Femoral Access-Site Complications with Tenecteplase versus Alteplase before Mechanical Thrombectomy for Large-Vessel-Occlusion Stroke.

BACKGROUND AND PURPOSE: IV thrombolysis with alteplase before mechanical thrombectomy for emergent large-vessel-occlusion stroke is associated with access-site bleeding complications. However, the incidence of femoral access-site complications with tenecteplase before mechanical thrombectomy requires exploration. Here, femoral access-site complications with tenecteplase versus alteplase before mechanical thrombectomy for large-vessel-occlusion stroke were compared. MATERIALS AND METHODS: All patients receiving IV thrombolytics before mechanical thrombectomy for large-vessel-occlusion stroke who presented from January 2020 to August 2022 were reviewed. In May 2021, our health care system switched from alteplase to tenecteplase as the primary thrombolytic for all patients with stroke, facilitating the comparison of alteplase-versus-tenecteplase femoral access-site complication rates. Major (requiring surgery) and minor (managed conservatively) access-site complications were assessed. RESULTS: One hundred thirty-nine patients underwent transfemoral mechanical thrombectomy for large-vessel-occlusion stroke, of whom 46/139 (33.1%) received tenecteplase and 93/139 (66.9%) received alteplase. In all cases (n = 139), an 8F sheath was inserted without sonographic guidance, and vascular closure was obtained with an Angio-Seal. Baseline demographics, concomitant antithrombotic medications, and periprocedural coagulation lab findings were similar between groups. The incidence of conservatively managed groin hematomas (2.2% versus 4.3%), delayed access-site oozing requiring manual compression (6.5% versus 2.2%), and arterial occlusion requiring surgery (2.2% versus 1.1%) was similar between the tenecteplase and alteplase groups, respectively (P = not significant). No dissection, arteriovenous fistula, or retroperitoneal hematoma was observed. CONCLUSIONS: Tenecteplase compared with alteplase before mechanical thrombectomy for large-vessel-occlusion stroke is not associated with an alteration in femoral access-site complication rates.

Outcomes of Mechanical Thrombectomy in the Early (<6-hour) and Extended (≥6-hour) Time Window Based Solely on Noncontrast CT and CT Angiography: A Propensity Score-Matched Cohort Study.

BACKGROUND AND PURPOSE: Current stroke care recommendations for patient selection for mechanical thrombectomy in the extended time window demand advanced imaging to determine the stroke core volume and hypoperfusion mismatch, which may not be available at every center. We aimed to determine outcomes in patients selected for mechanical thrombectomy solely on the basis of noncontrast CT and CTA in the early (<6-hour) and extended (≥6-hour) time windows. MATERIALS AND METHODS: Consecutive mechanical thrombectomies performed for acute large-vessel occlusion ischemic (ICA, M1, M2) stroke between February 2016 and August 2020 were retrospectively reviewed. Eligibility was based solely on demographics and noncontrast CT (ASPECTS) and CTA, due to the limited availability of perfusion imaging during the study period. Propensity score matching was performed to compare outcomes between time windows. RESULTS: Of 417 mechanical thrombectomies performed, 337 met the inclusion criteria, resulting in 205 (60.8%) and 132 (39.2%) patients in the 0- to 6- and 6- to 24-hour time windows, respectively. The ASPECTS was higher in the early time window (9; interquartile range = 8-10) than the extended time window (9; interquartile range = 7-10; P = .005). Propensity score matching yielded 112 well-matched pairs. Equal rates of TICI 2b/3 revascularization and symptomatic intracranial hemorrhage were observed. A favorable functional outcome (mRS 0-2) at 90 days was numerically more frequent in the early window (45.5% versus 33.9%, P = .091). Mortality was numerically more frequent in the early window (25.9% versus 17.0%, P = .096). CONCLUSIONS: Patients selected for mechanical thrombectomy in the extended time window solely on the basis of noncontrast CT and CTA still achieved decent rates of favorable 90-day functional outcomes, not statistically different from patients in the early time window.

The FRED for Cerebral Aneurysms of the Posterior Circulation: A Subgroup Analysis of the EuFRED Registry.

BACKGROUND AND PURPOSE: Flow diversion for the posterior circulation remains a promising treatment option for selected posterior circulation aneurysms. The Flow-Redirection Intraluminal Device (FRED) system has not been previously assessed in a large cohort of patients with posterior circulation aneurysms. The purpose of the present study was to assess safety and efficacy of FRED in this location. MATERIALS AND METHODS: Consecutive patients with posterior circulation aneurysms treated at 8 centers participating in the European FRED study (EuFRED) between April 2012 and January 2019 were retrospectively reviewed. Complication and radiographic and functional outcomes were evaluated. RESULTS: Eighty-four patients (median age, 54 years) with 84 posterior circulation aneurysms were treated with the FRED. A total of 25 aneurysms (29.8%) had previously ruptured, even though most aneurysms were diagnosed incidentally (45.2%). The intradural vertebral artery was the most common location (50%), and saccular, the most common morphology (40.5%). The median size was 7 mm. There were 8 (9.5%) symptomatic thromboembolic and no hemorrhagic complications. Thromboembolic complications occurred mostly (90.9%) in nonsaccular aneurysms. On last follow-up at a median of 24 months, 78.2% of aneurysms were completely occluded. Functional outcome at a median of 27 months was favorable in 94% of patients. All mortalities occurred in patients with acute subarachnoid hemorrhage and its sequelae. CONCLUSIONS: The largest cohort of posterior circulation aneurysms treated with the FRED to date demonstrated favorable safety and efficacy profiles of the device for this indication. Treatment in the setting of acute subarachnoid hemorrhage was strongly related to mortality, regardless of whether procedural complications occurred.

Immunohistochemical localization of placental alkaline phosphatase, carcinoembryonic antigen, and cancer antigen 125 in normal and neoplastic human lung.

Human placental alkaline phosphatase (HPLAP), carcinoembryonic antigen (CEA), and cancer antigen 125 (CA 125) were localized immunohistochemically in paraffin sections of normal lung tissue from 16 patients, using monoclonal antibodies and an indirect avidin-biotin-peroxidase staining procedure. HPLAP and CEA were present in epithelial cells of respiratory bronchioli and alveolar type I pneumocytes. CEA was also observed in the tracheal, bronchial, and bronchiolar epithelium. CA 125 was present in the tracheal, bronchial, bronchiolar, and terminal bronchiolar epithelium; in the tracheal and bronchial glands; and in the pleural mesothelium. Normal and hyperplastic type II pneumocytes were negative for HPLAP, CEA, and CA 125 but were histochemically positive for nonspecific alkaline phosphatase. Fetal lung tissue between 11 and 15 weeks of gestation was negative for HPLAP, CEA, and CA 125. The fetal tracheal and bronchial epithelium, tracheal glands, and pleural mesothelium were positive for CA 125. For ten malignant pulmonary tumors investigated, HPLAP staining was observed in five, CEA in nine, and CA 125 in seven. The localization of HPLAP, CEA, and CA 125 in apparently normal constituents of all pulmonary specimens is in disagreement with the concept that the expression of these substances in the lung is indicative of abnormal cellular activity.

The effects of heated and room-temperature abdominal lavage solutions on core body temperature in dogs undergoing celiotomy.

To document the magnitude of temperature elevation obtained with heated lavage solutions during abdominal lavage, 18 dogs were lavaged with sterile isotonic saline intraoperatively (i.e., during a celiotomy). In nine dogs, room-temperature saline was used. In the remaining nine dogs, saline heated to 43+/-2 degrees C (110+/-4 degrees F) was used. Esophageal, rectal, and tympanic temperatures were recorded every 60 seconds for 15 minutes after initiation of the lavage. Temperature levels decreased in dogs lavaged with room-temperature saline. Temperature levels increased significantly in dogs lavaged with heated saline after 2 to 6 minutes of lavage, and temperatures continued to increase throughout the 15-minute lavage period.

Okadaic acid, a specific protein phosphatase inhibitor, induces maturation and MPF formation in Xenopus laevis oocytes.

Micro-injection of, or incubation with okadaic acid (OA), a specific phosphatase inhibitor, can induce formation of maturation-promoting factor (MPF) and germinal vesicle breakdown (GVBD) in Xenopus laevis oocytes. Comparison of the dose-response curves of OA on maturation, isolated enzymes and phosphatase activities in crude oocyte preparations suggests that inhibition of both polycation-stimulated (PCS) and ATP,Mg-dependent (AMD) phosphatases is sufficient but requires that a critical phosphorylation level is attained of one or several of their substrates, resulting in the formation of active MPF and meiotic maturation.

Phosphorylation of the phosphatase modulator subunit (inhibitor-2) by casein kinase-1. Identification of the phosphorylation sites.

The isolated modulator subunit of the inactive protein phosphatase-1 is phosphorylated in vitro by casein kinase-1 at two different sites: Ser-86 and Ser-174. The Ser-86 site is a common target for casein kinase-1 and casein kinase-2, but is preferentially phosphorylated by the former enzyme. The Ser-174 site seems to be specific for casein kinase-1, and is phosphorylated at a slower rate. These results give a new insight into the in vitro phosphorylation pattern of the modulator subunit of the phosphatase and provides additional data on the specificity of casein kinase-1.

Cyclosporine nephrotoxicity: comparative cytochemical study of rat kidney and human allograft biopsies.

The aim of this study was to detect early renal changes in the rat. Female Wistar rats received oral doses of cyclosporine (12.5, 25 or 50 mg/kg daily). The duration of the experiment was 1, 2, and 3 weeks. Controls received the vehicle only (olive oil). The following alterations were seen by light microscopy: Hypertrophy of the juxtaglomerular apparatus (PAS stain). Cytoplasmic droplets of neutral fat (Oil Red 0) in clusters of cortical tubules, probably belonging to the same nephron. Both the above phenomena increased with dosage and duration of treatment and were absent in controls. In the fat containing tubulus (FCT) brush border staining (alkaline phosphatase) was decreased or absent. Since after PAS the brush border was visualized in many FCT, it is concluded that many FCT were proximal tubulus (PT) of which the brush border has been damaged. In FCT mitochondrial staining (Cytochrome oxidase activity) was strongly decreased or absent. Mean lysosomal volume (acid phosphatase and dipeptidase II) is increased in the PT; in some cyclosporine animals, lysosomes were enlarged, while in others they were comparable to controls. Electron microscopy showed in some PT cells an increased number of empty vacuoles and focal alteration of mitochondria. Normal mitochondria were present next to grossly altered mitochondria. Autophagocytosis of mitochondria was clearly present. The lysosomes appeared swollen and contained electron dense material, not organised in the typical 50 A pattern of myeloid figures. These morphological changes suggest a defect of mitochondrial metabolism, leading to lipid deposition in PT. The mitochondrial metabolism can be disturbed by a direct toxic effect of cyclosporine or indirectly via ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidural administration of bupivacaine, morphine, or their combination for postoperative analgesia in dogs.

OBJECTIVE: To compare the analgesic effects of epidural administration of morphine (MOR), bupivacaine hydrochloride (BUP), their combination (COM), and 0.9% sterile NaCl solution (SAL) in dogs undergoing hind limb orthopedic surgeries. DESIGN: Blinded, randomized clinical trial. ANIMALS: 41 healthy dogs admitted for elective orthopedic surgeries involving the pelvis or hind limbs. PROCEDURE: Analgesic and control agents were administered postoperatively prior to recovery from isoflurane anesthesia. Ten dogs received MOR, 0.1 mg/kg of body weight; 10 received BUP, 0.5%, 1 ml/10-cm distance from the occipital protuberance to the lumbosacral space; 11 received COM; and 10 received SAL epidurally. Dogs were monitored for 24 hours after epidural injection for pain score, heart and respiratory rates, blood pressure, time to required administration of supplemental analgesic agent, total number of supplemental doses of analgesic agent required, and plasma concentrations of cortisol, MOR, and BUP. RESULTS: Pain scores were significantly lower in dogs in the COM and BUP groups than in dogs in the SAL group. Pain scores also were significantly lower in dogs in the COM group than in dogs in the MOR group. Time to required administration of supplemental analgesic agent was longer for dogs in the COM group than for dogs in the MOR and SAL groups. Total number of supplemental doses of analgesic agent required was lower for dogs in the BUP and COM groups than for dogs in the SAL group. CLINICAL IMPLICATIONS: Postoperative epidural administration of COM or BUP alone provides longer-lasting analgesia, compared with MOR or SAL.

Tissue distribution and pharmacokinetics of 3-t-[methyl-14C] butyl-4-hydroxyanisole in rats.

Tissue distribution and pharmacokinetics of 3-t-[methyl-14C]butyl-4-hydroxyanisole was studied in male rats. 3-t-[methyl-14C]butyl-4-hydroxyanisole was administered by gavage at a single dose of 1.5 mmol/kg. Urine, feces, blood, and 20 major tissues were collected at 0.5, 1, 3, 6, 12, 16, 17, 18, 24, 48, 72, 168, and 240 hr after dosing and were analyzed for radioactivity. Almost all radioactivity was eliminated from rats in 48 hrs. Forty one per cent of the administered dose was recovered in urine, while feces accounted for 53%. At early time points radioactivity was mainly found in gastrointestinal tissues with concentrations remaining high up to 16-18 hr after administration indicating a slow absorption and elimination of the compound. The maximum concentration of radiolabel in kidney, liver, bladder, spleen, heart, pancreas, and brain was reached at 6 hr and remained up to 24 hr. The concentration of radioactivity in liver and kidney was approximately 10-fold higher than other tissues at the peak time of 16-18 hrs. Calculated absorption and elimination rate constants demonstrated slow uptake and clearance of label by many tissues. Covalent binding in eight representative tissues at 10 time points was also studied. Results indicate that binding increases slowly and exponentially with time reaching maximum levels at 12-24 hr in most of the tissues followed by a slow decline with time.

Effects of a selective and a nonselective muscarinic cholinergic antagonist on heart rate and intestinal motility in dogs.

The effects of methoctramine, a cardioselective muscarinic cholinergic antagonist, on heart rate and small intestinal motor activity were compared to those of the nonselective competitive muscarinic antagonist, atropine. Methoctramine or atropine, 6, 10, 30, 60 micrograms/kg, or sterile isotonic saline, was administered intravenously to six conscious dogs in cross-over studies. Methoctramine administration caused dose-dependent tachycardia without affecting intestinal motility, while atropine administration caused dose-dependent tachycardia accompanied by significant reductions in small intestinal motility. Additionally, methoctramine did not inhibit intestinal smooth muscle contractile activity initiated by the muscarinic agonist bethanechol, while atropine inhibited bethanechol-induced contractile activity in a dose-dependent manner. Calculated, dosages of methoctramine and atropine required to produce a 50% increase in heart rate over baseline were 35.1 +/- 5.3 and 39.5 +/- 6.2 micrograms/kg, respectively. This dosage of atropine caused a 93 +/- 13.9% reduction in intestinal motility. These findings suggest that selective muscarinic antagonists may be useful drugs for those veterinary patients in which nonselective muscarinic antagonists have the potential to produce untoward effects on intestinal motility.

Effect of short-term cimetidine administration on fecal bile acid losses in cystic fibrosis.

Eight children with cystic fibrosis and exocrine pancreatic insufficiency were voluntarily hospitalized in a clinical research setting so that diet and enzyme supplements could be well controlled for consecutive 72-h balance studies. We previously reported on these patients, as part of a larger study group, because they showed significantly reduced fecal losses of fat and nitrogen at the highest dose of cimetidine added to the otherwise constant regimen. Analysis of specimens from this same study shows a cimetidine-related reduction in fecal bile acid loss. Numerous variables thought to influence fecal bile acid loss were closely controlled and/or measured in this clinical study setting. In order to potentially learn more about this complex phenomenon, we carried out a stepwise regression analysis of the data which indicated that half of the variance in fecal bile acid loss is still unaccounted for by the five "independent" variables tested in the regression. However, in this variance analysis system cimetidine assumes a larger relative role in modulating bile acid loss than it does in fecal losses of fat and nitrogen.

Methoctramine, a cardioselective muscarinic cholinergic antagonist, prevents fentanyl-induced bradycardia in the dog.

A controlled study examining the effects of the cardioselective muscarinic cholinergic antagonist methoctramine on fentanyl-induced bradycardia was performed in six dogs. Five doses of methoctramine (6, 10, 20, 30 and 60 micrograms/kg) followed by fentanyl (20 micrograms/kg) were administered randomly on separate days. Fentanyl caused a significant reduction in heart rate from baseline values. Moreover, fentanyl produced a variety of arrhythmogenic actions indicative of vagal hyperactivity, including sinus bradycardia, second-degree atrioventricular block and ventricular and supraventricular escape beats. Administration of methoctramine 5 min before fentanyl injection prevented the bradycardic effects of fentanyl in a dose-dependent manner, with high doses of methoctramine causing sinus tachycardia. Using regression analysis, the dose of methoctramine necessary to prevent fentanyl-induced bradyarrhythmias without causing tachycardia was calculated as 14.4 micrograms/kg. The study confirmed that fentanyl administration in the conscious dog causes profound bradycardia with bradyarrhythmias. The cardioselective muscarinic antagonist agent methoctramine prevented the bradycardic effects of fentanyl.

Tubulin and MAP2 regulate the PCSL phosphatase activity. A possible new role for microtubular proteins.

Tubulin can stimulate specifically the aryl phosphatase activity of the low-Mr polycation-stimulated (PCSL) phosphatase, measured as p-nitrophenyl phosphatase activity, or using reduced carboxamidomethylated and maleylated (RCM) lysozyme, phosphorylated on tyrosyl residues, as a substrate. This stimulation is independent of the degree of polymerization of tubulin (A50 = 60 nM) and is due to an increase in Vmax. It is mechanistically different from the ATP-induced activation and resistant to heat and trypsin treatment. Chymotrypsin destroys the stimulatory effect of tubulin. The polycation-stimulated phosphorylase phosphatase activity is inhibited by tubulin, probably by a polycation/polyanion interaction. The microtubule-associated protein, MAP2, is inhibitory to the p-nitrophenyl phosphatase activity and tubulin can eliminate this inhibitory effect. MAP2 also inhibits the polycation-stimulated phosphorylase phosphatase activity.

Isolation and characterization of a tyrosyl phosphatase activator from rabbit skeletal muscle and Xenopus laevis oocytes.

PTPA, a specific phosphotyrosyl phosphatase activator of the PCSH2 and PCSL protein phosphatases, was purified up to apparent homogeneity from Xenopus laevis ovaries and rabbit skeletal muscle and highly purified from dog liver. PTPA appears as a 40-kDa protein in gel filtration, as well as in sucrose gradient centrifugation, and as a 37-39-kDa protein doublet in SDS-PAGE. Its estimated cellular concentration of 0.75 microM in oocytes or 0.25 microM in rabbit skeletal muscle is suggestive of an important role in the regulation of the cellular PTPase activity. The PTPase activation reaction of the PCSL phosphatase is time-dependent, ATP and Mg2+ being essential cofactors [A50(ATP) = 0.12 mM in the presence of 5 mM MgCl2]. With RCM lysozyme as substrate, the specific activity of the PTPA-activated PCSL phosphatase is 700 nmol of Pi/(min.mg). The pH optimum of the PTPase shifts from 8.5-9 in basal conditions to a neutral pH (7-7.5), and the A50 for the essential metal ion Mg2+ is decreased (3 mM). The activation is rapidly reversed in the presence of the substrate, and more slowly after removal of ATP.Mg. The PTPA-activated PCSL phosphatase represents a major PTPase activity in the cytosol of X. laevis oocytes (at least 50% of the measurable PTPase with RCM lysozyme phosphorylated on tyrosyl residues). The PTPA activation is specific for the PTPase activity of the PCSL and PCSH2 phosphatases, without affecting their phosphoseryl/threonyl phosphatase activity. However, effectors of the phosphorylase phosphatase activity, such as polycations and okadaic acid, also influence the PTPase activity. Phosphorylase alpha inhibits the activated PTPase activity (I50 = 5 microM). The PTPase activity of the other oligomeric PCS phosphatases (PCSH1 and PCSM) is not influenced, suggesting an inhibitory role for some of their subunits. This activation is compared with the recently described PTPase stimulation of the PCS phosphatases by ATP/PPi [Goris, J., Pallen, C. J., Parker, P. J., Hermann, J., Waterfield, M. D., & Merlevede, W. (1988) Biochem. J. 256, 1029-1034] and by tubulin [Jessus, C., Goris, J., Cayla, X., Hermann, J., Hendrix, P., Ozon, R., & Merlevede, W. (1989) Eur. J. Biochem. 180, 15-22].

Measurement of the daily dietary calcium and magnesium intake in Belgium, using duplicate portion sampling.

The daily dietary calcium and magnesium intakes in Belgium were evaluated by sampling duplicate portions of food, destruction in a microwave oven and their calcium and magnesium contents determined by atomic absorption spectroscopy. The mean intake value for calcium (618 +/- 125 mg/day) was found to be less than those values measured in most other countries and was below the recommended daily allowance (RDA). The mean intake value for magnesium (271 +/- 44 mg/day) was similar to levels found in most other countries, but was below the RDA value for healthy adult men (350 mg/day) whilst being adequate for healthy women (280 mg/day).

Detection of fetal blood contamination by amniotic fluid obtained during cordocentesis.

When a fetal blood sample is obtained by cordocentesis it is important to know whether the sample is diluted with amniotic fluid. This study was designed to assess whether contaminated fetal blood samples could be discriminated from noncontaminated ones by the ferning test, and if so what is the minimum dilution ratio of amniotic fluid/fetal blood that is detectable. Fetal blood samples were diluted with amniotic fluid and were tested for ferning under the microscope after the plasma was separated from the cells. At a dilution ratio of 0.2 ml of amniotic fluid to 1 ml of fetal blood, 30% of the samples tested positive for ferning. A rate of 100% detection of ferning was achieved at a dilution ratio of 0.6:1. In conclusion, screening fetal blood samples for ferning can detect amniotic fluid contamination. The sensitivity of the test for ferning depends on the dilution ratio. The test cannot assess how much amniotic fluid was added to the blood sample.

Actual daily dietary intake of selenium in Belgium, using duplicate portion sampling.

The dietary selenium (Se) intake in Belgium has been re-evaluated. Duplicate meal collection, wet acid destruction and flow injection hydride generation atomic absorption spectrometry were used as techniques. The daily intake ranged from 28.4 micrograms (Liège, Walloon part of the country) to 61.1 micrograms (Vilvoorde, central part of the country). Compared with intakes recently published for other countries, the actual Belgian value corresponds to intermediate ranges of Se intake.