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  • Marc E Freeman

    Lloyd Beidler Professor and Distinguished Research Professor Emeritus, Florida State University

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    • Pdf_icon_disabled A tale of two rhythms: the emerging roles of oxytocin in rhythmic prolactin release.

      Bertram R, Helena CV, Gonzalez-iglesias AE, Tabak J, Freeman ME
      Journal of neuroendocrinology 2010 Jun; 22(7)

      Hormone secretion often occurs in a pulsatile manner. In this review, we discuss two rhythms of in vivo prolactin release in female rats and the ongoing research that we and others have performed aiming to understand the mechanisms underlying them. T... expand abstracthe peptide hormone oxytocin appears to play an important role in both rhythms. One rhythm occurs during the first half of pregnancy, but can also be induced in ovariectomised rats. This is characterised by a circadian pattern with two prolactin surges per day. Two methods for triggering this rhythm are discussed, each utilising a unique physiological pathway that includes oxytocin action, presumably on pituitary lactotrophs. The second rhythm occurs during the oestrous cycle and is characterised by a surge of prolactin on the afternoon of pro-oestrus. We discuss recent findings that oxytocin is more effective at stimulating prolactin release from lactotrophs taken from animals on the afternoon of pro-oestrus than from those of animals on the morning of dioestrus 1, raising the possibility that this hormone plays a physiological role in the regulation of prolactin secretion during the oestrous cycle. collapse abstract

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    • Pdf_icon_disabled Variations in the response of pituitary lactotrophs to oxytocin during the rat estrous cycle.

      Tabak J, Gonzalez-iglesias AE, Toporikova N, Bertram R, Freeman ME
      Endocrinology 2010 Mar; 151(4)

      Although removal of dopamine inhibition is established as a major factor in prolactin (PRL) release, a large body of evidence suggests that hypothalamic oxytocin (OT) may serve as a PRL-releasing hormone in the rat. PRL release is modulated by estrad... expand abstractiol (E2), which rises between diestrus and proestrus of the estrous cycle, causing a PRL surge in the afternoon of proestrus. Given that E2 strongly modulates OT actions in both central and peripheral tissues, OT action on lactotrophs might also be modulated by the stage of the estrous cycle. To test this hypothesis, we have monitored PRL release and intracellular calcium levels ([Ca(2+)](i)) induced by OT in pituitary lactotrophs obtained from female rats in either diestrus 1 or proestrus. We found that both secretory and [Ca(2+)](i) responses to OT are significantly increased in lactotrophs obtained on proestrus. Moreover, we show that these differences are due to an increase in both the number of OT-responding lactotrophs and the magnitude of their individual [Ca(2+)](i) responses. Both secretory and [Ca(2+)](i) responses were abolished by a specific OT antagonist. Finally, dose-dependent studies show that the increased PRL-releasing effect of OT on proestrus is significant over a wide range of concentrations, particularly those observed in hypophyseal portal plasma. These results suggest that the rising E2 titers that culminate on proestrus facilitate the stimulatory action of OT on lactotrophs and support the notion that OT is a PRL-releasing hormone with an important role in the production of the proestrous surge of PRL. collapse abstract

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    • Pdf_icon_disabled Central clock regulates the cervically stimulated prolactin surges by modulation of dopamine and vasoactive intestinal polypeptide release in ovariectomized rats.

      Poletini MO, Kennett JE, Mckee DT, Freeman ME
      Neuroendocrinology 91(2)

      BACKGROUND/AIMS: Cervical stimulation induces a circadian rhythm of prolactin secretion and antiphase dopamine release. The suprachiasmatic nucleus (SCN) controls this rhythm, and we propose that it does so through clock gene expression within the SC... expand abstractN. METHODS: To test this hypothesis, serial blood samples were taken from animals injected with an antisense deoxyoligonucleotide cocktail for clock genes (generated against the 5' transcription start site and 3' cap site of per1, per2, and clock mRNA) or with a random-sequence deoxyoligonucleotide in the SCN. To determine whether disruption of clock genes in the SCN compromises the neural mechanism controlling prolactin secretion, we sacrificed another group of rats (under the same treatments) at 12.00 or 17.00 h. Dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured using HPLC/electrochemical detection in the median eminence as well as the intermediate and the neural lobe of the pituitary gland, and the DOPAC:dopamine ratio was used as an index of dopamine activity. Vasoactive intestinal polypeptide (VIP) content was determined in tissue punches of the SCN and paraventricular nucleus (PVN), an SCN efferent. RESULTS: Treatment with clock gene antisense deoxyoligonucleotide cocktail abolished both the diurnal and nocturnal prolactin surges induced by cervical stimulation. This treatment abolished the antiphase relationship established by cervical stimulation between dopamine neuronal activity and prolactin secretion. Also, VIP content increased in the SCN and decreased in the PVN. CONCLUSION: These results suggest that the SCN clock determines the circadian rhythm of prolactin secretion in cervically stimulated rats by regulating dopamine neuronal activity and VIP inputs to the PVN. collapse abstract

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    • Pdf_icon_disabled Dopamine-regulated adrenocorticotropic hormone secretion in lactating rats: functional plasticity of melanotropes.

      Oláh M, Fehér P, Ihm Z, Bácskay I, Kiss T, Freeman ME, Nagy GM, Vecsernyés M
      Neuroendocrinology 90(4)

      Pro-opiomelanocortin (POMC) is processed to adrenocorticotropic hormone (ACTH) and beta-lipotropin in corticotropes of the anterior lobe, and to alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin in melanotropes of the intermediate l... expand abstractobe (IL) of the pituitary gland. While ACTH secretion is predominantly under the stimulatory influence of the hypothalamic factors, hormone secretion of the IL is tonically inhibited by neuroendocrine dopamine (NEDA) neurons. Lobe-specific POMC processing is not absolute. For example, D(2) type DA receptor (D2R)-deficient mice have elevated plasma ACTH levels, although it is known that corticotropes do not express D2R(s). Moreover, observations that suckling does not influence alpha-MSH release, while it induces an increase in plasma ACTH is unexplained. The aim of the present study was to investigate the involvement of the NEDA system in the regulation of ACTH secretion and the participation of the IL in ACTH production in lactating rats. Untreated and estradiol (E(2))-substituted ovariectomized (OVX) females were also studied. The concentration of ACTH in the IL was higher in lactating rats than in OVX rats, while the opposite change in alpha-MSH level of the IL was observed. DA levels in the IL and the neural lobe were lower in lactating rats than in OVX rats. Suckling-induced ACTH response was eliminated by pretreatment with the DA receptor agonist, bromocriptine (BRC). Inhibition of DA biosynthesis by alpha-methyl-p-tyrosine (alphaMpT) and blockade of D2R by domperidone (DOM) elevated plasma ACTH levels, but did not influence plasma alpha-MSH levels in lactating rats. The same drugs had opposite effects in OVX and OVX + E(2) animals. In lactating mothers, BRC was able to block ACTH responses induced by both alphaMpT and DOM. Surgical denervation of the IL elevated basal plasma levels of ACTH. Taken together, these data indicate that melanotropes synthesize ACTH during lactation and its release from these cells is regulated by NEDA neurons. collapse abstract

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    • Pdf_icon_disabled Laser-assisted breast reduction: a safe and effective alternative. A study of 367 patients.

      Stevens WG, Cohen R, Schantz SA, Stoker DA, Vath SD, Hirsch EM, Heck R, Freeman ME
      Aesthetic surgery journal / the American Society for Aesthetic Plastic surgery 26(4)

      BACKGROUND: Although several studies have been published documenting the safety of laser-assisted breast reduction, they have involved only small numbers of patients. OBJECTIVE: The authors conducted a retrospective chart review of a series of 367 co... expand abstractnsecutive patients who underwent inferior pedicle laser-assisted breast reduction surgery at a single outpatient facility from 1995 through 2004. METHODS: All patients received appropriate preoperative intravenous antibiotics and had sequential compression devices placed on their lower extremities before induction of anesthesia. Pedicle deepithelialization was performed using a carbon dioxide laser in continuous mode. Following deepithelialization, an inferior pedicle Wise-pattern breast reduction was performed in standard fashion. In approximately 20% of cases, breast reduction was combined with lipoplasty, facial aesthetic surgery, or abdominoplasty. Minor complications assessed included seroma, hematoma, infection, dog-ear, and incisional wound breakdown. Major complications were defined as >25% nipple/areola necrosis, blood transfusion, deep vein thrombosis, pulmonary embolus, myocardial infarction, or death. RESULTS: No major complications were noted in our series. Two patients with infections required short-term hospitalization for administration of intravenous antibiotics. A total of 47 minor complications occurred in 42 patients (11%), including 36 incisional wound breakdowns, 6 infections, 3 hematomas, 1 seroma, and 1 dog-ear revison. The incisional breakdowns included 25 minor T-zone wounds, 2 nipple-areolar complex wounds, and 9 wounds of the vertical and transverse incisions. No inclusion cysts were noted in any patients. CONCLUSIONS: Complication rates for our series of patients who underwent laser-assisted breast reduction surgery were consistent with those reported for non-laser-assisted procedures. These results, combined with the benefits and efficient operating time afforded by laser deepithelialization, indicate that laser-assisted breast reduction surgery can provide an alternative to standard methods of deepithelialization for those surgeons with access to a carbon dioxide laser. collapse abstract

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    • Pdf_icon_disabled Is one-stage breast augmentation with mastopexy safe and effective? A review of 186 primary cases.

      Stevens WG, Stoker DA, Freeman ME, Quardt SM, Hirsch EM, Cohen R
      Aesthetic surgery journal / the American Society for Aesthetic Plastic surgery 26(6)

      BACKGROUND: Although some authors have reported that 1-stage breast augmentation with mastopexy does not increase the risks of surgery, recent literature has raised the question of whether better results might be achieved by staging the procedures. O... expand abstractBJECTIVE: The authors evaluated the safety and efficacy of 1-stage breast augmentation with mastopexy in their own patients by analyzing long-term complication and revision rates. METHODS: A retrospective chart review was performed of 186 consecutive patients who underwent primary 1-stage breast augmentation with mastopexy at a single outpatient facility. Patient data recorded included age, body mass index, smoking status, degree of breast ptosis, and any preoperative asymmetry. Operation-related data recorded included type of mastopexy performed, operating surgeon, length of surgery, American Society of Anesthesiologists level, and concomitant procedures. Data on implant type, volume, and position were also collected. Complication and revision rates were recorded and calculated. RESULTS: Ninety-six patients (44%) received saline implants; 104 (56%) received silicone implants. In most cases, textured implants were placed in submuscular pockets. The mean implant volume was 320 cc. Inverted T mastopexy was performed in 60% of cases, circumareolar in 24% of cases, and vertical or crescent accounted for most of the remainder. No severe complications occurred, although 1 patient developed a late infection that required removal of the breast implant. The most common complication was saline implant deflation (5.9%), although saline implants were used in less than half of cases. Thirty-one patients (16.7%) underwent some form of revision surgery within the average 42-month follow-up period. CONCLUSIONS: Our review of 1-stage breast augmentation with mastopexy procedures revealed no severe complications. Although the overall revision rate of 16.7% is significant, it is comparable to rates for breast augmentation alone and is significantly lower than the 100% reoperation rate required for a staged procedure. In our experience, it is a safe and effective procedure, although one that is not easy to perform. Patients should be advised of the possibility that a second procedure may be necessary. collapse abstract

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    • Pdf_icon_disabled Mastopexy revisited: A review of 150 consecutive cases for complication and revision rates.

      Stevens WG, Stoker DA, Freeman ME, Quardt SM, Hirsch EM
      Aesthetic surgery journal / the American Society for Aesthetic Plastic surgery 27(2)

      BACKGROUND: Although there is an abundance of data in the literature regarding the safety of breast reduction and augmentation, nearly all of the literature concerning mastopexy describes techniques. There are few studies regarding revision and compl... expand abstractication rates for mastopexy procedures. METHODS: A retrospective review was performed on a series of 150 consecutive patients who underwent a mastopexy procedure. Operations were performed by one of two surgeons (W.G.S. or D.A.S.) in an outpatient surgery center over a 6-year period (1999-2005), with an average follow-up of 36 months. Patients were identified as being either primary (no previous breast surgery) or secondary (history of at least one previous breast surgery). The type of mastopexy design was recorded (inverted-T or vertical), and trends were examined. Complication and revision rates were observed, and their rates were calculated. RESULTS: One hundred forty-eight women underwent bilateral and two underwent unilateral mastopexy for a total of 150 women and 298 breasts. There were 119 primary and 31 secondary patients. Mastopexy incision designs were as follows: 86% inverted-T and 14% vertical. There were no major complications. The most common complications were poor scarring (6%) and seroma formation (2.7%). The revision rate was 8.6%; 75% of revisions were for poor scarring. Some of these were performed with the patients under local anesthesia or at the time of a subsequent unrelated surgery. CONCLUSIONS: Our series of 150 consecutive patients, with no major complications and a revision rate of 8.6% over an average of 36 months, indicates that mastopexy may be considered a safe and effective procedure. collapse abstract

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    • Pdf_icon_disabled A review of 100 consecutive secondary augmentationmastopexies.

      Stevens WG, Spring M, Stoker DA, Freeman ME, Cohen R, Quardt SM, Hirsch EM
      Aesthetic surgery journal / the American Society for Aesthetic Plastic surgery 27(5)

      BACKGROUND: Simultaneous breast augmentation and mastopexy has historically been a controversial topic, and it has been considered by some to be a difficult and unpredictable procedure. Secondary breast augmentation and mastopexy after previous breas... expand abstractt surgery is rarely discussed in the literature, and little is known about the outcomes of these secondary procedures. OBJECTIVE: The authors present the indications, surgical techniques, and outcomes in a series of 100 consecutive secondary simultaneous breast augmentation and mastopexy cases. METHODS: One hundred consecutive patients who underwent secondary combined augmentation mammaplasty and mastopexy from 1992 to 2005 were retrospectively reviewed. The complications and revision rates in this group of patients were analyzed and compared with primary mastopexy alone, as well as with primary combined augmentation and mastopexy. Independent variables such as patient age, history of smoking, body mass index, type and size of implant, and type of mastopexy incision were analyzed for correlation with complication and revision rates. RESULTS: No major complications were noted in an average of 3.5 years follow-up (range 13 months to 13 years). Minor complications occurred in 13 patients, of whom 8 required revision surgery. The most common tissue-related complications were poor scarring (3%) and recurrent ptosis (3%). The most common implant-related complications were infection (3%) and capsular contracture (2%). In addition, 6 patients underwent reoperation for implant size exchange, and 1 patient underwent revision surgery to receive silicone implants. Patient age, history of smoking, body mass index, type and size of implant, type of mastopexy incision, type and number of previous breast surgeries, surgical time, concurrent non-breast operations, and preoperative ptosis grade were not statistically significant risks when correlated to the complication and revision rate. CONCLUSIONS: Simultaneous breast augmentation and mastopexy after previous breast surgery is a commonly performed procedure that is not adequately reported in the literature. Our study indicates that the procedure is safe and has complication and revision rates comparable to primary augmentation/mastopexy. collapse abstract

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    • pdf exist The rhythmic secretion of mating-induced prolactin secretion is controlled by prolactin acting centrally.

      Helena CV, Mckee DT, Bertram R, Walker AM, Freeman ME
      Endocrinology 2009 Jun; 150(7)

      Artificial copulomimetic cervical stimulation (CS) induces an immediate release of oxytocin (OT) and prolactin (PRL) followed by a daily PRL rhythm characterized by nocturnal and diurnal surges. Although we have shown that the initial release of PRL ... expand abstractis induced by the immediate release of OT, we tested whether the PRL that is released in response to CS is responsible for the initiation and maintenance of the subsequent PRL surges. Thus, we injected OVX rats centrally or peripherally with ovine PRL (oPRL) at 2200 h. Central oPRL induced PRL surges in OVX rats that were similar in size and timing to those of CS rats, whereas peripheral oPRL induced surges that were of smaller amplitude and delayed. We then infused a PRL antagonist (S179D, 0.1 ng/h) centrally into OVX and OVX-CS rats and measured the release of endogenous PRL and the activity of neuroendocrine dopaminergic neurons. Central infusion of S179D did not influence basal PRL secretion in OVX rats but prevented the expression of the CS-induced PRL surges and the accompanying noontime increase of CS-induced dopaminergic activity when continued for 3 d. However, central infusion of S179D only on the day of CS did not prevent the daily rhythm of PRL surges. These results demonstrate that PRL acts centrally to induce the PRL rhythm and that PRL in the brain is essential for the maintenance but not for the initiation of the CS-induced rhythmic PRL surges. collapse abstract

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    • Pdf_icon_disabled Clinical experience with a fourth-generation textured silicone gel breast implant: a review of 1012 Mentor MemoryGel breast implants.

      Stevens WG, Pacella SJ, Gear AJ, Freeman ME, Mcwhorter C, Tenenbaum MJ, Stoker DA
      Aesthetic surgery journal / the American Society for Aesthetic Plastic surgery 28(6)

      BACKGROUND: Since the introduction of fourth- and fifth-generation silicone gel implants, manufacturers have conducted several prospective, multicenter trials to examine their safety and efficacy. However, these studies were not standardized with reg... expand abstractard to surgeon skill, pocket placement, operative technique, adjunct therapies, or postoperative management. OBJECTIVE: The purpose of this study was to examine the surgical outcomes of a single surgeon (WGS) in a consecutive series of breast augmentation cases using a fourth-generation cohesive silicone MemoryGel breast implant (Mentor, Santa Barbara, CA). METHODS: A retrospective chart review was conducted to identify all patients who underwent silicone breast augmentation within the Mentor Adjunct Silicone MemoryGel breast implant by a single surgeon (WGS) within a single free-standing outpatient surgical center over a 13-year period (1992 to 2006). For each patient, demographic information, comorbidities, and surgical information (implant size and concomitant surgery) were recorded. In addition, outcomes were analyzed to identify complications and the need for surgical revision. RESULTS: A total of 1012 fourth-generation, textured, cohesive silicone gel implants were placed in 511 patients during the 13-year study period. The overall complication rate per implant was 5.5% (n=56 implants in 43 patients). The most common complication was capsular contracture (n=26; 2.6 %) followed by abnormal scarring (n=11; 1.1%). The overall revision rates per patient and per implant were 8.0% (n = 41 patients) and 6.8% (n = 69 implants), respectively. The average time interval between initial implantation and revision was 18.5 months (range, 2 weeks to 26 months). The most common indication for surgical revision was patient desire for implant size change (n=15 patients) followed by Baker class III or IV capsular contracture (n=13 patients). The presence of previous surgery for capsular contracture was not statistically correlated to the need for revision (P= .326). Age (P= .568), previous history of breast surgery (P= .704), and history of smoking (P= .138) were also not statistically correlated to revision. Placement of the implant in the subglandular position (n=30 implants), however, was statistically correlated with need for revision (P< .01). CONCLUSIONS: Mentor fourth-generation cohesive silicone gel implants possess a complication and revision profile that is superior to earlier-generation silicone gel implants. Implantation with MemoryGel implants, when standardized with regard to surgeon and operative technique, can have significantly reduced complication and revision rates compared to the Mentor Core Data. collapse abstract

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    • pdf exist Antagonism of oxytocin prevents suckling- and estradiol-induced, but not progesterone-induced, secretion of prolactin.

      Kennett JE, Poletini MO, Fitch CA, Freeman ME
      Endocrinology 2009 Apr; 150(5)

      In female rats, estradiol (E(2)) and suckling induce prolactin (PRL) secretion. This involves inhibition of hypothalamic dopaminergic tone and stimulation by a PRL-releasing hormone, possibly oxytocin (OT). Infusing an OT antagonist (OTA) i.v., we ev... expand abstractaluated the role of OT on suckling- and E(2)-induced PRL secretion. Three days after parturition at 0900 h, lactating dams were fitted with 24-h osmotic minipumps filled with saline or OTA. On d 5 of lactation, pups were separated from their dams for 6 h. Immediately or 20 min after the resumption of suckling, dam trunk blood was collected. Also, ovariectomized (OVX) rats were treated with E(2) (OVE) and OTA at 1000 h on d 1. Blood samples were obtained from 1300 to 2100 h on d 2 for PRL measurements. Additionally, OVX rats were evaluated on d 2 after receiving progesterone (P(4)). OTA blocked suckling and E(2)-induced release of PRL but not that induced by E(2)+P(4). Pups from treated dams failed to gain weight when allowed to nurse for 20 min on d 5 but gained more than 7 g when nursed on d 7 of lactation, indicating that the OTA was active 48 h later. Western blot analysis showed that E(2) treatment increased OT receptors in the anterior pituitary when compared with OVX animals. No further increase was observed in response to the P(4), suggesting that the enhancing effect of P(4) on E(2)-induced PRL release may act through mechanisms independent of OT. These data demonstrate the role of OT in the control of suckling and steroid-induced PRL secretion. collapse abstract

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    • Pdf_icon_disabled Surgical anatomy of the lower face: the premasseter space, the jowl, and the labiomandibular fold.

      Mendelson BC, Freeman ME, Wu W, Huggins RJ
      Aesthetic plastic surgery 2008 Feb; 32(2)

      The anatomic basis for the jowl has not been fully described. A formal analysis was performed of the sub-superficial musculoaponeurotic system (SMAS) areolar tissue layer, which overlies the lower part of the masseter. For this research, facial disse... expand abstractctions were performed on 16 fresh cadavers ages 12 to 89 years, and detailed anatomic observations were made during the course of several hundred rhytidectomy procedures. Tissue samples from varying age groups were examined histologically. The areolar cleavage plane overlying the lower masseter has specific boundaries and is a true space named the "premasseter space." This space is rhomboidal in shape, lined by membrane, and reinforced by retaining ligaments. The masseter fascia lines the floor, and branches of the facial nerve pass under its deep surface. Histologically, the floor is formed by a thin layer of dense connective tissue, which undergoes minor deterioration in architectural arrangement with age. The roof, lined by a thin transparent and adherent membrane on the underside of the platysma, has a less dense collagen network and contains more elastin. With age, there is a significant reduction in the collagen density of the roof. Expansion of the space with aging, secondary to weakness of the anterior and inferior boundaries, results in formation of the jowl. Medial to the premasseter space is the buccal fat in the masticator space, which descends with aging and contributes to the labiomandibular fold and jowl. Application of the premasseter space in surgery provides significant benefits. The SMAS incision should be forward of the traditional preauricular location to be over the space, not behind. Because the space is a naturally occurring cleavage plane, dissection is bloodless and safe, as all facial nerve branches are outside. The premasseter space should be considered as the preferred dissection plane for lower (cervicofacial) facelifts. collapse abstract

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    • Pdf_icon_disabled The influence of a twice-a-day feeding regimen after photostimulation on the reproductive performance of broiler breeder hens.

      Spradley JM, Freeman ME, Wilson JL, Davis AJ
      Poultry science 2008 Feb; 87(3)

      Broiler breeder hens are typically provided a restricted amount of feed once a day. This feed is rapidly consumed; therefore, the hens fast for an extended period of time before their next feeding. In the current research, the effects on reproductive... expand abstract performance of implementing a twice-a-day vs. a once-a-day feeding program after photostimulation were investigated. Pullets and cockerels were reared on a skip-a-day feeding program. Pullets were weighed at 20 wk of age and then distributed into 30 laying pens such that each pen had a similar BW distribution. Each individual laying pen consisted of 35 hens and 4 roosters. At 21 wk of age, the birds were photostimulated for reproduction and 15 of the laying pens were placed on a once-a-day feeding schedule, whereas the other 15 pens were placed on a twice-a-day feeding schedule. The total amount of feed provided per day to all the laying pens was the same. Birds fed once a day received all their feed at 0630 h, whereas birds fed twice a day received 60% of their total feed allotment at 0630 h and the other 40% at 1500 h. Even though both treatment groups began egg production at the end of wk 23, birds fed twice a day laid more (P < or = 0.05) eggs through 42 wk of age than those fed once a day. Additionally, the average egg weight for the entire production period, which lasted until the birds were 60 wk of age, was greater for hens fed twice a day. Overall BW uniformity for the entire experiment was significantly better for hens fed twice a day vs. once a day. However, cumulative mortality was significantly higher for hens fed twice a day than for those fed once a day. The results indicate that feeding broiler breeder hens twice a day after photostimulation may enhance reproductive performance during the early lay period. collapse abstract

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    • Pdf_icon_disabled A-type K(+) current can act as a trigger for bursting in the absence of a slow variable.

      Toporikova N, Tabak J, Freeman ME, Bertram R
      Neural computation 2008 Jan; 20(2)

      Models of bursting in single cells typically include two subsystems with different timescales. Variations in one or more slow variables switch the system between a silent and a spiking state. We have developed a model for bursting in the pituitary la... expand abstractctotroph that does not include any slow variable. The model incorporates fast, noninactivating calcium and potassium currents (the spike-generating mechanism), as well as the fast, inactivating A-type potassium current (I(A)). I(A) is active only briefly at the beginning of a burst, but this brief impulse of I(A) acts as a burst trigger, injecting the spike trajectory close to an unstable steady state. The spiraling of the trajectory away from the steady state produces a period of low-amplitude spiking typical of lactotrophs. Increasing the conductance of A-type potassium current brings the trajectory closer to the unstable steady state, increasing burst duration. However, this also increases interburst interval, and for larger conductance values, all activity stops. To our knowledge, this is the first example of a physiologically based, single-compartmental model of bursting with no slow subsystem. collapse abstract

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    • Pdf_icon_disabled Vasoactive intestinal polypeptide modulates the estradiol-induced prolactin surge by entraining oxytocin neuronal activity.

      Kennett JE, Poletini MO, Freeman ME
      Brain research 2008 Feb; 1196

      In female rats, estradiol is responsible for a circadian secretory prolactin (PRL) pattern which requires an intact suprachiasmatic nucleus (SCN). SCN outputs involved in this secretory profile remain elusive. Because oxytocin has been proposed to st... expand abstractimulate PRL secretion, we investigated whether the projections of vasoactive intestinal polypeptide (VIP) from the SCN to neurons producing oxytocin in the paraventricular and periventricular nuclei (PVN and PeVN, respectively) are responsible for timing PRL surges induced by estradiol (E(2)). E(2)-treated ovariectomized rats received an injection of antisense or random-sequence oligodeoxynucleotide for VIP in the SCN and blood samples were taken for PRL measurements by radioimmunoassay. Additionally, the percentage of oxytocin-positive neurons immunoreactive to FOS-related antigens was determined in the PVN and PeVN, as an index of neuronal activity. In the PVN, oxytocinergic neuronal activity increased in the early evening regardless of E(2) treatment, whereas E(2) induced an increase of activity in the PeVN. VIP antisense attenuated this increase observed in both neuronal populations. Additionally, in the PeVN, VIP antisense advanced this increase by 2 h (from 19:00 h to 17:00 h). This same effect was observed in the PRL surge that occurred at 17:00 h in the VIP antisense injected animals. Thus, the SCN influences the precise timing of the E(2)-induced PRL surge via VIP projections to oxytocinergic neurons of the PVN and PeVN. collapse abstract

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    • Pdf_icon_disabled Histologic and ultrastructural evaluation of sutures used for surgical fixation of the SMAS.

      Huggins RJ, Freeman ME, Kerr JB, Mendelson BC
      Aesthetic plastic surgery 31(6)

      In extensive SMAS face-lift surgery, retaining ligaments are released, and the SMAS is resutured to the deep fascia to maintain the advanced position. The suture used to reattach the SMAS should replicate the quality of support provided by the origin... expand abstractal ligaments. Nonabsorbable sutures (monofilament and braided) retrieved intraoperatively from 22 patients undergoing secondary face-lift procedures were examined by light microscopy and transmission electronmicroscopy. A distinctive enclosure of dense collagen and elastin formed around both types of suture. Based on the presence of inflammatory cells, fibroblasts, collagen, and elastin, the tissue reaction to monofilament suture was less than with the braided suture. The collagen and elastin were thicker around the braided suture, and, additionally the collagen matrix infiltrated between the individual filaments. Ultrastructural analysis of the braided suture showed significant collagen binding around each individual filament. The greater quantity of connective tissue around the thread which continued into the interstices of the braided suture has the characteristics of a ligament. This suggests a stronger and more lasting tissue fixation. collapse abstract

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    • Pdf_icon_disabled One-stage mastopexy with breast augmentation: a review of 321 patients.

      Stevens WG, Freeman ME, Stoker DA, Quardt SM, Cohen R, Hirsch EM
      Plastic and reconstructive surgery 2007 Oct; 120(6)

      BACKGROUND: One-stage mastopexy with breast augmentation is an increasingly popular procedure among patients. In the past 9 years, there has been a 506 percent increase in mastopexy procedures alone. Although some recommend a staged mastopexy and bre... expand abstractast augmentation, there are currently no large studies evaluating the safety and efficacy of a one-stage procedure. METHODS: A retrospective chart review was conducted of 321 consecutive patients who underwent one-stage mastopexy and breast augmentation. Data collected included the following: patient characteristics, implant information, operative technique, and postoperative results. Complication and revision rates were calculated to evaluate the safety and efficacy of the one-stage procedure. RESULTS: No severe complications were recorded over an average of 40 months' follow-up. The most common complication was deflation of a saline implant (3.7 percent), followed by poor scarring (2.5 percent), recurrent ptosis (2.2 percent), and areola asymmetry (2.2 percent). Forty-seven patients (14.6 percent) underwent some form of revision surgery following the one-stage procedure. Thirty-five (10.9 percent) of these were for an implant-related issue, whereas 12 patients (3.7 percent) underwent a tissue-related revision. This 10.9 percent implant-related revision rate is less than a previously documented 13.2 percent 3-year reoperation rate for breast augmentation alone. The authors' 3.7 percent tissue-related revision rate also compares favorably to an 8.6 percent revision surgery rate in patients who underwent mastopexy alone. CONCLUSIONS: Although it has been stated that the risks of a one-stage procedure are more than additive, the results of our review suggest otherwise. Although a revision rate of 14.6 percent is significant, it is far from the 100 percent reoperation rate required for a staged procedure. collapse abstract

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    • Pdf_icon_disabled Dietary nitrogen intake regulates hepatic malic enzyme messenger ribonucleic acid expression.

      Chendrimada TP, Freeman ME, Davis AJ
      Poultry science 2007 Aug; 86(9)

      Increased dietary protein intake rapidly (3 h) decreases malic enzyme and increases hepatic histidase mRNA expression. Experiments were conducted to determine the role that individual dispensable amino acids and nonprotein N sources might have in reg... expand abstractulating the activity of these enzymes and to determine if the addition of a N supplement to a practical broiler diet during the entire rearing period would reduce abdominal fat accumulation in broilers. Broiler chicks were fed a basal diet containing 22% protein or this diet supplemented with 9.5% l-Glu, 5% Gly, 6% l-Ala, 5.08% ammonium bicarbonate, or 4.25% dibasic ammonium phosphate for 24 h. Each of the dietary supplements added 0.90% total N to the diet. Hepatic malic enzyme mRNA expression was significantly (P < 0.05) depressed in chicks fed any of the supplemented diets compared with chicks fed the basal diet. Histidase mRNA expression, however, was only significantly increased in the chicks fed the basal diet supplemented with Gly. Broilers fed practical corn-soybean meal starter and developer diets supplemented with 2.3, 4.7, or 9.5% Glu from 0 to 40 d of age had significantly smaller abdominal fat pads relative to BW than broilers fed the unsupplemented corn-soybean meal diets. Feeding the Glu supplements, however, reduced the overall BW gain of broilers by 100 to 150 g compared with broilers fed the unsupplemented diets. The results suggest that hepatic mRNA expression of malic enzyme may be regulated by total dietary N intake, whereas hepatic mRNA expression of histidase may be regulated by specific amino acids. collapse abstract

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    • Pdf_icon_disabled Knockdown of clock genes in the suprachiasmatic nucleus blocks prolactin surges and alters FRA expression in the locus coeruleus of female rats.

      Poletini MO, Mckee DT, Kennett JE, Doster J, Freeman ME
      American journal of physiology. Endocrinology and metabolism 2007 Oct; 293(5)

      The nature of the circadian signal from the suprachiasmatic nucleus (SCN) required for prolactin (PRL) surges is unknown. Because the SCN neuronal circadian rhythm is determined by a feedback loop of Period (Per) 1, Per2, and circadian locomotor outp... expand abstractut cycles kaput (Clock) gene expressions, we investigated the effect of SCN rhythmicity on PRL surges by disrupting this loop. Because lesion of the locus coeruleus (LC) abolishes PRL surges and these neurons receive SCN projections, we investigated the role of SCN rhythmicity in the LC neuronal circadian rhythm as a possible component of the circadian mechanism regulating PRL surges. Cycling rats on proestrous day and estradiol-treated ovariectomized rats received injections of antisense or random-sequence deoxyoligonucleotide cocktails for clock genes (Per1, Per2, and Clock) in the SCN, and blood samples were taken for PRL measurements. The percentage of tyrosine hydroxylase-positive neurons immunoreactive to Fos-related antigen (FRA) was determined in ovariectomized rats submitted to the cocktail injections and in a 12:12-h light:dark (LD) or constant dark (DD) environment. The antisense cocktail abolished both the proestrous and the estradiol-induced PRL surges observed in the afternoon and the increase of FRA expression in the LC neurons at Zeitgeber time 14 in LD and at circadian time 14 in DD. Because SCN afferents and efferents were probably preserved, the SCN rhythmicity is essential for the magnitude of daily PRL surges in female rats as well as for LC neuronal circadian rhythm. SCN neurons therefore determine PRL secretory surges, possibly by modulating LC circadian neuronal activity. collapse abstract

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    • Pdf_icon_disabled Oxytocin action at the lactotroph is required for prolactin surges in cervically stimulated ovariectomized rats.

      Mckee DT, Poletini MO, Bertram R, Freeman ME
      Endocrinology 2007 Sep; 148(10)

      Cervical stimulation induces two daily rhythmic prolactin surges, nocturnal and diurnal, which persist for several days. We have shown that a bolus injection of oxytocin initiates a similar prolactin rhythm, which persists despite low levels of oxyto... expand abstractcin after injection. This suggests that oxytocin may trigger the cervical stimulation-induced rhythmic prolactin surges. To investigate this hypothesis, we infused an oxytocin antagonist that does not cross the blood-brain barrier for 24 h before and after cervical stimulation and measured serum prolactin. We also measured dopaminergic neuronal activity because mathematical modeling predicted that this activity would be low in the presence of the oxytocin antagonist. We thus tested this hypothesis by measuring dopaminergic neuronal activity in the tuberoinfundibular, periventricular hypophyseal, and tuberohypophyseal dopaminergic neurons. Infusion of oxytocin antagonist before cervical stimulation abolished prolactin surges, and infusion of oxytocin antagonist after cervical stimulation abolished the diurnal and significantly decreased the nocturnal surges of prolactin. The rhythmic prolactin surges returned after the clearance of the oxytocin antagonist. Hypothalamic dopaminergic activity was elevated in antiphase with prolactin surges, and the antiphase elevation was abolished by the oxytocin antagonist in the tuberoinfundibular and tuberohypophyseal dopaminergic neurons, consistent with the mathematical model. These findings suggest that oxytocin is a physiologically relevant prolactin-releasing factor. However, the cervical stimulation-induced prolactin surges are maintained even in the absence of oxytocin actions at the lactotroph, which strongly suggests the maintenance of prolactin surges are not dependent upon oxytocin actions at the pituitary gland. collapse abstract

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    • Pdf_icon_disabled Low dose of dopamine may stimulate prolactin secretion by increasing fast potassium currents.

      Tabak J, Toporikova N, Freeman ME, Bertram R
      Journal of computational neuroscience 2007 Mar; 22(2)

      Dopamine (DA) released from the hypothalamus tonically inhibits pituitary lactotrophs. DA (at micromolar concentration) opens potassium channels, hyperpolarizing the lactotrophs and thus preventing the calcium influx that triggers prolactin hormone r... expand abstractelease. Surprisingly, at concentrations approximately 1000 lower, DA can stimulate prolactin secretion. Here, we investigated whether an increase in a K+ current could mediate this stimulatory effect. We considered the fast K+ currents flowing through large-conductance BK channels and through A-type channels. We developed a minimal lactotroph model to investigate the effects of these two currents. Both IBK and IA could transform the electrical pattern of activity from spiking to bursting, but through distinct mechanisms. IBK always increased the intracellular Ca2+ concentration, while IA could either increase or decrease it. Thus, the stimulatory effects of DA could be mediated by a fast K+ conductance which converts tonically spiking cells to bursters. In addition, the study illustrates that collapse abstract

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    • Pdf_icon_disabled Newborn screening for cystic fibrosis: parents' preferences regarding counseling at the time of infants' sweat test.

      Tluczek A, Koscik RL, Modaff P, Pfeil D, Rock MJ, Farrell PM, Lifchez C, Freeman ME, Gershan W, Zaleski C... expand author list, Sullivan B collapse author list
      Journal of genetic counseling 2006 Jul; 15(4)

      Newborn screening (NBS) protocols for cystic fibrosis (CF) are the first regional population-based programs to incorporate DNA analysis into their procedures. Research about these programs can inform policy and practice regarding how best to counsel ... expand abstractfamilies with abnormal NBS results. The grounded theory method guided interviews with 33 families whose infants had abnormal CF NBS results. A dimensional analysis of these interviews provided a theoretical framework describing parents' preferences regarding counseling during their infant's sweat test appointment. This framework describes the contexts and characteristics of the two main dimensions of parents' preferences: factual information and emotional support. Factual information included learning about the probability of a CF diagnosis, CF disease facts, sweat test procedure, and CF genetics. Social support consisted of offering parents a choice about the timing and amount of CF information, showing empathy for their distress, instilling hope, personalizing counseling, and providing hospitality. This framework also explains the consequences of counseling that matched versus mismatched parental preferences in these domains. Counseling that matched parents preferences reduced parents' distress while mismatched counseling tended to increase parents' worry about their infant. collapse abstract

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    • Pdf_icon_disabled Prolactin secretory rhythm of mated rats induced by a single injection of oxytocin.

      Egli M, Bertram R, Toporikova N, Sellix MT, Blanco W, Freeman ME
      American journal of physiology. Endocrinology and metabolism 2006 Feb; 290(3)

      Mating or vaginocervical stimulation [copulatory stimulus (CS)] induces two daily surges of the hormone prolactin (PRL) in rats. This unique secretory pattern of PRL surges is characteristic for the first half of pregnancy and is also present in ovar... expand abstractiectomized (OVX) rats. Studies have shown that CS additionally provokes an acute release of the hormone oxytocin (OT). In this study, we tested whether a single injection of OT (iv) is sufficient to initiate the PRL secretion pattern of OVX/CS rats. Furthermore, we measured the 24-h profile of dopamine (DA) content in the anterior lobe of the pituitary gland, because DA is the major inhibitory factor of PRL secretion. The results indicated that a single injection of OT induces a PRL secretory rhythm and a DA release pattern similar to that initiated by CS. Immunocytochemical investigation showed that particular OTergic neurons in the hypothalamus express receptors for PRL, as well as for vasoactive intestinal polypeptide, which indicates an involvement in generating the PRL rhythm and entraining it to the ambient photoperiod. On the basis of this study, we suggest that the PRL-DA inhibitory feedback loop between lactotrophs and DAergic neurons plays a crucial role in generating the oscillatory PRL secretion pattern in CS rats. A timing signal, likely provided by the hypothalamic suprachiasmatic nucleus, entrains the autonomous PRL oscillation to a particular time of day. Mathematical modeling was used to illustrate the proposed network function. The experimental results further suggest an additional feedback mechanism in which certain hypothalamic OTergic neurons are influenced by PRL. collapse abstract

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    • Pdf_icon_disabled A mathematical model for the mating-induced prolactin rhythm of female rats.

      Bertram R, Egli M, Toporikova N, Freeman ME
      American journal of physiology. Endocrinology and metabolism 2006 Feb; 290(3)

      For the first 10 days of pregnancy and the first 12 days of pseudopregnancy, the secretion of prolactin (PRL) from pituitary lactotrophs is rhythmic, with two surges/day. This rhythm can also be triggered by bolus injection of oxytocin (OT). We descr... expand abstractibe a mathematical model for the initiation, maintenance, and termination of the OT-induced PRL rhythm. In our model, the mechanism for this circadian rhythm is mutual interaction between lactotrophs and neuroendocrine dopamine (DA) neurons. This rhythm is, under normal lighting conditions, entrained by the suprachiasmatic nucleus (SCN) but persists in the absence of input from the SCN. We postulate that OT injection triggers the rhythm by activating a population of bistable hypothalamic neurons that innervate and inhibit DA neurons. The bistable nature of these neurons allows them to act as a memory device, maintaining the rhythm long after OT has been cleared from the blood. The mechanism for this memory device and the arguments supporting it are detailed with computer simulations. Finally, we consider potential targets for a rhythm-terminating factor and make predictions that may be used to determine which mechanism is operational in terminating the OT- or mating-induced PRL rhythm. collapse abstract

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    • Pdf_icon_disabled Endothelin action on pituitary lactotrophs: one receptor, many GTP-binding proteins.

      Bertram R, Tabak J, Toporikova N, Freeman ME
      Science's STKE : signal transduction knowledge environment 2006 Feb; 2006(321)

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