Just whose autonomy is it?
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Analgesics, Opioid↗
Biomedical subjects
M L Smith
Publications and source records attributed to M L Smith.
Malignant rolandic-sylvian epilepsy in children: diagnosis, treatment, and outcomes.
OBJECTIVE: To describe the diagnosis, treatment, and outcomes in children with malignant rolandic-sylvian epilepsy (MRSE), defined as a form of epilepsy characterized by sensorimotor seizures, medical refractoriness, normal MRI, frontocentrotemporal EEG spikes, rolandic-sylvian spike sources on magnetoencephalography (MEG), and cognitive problems. METHODS: A retrospective chart analysis of seven patients who had shown these characteristics and undergone extensive diagnostic testing, including MEG and intracranial video-EEG was performed. RESULTS: Interictal scalp EEG spikes were seen over the frontocentrotemporal regions bilaterally (6) and unilaterally (1). MEG showed spike sources in the perisylvian region in two patients (both bilateral) and in the perirolandic fissure in five (two bilateral). Three patients required bilateral subdural strips to lateralize seizures before electrocorticography. Final electrocorticograms showed an ictal onset zone around the rolandic (four cases) and rolandic-sylvian regions (three cases). Six patients showed neuropsychological deficits. After cortical excision and multiple subpial transection, three were seizure free and four had seizures rarely (30 months' mean follow-up). No child had a permanent deficit in sensorimotor or cognitive functions, although two showed exacerbation of preexisting attentional deficits. Tissue analysis showed definite evidence of neuronal migration disorders (3) and gliosis (2). CONCLUSIONS: MEG was helpful for localizing both malignant rolandic-sylvian neuronal activities and functional cortex. Successive neuropsychological assessments are necessary to detect cognitive deterioration and indicate remedial programming. If, after careful observation over at least 5 years, surgery is considered to control refractory seizures, intracranial video-EEG is needed to localize the epileptogenic zone.
Adolescent↗
A CD2-green fluorescence protein-transgenic mouse reveals very late antigen-4-dependent CD8+ lymphocyte rolling in inflamed venules.
Intravital microscopy allows detailed analysis of leukocyte trafficking in vivo, but fails to identify the nature of leukocytes investigated. Here, we describe the development of a CD2-enhanced green fluorescence protein (EGFP)-transgenic mouse to characterize lymphocyte trafficking during inflammation in vivo. A CD2-EGFP plasmid construct including the CD2 promoter, the EGFP transgene, and the CD2 locus control region was injected into B6CBA/F1 pronuclei. EGFP+ offspring were backcrossed into C57BL/6 mice for six generations. Flow cytometry demonstrated that all peripheral blood EGFP+ cells were positive for CD2 and negative for the granulocyte Ag Ly 6-G (GR-1). EGFP(high) cells stained positive for CD2, CD3, CD8, TCR beta-chain, and NK1.1 but did not express the B cell and monocyte markers CD45RA, CD19, and CD11b. In vitro stimulation assays revealed no difference in lymphocyte proliferation and IL-2 secretion between EGFP+ and EGFP- mice. Intravital microscopy of untreated or TNF-alpha-treated cremaster muscle venules showed EGFP+ cells in vivo, but these cells did not roll or adhere to the vessel wall. In cremaster muscle venules treated with both TNF-alpha and IFN-gamma, EGFP(high) cells rolled, adhered, and transmigrated at a rolling velocity slightly higher (11 microm/s) than that of neutrophils (10 microm/s). Blocking alpha4 integrin with a mAb increased rolling velocity to 24 microm/s. These findings show that CD8+ T cells roll in TNF-alpha/IFN-gamma-pretreated vessels in vivo via an alpha4 integrin-dependent pathway.
Animals↗
Biventricular pacing decreases the inducibility of ventricular tachycardia in patients with ischemic cardiomyopathy.
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Cardiac Pacing, Artificial↗
Hox genes and the phylogeny of the arthropods.
The arthropods are the most speciose, and among the most morphologically diverse, of the animal phyla. Their evolution has been the subject of intense research for well over a century, yet the relationships among the four extant arthropod subphyla - chelicerates, crustaceans, hexapods, and myriapods - are still not fully resolved. Morphological taxonomies have often placed hexapods and myriapods together (the Atelocerata) [1, 2], but recent molecular studies have generally supported a hexapod/crustacean clade [2-9]. A cluster of regulatory genes, the Hox genes, control segment identity in arthropods, and comparisons of the sequences and functions of Hox genes can reveal evolutionary relationships [10]. We used Hox gene sequences from a range of arthropod taxa, including new data from a basal hexapod and a myriapod, to estimate a phylogeny of the arthropods. Our data support the hypothesis that insects and crustaceans form a single clade within the arthropods to the exclusion of myriapods. They also suggest that myriapods are more closely allied to the chelicerates than to this insect/crustacean clade.
Animals↗
Effect of P-wave timing during supraventricular tachycardia on the hemodynamic and sympathetic neural response.
BACKGROUND: Previous studies have shown the importance of the timing of atrial and ventricular systole on the hemodynamic response during supraventricular tachycardia (SVT). However, the reflex changes in autonomic tone during SVT remain poorly understood. METHODS AND RESULTS: Eleven patients with permanent dual-chamber pacemakers were enrolled in the study. Arterial blood pressure (BP), central venous pressure (CVP), and peripheral muscle sympathetic nerve activity (SNA) were recorded during DDD pacing at a rate of 175 bpm (cycle length 343 ms) with an atrioventricular (AV) interval of 30, 200 and 110 ms, simulating tachycardia with near-simultaneous atrial and ventricular systole, short-RP tachycardia (RP PR). Each pacing run was performed for 3 minutes separated by a 5-minute recovery period. All patients demonstrated an abrupt fall in BP, an increase in CVP, and an increase in SNA regardless of the AV interval. The decreases in SBP, DBP, and MAP and the increase in CVP were significantly less during long-RP tachycardia (AV interval 110 ms) than during the other 2 pacing modes (P:<0.05), and the increase in SNA in 7 of the 11 patients was significantly greater during closely coupled atrial and ventricular systole than during long-RP tachycardia (P:<0.05). CONCLUSIONS: These data suggest that the superior maintenance of hemodynamic stability during long-RP tachycardia is accompanied by reduced sympathoexcitation, which is primarily mediated by the arterial baroreceptors, with a modest cardiopulmonary vasodepressor effect.
Baroreflex↗
Isolation of an antimicrobial compound from Impatiens balsamina L. using bioassay-guided fractionation.
By using brine shrimp (Artemia salina) lethality test-guided fractionation, a single bioactive compound (LC(50)=26 ppm) was isolated from the 95% ethanol extract of the dried aerial parts of Impatiens balsamina L. and subsequently identified as 2-methoxy-1,4-naphthoquinone (MNQ). The structure of MNQ was confirmed by UV, FT-IR, MS, and 1-and 2-D NMR spectroscopy. The antimicrobial activity of MNQ was evaluated using 12 bacterial and eight fungal strains. Five gram-positive and two gram-negative bacteria as well as all eight fungi (including multi-drug resistant strains) tested were highly sensitive to MNQ. A tea prepared according to traditional methods was found to contain sufficient MNQ to account for its antimicrobial properties.
Animals↗
Necrotic arachnidism.
UNLABELLED: Necrotic arachnidism is the potential cutaneous reaction to spider bite venom. In the United States, members of 7 spider families may be responsible for envenomation sufficiently severe to warrant treatment. Characteristics of several spiders, in particular Loxosceles spiders, whose bite is toxic to humans are described, and diagnostic standards, preventive measures, and treatment options are reviewed. (J Am Acad Dermatol 2001;44:561-73.) LEARNING OBJECTIVE: After the completion of this learning activity, participants should be familiar with the characteristics of several different spider families endemic to the United States. Furthermore, this learning activity should aid in the prevention and diagnosis of spider bites as well as in the classification and treatment of specific bites.
Humans↗
Urinary excretion profiles for total morphine, free morphine, and 6-acetylmorphine following smoked and intravenous heroin.
Heroin is one of the major target drugs in workplace drug-testing programs because of its history of abuse, liability, and continued negative social impact. This study was a comprehensive examination of pharmacokinetics, pharmacodynamics, detection times, opiate immunoassay performance, and urine excretion profiles following single doses of heroin administered to human subjects via smoking and intravenous routes. Studies of the first four components of this investigation were previously published. This article describes the urine excretion profiles. Total morphine (Tmor), free morphine (Fmor), and 6-acetylmorphine (6-AM) were measured by gas chromatography-mass spectrometry (GC-MS) in 920 urine samples collected from 11 male human subjects following single doses of heroin. Eight received intravenous doses of 3, 6, and 12 mg heroin HCI and four smoked 3.5-, 5.2-, 7-, 10.5-, or 13.9-mg doses of heroin (base). In addition, 183 urine-based blind quality-control samples were added to the study set to assess assay performance. Creatinine was also measured in each sample by a colorimetric technique. The parameters studied were not significantly dependent on route of administration. Excretion half-life mean +/- SD for Tmor was 3.11 +/- 0.30 h. Range (median) of peak urine concentrations, time to peak, time to last positive sample for low cutoff (300 ng/mL) and high cutoff (2000 ng/mL) for Tmor following lower doses (< or = 7 mg) were, respectively, 1392-9250 (3620) ng/mL, 1.2-6.2 (2.3) h, 7.4-31.9 (7.4) h, and 0-10.1 (4.3) h. Following higher doses (> 10 mg) they were 2065-29,030 (16,470) ng/mL, 2.3-9.3 (4.5) h, 10.7-53.5 (34.4) h, 2.3-22.3 (8.3) h. Fmor peaked in the same sample as Tmor. Range (median) of peak Fmor concentrations and time to last positive using a cutoff of 100 ng/mL for low and high doses were, respectively, 117-1160 (415) ng/mL, 1.2-10.1 (4.5) h and 150-2580 (1400) ng/mL, 2.3-29.1 (9.3) h. The range (median) of peak urine concentrations for 6-AM was 6.1-568 (124) ng/mL. In general, the first urine void had the peak 6-AM concentration and was the only specimen positive at a 10-ng/mL cutoff. As previously reported urine concentrations varied greatly between subjects and within subjects with time after dosing but were much more predictable when values were reported as amount of drug per unit of creatinine. The range (median) values for percent of heroin excreted into urine as Tmor was 12.8-88.5% (51.0).
Administration, Inhalation↗
Characterization of AFLP markers in damselflies: prevalence of codominant markers and implications for population genetic applications.
Amplified fragment length polymorphism (AFLP) analysis is becoming increasingly popular as a method for generating molecular markers for population genetic applications. For practical considerations, it is generally assumed in population studies that AFLPs segregate as dominant markers, i.e., that present and absent are the only possible states of a given locus. We tested the assumption of dominance in natural populations of the damselfly Nehalennia irene (Hagen) (Odonata: Coenagrionidae). Electro-blotted AFLP products from 21 samples were probed with individual markers. Eleven markers were analyzed, of which two were monomorphic and nine were polymorphic. Only two of the polymorphic markers behaved in a strictly dominant manner. The remaining seven polymorphic markers displayed various degrees of codominance, with 2-10 visible alleles in the sample. Of the three markers displaying the highest degree of variability, two contained microsatellite repeat tracts. Our results suggest that the assumption of dominance is unfounded. As a result, AFLP analysis may be unsuitable for estimating several important population genetic parameters, including genetic diversity.
Alleles↗
Carotid baroreflex regulation of sympathetic nerve activity during dynamic exercise in humans.
We sought to determine whether carotid baroreflex (CBR) control of muscle sympathetic nerve activity (MSNA) was altered during dynamic exercise. In five men and three women, 23.8 +/- 0.7 (SE) yr of age, CBR function was evaluated at rest and during 20 min of arm cycling at 50% peak O(2) uptake using 5-s periods of neck pressure and neck suction. From rest to steady-state arm cycling, mean arterial pressure (MAP) was significantly increased from 90.0 +/- 2.7 to 118.7 +/- 3.6 mmHg and MSNA burst frequency (microneurography at the peroneal nerve) was elevated by 51 +/- 14% (P < 0.01). However, despite the marked increases in MAP and MSNA during exercise, CBR-Delta%MSNA responses elicited by the application of various levels of neck pressure and neck suction ranging from +45 to -80 Torr were not significantly different from those at rest. Furthermore, estimated baroreflex sensitivity for the control of MSNA at rest was the same as during exercise (P = 0.74) across the range of neck chamber pressures. Thus CBR control of sympathetic nerve activity appears to be preserved during moderate-intensity dynamic exercise.
Adult↗
Arterial baroreflex control of sympathetic nerve activity during acute hypotension: effect of fitness.
We examined arterial baroreflex control of muscle sympathetic nerve activity (MSNA) during abrupt decreases in mean arterial pressure (MAP) and evaluated whether endurance training alters baroreflex function. Acute hypotension was induced nonpharmacologically in 14 healthy subjects, of which 7 were of high fitness (HF) and 7 were of average fitness (AF), by releasing a unilateral arterial thigh cuff after 9 min of resting ischemia under two conditions: control, which used aortic and carotid baroreflex (ABR and CBR, respectively) deactivation; and suction, which used ABR deactivation alone. The application of neck suction to counteract changes in carotid sinus transmural pressure during cuff release significantly attenuated the MSNA response (which increased 134 +/- 32 U/14 s) compared with control (which increased 195 +/- 43 U/14 s) and caused a greater decrease in MAP (19 +/- 2 vs. 15 +/- 2 mmHg; P < 0.05). Furthermore, during both trials, the HF subjects exhibited a greater decrease in MAP compared with AF subjects despite an augmented baroreflex control of MSNA. These data indicate that the CBR contributes importantly to the MSNA response during acute systemic hypotension. Additionally, we suggest that an impaired control of vascular reactivity hinders blood pressure regulation in HF subjects.
Adult↗
Gender differences in cardiovascular regulation during recovery from exercise.
Are women more susceptible to acute postexercise orthostatic hypotension compared with men? We hypothesized that decreases in arterial pressure during recovery from dynamic exercise are greater in women compared with men. We studied 8 men and 11 women during inactive and active recovery from cycling exercise. Heart rate, stroke volume (SV), cardiac output, mean arterial pressure (MAP), and total peripheral resistance (TPR) were measured during and after 3 min of exercise at 60% of calculated maximum heart rate. At 1 min after exercise, MAP decreased less (P < 0.05) during inactive recovery in men (-18 +/- 2 mmHg) compared with women (-30 +/- 2 mmHg). This difference was due to greater decreases in SV and less increase in TPR during inactive recovery from exercise in women compared with men. These differences persisted for 5 min after exercise. MAP decreased less during active recovery in men compared with women. These findings suggest that women may have increased risk of postexercise orthostatic hypotension and that active recovery from exercise may reduce this risk.
Adult↗
The effect of methyl methanesulfonate (MMS)-induced excision repair on p53-dependent apoptosis in human lymphoid cells.
The tumor suppressor p53 product has been shown to play an important role in preventing carcinogenesis by at least two different mechanisms, by evoking cell cycle arrest and eliciting DNA repair on one hand, or by eliminating damaged cells by induction of apoptosis on the other hand. As a first step toward understanding the relationship between protective responses and apoptosis after genotoxic stress, we examined the effect of DNA strand breaks generated from repair processes in respect to acute cellular responses against DNA damage, and on p53-dependent apoptosis in human lymphoid cells. We used two isogenic cell lines, TK6 harboring wild-type p53, and WI-L2-NS, which carries a mutant p53. A significant difference in sensitivity was observed at 50 microg/ml methyl methane-sulfonate (MMS) between the two cell lines used. In addition, a clear p53-mediated contribution to apoptosis in MMS-induced cell death was observed. However, we did not observe any differences in repair of MMS-lesions, as determined by comet assay, between the two cell lines. These data suggest that the differences in apoptosis induction in the two lines are not a reflection of differences in strand-break frequency or repair capacity.
Alkylation↗
Biventricular pacing decreases sympathetic activity compared with right ventricular pacing in patients with depressed ejection fraction.
BACKGROUND: Although there have been few studies in which the hemodynamic effects of right ventricular (RV) and left ventricular (LV) pacing were compared with those of biventricular (BV) pacing, the autonomic changes during these different pacing modes remain unknown. We hypothesized that BV pacing results in improved hemodynamics and a decrease in sympathetic nerve activity (SNA) compared with single-site pacing. METHODS AND RESULTS: Thirteen men with a mean ejection fraction of 0.28+/-0.7 were enrolled in the study. Arterial blood pressure (BP), central venous pressure (CVP), and SNA were recorded during 3 minutes of right atrial (RA)-RV, RA-LV, and RA-BV pacing at a rate 10 beats faster than sinus rhythm. BP was greater during LV (151+/-7/85+/-3 mm Hg) and BV (151+/-6/85+/-3 mm Hg) pacing than during RV pacing (146+/-7/82+/-3 mm Hg) (P:<0.05). There were no differences in CVP among all pacing modes (P:=0.27). SNA was significantly less (P:<0.02) during both LV (606+/-35 U) and BV (582+/-41 U) pacing compared with RV pacing (685+/-32 U) (P:<0.02). Although not statistically significant (P:=0. 08 to 0.14), there was a trend for patients with a narrow QRS to have a lower mean BP and higher SNA during LV pacing than during BV pacing (r=0.42 to 0.49). CONCLUSIONS: LV-based pacing results in improved hemodynamics and a decrease in SNA compared with RV pacing in patients with LV dysfunction regardless of the QRS duration.
Aged↗
Antifungal rapamycin analogues with reduced immunosuppressive activity.
Several 1,2,3,4-tetrahydro- and 7-N-hydroxycarbamate derivatives of the natural product rapamycin were prepared and assayed for their immunosuppressive and antifungal profiles. Substitutions at the 7-position indicate the possibility of a differentiated immunosuppressive to antifungal profile, whereas 40-position variants of the tetrahydro-analogues did not show similar differentiated activity.
Animals↗
Refill program using pharmacy student interns in a primary care clinic.
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Colorado↗
Selective parasympathetic denervation following posteroseptal ablation for either atrioventricular nodal reentrant tachycardia or accessory pathways.
Baroreflex gain and coronary sinus norepinephrine and epinephrine levels were measured before and immediately after radiofrequency ablation in the posteroseptal region in 9 patients with atrioventricular nodal reentrant tachycardia or posteroseptal accessory pathways. Arterial baroreflex gain was significantly reduced after radiofrequency ablation (p = 0.046), whereas coronary sinus epinephrine and norepinephrine levels did not change significantly compared with preablation levels.
Baroreflex↗