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Biomedical subjects

S Atkinson

Publications and source records attributed to S Atkinson.

At least 19 recordsLinked to original sources

Prevention of deep vein thrombosis after major knee surgery--a randomized, double-blind trial comparing a low molecular weight heparin fragment (enoxaparin) to placebo.

Consecutive patients undergoing knee arthroplasty or tibial osteotomy at four participating hospitals received either enoxaparin, 30 mg subcutaneously every 12 h (n = 66) or an identical-appearing placebo (n = 65). All study medications started the morning after the operation and were continued up to a maximum of 14 days. Patients underwent surveillance with 125I-fibrinogen leg scanning and impedance plethysmography. Bilateral contrast venography was performed routinely at Day 14 or at time of discharge, if sooner. Deep vein thrombosis was detected by venography in 35 of 54 patients (65%) in the placebo group and in 8 of 41 patients in the enoxaparin group (19%), a risk reduction of 71%, P less than 0.0001. For the entire study group, deep vein thrombosis was detected by either venography of non-invasive tests in 37 of 64 patients (58%) in the placebo group and in 11 of 65 patients (17%) in the enoxaparin group, a risk reduction of 71%, P less than 0.0001. Proximal vein thrombosis was found in 19% of the placebo patients and in none of the enoxaparin patients, a risk reduction of 100%, P less than 0.001. Bleeding complications occurred in 5 of 65 patients (8%) in the placebo group and in 4 of 66 patients (6%) in the enoxaparin group, P = 0.71. There were no differences in the amount of blood loss, minimum hemoglobin levels and number of units of packed red cells given between the two treatment groups. We conclude that a fixed dose regimen of enoxaparin, started post-operatively, is an effective and safe regimen for reducing the frequency of deep vein thrombosis after major knee surgery.

Aged

Western blotting analysis in patients with MS using human brain vessels as antigen.

Serum samples from patients suffering from multiple sclerosis, other neurological diseases and normal controls were screened by "western blotting" for antibody directed against proteins of human brain vessels purified from a post mortem brain. A small number of sera contained autoantibodies against some of the proteins of the brain vessels, particularly in patients suffering from MS, epilepsy and migraine. The significance of these results is discussed.

Antibody Specificity

Interrelationships between left ventricular volume and output during exercise in healthy subjects.

To better characterize the relationship between left ventricular volume response and improved ventricular ejection and output during supine exercise in normal subjects, 36 healthy asymptomatic volunteers (age 39 +/- 17 yr) were studied with radionuclide ventriculography during recumbent bicycle ergometry. Relative changes in left ventricular end-diastolic and end-systolic volume were measured at rest and during exercise by a modification of the radionuclide counts-based method that accounted for variability in stress blood pool counts. A biphasic response was noted in left ventricular end-diastolic volume with an initial increase in early exercise (8.5 +/- 11% at 200 kpm/min and 11 +/- 12% at 300 kpm/min) followed by a progressive and significant decline at peak exercise (-3.3 +/- 18% at 547 +/- 140 kpm/min; P < 0.05). There was substantial variation in end-diastolic volume response at peak exercise in the group as a whole, which could be more closely related to changes in end-systolic volume (r = 0.84, P < 0.0001) than in heart rate (r = -0.57, P < 0.01) or age (r = 0.36, P < 0.05) of the study subjects. Despite the decline in ventricular filling, systolic function appeared to improve dramatically at peak exercise (change in left ventricular ejection fraction 15.5 +/- 6.4, P < 0.0001). Although not directly related to increasing systolic ejection, end-diastolic volume was directly related to the percent change in stroke volume at peak exercise among the study subjects (r = 0.88, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Seasonal testosterone pattern in Hawaiian monk seals (Monachus schauinslandi).

Blood samples from four captive male Hawaiian monk seals were collected at intervals of one month for one year for testosterone assay. Plasma testosterone concentrations, measured by radioimmunoassay, revealed a clear seasonal pattern. The lowest mean testosterone concentration (0.09 +/- 0.04 ng ml-1) occurred in January, and the highest (1.78 +/- 0.40 ng ml-1) in June. The seasonal occurrence of births and of injuries related to mating in wild populations of Hawaiian monk seals showed a distinct association with the period of high testosterone. This study supports other data that indicate that the Hawaiian monk seal is a seasonal breeder and is reproductively active for longer than monachine seals that live in higher latitudes.

Animals

Physiological mechanisms for metalloproteinase activation.

The activation of procollagenase and prostromelysin by mechanisms that might be functional in vivo has been investigated. Studies with cell monolayers plated onto collagen films have indicated key roles for plasmin and TIMP in these processes. Prostromelysin activation could be rapidly effected by fibroblast monolayers in the presence of plasminogen, with identical kinetics to plasminogen-streptokinase generated plasmin. Procollagenase activation by plasmin was shown to be poor, although an M(r) shift of 11,000 occurred. Activation was enhanced ten-fold by the presence of active stromelysin even at a very low molar ratio. A tumour cell line secreting procollagenase but not stromelysin was found to be dependent upon the addition of both stromelysin and plasminogen to effect degradation of collagen films. Biochemical studies of metalloproteinase activation were carried out using other purified proteinases synthesized by connective tissue cells including endopeptidase 24.11, endopeptidase-2, cathepsin B and cathepsin L. None was a particularly effective activator relative to plasmin, but cathepsin B was shown to activate stromelysin. By use of both cell model systems and biochemical studies of purified enzymes we have found that the role of plasmin as the major metalloproteinase activator in normal connective tissue cells remains unchallenged.

Amino Acid Sequence

IGF-II receptors and IGF-II-stimulated glucose transport in human fat cells.

Insulin-like growth factor II (IGF-II) receptors have been described in rat but not in human adipocytes. In both species, IGF-II has been reported to stimulate glucose transport by interacting with the insulin receptor. In this study, we have unequivocally demonstrated the presence of IGF-II receptors in human adipocytes. 125I-labeled IGF-II specifically binds to intact adipocytes, membranes, and lectin-purified detergent solubilized extracts. Through the use of 0.5 mM disuccinimidyl suberate, 125I-IGF-II is cross-linked to a 260-kDa protein that is identified as the IGF-II receptor by displacement experiments with unlabeled IGF-II, IGF-I, and insulin and either by immunoprecipitation or by Western blot analysis with mannose 6-phosphate receptor antibodies. The concentrations of IGF-II required for half-maximal and maximal stimulation of glucose transport in human adipocytes are 35 and 100 times more than that of insulin. The possibility of IGF-II stimulating glucose transport by interacting predominantly with the insulin receptor is suggested by the following: 1) the concentration of IGF-II that inhibits half of insulin binding is only 20 times more than that of insulin; 2) the lack of an additive effect of IGF-II and insulin for maximal stimulation of glucose transport; 3) the ability of monoclonal insulin receptor antibodies to decrease glucose transport stimulated by submaximal concentrations of both IGF-II and insulin; and 4) the ability of IGF-II to stimulate insulin receptor autophosphorylation albeit at a reduced potency when compared with insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue

Immunization of ovariectomized ewes against progesterone, oestrogen or cortisol to detect effects of adrenal steroids on reproduction.

Ovariectomized ewes were immunized against cortisol, oestrogen or progesterone to determine whether steroids of non-ovarian origin occur in sufficient amounts to influence the reproductive system. Ewes immunized against oestrogen (oestrone + oestradiol) had smaller uteri (P less than 0.05) and a lower concentration of oestradiol in uterine tissue (P less than 0.05), while the adrenal gland was heavier (P less than 0.05). In the peripheral plasma of immunized ewes, the concentration of FSH, but not LH, was increased (P less than 0.05). Ewes immunized against cortisol also had smaller uteri (P less than 0.05) and heavier adrenal glands (P less than 0.05), but gonadotrophins and the concentration of oestradiol in the uterus were unaffected. Immunization against progesterone, or injection with synthetic glucocorticoids, did not affect any of the characteristics measured. We conclude that the adrenal gland of the ewes produced sufficient oestrogen or aromatizable androgen to have significant effects on the reproductive system. In contrast, adrenal production of progesterone did not produce detectable biological effects. Immunization against cortisol did affect the reproductive system, but the mechanism of this action could not be determined.

Adrenal Glands

LH, FSH and ovulation rate in ewes treated with exogenous oestradiol.

In two experiments, mature Merino ewes were fitted with subcutaneous implants containing oestradiol-17 beta or empty implants (control). Peripheral concentrations of LH and FSH were measured during luteal and follicular phases, which were synchronized by means of intravaginal progestagen-impregnated sponges. The ovulation rates of the ewes were determined by laparoscopy, 1 week after luteolysis. In Exp. 1, small implants (3 mm) decreased the LH pulse frequency before luteolysis. In the ewes with oestradiol implants, the amplitude of the preovulatory surge of LH was reduced and the onsets of the LH and FSH surges were delayed. There was no effect of oestradiol on LH baseline, LH pulse amplitude or in the concentration of FSH during the luteal or follicular phases. In Exp. 2, larger implants (10 mm) were inserted for the luteal, follicular, or luteal + follicular phases. The control ewes had empty implants. In the ewes with oestradiol implants, LH pulse frequencies were decreased during the luteal phase. This decrease persisted throughout the follicular phase, even though the oestradiol implants had been removed. There were no differences in the other measures of LH or FSH in the luteal or follicular phases. Ovulation rates were not affected by oestradiol treatment in either experiment, indicating that the regulation of LH pulse frequency is not a critical factor in the determination of ovulation rate in ewes. This was supported by retrospective analysis of the gonadotrophin profiles of single and twin-ovulating ewes, in which all measures of LH were similar between the two groups. However, twin-bearing ewes had slightly higher circulating concentrations of FSH during the luteal phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of oestradiol implants on the ovulation rate of the ewe.

In a series of 5 experiments, ewes were treated with implants releasing oestradiol-17 beta and the effects on ovulation rate were observed. Large doses of oestradiol-17 beta (greater than 20 micrograms/day) produced anovulation while smaller amounts only reduced the proportion of twin ovulations. Amounts of exogenous oestradiol comparable to ovarian production rate in the luteal phase (less than 1 microgram/day) produced a significant (P less than 0.01) suppression in ovulation rate. Treatment during the follicular phase of the oestrous cycle was most effective, but treatment during the luteal phase alone also appeared to suppress ovulation rate. Furthermore, in 2 of 3 experiments ewes treated with low amounts of oestradiol during the first half of the luteal phase were less likely to have multiple ovulations at the subsequent oestrous period. The results support the hypothesis that oestrogen is involved in the physiological control of ovulation rate in the ewe, but this action is probably not restricted to the assertion of dominance by a maturing follicle during the follicular phase.

Animals

Nutrient costing.

For the purpose of computing changes in food cost over time as well as the planning of proper nutrition education and dietary counselling, the cost of important Ethiopian foods was collected in Addis Ababa markets for three and one-half years and computed for the amount of energy and protein yield per unit price. In general, cereals and legumes faired well in their contribution of these nutrients at low cost. Certain foods, such as vetch, sugar and marmalades were also found to contribute a significant amount of nutrients at low cost. Because of the neurotoxic content in vetch and the contribution of a single nutrient as an energy source in the case of the latter two, their utilization during meal planning is subject to careful consideration. Foods of animal origin are second to last in their nutrient contribution per cost although their nutrient density makes them important in consumer demand. Root crops and vegetables that are known for their bulk are at the bottom of the list of good nutrient contributors per cost.

Dietary Services

Inadequate function of corpora lutea following the induction of ovulation with monensin and FSH in seasonally anoestrous ewes.

Sixteen ewes in mid-seasonal anoestrus were stimulated to ovulate using sequential injections of FSH (total dose 10 mg) over a 4-day period. Half of the ewes received a dietary growth promotant (monensin) known to enhance the ovarian response to exogenous gonadotrophins. The ewes were ovariectomized on day 5 or 11 (day 0 = the initiation of FSH treatment). Serial blood samples were taken in half of the ewes to determine peripheral concentrations of LH and a single sample of ovarian venous blood was collected before ovariectomy. All luteal structures were dissected from the ovaries, counted and incubated in vitro to determine progesterone production. The luteal structures were then examined histologically for the abundance of luteal cells. The physical appearance of the ovary, along with plasma concentrations of LH and ovarian venous oestradiol indicated that the monensin-treated ewes ovulated before control ewes. The corpora lutea from control ewes produced significantly (P less than 0.05) more progesterone than did the corpora lutea from the monensin-treated group. Furthermore, only 7% of the remaining luteal structures in the monensin-treated group produced significant amounts of progesterone on day 11, whereas 61% of the luteal structures in the control group were actively secreting progesterone. The mean number of granulosa cells in the follicles was similar at ovulation in the two groups, but the mean numbers of large and small luteal cells were significantly (P less than 0.05) lower in luteal structures from the monensin-treated ewes than in those from the control ewes.(ABSTRACT TRUNCATED AT 250 WORDS)

Anestrus

Thyrotrophin-blocking antibodies in goitrous primary hypothyroidism: detection by a highly sensitive bioassay and determination of site of action.

Using a highly sensitive bioassay technique, the presence of antibodies capable of blocking the stimulation of thyrocyte function by TSH has been investigated in the sera of a group of 50 patients with primary hypothyroidism. TSH-blocking activity was detected in immunoglobulin (IgG) preparations from the sera of 13 patients (26%). All 13 IgG preparations blocked both TSH-stimulated iodide uptake and cyclic AMP generation (Spearman's rank correlation = 0.6, p = 0.02). However, only one IgG preparation blocked dibutyryl cyclic AMP-stimulated iodide uptake. The presence of TSH-blocking antibody activity was associated with goitrous (ten out of thirteen patients) as well as atrophic (two out of thirteen patients) primary hypothyroidism. Furthermore, TSH-blocking activity was not associated with other thyroid autoantibodies, as thyrotrophin-binding-inhibiting immunoglobulins and anti-TSH antibodies were undetectable in all cases and there was no correlation between TSH-blocking activity and the presence or titre of anti-thyroglobulin or anti-microsomal antibodies. This study indicates that TSH-blocking antibodies are present in the serum of some patients with primary hypothyroidism and are directed towards a site, presumably adjacent to or contiguous with the TSH receptor, that is not the binding site for TSH. The coexistence of TSH-blocking activity and goitre in the majority of these patients implies that these antibodies, although capable of blocking TSH-stimulated thyroid hormone biosynthesis, do not necessarily inhibit the mitogenic action of TSH in vivo.

Antibodies

Adrenal glands alter the concentration of oestradiol-17 beta and its receptor in the uterus of ovariectomized ewes.

To investigate the effects of adrenal hormones on oestrogen activity in the uterus, ovariectomized ewes were either adrenalectomized, administered glucocorticoid-like preparations (CORT), or remained as controls. The adrenalectomized ewes were maintained with a corticoid-replacement therapy and monitored daily for plasma glucose and Na+/K+ concentrations. Blood samples were collected from all ewes at 15-min intervals for 4 h and assayed for LH and FSH. The adrenalectomized ewes were killed 9 days after adrenalectomy, while the CORT ewes were killed after 3 weeks of drug therapy. The control ewes were killed simultaneously with the CORT ewes. Uterine tissues were homogenized and the numbers of oestradiol receptors and tissue concentrations of oestradiol-17 beta were measured. The adrenalectomized ewes had significantly higher concentrations of cytosolic oestrogen receptors in the uterus than did the control ewes, which had significantly higher concentrations than the CORT ewes (0.95 +/- 0.06, 0.76 +/- 0.02 and 0.60 +/- 0.02 (S.E.M.) mumol/kg protein respectively). The concentrations of oestradiol-17 beta measured in uterine tissues were significantly lower in adrenalectomized and CORT ewes than in control ewes (37.4 +/- 5.5, 61.7 +/- 25.7 and 135.5 +/- 12.8 pmol/kg respectively). There were no significant differences between any groups in the peripheral concentrations of LH or FSH. These results indicate that the adrenal gland affects the concentrations of both oestrogen and its receptor in the uterus of ovariectomized ewes, probably by different mechanisms. These effects are not mediated by gonadotrophins.

Adrenal Glands