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Biomedical subjects

G Cohen

Publications and source records attributed to G Cohen.

At least 37 records · Page 2Linked to original sources
PubMed2003

Near-fatal grape aspiration with complicating acute lung injury successfully treated with extracorporeal membrane oxygenation.

OBJECTIVE: In this report of a near-fatal case of grape aspiration successfully treated with extracorporeal membrane oxygenation (ECMO), we highlight the danger of feeding seedless grapes to young children and demonstrate that ECMO can provide cardiopulmonary support for cases of acquired large-airway disruption and can facilitate therapeutic intervention. DESIGN: Case report. SETTING: A tertiary pediatric intensive care unit and ECMO center. PATIENT: A healthy 14-month-old boy aspirated a seedless grape while playing at home and suffered a cardiopulmonary arrest of 15 mins in duration. He responded to advanced life support with return of cardiac output but developed intractable cardiopulmonary failure secondary to aspirated grape particles and postobstructive pulmonary edema. INTERVENTIONS: The patient was emergently transferred to the regional ECMO center and placed on venoarterial ECMO. Bronchoscopies were performed in the stable environment provided by ECMO, aspirated particles were removed from the large airways, and lung recovery was facilitated. MEASUREMENTS AND MAIN RESULTS: End-organ perfusion was restored via ECMO during a period of severe intractable cardiopulmonary failure. Pulmonary recovery occurred during a 6-day ECMO run and was facilitated by therapeutic bronchoscopy. The patient was reviewed 1 yr later and has made a full neurodevelopmental recovery, despite a 15-min out-of-hospital cardiac arrest. CONCLUSIONS: Aspiration of a seedless grape is a life-threatening event in a small child. This danger is not fully appreciated by parents in the UK. ECMO may be life saving in cases of acquired large-airway disruption resulting in severe cardiopulmonary failure, including foreign body aspiration, as long as end-organ perfusion is maintained.

Cardiac Output, Low↗
PubMed2002

Nasal midazolam as a novel anticonvulsive treatment against organophosphate-induced seizure activity in the guinea pig.

Seizures and status epilepticus, which may contribute to brain injury, are common consequences of exposure to organophosphorus (OP) cholinesterase inhibitors. Effective management of these seizures is critical. To investigate the efficacy of nasal midazolam as an anticonvulsive treatment for OP exposure, as compared to intramuscular midazolam, guinea pigs were connected to a recording swivel for electrocorticograph (ECoG) monitoring and clinical observation. The experimental paradigm consisted of pyridostigmine pretreatment (0.1 mg/kg i.m.) 20 min prior to sarin exposure (1.2x LD(50,) 56 micro g/kg i.m.). One minute post-exposure, atropine (3 mg/kg i.m.) and TMB-4 (1 mg/kg im) were administered. Within 3-8 min after sarin exposure all animals developed electrographic seizure activity (EGSA), with convulsive behavior. Treatment with midazolam (1 mg/kg i.m.) 10 min after the onset of EGSA abolished EGSA within 389+/-181 s. The same dose was not effective, in most cases, when given 30 min after onset. However, a higher dose (2 mg/kg) was found efficacious after 30 min (949+/-466 s). In contrast, nasal application of midazolam (1 mg/kg) was found most effective, with significant advantages, in amelioration of EGSA and convulsive behavior, when given 10 min (216+/-185 s) or 30 min (308+/-122 s) following the onset of EGSA ( P<0.001). Thus, nasal midazolam could be used as a novel, rapid and convenient route of application against seizure activity induced by nerve agent poisoning.

Administration, Intranasal↗
PubMed2002

Crack front waves and the dynamics of a rapidly moving crack.

Crack front waves are nonlinear localized waves that propagate along the leading edge of a crack. They are generated by both the interaction of a crack with a localized material inhomogeneity and the intrinsic formation of microbranches. Front waves are shown to transport energy, generate surface structure, and lead to localized velocity fluctuations. Their existence locally imparts inertia, which is not incorporated in current theories of fracture, to initially "massless" cracks. This, coupled to microbranch formation, yields both inhomogeneity and scaling behavior within the fracture surface structure.

Journal Article↗
PubMed2002

Hyperhomocysteinemia and arterial aneurysm.

Hyperhomocysteinemia (HCY) is an independent risk factor for atherosclerosis. Arterial aneurysm has rarely been described in association with heterozygous HCY. Here we report two cases of this association. Case 1 was 32-Year-old man who presented with distal trophic manifestations of the lower extremities. Upon investigation, occlusive arterial disease with fusiform aneurysm of both popliteal arteries and occlusion of the left cubital artery were found. Laboratory findings indicated HCY due to homozygous methylene tetrahydrofolate reductase (MTHFR) deficiency. Case 2 was 38-year-old man with no history of trauma who presented with repeated ischemic events involving the right hand in association with isolated aneurysm of the right cubital artery. Histological study demonstrated extensive dystrophic changes in the aneurysmal vessel wall, including sclerohyalin deposits. The only abnormality was homozygous MTHFR deficiency. Pathologic changes induced by HCY in vessel walls may be implicated in early arterial aneurysm. The association of anatomic lesions, young age, and absence of other causes suggests that the relationship between HCY and arterial aneurysm observed in these two patients was not coincidental.

Adult↗
PubMed2002

Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: a multicenter dose-finding study in women with breast cancer.

BACKGROUND: Neutropenia is common in patients receiving myelotoxic chemotherapy. Pegfilgrastim, a sustained-duration filgrastim is a once-per-cycle therapy for prophylactic neutrophil support. PATIENTS AND METHODS: Women, treated with four cycles of doxorubicin/docetaxel chemotherapy every 21 days, received pegfilgrastim or filgrastim 24 h after chemotherapy as a single subcutaneous injection per chemotherapy cycle (pegfilgrastim 30, 60 or 100 microg/kg) or daily subcutaneous injections (filgrastim 5 microg/kg/day). Safety, efficacy and pharmacokinetics were analyzed. RESULTS: The incidence of grade 4 neutropenia in cycle 1 was 95, 90 and 74%, in patients who received pegfilgrastim 30, 60 and 100 microg/kg, respectively, and 76% in patients who received filgrastim. Mean duration of grade 4 neutropenia in cycle 1 was 2.7,2 and 1.3 days for doses of pegfilgrastim, and 1.6 days for filgrastim. The pharmacokinetics of pegfilgrastim were non-linear and dependent on both dose and neutrophil count. Pegfilgrastim serum concentration was sustained until the neutrophil nadir occurred then declined rapidly as neutrophils started to recover, consistent with a self-regulating neutrophil-mediated clearance mechanism. The safety profiles of pegfilgrastim and filgrastim were similar. CONCLUSIONS: A single subcutaneous injection of pegfilgrastim 100 microg/kg provided neutrophil support and a safety profile comparable to daily subcutaneous injections of filgrastim during multiple chemotherapy cycles.

Adult↗
PubMed2001

Single-chain antibody against the common epitope of mutant p53: isolation and intracytosolic expression in mammalian cells.

The peptide epitope FRHSVV is cryptic in wild-type p53 and is exposed in many types of mutant p53 molecules isolated from various tumors. Mutant p53 marked by this epitope abrogates a tumor-suppressor function of wild-type p53 and possibly contributes to the transforming potential of other oncogenic processes. We report here the construction of a single-chain scFv antibody gene library derived from the mRNA of a mouse immunized with the epitope peptide FRHSVV which mimics the common epitope in p53 mutant protein molecules. The scFv was presented by phage display. The selected antibody gene, named ME1, was found to bind to the mutant p53 protein but not to the wild-type p53 protein. Preliminary studies show that the ME1 gene is expressed in the cytosol of mammalian cells. These findings suggest that the ME1 single-chain antibody may be useful as a tool for clarifying the role of mutant p53 in tumor transformation, especially in cells heterozygous in p53, and possibly for gene therapy of tumors.

Amino Acid Sequence↗
PubMed2001

Propagating solitary waves along a rapidly moving crack front.

A rapidly moving crack in a brittle material is often idealized as a one-dimensional object with a singular tip, moving through a two-dimensional material. However, in real three-dimensional materials, tensile cracks form a planar surface whose edge is a rapidly moving one-dimensional singular front. The dynamics of these fronts under repetitive interaction with material inhomogeneities (asperities) and the morphology of the fracture surface that they create are not yet understood. Here we show that perturbations to a crack front in a brittle material result in long-lived and highly localized waves, which we call 'front waves' These waves exhibit a unique characteristic shape and propagate along the crack front at approximately the Rayleigh wave speed (the speed of sound along a free surface). Following interaction, counter-propagating front waves retain both their shape and amplitude. They create characteristic traces along the fracture surface, providing cracks with both inertia and a new mode of dissipation. Front waves are intrinsically three-dimensional, and cannot exist in conventional two-dimensional theories of fracture. Because front waves can transport and distribute asperity-induced energy fluctuations throughout the crack front, they may help to explain how cracks remain a single coherent entity, despite repeated interactions with randomly dispersed asperities.

Journal Article↗
PubMed2001

Bretazenil, a benzodiazepine receptor partial agonist, as an adjunct in the prophylactic treatment of OP poisoning.

Benzodiazepines, mainly diazepam, are commonly used as anticonvulsants in the treatment of organophosphate casualties. Although very effective, diazepam usually is not used in prophylactic treatments because of its adverse effects on task performance and its abuse liability. Benzodiazepine (BZ) partial agonists are unique in that they are able to occupy all the population of a given receptor without eliciting the maximal physiological response. The BZ receptor agonistic occupancy was found to differ among the various physiological responses in the following order: antipanic > anticonvulsion > sedation > muscle relaxation. Thus, partial agonists, by the use of which controlled levels of agonistic activity can be achieved, might serve as effective anticonvulsants, with fewer side-effects. Bretazenil, a partial agonist, was found to counteract metrazol-induced convulsions in rats. At the anticonvulsive doses (125-250 microg x kg(-1), i.p.) bretazenil, in combination with pyridostigmine (100 microg x kg(-1), i.m.) and aprophen (4 mg x kg(-1), i.m.), conferred prophylactic protection against sarin and soman poisoning (protective ratios 2.6 and 2.1, respectively). Relevant doses of bretazenil (50-400 microg x kg(-1), i.p.) also were tested for general behavioural effects in the open field and for its anti-anxiety properties in the plus maze. The incapacitation was much lower compared with diazepam. Bretazenil should be considered as a candidate for incorporating into a prophylactic mixture as a central nervous system protectant, with significant advantages concerning incapacitation.

Animals↗
PubMed2001

Prophylaxis against organophosphate poisoning by sustained release of scopolamine and physostigmine.

Protection efficacy of continuous prophylactic administration of physostigmine and scopolamine against sarin-induced toxicity was evaluated previously in guinea pigs. The present study in large animals used Beagle dogs, that serve as an animal model with cholinergic sensitivity similar to that of humans. Pretreatment with physostigmine salicylate and scopolamine hydrochloride at dose rates of 2.5 and 1 microg x kg(-1) x h(-1), respectively, was administered via Alzet mini-osmotic pumps. At the time of exposure, the physostigmine salicylate concentration in plasma was 0.7 ng x ml(-1) and the scopolamine hydrochloride concentration was ca. 0.2 ng x ml(-1), both of which are levels known to be well tolerated in humans. Whole-blood cholinesterase inhibition was 15-20%. This regimen conferred full protection against 2.5 x LD50 i.v. of sarin. Albeit the high-dose exposure, cholinergic toxicity symptoms were mild with no convulsions. About 11-14 min following poisoning the treated animals started to walk and 15-20 min following exposure full recovery was observed and the dogs behaved normally. With higher dose rates of physostigmine salicylate and scopolamine hydrochloride, at plasma concentrations of 2.1 and 0.6 ng x ml(-1), respectively, treated dogs regained normal posture 6-10 min after exposure.

Animals↗
PubMed2001

Effects of metabolic stimulation on cardiac allograft recovery.

BACKGROUND: We previously demonstrated that continuous perfusion of cardiac allografts during hypothermic storage with donor blood harvested at the time of organ retrieval improves myocardial recovery after transplantation. However, myocardial metabolism and function remain depressed compared to base line values. This study evaluated the use of a continuous infusion of donor blood enhanced with insulin to augment aerobic myocardial metabolism during and after hypothermic storage. METHODS: Yorkshire pigs (45 to 50 kg) were used to perform 14 orthotopic cardiac transplants using either continuous perfusion with donor blood (blood group, n = 7) or perfusion with donor blood enhanced with 10 IU/L insulin (insulin group, n = 7). After heparinization, hypothermic (4 degrees C) cardioplegic arrest, and donor heart extraction, donor blood (2,844 +/- 210 mL) was harvested in both groups and perfused at room temperature (20 degrees C) at a pressure of 60 mm Hg for 3 hours. Blood cardioplegia was delivered after each anastomosis in both groups and arterial and coronary sinus blood samples were obtained to examine myocardial metabolism. A Millar micromanometer was used to measure left ventricular developed pressure and the rate-pressure product at varying preloads. RESULTS: There were no differences in either myocardial lactate or acid release between the two groups. Hearts in the insulin group displayed higher myocardial oxygen extraction than those in the blood group. The recovery of developed pressure was higher in the insulin group compared to the blood group (91% +/- 19% vs 73% +/- 2%, p = 0.04). CONCLUSIONS: In this model, continuous perfusion of cardiac allografts with donor blood and insulin preserves myocardial metabolism during hypothermic storage and improves metabolic and functional recovery after orthotopic cardiac transplantation.

Animals↗
PubMed2001

The radial artery versus the saphenous vein graft in contemporary CABG: a case-matched study.

BACKGROUND: Although use of the internal thoracic artery has been shown to improve outcomes after coronary artery bypass grafting, the same cannot be said of alternative arterial conduits. To determine the benefit of radial artery (RA) grafting, a case-matched review was undertaken. METHODS: Between March 1994 and March 1999, 2,847 patients underwent isolated coronary artery bypass grafting with a left internal thoracic artery graft, plus saphenous vein grafts (SVGs). Of these patients, 478 also received an RA graft (RA group). The RA patients were matched at a ratio of 1:2 with patients receiving only SVGs and a left internal thoracic artery graft (SVG group; n = 956) using six prognostic risk factors: age, sex, Canadian Cardiovascular Society class, left ventricular grade, number of diseased vessels, and timing of operation. Target vessels were graded according to quality and graftability and were similar between groups. Outcomes were evaluated by univariate and multivariate analyses. RESULTS: There was a significantly higher prevalence of diabetes, hypertension, and peripheral vascular disease in the RA group (p < 0.05). Although stay in the intensive care unit was shorter in the RA group (RA, 30 +/- 2 hours, and SVG, 37 +/- 2 hours; p = 0.0002), total hospital stay was similar between groups. The incidence of perioperative myocardial infarction was higher in the SVG group (SVG, 31 of 956 or 3.2%, and RA, 6 of 478 or 1.3%; p = 0.02). Multivariate analysis revealed RA grafting to be protective against early mortality and morbidity (odds ratio = 0.58; 95% confidence interval, 0.37 to 0.90; p = 0.015) and late mortality and morbidity including late reintervention (risk ratio = 0.60; 95% confidence interval, 0.37 to 0.93; p = 0.02). Actuarial freedom from events at 36 months postoperatively was greater in the RA group (RA, 95% +/- 2%, and SVG, 86% +/- 4%; p = 0.01). CONCLUSIONS: Despite a higher prevalence of preoperative comorbidity, patients in the RA group demonstrated improved outcomes after coronary artery bypass grafting. The RA is a viable and beneficial conduit for this operation.

Case-Control Studies↗
PubMed2001

Lactate release during reperfusion predicts low cardiac output syndrome after coronary bypass surgery.

BACKGROUND: Cardioplegic arrest induces anaerobic myocardial metabolism with a net production of lactate from glycolysis. However, persistent lactate release during reperfusion suggests a delayed recovery of normal aerobic metabolism and may lead to depressed myocardial function necessitating inotropic or intraaortic balloon pump support (low output syndrome [LOS]). We examined the relation between perioperative myocardial metabolism and postoperative clinical outcomes in patients undergoing isolated coronary artery bypass surgery (CABG). METHODS: We reviewed 623 patients who were enrolled in clinical studies evaluating perioperative myocardial metabolism between 1983 and 1996. Arterial and coronary sinus blood samples were obtained intraoperatively to assess myocardial metabolism. Clinical data regarding patient demographics and postoperative outcomes were prospectively collected and entered into our institutional database. RESULTS: Low output syndrome developed in 36 patients (5.8%). Myocardial lactate release was higher in these patients compared with those who did not develop postoperative LOS. Advanced age and poor preoperative left ventricular function were independent predictors of lactate release during reperfusion. Persistent lactate release after 5 minutes of reperfusion was the only independent predictor of postoperative LOS in this low-risk population. CONCLUSIONS: Persistent lactate release during reperfusion occurs in a significant proportion of low-risk patients undergoing isolated CABG and is an independent predictor of postoperative low cardiac output syndrome. Persistent lactate release during reperfusion suggests a delayed recovery of aerobic myocardial metabolism and may be related to intraoperative misadventure or inadequate myocardial protection. Myocardial lactate release may be useful as an alternative end-point in clinical trials evaluating perioperative myocardial protection.

Aged↗