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Biomedical subjects

C A Pedersen

Publications and source records attributed to C A Pedersen.

At least 37 records · Page 2Linked to original sources

Postpartum mood and anxiety disorders: a guide for the nonpsychiatric clinician with an aside on thyroid associations with postpartum mood.

This article summarizes the considerable progress that has been made in recent years in our understanding of the risks of pregnancy-associated mood and anxiety disorders, effective somatic and nonsomatic treatments for those disorders, and the risks and benefits of psychotropic medications during pregnancy and breast-feeding. Ten to 15% of women develop syndromal depressions within the first 2 to 3 months postpartum, making this the most common serious medical complication of the puerperium. Prior history of depressive disorders, lack of social support, and stressful life events all increase the risk of postpartum depression. Psychotic mood disorders (commonly called postpartum psychosis) occur after approximately 1 to 2 deliveries per 1000. To ensure safety, women who develop postpartum psychotic symptoms should be hospitalized. History of bipolar illness increases the risk of postpartum psychosis to as much as 25%. Prior episodes of postpartum psychosis further increase the risk to 50%-75%. The risk of first onset or exacerbation of panic disorder or obsessive-compulsive disorder appears to increase during pregnancy and the puerperium. Postpartum mood and anxiety disorders are highly responsive to psychotherapy and in more serious cases, to medication. Fortunately, several classes of psychotropic medications, especially tricyclic and selective serotonin reuptake inhibitor antidepressants, appear to be reasonable safe during pregnancy and breast-feeding. Electroconvulsive therapy is the most effective treatment for very severe postpartum mood disorders, including postpartum psychosis. Preliminary results are also presented that suggest that lower range total and free thyroxine concentrations during late pregnancy are related to postpartum depressive symptoms.

Anxiety Disorders↗

Dysregulation of cardiovascular and neuroendocrine responses to stress in premenstrual dysphoric disorder.

Twelve women with prospectively confirmed premenstrual dysphoric disorder (PMDD or PDD) were compared with 12 healthy control subjects for cardiovascular and neuroendocrine responses to speech and mental arithmetic (Paced Auditory Serial Addition Task) stressors during both the follicular and luteal phases of the menstrual cycle. Structured clinical interview was used to assess psychiatric and abuse histories, and standardized questionnaires were administered to assess current life stress. Results revealed that PMDD women had significantly lower stroke volume, cardiac output and cortisol levels but significantly elevated norepinephrine and total peripheral resistance at rest and also during mental stressors compared with control subjects. These effects were evident in both cycle phases. Significantly more women with PMDD had histories of sexual abuse, and they also reported greater current life stress than control subjects. Consistent with a history of trauma, the PMDD women exhibited significantly greater ratios of norepinephrine to cortisol at rest and during stress. These results are interpreted as reflecting dysregulation of the stress response and may be related to histories of severe and/or chronic exposure to stress for a subgroup of PMDD women.

Adult↗

Subchronic dietary toxicity of strychnine: bobwhite quail are less sensitive than mallard ducks.

Separate, 28-day, subchronic studies of strychnine dietary toxicity were conducted using northern bobwhite quail (Colinus virginianus) and mallard ducks (Anas platyrhynchos). Five groups (five males five females/group) of 29-week-old quail were fed Purina(R) Game Bird Breeder Layena(R) diets containing mean (+/-SD) 484.2 (+/-17.0), 972. 6 (+/-54.0), 1,870.8 (+/-176.1), 3,516.7 (+/-68.0), and 6,083.3 (+/-269.6) microgram/g strychnine; whereas five groups of 27-week-old mallards (five males five females/group) were fed similar diets containing mean (+/-SD) 18.8 (+/-1.3), 91.1 (+/-27.3), 235.0 (+/-33. 8), 484.2 (+/-17.0), and 972.6 (+/-54.0) microgram/g strychnine. Separate "vehicle control" (0.0 microgram/g strychnine) groups (five males, five females/group) were included in each study. Strychnine toxicity was much less pronounced in quail; no observed effect concentrations (NOECs) were 972.6 (+/-54.0) and 91.1 (+/-27.3) microgram/g strychnine for quail and ducks, respectively. Several possible explanations for the species effects are offered, and some practical issues affecting the conduct of long-term, dietary toxicity studies are discussed.

Animals↗

Percutaneous pulmonary endoarterial biopsy in an experimental model of pulmonary hypertension.

STUDY OBJECTIVES: The aims of this study were: to evaluate the performance of a novel arterial biopsy catheter in obtaining pulmonary endovascular samples in hypertensive dogs; to compare the results of pulmonary endoarterial biopsy in hypertensive vs normotensive dogs; and to assess the histologic changes in the hypertensive model. DESIGN AND INTERVENTIONS: Thirty-four dogs (27 with normal pulmonary arterial pressures and seven with pulmonary hypertension) were catheterized through an external jugular vein to obtain endovascular biopsy samples from distal pulmonary arteries 2 to 3 mm in luminal diameter. To induce pulmonary hypertension, seven dogs were given repeated infusions of 0.6- to 0.9-mm ceramic microspheres into the superior vena cava. Endoarterial samples were obtained at pulmonary systolic arterial pressures ranging from 10 to 110 mm Hg. MEASUREMENTS AND RESULTS: Sixty-two biopsy catheterization procedures were performed in the 34 dogs. After 12 initial procedures of technique refinement, endoarterial samples were obtained in each of the last 50 procedures (21 in normotensive dogs and 29 in hypertensive dogs). The average number of endovascular biopsy samples retrieved was 7.1 (range, 2 to 12) from a mean of 8.6 (range, 2 to 15) biopsy attempts per catheterization (success rate=83%). The average biopsy piece measured 1.13 mm in length, 0.33 mm in depth, and up to 1.0 mm in width. The biopsy success rates and endoarterial sample sizes were similar in normotensive and hypertensive dogs. Smooth muscle cells and endothelial cells were grown from the biopsy samples. There were no significant procedural complications, except for one self-limited hemorrhage. Histologically, samples obtained from dogs with pulmonary hypertension showed characteristic changes when compared with biopsies from normotensive dogs. CONCLUSION: This new endoarterial biopsy catheter was safe and effective when used to obtain pulmonary endoarterial samples in dogs with normal and experimentally elevated pulmonary arterial pressures. The quality and quantity of the biopsy samples allowed identification of pathologic changes.

Animals↗

Antibodies against the fibrin beta-chain amino-terminus detect active canine venous thrombi.

BACKGROUND: This study was performed to determine whether antibodies against the amino-terminus of the beta-chain of fibrin (anti-beta) could noninvasively distinguish actively enlarging thrombi from thrombi stabilized with anticoagulants. METHODS AND RESULTS: Dogs with unilateral femoral vein thrombi were allocated into three groups: (1) no anticoagulation, (2) intravenous heparin maintained in the "therapeutic" range (0.2 to 0.5 U/mL plasma), and (3) "excess" heparin, maintained at >1.0 U/mL plasma. Thrombolysis was suppressed with tranexamic acid. (111)In-labeled anti-beta was infused, and gamma scans of the legs were performed at regular intervals for 24 hours. Scans were interpreted in a blinded fashion. In addition, for each scan, the number of gamma counts from the femoral area on the thrombosed side was compared with the contralateral side. Clot/blood isotope density was determined postmortem. Leg thrombi in the no-anticoagulation group were 100% detectable, mean (+/-SD) relative count in the thrombosed femoral area was 186% (+/-30%) of the contralateral side, and clot/blood ratio was 14.7 (+/-2.0). Thrombi in the therapeutic heparin group were only 75% detectable, relative counts in the thrombosed femoral areas decreased to 125% (+/-20%), and clot/blood ratio declined to 11.3 (+/-3.5). In the "excess heparin" group, leg thrombi were only 50% detectable, the thrombosed femoral area had relative counts of 118%+/-17%, and the clot/blood ratio fell to 7.8+/-1.9. CONCLUSIONS: Radiolabeled anti-beta noninvasively distinguishes propagating thrombi from those stabilized by anticoagulants. They may be useful for detecting thrombosis clinically as well as for monitoring the efficacy of anticoagulation.

Animals↗

Local delivery of c-myb antisense oligonucleotides during balloon angioplasty.

Intraluminal delivery of antisense oligonucleotides to c-myb was assessed following balloon angioplasty in swine peripheral arteries. Successful delivery and intramural persistence of oligonucleotide for over 24 h were demonstrated following angioplasty with hydrogel balloons coated with 32P-labeled antisense. Delivery of fluorescein-labeled antisense demonstrated further localization within the arterial media and intracellularly. Preliminary in vitro studies demonstrated the feasibility of inhibition of porcine lymphocyte proliferation using the murine antisense to c-myb. Twelve iliac or carotid arteries underwent angioplasty with antisense-coated balloons, while the contralateral vessels underwent angioplasty with the same-sized balloons coated with the complementary sense strand. Six to seven days later, dilated arterial segments were surgically isolated. In 10 of 12 vessel pairs, antisense-treated vessels demonstrated less cellular proliferation than did contralateral sense-treated vessels, as assessed by quantitative immunohistochemical staining of proliferating cell nuclear antigen, and smooth muscle cell proliferation was reduced 18% in antisense-treated vessels compared to the contralateral sense-treated vessels (PCNA-positive nuclear area: 7.7 +/- 4.9% vs. 9.3 +/- 5.2%, P < 0.04)-intraluminal delivery of antisense oligonucleotides to c-myb is feasible with a catheter-based system and may reduce smooth muscle cell proliferation following arterial injury.

Angioplasty, Balloon, Coronary↗

Effects of short- and long-term withdrawal from gestational cocaine treatment on maternal behavior and aggression in Sprague-Dawley rats.

Pregnant rats were treated with 30 mg/kg per day cocaine or normal saline either throughout gestation (GD 1-20, cocaine and saline withdrawal) or throughout the gestation and continuing into lactation for 10 days postpartum (cocaine and saline nonwithdrawal). All cocaine-treated dams exhibited more disruptions in the onset of maternal behavior (retrieval, licking, crouching) and were more aggressive (threats and attacks) towards an intruder on postpartum day 6 than saline-treated dams. There were no significant differences in these behaviors between withdrawn and nonwithdrawn cocaine-treated dams. These findings indicate that changes in maternal behavior following chronic moderate cocaine treatment are not simply the result of withdrawal from cocaine treatment following gestation and that other possible mechanisms should be examined.

Aggression↗

A comparison of thoracoscopic talc insufflation, slurry, and mechanical abrasion pleurodesis.

The purpose of this study was to compare the anatomic and histopathologic results of four different methods of pleurodesis in 10 dogs. Each animal was randomly assigned to receive two of the following methods of pleurodesis: thoracoscopic talc insufflation (poudrage), talc slurry administration, focal gauze abrasion by limited thoracotomy, and mechanical abrasion by thoracoscopy using a commercially available pleural abrader. Animals were killed 30 days after pleurodesis. At autopsy, the efficacy of pleurodesis was graded by evaluating the gross appearance of each pleural cavity and lung (pleurodesis score), and by determining the extent of adhesion formation (obliteration grade). Pleural and lung biopsy specimens were obtained from the areas most representative of adhesion formation for histopathologic evaluation. Pleurodesis scores (on a scale of 0 to 4) were 3.0 +/- 0.7 for talc poudrage (p < 0.05 when compared with talc slurry), 2.2 +/- 1.7 for thoracotomy, and 1.6 +/- 1.1 for talc slurry. Adhesions produced by gauze abrasion during thoracotomy were mostly peri-incisional. Thoracoscopic pleural abrasion using the pleural abrader was uniformly unsatisfactory. Granulation tissue formation was greatest in both talc models. The degree of parietal pleural thickening was greatest in the talc slurry model, but fibrosis and inflammation occurred mostly in gravity-dependent areas within the pleural cavity. Although differences were not statistically significant, thoracoscopic talc insufflation consistently produced the most widespread, firm fibrotic adhesions as evidenced by higher obliteration grades.

Animals↗

Transvenous procurement of pulmonary artery smooth muscle and endothelial cells using a novel endoarterial biopsy catheter in a canine model.

OBJECTIVES: The aim of this study was to evaluate the performance of a new arterial biopsy catheter in obtaining pulmonary endovascular samples in a canine model. BACKGROUND: Percutaneous endomyocardial biopsy is a widely used and valuable procedure in the management of posttransplant rejection and selected cardiomyopathies. A similar method of obtaining endoarterial biopsy samples would aid in the study, diagnosis and management of arterial diseases. METHODS: Catheterization was performed in 19 dogs, each weighing 20 to 30 kg, through an 8F sheath in the external jugular vein to obtain pulmonary endoarterial samples. The catheter consists of two sliding tubes: an inner one with a beveled opening that accommodates endoarterial tissue by means of a vacuum and an outer tube with a sharp distal edge that cuts the tissue when activated. RESULTS: Overall, a total of 266 separate biopsy attempts were performed, and 161 tissue samples were obtained (success rate 61%). With modifications in technique in the last nine dogs, 54 (93%) of 58 attempts were successful. There were no deaths, extravasation of contrast material on angiography or thrombi. Of 20 vessels with prebiopsy and postbiopsy angiograms, 1 developed transient spasm (5%). On microscopic examination of cross sections of 50 separate pulmonary endoarterial biopsy samples, all had smooth muscle cells and 30 contained endothelial cells (60%). The arteries of origin showed small intimal and medial tears and mild perivascular hemorrhage. Angiographic and pathologic examination of previously biopsied arterial segments 2 weeks (two dogs) and 8 weeks (two dogs) after the procedure showed patent vessels and no thrombi. Histologically, the biopsy sites revealed mild neointimal and medial proliferation. CONCLUSIONS: This new endoarterial biopsy catheter is safe and effective in obtaining pulmonary artery samples in normotensive dogs.

Angiography↗

The role of immunocytochemical markers in the differential diagnosis of proliferative and neoplastic lesions of the breast.

The differential expression of keratins in myoepithelial and epithelial cells of the breast makes immunohistochemical distinction of lesions an attractive possibility. High molecular weight keratin, 34BE12, is a monoclonal antibody that recognizes keratins 1, 5, 10, and 14. Because myoepithelial cells predominantly express keratins 5 and 14 and epithelial cells predominantly express keratins 8 and 18, it is natural to assume that 34BE12 may be a good marker of myoepithelial cells but not epithelial cells. However, recent studies of the breast have reported conflicting results. To determine the potential role of 34BE12 in the breast, we studied by immunohistochemistry 19 tubular carcinomas, 14 radial scars, two microglandular adenoses, and 9 sclerosing adenoses, using monoclonal antibodies to high molecular weight keratin, smooth muscle actin, type IV collagen, and antiserum to S100 protein. Actin was negative in all 19 (100%) tubular carcinomas, but it delineated the myoepithelial cells in 22 of 23 (95.6%) benign lesions of sclerosing adenosis and radial scars; it was also negative in microglandular adenosis. In comparison, epithelial cytoplasmic 34BE12 reactivity was seen in 3 of 19 (15.8%) tubular carcinomas, whereas myoepithelial cells failed to react in 4 of 23 (17.3%) benign conditions. Antiserum to S100 protein had a similar disadvantage of labeling both epithelial and myoepithelial cells with reactivity in 5 of 19 (26.3%) tubular carcinomas. In microglandular adenosis, the epithelial cells were strongly S100 protein positive and focally 34BE12 positive, but no staining was observed for actin. Type IV collagen staining outlined distinct basement membranes in microglandular adenosis and other benign conditions but not in tubular carcinomas. However, staining for type IV collagen requires enzymatic pretreatment and is difficult to perform, especially in sclerotic breast tissue. In conclusion, actin appears to be the most consistent and specific marker for distinguishing tubular carcinomas from other benign conditions, and type IV collagen has a contributory role, whereas 34BE12 is less valuable than in prostatic biopsies.

Actins↗

Characterization of progesterone-3-[125I-BSA] binding sites in the medial preoptic area and anterior hypothalamus.

In this study we utilized radiolabeled progesterone (P) conjugated to bovine serum albumin (BSA) at position 3 (P-3-[125I-BSA]) to examine steroid receptors in membrane fractions from the medial preoptic area-anterior hypothalamus (MPOA-AH) of ovariectomized (OVXed) rats. In the MPOA-AH binding of P-3-[125I-BSA] was linear across a tissue concentration range of 0.005 to 0.02 mg protein/0.1 ml of membrane suspension. Kinetic experiments revealed an association t(1/2) of 51.4 min and a dissociation t(1/2) of 122.5 min for P-3-[125I-BSA] at 0 degrees C. Analysis of data from competition binding experiments using P-3-BSA revealed high- and low-affinity binding sites in the MPOA-AH. Involvement of MPOA-AH binding sites with a G-protein was suggested by a reduction of P-3-[125I-BSA] binding in the presence of the non-hydrolyzable GTP analog GTPgammaS but not ATPgammaS. In addition, if homogenates from the MPOA-AH were preincubated with 10(-5) M of the G-protein antagonist cholera toxin for 30 min at 37 degrees C, competition binding data indicated only high-affinity binding sites. Once daily injections of OVXed rats with 4 mg P for 12 days significantly increased the density of P-3-[125I-BSA] binding sites in the MPOA-AH. This treatment did not affect P-3-[125I-BSA] binding in the dorsal tectum, medial basal hypothalamus, ventral tegmental area or the thymus.

Albumins↗

Thyroid axis function during the menstrual cycle in women with premenstrual syndrome.

Fifteen women with premenstrual syndrome (PMS) and 15 control women were tested twice for thyroid axis measures, once during the follicular and once during the luteal phase of the menstrual cycle. While PMS and control women did not differ in mean hormone values during either phase of the menstrual cycle, PMS women showed significantly greater variability in hormone measures including TSH, T3 uptake, T4, and FTI relative to controls. These findings are consistent with the conceptualization that, for a subset of women with PMS, thyroid axis abnormalities may contribute to their disorder. Additionally, when analyzed in the sample as a whole, the menstrual cycle exerted a significant effect on reverse T3 with greater levels observed in the luteal relative to the follicular phase of the cycle.

Adult↗

Interfering with somatosensory stimulation from pups sensitizes experienced, postpartum rat mothers to oxytocin antagonist inhibition of maternal behavior.

Proximal separation (PS) refers to isolating pups in small cages so dams can hear, smell, and see pups but have very limited physical contact with them. Six days of PS diminished the number of discernible oxytocin- (OT) immunostaining perikarya in forebrain areas of rat dams compared with 6 days of total separation (TS) or no separation (NS) from pups. Dams exhibited a more rapid resurgence of maternal behavior after 4-6 days of PS than after 4-6 days of TS. Bilateral infusion of the OT antagonist (OTA; 1 microgram/microliter/side) into the ventral tegmental area blocked the resurgence of maternal behavior after 3-6 days of PS but not after 2 days of PS or 4-6 days of NS. The conclusion was that PS for 3 or more days reinstates OT as necessary and sufficient for the activation of maternal behavior in experienced rat mothers. These findings suggest that some aspects of somatosensory stimulation from pups regulate the role of OT in the control of maternal behavior.

Animals↗

Antisense oligodeoxynucleotide complementary to oxytocin mRNA blocks lactation in rats.

The posterior lobe peptide oxytocin (OT) is known to control lactation and parturition, as well as maternal and sexual behavior. An antisense oligodeoxynucleotide (ODN) directed against the mRNA of OT was injected intracerebroventricularly 6 times in 12 hour intervals to manipulate the transcriptional message of OT in lactating rats. OT immunoreactivity in magnocellular hypothalamic nuclei and in the posterior lobe of the pituitary was reduced in antisense treated animals in comparison to ODN with scrambled base composition and vehicle controls. This decline in OT levels was associated with a decrease of pup weight. Our results demonstrate that central infusions of antisense ODN significantly reduce OT expression in vivo.

Animals↗

CNS oxytocin receptor mRNA expression and regulation by gonadal steroids.

A genomic clone was used to generate a rat oxytocin receptor (OTR) probe for in situ hybridization studies in order to monitor changes in expression of OTR mRNA in the CNS of male and female rats in brain regions reported to be rich in OTR binding. This probe predominantly detects expression in the ventromedial hypothalamus (VMH). Quantitatively greater expression of OTR mRNA was more evident in the male VMH than in that of the female. OTR mRNA expression in the VMH is also enhanced in gonadectomized rats treated with either estrogen or testosterone. Previous studies of VMH OTR mRNA expression during the estrous cycle revealed a role of estrogen in proestrous OTR mRNA expression and also provided evidence for progesterone's modulatory effect on OTR expression. A related study which examined OTR mRNA expression during gestation, parturition, and lactation further supported the regulation of the OTR by gonadal steroids, as a pronounced induction of expression occurred at parturition when estrogen levels were highest. These results support previous studies which have documented the regulation of OTR binding by gonadal steroids and suggest that this regulation may be the result of altered expression of the OTR gene. Induction of OTRs in anatomically distinct regions of the VMH may be important in promoting OT'ergic neurotransmission required for sexual behavior or the induction of gonadotropin release by OT, which requires estrogen and progesterone priming. The anatomical variation in OTR mRNA localization and its restricted detection in the VMH by this probe suggests potential CNS OTR heterogeneity.

Animals↗

Neonatal stress transiently alters the development of hippocampal oxytocin receptors.

The development of brain oxytocin (OXT) receptors was examined following the mild stress of daily, 20 min separations of infant rats from their mothers (repeated separation condition) or in undisturbed controls. Changes in OXT receptors were characterized in cell membrane preparations, using the OXT receptor ligand [125I]d(CH2)5[Tyr(Me)2Thr4Tyr-NH9(2)]-ornithine vasotocin ([125I]OTA), from rats at 4, 8, 14, 22 postnatal days of age or as adults. In the hippocampus of control animals, [125I]OTA binding was highest at day 4 or 8 and declined thereafter. Repeated separation decreased the Bmax of [125I]OTA binding in whole hippocampus at day 8, an effect that did not persist into adulthood. This effect was found to be confined to the rapidly proliferating, dorsal hippocampus. It has been suggested that brain OXT is involved in both affiliative/social and stress-related behaviors. While the specific function of OXT receptors in hippocampus is currently unknown, mild stress to the infant and the disruption of infant-mother contact transiently alters the normal development of this system.

Animals↗