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Biomedical subjects

L D Anderson

Publications and source records attributed to L D Anderson.

At least 37 records · Page 2Linked to original sources

Hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) is a genetically determined condition that is often confused with, and misdiagnosed as, spastic diplegic cerebral palsy. Both autosomal dominant and recessive forms have been reported. We present three index patients in a single family with this disease. The pedigree of three generations strongly supports the genetic basis of an autosomal dominant condition. Awareness of this entity may help in genetic counseling and possibly avoiding some medical litigation related to cerebral palsy patients.

Adult↗

Superficial temporal artery laceration. A complication of skull tong traction.

Complications associated with the use of skull tongs are not uncommon. We report a case of superficial temporal artery injury as a complication of Gardner-Wells tong application. Chronic recurrent episodes of pulsatile bleeding from the pin site necessitated arterial ligation to control the bleeding.

Cervical Vertebrae↗

Bifunctional antibody: a binary radiopharmaceutical delivery system for imaging colorectal carcinoma.

In clinical studies we have evaluated a unique monoclonal antibody-based drug delivery system, a bifunctional antibody designed to deliver imaging or therapeutic agents, such as radioisotopes, drugs, or biologics, to tumor cells, while minimizing the dose to normal tissue. The bifunctional antibody, with one specificity to a tumor-associated antigen (carcinoembryonic antigen) and another specificity to a hapten, is injected and allowed to localize at a tumor site for 4 days. A hapten, tagged with a radioisotope, is subsequently injected for delivery to and capture by the prelocalized antibody at the tumor site. In studies reported here, the sulfhydryl groups of Fab' fragments of ZCE-025 and CHA-255 were linked with bis-maleimidomethyl ether to form an F(ab')2 bifunctional antibody coupled by a stable thioether linkage. EOTUBE, a hydroxyethylthiourido derivative of benzyl EDTA, was used as the hapten carrier of 111In. Fourteen patients 62-82 years old with recurrent or metastatic adenocarcinoma of the colon were studied. Twenty of 21 known lesions were imaged, and eight of nine new lesions were confirmed. With this fundamentally new approach to drug delivery, clearance from normal tissue is rapid, and high tumor:normal tissue ratios are expeditiously achieved.

Adenocarcinoma↗

Plastic deformation of the forearm: a review and case reports.

Plastic deformation of long bones can occur in any age group but it is more common in children. Based on our experience with this condition and the suggested guidelines for treatment in the literature, we believe that significant deformity (15 degrees or more) in children over 10 years of age should be manipulated and corrected. In children 6 to 10 years of age, attempts should be made to correct a severe deformity (20 degrees or more). Children under 5 years of age probably require no treatment, since remodelling most likely will restore the correct anatomy and function.

Adolescent↗

Androgen metabolism by porcine granulosa cells during the process of luteinization in vitro: identification of 19-oic-androstenedione as a major metabolite and possible precursor for the formation of C18 neutral steroids.

The present studies were conducted to define the pathway(s) by which androstenedione is metabolized in porcine granulosa cells (pGC) and determine whether metabolism of this steroid is affected by in vitro luteinization. pGC isolated from large preovulatory follicles were cultured for up to 2 days in the presence of 5 microM unlabeled or [4-14C]-labeled androstenedione. Metabolism of androstenedione was assessed by HPLC, using in-line liquid scintillation detection. Metabolite identification was confirmed by gas chromatography-mass spectrometry of HPLC fractions isolated from medium conditioned by granulosa cells (pGCCM) cultured for 48 h in the presence of unlabeled androstenedione. The metabolites identified were 19-oic-androstenedione (3,17-dioxo-4-androsten-19-oic acid), 19-hydroxytestosterone, 19-hydroxyandrostenedione, 19-nor-testosterone, an estrenolone of as yet unproven stereoisomerism, 5(10)-estrene-3 beta, 17 beta-diol, 17 beta-estradiol, testosterone, and 19-nor-androstenedione. Results indicate that 19-nor-androstenedione is artifactually derived from 19-oic-androstenedione as a result of degradation in storage and during isolation. After metabolite identification, studies of the time course of androstenedione metabolism by pGC during in vitro luteinization were conducted. 17 beta-Estradiol and 19-oic-androstenedione were the predominant metabolites, and accumulation of these steroids was virtually identical. Production of these metabolites was maximal during the first 12 h of culture. The accumulation of 5(10)-estrene-3 beta,17 beta-diol and 19-nor-testosterone was maximal at 48 h of culture, with 5(10)-estrene-3 beta,17 beta-diol consistently accumulating in greater concentrations than 19-nor-testosterone. Aromatase activity of pGC was negligible from 36-48 h of culture, as demonstrated by minimal accumulation of 17 beta-estradiol during this period of culture. The accumulation of 19-oic-androstenedione, 5(10)-estrene-3 beta,17 beta-diol, and 19-nor-testosterone was also negligible during this latter time period, suggesting that their formation is associated with aromatase. From these results, pGC from preovulatory follicles undergoing luteinization in vitro lose the ability to convert androstenedione to estrogens. The formation of 19-oic-androstenedione, shown here for the first time, parallels the formation of 17 beta-estradiol, and this acidic steroid is proposed to be a product of aromatase. As reported in previous studies, pGC do produce C18 neutral steroids from exogenous androstenedione. The production of these steroids requires an active aromatase to produce their immediate precursor, which is here hypothesized to be 19-oic-androstenedione. However, their maximal production does not commence until aromatase activity has declined, and it is hypothesized that their production depends on modifications in steroid metabolism associated with luteinization.

Androgens↗

Assessment and validation of animal models to evaluate topical effects of substances on gastrointestinal mucosa.

The in situ rabbit colon model is a sensitive and reproducible test to evaluate the topical effect of up to three substances applied to the colonic mucosa. Vibra-Tabs (doxycycline hyclate), Inderal (propranolol hydrochloride), and Slow-K (potassium chloride) were compared for topical effects in the Carlborg-Densert cat esophagus model, the Alphin-Droppleman cat gastric mucosa model adapted for dog intestine, and the rabbit colon. Because results were comparable in all models, additional dosage formulations were subsequently tested only in the rabbit colon model. After exposure of the tissue to drugs, macroscopic and histologic effects were scored on four- and eight-point scales, respectively. In all three models, Vibra-Tabs and Inderal produced the highest macroscopic and histologic scores, although Slow-K was also irritating. In the rabbit colon model, potassium released from Slow-K and Micro-K Extencaps caused more irritation than from controlled-release GITS (KCl) (gastrointestinal therapeutic system KCl).

Animals↗

Avulsion fracture of the tibial tuberosity in late adolescence.

Between January 1982 and May 1985, eight patients with avulsion fractures of tibial tuberosity were seen at the University of South Alabama Medical Center. All were boys, average age, 15 years 8 months. Six of eight had a positive history of Osgood-Schlatter disease. Seven patients underwent open reduction and internal fixation, one had closed reduction and cast. Followup ranged from 5 months to 3.5 years, averaging 19.5 months. All, except one who had lateral meniscectomy, regained practically full ROM and reported no pain or limitation of activities. No patient developed genu recurvatum deformity or leg length discrepancy due to the injury. Open reduction and internal fixation is the treatment of choice in displaced intra-articular fractures. Lateral parapatellar incision is a more direct approach to this fracture and is less likely to injure the infrapatellar branch of the saphenous nerve.

Adolescent↗

Fibroblast growth factors from bovine pituitary and human placenta and their functions in the maturation of porcine granulosa cells in vitro.

Both acidic and basic fibroblast growth factors (FGFs) are present in pituitary, as demonstrated by Affigel-heparin affinity chromatography and immunoblot analysis. Unlike in the pituitary, only basic FGF appears to be present in human placenta. The purification of these growth factors from bovine pituitary and human placenta has been described. Immunoblot analysis using polyclonal antibodies specific for either basic FGF or both acidic and basic FGF have verified the results of purification. We have determined a novel function of acidic and basic FGF in the maturation of porcine granulosa cells in vitro. Basic FGF (1.0 ng/ml), purified from bovine pituitary functioned as a potent inhibitor of LH/hCG receptor induction (91 +/- 1.2%; P less than 0.0001), and progesterone secretion (45 +/- 2.9%; P less than 0.0001), two key steps in the maturation of granulosa cells. Human placental basic FGF demonstrated comparable inhibition characteristics. Bovine pituitary acidic FGF (50 ng/ml) appear to function as a relatively weak inhibitor (63.5 +/- 5.1% for LH/hCG receptor induction; 50 +/- 1.8% for progesterone secretion). Consequently, our analysis indicates that FGF may play an important role(s) in the maturation of ovarian granulosa cells.

Animals↗

Regulation of progesterone formation by human placental cells in culture.

In the present study, a culture system of human placental cells was established to examine the role of estrogen and androgen in progesterone (P4) formation. Normal human placentae were obtained at term, and cells were dispersed in Hank's Balanced Salt Solution (5 ml/g tissue) containing 0.1% collagenase, 0.1% hyaluronidase, 0.01% deoxyribonuclease, and 1% fetal bovine serum for 2 h at 37 C. Dispersed placental cells (10(6) cells/ml) were placed in medium 199 with modified Earle's salts (pH 7.4) containing 10% fetal bovine serum, 12.5 mM HEPES buffer, 26 mM NaHCO3, and 40 micrograms/ml Gentamycin-SO4 and incubated for 72 h at 37 C and 5% CO2 in air to allow cell attachment. Medium was then changed (time zero), and P4 formation was studied thereafter. Culture of placental cells for 96 h resulted in linear increases in P4 and estradiol (E2) formation, indicating the maintenance of cell viability and steroidogenic function. Mean +/- SE P4 formation at 48 h was 246 +/- 16 pg/micrograms DNA. To assess the role of estrogen on P4 formation, placental cells were incubated for a period of 48 h with various amounts (10(-7)-10(-4)M) of the antiestrogen ethamoxytriphetol (MER-25), the aromatase inhibitor 4-hydroxyandrostenedione (4-OHA), and/or E2. Both MER-25 and 4-OHA resulted in a dose-dependent decline (P less than 0.01) in P4 formation (greater than 80% decline at 10(-4)M MER-25 or 4-OHA). The marked reduction in P4 formation caused by 4-OHA alone was reversed by concomitant addition of E2; however, E2 alone had no effect. To assess the role of androgens on P4 formation, cells were incubated for 48 h with increasing amounts (10(-7)-10(-4)M) of androstenedione, dehydroepiandrosterone (DHA), or dihydrotestosterone. Although the formation of E2 was enhanced by DHA, formation of P4 was not affected by the aromatizable androgens DHA or androstenedione or the nonaromatizable dihydrotestosterone. The decline in P4 formation by human placental cells in culture elicited by MER-25 or 4-OHA supports the hypothesis of a regulatory role for estrogen in placental P4 formation during human pregnancy. The lack of effect of exogenous estrogen suggests that the action of estrogen on P4 formation may be permissive.

Androstenedione↗

Follicular fluid modulation of functional LH receptor induction in pig granulosa cells.

Follicular fluid was collected from small (1-2 mm), medium (3-5 mm) and large (6-12 mm) follicles of pigs, treated with charcoal to remove steroids, and tested for effects on the induction of functional LH/hCG receptors in cultures of granulosa cells from small antral pig follicles. Granulosa cells were cultured for 2, 4 or 6 days in Medium 199 + 10% pig serum. Granulosa cells cultured in the presence of purified human FSH (0.1 microgram/ml, LER 8/117), insulin (1 mU/ml), cortisol (0.01 microgram/ml) and thyroxine (10(-7) M) accumulated a 4- to 8-fold increase in LH/hCG receptors compared to control cultures. The amounts of cyclic AMP and progesterone secreted after exposure to ovine LH (1 microgram/ml: NIH-S19) were also increased 2-3-fold and 80-100-fold, respectively. Exposure to FSH alone resulted in lower amounts of LH/hCG receptors with a concomitant decrease in optimum LH responses. Addition of 12.5-50% follicular fluid obtained from small (1-2 mm) follicles led to a dose-dependent inhibition of the FSH plus insulin, cortisol and thyroxine induction of LH/hCG receptors after 4 days of culture. Fluid from medium follicles showed reduced ability to inhibit LH/hCG receptor induction, and fluid from large follicles exerted only a slight inhibition or no inhibition of receptor induction. Fluid from medium-sized and large follicles exerted a progressive dose-dependent stimulation of progesterone secretion by the granulosa cell cultures. The inhibitory activity was precipitated primarily with 70% ethanol and to a lesser degree by 36 and 90% ethanol. These studies demonstrate that induction of functional LH/hCG receptors in cultures of pig granulosa cells from immature follicles is enhanced by including insulin, cortisol and thyroxine, in addition to FSH, in the culture medium, and that follicular fluid modulates both receptor induction and progesterone secretion as a function of follicular maturation.

Animals↗

The role of polytomography in the diagnosis and treatment of cervical spine injuries.

Ninety-one sets of polytomograms were analyzed for diagnosis and treatment of 123 patients with cervical spine injuries. Pluridirectional polytomographis is valuable in evaluation of acute cervical spine injuries when the findings on plain roentgenograms do not correlate well with the clinical symptoms and signs. The polytomographic study had a dramatic impact on the diagnosis and a lesser but nevertheless significant impact on the treatment of cervical spine injuries. Polytomograms were especially valuable for the diagnosis and treatment of atlantoaxial injuries.

Adolescent↗