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Dynorphin A (1-13) and responsiveness of the newborn rat to a surrogate nipple: immediate behavioral consequences and reinforcement effects in conditioning.

The role of endogenous opioid system in learning (Pavlovian conditioning) and reinforcement was studied in newborn rats by pairing central injection of dynorphin A (1-13), an endogenous ligand with high affinity for kappa opioid receptors, with a surrogate nipple. For conditioning, the nipple served as the conditioned stimulus and dynorphin as the unconditioned stimulus. Dynorphin was found to elicit an immediate unconditioned, dose-dependent increase in the neonatal responsiveness to a surrogate nipple providing water, an effect apparently mediated through the kappa opioid receptors. This immediate effect of dynorphin was evident in the context of suckling behavior but not in the context of adult-like drinking when water was delivered through an intra-oral cannula. One hour after injection, the unconditioned stimulatory effect of dynorphin had dissipated and no longer affected responsiveness to the nipple. However, pairing of centrally injected dynorphin and suckling on a nipple delivering water substantially enhanced responsiveness to a nipple 1h later. This suggested conditioning, and hence reinforcement, by the centrally injected dynorphin. The conditioned sustained nipple attachment was mediated through both kappa and micro opioid receptors. These experiments confirm a central role for the brain opioid systems in reinforcement of neonatal behavior on the nipple.

Animals↗

Afferent nipple valve malfunction caused by anchoring collar: an unexpected late complication of the Kock continent ileal reservoir.

In the construction of a Kock continent ileal reservoir for urinary diversion, significantly high rates of late postoperative complications regarding nipple valves, the efferent limb in particular, have been reported. There are only a few reports on afferent nipple valve malfunction. A total of 42 patients who underwent a Kock pouch operation and were observed for more than 12 months (mean 38 months) was evaluated in terms of afferent nipple valve malfunction. Late afferent nipple valve complications were observed in 10 of the 42 patients (24%). These complications included erosion of the polyester fiber fabric used as a collar (5 patients), stenosis of the afferent limb (2) and obstruction of the afferent nipple by a mucous plug or fungus ball (3). The latter 2 complications were due to mechanical or dynamic obstruction of urine flow caused by a nonabsorbable collar. None of the 10 patients had problems with efferent nipple valve function. Our results suggest that the peristaltic direction of the intestine and the use of nonabsorbable material as a collar are primarily responsible for the late afferent nipple valve complications. Further modifications are needed to produce a stable nipple valve. Otherwise, simpler and more reliable alternative techniques of antireflux anastomosis should be considered.

Adult↗

Breast conservation surgery using nipple-areolar resection for central breast cancers.

HYPOTHESIS: Resection of the nipple-areolar complex (NAC) for central breast cancers that involve the nipple or areola, with postoperative radiation therapy, adheres to the oncologic principles established for breast conservation surgery of other breast cancers. Good or excellent cosmetic results can be achieved. The rate of ipsilateral breast recurrence will be similar to that seen with peripheral breast cancers. The indications for breast conservation surgery can be safely extended to include patients with breast cancers that involve the NAC. DESIGN: Retrospective medical record review; follow-up patient questionnaire. SETTING: Community teaching hospital. PATIENTS: Fifteen patients, aged 46 to 88 years, whose central breast cancers involved the NAC precluding preservation of the NAC. INTERVENTIONS: Nipple-areolar complex resection, postoperative radiation therapy. MAIN OUTCOME MEASURES: Ipsilateral breast recurrence, survival, cosmesis. RESULTS: Ten patients had subareolar cancers that directly involved the nipple or areola; 5 patients had Paget disease of the nipple. Average tumor size was 1.6 cm (range, 0.2-3.5 cm). With a mean follow-up of 32 months (range, 4-109 months), there has been only 1 recurrence (7%), which was treated successfully by modified radical mastectomy. All 15 patients are alive and free of disease. Cosmetic results are satisfactory to excellent, as judged by both the patients and the surgeons. CONCLUSIONS: Nipple-areolar complex resection for central subareolar cancers that directly involve the NAC, as well as for Paget disease of the nipple, extends the indications for breast conservation in other areas of the breast, and with acceptable cosmesis.

Aged↗

Oral grasping of a surrogate nipple by the newborn rat.

Newborn rat pups exhibit oral appetitive behaviors when presented with an artificial nipple. These behaviors include mouthing and licking movements and expression of stereotyped oral grasp response. Caesarean-delivered pups show increased responding to the nipple over the first 5 h after birth that is independent of experience with the nipple. Mimicking maternal licking by stimulating the anogenital region of the newborn rat with a soft paintbrush increases response to the nipple. Pups tested after 24 hr of normal experience respond to the artificial nipple when tested immediately after separation from the mother. However, oral grasping of the nipple is more frequent in 1-day-old pups tested 3 or 5 hr after separation from the mother. Study of behavioral responses to the artificial nipple promises to provide information about sensory and neurochemical controls of the initial suckling episode.

Age Factors↗

How the neonatal rat gets to the nipple. II. Changes during development.

In the course of postnatal development, the motor sequence executed by pups in order to attach to the dam's nipple undergoes extensive changes. During the 1st postnatal week, the pup performs a rotation along the longitudinal axis of its trunk to achieve a supine posture under the mother. The pup then crawls on the maternal ventrum while in the supine posture, searching for, finding, and attaching to a nipple. During the 2nd postnatal week, this sequence is modified and the pup first searches and establishes contact with a nipple before rotating to the supine posture. This sequence of movements is then truncated. By postnatal Day 11, pups may attach to a nipple while in a prone posture. Developmental changes in supination before attaching to the nipple are reminiscent of changes in righting during a similar period of development. These observations support the idea that both righting and postural adjustments involved in attachment to the nipple derive from common motor modules, with righting executed in the direction of gravity and rotation to the nipple executed against the force of gravity. The parallel structure of these behaviors is consistent with a common origin and similar control mechanisms for these distinct motor behaviors that are expressed early in postnatal development.

Animals↗

Calcitonin gene-related peptide (CGRP) in the nipple of the rat mammary gland.

The distribution of nerve fibres immunoreactive to calcitonin gene-related peptide (CGRP) was investigated by immunohistochemistry in nipples and mammary glands from lactating and non-lactating rats and compared to the immunoreactivity of other neuropeptides including substance P (SP), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP) and somatostatin (SOM). The study revealed an extensive innervation of the mammary nipples, in which CGRP-immunoreactive (IR) nerve fibres were abundantly present in the epidermis, dermal connective tissue and intralobular connective tissue of the mammary gland parenchyma. Several of the dermal CGRP-IR fibres seemed to follow blood vessels, or formed "ringlet-like" structures. The latter were mostly observed in the dermal connective tissue of the nipple from the lactating rat and may have a mechanoreceptive function, e.g. for the suckling stimuli. The location of SP-IR appeared to be comparable to CGRP-IR, but in fewer fibres. Dense NPY-IR networks of nerve fibres were closely associated with the fascicles of smooth musculature in the core of the nipple base. In contrast, VIP-IR fibres were only sparsely present, and SOM-IR was not detected in the mammary nipples. The immunoreactive content of CGRP and SP was determined by radioimmunoassays. The total amount of immunoreactive CGRP was significantly higher in the nipples from the pregnant and the lactating rats when compared to SP. The maximum concentration of CGRP (65.9 +/- 4.0 pmol/g) measured in the nipples of the pregnant (day 10) rats exceeded almost ninefold the maximum concentration of SP (7.7 +/- 2.0 pmol/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Substance P immunoreactivity in the rat mammary nipple and the effects of capsaicin treatment on lactation.

Tissue concentrations of substance P immunoreactivity (SP-I) were measured in rat mammary nipples and were significantly greater than in ventral abdominal skin in nonpregnant and pregnant rats. In contrast, the concentration of nipple SP-I was lower than that of skin in twelve day lactating animals. The mean total SP-I content of the pooled twelve nipples from each rat was not significantly different in nonpregnant, pregnant or lactating rats. However, the mean weight of the pooled twelve nipples from each rat was significantly higher in the lactating rats than in pregnant rats. Immunohistochemistry revealed SP-I nerve trunks and single fibers throughout the nipples of lactating rats. Nerve fibers were observed among smooth muscle and along blood vessels throughout the dermis and in association with epidermal structures. Some SP-I fibers were also observed in association with the main lactiferous duct and mammary gland secretory parenchyma. Radioimmunoassay and immunohistochemistry of nipples from lactating rats treated with capsaicin as neonates revealed a marked depletion of SP-I. Rats treated with capsaicin as neonates had a normal gestation period and produced litters of normal size and birth weight. However, the litters of these lactating rats grew at a significantly slower rate than litters from controls. The quantity of milk obtained from capsaicin-treated lactating dams, following a one hour suckling period on the twelfth day of lactation, was significantly less than that obtained by litters of control dams. It is concluded that capsaicin-sensitive primary sensory nerves of the mammary nipple play a role in the afferent limb of the suckling reflex. One transmitter candidate for these nerves is substance P.

Animals↗

Adenoma of the nipple in an adolescent.

We recently treated a 14-year-old girl with a clinically and histologically diagnosed with adenoma of the nipple. Enucleation of a mass preserving the nipple was successfully performed. Adenoma of the nipple is a rare disease which is often mistaken clinically for Paget's disease. About 200 cases of the tumors have been reported worldwide so far. The most common symptom is erosion of the nipple and nipple discharge. Our case had erosion of the nipple but no discharge. Adenoma of the nipple is a benign lesion which can be successfully treated by a simple surgery.

Adenoma↗

A method for correcting an inverted nipple with an artificial dermis.

Various methods have been reported to correct an inverted nipple. Although a satisfactory outcome has been reported with most techniques, each method carries a drawback inherent in the technique itself, including complicated operative technique, sensory disturbance of the nipple, marked scarring of the nipple areola and other donor regions, destruction of breast function, and incomplete correction. This report describes a simple method for correcting an inverted nipple. It incorporates a new concept of using artificial dermis for tissue augmentation and is performed without sacrificing any donor site and complex design. It was applied to four nipples in two nulliparous cases. For all four corrected inverted nipples, good results were obtained, and there have been no complications. There were no deformities of the nipples or the areolas after this procedure, and the surgical scars were inconspicuous.

Adult↗

MR imaging of the skin and nipple of the breast: differentiation between tumour recurrence and post-treatment change.

Contrast-enhanced MR imaging of the breast has been found to be valuable in the assessment of local recurrence of previously treated breast cancer. We looked specifically at the appearances of the skin and nipple of the treated breast in order to describe the appearances of post-treatment change and recurrence in this region. Thirty-nine women treated for breast cancer had MR imaging of one or both breasts reviewed retrospectively with particular attention to the nipple and skin. The skin and chest wall were assessed for patients with mastectomies. All available histology of the skin and/or nipple, obtained following MR imaging, was reviewed. In patients who did not undergo surgery following MR imaging, clinical follow-up was obtained. Six of 39 cases had nodular enhancing areas seen on MR imaging, which correlated with histology demonstrating tumour recurrence within the skin and/or nipple. Of the remaining 33 patients, changes of linear or diffuse enhancement were seen in the skin and/or nipple of 15 patients. These changes were shown to be benign post-treatment changes at surgery/biopsy in 4 cases or by clinical follow-up in the remainder. In this article we demonstrate differing patterns of contrast enhancement within the skin and nipple in recurrent breast carcinoma vs. post-treatment changes. This suggests that contrast-enhanced MR imaging of the breast may be a useful tool in differentiating tumour recurrence from post-treatment changes within the skin and nipple.

Adenocarcinoma, Mucinous↗

Postburn reconstruction of nipple-areola complex.

Reconstruction of burned nipple-areola complex is a significant problem. Many techniques are available. Most have been fraught with loss of nipple projection within 6 months. Local flaps seem to give better results. Drawbacks of these procedures in burned patients are excessive nipple flattening and difficulty in nipple reconstruction due to the low amount of subcutaneous fat and thin dermis because of tight scar. The modified star flap is a derivative of the skate design and includes the significant advantage of primary closure of the donor site. This article describes some modifications to the star flap, intended to decrease nipple flattening and improve flap stabilization, even in burned breasts. We performed seven nipple reconstructions in six young females who were victims of childhood burn injury. The final projection of nipples was 5 +/- 1mm. We think that our technique is a good alternative to previous ones and may be applied in all burned patients.

Adolescent↗

Evaluation of nipple-areola complex sensitivity after the latero-central glandular pedicle technique in breast reduction.

INTRODUCTION: Previous anatomical and clinical studies have shown that nipple-areola sensitivity decreased significantly after conventional superior and inferior pedicle technique for 3-6 months postoperatively. We found it necessary to modify our techniques in breast reduction to achieve a better outcome regarding breast sensation. Since 1999, we have been using a new technique of breast reduction with a latero-central glandular pedicle. The pedicle for the nipple-areola is based on a horizontal septum and it is designed to incorporate the anterior ramus of the lateral branch of the fourth inter-costal nerve and perforator vessels. Using this technique, a prospective study was conducted in order to quantitatively assess the nipple-areola sensitivity. MATERIAL AND METHODS: The sensitivity of the nipple-areola complex (NAC) was evaluated in 20 consecutive patients undergoing breast reduction with the septum-based lateral pedicle technique. The sensitivity was assessed preoperatively, 2 weeks and 3 months postoperatively by the same examiner. The nipple and four cardinal points of the areola were tested. Pressure thresholds were measured with Semmes-Weinstein monofilaments, temperature sensitivity with hot (40 degrees C) and cold (4 degrees C) metal probes and vibratory thresholds with the Biothesiometer. Average sensation of the areola was calculated by means of the four areas tested. RESULTS: Average values of different patterns of sensitivity decreased significantly on the tested areola 2 weeks postoperatively. Three months postoperatively, pressure and vibration values were statistically comparable in averages to preoperative values (nipple: 46.2+/-3.8 versus 34.6+/-2.2 g/mm2 and 6.4+/-1.2 versus 3.7+/-1 micron; areola: 57.4+/-5.7 versus 49+/-6.8 g/mm2 and 6.7+/-1.2 versus 3.1+/-0.6 micron). Concerning the ability to recognise temperature, 27.5 and 20% of patients could not distinguish between cold and hot 3 months after surgery, on the nipple and the areola, respectively. Numbness was found only on two NAC despite the significant decrease of sensitivity after 2 weeks. This may be attributed to postoperative oedema or neuropraxia. CONCLUSION: Our results showed that using the latero-central glandular pedicle technique preserves the sensitivity of the NAC.

Adolescent↗

The use of nipple shields by breastfeeding women.

The use of nipple shields when breastfeeding has given rise to concerns about possible harmful effects. A study was carried out to examine this issue. A lactation consultant's (LC) patients using nipple shields were compared with her other patients who were not using nipple shields, and an incidental sample of all postnatal breastfeeding women. The three groups were compared on discharge from hospital and at 3 months. Breastfeeding rates and problems (nipple trauma and mastitis) were studied: on discharge from hospital the LC patients who were not using nipple shields were significantly less likely to be breastfeeding than either of the other two groups. At 3 months, both LC groups were less likely to be breastfeeding than the postnatal group; there was no significant differences between the women using nipple shields and those who were not. There were no significant difference in reported problems in the 3 groups. It is concluded that women with breastfeeding problems are more likely to give up breastfeeding than those women who do not have major problems, and that the use of nipple shields is not a contributing factor and does not appear to compromise lactation.

Breast Diseases↗

Cancer of the breast with nipple involvement.

In the absence of gross deformity of the nipple, such as its retraction or Paget's disease, histological examination of this area is often neglected, or at best confined to a cursory look at a single sagittal section. The inadequacy of this approach is illustrated by this study of 33 consecutive cases of carcinoma of the breast treated with mastectomy. Multiple transverse sections showed tumour in 19 nipples (58%) involving one or more levels. Of these, 17 showed non-invasive tumour, either ductal or lobular type. Invasive tumour was seen in only two nipples, one of which was metastatic extension from the underlying breast tumour. Paget's cells were seen in two cases. The most significant finding was the eccentric location of tumour in 14 nipples. A single central sagittal section would have detected only five cases involving the centrally situated duct. An inexplicable finding was a preponderance of right nipple with tumour. No statistically significant correlation between nipple involvement and the size, location, multicentricity, type of tumour in the breast and metastases in axillary lymph nodes could be found. It became evident from this study that malignant changes in the nipple occur more commonly than is realised, and that it is also one of the sites of multicentric origin of the tumour. This factor will have to be taken into account in planning conservative therapeutic programmes.

Breast↗

Clear cells of Toker in accessory nipples.

BACKGROUND: Clear cells of Toker are intraepithelial cells with clear to pale staining cytoplasm and bland cytologic features found in approximately 10% of normal nipples. Toker cells have been hypothesized as a precursor of extramammary Paget's disease (EMPD), although the distribution of Toker cells outside of the nipples has not been studied. Using immunohistochemistry, we studied 20 cases of accessory nipples for the presence of Toker cells. METHODS: A retrospective study of 20 cases of accessory nipples was performed using routine hemotoxylin and eosin staining, as well as immunohistochemical staining for CK7, CK20, EMA, and GCDFP-15. RESULTS: Thirteen out of 20 accessory nipples (65%) demonstrated Toker cells with CK7 staining. Toker cells in six of the 13 cases were also positive for EMA. Only one case with Toker cells showed immunoreactivity for antibodies to GCDFP-15. CONCLUSIONS: Toker cells occur outside the normal nipple epidermis in the epidermis of accessory nipples. The distribution of Toker cells along the milk line correlates with the distribution of most cases of EMPD along the milk line, especially in the groin and axillae. Further studies are necessary to define the relationship between Toker cells and EMPD.

Apolipoproteins↗

Occurrence of supernumerary nipples in children with kidney and urinary tract malformations.

The reported data on the association of kidney and urinary tract malformations with supernumerary nipples are contradictory. We examined 200 children, ages 1 month-16 years, who were being followed because of recurrent urinary tract infection for supernumerary nipples. The patients were divided into two groups: those who were found to have urinary tract malformations on radiographic studies (n=92) and those who were not (n=108). All children were examined for any abnormal pigmentation along the milk line, and the entire body was examined for ectopic supernumerary nipples. Two of the children with proved urinary tract pathology and two of the children with no urinary tract pathology had supernumerary nipples. The odds ratio for having supernumerary nipples among the first group was 1.18 (95% CI: 0.084-16.53, p=0.627). Our results indicate no association between kidney and urinary tract malformations and supernumerary nipples. We believe the message to the practicing physician is that there is no need for radiographic or ultrasonographic investigation of the urinary tract in asymptomatic children found to have supernumerary nipples on routine physical examination.

Abnormalities, Multiple↗

Two innovations of the star-flap technique for nipple reconstruction.

Two innovations of the star-flap technique for nipple reconstruction are described. A combination of the star-flap technique and a contralateral nipple graft is indicated in patients with a large nipple and small areola on the contralateral side. It provides sufficient volume for the new nipple and improves the shape of the donor nipple. A combination of the star-flap technique and a banked costal-cartilage graft offers better nipple contour and projection than the conventional star-flap technique. Preparation of the cartilage graft is easy and does not result in additional scarring; the nipple projection can be expected to be maintained over a long period.

Adult↗

[Three case reports of breast abscess after nipple piercing: underestimated health problems of a fashion phenomenon].

OBJECTIVE: Piercing is a growing fashion trend among young people. Nipple piercing has shown an increase over the last years. We report about three coincidental cases of breast abscess after nipple piercing within the last months in our clinics and discuss the related problems for health and society. MATERIAL AND METHODS: Retrospective analysis of three case reports regarding course of illness and reasons as well as review of literature and internet. RESULTS: Three patients average age 31.9 (28-35) years were hospitalized with breast abscess after nipple piercing (2 x left, 1 x right). The distance piercing to infection was on average 7.7 (5-12) months. In all patients the abscess was incised and the abscess cavity removed, two had an irrigation tubing for a three days, all received i. v. antibiotics postoperatively. Evidence for bacteria was found in case 1: PCR-confirmation of atypical mycobacteria and coagulase negative staphylococcus, case 2: coagulase negative staphylococcus and group B-streptococcus and case 3: green and microaerophilic staphylococcus. The length of hospital stay was on average 8.0 (6-9) days/case, the hospital costs were 3 624,54 e (3 000,26-4 310,58 e) euro;/case. In a follow-up period of 10,0 (5-15) months one relapse occurred which had to be re-operated. CONCLUSION: Nipple piercing has grown in popularity within the last years and is in general not a stigma of a subculture or lower social classes any more. However, the risk for breast infection is on the one hand underestimated by the women and on the other hand played down by piercing studios. Breast infection after nipple piercing is rarely documented in scientific literature and data bases. Only seven case reports are scientifically published so far. Healing of the wound channel varies and can take up to 6-12 months. The risk for infection is approximately 10-20 %, often in a interval of months after the procedure. Insufficient understanding as well as inconsequent performance of hygienic preparation of the wound beneath other risk factors like nicotine abuse, wrongs size of jewelry, post breast enlargement with prosthesis etc. increase the risk of breast infection after nipple piercing. Due to obvious under documentation this is the largest series of breast infection after nipple piercing in the world.

Abscess↗