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Biomedical subjects

J Ide

Publications and source records attributed to J Ide.

At least 19 recordsLinked to original sources

Compression and stretching of the brachial plexus in thoracic outlet syndrome: correlation between neuroradiographic findings and symptoms and signs produced by provocation manoeuvres.

In order to investigate the mechanism of nerve irritation in thoracic outlet syndrome (TOS), we studied 150 patients who presented with symptoms of neurologic TOS between 1985 and 1999. They first performed various provocative physical manoeuvres and then underwent injection of contrast medium into the supraclavicular part of the brachial plexus. Several of the provocative manoeuvres were then repeated and radiographs were again obtained. Based on the neuroradiographs, we identified three subsets of patients; those with only compression (type 1 TOS, n=27, 18%), those with combined compression and stretching (type 2 TOS, n=111, 74%), and those with only stretching (type 3 TOS, n=12, 8%). We were able to correlate the neuroradiological subsets with symptoms elicited by pre-radiographic provocative manoeuvres; in 92 patients (61%) these were elicited by traction manoeuvres. We conclude that stretching is an important factor of nerve irritation in TOS.

Adolescent↗

The implication of repeated versus continuous strain on nerve function in a rat forelimb model.

We studied the effect of repeated and continuous nerve strain using a rat forelimb model to investigate whether an innocuous level of strain applied continuously affects nerve function when applied repeatedly. We used the rat medial cord of the brachial plexus and assessed the effects of strain by studying nerve histology (blood-nerve barrier), function (grasping strength), and electrophysiology. Continuous stretching was applied to the rat forelimb for 1 hour at 2 N. After this strain neither histologic analysis, grasping strength, nor electrophysiologic analysis revealed any effect. We then applied repeated strain at both 60 and 120 times per hour; after the latter strain abnormalities in histology, grasping strength, and nerve conduction were identified. There results suggest that a small nerve strain applied repeatedly results in nerve dysfunction. Our data may help explain the cause of nonspecific neural symptoms in the upper extremities of patients with no objective findings.

Animals↗

Symptoms and signs of irritation of the brachial plexus in whiplash injuries.

We investigated the incidence of evidence of irritation of the brachial plexus in 119 patients with whiplash injuries sustained in road-traffic accidents. We compared the symptoms, physical signs, autonomic status, psychological status and findings from radiographs of the cervical spine using examination charts and a modified Cornell Medical Index Health questionnaire, in patients in two distinct groups: those with irritation of the brachial plexus and those without. There were 45 patients (37.8%) in the first group. The ratio of women to men was significantly higher in patients with irritation of the plexus as was the incidence of symptoms other than neck pain. There was no significant difference between the two groups with regard to psychological status or findings in radiographs of the cervical spine. Symptoms and signs attributable to stretching of the brachial plexus do occur in a significant proportion of patients after a whiplash injury. Their presence and persistence are associated with a poor outcome.

Adolescent↗

Screening patients in general practice with COPD for long-term domiciliary oxygen requirement using pulse oximetry.

Epidemiological data suggest long-term oxygen therapy (LTOT) delivered by oxygen concentrators in patients with severe hypoxic chronic obstructive pulmonary disease (COPD) is under-prescribed by General Practitioners (GPs) in England and Wales. One reason for this may be the unavailability to GPs of a measure of arterial oxygenation needed to fulfil the defined prescription criteria. Provision of a non-invasive measure of oxygenation may improve detection of hypoxic subjects and increase appropriate prescribing. This study aimed to evaluate pulse oximetry in a general practice setting and to screen for severe undetected hypoxaemia fulfilling the LTOT prescription criteria in patients with COPD. All COPD patients attending surgery in two practices were screened with oximeters for hypoxaemia. Those with an oxygen saturation of < or = 92% were referred to hospital for formal arterial blood gas analysis and an oxygen concentrator assessment. GPs were asked to evaluate their experience in the ease of use and application of oximetry. The number of patients receiving oxygen by concentrator before the study was compared with the national rate and the number after the study with the estimated need suggested by epidemiological studies. Over a 12-month period a total of 114 patients were screened in the two practices with a combined list size of 15,742. Thirteen patients had saturations of < or = 92%. Two refused and 11 underwent formal arterial gas analysis. Three had PaO2 < 7.3 kPa and new prescriptions for oxygen concentrators were made in these previously unsuspected severely hypoxaemic subjects as a result. One other hypoxaemic subject was referred and found to have another treatable medical condition. The initial prevalence of concentrator prescription (0.013% CI 0.003, 0.047) was similar to the national rate (0.024%) and the prevalence observed after screening (0.031%, CI 0.013, 0.073) fell within the lower suggested prescription need of previous epidemiological data (0.02-0.10%). All practitioners found the oximeters simple to use and helpful in assisting with assessment of the severity of their patient's condition. Oximetry provides a readily usable non-invasive method of screening and when applied to all COPD patients seen in general practice can reveal those fulfilling the criteria for long term oxygen who would otherwise not be identified as needing this treatment.

Aged↗

Quantitative evaluation of sympathetic nervous system dysfunction in patients with reflex sympathetic dystrophy.

The sympathetic nervous system function in 20 patients with reflex sympathetic dystrophy (RSD) of one upper extremity was examined by a non-invasive laser Doppler method to assess fingertip blood flow and vasoconstrictor response to deep inspiration. We observed an increased blood flow but an unchanged vasoconstrictor response in the affected hand in stage 1 of the disorder, but in stage 2 there was a decreased blood flow and a stronger vasoconstriction following an inspiratory gasp. Skin blood flow and vasoconstrictor response returned to normal following successful treatment of the condition. These results suggest that in RSD patients the sympathetic nervous system function is altered and is different in the various stages. The objective method used in our study may be of value in the diagnosis and management of RSD.

Adult↗

Reduced ischemia-reperfusion injury in muscle. Experiments in rats with EPC-K1, a new radical scavenger.

L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl- 2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl hydrogen phosphate] potassium salt (EPC-K1), a phosphate diester of alpha-tocopherol and ascorbic acid, is a potent antioxidant. We examined the effects of EPC-K1 on ischemia-reperfusion injury in the skeletal muscle of rats, using an ischemic revascularized hind limb model. Warm ischemia (25 degrees C), produced by vascular pedicle clamping, was sustained for 4 hours. After 24 hours of reperfusion, skeletal muscle injury was evaluated in 2 groups: one group treated by intravenous injection of EPC-K1 (10 mg/kg) prior to ischemia, and a group of controls. The EPC-K1-treated group showed a statistically significant amelioration in the reduction of the isometric muscle contraction, inhibition of the elevation of the muscle wet- to dry-weight ratio, limitation of the muscle level of thiobarbituric acid reactive substances and the serum levels of creatine phosphokinase, lactate dehydrogenase and mitochondrial glutamic oxaloacetic transaminase, and reduction of the extent of muscle injury according to the histological findings. These observations indicate that EPC-K1 acted effectively on ischemia-reperfusion injury in the rat skeletal muscle and thereby improved muscle function.

Animals↗

Acute stretching of peripheral nerves inhibits retrograde axonal transport.

The conjugation of horseradish peroxidase with wheat germ agglutinin was used to identify the effect on retrograde axonal transport of stretching the rat sciatic nerve indirectly by 10% and 20% femoral lengthening with a unilateral external fixator. To investigate the relationship between retrograde axonal transport and blood flow in the stretched nerve, nerve blood flow in the sciatic nerve was measured by a hydrogen washout technique. At 11% strain (20% femoral lengthening), the numbers of horseradish peroxidase-labelled motor neuron cells and nerve blood flow had decreased by 43% and 50%, respectively. Histological examination demonstrated ischaemic changes, but not mechanical damage. However, at 6% strain (10% femoral lengthening) there were no significant abnormalities. These findings suggest that the inhibition of retrograde axonal transport can be induced by acute stretching of the peripheral nerve and that circulatory disturbance is the main cause of the inhibition of retrograde axonal transport at the low strain.

Animals↗

Milbemycin derivatives: modification at the C-5 position.

Protection of the hydroxyl group at the C-5 position of milbemycin A4 and D was carried out to investigate the influence of the C-5 hydroxyl group on the anthelmintic potency of these derivatives. Moreover, the hydroxyl group was converted into amide groups as bioisosters. Biological activities of these derivatives were measured against Nippostrongylus brasiliensis in vitro, and minimal concentrations which induce 100% immotility in worms were determined for each derivative. Biological testing revealed that the hydroxyl group at C-5 is a structural requirement for retaining anthelmintic activity.

Animals↗

Milbemycin derivatives: epoxidation of milbemycins.

Epoxidation reactions (MCPBA epoxidation and Sharpless epoxidation) were examined as a means of chemically modifying milbemycins as part of our program for discovering anthelmintics. 8,9-Epoxy-, 14,15-epoxy-, 8,9-14,15-diepoxy-, and 3,4-8,9-14,15-triepoxymilbemycin A4 were selectively obtained from milbemycin A4 and its derivatives, in which either the C-5 and C-7 hydroxyl groups or C-5 alone were protected as appropriate by a silyl ether (in the former case) or a carbonyl group. Further silylation or epoxidation on these epoxidized compounds indicated that the configuration of each epoxide moiety of the mono- and diepoxides is in accord with that of the corresponding epoxide moiety of the triepoxide. Furthermore, in order to confirm the absolute configurations of these epoxide functionalities, an X-ray analysis of a carbamate derivative from the triepoxymilbemycin was conducted.

Anthelmintics↗

Cephalosporin antibiotics. I. Synthesis and structure-activity relationships of 3-thiazoliomethyl derivatives.

The synthesis and the structure-activity relationships of 3-thiazoliomethyl cephalosporins are described. In a series of these parenteral compounds, 2-(2-aminothiazol-4-yl)-(Z)-2-methoxy-iminoacetamido group was found to be a favorable substituent for the C-7 position of the cephem nucleus. They showed potent antibacterial activity against both Gram-positive and Gram-negative bacteria including some beta-lactamase producing species.

Cephalosporins↗

Cephalosporin antibiotics. II. Synthesis and biological properties of CS-461 and related compounds.

The synthesis, structure-activity relationships, and biological properties of 3-thiazoliomethyl cephalosporins are described. 7-[2-(2-Aminothiazol-4-yl)-(Z)-2- methoxyiminoacetamido]-3-[5-(2-hydroxyethyl)-4-methylthiazoliomethyl+ ++]-3- cephem-4-carboxylate sulfate (CS-461) showed potent antibacterial activity against a wide variety of bacteria both in vitro and in vivo. Furthermore, CS-461 exhibited significantly low acute toxicity in mice.

Animals↗

Synthesis of 5-keto-5-oxime derivatives of milbemycins and their activities against microfilariae.

Starting from milbemycin D (1), milbemycin A4 (2) and milbemycin A3 (3), a series of 5-keto-5-oxime derivatives were synthesized by selective oximation at the alpha,beta-conjugated carbonyl function of the 5-ketomilbemycins (4-6). The activities of the synthesized compounds were studied in dogs naturally infested with microfilariae of Dirofilaria immitis. The 5-keto-5-oximes of milbemycin D (7), A4 (8) and A3 (9) had quite high efficacy to control the microfilariae and more potency than their parents, while the 5-O-acyl oximes (11-15) also exhibited high activity.

Animals↗

Studies on orally active cephalosporin esters. V. A prodrug approach for oral delivery of 3-thiazoliomethyl cephalosporin.

Oral delivery of 3-thiazoliomethyl cephalosporin 1 was attempted through a prodrug approach by applying thiamine chemistry. The 3-thiazoliomethyl group was modified to a ring-opened structure with no ionic charge, and the 4-carboxyl group was converted to pivaloyloxymethyl ester. Lipophilicity of the resulting derivatives (8-10) was suitable for passive absorption from the intestinal tract, and chemical stability in phosphate buffer solution (pH 6.86) was moderate. When administered orally to mice, these derivatives were mainly transformed to a novel 3-spiro cephalosporin 11, and desired reconversion to the 3-thiazoliomethyl cephalosporin was minor. Isomerization to delta 2-cephalosporin 14 was also observed. These results showed that the derivatives (8-10) tested in this study did not serve as orally active prodrugs of 3-thiazoliomethyl cephalosporin 1.

Administration, Oral↗

Studies on orally active cephalosporin esters. VI. Synthesis and antimicrobial activity of 3-(3-isoxazolyl)oxymethylcephalosporin derivatives.

The synthesis and biological activities of a series of 3-(isoxazol-3-yl)oxymethyl cephalosporins are described. 7-[2-(2-Aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3- [(isoxazol-3-yl)oxymethyl]-3-cephem-4-carboxylic acid (7a) showed potent activity against both Gram-positive and Gram-negative bacteria including some beta-lactamase producing species. Its pivaloyloxymethyl ester provided a good urinary recovery after oral administration to mice.

Bacteria↗

Studies on orally active cephalosporin esters. II. Chemical stability of pivaloyloxymethyl esters in phosphate buffer solution.

The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH 6-8) were investigated. The degradation of the starting delta 3 cephalosporin ester proceeded mainly via isomerization to the delta 2 ester and subsequent hydrolysis to the delta 2 acid. Hydrolysis to the delta 3 acid (the parent acid) was very slow. Analysis of the rate constants indicated that the isomerization rate k12 was approximately equal to the apparent degradation rate of the delta 3 ester kdeg, and slower than the hydrolysis rate of the delta 2 ester k24. The isomerization process to the delta 2 ester was found to be the rate-determining step in the degradation of cephalosporin esters. The substituent at the C-3 position of the cephalosporins affected the degradation kinetics. The degradation was accelerated by increase of pH, buffer concentration and added protein.

Administration, Oral↗

Studies on orally active cephalosporin esters. III. Effect of the 3-substituent on the chemical stability of pivaloyloxymethyl esters in phosphate buffer solution.

The effect of substituents at the C-3 position on the degradation kinetics of the pivaloyloxymethyl (POM) ester of delta 3 cephalosporin in phosphate buffer solution (pH 6-8) was investigated. In the degradation, the isomerization process to the delta 2 ester was the rate-determining step. In this study, the logarithm of the isomerization rate to the delta 2 ester (log k12) correlated with the carbon-13 nuclear magnetic resonance chemical shift difference value at C-3 and C-4 of the delta 3 ester (delta delta (4-3)). The energy level of the lowest unoccupied molecular orbital (LUMO) of the delta 3 esters also correlated with log k12. The electronic properties at the C-2 position had no effect on the isomerization reaction. On the other hand, the logarithm of the isomerization rate back to the delta 3 ester (log k21) correlated with the van der Waals volume (MV) of the 3-substituent. These results show that the substituent at the C-3 position influences mainly the electronic structure of the conjugated pi-bond system (C3 = C4 - C4 = O) and consequently affects the feasibility of isomerization to the delta 2 ester, i.e., the stability to degradation.

Administration, Oral↗

Studies on orally active cephalosporin esters. IV. Effect of the C-3 substituent of cephalosporin on the gastrointestinal absorption in mice.

The effect of the C-3 substituent on the oral absorbability of pivaloyloxymethyl (POM) ester of cephalosporin in mice is described. The C-3 substituent affects the physicochemical and biochemical properties of POM ester, such as lipophilicity, water solubility, chemical stability and enzymatic stability. Quantitative analyses of the relationships between these properties and the oral bioavailability have been attempted. Lipophilicity made a parabolic contribution to the absorption. The optimum log P octanol/water value was estimated to be around 2.22. The chemical isomerization of the cephem double bond from delta 3 to delta 2 in the intestinal lumen prior to absorption contributed linearly to decrease of absorption. In the case of POM ester having a larger isomerization rate, more delta 2 isomer was detected in feces and urine. Enzymatic hydrolysis of POM ester to the parent acid in intestinal tissue was faster for a more lipophilic ester. Hydrolytic activity, which was detected in the content of the intestinal lumen, would lower the absorption. The effect of the C-3 substituent on water solubility was not important for the absorption of cephalosporin employed in the present study. Isomerization of the double bond, which was found to be characteristic for cephalosporin ester, presented a problem in the prodrug approach for oral use.

Animals↗