Utilization of intravenous tissue plasminogen activator for acute ischemic stroke

BACKGROUND: Intravenous tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke, although only 2% of patients with stroke receive intravenous tPA nationally. OBJECTIVE: To determine the rate of tPA use for stroke in the Cleveland, Ohio, community and the reasons why patients were excluded from thrombolysis treatment. DESIGN: Retrospective cohort study. SETTING: Community.Subjects Patients admitted because of stroke to the 9 Cleveland Clinic Health System hospitals from June 15, 1999, to June 15, 2000. MAIN OUTCOME MEASURES: Utilization of intravenous tPA and reasons for ineligibility. RESULTS: There were 1923 admissions for ischemic stroke in the 1-year period. Of these, 288 (15.0%) arrived within the 3-hour time window, and approximately 6.9% were considered eligible for tPA. The most common reasons for exclusion among patients arriving within 3 hours were mild neurologic impairment and rapidly improving symptoms. The overall rate of tPA use among patients presenting within 3 hours was 19.4%, and the rate of use among eligible patients was 43.4% (n = 56). The use of tPA did not differ significantly according to race or sex. CONCLUSIONS: Only 15% of patients arrived within the 3-hour time window for intravenous tPA, making delay in presentation the most common reason patients were ineligible for i.v. thrombolysis. Neurologic criteria were the second most common group of exclusions. Overall tPA use was low, but it was used in nearly half of all patients with no documented contraindications. Intravenous tPA use in a community setting can compare favorably with the rate of use seen in academic medical settings.     

Limitations in the histopathologic diagnosis and prognosis of neuroblastoma

Neuroblastoma is the most common nonhematopoietic solid tumor of childhood and has been intensively studied for at least 4 decades. Despite this, few predictive histopathologic clues to its behavior exist. Ages, anatomic sites of occurrence, histopathology of the tumor and clinical stage have traditionally been the only reliable prognostic factors in this disease. In the present study we analyzed these prognostic factors in 72 neuroblastic tumors and our histopathological possibilities of diagnosis.     

Design of beta-lactams with mechanism based nonantibacterial activities

The majority of nonantibacterial activities discovered for beta-lactam derivatives during the last 15 years are based on their ability to form a stable covalent complex with nucleophile in the active site of enzymes regulating fundamental physiological processes in mammalian organism such as serine and cysteine proteases, LDL phospholipase A(2), A-independent transacylase and some still indeciphered enzymes. Regulation of their catalytic activity both in vitro and in vivo by compounds designed on the cephalosporin, penicillin and 2-azetidinone base was successfully exploited in the treatment of inflammatory, respiratory, cardiovascular disorders, cancer and other pathologic processes. Availability of X-ray crystallographic data for target enzymes and computational molecular modelling in combination with wide possibilities of structural modifications for commercial natural and synthetic beta-lactams and the chiral blocks allow to consider this class of organic compounds as a perspective source of mechanism based nonantibacterial drugs.     

In vitro study of guide wire entrapment in currently available inferior vena cava filters

PURPOSE: Guide wire entrapment by some older inferior vena cava (IVC) filters is known to occur, particularly with J-tipped wires. Three new IVC filters have recently been approved for use in the United States. An in vitro study was performed to compare the risk of engaging and entrapping guide wires in eight of the IVC filters currently available in the United States. MATERIALS AND METHODS: Titanium Greenfield, over-the-wire stainless-steel Greenfield, Simon nitinol, Bird's Nest, Vena Tech LGM, Vena Tech LP, TrapEase, and Günther Tulip IVC filters were deployed separately in an in vitro IVC flow model. Four different wires (15-mm, 3-mm, and 1.5-mm J-tipped, and straight) were passed 100 times each through the filters (50 from a jugular approach and 50 from a femoral approach). The frequency and specific patterns of engagement of the wires by the filters were recorded. Engagement was defined as a filter/wire interaction that caused either the filter or the wire to be deformed. The second part of the experiment measured the force (in pounds) that was required to release wires that became engaged in the filters with use of an electromechanical test stand with a specially designed low-capacity load cell of 20 pounds. Entrapment was defined as inability to separate an engaged wire from the filter without damage to either the wire or filter. RESULTS: Guide wire engagement occurred in all filters tested with the 15-mm, 3-mm, and 1.5-mm J-tipped wires. The straight wire did not engage any of the filters. The wires engaged the TrapEase filter with the greatest frequency overall (72.8%; 291 of 400). The 15-mm J wire engaged the filters more often than the other wires (98.5%; 788 of 800), but never became entrapped in a filter. The Vena Tech LP and Günther Tulip filters did not entrap any of the wires. The TrapEase filter, the stainless-steel Greenfield filter, and the Vena Tech LGM filter entrapped the 3-mm and 1.5-mm J wires. The force required to disengage the wires from these filters exceeded 4 pounds and resulted in structural damage to the wire and/or filter. CONCLUSIONS: Among the IVC filters recently approved by the Food and Drug Administration, the TrapEase filter entrapped 3-mm and 1.5-mm J-tipped guide wires, whereas the Vena Tech LP and Günther Tulip filters did not. This study corroborates previously described wire entrapment by the stainless-steel Greenfield and Vena Tech LGM devices.     

Clinico-morphological features of acute gastroduodenal erosion and ulcers in an unstable course of myocardial ischemia and role in disturbances of microcirculation,stomach function and their development

AIM: Determination of clinicomorphological characteristics of acute gastroduodenal erosions and ulcers in unstable course of IHD and the role of disorders in microcirculation, hemostasis, gastric function in development of these erosions. MATERIAL AND METHODS: Clinically and endoscopically were examined 124 patients with unstable IHD. By detected gastroduodenal changes the patients were divided into three groups. The study was also made of local and systemic microcirculation, hemostasis, gastric functions. RESULTS: Acute gastroduodenal erosions and ulcers in unstable course of ischemic heart disease manifest with mild abdominal pains and gastric dyspepsia for several days. Disorders in the gastroduodenal zone arise because of focal disturbances of terminal circulation in the mucose according to thromboischemic or thrombohemorrhagic types related to generalized changes of microcirculation and hematasis. High activity of acid-peptic factor, low production of gastromucoproteins and hypomotor dyskinesia of the stomach contribute to development of erosive-ulcerous lesions. CONCLUSION: The above information is useful for early diagnosis of acute gastroduodenal erosions and ulcers in unstable course of IHD and upgrading of therapeutic measures.     

NK and trophoblast cells interaction: cytotoxic activity on recurrent pregnancy loss

Abstract

The trial objective was to determine the peripheral blood NK cells cytotoxic activity effect on trophoblast cells at recurrent pregnancy loss (RPL). The investigation involved non-pregnant women with PRL in proliferating and secretory menstrual cycle phases (PMCPh and SMCPh, respectively); women of 6–7 weeks pregnancy with RPL in past medical history; healthy fertile non-pregnant women in PMCPh and SMCPh, women of 6–7 weeks physiological pregnancy, nulliparity healthy women with regular menstrual function in PMCPh and SMCPh. NK cells cytotoxic activity was determined using peripheral blood mononuclear cells. The target cells were JEG-3?line trophoblasts. It has been established that NK cells cytotoxic activity effect on trophoblasts is lower in SMCPh than in PMCPh in non-pregnant fertile women. The NK cells cytotoxic activity was higher in SMCPh than in PMCPh in non-pregnant women with PRL and also higher than the same value in SMCPh in non-pregnant fertile women. The increased NK cells cytotoxic activity values in SMCPh in women with RPL may be the reason for miscarriage.     

Quality of Life in a Randomized Trial of Nasogastric Tube Feeding in Acute Pancreatitis

Background: Recent clinical studies have shown that nasogastric tube feeding is safe in the majority of patients with acute pancreatitis. Patient‐reported outcomes are important, but the impact of nasogastric tube feeding on the quality of life has not been investigated. This study aims to compare quality of life between nasogastric tube feeding and nil‐by‐mouth groups during and after hospitalization. Methods: Patient‐reported outcomes were recorded daily in a patient diary during hospitalization. The Abdominal Surgery Impact Scale questionnaire was used to determine patients' quality of life. The patients were then followed up at 1 week and 1, 3, and 6 months after discharge. Results: While 17 patients were randomized to nasogastric tube feeding, 18 were put on nil‐by‐mouth. The overall quality of life and individual domains did not differ significantly between the groups during hospitalization (P = .500) or follow‐up. For the entire cohort, individual quality‐of‐life domains during hospitalization improved significantly, including functional impairment (P < .001), pain (P < .001), sleep (P = .035), and psychological function (P < .001). Quality of life further improved for all patients from time of hospital discharge to 3 (P = .002) and 6 months follow‐up (P < .001) but not to 1 week and 1 month. Conclusions: The use of nasogastric tube feeding, in comparison with nil‐by‐mouth, does not impair patients' quality of life. Given the clinical benefits of nasogastric tube feeding, nasogastric feeding should be considered the first‐line approach in all acute pancreatitis patients requiring enteral nutrition.     

Coding polymorphisms in Casp5, Casp8 and DR4 genes may play a role in predisposition to lung cancer

Apoptosis plays a role in the elimination of DNA-damaged cells thus protecting the host from cancer development. Some data indicate that normal variations within the sequence of apoptotic genes may lead to suboptimal apoptotic capacity and therefore increased cancer risk. We tested 19 coding apoptotic gene SNPs in 2-stage molecular epidemiological study. For the preliminary sorting of SNP candidates, we employed a “comparison of extremes” approach, where 111 patients with highly pronounced LC susceptibility (non-smokers or young-onset light smokers) were analyzed against 110 subjects with the evidence for LC tolerance (elderly tumor-free heavy smokers). Three genotypes demonstrated possible association with LC risk (Leu/Leu-homozygotes for Casp5 Val318Leu versus other genotypes: OR = 2.47 (95% CI: 1.07–5.69), p = 0.03; His-carriers for Casp8 His302Asp: OR = 2.26 (95% CI: 1.18–4.31), p = 0.02; Arg-carriers for DR4 Lys441Arg: OR = 1.89 (95% CI: 1.05–3.40), p = 0.03), and therefore were selected for the validation. The extended study included 2 case-control series, namely subjects from Russia (351 LC cases and 538 controls) and Moldova (296 LC cases and 295 controls). Interestingly, all three candidate genotypes consistently demonstrated OR above 1 both in Russian and in Moldovian groups. Although the combined Mantel–Haenszel analysis yet failed to reach statistical significance (OR = 1.22 (95% CI: 0.90–1.65), p = 0.21; OR = 1.17 (95% CI: 0.92–1.50), p = 0.21; OR = 1.19 (95% CI: 0.95–1.51), p = 0.14, respectively), the obtained data indicate that Casp5, Casp8 and DR4 gene polymorphisms may deserve consideration in large-scale case-control studies of LC risk modifiers.     

Wavelets and functional magnetic resonance imaging of the human brain

The discrete wavelet transform (DWT) is widely used for multiresolution analysis and decorrelation or "whitening" of nonstationary time series and spatial processes. Wavelets are naturally appropriate for analysis of biological data, such as functional magnetic resonance images of the human brain, which often demonstrate scale invariant or fractal properties. We provide a brief formal introduction to key properties of the DWT and review the growing literature on its application to fMRI. We focus on three applications in particular: (i) wavelet coefficient resampling or "wavestrapping" of 1-D time series, 2- to 3-D spatial maps and 4-D spatiotemporal processes; (ii) wavelet-based estimators for signal and noise parameters of time series regression models assuming the errors are fractional Gaussian noise (fGn); and (iii) wavelet shrinkage in frequentist and Bayesian frameworks to support multiresolution hypothesis testing on spatially extended statistic maps. We conclude that the wavelet domain is a rich source of new concepts and techniques to enhance the power of statistical analysis of human fMRI data.