Locomotor milestones and babywalkers: cross sectional study.
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Child Development↗
Biomedical subjects
M Garrett
Publications and source records attributed to M Garrett.
Functional instability of the ankle: differences in patterns of ankle and knee movement prior to and post landing in a single leg jump.
The aim of this study was to investigate motor control in subjects with functional instability of the ankle joint. This was achieved by analysing patterns of lower extremity motion prior to and immediately following landing during single leg jumping in subjects with functional instability of the ankle. Fourteen subjects with unilateral functional instability and 10 healthy control subjects performed single leg jumps from a 40 cm height whilst angular displacement of their ankle and knee joints were recorded. Subjects with functional instability demonstrated significantly greater ankle dorsiflexion over the period encompassing 10 ms pre landing to 20 ms post landing (p < 0.05). They also exhibited a significantly greater level of knee flexion than controls over the period from 20 ms pre landing to 60 ms post landing (p < 0.05). The timing of these significant differences leads us to conclude that they do not arise as a result of reflexively mediated peripheral events following landing.
Adolescent↗
Semantic factors in the production of number agreement.
This paper examines the role of semantic factors in the production of subject-verb number agreement. As an ostensibly grammatical process, number agreement provides an interesting case for examining the flow and interaction of semantic and syntactic information through the language-production system. Using a sentence-completion task, agreement errors can be elicited from subjects by presenting them with sentence fragments containing a complex noun-phrase, in which the nonhead noun is plural (e.g., The key to the cabinets ... WERE missing.). Previous research has demonstrated that the probability of making an error can be affected by varying the properties of the nouns in the complex noun phrase. By investigating which variables do and do not affect error rates, constraints on the flow of information through the production system can be inferred. In three experiments, we investigated the possible effects of three different semantic manipulations of the nouns in the complex NP: animacy, semantic overlap, and plausibility of modification by the sentence predicate. We found that both animacy and semantic relatedness had reliable effects on error rates, indicating that the mechanism involved in implementing agreement cannot be blind to semantic information. However, the plausibility with which each noun could serve as the subject of the sentence predicate had no effect on error rates. Taken together, these results suggest that while semantic information is visible to the agreement mechanism, there are still constraints on when this information can affect the process. Specifically, it may be the case that only information contained within the complex NP is considered for the purposes of implementing agreement.
Humans↗
Increased H(max):M(max) ratio in community walkers poststroke without increase in ankle plantarflexion during walking.
OBJECTIVE: To investigate whether changes in H-reflex response at midswing and midstance are related to excessive plantarflexion during walking in community walkers poststroke compared with control subjects without stroke. DESIGN: Survey of functional walking handicap in a random sample of an annual stroke cohort followed by H-reflex and M(max) testing of a smaller sample. SETTING: Community and laboratory testing. PARTICIPANTS: Forty individuals with stroke (IWS group) completed the functional walking handicap survey, 10 of whom agreed (with 10 age-matched controls) to enroll in a study of of the H(max):M(max) ratio in soleus during walking. INTERVENTION: Electromyography during treadmill walking. MAIN OUTCOME MEASURES: Functional Walking Handicap Scale, soleus H(max):M(max) ratio, and the ankle joint's angle of displacement. RESULTS: Nine of the 10 stroke patients were community walkers. All had significantly (p <.05) more variable ankle movement during walking than the controls. The H(max):M(max) ratio was significantly (p <.01) increased in the IWS group because of a decrease in M(max) response without significant (p >.05) increase in H(max) response. CONCLUSIONS: Individuals with community-level walking ability after stroke have significantly (p <.05) less repeatability of ankle joint movement than controls at both midswing and midstance. Simultaneous soleus H(max) and M(max) testing showed a significant (p <.01) reduction in the H(max) and H(max):M(max) ratio at midswing in controls only. This inhibition at midswing was lost by the IWS group without significant increase in H(max), suggesting that central synaptic excitability was within the normal range, and possibly accounting for the absence of excessive ankle plantarflexion during walking in the IWS group with community level walking ability.
Aged↗
Current use of outcome measures for stroke and low back pain rehabilitation in five European countries: first results of the ACROSS project.
Objectives were to obtain a view on the current use of outcome measures for stroke and low back pain rehabilitation in five European countries. A postal questionnaire, comparable for different cultural situations, was distributed in August 1998 to 581 rehabilitation facilities in Ireland, Germany, Italy, Austria and the Netherlands. Of these, 102 settings responded. In stroke rehabilitation the Barthel Index is the dominant outcome measure, followed by the Functional Independence Measure and the Frenchay Activities Index. Besides the Visual Analogue Scale, the most used outcome measures in low back pain rehabilitation were the Oswestry Pain Disability Questionnaire and the Roland Disability Questionnaire. Outcome measures are more frequently used in stroke than in low back pain rehabilitation. The purpose of use is mainly for the measurement of effectiveness, while a relation with quality management is seldom made. There appears to be little agreement on which outcome measures to use. Little attention was found to have been given to the assessment of handicap, quality of life and patient satisfaction.
Austria↗
Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases.
The identification of 8-ethyl-2-phenylamino-8H-pyrido[2, 3-d]pyrimidin-7-one (1) as an inhibitor of Cdk4 led to the initiation of a program to evaluate related pyrido[2, 3-d]pyrimidin-7-ones for inhibition of cyclin-dependent kinases (Cdks). Analysis of more than 60 analogues has identified some clear SAR trends that may be exploited in the design of more potent Cdk inhibitors. The most potent Cdk4 inhibitors reported in this study inhibit Cdk4 with IC(50) = 0.004 microM ([ATP] = 25 microM). X-ray crystallographic analysis of representative compounds bound to the related kinase, Cdk2, reveals that they occupy the ATP binding site. Modest selectivity between Cdks is exhibited by some compounds, and Cdk4-selective inhibitors block pRb(+) cells in the G(1)-phase of the cell division cycle.
Adenosine Triphosphate↗
Medicare: healthier for now. But a windfall masks the coming problem.
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Aged↗
Dorzolamide, visual function and ocular hemodynamics in normal-tension glaucoma.
The purpose of this study was to determine how a topical carbonic anhydrase inhibitor, dorzolamide, alters visual function and ocular blood flow in persons with normal-tension glaucoma. Eighteen normal tension glaucoma patients, after washout of other ocular medications, were treated for four weeks with 2% dorzolamide, three times daily. A control group of eleven other normal-tension glaucoma patients received placebo eye drops. Patients were studied before treatment, and after two and four weeks of treatment. Each study included assessment of central visual function (contrast sensitivity), intraocular pressure (IOP), and several aspects of ocular hemodynamics, including measures of retinal arteriovenous passage time, retinal arterial and venous diameters, and flow velocities in the ophthalmic, central retinal, and posterior ciliary arteries. Dorzolamide significantly reduced IOP at two and four weeks (each p<0.01), and at the same time increased contrast sensitivity at both three and six cycles per degree (each p<0.05). Neither of these variables changed significantly in the control group. Dorzolamide also accelerated retinal arteriovenous passage time of fluorescein dye, at constant retinal arterial and venous diameters (p<0.05), but failed to change flow velocities in any retrobulbar vessel. The ability of dorzolamide to improve contrast sensitivity in persons with normal-tension glaucoma may be related to either IOP reduction or altered ocular perfusion.
Blood Pressure↗
Glaucoma patients demonstrate faulty autoregulation of ocular blood flow during posture change.
BACKGROUND/AIMS: Autoregulation of blood flow during posture change is important to ensure consistent organ circulation. The purpose of this study was to compare the change in retrobulbar ocular blood flow in glaucoma patients with normal subjects during supine and upright posture. METHODS: 20 open angle glaucoma patients and 20 normal subjects, similar in age and sex distribution, were evaluated. Blood pressure, intraocular pressure, and retrobulbar blood velocity were tested after 30 minutes of sitting and again after 30 minutes of lying. Retrobulbar haemodynamic measures of peak systolic velocity (PSV), end diastolic velocity (EDV), and resistance index (RI) were obtained in the ophthalmic and central retinal arteries using colour Doppler imaging (CDI). RESULTS: When changing from the upright to supine posture, normal subjects demonstrated a significant increase in OA EDV (p = 0.016) and significant decrease in OA RI (p = 0.0006) and CRA RI (p = 0.016). Glaucoma patients demonstrated similar changes in OA measures of EDV (p = 0.02) and RI (p = 0.04), but no change in CRA measures. CONCLUSION: Glaucoma patients exhibit faulty autoregulation of central retinal artery blood flow during posture change.
Blood Flow Velocity↗
Phase-dependent inhibition of H-reflexes during walking in humans is independent of reduction in knee angular velocity.
The purpose of this investigation was to investigate whether reduction in impulses arising from stretch of the quadriceps by restricting rapid knee flexion in early swing would affect inhibition of the H-reflex during swing. The contribution of afferent input arising from knee angular velocity to phase-dependent modulation of short-latency responses in the soleus was studied by simultaneously measuring joint velocity and soleus H-reflex responses at midstance and midswing phases of treadmill walking in 15 normal subjects. Stimulus strength was varied so that both maximal M and H waves were identified in each subject at midswing and midstance with the knee unrestricted (UK) and with knee movement restricted (RK), using a full leg bivalved cast to immobilize the knee joint. All subjects exhibited short-latency reflex responses in the soleus muscle. The H/M ratio at midswing was significantly reduced compared with midstance under both UK and RK walking conditions (P < 0.0001). When compared with UK walking, knee joint angular velocity during RK walking was significantly reduced at midswing (P < 0.001) and midstance (P < 0.005) compared with UK. There were, however, no significant differences in H/M ratios at midswing and midstance between UK and RK walking tests. Inhibition of the H-reflex in the soleus muscle during swing was not affected by significant reduction in knee angular velocity. These results indicate that the sensory input from changes in angular velocity at the knee does not lay the inhibitory foundation of phase-related reflex modulation in the ankle extensors during walking as suggested by Brooke and colleagues.
Adult↗
Linkage mapping of rat chromosome markers generated from chromosome-sorted DNA.
Ninety-one new rat microsatellite chromosome markers were generated through screening chromosome-sorted DNA libraries. Of the 91 markers, 29 have been mapped to various rat chromosomes. Because of a lack of suitable polymorphisms among the appropriate rat strains of our interest, the remaining 62 markers are still unassigned, but are likely to be useful for genotyping different rat strains employed to study a wide range of genetic traits other than blood pressure. With these new markers, two genes, encoding alpha 2 adrenergic receptor, class II and gastric H,K-ATPase beta subunit, were mapped to regions on rat Chromosomes (Chrs) 1 and 16 respectively.
Animals↗
Pure endotoxin does not pass across the intestinal epithelium in vitro.
Numerous reports suggest that endotoxin (LPS) may play a central role in triggering the inflammatory cascade that leads to the systemic inflammatory response syndrome. Although conditions that promote bacterial translocation in vivo may also facilitate direct translocation of LPS, the exact mechanisms by which LPS crosses the intestinal barrier to reach the systemic circulation are unknown. This study was designed to determine whether pure endotoxin could pass across injured rat ileal mucosa in the Ussing chamber. Sprague-Dawley rats were subjected to mild or severe hemorrhagic shock following carotid artery cannulation, and then resuscitated. Control animals underwent carotid artery cannulation only (sham-shock). Bacterial translocation to the mesenteric lymph nodes, liver, or spleen was measured after 24 h. Transmucosal passage of fluorescein isothiocyanate (FITC)-labeled E. coli C-25, or FITC-conjugated LPS was measured in the Ussing chamber. Intestinal membranes were examined by light and confocal laser microscopy. Severe hemorrhagic shock resulted in a 60% mortality rate and a 100% incidence of bacterial translocation in surviving animals. Sham-shock rats had a 100% survival rate and a 33% incidence of bacterial translocation. Transmucosal passage of FITC-E. coli C-25 was similar in both groups; however, passage of FITC-LPS was never detected. Histologic analysis confirmed mucosal injury to the intestinal epithelium of rats subjected to severe hemorrhagic shock, and confocal laser microscopy demonstrated passage of FITC-E. coil C-25, but not of FITC-LPS across the ileal membranes. Disruption of the intestinal epithelium with a potent mucolytic agent did not result in significant increase in transmucosal passage of FITC-LPS. We conclude that pure LPS does not pass across the intestinal mucosa in vitro. Transmucosal passage of LPS in vivo may be due, at least in part, to the release of bacterial cell wall fragments containing LPS from killed bacteria that had previously translocated.
Animals↗
Immunoglobulin A supplementation abrogates bacterial translocation and preserves the architecture of the intestinal epithelium.
BACKGROUND: Breast milk has been shown to prevent gut-origin infections in neonates through undefined mechanisms. Putative protective factors in breast milk include immunoglobulin (Ig)A, IgG, and lactoferrin. We examined their role in bacterial translocation in neonatal rabbits. METHODS: IgA, IgG, and lactoferrin were isolated from rabbit breast milk through gel filtration and ion-exchange chromatography. Neonates were randomized to receive breast milk, formula alone, or formula supplemented with IgA, IgG, or lactoferrin. Quantitative cultures were performed on day 7 for bacterial translocation. Hematoxylin-eosin-stained sections of distal ileum were examined by light microscopy. Transmucosal bacterial passage was determined in vitro, and the ileal mucosal membranes were examined by confocal microscopy. RESULTS: IgA supplementation abrogated bacterial translocation. IgG and lactoferrin had no significant effect. Neonates that received IgA or breast milk gained more weight than those in the other groups. IgA reduced transmucosal bacterial passage in vitro. In contrast to the normal-appearing distal ileum of neonates fed breast milk, intestinal epithelium from neonates that received formula or formula with IgG or IgA demonstrated prominent vacuoles by light microscopy. Those fed formula alone or formula with lactoferrin had slightly shortened villi. CONCLUSIONS: IgA supplementation prevents bacterial translocation by enhancing gut mucosal barrier function.
Animals↗
Human neutrophil elastase activates human factor V but inactivates thrombin-activated human factor V.
The effect of human neutrophil elastase (HNE) on human factor V (F.V) or alpha-thrombin-activated human factor V (F.Va) was studied in vitro by prothrombinase assays, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and NH2-terminal sequence analysis. Incubation of F.V (600 nmol/L) with HNE (2 nmol/L) in the presence of Ca2+ resulted in a time-dependent increase in its cofactor activity. In contrast, treatment of F.Va (600 nmol/L) with HNE (60 nmol/L) in the presence of Ca2+ resulted only in a time-dependent decrease in its cofactor activity. Under the conditions of these experiments, the maximum extent of F.V activation accomplished by incubation with HNE was approximately 65% to 70% of that observed with alpha-thrombin in presence of Ca2+. The extent of both the HNE-dependent enhancement in F.V cofactor activity and the HNE-dependent decrease in F.Va cofactor activity was not influenced by the addition of phosphatidylcholine/phosphatidylserine (PCPS) vesicles (50 micromol/L). The HNE-derived cleavage products of F.V, which correlated with increased cofactor activity, as demonstrated by SDS-PAGE under reducing conditions, were different from those generated using alpha-thrombin. Treatment of F.V (600 nmol/L) with HNE (2 nmol/L) in the presence of Ca2+ resulted in the production of three closely spaced doublets of: 99/97, 89/87, and 76/74 kD whose appearance over time correlated well with the increased cofactor activity as judged by densitometry. Treatment of F.Va (600 nmol/L) with HNE (60 nmol/L) in the presence of Ca2+ resulted in the cleavage of both the 96 kD heavy chain and the 74/72 kD light chain into products of: 56, 53, 35, 28, 22, and 12 kD. Although densitometry indicated that both the heavy and light chains of F.Va were hydrolyzed by HNE, cleavage of the 96 kD heavy chain was more extensive during the time period (10 to 30 minutes) of the greatest loss of F.Va cofactor activity. NH2-terminal sequence analysis of F.V treated with HNE indicated cleavage at Ile819 and Ile1484 under conditions during which the procofactor expressed enhanced cofactor activity in the prothrombinase complex. NH2-terminal sequence analysis of F.Va treated with HNE indicated cleavage at Ala341, Ile508, and Thr1767 under conditions, which the cofactor became inactivated, as measured by prothrombinase activity. The activation and inactivation cleavage sites are close to those cleaved by the physiological activator and inactivator of F.V and F.Va, namely alpha-thrombin (Arg709 and Arg1545) and Activated Protein C (APC) (Arg306 and Arg506), respectively. These results indicate that HNE can generate proteolytic products of F.V, which initially express significantly enhanced procoagulant cofactor activity similar to that observed following activation with alpha-thrombin. In contrast, HNE treatment of F.Va resulted only in the loss of its cofactor activity, but again, this is similar to that observed following inactivation by APC.
Calcium↗
Interactions of nucleotide release factor Dss4p with Sec4p in the post-Golgi secretory pathway of yeast.
SEC4 is an essential gene encoding a small GTPase that is involved in Golgi to cell surface transport in Saccharomyces cerevisiae and is a paradigm for studies on the mode of action of Rab proteins. We describe here the features of interaction of Sec4p with the accessory protein Dss4p. Dss4p is found both on membranes and in the cytosol; however, it is the membrane fraction that is complexed to Sec4p. Dss4p, like its mammalian counterpart, Mss4, binds zinc, and disruption of the zinc-binding site disrupts the ability of the protein to interact with Sec4p. DSS4 overexpression can rescue the lethal phenotype of two alleles of SEC4, corresponding to dominant mutations of Ras. We demonstrate that this suppression is due to the ability of Dss4p to form a tight complex with the mutant forms of Sec4p and hence sequester the mutant protein from its inhibitory effect. These results imply an in vivo role for Dss4p as a guanine nucleotide dissociation stimulator. In vitro the protein has the ability to stimulate the dissociation rate of both GDP and GTP from Sec4p. We examined the relationship of GDI1 and DSS4 with SEC4 both genetically and biochemically. These results exclude a role for DSS4 in the recruitment of Sec4p/GDI onto membranes.
Alleles↗
Pseudomonas aeruginosa lipopolysaccharide binds galectin-3 and other human corneal epithelial proteins.
The aim of this study was to test whether galectin-3 is present in human corneal epithelium and whether lipopolysaccharide (LPS) purified from Pseudomonas aeruginosa ATCC 19660 binds to this animal lectin and/or to another human corneal epithelial protein(s) (HCEP) and to confirm which component of LPS (inner or outer core or lipid A) is important in bacterial binding by using the eye in organ culture. LPS isolated and purified from P. aeruginosa ATCC 19660 and a commercial LPS (serotype 10) differed in polyacrylamide gel analysis but bound similarly to blotted HCEP. Binding was determined to be a receptor-ligand type of interaction by the solid-phase assay, because it was both specific and saturable. Several LPS binding proteins in HCEP were identified by an overlay method. Western blotting with antibody against galectin-3 revealed the presence of this protein in both freshly isolated and cultured transformed human corneal epithelium. Binding inhibition assays showed that antibody specific for the outer core region of LPS and an anti-galectin antibody significantly inhibited bacterial binding in vitro. These data provide further evidence that LPS is an important adhesin of P. aeruginosa, that it binds to protein receptor molecules in HCEP, that one of the LPS binding proteins is galectin-3, and that the outer core portion of the molecule appears to be critical for LPS binding to the eye.
Antigens, Differentiation↗
Paclitaxel/5-fluorouracil/leucovorin in metastatic breast cancer: a Vanderbilt Cancer Center phase II trial.
Fifty-five women with metastatic breast cancer were treated with a regimen consisting of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 175 mg/m2 administered intravenously over 3 hours on day 1 only plus leucovorin given intravenously over 30 to 60 minutes followed by 5-fluorouracil 350 mg/m2 via intravenous push on days 1 to 3 every 28 days for six cycles. Eight patients were chemotherapy naive. Of 47 previously treated women, 30 had received anthracyclines. Fifty-two patients were evaluable for response. Three (6%) experienced a complete response and 24 (46%) had a partial response, for an overall response rate of 52%. Patients previously exposed to doxorubicin had a response rate similar to those with no prior doxorubicin exposure (50% v 54%, respectively). The median duration of response was 8.6 months and median survival was 17.7 months. Toxicity was modest, with grade 3 or 4 neutropenia observed in only 5.5% (15 of 274) of cycles. Preliminary results indicate that paclitaxel/5-fluorouracillleucovorin is an active, well-tolerated regimen for treating metastatic breast cancer.
Adult↗
Inhibition of nitric oxide with aminoguanidine reduces bacterial translocation after endotoxin challenge in vivo.
BACKGROUND: Administration of lipopolysaccharide (LPS) has been shown to increase bacterial translocation (BT) in vivo and in vitro. In addition, LPS upregulates inducible nitric oxide synthase expression in the intestinal epithelium-a phenomenon that can either enhance microbial killing, or alternatively, promote BT by impairing the gut barrier. OBJECTIVE: To determine the effect, if any, of an inhibitor of nitric oxide synthase, namely, aminoguanidine (AG), on BT after LPS challenge. DESIGN: Sprague-Dawley rats were randomized to receive either AG or normal saline solution via subcutaneously placed osmotic pumps (Alzet), followed 18 hours later by LPS injection (5 mg/kg or 20 mg/kg intraperitoneally). Quantitative cultures of the cecum, mesenteric lymph nodes, liver, and spleen were obtained, and plasma nitrite and nitrate levels were measured at 24 hours. Transmembrane potential difference and mucosal permeability to fluorescein isothiocyanate-labeled dextran and fluorescein isothiocyanate-labeled Escherichia coli C25 were measured in the Using chamber. The intestinal membrane was examined by light, transmission electron, and confocal laser microscopy. RESULTS: Rats that were given high-dose LPS had elevated levels of nitrite and nitrate and a 100% incidence of BT. In contrast, AG infusion significantly reduced both BT (22%) and nitrite and nitrate levels. Animals that received LPS and normal saline solution had a significantly lower transmembrane potential difference than those that received LPS and AG. High-dose LPS resulted in sloughing of the apical enterocytes at the villus tips where bacterial entry seemed to occur, as seen with confocal laser microscopy. CONCLUSIONS: Inhibition of nitric oxide production with AG decreases BT after high-dose LPS challenge. The mechanism may involve increased cellular viability and decreased damage to the gut mucosal barrier in rats that receive AG.
Animals↗