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Biomedical subjects

C L Blackburn

Publications and source records attributed to C L Blackburn.

7 recordsLinked to original sources

A marine natural product inhibitor of kinesin motors.

Members of the kinesin superfamily of motor proteins are essential for mitotic and meiotic spindle organization, chromosome segregation, organelle and vesicle transport, and many other processes that require microtubule-based transport. A compound, adociasulfate-2, was isolated from a marine sponge, Haliclona (also known as Adocia) species, that inhibited kinesin activity by targeting its motor domain and mimicking the activity of the microtubule. Thus, the kinesin-microtubule interaction site could be a useful target for small molecule modulators, and adociasulfate-2 should serve as an archetype for specific inhibitors of kinesin functions.

Adenosine Diphosphate↗

Identification of glucokinase mutations in subjects with gestational diabetes mellitus.

Recent studies have shown that mutations in the glucokinase gene on chromosome 7 can cause an autosomal dominant form of NIDDM with a variable clinical phenotype and onset during childhood. The variable clinical phenotype includes mild fasting hyperglycemia (i.e., a plasma glucose value of > 110 mg/dl, a value that is at least 2-3 SDs above normal), impaired glucose tolerance, gestational diabetes mellitus, as well as overt NIDDM as defined using National Diabetes Data Group or World Health Organization criteria. Because gestational diabetes mellitus was a clinical feature associated with glucokinase mutations, we have screened a group of women with gestational diabetes who also had a first-degree relative with diabetes mellitus for the presence of mutations in this gene. Among 40 subjects, we identified two mutations, suggesting a prevalence of approximately 5% in this group. Extrapolating from this result, the prevalence of glucokinase-deficient NIDDM among Americans may be approximately 1 in 2500.

Amino Acid Sequence↗

[Apnea following epidural administration of sufentanil].

Four patients developed apnoea after epidural administration of 50 micrograms of sufentanil. In three of these patients apnoea occurred within two minutes after administration. In all cases catheter position was verified to be in the epidural space. It is possible that accumulation plays a causative role in some of those cases in which the drug is given on demand. Because sufentanil-induced apnoea may occur fast and unexpected it is advised that patients should be kept under close supervision for at least two hours following administration.

Adult↗

The pharmacokinetics of sufentanil in surgical patients.

The pharmacokinetics of sufentanil, a new thienyl analogue of fentanyl, were studied in 10 surgical patients. Sufentanil, 5 micrograms/kg, was given intravenously as a bolus injection and plasma concentrations measured at intervals up to 8 h. Plasma sufentanil concentrations decreased rapidly after injection--98% of the administered dose having left the plasma within 30 min. In 9 of the 10 patients, a tri-exponential equation optimally described the sufentanil concentration decay curve, with average (+/-SEM) half-lives for the rapid (pi) and slow (alpha) distribution phases of 1.4 +/- 0.3 min and 17.7 +/- 2.6 min, respectively. The average terminal elimination (beta) half-life was 164 +/- 22 min. The average value for Vd beta was 2.9 +/- 0.2 1/kg, Vdss 1.7 +/- 0.2 1/kg and total plasma clearance 12.7 +/- 0.8 ml X kg-1 X min-1 (935 +/- 50 ml/min). In one patient, a bi-exponential equation was sufficient to describe the concentration-time data, yielding a distribution half-life of 4.7 min and an elimination half-life of 117 min.

Adult↗

The pharmacokinetics of alfentanil (R39209): a new opioid analgesic.

The pharmacokinetics of alfentanil (R39209), a new short-acting opioid analgesic, have been studied in eleven patients. Six patients were given 50 micrograms/kg alfentanil and five patients 125 micrograms/kg as an intravenous bolus injection. Plasma concentrations were measured at intervals up to 6 h (50 micrograms/kg) or 8-10 h (125 micrograms/kg), using a specific radioimmunoassay technique. Plasma concentrations declined triexponentially in both groups. The initial elimination of alfentanil from the plasma was very rapid with 90% of the administered dose leaving the plasma within 30 min. The average half-lives for the three phases were similar for both groups. The combined mean (+/- SEM) half-lives for the 11 patients for the rapid and slow distribution phases were short (t 1/2 pi = 1.2 +/- 0.26 min, t 1/2 alpha = 11.6 +/- 1.63 min). The elimination half-life, t 1/2 beta was 94 +/- 5.87 min which is considerably shorter than that of other opioids. The mean (+/- SEM) total body clearance was 6.4 +/- 1.39 ml . kg-1 . min-1 and the volume of distribution (Vd) was 0.86 +/- 0.194 l/kg. The latter is considerably less than reported values for the chemically related drug, fentanyl, and suggests that alfentanil may have a lower tissue binding affinity than fentanyl. The rapid elimination and short duration of clinical action suggests the feasibility of repeated administration of alfentanil and its use by continuous intravenous infusion.

Adult↗

Comparison of speed of onset of fazadinium, pancuronium, tubocurarine and suxamethonium.

Under light general anaesthesia the speed of onset of action of fazadinium, pancuronium, tubocurarine and suxamethonium has been assessed by measuring the decrease in the twitch height of the adductor pollicis muscle following administration of the drugs. Suxamethonium produced 95% depression of the twitch height significantly faster than any of the other drugs, while the onset of fazadinium was significantly more rapid than that of the other non-depolarizing neuromuscular blocking drugs.

Humans↗