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Biomedical subjects

C Lewandowski

Publications and source records attributed to C Lewandowski.

At least 19 recordsLinked to original sources
PubMed2005

MRI-guided, open trial of abciximab for ischemic stroke within a 3- to 24-hour window.

The authors assessed the effect of IV abciximab on early neurologic improvement and ischemic lesion growth in 29 patients with supratentorial stroke and NIH stroke scale score (NIHSSS) > or = 4 (11.1 +/- 5.9), treated within 3 to 24 (13.6 +/- 5.5) hours of onset. The 48 to 72-hour NIHSSS improvement was 4.4 +/- 3.2 and the 24-hour lesion growth on DWI was +23% (-50%, +103%); 7/26 (27%) patients experienced lesion size decrease. Treatment of sub-24-hour stroke with abciximab improves early post-treatment neurologic status and often attenuates ischemic lesion growth.

Abciximab↗
PubMed2001

Treatment of acute ischemic stroke.

Acute ischemic stroke is the third leading cause of death in the United States and the leading cause of adult disability. The direct and indirect costs of stroke care exceed $51 billion annually. In 1996, the US Food and Drug Administration approved the first treatment for acute ischemic stroke, intravenous tissue plasminogen activator. Later that year, the National Institute of Neurologic Disorders and Stroke (a branch of the National Institutes of Health) convened a consensus conference on the Rapid Identification and Treatment of Acute Ischemic Stroke, setting goals for stroke care in the United States. Since then, it has become imperative that emergency physicians understand the pathophysiology of stroke, the basis and rationale for treatment, and the therapeutic approaches. This article reviews the state of the art of acute stroke treatment, its foundation, as well as its future.

Acute Disease↗
PubMed2001

Recombinant chemosensory protein (CSP2) from the moth Mamestra brassicae: crystallization and preliminary crystallographic study.

Chemosensory proteins (CSPs) are small proteins (13 kDa on average) present in several sensory organs from a wide range of insect species. They are believed to be involved in chemoperception (olfaction or taste) and to play a role in chemical transport from air or water to chemosensitive receptors. Here, the first crystals of a CSP originating from the moth Mamestra brassicae (Mbra) proboscis and expressed as recombinant protein in Escherichia coli periplasm are reported. Crystals of MbraCSP2 were obtained by the hanging-drop vapour-diffusion method under the following conditions: 1 microl of a 46 mg ml(-1) protein solution in 50 mM Tris pH 8.0 containing cetyl alcohol as ligand (1:5 molar ratio) was mixed with 1 microl of well solution containing 30% PEG 4000, 0.2 M sodium acetate in 100 mM Tris at pH 8.4. The protein-cetyl alcohol complex crystallizes in space group P2(1), with unit-cell parameters a = 47.9, b = 49.7, c = 50.3 A, beta = 110.1 degrees. With two molecules in the asymmetric unit, the V(M) is 2.15 A(3) Da(-1) and the solvent content is 42%. A complete data set has been collected at 1.6 A resolution on beamline ID14-2 (ESRF, Grenoble). Se-Met expression has been performed with a view to solving the CSP2 structure with MAD data collection using the Se absorption edge.

Animals↗
PubMed1999

Tobacco mosaic virus inoculation inhibits wound-induced jasmonic acid-mediated responses within but not between plants.

Jasmonic acid (JA) and salicylic acid (SA) have both been implicated as important signal molecules mediating induced defenses of Nicotiana tabacum L. against herbivores and pathogens. Since the application of SA to a wound site can inhibit both wound-induced JA and a defense response that it elicits, namely nicotine production, we determined if tobacco mosaic virus (TMV) inoculation, with its associated endogenous systemic increase in SA, reduces a plant's ability to increase JA and nicotine levels in response to mechanical damage, and evaluated the consequences of these interactions for the amount of tissue removed by a nicotine-tolerant herbivore, Manduca sexta. Additionally, we determined whether the release of volatile methyl salicylic acid (MeSA) from inoculated plants can reduce wound-induced JA and nicotine responses in uninoculated plants sharing the same chamber. The TMV-inoculated plants, though capable of inducing nicotine normally in response to methyl jasmonate applications, had attenuated wound-induced JA and nicotine responses. Moreover, larvae consumed 1.7- to 2.7-times more leaf tissue from TMV-inoculated plants than from mock-inoculated plants. Uninoculated plants growing in chambers downwind of either TMV-inoculated plants or vials releasing MeSA at 83- to 643-times the amount TMV-inoculated plants release, exhibited normal wound-induced responses. We conclude that tobacco plants, when inoculated with TMV, are unable to elicit normal wound responses, due likely to the inhibition of JA production by the systemic increase in SA induced by virus-inoculation. The release of volatile MeSA from inoculated plants is not sufficient to influence the wound-induced responses of neighboring plants.

Animals↗
PubMed1998

Hypertension and its treatment in the NINDS rt-PA Stroke Trial.

BACKGROUND AND PURPOSE: We examined the frequency, course, and treatment of hypertension in the NINDS rt-PA Stroke Trial. METHODS: Blood pressure (BP) was measured at the time of admission, at randomization, and then 36 times during the first 24 hours after randomization. Patients with a systolic BP of >185 mm Hg and a diastolic BP of >110 mm Hg at admission were defined as hypertensive before randomization, and those with a systolic BP of >180 mm Hg or a diastolic BP of >105 mm Hg within the first 24 hours after randomization were defined as hypertensive after randomization. Standardized clinical assessments were conducted at 24 hours and at 3 months. Post hoc analyses were conducted to evaluate the association of antihypertensive therapy with clinical outcomes. RESULTS: Of the 624 patients, 121(19%) had hypertension on admission and 372 (60%) had hypertension in the 24 hours after randomization. The use of antihypertensive therapy before randomization (tPA 9%, placebo 9%) and after randomization (tPA 24%, placebo 29%) was similar between placebo- and tPA-treated patients. No adverse effects of prerandomization antihypertensive therapy on 3-month favorable outcome were detected for either the placebo- or tPA-treated groups. For placebo patients with hypertension in the 24 hours after randomization, clinical outcome measures were similar for those patients who did and did not receive antihypertensive therapy after randomization (P > or = 0.26); antihypertensive therapy was not associated with declines in BP (P = 0.44) or with abrupt declines (P = 0.14). Those tPA patients who were hypertensive after randomization and received antihypertensive therapy were less likely to have a favorable outcome at 3 months (P < 0.01) than those who were hypertensive and did not receive antihypertensive therapy. CONCLUSIONS: The frequency of hypertension and the use of antihypertensive therapy were similar between the tPA and placebo groups in the NINDS rt-PA Stroke Trial. In the placebo group, antihypertensive therapy was not associated with less favorable outcomes at 3 months; postrandomization antihypertensive therapy was associated with less favorable outcomes for the tPA patients who were hypertensive. However, because of the nonrandomized use of antihypertensive therapy and the many post hoc comparisons leading to type 1 errors, the significance of this observation is unclear. Careful attention to BP and gentle management remain warranted for stroke patients treated with tPA.

Antihypertensive Agents↗
PubMed1997

Post-hoc Rasch analysis of optimal categorization of an ordered-response scale.

The purpose of this study was to determine the optimal categorization of a self-efficacy ordered-response scale using the Rasch analysis and compare the performance of the Rasch statistics and parameter estimates with conventional statistics. A 50-item scale to measure psychomotor self-efficacy was administered to a total of 2,022 children, including 1,009 boys and 1,013 girls. The data analysis started by collapsing the original five adjacent categories into two, three, and four categories, and a total of 14 data sets were derived. Each of these data sets, including the original one, was analyzed using the Rasch rating scale model, and a set of Rasch model-data fit, category, and separation statistics and parameter estimates, as well as three conventional statistics, were computed and compared. It was found that, instead of the five-category construct designed, the best order of category meanings of the scale in respondents' perceptions was a three-category construct. The Rasch threshold estimates were sensitive indexes in determining the order of the categorization, and that item separation statistics were useful in determining the optimal categorization after its order was confirmed. The commonly used coefficient alpha was found not helpful at all in determining the optimal categorization. The Rasch analysis was demonstrated to be a useful post-hoc analytic approach in determining the optimal categorization of an ordered-response scale.

Adolescent↗
PubMed1995

A technique revisited: hemodynamic comparison of closed- and open-chest cardiac massage during human cardiopulmonary resuscitation.

OBJECTIVE: To compare the hemodynamics of closed-chest cardiac massage vs. open-chest cardiac massage in patients resuscitated from cardiac arrest that occurred outside of the hospital. DESIGN: Prospective, non-outcome, case series. SETTING: Large urban emergency department. PATIENTS: Ten adult, normothermic, nontraumatic, out-of-hospital, cardiac arrest patients who failed advanced cardiac life support (ACLS) therapy. INTERVENTIONS: Patients presenting to the hospital in cardiac arrest were managed according to the ACLS protocol at the clinician's discretion. Proximal aortic and central venous pressure catheters were placed to measure arteriovenous compression- and relaxation-phase pressure gradients. After 5 mins of baseline measurements during closed-chest cardiac massage, patients underwent a left lateral thoracotomy, and open-chest cardiac massage was performed for 5 mins. MEASUREMENTS AND MAIN RESULTS: The mean coronary perfusion pressure and compression-phase pressure gradients were 7.3 +/- 5.7 and 6.2 +/- 5.4 mm Hg, respectively, during closed-chest cardiac massage, while increasing to 32.6 +/- 17.8 and 32.6 +/- 29.9 mm Hg, respectively, during open-chest cardiac massage. The differences between both measurements were statistically significant (p < .05). CONCLUSIONS: Open-chest cardiac massage is superior to closed-chest cardiac massage in providing relaxation-phase and compression-phase pressure gradients during cardiac arrest in patients failing current ACLS protocols. During open-chest cardiac massage, all patients exceeded the minimum coronary perfusion pressure of 15 mm Hg, which is recommended to obtain a return of spontaneous circulation. Further outcome studies are needed to determine the timeliness and appropriate indications for open-chest cardiac massage.

Aged↗
PubMed1992

[Ibuprofen--successful in activated arthrosis. Results of a administration study].

Within the framework of an observational study carried out on a national basis and involving some 4,000 patients, a total of 1,156 patients with activated arthrosis were treated with oral ibuprofen and observed over a period of three weeks. It was found that, at a dose of 600 mg tid, ibuprofen led to significant remission rates in terms of the symptoms pain at rest, pain on movement, tenderness, restriction of movement, swelling, joint effusion, and morning stiffness. After the third week of treatment, these rates reached 90%. In the first week, rapid onset of action within the first 30 minutes was noted in about 50%, which increased in the third week to 65%. Since at the same time the tolerability of ibuprofen was also found to be good--4% side effects--it can be recommended also for long-term use in this indication.

Arthritis, Rheumatoid↗
PubMed1992

Health care worker exposure to HIV-1 and HTLV I-II in critically ill, resuscitated emergency department patients.

STUDY OBJECTIVE: Exposure to HIV-1 is of profound concern to health care workers. HTLV-I and HTLV-II, retroviruses with similar modes of transmission as HIV-1, also cause disease in human beings. Emergency department resuscitations are high-risk situations for such exposure. The purpose was to determine the seroprevalence of HIV-1 and HTLV I-II in patients undergoing ED resuscitations, the magnitude of health care worker exposure, and risk factors associated with infection. DESIGN: Prospective identity-unlinked seroepidemiologic study. SETTING: ED of a 950-bed private inner-city teaching hospital. Participants included 370 patients undergoing ED resuscitations. MEASUREMENTS: Serum was tested for antibodies to HIV-1 and HTLV I-II. Questionnaires were completed by the physician in charge of the ED resuscitations. RESULTS: Fifteen (4.1%) (95% confidence interval [CI], 2.1% to 6.1%) patients were HIV-1 seropositive, and seven (1.9%) (95% CI, 0.7% to 3.1%) were HTLV I-II positive. Eleven (5.6%) (95% CI, 2.4% to 8.8%) of 197 trauma patients and 11 (6.4%) (95% CI, 2.8% to 10.0%) of 173 medical patients were infected with one of these viruses. Health care workers had direct cutaneous contact with patient blood during 114 (31%) ED resuscitations and with infected patient blood during 11 (3%) ED resuscitations. An additional 11 ED resuscitations involved parenteral exposures, one to HIV-1-infected blood. No factors could be identified that would quickly and reliably predict infection. CONCLUSION: Health care workers must protect themselves in such high-risk situations by strict compliance to mandatory universal precautions.

Adolescent↗
PubMed1991

In vitro and in vivo studies on the prenatal toxicity of five virustatic nucleoside analogues in comparison to aciclovir.

Several virustatic agents are known to be teratogenic in laboratory animals. Since routinely performed in vivo studies do not always offer the best conditions to detect the teratogenic potential of a drug, we used a combined in vivo/in vitro approach for comparative studies on the prenatal toxicity of five nucleoside analogues. Rat embryos were exposed for 48 h to various concentrations of vidarabine-phosphate (VAP), ganciclovir (GCV), 2',3'-dideoxyadenosine (ddA), 2',3'-dideoxycytidine (ddC) and zidovudine (= azidothymidine, AZT) in a whole-embryo culture system. The steepness of the concentration-response curves as well as the induced abnormality pattern (head, neural tube, shape) were similar for these compounds. However, a wide range in embryotoxic potency was observed: VAP was the most potent compound (100% abnormal embryos at 25 microM) in this in vitro system, while AZT showed the lowest potency to interfere with normal embryonic development (40% abnormal embryos at 3000 microM). In addition to these experiments we treated rats on day 10 of gestation with three s.c. injections (8 a.m.; 12 a.m.; 4 p.m.) of 200 mg of each drug/kg body wt. The embryos were evaluated on day 11.5 of gestation, i.e. at a time of development corresponding to the developmental stage at the end of the whole-embryo culture. The same criteria were used as during the in vitro studies for the evaluation of these in vivo exposed embryos. With VAP and GCV we obtained similar results with both exposure routes (in vitro and in vivo), while no abnormalities were detectable with the other compounds after exposure in utero.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed1990

Effects of valproic acid, some of its metabolites and analogues on prenatal development of rats in vitro and comparison with effects in vivo.

Using a whole-embryo culture system valproic acid (VPA) and some of its metabolites (2-en-VPA, 4-en-VPA, 4,4'-dien-VPA) and analogues (ethyl-propyl-acetic acid, propyl-butyl-acetic acid, di-butyl-acetic acid, 2-methyl-2-ethyl-hexanoic acid, 1-methyl-1-cyclohexanoic acid) were tested for their potential to induce abnormal development. With regard to embryonic growth, development and abnormality rate, the tested compounds showed a wide range of "teratogenic potency" in vitro. In order to verify some of the in vitro results, in vivo experiments were performed. Pregnant rats were treated subcutaneously on day 10 of gestation with 2 x 330 mg VPA/kg, or 2 x 400 mg 2-en-VPA/kg, respectively. Evaluation of the embryos was performed on day 11.5 of gestation, corresponding to the in vitro experiments. VPA showed a high potential to induce abnormal development in vivo as well as in vitro, whereas 2-en-VPA was inactive under our experimental conditions. Problems connected with the evaluation of the predictive value of an in vitro test system for the detection of embryotoxic effects, such as "validation" and significance of pharmacokinetic data, are discussed.

Animals↗
PubMed1990

Esophageal involvement in secondary amyloidosis mimicking achalasia.

Amyloidosis is usually considered as a cause of motor disorders of the esophagus, including achalasia. However, most patients with amyloid in the esophagus are AL-type amyloid. We report what we believe is the fourth case of secondary amyloidosis (AA-type) resulting from rheumatoid arthritis. Clinically and radiologically the picture was that of achalasia.

Amyloidosis↗
PubMed1989

All-trans retinoic acid and 13-cis-retinoic acid in the rat whole-embryo culture: abnormal development due to the all-trans isomer.

9.5-day-old rat embryos were exposed to 3 micrograms 13-cis retinoic acid (13-cis-RA)/ml culture medium or 1 microgram all-trans retinoic acid (all-trans-RA)/ml culture medium for different time intervals of the culture period (test substance-exposure periods alternated with test substance-free periods). These studies were performed to confirm the hypothesis (Klug et al. 1989) that the effect of 13-cis-RA on embryonic development in vitro is predominantly caused by its isomerisation to all-trans-RA. A 12 h exposure of the rat embryos to 13-cis-RA during different periods of culture did not interfere with normal development. However, a 12 h exposure of the embryos to all-trans-RA in the first three quarters of the culture period significantly interfered with normal development and caused clear-cut and typical abnormalities. Embryonic exposure to 13-cis-RA, for periods of more than 12 h, caused severe interference with normal development and led to branchial effects very similar to those observed following to a 12 h exposure to all-trans-RA.

Animals↗
PubMed1989

Prolonged hyperinsulinism and hypoglycemia. In an asphyxiated, small for gestation infant. Case management and literature review.

The authors describe a term female, asphyxiated, small for gestational age (SGA) infant with documented hyperinsulinism and hypoglycemia occurring at approximately 45 hours of age. The hypoglycemia was refractory to a high rate glucose infusion and steroid administration but responded to diazoxide. The subsequent hospital course was complicated by right-sided heart failure and sepsis. With the onset of sepsis, a transient hyperglycemia was noted that required intermittent insulin therapy for 10 days. Hypoglycemia and hyperinsulinism reemerged and responded to diazoxide therapy. An attempt to discontinue diazoxide at age 6 months was aborted at 2 weeks when hyperinsulinism and hypoglycemia recurred. The infant required diazoxide for 7 more months, then she recovered without having any sequelae. The review of this uncommon hypoglycemia etiology in an SGA and asphyxiated infant and the merits of long-term diazoxide treatment are discussed.

Asphyxia Neonatorum↗
PubMed1988

Prenatal toxicity of acyclovir in rats.

Pregnant rats were treated during organogenesis with s.c. injections of acyclovir and the embryos were evaluated on day 11.5 of gestation (crown-rump length, somites, protein content, score, abnormalities, histological examination). After eight injections of 50 mg/kg body wt on days 9, 10, and 11 of pregnancy a reduction of the crown-rump length was noticed. After 100 mg/kg this effect was more pronounced. With two or three applications of this dose on day 10 specific embryonic abnormalities were visible: the shape of the head was abnormal, the width of the skull had decreased resembling a beak-like visceral cranium. With a single administration of 200 mg/kg on day 10 we found a similar but slightly more pronounced outcome. A drastic change of all variables was obtained after eight injections of 100 mg/kg on days 9, 10, and 11. Comparatively we measured maternal plasma concentrations of acyclovir 1 h after the administration of 50, 100 or 200 mg/kg body wt. After an injection of 50 mg/kg on days 9, 10, and 11 of gestation (three injections/day) the plasma levels ranged from 19.1 to 40.0 mg/l (1 mg/l = 4.44 microM). No cumulation was observed. In contrast, a cumulative effect was detected following a dose of 100 mg/kg. After the first injection of this dose a mean value (+/- SD) of 60.3 +/- 14.7 mg/l (n = 16) was obtained. In this case a third injection increased the mean plasma level to 124.6 +/- 16.6 mg/l (n = 5). Further injections, however, led to decreasing levels. One hour after administration of 200 mg/kg body wt acyclovir levels ranged from 120.0 to 163.9 mg/l. We conclude that acyclovir, at doses leading to plasma concentrations well above the therapeutic level in the dam, interferes with the embryonic development in the rat. Acyclovir induces typical gross structural abnormalities which have been first observed using a whole embryo culture system.

Acyclovir↗
PubMed1986

Pharmacokinetic aspects of drug effects in vitro: effects of serum protein binding on concentration and teratogenicity of valproic acid and 2-en-valproic acid in whole embryos in culture.

Pharmacokinetic studies were performed in connection with culture experiments. Using the technique of cultivating whole rat embryos of the early postimplantation stage, we measured the concentration of valproic acid (VPA) and 2-en-VPA in the culture medium (free and protein-bound form) and in embryonic tissue. The following results were obtained: The concentrations of VPA and 2-en-VPA reached in the embryos were lower than corresponding total concentrations added to the culture medium, but exceeded the free concentrations in the medium. The concentrations of 2-en-VPA found in the embryo were lower than the comparable VPA total levels because of the more extensive protein binding of 2-en-VPA in the culture serum. The percentage of binding to serum proteins decreased with increasing total drug concentrations in the medium; the concentration of the free drug in the medium increased overproportionally with increasing total drug concentrations. Therefore, the free drug concentrations in the medium were not proportional to the dose of the drug dissolved in the medium (for a drug bound to plasma proteins). The concentrations of VPA and 2-en-VPA found in the embryos after incubation in vitro were not proportional to the drug concentrations dissolved in the medium. This result has to be taken into account when dose-response relationships are evaluated. VPA concentrations of 40 micrograms/g wet weight and above in the embryos clearly induced abnormal development in about 30% of the embryos, while 2-en-VPA concentrations as high as 200 micrograms/g embryo (wet weight) were inactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗