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Biomedical subjects

M Rowe

Publications and source records attributed to M Rowe.

At least 181 records · Page 10Linked to original sources
PubMed1981

Bioavailability of 11 quinidine formulations adn pharmacokinetic variation in humans.

The bioavailabilities of eight quinidine sulfate, two gluconate, and one polygalacturonate formulations were compared, with one of the sulfate formulations as a reference (R) in a panel of 24 volunteers, according to a design comprising duplicate 6 x 6 Latin squares in two subject groups. Only one gluconate formulation (H) gave a significantly lower (p less than 0.05) area under the curve from 0 to 30 hr (AUC30), 90% or R, which was not as significant as AUC infinity (94% of R). Formulation H also gave a significantly lower peak concentration (Cmax) and a longer time to peak concentration (tmax) and generally exhibited some characteristics of sustained-release product. In addition, one product (F) gave a significantly higher Cmax while another formulation (D) gave a longer tmax. The wide range of dissolution times obtained with these products with three test conditions was not reflected in the AUC, Cmax, or tmax values obtained, except the Formulation H was consistently the slowest to dissolve. The terminal rate constants, expressed as t 1/2, of the 24 subjects gave an overall mean of 7.49 +/- 0.77 hr and ranged from 6.24 +/- 0.28 to 0.49 +/- 0.90 hr in individuals. The estimated total body clearance, with the assumption that the oral bioavailability was 70%, gave an overall mean of 4.22 +/- 1.05 and ranged from 2.49 +/- 0.28 to 6.42 +/- 0.70 mg/min/kg in individuals, demonstrating the wide range of quinidine disposition even in healthy subjects; this finding is in agreement with recently published results.

Adult↗
PubMed1980

Lymphocyte 5'-nucleotidase in primary hypogammaglobulinaemia and cord blood.

The 5'-nucleotidase (5'-N) deficiency on circulating mononuclear cells of patients with 'common variable' hypogammaglobulinaemia (CV-H) was shown to be the result of one or more of three factors: reduced T cell 5'-N activity, a reduced percentage of circulating B cells, and a low B cell 5'-N activity. A lack of circulating B lymphocytes, together with a low T cell 5'-N activity in some cases, was found to be responsible for the deficiency of lymphocyte 5'-N in patients with X-linked hypogammaglobulinaemia (X-H). The low levels of 5'-N activity in CV-H and X-H patients were not due to abnormal compartmentalization of the enzyme, altered enzyme kinetics, or the presence of a regulatory factor. Cord Blood B and T cells have a lower 5'-N activity than adult lymphocytes. The patient and cord blood data are discussed in relation to the stage of cellular maturity.

Adolescent↗
PubMed1979

Metabolism and disposition of trimethadione in pregnant rats.

The metabolism and disposition of a suspected human teratogen, trimethadione (TMO), was studied in pregnant rats following administration of the drug at doses of 60 and 240 mg/kg/day during 6 to 15 days of gestion, with a view to understanding the fetotoxicity of the drug. Following the last dose, animals were sacrificed at 6, 12, and 24 hr, and the fetuses were removed by caesarean section. The concentrations of TMO and its N-demethylated metabolite, dimethadione (DMO), were determined by a specific GLC procedure in maternal plasma, urine, brain, and liver, as well as in placenta and whole fetus. The plasma and liver concentrations of TMO and DMO suggested that the parent drug is rapidly converted to DMO. Total 24 hr urinary recoveries of the unchanged drug and the metabolite were 61 and 82% following 240 and 60 mg/kg/day doses of TMO, respectively. The DMO concentrations in brain and all other tissues analyzed were far greater than those of TMO. The fetus to maternal plasma concentration ratios of TMO suggested that the placental transfer of the drug was greater than the clearance from the fetus over the periods examined, whereas the transfer of the metablite seemed to be independent of dose. Furthermore, the rate of decline of DMO in fetus was far slower than that of the placenta and maternal plasma, causing accumulation of DMO in the fetus. The results suggest that the fetotoxic effects produced by TMO when given to pregnant rats could be due to accumulation of DMO in fetus.

Abnormalities, Drug-Induced↗
PubMed1979

5'-nucleotidase of B and T lymphocytes isolated from human peripheral blood.

The ecto-5'-nucleotidase activities of highly purified T and B lymphocytes from human peripheral blood have been investigated using biochemical and histochemical techniques. The enzyme activity of the purified B cells was about 3.5 times that of the T cells. Using a histochemical assay, 21--55% of the B cells stained positively for 5'-nucleotidase, but only 2--22% of the T cells were positive. These results are discussed in relation to the low 5'-nucleotidase activities found on peripheral blood lymphocytes from patients with chronic lymphatic leukaemia and some patients with primary hypogammaglobulinaemia.

Agammaglobulinemia↗
PubMed1978

Ecto 5'-nucleotidase deficiency in primary hypogammaglobulinaemia.

The activity of the lymphocyte ectoenzyme 5'-nucleotidase is very low in the majority of patients with primary 'common variable' hypogammaglobulinaemia. In order to test whether this can be explained by lymphocyte subpopulation deficiencies we measured 5'-nucleotidase activity, using both biochemical and histochemical techniques, in purified T and B cells from patients and healthy subjects. Purified B cells from normal subjects have about four times the activity of T cells. This explains why the levels of lymphocyte 5'-nucleotidase activity are at the lower limit of the normal range in patients with X-linked hypogammaglobulinaemia who lack B cells. The low levels in the 'common variable' group can be explained by low activity in their T lymphocytes associated with either low activity in their B cells or depletion of B cells. The finding that inhibition of the enzyme does not interfere with in vitro lymphocyte transformation or immunoglobulin production in normal subjects indicates that the enzyme deficiency is not directly responsible for the hypogammaglobulinaemia. These and other studies suggest that this enzyme appears on lymphocytes at a certain stage of development and that both T and B lymphocytes in some patients with 'common variable' hypogammaglobulinaemia are developmentally immature.

Agammaglobulinemia↗
PubMed1978

Coding of information about tactile stimuli by neurones of the cuneate nucleus.

1. The responses of cuneate neurones to controlled tactile stimulation of the foot pads were examined in unanaesthetized, decerebrate cats. The neurones were divided into three functional classes; one sensitive to steady tactile stimuli, and two dynamically sensitive classes which could be readily differentiated by their responsiveness to cutaneous vibration. Each class appeared to receive an exclusive input from only one of the three known groups of tactile receptors associated with the foot pads, namely the Pacinian corpuscles, the Merkel endings and the intradermal, encapsulated endings known as Krause or Meissner corpuscles. 2. Cuneate neurones responsive to steady indentation of the skin displayed approximately linear or sigmoidal stimulus-response relations over indentation ranges up to approximately 1.5--2 mm. Response variability at a fixed stimulus intensity was relatively low and showed little systematic change over the full range of the stimulus-response curves. 3. One class of dynamically sensitive cuneate neurones responded to cutaneous vibration over a range of approximately 5-80 Hz with maximal responsiveness around 30 Hz. The other class, the Pacinian neurones, responded over a range of approximately 80- greater than 600 Hz with maximal responsiveness at 200-400 Hz. The thresholds and combined band width of vibratory sensitivity of these populations were comparable with known subjective thresholds and range of cutaneous vibratory sensibility. 4. Responses of cuneate neurones were phase-locked to the vibratory stimulus suggesting that information about vibration frequency could be coded by the patterns of impulse activity. Quantitative measures indicated that maximal phase-locking occurred in responses to vibration frequencies of 10-50 Hz with a progressive decline at higher frequencies. Above 400 Hz, impulse activity occurred almost randomly throughout the vibratory stimulus cycle and therefore carried little further signal of vibratory frequency. The decline, with increasing frequency, in the ability of cuneate neurones to signal information about vibratory frequency parallels the known subjective capacities for frequency discrimination. 5. A switch-over occurred at approximately 80 Hz in the population of cuneate neurones able to provide the more reliable signal of vibratory frequency; above 80 Hz, the Pacinian neurones; below 80 Hz, the neurones receiving intradermal, rapidly adapting receptor input from the pads. 6. The observed properties of cuneate neurones are compatible with a role in signalling information which could contribute to subjective tactile abilities.

Action Potentials↗
PubMed1977

Inhibition of cuneate neurones: its afferent source and influence on dynamically sensitive "tactile" neurones.

1. Responses were recorded in decereberate, unanaesthetized cats from individual cuneate neurones in order to determine firstly, the afferent sources of inhibition on cuneate neurones and secondly, the influence of afferent-induced inhibition on those response features of dynamically sensitive tactile neurones which determine their capacity to code information about parameters of tactile stimuli.2. For all cuneate neurones which displayed afferent-induced inhibition from areas surrounding or within their excitatory receptive field (71% of the sample) it was consistently found that 300 Hz vibration at low amplitudes (< 25-50 mum) which selectively engages Pacinian corpuscles was an effective source of inhibition. In contrast, steady indentation which activates slowly adapting tactile afferents was quite ineffective, as was low frequency vibration (30 Hz) at amplitudes of < 50-100 mum. The latter stimulus can be used to engage rapidly adapting receptors either within glabrous skin (presumed to be Meissners corpuscles) or in association with hair follicles. It is concluded that afferents from Pacinian corpuscles are the dominant or exclusive source of afferent-induced inhibition of cuneate neurones.3. For dynamically sensitive neurones responsive to low frequency cutaneous vibration (30 Hz) there was a reduction in the slope of stimulus-response relations with afferent-induced inhibition, but no expansion of the range of stimulus amplitudes over which the neurone responded.4. The influence of afferent-induced inhibition on the phase-locking of impulse activity to a cutaneous vibratory wave form was examined by constructing post-stimulus time histograms and cycle histograms. Measures of dispersion of impulse activity around the preferred point of firing in the vibratory waveform indicated that the capacity of individual cuneate neurones to code information about the frequency of the cutaneous vibration was not systematically changed in the presence of afferent-induced inhibition.

Adaptation, Physiological↗
PubMed1977

Human tactile detection thresholds: modification by inputs from specific tactile receptor classes.

1. Human detection thresholds for a vibratory stimulus applied to the volar surface of the index finger were examined under conditions where afferents from specific tactile receptor classes were simultaneously activated from the thenar eminence. The experiments were designed to test whether stimuli which have been shown previously to induce afferent inhibition of ;tactile' neurones in the cuneate nucleus of the cat could modify human subjective performance in a tactile detection task. Conditioning stimuli to the thenar eminence were usually of three forms; steady indentation to engage slowly adapting tactile receptors; 300 Hz vibration to engage Pacinian corpuscles; and 30 Hz vibration to engage the intradermal, rapidly adapting tactile receptors which are thought to be Meissner's corpuscles.2. In ten subjects the mean detection threshold for a 30 Hz test stimulus in the absence of conditioning stimulation was 8.6 +/- 1.0 mum (S.E.). Detection thresholds were increased substantially in the presence of a 300 Hz, 100 mum conditioning stimulus (mean increase 11.1 +/- 2.0 mum), whereas minor or insignificant effects were seen with conditioning stimuli consisting of (a) 30 Hz, 100 mum (mean increase 1.4 +/- 0.8 mum), (b) steady indentation, 1.5 mm in amplitude (mean increase 1.3 +/- 0.7 mum) or (c) 300 Hz, 100 mum to the contralateral thenar eminence (mean increase 0.4 +/- 0.5 mum).3. The 300 Hz conditioning stimulus to the ipsilateral thenar eminence caused a marked increase in detection thresholds at all test stimulus frequencies over the range 10-450 Hz. The effects of the conditioning stimulation therefore operated on inputs from Pacinian corpuscles, which are responsible for vibration detection at 80-450 Hz, and on inputs from the intradermal, rapidly adapting receptors which are responsible for vibration detection at 10-80 Hz.4. The band width of conditioning vibratory frequencies which was effective at amplitudes of 100 mum in bringing about increases in detection threshold extended from 50-80 Hz to 300 Hz, the maximum tested.5. Whereas amplitudes of 1-2 mum produced clear increases in detection thresholds with conditioning stimuli of 300 Hz, amplitudes of > 200 mum were needed at 30 Hz.6. The observed elevations in detection threshold are consistent with an afferent-induced inhibitory action exerted at synaptic relays of the sensory pathway by tactile inputs arising exclusively or predominantly from Pacinian corpuscles.

Adult↗