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Biomedical subjects

S Meisel

Publications and source records attributed to S Meisel.

At least 19 recordsLinked to original sources

[Cortical blindness following coronary angiography].

Cortical blindness has been occasionally reported as a complication after cerebral angiography, but is rare after coronary angiography. The contrast agent is believed to be responsible for the sudden development of blindness. Although the exact mechanism is unknown, it appears that the contrast agent disrupts the blood brain barrier, mostly in the occipital areas. We report a 77-year-old man who suddenly developed transient, bilateral cortical blindness 4 hours after coronary angiography. Using contrast enhancement, the CT scan showed typical, symmetrical involvement of both occipital lobes. There were no other neurological deficits. Vision and CT findings returned to normal within 48 hours.

Aged↗

Membrane type 1 matrix metalloproteinase expression in human atherosclerotic plaques: evidence for activation by proinflammatory mediators.

BACKGROUND: Matrix metalloproteinases (MMPs) are expressed in atherosclerotic plaques, where in their active form, they may contribute to vascular remodeling and plaque disruption. In this study, we tested the hypothesis that membrane type 1 MMP (MT1-MMP), a novel transmembrane MMP that activates pro-MMP-2 (gelatinase A), is expressed in human atherosclerotic plaques and that its expression is regulated by proinflammatory molecules. METHODS AND RESULTS: MT1-MMP expression was examined in normal and atherosclerotic human arteries by immunocytochemistry with specific antibodies. MT1-MMP expression in human saphenous vein-derived smooth muscle cells (SMCs) maintained in tissue culture was determined under basal conditions and in response to proinflammatory molecules (interleukin [IL]-1alpha, tumor necrosis factor [TNF]-alpha, and oxidized LDL [ox-LDL]) by use of Northern blot and ribonuclease protection assays for mRNA, Western blot and immunoprecipitation for protein, and gelatin zymography for catalytic activity. Medial SMCs of normal vessel wall expressed MT1-MMP. In atherosclerotic arteries, MT1-MMP expression was noted within the complex atheroma colocalizing with SMCs and macrophages (Mphi). Cultured SMCs constitutively expressed MT1-MMP mRNA and protein, which increased 2- to 4-fold over control in a time-dependent manner within 4 to 8 hours of exposure to IL-1alpha, TNF-alpha, and ox-LDL (thiobarbituric acid-reactive substances, 13.4 nmol/mg LDL protein), whereas native LDL had no effect. Flow cytometry revealed MT1-MMP expression by human monocyte-derived Mphi, which increased 3.8-fold over baseline within 6 hours after exposure to 10 ng/mL TNF-alpha. CONCLUSIONS: This study demonstrates that MT1-MMP, an activator of pro-MMP-2, is expressed by SMCs and Mphi in human atherosclerotic plaques. Furthermore, proinflammatory molecules upregulate MT1-MMP expression in vascular SMCs and Mphi. Thus, activation of SMCs and Mphi by proinflammatory molecules may influence extracellular matrix remodeling in atherosclerosis by regulating MT1-MMP expression.

Antibodies, Monoclonal↗

Reducing adverse drug events and medication errors using rapid cycle improvement.

The article describes Fairview Health System's participation in the Institute for Healthcare Improvement Breakthrough Series on adverse drug events and medication errors. Fairview commissioned an interdisciplinary team to design, plan, and lead activities focused on reducing adverse drug events and medication errors. This team managed, facilitated, or led 15 separate projects, each focusing on a specific aspect of the medications process. Specific systems improvements were identified, leading to reductions in errors or adverse events. As a result of this effort, Fairview has committed to a long-term plan to reduce the risk of adverse drug events and medication errors to the lowest possible rate.

Anticoagulants↗

Ascitic fluid to serum bilirubin concentration ratio for the classification of transudates or exudates.

OBJECTIVE: We compared the ascitic fluid to serum bilirubin ratio with three other ways of classifying ascitic fluid to the categories of exudate or transudate: the serum-ascites albumin gradient, the total protein concentration of the fluid, and the adaptation of Light's criteria for the detection of pleural fluid exudate, i.e., fluid to serum protein or LDH ratio or fluid LDH concentration. (Recently it has been reported that the pleural fluid to serum bilirubin ratio is statistically equivalent to Light's criteria.) Also, we evaluated whether the addition of the bilirubin ratio to the other criteria increases their diagnostic accuracy. METHODS: Eighty-one specimens of ascitic fluid from 81 different patients were obtained. They were analyzed prospectively by SMA12, whereas the category of the fluid was determined according to the clinical diagnosis. The diagnostic accuracy of each criterion alone and in combination with the bilirubin ratio, with reference to the contended etiology, were evaluated. RESULTS: The best criterion is the albumin gradient (overall accuracy = 0.84). The bilirubin and LDH ratio criteria had equivalent overall accuracy (0.815 and 0.802, respectively). The addition of the bilirubin ratio to any criterion did not improve its predictive or overall accuracy. CONCLUSIONS: Ascitic fluid to serum bilirubin ratio is an additional marker for the distinction of transudate from exudate. A ratio > 0.6 has a statistically significant association with exudate.

Ascitic Fluid↗

Production of follistatin in porcine endothelial cells: differential regulation by bacterial compounds and the synthetic glucocorticoid RU 28362.

Follistatin (FS) is the specific binding protein of activin; it has a broad tissue distribution and is also found in serum. The ovary has the highest level of FS expression, but ovariectomy does not cause a permanent reduction in the serum FS level. Therefore, the source of FS in serum is still elusive. As a regulatable, nongonadal source of serum FS could influence ovarian and pituitary-derived hormone secretion and thus reproductive function, we searched for a source of extragonadal FS expression that might contribute to the FS protein level in serum. We found that endothelial cells from blood vessels express FS messenger RNA (mRNA) and protein; therefore, we studied the regulation of steady state levels of FS mRNA in porcine endothelial cells from aorta (AEC) and brain microvessels (BMVEC) in tissue culture. For detection of FS mRNA, a specific 32P-radiolabeled antisense probe and a S1-nuclease protection assay were used. FS steady state levels of AEC decreased with time in culture, i.e. postconfluent AEC had lower FS mRNA levels than confluent cultures, which, in turn, had lower FS mRNA levels than subconfluent cell cultures. FS mRNA levels in AEC were induced by increasing concentrations of FCS and stimulated by 30 micrograms/ml endothelial cell growth supplement. FS mRNA levels in AEC and BMVEC increased approximately 20-fold within 4 h during incubation of the cells with 100 nM phorbol 12-myristate, 13-acetate, whereas 0.5 nmol/ml forskolin tested in AEC for between 4-48 h had no significant effect. Furthermore, 0.1 microM ocadaic acid, an inhibitor of serine/threonine phosphatases 1 and 2A, caused a significant increase in FS mRNA levels. FS mRNA levels in AEC were not significantly affected by various concentrations of porcine FSH, epidermal growth factor, or retinoic acid for between 4-48 h. Treatment of the cells with 0.01-10 micrograms/ml bacterial lipopolysaccharides (LPS) caused a dose-dependent increase (up to 10-fold) in FS mRNA steady state level in AEC, whereas 1-1000 nM RU 28362, a synthetic glucocorticoid, inhibited FS mRNA steady state levels in a dose-dependent manner. The induction of FS mRNA with 1 microgram/ml LPS was completely blocked by 100 nM RU 28362, and the stimulatory effects of LPS were only visible after 4 h of treatment, not after 24 or 48 h. The same effects were observed with BMVEC. We, furthermore, analyzed FS protein secretion of AEC by Western blotting and demonstrated that FS proteins were secreted into the culture medium upon stimulation with LPS. None of these treatments had an obvious effect on the ratio of the two different forms of FS mRNA (FS 344:FS 317). Besides the expression of FS mRNA in AEC and BMVEC, FS mRNA is also expressed in uncultured plexus choroideus epithel and meninges, and FS protein is found in human cerebrospinal fluid. From this study it is concluded that 1) endothelial cells from different tissues produce FS mRNA; 2) the FS mRNA levels of AEC and BMVEC are subjected to regulation by FCS, endothelial cell growth supplement, bacterial LPS, and the glucocorticoid RU 28362; 3) phosphatases and the protein kinase C-dependent, but not the protein kinase A-dependent, pathway are involved in regulating the steady state levels of FS mRNA in AEC and BMVEC; and 4) endothelial cells produce and secrete FS protein and are thus a likely source of FS in serum.

Androstanols↗

Clinical pharmacokinetics of ramipril.

Ramipril is a long-acting nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor introduced for clinical use about a decade ago. Ramipril is a prodrug that undergoes de-esterification in the liver to form ramiprilat, its active metabolite. Ramipril rapidly distributes to all tissues, with the liver, kidneys and lungs showing markedly higher concentrations of the drug than the blood. After absorption from the gastrointestinal tract, rapid hydrolysis of ramipril occurs in the liver. In the therapeutic concentration range, protein binding of ramipril and ramiprilat is 73 and 56%, respectively. Ramiprilat binds to ACE with high affinity at concentrations similar to that of the enzyme and establishes equilibrium slowly. Although ramipril is metabolised by hepatic and renal mechanisms to both a glucuronate conjugate and a diketopiperazine derivative, most of the drug is excreted in the urine as ramiprilat and the glucuronate conjugate of ramiprilat. Elimination from the body is characterised by a relatively rapid initial phase with a half-life of 7 hours and a late phase with a half-life of about 120 hours. No clinically significant pharmacokinetic interactions between ramipril and other drugs have been reported. The drug has been generally well tolerated with the most prevalent adverse effects being dizziness (3.4%), headache (3.2%), weakness (1.9%) and nausea (1.7%). Ramipril is an effective and well tolerated drug for the treatment of hypertension and congestive heart failure in all patients, including those with renal or hepatic dysfunction, and the elderly.

Drug Interactions↗

Acute hypertensive response to +Gz acceleration in mildly hypertensive pilots.

Two fighter pilots with mild hypertension and a mildly hypertensive response to exercise underwent ambulatory blood pressure monitoring during a routine flight that included a brief exposure to +4 Gz stress. They exhibited an acute elevation of both systolic and diastolic blood pressures during +4 Gz stress: from 140/90 and 135/90 mm Hg to 179/139 and 180/140 mm Hg, respectively. Heart rate reached 182 and 132 beats/min. These responses of hypertensives may reflect exaggerated baroreceptor and sympathetic responses which cause a pronounced over-shoot of blood pressure. The findings demonstrate the value of 24-h ambulatory blood pressure monitoring for documenting episodic elevations of blood pressure that do not influence the "normal" average blood pressure, but may nevertheless have important clinical implications.

Acute Disease↗

Essential thrombocythemia: a relative benign long-term course.

The disease manifestations, response to therapy, and follow-up course of 35 patients with essential thrombocythemia seen in a single center were evaluated. The median age was 53 years (range 17-81). Twelve patients were asymptomatic on presentation and the diagnosis was incidental. Twenty-three patients presented with thrombocytosis-related symptoms, most commonly neurological, microcirculatory, or thromboembolic. In no patient did hemorrhage occur as a presenting symptom. The mean platelet count (+/- SD) at diagnosis was 858 +/- 223 x 10(9)/l and the mean maximal count during the follow-up period was 989 +/- 269 x 10(9)/l. The median follow-up of the entire group was 54 months (range 12-172). Ten of the 12 patients who were asymptomatic on presentation remained so during the observation period, while 10 patients who presented with thrombocytosis-related symptoms became asymptomatic following a single course of treatment with no recurrence of symptoms. Thirty of the 35 patients were treated with busulfan or hydroxyurea or both. Response to cytoreductive therapy was prompt and continuous in most patients. Essential thrombocythemia might be a disease of grave consequence but it seems that in general its course under treatment is more benign than previously thought.

Adolescent↗

Prospective evaluation of risk factors for antibiotic-associated bleeding in critically ill patients.

A prospective surveillance program was initiated to determine the relative role of antibiotics containing N-methylthiotetrazole (NMTT) versus patient risk factors in producing antibiotic-associated bleeding. Five hundred forty-six critically ill patients with serum albumin 30 g/L or below were evaluated for evidence of a bleeding event as documented by clinical observation, hemoglobin changes, and transfusions. Bleeding events occurred in 16% of patients receiving an aminoglycoside combination, 10% receiving antibiotics with the NMTT side chain, and 14.5% receiving antibiotics not containing NMTT (p greater than 0.05). The bleeding rate was highest in febrile patients with cancer (14.5%) and lowest in those with a suspected or documented abdominal infection (10%) (p = 0.04), but within each patient group there was no difference among the antibiotics. We conclude that the use of NMTT-containing antibiotics is not an independent risk factor for bleeding, but the role of severity of illness may be underappreciated.

Abdomen↗

Pleural fluid to serum bilirubin concentration ratio for the separation of transudates from exudates.

Whether fluid accumulating in the pleural space is a transudate or an exudate is determined by the widely used criteria of the pleural fluid to serum LDH and protein concentration ratios. Such a distinction is important for limiting the extent of the differential diagnosis of possible causes for this condition. We have found that a pleural fluid to serum total bilirubin ratio can serve the same purpose. The correlation of a bilirubin concentration ratio of 0.6 or more with the presence of an exudate as determined by established criteria is statistically highly significant; and its sensitivity, specificity, positive predictive accuracy, and overall accuracy in relation to etiology and LDH or protein criteria (Light's criteria) are about 90 percent. Hence, the bilirubin criterion is statistically equivalent to the widely accepted LDH and protein criteria.

Bilirubin↗

Another complication of thoracostomy--perforation of the right atrium.

Tube thoracostomy is an invasive procedure that is frequently life-saving but carries a risk of complications. We describe herein a complication not documented before-laceration of the right atrium. This occurred in a severely kyphoscoliotic patient with a markedly narrowed chest and led to his demise. This case attests to the extreme caution warranted when using trocar-type thoracostomy in patients with thoracic deformities.

Aged↗

[Carotid endarterectomy].

Carotid endarterectomy was performed 77 times in 73 symptomatic patients. In 67 of them there had been 1 or more transient ischemic attacks (TIA), in 4 transient atypical symptoms, and in 2 mild persistent neurological deficits. After operation 1 died of a stroke and 1 had a nonfatal myocardial infarction. In 3.3% of 33 low-risk patients (Sundt's classes 1 and 2) there was mild postoperative neurological deficit. The rate of neurological complications was much higher in 40 high-risk patients (classes 2 and 3), including 5 with postoperative stroke. Followup averaged 21.5 months (longest 54 months), the 5-year survival (by extrapolation from a life table analysis curve) was 87%, and there was only 1 fatal stroke. Those who recovered from operation without complications had an 86% chance of having no further neurological problems.

Carotid Arteries↗

Castleman's disease. An uncommon computed tomographic feature.

A case of localized intrathoracic Castleman tumor demonstrated, on CT scan, calcifications in a circumferential distribution. The prevalence of calcifications in Castleman's disease and the differential diagnosis of the above unusual CT findings are discussed.

Adult↗