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Biomedical subjects

L R Beck

Publications and source records attributed to L R Beck.

At least 19 recordsLinked to original sources
PubMed1994

Remote sensing as a landscape epidemiologic tool to identify villages at high risk for malaria transmission.

A landscape approach using remote sensing and geographic information system (GIS) technologies was developed to discriminate between villages at high and low risk for malaria transmission, as defined by adult Anopheles albimanus abundance. Satellite data for an area in southern Chiapas, Mexico were digitally processed to generate a map of landscape elements. The GIS processes were used to determine the proportion of mapped landscape elements surrounding 40 villages where An. albimanus abundance data had been collected. The relationships between vector abundance and landscape element proportions were investigated using stepwise discriminant analysis and stepwise linear regression. Both analyses indicated that the most important landscape elements in terms of explaining vector abundance were transitional swamp and unmanaged pasture. Discriminant functions generated for these two elements were able to correctly distinguish between villages with high and low vector abundance, with an overall accuracy of 90%. Regression results found both transitional swamp and unmanaged pasture proportions to be predictive of vector abundance during the mid-to-late wet season. This approach, which integrates remotely sensed data and GIS capabilities to identify villages with high vector-human contact risk, provides a promising tool for malaria surveillance programs that depend on labor-intensive field techniques. This is particularly relevant in areas where the lack of accurate surveillance capabilities may result in no malaria control action when, in fact, directed action is necessary. In general, this landscape approach could be applied to other vector-borne diseases in areas where 1) the landscape elements critical to vector survival are known and 2) these elements can be detected at remote sensing scales.

Animals↗
PubMed1990

A baboon model for pregnancy-associated antigens (PAPP-A, PP5, PP14).

By radioimmunoassays established on human derived antigens, PAPP-A, PP5 and PP14 immunoreactivity was detected in placental extracts and blood of pregnant baboons. None of the serial dilution curves suggested parallelism between respective human and baboon samples. Based on slopes of regressed logit-log transformed binding data, PAPP-A demonstrated the greatest degree of interspecies immunological crossreactivity. PP14 showed the least conservation of antigenic determinants. Physicochemical characterization on heparin, zinc chelate and bovine thrombin affinity matrices could not distinguish human from baboon-derived antigens. As in the human, baboon PAPP-A and PP5 were not detected in blood of male or non-pregnant animals. PP14 was detected in baboon follicular fluid, and only PP5 immunoreactivity was measured in culture media of baboon embryos. Of the three antigens, PAPP-A was detected in pregnant baboons at about 61 days gestation, that is, 4 weeks before PP5 and PP14. With the exception of PP14 which attained peak concentration at 118 days of pregnancy, PAPP-A and PP5 concentrations were greatest at term. In conjunction with physicochemical and immunological criteria, these physiological kinetics clearly support a role for developing a baboon model to serve for further studies into feto-maternal signals, particularly antigens such as PAPP-A and PP5.

Animals↗
PubMed1986

Cryopreservation and transfer of baboon embryos.

The feasibility of modifying bovine cryopreservation methods for use with baboon embryos was evaluated. Twenty-six baboon embryos at the eight-cell to blastocyst stage of development were transferred after being frozen using glycerol as cryoprotectant. Either a two-step fast of a controlled linear temperature depression was achieved to -40 degrees C, followed by plunging into liquid nitrogen. After thawing, embryos were rehydrated in medium containing sucrose (0.5 to 1.0 M) using various methods of glycerol dilution. Embryos were transferred nonsurgically to anesthetized recipient baboons. Two term pregnancies resulted from six embryos frozen using the controlled linear cooling method and rehydrated by dropwise dilution of the sucrose (0.8 M) medium. Later cell stages had a greater morphological integrity postthaw than did earlier developmental stages, and embryos frozen by the linear cooling-rate method had less cell damage than those frozen by the fast method.

Animals↗
PubMed1985

Long-acting injectable microsphere formulation for the parenteral administration of levonorgestrel.

The pharmacokinetic and pharmacodynamic effects of a long-acting formulation of levonorgestrel microencapsulated in a biodegradable polymer poly(DL-lactide-CO-glycolide) was tested in baboons. The polymer microspheres provided continuous release of levonorgestrel for up to 6 months following a single intramuscular injection. The treatment inhibits ovarian function for 3-6 months, depending on the dose. The duration and pattern of levonorgestrel release varies according to the quality and size of the microspheres. The microsphere delivery system offers a promising new approach to developing a long-acting injectable contraceptive based on levonorgestrel.

Animals↗
PubMed1984

Controlled-release delivery systems for hormones. A review of their properties and current therapeutic use.

Biomedical engineering approaches used to develop controlled-release delivery systems for hormones are here reviewed regarding system design and therapeutic applications. The biomedical engineering approach uses a system of non-drug components to control the rate and duration of hormone delivery. The non-drug components vary from system to system, but generally include: a reservoir for the hormone; a barrier or regulator to contain the hormone within the reservoir and to control its release; an energy source to remove the hormone from the reservoir; and a pathway for egress of the hormone from the system. Controlled-release delivery systems for hormones discussed in this review include mechanical and osmotic pumps; intraocular, intravaginal and intrauterine platform devices; biodegradable and non-biodegradable subcutaneous implants; and small particulate systems including microcapsules, microspheres and liposomes. Examples of the therapeutic application of the various systems are given along with a discussion of design factors and pharmacological aspects relevant to their clinical use.

Amenorrhea↗
PubMed1983

Clinical evaluation of an improved injectable microcapsule contraceptive system.

Pharmacokinetics and pharmacodynamics of a long-acting injectable microcapsule, poly(DL-lactide-co-glycolide), delivery system were tested in 10 women. Two doses (75 or 100 mg of norethindrone) were administered by intramuscular injection. Treatment suppressed ovarian function and inhibited ovulation for 3 months in all subjects. Levels of norethindrone in subjects who received the 100 mg dose were proportionately higher than those in subjects who received the 75 mg dose. Subsequent to the injection, there was a rapid rise in the serum levels of norethindrone followed by a gradual decline until 8 to 10 weeks. Between 10 and 20 weeks after treatment, there was a secondary rise and fall in the serum levels of norethindrone. Treatment caused suppression of the endometrium for 3 months, and, except for spotting and irregular menstrual cycles, there were no adverse side effects. Treatment had no significant effect on serum lipids.

Adult↗
PubMed1983

The abortifacient effect of synthetic androstane derivatives in the baboon.

Synthetic androstane derivatives have been tested for their ability to induce abortion during early pregnancy in primates. Two compounds were studied following intramuscular (IM) and oral treatment in fourteen baboons. A five-day treatment regimen was started at approximately day 20 of pregnancy in 12 baboons, with treatment delayed until after day 40 in two baboons. All seven baboons treated IM with either compound aborted following intramuscular treatment, although three required a second treatment series beginning on approximately day 40 of pregnancy. Two of five baboons treated orally aborted following the single treatment series initiated around day 20 of pregnancy. The two baboons treated only after day 40 continued to term and delivered healthy infants. These compounds are therefore effective at terminating pregnancy when given around the time of the missed menstrual period. Further studies are necessary to determine optimal dose and treatment schedule.

Abortifacient Agents↗
PubMed1983

Poly(DL-lactide-co-glycolide)/norethisterone microcapsules: an injectable biodegradable contraceptive.

Microcapsules made from a biocompatible, biodegradable polymeric excipient, poly(DL-lactide-co-glycolide) (DL-PLGA) that contained 22 weight percent (wt %) norethisterone (NET), were prepared by a solvent-evaporation microencapsulation process. The effects of changing both the lactide-to-glycolide ratio of the DL-PLGA and the size of the microcapsules on the rate of NET release and the rate of excipient biodegradation were determined in vivo. NET release rates were determined in baboons after injecting the microcapsule formulations intramuscularly. Serum samples obtained at various times following treatment were analyzed for NET, progesterone, and estrogen by radioimmunoassay (RIA). Biodegradation kinetics were determined by injecting NET microcapsules made from radiolabeled DL-PLGA intramuscularly into the hind legs of rats. Residual radioactivity at the injection site was determined at various times after treatment by combustion analysis of the muscle tissue. Changing the ratio of the comonomers to include more glycolide (DL-lactide:glycolide-96:4, 92:8, 87:13, 74:26) increased the rate of NET release and accelerated the biodegradation of the copolymer excipient. Decreasing the size of the microcapsules increased the rate of NET release. On the basis of these studies a NET microcapsule formulation has been identified for clinical testing which releases NET for 3 months and biodegrades completely within 6 months.

Animals↗
PubMed1982

Demonstration of an early abortifacient effect of norethisterone (NET) in the primate (baboon).

A long-acting injectable contraceptive which provides continuous controlled release of norethisterone (NET) for three months following a single intramuscular injection was tested for antifertility effects in baboons using a low dose of microcapsules (total NET dose 2.5 mg; daily dose approximately 0.03 mg/day) which has no effect on ovarian function or ovulation. The continuous administration of NET during the cycle of conception had no effect on ovulation, fertilization or implantation as evidenced by the occurrence of nine pregnancies following 23 test matings. Pregnancy was diagnosed by the measurement of baboon chorionic gonadotropin hormone and the maintenance of elevated serum progesterone levels past the normal time of menstruation. Six of the nine pregnancies, however, ended in abortion between days 27 and 35 of pregnancy. The remaining three pregnancies continued to term and normal, healthy babies were delivered. Five control baboons included in this study became pregnant and all delivered normal, healthy infants. The results of this study demonstrate that early abortion should be considered as a mechanism of antifertility action of NET when administered continuously in low doses. These findings are contrary to the generally accepted explanation that low-dose synthetic progestins exert their contraceptive effect by inhibiting sperm transport and/or preventing implantation.

Abortion, Spontaneous↗
PubMed1981

Clinical evaluation of injectable biodegradable contraceptive system.

A new long-acting injectable contraceptive system was tested in 24 women. The system consists of microspheres made of biodegradable d,l-polylactic acid in which micronized crystals of norethisterone (NET) are homogeneously dispersed. In previous animal studies we showed that NET is slowly released from the microspheres for 6 months, and after the drug is released, the microspheres biodegrade into lactic acid by the process of hydrolysis. The serum levels of NET, estrogen, and progesterone were monitored by radioimmunoassay, and the effects of treatment on ovarian function and menstrual bleeding were evaluated. The doses ranged from 29 to 370 mg of microspheres containing 7.25 to 94.5 mg of NET or 0.134 to 2.30 mg of NET/kg of body weight. The duration of the NET release was 6 months, and the serum NET profiles in women were similar to those previously described in subhuman primates. Following a small burst, there was a gradual decline in the serum levels of NET over 6 months after treatment. The serum levels of NET varied in proportion to the dose. Doses less than 0.267 mg of NET/kg had no discernible effect on either ovarian function or menstrual bleeding. Doses ranging from 0.419 to 2.30 mg had variable effects on ovarian function and menstrual bleeding. Higher doses caused suppression of ovarian function for longer periods of time, increased the interval between episodes of menstrual bleeding, and decreased the quantity of blood loss during each episode. The treatment was well tolerated by all subjects, and, with the exception of spotting and irregular menstrual cycles, there were no adverse side effects. Based on this initial study, it was determined that doses ranging from 1.33 to 3.45 mg of NET/kg are necessary to suppress ovulation for 6 months. Additional studies with the use of higher doses are currently under way.

Adult↗
PubMed1979

New long-acting injectable microcapsule contraceptive system.

A new long-acting, injectable contraceptive which provides continuous controlled release of the steroid norethisterone (NET) for a precise period of 6 months following a single intramuscular injection is described. The prototype system consists of microcapsules made of the biodegradable polymer d, l-polylactic acid, in which micronized crystals of NET are homogeneously dispersed. NET is slowly released from the microcapsules following intramuscular injection at a rate of 0.90 microgram NET/day/mg of microcapsule by diffusion of the steroid from the polymer matrix. Three different doses of a standard preparation of microcapsules were tested in normally cycling female babbons (4 to 5 baboons/group). Following injection of either 300, 200, or 100 mg of microcapsules containing 75, 50, or 25 mg of NET, blood samples were collected at selected intervals and analyzed for NET, estrogen, and progesterone by radioimmunoassay. All three doses provided continuous NET release for 6 months following injection. The NET serum profiles for the different doses are parallel, and ovulation was inhibited in all baboons for 6 months following treatment.

Animals↗
PubMed1979

The baboon as a primate model for the study of endometrium.

A series of transcervical uterine biopsy specimens were obtained at various stages of the menstrual cycle from a colony of 11 normally cycling female baboons, Papio anubis and Papio cynocephalus. Morphologically, baboon endometrium appeared to be similar to human endometrium. Alkaline phosphatase activity was maximal throughout the preovulatory phase and during the late postovulatory period. During the preovulatory phase acid phosphatase was not demonstrable but increased after ovulation to reach maximal activity prior to menstruation. While differences exist between human and baboon endometria, the overall morphologic and histochemical changes are similar. In addition, the baboon's endometrium is readily accessible by transcervical uterine biopsy, thus making these animals valuable primate models for study of human reproductive problems.

Acid Phosphatase↗
PubMed1979

A new long-acting injectable microcapsule system for the administration of progesterone.

A long-acting injectable microcapsule system for the controlled-release systemic administration of progesterone (P4) is described. The system consists of microcapsules made of the biodegradable polymer, d,l-polylactic acid, which contain crystalline P4. Following injection, P4 is released from the microcapsules by diffusion and biodegradation of the polymer matrix. The rate of P4 release from the prototype microcapsule system in vivo is 1.3 microgram of P4/day/mg of microcapsules, and the duration of release is 30 days. Vaginal estrous cycles in rats and cyclic ovarian function in baboons were inhibited for 1 month following a single injection of P4 microcapsules. The effects of continuous progesterone therapy on reproductive function in both rats and baboons are dose-dependent. The utility of the system as a once-a-month injectable contraceptive is established in the baboon model.

Animals↗
PubMed1979

The effects of oxytocin on fetal scalp temperature.

During a study of fetal temperature, it was found that there was a significantly higher temperature among infants whose mothers received oxytocin than among a comparable control group. These data indicate that normal-appearing oxytocin-induced contractions may reduce uterine blood flow and thereby raise the intrauterine fetal temperature.

Female↗