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Biomedical subjects

I Lim

Publications and source records attributed to I Lim.

At least 19 recordsLinked to original sources
PubMed2007

Cueing training in the home improves gait-related mobility in Parkinson's disease: the RESCUE trial.

OBJECTIVES: Gait and mobility problems are difficult to treat in people with Parkinson's disease. The Rehabilitation in Parkinson's Disease: Strategies for Cueing (RESCUE) trial investigated the effects of a home physiotherapy programme based on rhythmical cueing on gait and gait-related activity. METHODS: A single-blind randomised crossover trial was set up, including 153 patients with Parkinson's disease aged between 41 and 80 years and in Hoehn and Yahr stage II-IV. Subjects allocated to early intervention (n = 76) received a 3-week home cueing programme using a prototype cueing device, followed by 3 weeks without training. Patients allocated to late intervention (n = 77) underwent the same intervention and control period in reverse order. After the initial 6 weeks, both groups had a 6-week follow-up without training. Posture and gait scores (PG scores) measured at 3, 6 and 12 weeks by blinded testers were the primary outcome measure. Secondary outcomes included specific measures on gait, freezing and balance, functional activities, quality of life and carer strain. RESULTS: Small but significant improvements were found after intervention of 4.2% on the PG scores (p = 0.005). Severity of freezing was reduced by 5.5% in freezers only (p = 0.007). Gait speed (p = 0.005), step length (p<0.001) and timed balance tests (p = 0.003) improved in the full cohort. Other than a greater confidence to carry out functional activities (Falls Efficacy Scale, p = 0.04), no carry-over effects were observed in functional and quality of life domains. Effects of intervention had reduced considerably at 6-week follow-up. CONCLUSIONS: Cueing training in the home has specific effects on gait, freezing and balance. The decline in effectiveness of intervention effects underscores the need for permanent cueing devices and follow-up treatment. Cueing training may be a useful therapeutic adjunct to the overall management of gait disturbance in Parkinson's disease.

Aged↗
PubMed2006

The effect of rhythmic somatosensory cueing on gait in patients with Parkinson's disease.

BACKGROUND AND AIMS: Gait and gait related activities in patients with Parkinson's disease (PD) can be improved with rhythmic auditory cueing (e.g. a metronome). In the context of a large European study, a portable prototype cueing device was developed to provide an alternative for rhythmic auditory cueing: rhythmic somatosensory cueing (RSC, a miniature vibrating cylinder attached to the wrist). We investigated whether PD patients could adapt their walking pattern using RSC under conditions of changing walking speed and the presence of potentially distracting visual flow while walking on a treadmill. METHODS: A total of 17 patients with PD participated (mean age 63.4+/-10.3 years; Hoehn-Yahr score 2.5+/-0.9, mean Unified Parkinson's Disease Rating Scale score 49.8+/-13.7, mean disease duration 7.7+/-5.1 years). They performed systematic walking speed manipulations under 4 conditions in a random order: (1) no cue, no visual flow, (2) no cue, visual flow, (3) cue, no visual flow and (4) cue, visual flow. Visual flow in the form of a virtual corridor that moved at the current walking speed was projected on a 2 x 2 m rear-projection screen. The cueing rhythm was set at -10% of preferred stride frequency at each speed. Stride frequency was assessed using peaks in the trajectories of thigh sagittal plane segmental angles. RESULTS: Walking with RSC resulted in lower stride frequencies, and thus larger step lengths (p-values <0.05), regardless of walking speed. The presence of visual flow did not impair the use of RSC, as evidenced by the lack of differences between conditions 3 and 4 (p>0.05). CONCLUSION: Rhythmic somatosensory cueing may be a viable alternative for auditory cueing and is robust to changes in walking speed and visual distractors.

Aged↗
PubMed2005

The effects of visual rhythms and optic flow on stride patterns of patients with Parkinson's disease.

This study was aimed at determining the effects of rhythmic visual cueing under changing visual conditions on stride frequency in patients with Parkinson's disease (PD; n = 21) and healthy age matched controls (n = 7) while walking at different speeds on a treadmill. Stride frequency and stride length in patients with PD as well as controls were not rigidly coupled to walking speed and could be manipulated with walking speed as well as by using spatial and temporal rhythmic visual cues.

Aged↗
PubMed2005

Nitric oxide stimulates a large-conductance Ca-activated K+ channel in human skin fibroblasts through protein kinase G pathway.

In order to investigate the large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel and determine the effects of nitric oxide (NO) on the channel in human skin fibroblasts, we performed electrophysiological patch clamp recordings on 5th-passage cells of human genital skin cultures. The whole-cell outward K(+) current was increased with depolarization, and proved to be sensitive to NS1619 (a selective BK(Ca) channel activator) and iberiotoxin (a specific BK(Ca )channel inhibitor). The single-channel currents showed 226 pS of mean conductance in symmetrical K(+). Sodium nitroprusside (SNP; an NO donor) significantly increased the K(+) current amplitude in the whole-cell mode, and open probability of the channel (NPo) in the cell-attached mode, but not in the inside-out mode. S-nitroso-N-acetylpenicillamine (an NO donor) and 8-Br-cGMP (a membrane-permeant cGMP analogue) also increased the BK(Ca )channel activity. The stimulatory effect of SNP on BK(Ca) channels was inhibited by pretreatment with 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (a soluble guanylyl cyclase inhibitor), or KT5823 [a specific protein kinase G (PKG) inhibitor]. Cytoplasmic PKG also increased the channel activity in inside-out patches. In conclusion, the present data indicate that BK(Ca) channels constitute a significant fraction of K(+) current in human skin fibroblasts, and that NO increases NPo of BK(Ca) channels, which are mediated via the cGMP/PKG pathway, without direct effects on the channel.

Benzimidazoles↗
PubMed2005

Effects of external rhythmical cueing on gait in patients with Parkinson's disease: a systematic review.

OBJECTIVE: To critically review studies evaluating the effects of external rhythmical cueing on gait in patients with Parkinson's disease. METHODS: Articles published from 1966 to January 2005 were searched by two physiotherapists in MEDLINE, PiCarta, PEDRo, Cochrane, DocOnline, CINAHL and SUMSEARCH. To be included, articles had to investigate the effects of external rhythmical cueing (i.e., auditory, visual or tactile cueing) on gait parameters in patients with idiopathic Parkinson's disease. Both controlled and noncontrolled studies were included. Based on the type of design and methodological quality a meta-analysis or best-evidence synthesis was applied. RESULTS: Twenty-four studies (total number of patients = 626) out of the 159 screened studies were evaluated in this systematic review. Two out of 24 were randomized controlled trails (RCT), both of high methodological quality. One RCT did not focus specifically on external rhythmical cueing of individual patients with Parkinson's disease, but on group exercises in general, including walking with cues. All other studies were pre-experimental studies. Best-evidence synthesis showed strong evidence for improving walking speed with the help of auditory cues. Insufficient evidence was found for the effectiveness of visual and somatosensory cueing. CONCLUSION: Only one high-quality study, specifically focused on the effects of auditory rhythmical cueing, suggesting that the walking speed of patients with Parkinson's disease can be positively influenced. However, it is unclear whether positive effects identified in the laboratory can be generalized to improved activities of daily living (ADLs) and reduced frequency of falls in the community. In addition, the sustainability of a cueing training programme remains uncertain.

Acoustic Stimulation↗
PubMed1999

Regulation of Drosophila FMRFamide neuropeptide gene expression.

Physiologically important peptides are often encoded in precursors that contain several gene products; thus, regulation of expression of polypeptide proteins is crucial to transduction pathways. Differential processing of precursors by cell- or tissue-specific proteolytic enzymes can yield messengers with diverse distributions and dissimilar activities. FMRFamide-related peptides (FaRPs) are present throughout the animal kingdom and affect both neural and gastrointestinal functions. Organisms have several genes encoding numerous FaRPs with a common C-terminal structure but different N-terminal amino acid extensions. We have isolated SDNFMRFamide, DPKQDFMRFamide, and TPAEDFMRFamide contained in the Drosophila FMRFamide gene. To investigate the regulation of expression of FMRFamide peptides, we generated antisera to distinguish among the three neuropeptides. We have previously reported the distribution of SDNFMRFamide and DPKQDFMRFamide. In this article, we describe TPAEDFMRFamide expression. TPAEDFMRFamide antisera stain cells in embryonic, larval, pupal, and adult thoracic and abdominal ganglia. In addition, TPAEDFMRFamide-immunoreactive material is present in a lateral protocerebrum cell in adult. Thus, TPAEDFMRFamide antisera staining of neural tissue is different from SDNFMRFamide or DPKQDFMRFamide. In addition, TPAEDFMRFamide antisera stain larval, pupal, and adult gut, while SDNFMRFamide and DPKQDFMRFamide do not. TPAEDFMRFamide immunoreactivity is present in cells stained by FMRFamide antisera. Taken together, these data support the conclusion that TPAEDFMRFamide is differentially processed from the FMRFamide polypeptide protein precursor and may act in both neural and gastrointestinal tissue.

Animals↗
PubMed1999

Neuropeptide precursor processing detected by triple immunolabeling.

Peptides that play critical physiological roles are often encoded in precursors that contain several gene products. Differential processing of a polypeptide precursor by cell-specific proteolytic enzymes can yield multiple messengers with diverse distributions and functions. We have isolated SDNFMRFamide, DPKQDFMRFamide, and TPAEDFMRFamide from Drosophila melanogaster. The peptides are encoded in the FMRFamide gene and have a common C-terminal FMRFamide but different N-terminal extensions. In order to investigate the regulation of expression of FMRFamide peptides, we generated antisera to distinguish between the structurally related neuropeptides. We established a triple-label immunofluorescence protocol using antisera raised in the same host species and mapped the neural distribution of SDNFMRFamide, DPKQDFMRFamide, and TPAEDFMRFamide. Each peptide has a unique, nonoverlapping cellular expression pattern, suggesting that the precursor is differentially processed. Thus, our data indicate that D. melanogaster contains cell-specific proteolytic enzymes to cleave a polypeptide protein precursor, resulting in unique expression patterns of neuropeptides.

Animals↗
PubMed1999

Antisera to multiple antigenic peptides detect neuropeptide processing.

Peptides act as critical messengers of essential physiological function. Frequently, several peptides are encoded in the same precursor and, often, there is structure relatedness among the gene products. The complexity of protein precursors and presence of homologous peptides raises issues about regulation of gene expression and function of structurally-related peptides. We have determined the cellular location of DPKQDFMRFamide and SDNFMRFamide encoded in the Drosophila FMRFamide gene. We raised antisera that distinguish between the two peptides and conducted double label immunostaining utilizing antisera raised in the same host species. We found that DPKQDFMRFamide and SDNFMRFamide are present in distinct distribution patterns. We also established that the peptides are present in cells stained by FMRFamide antisera. Thus, our data are consistent with the conclusion that Drosophila contains cell-specific proteolytic processing enzymes capable of posttranslationally cleaving a polypeptide protein precursor to yield unique expression patterns of neuropeptides that may have diverse activities.

Animals↗
PubMed1997

Dromyosuppressin and drosulfakinin, two structurally related Drosophila neuropeptides, are uniquely expressed in the adult central nervous system.

Drosophila myosuppressin (TDVDHVFLRFamide; DMS) and sulfakinin (FDDYGHMRFamide; DSK) have similar C-terminal structures. To determine the neuronal expression patterns of these structurally related peptides, we have generated DMS- and DSK-specific antisera to multiple antigenic peptides and performed double-label immunochemistry with antisera raised on different animals of the same species host animal. Our data indicate that DMS and DSK staining patterns in the adult central nervous system are unique and nonoverlapping.

Amino Acid Sequence↗
PubMed1997

Multiple antigenic peptides designed to structurally related Drosophila peptides.

We have isolated TDVDHVFLRFamide (DMS), FDDYGHMRFamide (DSK), and DPKQDFMRFamide from Drosophila melanogaster. These peptides, structurally related by a common C-terminus -XRFamide, where X = L or M, are encoded by three different genes. To determine cellular expression, we have generated antisera to multiple antigenic peptides and performed double-label immunofluorescence using antisera raised in the same species host animal. Our results indicate that DMS and DSK immunoreactive materials have unique, non-overlapping expression patterns, while DMS and DPKQDFMRFamide immunoreactive materials colocalize in two superior protocerebrum neurons, and DSK and DPKQDFMRFamide immunoreactive materials colocalize in one superior protocerebrum neuron, one subesophageal ganglion neuron, and three thoracic ganglia neurons.

Animals↗
PubMed1995

Cellular expression of the Drosophila melanogaster FMRFamide neuropeptide gene product DPKQDFMRFamide. Evidence for differential processing of the FMRFamide polypeptide precursor.

DPKQDFMRFamide is one of five different FMRFamide-containing peptides encoded in the Drosophila FMRFamide gene. To study the cellular expression of DPKQDFMRFamide, we have generated antisera to DPKQD, the N-terminal sequence of the peptide, to avoid crossreactivity with other -FMRFamide-containing peptides. The antisera were purified and the specificity characterized. DPKQDFMRFamide immunoreactive material is first observed in the embryonic central nervous system (CNS) in one cell of the subesophageal ganglion and one cell in each of the three thoracic ganglia. This pattern of expression is observed in larval, pupal, and adult neural tissue, albeit with increased signal intensity. In larva, pupa, and adult, additional cells in the superior protocerebrum, a thoracic ganglion, and an abdominal ganglion express DPKQDFMRFamide immunoreactive material. Immunoreactivity is observed in a cell in the lateral protocerebrum of pupa and adult and cells in the optic lobe of adult. No immunoreactive material was observed in gut tissue. DPKQDFMRFamide antisera stain a subset of cells previously identified by in situ hybridization and immunocytochemistry to express the FMRFamide transcript and polypeptide precursor. These data suggest that the Drosophila FMRFamide polypeptide precursor undergoes differential processing to produce DPKQDFMRFamide immunoreactive material in a limited number of cells expressing the FMRFamide precursor.

Amino Acid Sequence↗
PubMed1993

Rule based artificial intelligence expert system for determination of upper extremity impairment rating.

Quantitative evaluation of upper extremity impairment, a percentage rating most often determined using a rule based procedure, has been implemented on a personal computer using an artificial intelligence, rule-based expert system (AI system). In this study, the rules given in Chapter 3 of the AMA Guides to the Evaluation of Permanent Impairment (Third Edition) were used to develop such an AI system for the Apple Macintosh. The program applies the rules from the Guides in a consistent and systematic fashion. It is faster and less error-prone than the manual method, and the results have a higher degree of precision, since intermediate values are not truncated.

Arm Injuries↗
PubMed1990

Comparative evaluation of nonradiometric BACTEC and improved oxoid signal blood culture systems in a clinical laboratory.

The BACTEC NR660 blood culture system, which uses infrared spectroscopy to detect carbon dioxide generated by bacterial growth, was compared with the new medium formulation of the Oxoid Signal system. Two trials were conducted: a comparative study of 88 organisms in simulated blood cultures and a clinical trial of 3,321 paired patient blood culture samples. Both trials showed that overall the BACTEC system performed better in the recovery of organisms. The Oxoid system was unable to detect by signal the growth of the majority of yeasts, nonfermentative gram-negative bacilli, Neisseria meningitidis, Nocardia spp., and Corynebacterium jeikeium. There were no significant differences in the yield of Staphylococcus spp., members of the family Enterobacteriaceae, Streptococcus spp., or anaerobic organisms. BACTEC detected growth more quickly than did the Oxoid system; 61% of the isolates were detected by BACTEC at 24 h, while 49% of the isolates were detected by Oxoid. The Oxoid system had a high proportion (58.5%) of false-positives, compared with 7.7% for the BACTEC system. Despite the new medium formulation of the Oxoid system, its performance is still not equivalent to that of the BACTEC system.

Bacteria↗
PubMed1990

Stereoselective sulfoxidation of a series of alkyl p-tolyl sulfides by microsomal and purified flavin-containing monooxygenases.

The enantioselective sulfoxidation of a series of alkyl p-tolyl sulfides was compared using purified rabbit lung and mini-pig liver flavin-containing monooxygenase (FMO). Analysis was performed by chiral-phase high pressure liquid chromatography, which afforded baseline resolution of each pair of enantiomers. The extent of enantioselective sulfoxidation was found to be a function of (a) the isozyme employed, (b) the steric bulk of the alkyl substituent, and (c) pH. At pH 8.5, rabbit lung FMO catalyzed the oxidation of methyl, ethyl, propyl, and isopropyl sulfides to products with greater than 99, 91, 85, and 63% (R)-(+)-stereochemistry, respectively. Corresponding values for the mini-pig liver form were 91, 82, 72, and 41% (R)-(+)-sulfoxide. The stereochemical profile obtained with the isolated rabbit lung form could be duplicated exactly in microsomal preparations if precautions were taken to abolish the contribution that P-450 makes to net stereochemistry. It was noted that increasing the reaction mixture pH from 8.5 to 10 led to a decrease in the stereochemical purity of products obtained from the lung form. In contrast, the stereochemical profile obtained with the isolated mini-pig liver form could not be exactly duplicated in suitably treated microsomal preparations. No evidence for multiple forms of mini-pig liver FMO was obtained, and it was concluded that discrepancies between microsomal and purified FMO metabolic profiles were most consistent with a minor modification to active site geometry occurring during purification of the mini-pig form. These data show that the active site chirality of rabbit lung and mini-pig liver FMO is largely retained following removal from microsomal membranes. Qualitative similarities in the structure-activity relationships exhibited by microsomal or purified FMO from rabbit lung and mini-pig liver suggest some conservation of active site geometry between these two otherwise distinct FMOs. Quantitative differences in the structure-activity relationships exhibited by the two FMO forms indicate that analysis of product stereochemistry may be a useful method for the discrimination of catalytically distinct FMO isozymes.

Animals↗
PubMed1989

A prospective hospital study of the aetiology of community-acquired pneumonia.

In a one-year prospective study of 106 adults (mean age, 60 years) who were admitted to hospital with community-acquired pneumonia, an aetiological diagnosis was made in 82 (77%) patients. Streptococcus pneumoniae was considered to be responsible for 44 (42%) and respiratory viruses for 19 (18%) infections. Other aetiological agents that were found in a smaller number of patients included Haemophilus influenzae (9% of patients), enteric Gram-negative bacilli (8% of patients), Staphylococcus aureus (3% of patients), Legionella spp. (3% of patients), Mycobacterium tuberculosis (3% of patients), Mycoplasma pneumoniae (8% of patients) and Chlamydia psittaci (5% of patients). The mortality was 10% and was related significantly to increasing age and to coexisting heart and lung disease. Antibiotic treatment that was commenced before admission to hospital and investigations were undertaken reduced significantly the isolation rate of susceptible bacterial pathogens. The Gram-stained smear of sputum was valuable in establishing a tentative diagnosis of bacterial pneumonia. The most-useful tests in making an early diagnosis proved to be those which detected pneumococcal and mycoplasmal antigens, blood cultures and culture of sputum for appropriate bacterial pathogens.

Adolescent↗