Cardiac assessment for renal transplantation should be evidence based.
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Biomedical subjects
Publications and source records attributed to J Beckman.
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OBJECTIVE: To determine the effectiveness of an Acute Stroke Triage Pathway in reducing door to needle times in acute stroke treatment with IV t-PA. BACKGROUND: A previous study at our tertiary referral centre, examining IV t-PA door to needle times, was completed in 2000. The median door to needle time was beyond the recommended National Institute for Neurological Disorders and Stroke (NINDS) standard of 60 minutes. In November 2001, an Acute Stroke Triage Pathway was introduced in the emergency room (ER) to address this issue. The goal of this pathway was to rapidly identify patients eligible for treatment for IV t-PA, so that CT scans and lab studies could be arranged immediately upon ER arrival. Our hypothesis was that the Triage Pathway would shorten door to CT and door to needle times. DESIGN/METHODS: Using retrospective data, pre (n=87) and post (n=47) triage pathway times were compared. The door to CT time was reduced by 11 minutes (p=0.015) and door to needle time was reduced by 18 minutes (p=0.0036) in a subgroup of patients that presented directly to our hospital. CONCLUSIONS: These results indicate that the Acute Stroke Triage Pathway is effective in reducing Door to CT and Door to Needle Times in patients presenting directly to our ER. However, a majority of treatment times were still beyond NINDS recommendations. Stroke Centers require periodic review of their efficiency to ensure that target times are being obtained and may benefit from the use of an Acute Stroke Triage Pathway.
STUDY DESIGN: Controlled study to assess the efficacy of aprotinin and Amicar in reducing blood loss during complex spinal fusions. OBJECTIVES: To compare blood loss and the clotting profile with a thromboelastogram in patients with spinal deformities undergoing sequential anterior and posterior spinal fusions treated intraoperatively with either aprotinin or Amicar. SUMMARY OF BACKGROUND DATA: Spinal fusion for correction of adult spinal deformities is associated with large blood losses despite the implementation of multiple factors to reduce this blood loss. The antifibrinolytics aprotinin and Amicar have both been shown to reduce blood loss in other surgical procedures with the potential for large blood loss. Hence, we compared their efficacy for reducing blood loss in complex spinal fusions. METHODS: Sixty patients for elective sequential anteroposterior thoracolumbosacral fusions were randomly assigned to three groups: control, aprotinin, and Amicar. Patients were assessed for blood loss, transfusion requirements, postoperative complications, and coagulation profile using a thromboelastogram. RESULTS: The study demonstrated a significant reduction in total blood loss (aprotinin 3628 mL, Amicar 4056 mL, control 5181 mL) and transfusion requirements using the half-dose aprotinin regimen compared with Amicar or control. Aprotinin also preserved the thromboelastogram mean clot formation time, clot strength, and clotting index compared with Amicar or control. CONCLUSIONS: For complex spinal operations with large blood losses, the half-dose aprotinin regimen will reduce blood loss and the need for blood components and may have a role in reducing postoperative lung injury.
Bms1p and Tsr1p define a novel family of proteins required for synthesis of 40S ribosomal subunits in Saccharomyces cerevisiae. Both are essential and localize to the nucleolus. Tsr1p shares two extended regions of similarity with Bms1p, but the two proteins function at different steps in 40S ribosome maturation. Inactivation of Bms1p blocks at an early step, leading to disappearance of 20S and 18S rRNA precursors. Also, slight accumulation of an aberrant 23S product and significant 35S accumulation are observed, indicating that pre-rRNA processing at sites A0, A1, and A2 is inhibited. In contrast, depletion of Tsr1p results in accumulation of 20S rRNA. Because processing of 20S to 18S rRNA occurs in the cytoplasm, this suggests that Tsr1p is required for assembly of a transport- or maturation-competent particle or is specifically required for transport of 43S pre-ribosomal particles, but not 60S ribosome precursors, from the nucleus to the cytosol. Finally, Bms1p is a GTP-binding protein, the first found to function in ribosome assembly or rRNA processing.
BACKGROUND: Inhalational anesthetics are neuroprotective in rat models of global ischemia. To determine whether isoflurane at a clinically relevant concentration is neuroprotective in a canine model of cardiac arrest, we measured neurologic function and hippocampal Ca2+/calmodulin-dependent protein kinase II (CaMKII) content 20 h after cardiac arrest. METHODS: We tested the neuroprotective effect of 30 min of 1.5% isoflurane exposure before 8 min of global ischemia induced with ventricular fibrillation. Animals were randomized to four groups: control, isoflurane-control, ischemia, and isoflurane-ischemia. After resuscitation and 20 h of intensive care, each animal's neurologic deficit score was determined by two blinded evaluators. The hippocampal content of CaMKII, determined by immunoblotting, was measured by an individual blinded to the treatment groups. CaMKII activity was measured in samples from the cortex, hippocampus, and striatum of animals in each group. RESULTS: Isoflurane-ischemic animals had a median neurologic deficit score of 22.6% compared with 43.8% for the ischemic animals (P < 0.05). Hippocampal levels of the beta-subunit of CaMKII (CaMKIIbeta) were relatively preserved in isoflurane-ischemic animals (68 +/- 4% of control) compared with ischemic animals (48 +/- 2% of control; P < 0.001), although both groups were statistically significantly lower than control (P < 0. 001 ischemia vs. control and P < 0.05 isoflurane-ischemia vs. control). CONCLUSIONS: Isoflurane is an effective neuroprotective drug in a canine cardiac arrest model in terms of both functional and biochemical criteria.
BACKGROUND AND PURPOSE: In the United States, tissue plasminogen activator (tPA) was approved for treatment of acute ischemic stroke in 1996. Its use has only recently been approved in Canada. We sought to evaluate the safety, feasibility, and efficacy of treatment in a Canadian hospital setting. METHODS: A combined retrospective and prospective review is presented of 46 consecutive patients treated with intravenous tPA at our hospital with a treatment protocol similar to that of the National Institute of Neurological Disorders and Stroke (NINDS) trial. RESULTS: Symptomatic intracranial hemorrhage at 36 hours occurred in 1 patient (2.2%). The median time to treat was 165 minutes, with a median "door-to-needle" time of 84 minutes. Compared with patients presenting initially at our hospital, patients transferred from another institution for tPA therapy were treated closer to the 3-hour time window (mean 173 versus 148 minutes, P:<0.001) but had a shorter door-to-needle time (43 versus 102 minutes, P:<0.001). For every 10 minutes closer to the 3-hour time window that any patient arrived at the hospital, 7 minutes was saved in the door-to-needle time (correlation coefficient 0.9, P:<0.001). Patient outcome did not differ from that in the NINDS trial (P:>0.75). CONCLUSIONS: Our safety and patient outcome data compare favorably with NINDS and Phase IV data. Although a 3-hour treatment window was feasible, the median door-to-needle time lengthened as more treatment time was available and the door-to-needle time was beyond recommended standards. This review has prompted changes in our community to improve treatment efficiency.
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A 63-year-old man was seen with a history of nonfluent dysphasia and headaches. His blood tested positive for anticardiolipin antibodies. Transthoracic echocardiography showed a mass in the left ventricular apex. The transgastric five-chamber view identified this mass as an anomalously placed papillary muscle. In the presence of an apical mass, if the transthoracic echocardiogram is equivocal, a transesophageal echocardiogram, using the transgastric five-chamber view may be helpful in making the correct diagnosis.
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The conditions under which nitric oxide (.NO) may modulate or promote lung injury have not been identified. We hypothesized that .NO-induced injury results from peroxynitrite, formed by the reaction of .NO with superoxide. The simultaneous generation of .NO and superoxide by 3-morpholinosydnonimine (SIN-1, 0.1-2 mM) resulted in oxidation of dihydrorhodamine, a marker of peroxynitrite production, and a dose-dependent decrease in the ability of SP-A to enhance lipid aggregation. Western blot analysis of SIN-1 exposed SP-A samples, overlaid with a polyclonal antibody against nitrotyrosine, were consistent with nitration of SP-A tyrosine residues. Superoxide dismutase (100 U/ml), L-cysteine (5 mM), xanthine oxidase (10 mU/ml) and xanthine (500 microM), or urate (100 microM) prevented the SIN-1-induced dihydrorhodamine oxidation and injury to SP-A. .NO alone, generated by S-nitroso-N-acetylpenicillamine plus 100 microM L-cysteine, or superoxide and hydrogen peroxide, generated by pterin and xanthine oxidase in the absence of iron, did not damage SP-A or oxidize dihydrorhodamine. We concluded that peroxynitrite, but not .NO or superoxide and hydrogen peroxide, in concentrations likely to be encountered in vivo, caused nitrotyrosine formation and decreased the ability of SP-A to aggregate lipids.
Educationally significant hearing loss has been reported in 10% to 15% of children with congenital toxoplasmosis. As part of a pilot study to assess feasibility and safety of prolonged therapy for congenital toxoplasmosis, 30 congenitally infected infants and children were evaluated for auditory function. Serial testing, beginning within 2 months of birth, was performed. Availability of auditory brainstem response (ABR) testing made evaluation at an earlier age than previously possible. Six (20%) of the 30 infants had mild to moderate conductive type hearing loss associated with otitis media. No infant or child had sensorineural hearing loss. The better outcome we observed compared to previous reports of a 15% to 26% incidence of sensorineural hearing loss and 10% to 15% incidence of educationally significant, bilateral hearing impairment may be related to early initiation and/or prolonged institution of antimicrobial therapy. Continued followup to exclude progressive hearing impairment and study of larger numbers of children are needed to verify these preliminary findings.
The above data continue to demonstrate the metabolic well being of the aged red cell as it is isolated from rabbits. The abundance of ATP, the absence of surface-bound IgG and a variety of other observations at this time lead to the tentative conclusion that the senescent red cell is amazingly healthy. Many investigators have predicted that the red cell is removed from the circulation as a metabolically exhausted effete cell. There is currently no evidence to support this other than a decrease in deformability of the cells with time, but it is not clear that this decline in deformability is sufficient to keep the cell from circulating. In either case, many of the previously proposed causes of cellular removal are clearly incorrect for the rabbit, and it is now time to focus on new directions for observing either cellular impairment or perhaps the presence of a cellular clock which is independent of the cell's metabolic state. Another point which should be addressed is the reliability of the biotinylation model in rabbits as it relates to red cells in other species. So far several observations in aged red cells isolated with valid models have been reproduced across species boundaries including the rise in ATP, the fall in AMP deaminase activity, the shift in the 4.1a to 4.1b protein ratio, the stability of a number of glycolytic enzymes, and the instability of pyrimidine 5'-nucleotidase activity. To this point, the rabbit has been a reliable model of red cell aging and one with implications for other species.
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This study assessed the effect of low (40 mg) and high (324 mg) single dose aspirin on cardiac release of thromboxane A2 and prostacyclin as assessed by measurement of coronary sinus levels of metabolites in patients with coronary artery disease. Measurements were done in the resting state and in the presence of pacing stress prior to and 24 h after aspirin administration. There was no consistent response in prostaglandin release under conditions of tachycardia stress as compared to control. Following both doses of aspirin, thromboxane could not be detected at rest or with pacing, and prostacyclin metabolic levels were undetectable in six of seven patients. Prostaglandin levels were not related to myocardial lactate extraction or production and lactate levels had no consistent relationship to aspirin administration. These data indicate that both low and high doses of aspirin inhibit both thromboxane A2 and prostacyclin production in humans. Selective thromboxane inhibition might not be possible.
Dopamine agonists have yielded two important advances to our understanding of the basal ganglia--they have facilitated the subdivision of different classes of dopamine receptors, and they have established the fact that important dopaminergic effects can be achieved by activation of dopamine receptors in a manner that is unrelated to anoxal impulse traffic in dopaminergic neurons--a phenomenon similar in its diffuse, slow, characteristics to an endocrine effect. The tangible clinical benefit of dopamine agonists has been evident in patients with prominent dyskinesia or wearing off reactions. It is possible that earlier use of agonists, in low doses combined with similarly low doses of levodopa, may improve the long term treatment of Parkinson's disease, but as yet there is no firm evidence. In the future, we can expect to see agonists with more prolonged effects, deriving from the formation of active metabolites. We can also hope to gain further insight into the correlations between the various animal models of dopaminomimetic activity, and specific aspects of drug efficacy and toxicity in parkinsonian patients. Such information should allow the design of improved pharmacotherapy.
Recurrent and advanced cancer in the head and neck region is usually associated with limited therapeutic concepts and a dismal prognosis. Efforts mainly focus on palliative treatment in order to improve the patient's quality of life. From May 1989 to December 1994, a total of 120 intra-operative radiotherapy (IORT) procedures with high-energy electron beams (mean energy: 7 MeV: mean dose: 20 Gy) were performed in 95 patients. Therapy was usually performed under endotracheal anaesthesia (84%). There were 91 cases (75.8%) of recurrence in the lymph nodes of the neck and 14 cases (11.7%) of local recurrence. 15 patients (12.5%) received IORT as part of the initial treatment. Considering the palliative nature of IORT in these patients, only an R2 resection (gross residual tumour) was achieved in 71.7%. Local tumour control was nonetheless possible in 17% (R2 resection) to 64% (complete R0 resection), with a mean 11-month follow-up period for survivors (mean for deceased patients: 8 months). Regarding palliative criteria, IORT proved to be feasible since patients profited from short hospitalisation (median: 10 days), a low complication rate (27 instances; e.g. tracheostomy: 11; necrosis: 8, or fistula: 3) and, in part, a substantial reduction of pain (73.8%). Most of them regained physical and psychic integrity for weeks to months and were able to take part in social life during the final stage of their disease.
Surveillance data show that pesticide-related illness is an important cause of acute morbidity among migrant farm workers in California. A few categories (organophosphates and carbamates, inorganic compounds, and pyrethroids) account for over half of the cases of acute illness. Skin effects dominate the illnesses, although ocular and systemic effects are also common. Exposures occur in various ways (e.g., residues, drift), suggesting that the use of pesticides creates a hazardous work environment for all farm workers. The health care system provided through the Migrant Health Program appears to be underutilized, partially due to barriers to health care access. Pesticide hazards should be ranked based on acute toxicity, chronic toxicity (including reproductive risks), carcinogenic potency, volume applied, and magnitude of worker poisonings. Current surveillance effort should be supported. Risk prevention should focus on substitution of safer compounds, establishing effective protections, and ensuring that these measures are enforced. Improved education for health care providers should be a priority. Growers should be educated about alternative forms of pest control and incentives should be provided to encourage their use.