for a zwitterionic phospholipid bilayer. The bilayer lipid is in the form of micelles composed of dihexanoylphosphatidylcholine (DHPC) and dimyristoylphosphatidylcholine (DMPC) mixtures, where the DMPC forms the bilayer structure. At high lipid concentration (25% w/w) these micelles orient in the magnetic field of an NMR spectrometer. The resulting 1H-13C dipolar couplings and chemical shift changes in the natural abundance 13C resonances for the Tyr and Phe aromatic rings were used to characterize the orientations in the bilayer micelles of these two key pharmacophores.

Biophysical Phenomena↗
PubMed1997

Ofloxacin penetration into the eye after intravenous and topical administration.

PURPOSE: To determine the aqueous and vitreous fluid penetration of ofloxacin after a combined topical and single intravenous dose protocol before vitrectomy surgery. MATERIALS AND METHODS: Before undergoing vitrectomy surgery, patients were given two drops of ofloxacin 0.3% topically and a single intravenous dose of ofloxacin 400 mg. Aqueous (mean, 43 minutes) and vitreous (mean, 53 minutes) fluid samples were collected at the start of the surgical procedure. The samples were analyzed for ofloxacin penetration. RESULTS: The mean aqueous fluid concentration was 1.083 micrograms/mL +/- 0.406. The mean +/- SD vitreous fluid concentration in nondiabetic patients with intact vitreous was 0.352 microgram/mL +/- 0.301. Vitreous levels obtained more than 50 minutes after administration (0.414 microgram/mL +/- 0.336) were generally higher than those obtained after less than 50 minutes (P = 0.12). Eyes with prior vitrectomies achieved better ofloxacin penetration (0.984 microgram/mL +/- 0.680) than did nonvitrectomized eyes. CONCLUSION: Ofloxacin achieved measurable aqueous fluid penetration after topical and intravenous administration. Aqueous levels were above the minimum inhibitory concentration for most ocular pathogens. Vitreous levels were adequate in vitrectomized eyes to achieve inhibitory concentrations against many common ocular pathogens. Combined preoperative topical and a single dose of intravenous ofloxacin may provide inhibitory aqueous and vitreous antibiotic levels in vitrectomized eyes in cases where intravitreal antibiotics are not considered and oral administration is not practical.

Administration, Topical↗