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Biomedical subjects

J Liddle

Publications and source records attributed to J Liddle.

At least 19 recordsLinked to original sources
PubMed1999

3-(1',1'-Dimethylbutyl)-1-deoxy-delta8-THC and related compounds: synthesis of selective ligands for the CB2 receptor.

The synthesis and pharmacology of 15 1-deoxy-delta8-THC analogues, several of which have high affinity for the CB2 receptor, are described. The deoxy cannabinoids include 1-deoxy-11-hydroxy-delta8-THC (5), 1-deoxy-delta8-THC (6), 1-deoxy-3-butyl-delta8-THC (7), 1-deoxy-3-hexyl-delta8-THC (8) and a series of 3-(1',1'-dimethylalkyl)-1-deoxy-delta8-THC analogues (2, n = 0-4, 6, 7, where n = the number of carbon atoms in the side chain-2). Three derivatives (17-19) of deoxynabilone (16) were also prepared. The affinities of each compound for the CB1 and CB2 receptors were determined employing previously described procedures. Five of the 3-(1',1'-dimethylalkyl)-1-deoxy-delta8-THC analogues (2, n = 1-5) have high affinity (Ki = < 20 nM) for the CB2 receptor. Four of them (2, n = 1-4) also have little affinity for the CB1 receptor (Ki = > 295 nM). 3-(1',1'-Dimethylbutyl)-1-deoxy-delta8-THC (2, n = 2) has very high affinity for the CB2 receptor (Ki = 3.4 +/- 1.0 nM) and little affinity for the CB1 receptor (Ki = 677 +/- 132 nM).

Animals↗
PubMed1998

Synthesis and pharmacology of the isomeric methylheptyl-delta8-tetrahydrocannabinols.

The synthesis of the 3-heptyl, and the eleven isomeric 3-methylheptyl-delta8-tetrahydrocannabinols (3-7, R and S methyl epimers, and 8) has been carried out. The synthetic approach entailed the synthesis of substituted resorcinols, which were subjected to acid catalyzed condensation with trans-para-menthadienol to provide the delta8-THC analogue. The 1'-, 2'- and 3'-methylheptyl analogues (3-5) are considerably more potent than delta8-THC. The 4'-, 5'- and 6'-methylheptyl isomers (6-8) are approximately equal in potency to delta8-THC.

Animals↗
PubMed1996

Can occupational therapy intervention play a part in maintaining independence and quality of life in older people? A randomised controlled trial.

The main objective of this study was to see if older people could maintain their quality of life and independence after their homes had been modified and they were using community services as recommended by an occupational therapist. There were 167 study participants aged 69 to 94 years from the Northern Sydney Area. After being assessed at home by an occupational therapist, 105 were randomly allocated to one of two groups, to either have or not have the occupational therapist's recommendations carried out. They were assessed again after six months. A third group did not require any intervention. This group was followed up by telephone and postal questionnaire at six months. The main outcome measures used were the Sickness Impact Profile, the Philadelphia Geriatric Center Morale Scale, the Life Satisfaction Index, assessment of Activities of Daily Living, the Health Assessment Questionnaire and change in residence. After six months there were no difference in outcomes among the three groups. Most study participants remained at a satisfactory level on each measure. Three people had died. One had moved to hostel care and one had moved to a nursing home. A further 14 from the group having no intervention had withdrawn from the study. A secondary objective of this study was to indicate the responsiveness of these outcome measures to change in the short term (over six months) in an elderly population. Twelve-month assessments are in progress and may indicate what to expect from these outcome measures in the medium term.

Activities of Daily Living↗
PubMed1987

Convulsions caused by endrin poisoning in Pakistan.

From July through September 1984, acute convulsions caused by endrin poisoning occurred in the subdistrict of Talagang, Attock District, Punjab province, Pakistan. Eighteen of the 21 affected villages were surveyed; 70% of the cases for which ages were known (106 of 152) were in children 1 to 9 years of age; 9.8% of all affected persons (19 of 194) died. The outbreak occurred in villages on the main roads of the subdistrict and peaked in early September. Endrin was detected in the blood of 12 of 18 patients with a history of convulsions but was not found in the blood of four hospitalized control patients. One composite sugar sample taken from the homes of three persons had an endrin level of 0.04 ppm. Because of the high toxicity, repeated association with large-scale outbreaks of neurologic illness, and the difficulties of monitoring distribution, endrin should not be used for agricultural purposes.

Child↗
PubMed1986

Dose independent pharmacokinetics of mexiletine in healthy volunteers.

In 12 healthy volunteers who received orally 100, 200, 300, 400 and 600 mg mexiletine at weekly intervals, the maximum plasma concentration of mexiletine and AUC increased linearly with the dose of mexiletine. Between doses there were no significant differences in the values for clearance and volume of distribution of mexiletine but there were for plasma elimination half-life. These results indicate that the kinetics of mexiletine are linear.

Administration, Oral↗
PubMed1983

The effect of propranolol on CSF amine metabolites in psychiatric patients.

In view of the central side effects of beta-adrenoceptor blocking agents and their alleged antipsychotic action in the absence of DA receptor blockade, it is important to establish which neurotransmitters are likely to be involved. Previous animal and patient studies have, however, produced conflicting data on this point. The changes in CSF HVA, 5HIAA and MHPG during treatment with propranolol (960 mg/day) in chronic schizophrenic patients were monitored on four occasions over 30 days. Clinical changes were monitored by the Wing and Krawiecka Scales and motor activity was assessed by pedometer. CSF HVA levels were significantly increased by propranolol and the rise continued throughout the 30 day period. There were no significant changes in the other metabolites. There was no evidence of any therapeutic benefit from propranolol treatment in these patients. These findings may explain the central side-effects and occasional reports of schizophreniform psychosis after propranolol, since an increase in DA turnover occurs without DA receptor blockade.

Adult↗
PubMed1980

Some clinical and metabolic aspects of propranolol in chronic schizophrenia.

No benefit attributable to propranolol (1000 mg/day) could be detected in a trial lasting at least 22 weeks, 6 weeks of which was double-blind placebo-controlled, in 5 chronic schizophrenic patients. The mean propranolol CSF/plasma ration was 0.08, and there was good agreement between CSF and free plasma propranolol levels. Basal plasma prolactin was slightly but insignificantly reduced by propranolol, and metoclopramide-stimulated prolactin release was unaffected. Propranolol was associated with a significant temporary increase in HVA, a non-significant rise in 5-HIAA and a significant decrease in MHPG, in the lumbar cerebrospinal fluid of 4 patients.

Adult↗
PubMed1979

Determination of paraquat in marijuana by reversed-phase paired-ion high performance liquid chromatography.

A sensitive and selective method is described for the quantitative determination of paraquat in marijuana. Paraquat is extracted from finely ground plant material with hydrochloric acid with sonification, and the resulting acidic solution is extracted with chloroform:isopropanol (9:1) and evaporated to dryness. The residue is reconstituted with aqueous phosphate buffer pH 7.0; the solution is passed through a C-18 SEP-PAK TM and is analyzed with high performance liquid chromatography, using a reversed-phase column and an "ion pairing" reagent in the mobile phase. The recovery of paraquat in laboratory-spiked material varied from 90-97%. Results obtained with confiscated, field-sprayed marijuana by the procedure described were in excellent agreement with those obtained with a well-established ultraviolet procedure. The calculated limit of detection with this method is 2 ng of paraquat.

Cannabis↗
PubMed1977

Lead Absorption in a community of potters in Barbados.

In a community of potters in Barbados where lead glazes traditionally have been used, a survey of 12 potters, 19 of their family members, and 24 controls revealed elevated blood lead levels in the potters, their family members, and the neighbours who used pottery for culinary purposes. Dust from the potters' homes and work areas contained lead in concentrations up to 320,000 ppm. Pottery was found to have lead release levels up to 3,125 microgram/ml. Six people had upper extremity tremor associated with elevated blood lead levels. This survey demonstrates the risk of using lead glazes in pottery production to family members of potters as well as the potters themselves and emphasizes the need for surveillance of occupational hazards in developing countries.

Adolescent↗