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Biomedical subjects

T Lloyd

Publications and source records attributed to T Lloyd.

At least 73 records · Page 4Linked to original sources

Assessment of the risk of vertebral fracture in menopausal women.

The decision to institute prophylaxis in women with menopausal osteopenia is hampered by the absence of quantitative criteria for appraising the risk of fracture in the individual. We have developed standards for assessing the risk of fracture by relating the prevalence of atraumatic vertebral compression fractures to bone density in sixty-five menopausal women, forty-nine to ninety-two years old. To define the upper limit of the spectrum of bone density, we also studied thirty-one young women, seventeen to twenty-two years old. The density of trabecular bone in a vertebral body was determined by quantitative computed tomography and expressed in terms of milligrams per milliliter of dipotassium hydrogen phosphate. Twenty-five of the menopausal women exhibited at least one fracture (range, one to six fractures), and forty had no fracture. The bone density ranged from -9 to sixty-nine milligrams per milliliter in those with fractures and from twelve to 122 milligrams per milliliter in those without a fracture. The densities in the young women averaged 173 milligrams per milliliter and ranged from ninety-five to 248 milligrams per milliliter. The percentage of subjects with fractures increased as the bone density decreased. It was zero per cent in women with a density of seventy milligrams per milliliter or more, 38 per cent in women with a density between fifty and less than seventy milligrams per milliliter, 71 per cent in those with a density between thirty and less than fifty milligrams per milliliter, and 82 per cent in women with a density of less than thirty milligrams per milliliter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of vaginal contraceptive sponges on growth of toxic shock syndrome-associated Staphylococcus aureus in vitro.

Toxic Shock Syndrome (TSS) is associated with certain toxin-producing strains of Staphylococcus aureus (TSS-S aureus), and with the use of some vaginal devices such as tampons or contraceptive diaphragms. The present study was designed to examine the effect of Nonoxynol-9 (N-9), and of a newly-approved vaginal contraceptive sponge (VCS) containing N-9 on the growth of TSS-S aureus in vitro. Flasks containing culture media inoculated with TSS-S aureus were incubated at 37 degrees C for 30 hours, in the presence or absence of either a VCS, or N-9 alone. At 0.5, 1, 2, 6, and 12 hours, there was suppression of TSS-S aureus colony counts in media containing VCS, compared to control. Colony counts from media containing N-9 demonstrated suppression at 0.5, 1, 2, and 6 hours. After incubation as long as 30 hours, colony counts from VCS-containing media approached, but did not exceed, counts from control media. From these data, it is concluded that this VCS containing N-9 does not enhance the growth of TSS-S aureus in vitro. Instead, an inhibition of bacterial growth for at least 12 hours is observed in media containing VCS, consistent with a bacteriostatic effect. If such an effect is also present in vivo, it would suggest that this type of VCS is unlikely to increase the risk of TSS.

Contraceptive Agents↗

Women athletes with menstrual irregularity have increased musculoskeletal injuries.

We have performed a retrospective three-phase study to evaluate the effect of menstrual status upon musculoskeletal injuries in women athletes. Initially, we collected the menstrual and running histories of women participants in a regional 10-km footrace. In this study, 61% of the respondents to our questionnaire reported a continuous running program, and 39% reported an interruption of at least 3 months of their running program. The most common cause for interruption was injury. Those who had interrupted their running were more likely to have had irregular or absent menses and less likely to have been using oral contraceptives than the group of continuous runners. Secondly, we obtained information on the relationship between bone injury and menstrual status by reviewing the sports medicine records of 207 collegiate women athletes. We found that X-ray-documented fractures occurred in 9% of women athletes with regular menses and in 24% of women athletes with irregular or absent menses. Subsequently, we collected data from a larger population of more serious, but still recreational runners, participating in a national 10-km race. Each portion of this study has yielded similar results: those women who had been injured during their running program were more likely to have had absent or irregular menses, were less likely to have used oral contraceptives, and had been running for more years. We conclude that premenopausal women who have absent or irregular menses, while engaged in vigorous exercise programs, are at increased risk for musculoskeletal injury.

Adult↗

The effect of sympathectomy upon iris tyrosinase activity.

It is generally accepted that interruption of the sympathetic pathway to the eye may result in iris hypochromia in human infants. Weanling Dutch belted rabbits were used as a model system to investigate whether the melanin synthesizing enzyme, tyrosinase, is regulated in the iris of the juvenile animal by adrenergic innervation. Although we did not find a significant decrease in tyrosine activity isolated from the sympathetically denervated iris, we did observe a tenfold fall in iris tyrosine activity between the 30th and 120th days of life in both intact and denervated irides. About 90% of the iris tyrosine activity was localized in the pigmented epithelium and the remaining tyrosinase activity was found in the stromal tissue. This distribution of tyrosine activity was not affected by sympathetic denervation or time.

Aging↗

Renal cell carcinoma arising in a multicystic dysplastic kidney.

Surgical management of the patient with a multicystic dysplastic kidney is a subject of major controversy. Significant improvement in diagnostic techniques has persuaded many clinicians to advocate nonoperative management. The malignant potential of cystic renal dysplasia remains undefined.

Adenocarcinoma↗

In vitro penetration of human sperm into bovine cervical mucus: effects of sperm washing and exposure to low temperature.

Standardized bovine cervical mucus penetration by human sperm in vitro provides information for evaluating male fertility. Normal semen specimens from 20 sperm donors and 17 infertile men were tested for cervical mucus penetration. Rigorous control of test temperature was necessary to guarantee the reliability and reproducibility of cervical mucus penetration. Sperm washing was found to significantly improve cervical mucus penetration for infertile men, from 18 +/- 2.2 to 27 +/- 3.4 mm, P less than .025. Sperm washing for normal donors had no apparent effect on cervical mucus penetration (58 +/- 1.5 mm prewash, 55 +/- 1.7 mm postwash, P greater than .1). The authors conclude that: 1) temperature for cervical mucus penetration testing is critical to reliability, and 2) cervical mucus penetration is a useful screening tool for in vitro procedures proposed to improve sperm function.

Adult↗

The relationship between reproductive performance and blood pressure in the spontaneously hypertensive rat.

Blood pressure was measured serially throughout pregnancy in spontaneously hypertensive rats and in normotensive control rats of the Wistar-Kyoto strain. Changes in blood pressure were also correlated with the outcome of pregnancy. In control rats there was a small but significant decrease in blood pressure between days 20 and 22 of pregnancy (day of birth = day 22.5). In the spontaneously hypertensive rat this decrease occurred earlier, between days 18 and 19 of pregnancy, and was of greater magnitude. There was a positive correlation in the spontaneously hypertensive rat between the number of live-born pups and the magnitude of the decrease in blood pressure. Perinatal mortality, but not litter size, was greater in the spontaneously hypertensive rat than in control rats. Thus the physiologic mechanisms responsible for the decrease in blood pressure in the normal rat are preserved in the spontaneously hypertensive rat, and the successful completion and outcome of pregnancy depend on the capacity of the hypertensive rat to amplify these processes. Consequently, the spontaneously hypertensive rat is not an appropriate experimental model for hypertension of human pregnancy, in particular for preeclampsia, in which the presence of the conceptus characteristically causes blood pressure to rise, especially during the last trimester. However, an investigation of the factors responsible for the profound antihypertensive effect of pregnancy in rats could provide new insights into the mechanisms by which blood pressure is regulated during pregnancy and suggest new therapeutic approaches.

Animals↗

Food restriction increases life span of hypertensive animals.

Food restriction was used to increase the life span of normotensive (WKY) and Spontaneously Hypertensive Rats (SHR). When SHR's were maintained on 40% of an otherwise typical lab rat diet, their mean life spans increased from 18 months to over 30 months. The mean life times of normotensive rats which were similarly food restricted were expanded from 24 months to over 32 months. Histological examination of heart, adrenals, kidneys and brain showed that freely fed hypertensive rats died of end-organ damage associated with high blood pressure. In contrast, deaths of food restricted hypertensive rats appeared due to changes associated with old age, rather than specific lesions due to hypertension. Thus, food restriction allows a genetically hypertensive animal to reach a normal life span and to die of age-related rather than hypertension-related events.

Animals↗

Dua Dua Theatre: an experiment in health education.

This is an account of an attempt to use theatre as a tool to alleviate health problems. The advantages of using a trained theatre group, and the benefits to audiences and to performers are discussed in the context of two plays devised and presented to community (primary) schools within a province of Papua New Guinea. No formal evaluation has been attempted, but audience involvement and participation has been enthusiastic.

Accident Prevention↗

Effects of temperature on in vitro penetration of human sperm into bovine cervical mucus.

A standardized bovine cervical mucus preparation was used to test the hypothesis that the penetration of human sperm into cervical mucus is a temperature-dependent process. Cervical mucus penetration (CMP) was tested in vitro at several incubation temperatures around "room" temperature. Semen specimens were also exposed to cold (0 C) for various periods of time and then tested for CMP at 37 C incubation. We found that incubation at 37 C produced optimal sperm-mucus penetration. Minor fluctuations in ambient laboratory temperature, such as may occur during a workday or between seasons, produced significant variations in CMP results and precluded the comparison of test results longitudinally over time. Prior exposure of normal semen specimens to 0 C for as long as 45 minutes, such as might occur in transport, did not reduce CMP significantly if incubation was performed at 37 C. We conclude that 37 C is the optimal incubation temperature for CMP testing and that if temperature is controlled, CMP is sufficiently simple and reproducible for routine use in physicians' offices and clinical laboratories.

Adult↗

The antihypertensive effect of U-0521 (3',4'-dihydroxy-2-methylpropiophenone).

The synthetic catechol, U-0521, (3',4'-dihydroxy-2-methylpropiophenone) is a competitive inhibitor of both tyrosine hydroxylase and catechol-O-methyltransferase. Continuous subcutaneous administration of 10 mumoles per day of U-0521 via Alzet osmotic minipumps to adult male Spontaneously Hypertensive Rats (SHR) reduced blood pressure from 160 mmHg to 125 mmHg. This effect occurred within two days, persisted for the two weeks that the pumps were in place, and reversed gradually upon cessation of U-0521 administration. Similar treatment of U-0521 to normotensive Wistar Kyoto rats (WKY) did not result in a similar hypotentensive effect. Subcutaneous administration of the same dose to juvenile SHRs led to a blockade in the expression of hypertension. After the five week treatment period, the blood pressure of the U-0521 treated animals escalated rapidly to match the saline treated controls. The antihypertensive effect of U-0521 on SHRs also occurred when the compound was delivered by the oral route at the rate of 50 mg/kg/day.

Aging↗

A comparison of 2-hydroxyestradiol and U-0521 (3'4'-dihydroxy-2-methylpropiophenone, Upjohn) as in situ and in vitro inhibitors of tyrosine hydroxylase.

Feedback inhibition of tyrosine hydroxylase by catechols was evaluated using in situ and in vitro enzyme assays. The three catechol compounds used were norepinephrine, 2-hydroxyestradiol, and 3'4'-dihydroxy-2-methylpropiophenone (U-0521, Upjohn); representing endogenous catecholamines, catechol estrogens, and a synthetic catechol, respectively. The in situ experiments were performed with dissociated retinal cells from rats and with stationary phase adrenergic-like neuroblastoma cells (N1E-115). The catechol estrogen, 2-hydroxyestradiol, resembled the endogenous catecholamine in its potency to inhibit in vitro and in situ tyrosine hydroxylations with IC50 values of 10 microM in vitro and 100 microM in situ. The drug U-0521, which has been used as an inhibitor of catechol-O-methyltransferase (COMT), was also found to be an inhibitor of tyrosine hydroxylase. Further, it was shown to be more potent than the natural catechols, both in vitro and in situ, with IC50 values of 30--600 nM.

Adrenal Glands↗

The catechol estrogen, 2-hydroxyestradiol-17 alpha, is formed from estradiol-17 alpha by hypothalamic tissue in vitro and inhibits tyrosine hydroxylase.

The ability of estradiol-17 alpha to serve as a substrate for estrogen-2/4-hydroxylase in rabbit hypothalamic tissue was determined and compared to that of estradiol-17 beta. Both 2- and 4-hydroxy metabolites of estradiol-17 alpha were formed by the hypothalamic tissue in vitro. The rates of formation of 2-hydroxyestradiol (2-OHE2)-17 alpha and -17 beta were similar as were their kinetic constants (Km and Vmax). In addition, 2-OHE2-17 alpha was shown to inhibit purified rat adrenal tyrosine hydroxylase with a potency comparable to that of 2-OHE2-17 beta, a finding similar to that reported by others with respect to catechol-o-methyltransferase. Since estradiol-17 alpha has a markedly reduced affinity for estrogen receptors compared with extradiol-17 beta, this steroid could be useful in studies designed to distinguish between receptor mediated effects of estrogens and effects that locally formed catechol estrogens may have through their direct interaction with catecholaminergic system in neural tissue.

Animals↗

The receptor-mediated activation of tyrosine hydroxylation in the superior cervical ganglion of the rat.

The addition of carbachol to superior cervical ganglia causes a rapid increase in tyrosine hydroxylation in situ. The increase occurs in ganglia from both newborn and adult animals, and in ganglia from animals pretreated with reserpine. The increase is not due to increased transport of the substrate. The increase is dependent upon the presence of calcium, and is additive to the stimulation produced by dibutyryl cyclic AMP. The stimulation seems specific for tyrosine hydroxylation; dopamine beta-hydroxylation is not increased. Preincubation experiments suggest that the carbachol-induced stimulation is due to a change in the availability of, or the affinity of the enzyme for, reduced pterin cofactor. The stimulation is inhibited by atropine and also by low concentrations of phenoxybenzamine or haloperidol, which suggests that it is caused by an action of carbachol on the interneurons in the ganglia.

Aging↗

Catechol estrogen formation by brain tissue: a comparison of the release of tritium from [2-3H]estradiol with [6,7-3H]2-hydroxyestradiol formation from [6,7-3H]estradiol by rabbit hypothalami in vitro.

In the course of establishing an assay for estrogen-2-hydroxylase activity, a detailed comparison was made between the formation of tritiated water (3H2O) and [6,7-3H]2-hydroxyestradiol (2-OHE2) by rabbit hypothalami in vitro from 2-3H- and 6,7-3H-labeled estradiol, respectively. The amounts of both 3H2O and [6,7-3H]2-OHE2 formed were stimulated several-fold by the nonionic detergent Tween-80. Maximum activity for both functions was associated with the soluble fractions (S2, 17,500 X g supernatant, for tritium release; S3, 100,000 X g supernatant, for 2-OHE2 formation). In contrast, maximal 3H2O formation by rat liver was associated with the microsomal (P3, 100,000 X g pellet) fraction and was virtually abolished by Tween-80. The amount of 3H2O formed exceeded, up to severalfold, the amount of 2-OHE2 produced under all conditions examined and in all subcellular fractions. The bulk of the excess 3H2O formation, unrelated to the production of 2-OHE2, could be eliminated by adding ascorbic acid (10 mM) to the incubation medium. However, a second, smaller component of spurious 3H2O release could not be suppressed. This component was responsible for a persistent lack of stoichiometry between the formation of 3H2O and 2-OHE2, with the former exceeding the latter by up to 2-fold. This discrepancy was unaffected by ascorbic acid (up to 20 mM), unlabeled 2-OHE2 (up to 10 microM), and reducing the temperature of incubation from 37 to 30 C, measures that prolonged the t1/2 of 2-OHE2 during incubation with hypothalamic tissue from under 3 min to over 100 min. These findings 1) raise doubts about the validity of using 3H2O formation from [2-3H]estradiol as a quantitative index of estrogen-2-hydroxylase activity, and 2) establish conditions under which further metabolism of 2-OHE2 is inhibited, thereby making it practical to quantify enzyme activity on the basis of the amount of catechol estrogen formed. Evidence is also presented that the release of 3H2O from [2-3H]estradiol by hypothalamic tissue, unrelated to 2-OHE2 formation, may be enzymatically mediated.

Animals↗