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Biomedical subjects

R Landesman

Publications and source records attributed to R Landesman.

At least 19 recordsLinked to original sources

In vivo analysis of the half-life of the osteoinductive potential of demineralized bone matrix using diffusion chambers.

Subcutaneous implantation of demineralized bone matrix (DBM) from rat initiates a sequence of developmental events that results in endochondral bone formation. This investigation examined the modification of the osteoinductive potential of DBM during the initial stages of this developmental cascade. Diffusion chambers (DC), constructed with filters of known pore size, permitting or excluding cells from entering the chambers, and containing DBM were subcutaneously implanted into Long-Evans male rats for specific time periods (1-7 days). DC were recovered and the osteoinductive potential of the matrix from these chambers was then tested by subcutaneous implantation and assaying the resulting day 11 plaque tissue enzymatically for alkaline phosphatase activity, and histologically for evidence of chondrogenesis and osteogenesis. The possible modification of DBM by local systemic factors (enzymatic degradation) or contact by polymorphonuclear leukocytes (PMNs) was also investigated. We have concluded from this study that the osteoinductive potential of DBM has a half-life of 5-7 days following implantation and although the enzymes collagenase, elastase, and trypsin abolished this activity, pepsin significantly enhanced it. Culture of PMNs with matrix prior to its implantation appeared to have little effect. Furthermore, during the initial stages of matrix-induced endochondral bone formation, DBM serves as both the instructive inducer and permissive substratum required in this process.

Alkaline Phosphatase↗

Treatment of polyhydramnios with prostaglandin synthetase inhibitor (indomethacin).

Polyhydramnios, which is caused by an excess of amniotic fluid, was diagnosed uniformly in eight patients by ultrasound examination and clinical symptoms, namely, premature uterine contraction, abdominal pain, and respiratory discomfort that resulted from excessive pressure on the diaphragm. Fetal anomalies incompatible with extrauterine existence were excluded by serum alpha-fetoprotein levels, repeated sonography, amniocentesis, and chromosomal analyses. Patients were treated with 2.2 to 3.0 mg of indomethacin/kg body weight/day. The treatment was started at an average gestational age of 24 +/- 0.5 weeks and continued for 2 to 11 weeks. All patients had significant improvement with a simultaneous reduction in amniotic fluid volume, fundal height, and umbilical perimeter. All patients were delivered satisfactorily at an average of 39 weeks' gestation. The fetuses were within the normal body weight range of 2750 to 3600 gm and showed normal development during the neonatal period of 2 to 6 months. Before delivery without indomethacin, the polyhydramnios reformed. Adverse effects or intolerance to the drug was avoided by either a reduction in the dose or cessation of indomethacin therapy. Our studies suggest that indomethacin therapy is an effective way to manage pregnancy complicated by polyhydramnios.

Adult↗

Chemotaxis of muscle-derived mesenchymal cells to bone-inductive proteins of rat.

In this investigation we examined the chemotaxis of muscle-derived mesenchymal cells from neonatal rats to partially purified extracts of demineralized bone matrix with osteoinductive properties. Using the modified Boyden chamber assay and muscle-derived mesenchymal cells obtained from neonatal Long-Evans rats, we tested the chemotactic properties of the 4 M guanidine-HCl extract from demineralized rat bone matrix and fractions thereof that were derived from sequential Sepharose CL-6B, TSK-3000 and HPLC-C18 chromatography. We have identified that those fractions exhibiting chemotactic properties were also osteoinductive. Therefore, demineralized bone matrix serves as its own soluble signal and insoluble substratum in the inductive process leading to endochondral bone formation in vivo.

Animals↗

Temporal analysis of the role of growth hormone in the initiation and maintenance of limb regeneration in the hypophysectomized newt Notophthalmus viridescens.

This study was designed to investigate and determine for how long, after either hypophysectomy or the third (last) growth hormone injection (to previously hypophysectomized newts), the circulating and now declining titers of endogenous or exogenous hormone remained at a sufficient concentration to permit a morphologically normal forelimb regeneration response in the adult newt Notophthalmus viridescens. To examine the declining levels of endogenous hormone (hormone withdrawal series [HW]), left forelimbs were amputated at specific times following hypophysectomy. Right forelimbs were amputated 5 days prior to hypophysectomy. The declining levels of exogenous hormone (hormone replacement series [HR] were examined in newts whose left forelimbs were amputated at specific times following the last of three consecutive alternate-day growth hormone injections that were initiated 5 days post hypophysectomy. Right forelimbs were amputated immediately following the first hormone injection. All experimental animals were sacrificed when their right forelimbs regenerated to an advanced digitiform regenerate. In both series right forelimbs regenerated normally. In the HW series normal regeneration resulted only when forelimbs were amputated within 48 hours post hypophysectomy, whereas in the HR series normal regeneration occurred in only those newts whose forelimbs were amputated within 12 hours of the last hormone injection. The regeneration response of left forelimbs in both series gradually declined with the time interval between either hypophysectomy or hormone injection and forelimb amputation. As the hormone titer declined, fewer limbs initiated a normal response; they became progressively more hypomorphic and eventually failed to undergo typical regeneration.

Animals↗

Contraceptive efficacy of bioabsorbable pellets of norethindrone (NET) as subcutaneous implants: phase II clinical study.

The contraceptive efficacy of norethindrone (NET) fused pellets was evaluated over 12 months in a Phase II clinical study with three and four pellets, each pellet containing 35 mg of NET. Volunteers were healthy, fertile, sexually active women. The release rate of NET from three and four pellets, respectively, was 150.3 +/- 7.2 micrograms and 212.5 +/- 8.6 micrograms NET/day. Following the implantation of NET pellets, serum NET levels did not show any 'burst effect' and were sustained at levels between 0.4 and 0.6 ng NET/ml serum with three pellets and 0.6-0.7 ng NET/ml serum with four pellets. With three and four pellets, respectively, 40% and 27% of the women had normal menstrual cycles; 20% and 14% were amenorrheic; 27% and 37% had mid-menstrual spotting or bleeding; and 13% and 22% had prolonged episodes of bleeding. Cardiovascular, hepatic, and renal functions were normal throughout the study. Ovulation was inhibited in 85% and 92% of the cycles with three and four pellets, respectively. In women using three pellets, two pregnancies occurred, one at the 6th cycle and another at the 12th cycle. In women using four pellets, no pregnancies occurred during the entire period of study.

Adult↗

Induction of endochondral bone by demineralized bone matrix from diabetic rats.

In this investigation we examined the osteoinductive potential of demineralized bone matrix derived from chronically diabetic (streptozotocin-induced) rats. Long-Evans rats (28-31 days) were made diabetic with a single injection of streptozotocin (65 mg/kg) and provided food and water ad lib for 2 months. Diaphyseal shafts of femurs and tibias removed from the diabetic rats and their sibling controls were dehydrated, pulverized, sieved to 74-420 micron particles, and demineralized. Matrix was then bioassayed for its ability to induce endochondral bone on day 11 following subcutaneous implantation over the thorax of Long-Evans rats. The resulting plaques of tissue were subjected to histological analysis, determination of alkaline phosphatase activity, and calcium content. Bone matrix derived from diabetic animals proved to be a significantly better inducer of endochondral bone than did control matrix.

Animals↗

Abdominovaginal delivery: modification of the cesarean section operation to facilitate delivery of the impacted head.

The abdominovaginal delivery is a modification of the cesarean section operation in the presence of an impacted fetal head, usually after a prolonged second stage of labor with ruptured membranes. With the legs abducted in either the "Whitmore" or the "frog" position, the wedged vertex is gently lifted with the cupped hand into the open transverse uterine incision, thereby reducing injury to the fetal head and the uterus. With the greater use of cesarean section operation and the sharp reduction in rotational and midforceps deliveries, the abdominovaginal procedure has an increasingly important place in our obstetric armamentarium.

Cesarean Section↗

Subcutaneous bioabsorbable pellets of norethindrone for contraception in women: Phase I. Clinical study.

Ten healthy, normally menstruating female volunteers participated in a 1-year phase I clinical study in which subcutaneous pellet implants of norethindrone (NET) were employed as a low-dose and long-acting potential contraceptive. Two NET pellets were implanted subcutaneously by the aid of a trocar in the forearm of each volunteer on the fifth day after the start of menstrual bleeding. Serum levels of NET, follicle-stimulating hormone, luteinizing hormone, 17 beta-estradiol, and progesterone were determined weekly by radioimmunoassay. The daily NET release from the pellets, based on mean values (+/- standard error of the mean) in five subjects was 79.4 +/- 7.6 micrograms. The mean serum NET level was initially 1.0 +/- 0.34 ng/ml; thereafter, it gradually lowered during the 343 days of the study period to the level of 0.43 +/- 0.09 ng/ml. The ovarian response, days of bleeding, and cycle lengths with continuously sustained release of NET from the pellets were similar to those observed in women taking the daily oral "minipill" of 300 micrograms NET. The results of the phase I study suggest that NET pellet implants may provide a simple and acceptable approach to long-term contraception in women.

Absorption↗

Enzyme assays to detect preovulatory human luteinizing hormone surge.

Nonradioisotopic enzyme assays have been developed to detect the preovulatory luteinizing hormone (LH) surge in the unextracted urine of normally menstruating women. The amino groups on 6-mm glass beads were activated and coupled to the anti-LH-gamma-globulin for enzyme immunoassay or to the LH receptor prepared from bovine corpora lutea for enzyme receptorassay. The LH was conjugated with alkaline phosphatase. The enzyme assays detected preovulatory LH surge in the morning urine samples of 12 normally menstruating women. The LH surge was coincidental with preovulatory serum estradiol rise, shift in basal body temperature, and 4+ spinnbarkeit of the cervical mucus. The serum estradiol and progesterone levels in the luteal phase were indicative of corpus luteum formation.

Adult↗

Hormonal profile as a prognostic index of early threatened abortion.

Twelve pregnancies, in which the initial serum hCG titer as measured by RRA was subnormal, were studied to determine if a hormonal profile would serve as a prognostic index of spontaneous abortion. Three of the 12 patients delivered term babies. The hCG titers remained subnormal throughout the pregnancy, however, the serum E2, P, 17alpha-OHP, and PRL remained normal. One of the 12 patients aborted in week 25 of gestation. The serum hCG and PRL were subnormal; however, the serum E2, P, and 17alpha-OHP were normal. Eight of the 12 patients aborted prior to 100 days' gestation. The serum hCG, E2, and PRL were subnormal whereas the P and 17alpha-OHP were normal. Therefore, in patients who have subnormal serum hCG titers, serum E2 and PRL may provide a prognostic index of spontaneous abortion.

Abortion, Threatened↗