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Biomedical subjects

G A Clark

Publications and source records attributed to G A Clark.

14 recordsLinked to original sources
PubMed1989

Pharmacokinetics, efficacy and adverse effects of sublingual salbutamol in patients with asthma.

Administration of drugs by the sublingual route provides rapid systemic absorption and avoids first-pass metabolism. The purpose of the present study was to assess the pharmacokinetics, efficacy and adverse effects of standard salbutamol tablets given by this route to patients with asthma. Seven asthmatic patients were given either sublingual salbutamol tablet 2 mg (SL), swallowed tablet 2 mg (O), metered dose inhaler 200 micrograms (MDI) or placebo (PL), in a randomized single-blind cross-over design. Airways responses (FEV1, FVC, PEFR), finger tremor (Tr), heart rate (HR), plasma potassium (K) and plasma salbutamol were measured over a 6 h period following drug administration. There were highly significant changes in FEV1 with MDI, O and SL routes compared with PL, although the response to MDI was greater and more rapid than with O or SL. There were similar findings for FVC and PEFR responses. There were no adverse effects with MDI, whereas both 0 and SL produced significant tremor responses. There were no differences between O and SL for any of the pharmacodynamic parameters. In addition, pharmacokinetic profiles for O and SL were also similar apart from an initial delay in absorption with SL. There were however, no significant differences in any of the pharmacokinetic parameters, between O and SL. This suggest that buccal absorption of salbutamol was negligible, and that systemic absorption occurred after swallowing of the dissolved sublingual tablet. These results show that sublingual administration of salbutamol tablet has no clinical benefit over the oral route.

Administration, Inhalation↗
PubMed1989

Classical conditioning of the Aplysia siphon-withdrawal reflex exhibits response specificity.

The gill- and siphon-withdrawal reflex of Aplysia undergoes classical conditioning of its amplitude and duration when siphon stimulation (the conditioned stimulus, CS) is paired with tail or mantle shock (the unconditioned stimulus, US). This conditioning of a preexisting response exhibits both temporal and stimulus specificities, which can be accounted for by activity-dependent enhancement of presynaptic facilitation of the siphon sensory neurons. To test whether conditioning of the reflex also exhibits response specificity (development of a new type of response to the CS that often resembles the response to the US), we measured the direction of siphon withdrawal in response to siphon stimulation (the CS) with tail or mantle shock as the US. The unlearned response to siphon stimulation is straight contraction, the response to tail shock is backward bending, and the response to mantle shock is forward bending. In the first experiment, we trained different animals with the tail or mantle US paired or unpaired with the CS; in a second experiment, we trained each animal with two CSs, one of which was paired with the US; in a third experiment, we varied US intensity; and in a fourth experiment, we trained each animal with two USs, one of which was paired with the CS. There was a significant, pairing-specific tendency for the direction of the response to the CS to resemble the response to the US after training in each experiment, demonstrating response specificity in conditioning of the withdrawal reflex. This feature of conditioning could in principle be accounted for by an elaboration of activity-dependent facilitation.

Animals↗
PubMed1988

New method for assessing changes in growth and sexual dimorphism in paleoepidemiology.

This paper has three goals. First, traditional methods used for analyzing growth disruption (GD) and sexual dimorphism (SD) in prehistoric skeletal populations are critiqued. Second, a new method, using adult vertebrae, is presented which helps overcome these limitations. Third, this new method is then tested in the Dickson Mounds skeletal population. Between A.D. 950 and 1300 this population underwent a transition from hunting and gathering (PreMississippian: PreMiss.) to maize horticulture (Mississippian: Miss.). Previous research has found a decrease in long bone length in Miss. children, but no difference in adults, or a change in SD. Could this be due to catch-up growth? In the adult skeleton vertebral neural canals (VNCs) size and vertebral body heights (VBHs) can easily be measured. VNCs generally cease growth by early childhood, whereas VBHs grow through young adulthood. This new method offers inference into prehistoric GD and SD previously thought impossible. For example, if VNCs are reduced, but not VBHs, it implies early GD with subsequent catch-up growth. If both VNCs and VBHs are reduced, GD was presumably chronic. Moreover, within this framework, preadult SD can be examined. Results from Dickson show that early GD was followed by catch-up growth. There was a significant change in SD, with females becoming smaller. They had chronic GD. Miss. males had early GD, followed by catch-up growth. Indeed, Miss. males, compared to PreMiss. males, had significantly larger VBHs. Together, these results suggest females lost, but males gained, social status. Thus, vertebral morphometrics may be an invaluable new tool for paleoepidemiologists.

Adolescent↗
PubMed1988

Parallel processing of short-term memory for sensitization in Aplysia.

How is the short-term memory for a single form of learning distributed among the various elements of a neuronal circuit? To answer this question, we examined the short-term memory for sensitization, using the siphon component of the defensive gill- and siphon-withdrawal reflex. We found that the memory for short-term sensitization is represented by at least four sites of circuit modification, each involving a different type of plasticity. These include (1) presynaptic facilitation of the sensory neuron connections onto both interneurons and motorneurons; (2) presynaptic inhibition at the connections of the L30 inhibitory neurons onto the excitatory interneuron L29; (3) posttetanic potentiation of the excitatory connections made by L29 onto a specific subclass of siphon motorneurons, the LFS cells; and (4) an increase in the tonic firing rate of the LFS siphon motor neurons, resulting in neuromuscular facilitation. Each of the heterosynaptic changes seems to involve a common modulatory transmitter and to utilize a common second messenger system. Moreover, each of these sites seems capable of encoding a different component of the short-term memory. Facilitation of the connections of sensory neurons should contribute to the increase in amplitude of the response; the disinhibition of the L29 interneurons and the posttetanic potentiation at L29 synapses should contribute to an increase in the duration of the response; and the increase in tonic firing of the LFS subclass of siphon motor neurons seems capable of contributing both to an increase in response amplitude and to changes in response topography.

Animals↗
PubMed1986

Poor growth prior to early childhood: decreased health and life-span in the adult.

Previous studies in animal populations have shown that stunted neural and thymolymphatic growth early in development may result in permanently impaired neural and immune function, decreased body growth, vertebral wedging, and decreased life-span. In the human adult, small vertebral neural canal (VNC) diameters may reflect early stunted neural and immune development and impaired function that leads to decreased health (inferred by greater vertebral wedging) and life-span in the adult. VNC, which complete their growth by early childhood (age 4), are markers of early development in adults. On the other hand, features following general body growth, such as height, weight (represented here by vertebral body height) continues to grow until young adulthood. They are less reliable, because they readily experience catch-up growth (even in chronically stressed populations) and, unlike VNC, may mask poor early growth. To test associations between early growth and adult health and life-span in humans, we measured 2,060 VNC, vertebral heights, vertebral wedging, nerve-root tunnel lengths, severity of vertebral osteophytosis, and ages at death in 90 adult (aged 15-55 years) prehistoric skeletons (950-1300 A.D.). Tibial lengths were also measured in a subsample (n = 30). Multivariate, bivariate, and nonparametric analyses showed that small VNC are significantly associated with greater vertebral wedging and decreased life-span (P less than 0.05-0.00001). VNC are independent of vertebral body heights and tibial lengths (general body growth). VNC, but not statural components, are useful in predicting adult health, presumably because they reflect neural and immune development and do not readily experience catch-up growth. Thus, longitudinal retrospective measures of early growth and adult health were systematically linked within individuals regardless of confounding factors operating over the 350-year time period. Since this research was completed, this model has repeatedly been independently confirmed in four living urban industrial populations. Longitudinal retrospective analysis was employed together with direct measures of VNC, neural and immune function. Together these results suggested that it may be essential to improve growth prior to early childhood in order to maximize adult health and life-span.

Adolescent↗
PubMed1986

Rapid extraction of plasmids from Clostridium perfringens.

Two rapid methods were evaluated for their extraction of plasmids from Clostridium perfringens. The first method involved lysis of 1 to 2 ml of C. perfringens culture by treatment with hyaluronidase, lysozyme, and sarcosyl. DNA, extracted with phenol-chloroform, was treated with RNase, boiled, and electrophoresed in a 1.2% agarose gel. The second method involved lysis of 2 ml of culture by lysozyme treatment and extraction with alkaline sodium dodecyl sulfate (SDS). Extracted DNA was treated with RNase, boiled, and electrophoresed in a 0.7% agarose gel. Of 57 strains of C. perfringens analyzed by both extraction procedures, 11 were shown to have plasmids by the alkaline SDS method which were missed by the phenol-chloroform extraction method. These new plasmids were of higher molecular mass and ranged up to 68 megadaltons. Use of the DNase inhibitor diethyl pyrocarbonate did not further improve the yield of plasmid DNA. An additional 159 isolates of C. perfringens screened by the alkaline SDS method revealed plasmids up to 80 megadaltons in mass and an overall plasmid carriage rate of 69%.

Clostridium perfringens↗
PubMed1985

Can infant malnutrition cause adult vertebral stenosis?

Does infant malnutrition produce smaller adult spinal canals? Lumbar and thoracic vertebrae (n X 1073), from a prehistoric American Indian population (15-55 yrs of age), were measured for anteroposterior (AP) and transverse (TR) vertebral canal sizes, nerve root tunnel (intervertebral foramen) widths (NRT), vertebral heights (VH), vertebral osteophytosis (VO), and tibial lengths. They underwent a dietary change from hunting-gathering, protein rich (PR), to maize agriculture, protein deficient (PD), between 950 and 1300 A.D. Multivariate analyses controlled for age, sex, culture, NRT, VH, VO, and wedging. Canal size was significantly smaller in the PD. AP diameters were generally and highly correlated with NRT, and thus both spinal stenosis and sciatica may have a developmental basis. Canal size was independent of statural components. Consequently, canal size is a most powerful tool in assessing the presence infant malnutrition. Moreover, perhaps the association between canal size and low-back pain (LBP) found in living populations has been underestimated, and this component of LBP is preventable.

Adult↗
PubMed1978

Measurement of the bioavailability of iron, using the rat hemoglobin repletion test.

Variations in the AOAC official first action rat hemoglobin repletion test for iron were studied. These changes included (1) use of a simplified basal diet to eliminate ingredients which sometimes contribute too much iron; (2) increased fortification of the basal diet with vitamin E, pantothenic acid, and pyridoxine; (3) increased dietary copper; (4) variations in the carbohydrate source in the basal diet; (5) changes in the length of the depletion and repletion periods; and (6) comparison of prophylactic and curative procedures. The changes yielded results comparable to those obtained with the present official method. Further study may reveal that the depletion period can be shortened or eliminated. To fully meet the rat's vitamin requirements, increased levels of vitamin E, pantothenic acid, and pyridoxine are recommended. It is further recommended that the present method remain in official first action status, and that study be continued.

Animals↗
PubMed1975

Estimation of the bioavailability of iron.

Eight laboratories conducted a test for the estimation of the bioavailability of iron from 4 sources, using depleted male albino rats. Ferrous sulfate was used as the reference standard. Ferric orthophosphate was found to have a relative biological value of 11 (range 6-22), an old sample of hydrogen-reduced iron 27 (range 15-41), and ferric citrate 96 (range 75-125). Good results were obtained with a simplified basal diet prepared without ingredients that had previously contributed variable quantities of iron. There was no apparent advantage in using the change in hemoglobin during the repletion period instead of the final homoglobin value as the criterion of response to iron supplements. Several statistical treatments of the data yielded similar conclusions regarding relative biological values of the iron sources.

Animals↗