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Biomedical subjects

S J Atlas

Publications and source records attributed to S J Atlas.

At least 37 records · Page 2Linked to original sources

Application of outcomes research in occupational low back pain: the Maine Lumbar Spine Study.

Outcomes research represents an expansion of traditional clinical research to include issues of cost and quality of care in usual clinical practice, emphasizing outcomes that matter most to patients. In low back disorders, outcomes research has focused on the lack of reliable information to support much of clinical practice and has demonstrated marked variability in the treatment of these common problems. The Maine Lumbar Spine Study represents an example of an outcomes research study to investigate the treatment of patients with sciatica in usual clinical practice. Because low back symptoms are a frequent cause of occupational disability, Workers' Compensation patients were explicitly oversampled. Baseline features were significantly different in those patients who were receiving Workers' Compensation versus those who were not. Efforts to compare outcomes by disability status need to control for these differences. Whereas most Workers' Compensation patients were still receiving disability compensation regardless of treatment at 6 months, patients who were treated surgically were more likely to have come off disability and returned to work than nonsurgically treated patients. Long-term follow-up is necessary to determine whether these differences persist.

Adult↗

Assessing health-related quality of life in patients with sciatica.

STUDY DESIGN: This study analyzed health-related quality-of-life measures and other clinical and questionnaire data obtained from the Maine Lumbar Spine Study, a prospective cohort study of persons with low back problems. OBJECTIVE: For persons with sciatica, back pain-specific and general measures of health-related quality-of-life were compared with regard to internal consistency, construct validity, reproducibility, and responsiveness in detecting small changes over a 3-month period. SUMMARY OF BACKGROUND DATA: Data were collected from 427 participants with sciatica. Baseline in-person interviews were conducted with surgical and medical patients before treatment and by mail at 3 months. METHODS: Health-related quality-of-life measures included symptoms (frequency and bothersomeness of pain and sciatica) functional status and well-being (modified back pain-specific Roland scale and Medical Outcomes Study 36-item Short Form Health Survey (SF-36), and disability (bed rest, work loss, and restricted activity days). RESULTS: Internal consistency of measures was high. Reproducibility was moderate, as expected after a 3-month interval. The SF-36 bodily pain item and the modified Roland measure demonstrated the greatest amount of change and were the most highly associated with self-rated improvement. The specific and generic measures changed in the expected direction, except for general health perceptions, which declined slightly. A high correlation between clinical findings or symptoms and the modified Roland measure, SF-36, and disability days indicated a high degree of construct validity. CONCLUSIONS: These measures performed well in measuring the health-related quality-of-life of patients with sciatica. The modified Roland and the physical dimension of the SF-36 were the measures most responsive to change over time, suggesting their use in prospective evaluation. Disability day measures, although valuable for assessing the societal impact of dysfunction, were less responsive to changes over this short-term follow-up of 3 months.

Adolescent↗

Changing blood use in the AIDS era: the case of elective hip surgery.

BACKGROUND: Concern about the transmission of human immunodeficiency virus via blood has substantially increased the public's anxiety about the safety of the blood supply and has encouraged practices to minimize risks deriving from transfusions. STUDY DESIGN AND METHODS: To assess changes in transfusion practices in elective surgery as awareness of transfusion-transmitted human immunodeficiency virus emerged, 80 randomly selected patients per year undergoing elective total hip replacement in five calendar years between 1977 and 1989 at a large university teaching hospital were studied. RESULTS: Total blood use decreased significantly from an average of 3.3 units per patient in 1977 to 2.1 units per patient in 1989 (p = 0.0003). Autologous blood use increased from essentially zero in 1977 to 82 percent of total blood use in 1989 (p < 0.0001). The threshold hematocrit for postoperative transfusion of allogeneic blood (defined by use of logistic regression models) decreased from 30.1 percent (0.30) in 1977 to 26.7 percent (0.27) in 1989 (p = 0.01). As a result of these changes, the proportion of patients exposed to allogeneic blood decreased from 90 to 16 percent across the study period (p < 0.0001). The dramatic decrease in the use of allogeneic blood in elective total hip replacement surgery during the study period was due to decreased demand for blood during and after the operation and to a striking shift in the blood supply from allogeneic to autologous sources. CONCLUSION: These findings demonstrate that physicians can appropriately alter practices when there are perceived health risks.

Acquired Immunodeficiency Syndrome↗

Inhibition of gonadotrophin-induced ovulation in rabbits by perfusion with dibutyryl cAMP via reduction of ovarian prostaglandin production.

The role of cAMP in ovulation, oocyte maturation and prostaglandin production was assessed using a rabbit ovary preparation perfused in vitro. Dibutyryl cAMP (10(-3), 10(-4) or 10(-5) mol l-1) was added to the perfusate of one ovary. The contralateral, control ovary was perfused with medium alone. Thirty minutes after the onset of perfusion, 50 iu hCG was added to the perfusate of all ovaries. Dibutyryl cAMP inhibited hCG-induced ovulation in a dose-related fashion. No difference in ovum maturity or degeneration was found between control ovaries and ovaries treated with dibutyryl cAMP. Ovarian progesterone production was not affected by exposure to dibutyryl cAMP. The concentrations of 6-keto PGF1 alpha (the stable metabolite of prostacyclin) and PGF2 alpha in the perfusate of ovaries treated with dibutyryl cAMP were 49.6% and 32.0% of the control values, respectively, 12 h after hCG administration. Inhibition of 6-keto PGF1 alpha production by dibutyryl cAMP was dose related. Production of PGE2 was unaffected by dibutyryl cAMP. These data raise the possibility that continuous exposure to dibutyryl cAMP may inhibit hCG-induced ovulation in the perfused rabbit ovary via a reduction in PGF2 alpha and prostacyclin production.

6-Ketoprostaglandin F1 alpha↗

Epidermal growth factor inhibits follicular response to human chorionic gonadotropin: possible role of cell to cell communication in the response to gonadotropin.

Epidermal growth factor (EGF) affects follicular steroidogenesis and expression of gonadotropin receptors. The effects of EGF on hCG-induced estradiol and progesterone secretion and ovulation were examined in the in vitro perfused rabbit ovary. We also examined the effects of EGF on hCG-induced progesterone secretion by isolated granulosa cells. In addition, distribution of hCG within the follicle was probed by immunohistochemical means 30 min after its administration to the in vitro perfused ovary. EGF significantly (P less than 0.05) reduced hCG-induced secretion of estradiol (control, 117 +/- 12 pg/min.follicle; 10 ng/ml EGF, 55 +/- 10) and progesterone (control, 18.2 +/- 1.2 ng/min.follicle; 10 ng/ml EGF, 11.9 +/- 0.8) by the perfused ovary. In contrast, EGF did not inhibit hCG-induced progesterone secretion by isolated granulosa cells. Ovulatory efficiency (number of ovulated ova per number of mature follicles x 100) when EGF was given 30 min before hCG was reduced dose-dependently from 58.2% with no EGF to 8.3% with 10 ng/ml EGF (P less than 0.001). Ovulation was not inhibited by EGF when it was given 30 min after hCG. Distribution of hCG in the preovulatory follicle was confined to the basement membrane, thecal cell layer, and a small fraction of the outer granulosa cell layer. These observations suggest that gonadotropin stimulates the follicle through the release of a secondary signal(s) from ligand-bound granulosa cells near the follicle wall to unexposed cells of the inner avascular area. EGF may inhibit the follicular response to hCG by attenuation of this cell to cell communication.

Animals↗

Effects of intravenous cocaine on reproductive function in the mated rabbit.

A dramatic increase in the use of crack cocaine by young women has resulted in the exposure of a substantial number of fetuses to the drug in utero. The goal of these experiments was to investigate the effects of intravenous cocaine (a model for crack) on reproductive function in the female rabbit. We used two protocols: (1) single daily injections over the course of pregnancy ("single daily" protocol), with animals examined on day 1, 8, 15, 22, or 29, and (2) six hourly injections on the day of mating ("binge" protocol). The maximum tolerated dose of cocaine, 4 mg/kg, was administered at 0.5 ml/min. The single daily protocol increased ovulation but had no effect on fetal and placental weights or preterm delivery. The binge protocol significantly reduced in vitro development of retrieved embryos but did not affect implantation assessed on day 8 of pregnancy.

Animals↗

Do prostaglandins lead to ovulation in the rabbit by stimulating proteolytic enzyme activity?

OBJECTIVE: To determine if prostaglandins (PGs) have a direct effect on the ovarian proteolytic enzyme system by examining ultrastructure of the follicle wall and the microvasculature in the presence and absence of indomethacin and by using the isolated perfused rabbit ovary. DESIGN: Nine hours after administration of human chorionic gonadotropin (hCG) or hCG plus indomethacin, follicles were removed and processed for scanning and transmission electron microscopy. Isolated perfused rabbit ovaries were induced to ovulate with PGF2 alpha (100 ng/mL) in the presence and absence of tranexamic acid (0.1, 1.0, or 10 mM), a plasminogen activator inhibitor. RESULTS: The addition of indomethacin to hCG inhibited ovulation and production of PGs without affecting the follicular microvasculature. However, the changes in follicle wall architecture were less pronounced after treatment with indomethacin. Ovulatory efficiency in response to PGF2 alpha (the percent of follicles greater than 1.5 mm that ovulate) was significantly reduced (P less than 0.01) by 10 mM tranexamic acid. CONCLUSIONS: These results suggest that PGs induce follicular rupture by activation of proteolytic enzymes located in the follicle wall.

Animals↗

Effect of inhibition of oxygen free radical on ovulation and progesterone production by the in-vitro perfused rabbit ovary.

The potential role of oxygen free radicals in hCG-induced ovulation was investigated using the free radical scavenging enzymes superoxide dismutase (SOD) and/or catalase with the in-vitro perfused rabbit ovary preparation. SOD (25 micrograms/ml) and SOD + catalase (25 micrograms/ml) significantly reduced the % of large follicles that ovulated during perfusion (P less than 0.005). Neither maturity nor degeneration of ovulated ova and follicular oocytes was affected by SOD and/or catalase. Progesterone concentration in the perfusate was significantly increased in the SOD + catalase treatment group (P less than 0.01). These results indicate a significant role for oxygen free radicals in the process of ovulation.

Animals↗

Direct effect of angiotensin II on in-vitro perfused rabbit ovary.

The effects of angiotensin II (AII) and its receptor blocker, saralasin (SAR), on ovulation and oocyte maturation were investigated in an isolated, in-vitro perfused rabbit ovary. Ovulation and oocyte maturation were induced by AII in the absence of human chorionic gonadotrophin (hCG). SAR inhibited ovulation induced by AII or hCG, but not oocyte maturation. AII appears to play a critical role in follicle rupture, but not in resumption of oocyte meiosis.

Angiotensin II↗

In vivo administration of allopurinol affects ovulation and early embryonic development in rabbits.

The potential role of the hypoxanthine-xanthine oxidase system in human chorionic gonadotropin-induced ovulation, nuclear maturation, and preimplantation development was investigated in the rabbit by use of the xanthine oxidase inhibitor allopurinol. Allopurinol (50 mg/kg) or vehicle was injected, followed by human chorionic gonadotropin (100 IU). Administration of inhibitor or vehicle was repeated 3 hours later. Ovaries and ovulated ova were inspected 12 or 24 hours after human chorionic gonadotropin administration for follicle rupture, cumulus dispersal, and nuclear maturation. Ova were inseminated in vitro and assessed for development to the blastocyst stage, up to 96 hours after insemination. Allopurinol significantly reduced ovulatory efficiency, defined as the percent of large follicles that ovulate, and decreased the percent of ova with cumulus dispersal. Allopurinol significantly inhibited morula and blastocyst formation. These data suggest that the xanthine oxidase system may play a role in ovulation and early embryonic development.

Allopurinol↗

Developmental potential of rabbit oocyte matured in vitro: the possible contribution of prolactin.

The present study was undertaken to define hormonal conditions for in vitro maturation that support subsequent fertilization and embryonic development. Follicular oocytes were recovered from nonstimulated rabbit ovaries and cultured for 12 h in Brackett's medium supplemented with or without hormones. Matured oocytes were inseminated in vitro and transferred 12 h later to Ham's F-10 medium supplemented with 20% fetal calf serum. The initial cleavage frequency of matured oocytes in Brackett's medium was comparable to the frequency of development for in vitro-matured oocytes under various hormonal conditions. However, the addition of estradiol (E2, 1 microgram/ml) to incubation medium containing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) increased significantly (p less than 0.001) the percentage of embryos achieving morula or blastocyst formation (16/98, 16.3%), as compared to the mature oocytes in medium containing LH, LH plus FSH, or no hormone. The addition of prolactin (PRL) to the maturation medium increased the percentage of development to organized embryos in a dose-dependent manner. In vitro-matured oocytes in medium containing LH, FSH, and PRL exhibited a significantly (p less than 0.001) lower incidence of developmental competence (5/95, 5.3%) than oocytes matured in the presence of E2 in conjunction with pituitary hormones (43/89, 48.3%). These results demonstrate that hormonal composition in the environment of the oocyte is critical for acquisition of developmental capacity. PRL as well as E2 appears to be an important constituent in the process of oocyte maturation, promoting preimplantation embryonic development.

Animals↗

Prostaglandins and progesterone secretion in the in vitro perfused pseudopregnant rabbit ovary.

The relationship between progesterone and prostaglandin (PG) secretion in the pseudopregnant rabbit corpus luteum was investigated using isolated in vitro perfused ovaries. Progesterone and PG secretion were measured on days 1, 11, and 18 of hCG-induced pseudopregnancy. The mean progesterone secretion increased significantly from days 1 to 11, and then decreased significantly by day 18. PG secretion was inversely correlated with progesterone secretion, suggesting that PG might inhibit progesterone secretion. To test this hypothesis, indomethacin, an inhibitor of PG secretion, was administered to intact rabbits from days 11-18 of pseudopregnancy and/or on day 18 ovaries were perfused in vitro with indomethacin. Indomethacin administered in vivo, in vitro, or both in vivo and in vitro significantly reduced PG secretion compared to that in controls, but did not affect progesterone secretion. In addition, perfusion of ovaries in vitro with PGF2 alpha did not alter progesterone secretion on either day 11 or day 18. Thus, although there is an inverse relationship between progesterone and PG secretion during pseudopregnancy, PGF2 alpha alone had no effect on progesterone secretion. These results question the hypothesis that PGF2 alpha alone is the luteolytic factor.

6-Ketoprostaglandin F1 alpha↗

Effects of dibutyryl cyclic AMP on oocyte maturation and ovulation in the perfused rabbit ovary.

The involvement of cyclic AMP (cAMP) in mammalian oocyte maturation was assessed using cultures of rabbit cumulus-oocyte complexes and in-vitro perfused rabbit ovaries. Rabbit cumulus-oocyte complexes were cultured in Brackett's medium with or without dibutyryl cyclic AMP [Bu)2cAMP) at 10(-3), 10(-4) or 10(-5) M for 4-12 h. At 4 h spontaneous meiotic maturation was significantly inhibited by (Bu)2cAMP (P less than 0.025). With prolonged incubation, spontaneous maturation progressed despite exposure to (Bu)2cAMP. When ovaries were continuously perfused in vitro for 12 h with (Bu)2cAMP (10(-3) M) or medium alone, (Bu)2cAMP stimulated ovarian progesterone production, but did not affect ovulation or maturation of follicular oocytes. When ovaries were perfused in vitro with or without (Bu)2cAMP (10(-3), 10(-4) or 10(-5) M) for the first 2 h and then transferred to medium without (Bu)2cAMP for an additional 10 h, ovulation did not occur, but transient exposure to (Bu)2cAMP stimulated a dose-related increase in maturation of follicular oocytes. Degeneration of follicle-enclosed oocytes and cumulus-oocyte complexes was not affected by exposure to (Bu)2cAMP. These results suggest that transient, but not continuous, elevation of cAMP after the gonadotrophin surge may be required for the initiation of oocyte maturation.

Animals↗

In-vivo and in-vitro determination of components of rabbit early pregnancy factors.

Two types of rabbit early pregnancy factor (EPF) components, prepared from the in-vitro perfused ovary and oviduct and from serum ammonium sulphate fractions, were investigated to elucidate the source of EPF production. The state of the animals, i.e. pregnant, pseudopregnant, unstimulated or platelet activating factor (PAF)-treated, and order of addition of the components to the assay lymphocytes were varied to characterize conditions of production and expression of EPF activity. Although each component alone had no EPF activity, combination of two components, i.e. ovary and oviduct components, or serum precipitate and supernatant components, expressed EPF activity. The oviduct and serum supernatant components were produced in pregnancy and pseudopregnancy but the ovary and serum precipitate components were produced only in pregnancy. The similarity of the production pattern and ability of the perfusate and serum components to yield EPF activity when combined suggests that they are similar or the same. The sources of stimulation of EPF production did not appear to affect component production because the activity produced by the perfused ovary and oviduct in pregnancy or in response to PAF stimulation appeared similar. Oviduct and supernatant components apparently bound directly to lymphocytes. These results suggest that EPF components are produced in the ovary and oviduct individually and that the combination of the two components expresses EPF activity in the rabbit.

Animals↗

Platelet activating factor-induced early pregnancy factor activity from the perfused rabbit ovary and oviduct.

Early pregnancy factor, a glycoprotein, and platelet activating factor, a phospholipid, are early signals of pregnancy appearing during the preimplantation period. The aim of this study was to determine if the administration of platelet activating factor to rabbits would stimulate the production of early pregnancy factor and, if so, to ascertain the organs responsible. Early pregnancy factor was assayed after the administration of synthetic platelet activating factor to intact rabbits, rabbits that had undergone bilateral salpingo-oophorectomy, and isolated in vitro perfused rabbit ovary and/or oviduct. Although serum early pregnancy factor activity was detectable 30 minutes after platelet activating factor injection in intact rabbits, no activity was found in rabbits whose ovaries and oviducts had been removed. Perfusate early pregnancy factor activity was detectable only in the presence of both ovary and oviduct, and was first evident 120 minutes after platelet activating factor exposure. However, combined samples of perfusates from the ovary alone and oviduct alone expressed positive early pregnancy factor activity. Furthermore, the addition of platelet activating factor to either single or combined perfusates did not increase early pregnancy factor activity. Our data imply that platelet activating factor induces the production of ovary and oviduct early pregnancy factor components independently.

Animals↗

Effects of prostacyclin on ovulation and microvasculature of the in vitro perfused rabbit ovary.

Prostacyclin (prostaglandin I2) methyl ester at 0.1, 1, or 10 micrograms/ml was added to the perfusate of one rabbit ovary every 2 hours for the first 10 hours of perfusion. The contralateral ovary was perfused with medium alone. Prostacyclin methyl ester at 1 and 10 micrograms/ml induced ovulation in the absence of gonadotropin, with ovulatory efficiencies of 26.7% +/- 3.8% and 46.5% +/- 5.0%, respectively. Most ovulated ova (77.4%) did not progress beyond the germinal vesicle stage, and there was no significant degeneration of ovulated ova or follicular oocytes. Examination of the follicular microvasculature 5 hours after exposure to prostacyclin revealed marked vessel dilatation and filling defects at the apex. By 7 hours after prostacyclin exposure, the intrafollicular space contained extravasated resin, reflecting increased vascular permeability. The vascular changes paralleled those previously observed in gonadotropin-induced ovulation. These results indicate that prostacyclin acting locally alters the vascular integrity of the follicle wall and facilitates follicle rupture.

Animals↗

Quantitative light microscopic analysis of corpus luteum growth during pseudopregnancy in the rabbit.

We employed stereological methods at the light-microscope level to examine the mechanism by which corpora lutea (CL) grow during the course of pseudopregnancy in the rabbit. Corpus luteum volume per ovary, the absolute volume of luteal cells per CL, individual luteal cell volume, the number of luteal and endothelial cells per CL, and capillary surface area per CL were examined in rabbits at Days 1, 4, 7, 11, and 18 of pseudopregnancy. Total CL volume increased from 3.7 +/- 0.1 microliter to 30.3 +/- 0.5 microliter over Days 1 to 11 and thereafter decreased to 15.2 +/- 1.1 microliter by Day 18. Stereological analyses showed that the increases in CL volume from Day 1 to Day 11 were due primarily to increases in the volume of individual luteal cells (from 2.6 +/- 0.2 pl on Day 1 to 23.5 +/- 1.7 pl on Day 11, 1 pl = (10 mu)3; r = 0.96), and that the decrease in CL volume after Day 11 resulted largely from a decrease in luteal cell volume (to 12.8 +/- 1.5 pl). In contrast, no change was seen in the number of luteal cells per CL (range 9.1 x 10(5)-12.5 x 10(5)). These data show that CL growth and subsequent regression during pseudopregnancy result primarily from changes in the volume of individual luteal cells, and not from changes in the number of luteal cells. These data support the hypothesis that modulation of progesterone production during pseudopregnancy is due to changes in individual luteal cell volume and not to changes in cell number.

Animals↗