Neoadjuvant Endocrine Therapy Versus Neoadjuvant Chemotherapy in Node-Positive Invasive Lobular Carcinoma.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is often recommended for patients with node-positive invasive lobular carcinoma (ILC) despite unclear benefit in this largely hormone receptor-positive (HR+) group. We sought to compare overall survival (OS) between patients with node-positive ILC who received neoadjuvant endocrine therapy (NET) and those who received NACT. METHODS: Women with cT1-4c, cN1-3 HR+ ILC in the National Cancer Data Base (2004-2014) who underwent surgery following neoadjuvant therapy were identified. Kaplan-Meier curves and Cox proportional hazards modeling were used to estimate unadjusted and adjusted overall survival (OS), respectively. RESULTS: Of the 5942 patients in the cohort, 855 received NET and 5087 received NACT. NET recipients were older (70 vs. 54 years) and had more comorbidities (Charlson-Deyo score ≥ 1: 21.1% vs. 11.5%), lower cT classification (cT3-4: 44.2% vs. 51.0%), lower rates of mastectomy (72.5% vs. 82.2%), lower rates of pathologic complete response (0% vs. 2.5%), and lower rates of postlumpectomy (73.2% vs. 91.0%) and postmastectomy (60.0% vs. 80.8%) radiation versus NACT recipients (all p < 0.001). NACT recipients had higher unadjusted 10-year OS versus NET recipients (57.9% vs. 36.0%), but after adjustment, there was no significant difference in OS between the two groups (p = 0.10). CONCLUSIONS: Patients with node-positive ILC who received NET presented with smaller tumors, older age, and greater burden of comorbidities versus NACT recipients but had similar adjusted OS. While there is evidence from clinical trials supporting efficacy of NET in HR+ breast cancer, our findings suggest the need for further, histology-specific investigation regarding the optimal inclusion and sequence of endocrine therapy and chemotherapy in ILC.

Senile hair graying: H2O2-mediated oxidative stress affects human hair color by blunting methionine sulfoxide repair.

Senile graying of human hair has been the subject of intense research since ancient times. Reactive oxygen species have been implicated in hair follicle melanocyte apoptosis and DNA damage. Here we show for the first time by FT-Raman spectroscopy in vivo that human gray/white scalp hair shafts accumulate hydrogen peroxide (H(2)O(2)) in millimolar concentrations. Moreover, we demonstrate almost absent catalase and methionine sulfoxide reductase A and B protein expression via immunofluorescence and Western blot in association with a functional loss of methionine sulfoxide (Met-S=O) repair in the entire gray hair follicle. Accordingly, Met-S=O formation of Met residues, including Met 374 in the active site of tyrosinase, the key enzyme in melanogenesis, limits enzyme functionality, as evidenced by FT-Raman spectroscopy, computer simulation, and enzyme kinetics, which leads to gradual loss of hair color. Notably, under in vitro conditions, Met oxidation can be prevented by L-methionine. In summary, our data feed the long-voiced, but insufficiently proven, concept of H(2)O(2)-induced oxidative damage in the entire human hair follicle, inclusive of the hair shaft, as a key element in senile hair graying, which does not exclusively affect follicle melanocytes. This new insight could open new strategies for intervention and reversal of the hair graying process.

17beta-estradiol regulates the secretion of TGF-beta by cultured human dermal fibroblasts.

Estrogen plays an important role in skin homeostasis, as demonstrated by the changes seen in the skin of post-menopausal women, changes reversed by HRT. Estrogen also has a role in wound healing, since estrogen deficiency as occurs post-menopausally and in ovariectomised animals, is associated with a reduced rate of wound healing. Estrogen appears to modulate all phases of wound healing with effects on inflammatory cells, epithelialization, angiogenesis, extracellular matrix deposition and tissue remodelling. This study was designed to investigate the effects of 17beta-estradiol on cultured human dermal fibroblasts using an in vitro wound-healing assay. The end points investigated were cell migration, proliferation, total collagen secretion and active TGF-beta1 secretion. 17beta-estradiol significantly increased the migration and proliferation of cultured dermal fibroblasts following mechanical wounding, although the secretion of total soluble collagen was not altered. An increase in TGF-beta1 was demonstrated by unwounded confluent dermal fibroblast monolayers in response to 17beta-estradiol, but paradoxically, a decrease in the secretion of TGF-beta1 was demonstrated in the mechanically wounded dermal fibroblasts. These results identify human dermal fibroblasts as estrogen target cells and provide further evidence for a role by which estrogen regulates this particular cell type as part of the wound-healing process. However, the paradoxical nature of the effect of estrogen on TGF-beta1 secretion following mechanical wounding suggests that the cellular mechanism of action is complex. A greater understanding of the cell-specific action of estrogen may help to develop therapies that will improve cutaneous wound healing in the future.

Sexual hormones in human skin.

The skin locally synthesizes significant amounts of sexual hormones with intracrine or paracrine actions. The local level of each sexual steroid depends upon the expression of each of the androgen- and estrogen-synthesizing enzymes in each cell type, with sebaceous glands and sweat glands being the major contributors. Sebocytes express very little of the key enzyme, cytochrome P450c17, necessary for synthesis of the androgenic prohormones dehydroepiandrosterone and androstenedione, however, these prohormones can be converted by sebocytes and sweat glands, and probably also by dermal papilla cells, into more potent androgens like testosterone and dihydrotestosterone. Five major enzymes are involved in the activation and deactivation of androgens in skin. Androgens affect several functions of human skin, such as sebaceous gland growth and differentiation, hair growth, epidermal barrier homeostasis and wound healing. Their effects are mediated by binding to the nuclear androgen receptor. Changes of isoenzyme and/or androgen receptor levels may have important implications in the development of hyperandrogenism and the associated skin diseases such as acne, seborrhoea, hirsutism and androgenetic alopecia. On the other hand, estrogens have been implicated in skin aging, pigmentation, hair growth, sebum production and skin cancer. Estrogens exert their actions through intracellular receptors or via cell surface receptors, which activate specific second messenger signaling pathways. Recent studies suggest specific site-related distribution of ERalpha and ERbeta in human skin. In contrast, progestins play no role in the pathogenesis of skin disorders. However, they play a major role in the treatment of hirsutism and acne vulgaris, where they are prescribed as components of estrogen-progestin combination pills and as anti-androgens. These combinations enhance gonadotropin suppression of ovarian androgen production. Estrogen-progestin treatment can reduce the need for shaving by half and arrest progression of hirsutism of various etiologies, but do not necessarily reverse it. However, they reliably reduce acne. Cyproterone acetate and spironolactone are similarly effective as anti-androgens in reducing hirsutism, although there is wide variability in individual responses.

Extracorporeal magnetic stimulation of the pelvic floor: impact on anorectal function and physiology. A pilot study.

PURPOSE: This study was designed to investigate the effect of extracorporeal magnetic stimulation on anorectal function and physiology. METHODS: A pilot study comparing the physiology of ten incontinent (9 females) and five continent (4 females) patients with and without perineal magnetic stimulation (10 Hz and 50 Hz) was performed. The ten incontinent patients were treated with two sessions weekly for five weeks of perineal magnetic stimulation. At treatment completion, precontinent and postcontinent scores and resting and squeeze anal pressure were compared. Patients also reported symptom improvement and satisfaction on a linear analog scale. RESULTS: The patients' mean age was 57 years. Sitting resting and squeeze anal pressures were significantly greater than lying pressures (P = 0.007, 0.047). Both 10-Hz and 50-Hz stimulation effected a significant increase in anal pressures compared with the baseline resting pressure (P = 0.005). The baseline squeeze pressures were significantly higher than the stimulated pressures compared with 50-Hz pressures (P = 0.022). After six weeks of treatment, there was a statistically significant increase in resting and squeeze anal pressures and a significant decrease in continence scores (P = 0.007, P = 0.008, P = 0.017). The mean percentage subjective improvement was 16 percent, and the mean patient satisfaction score was 3.3, positively correlating with an improvement in the continence score. CONCLUSIONS: Extracorporeal magnetic stimulation results in a significant increase in anal resting pressure irrespective of pretreatment continence. Although the subjective improvement in continence after treatment is small, there is a significant improvement in both resting pressures and patient continence scores.

Oestrogen functions in skin and skin appendages.

Oestrogens have significant effects on different cell types important in skin physiology, including the epidermal keratinocytes, dermal fibroblasts and melanocytes. In addition, they can also modulate skin appendages such as the hair follicle, the sebaceous gland and the apocrine glands. Oestrogens may also have important modulatory roles in events such as skin ageing, pigmentation, hair growth, sebum production and skin cancer. It is now recognised that oestrogens can modulate their actions via two distinct intracellular receptors (ERalpha and ERbeta) or via cell surface receptors, which activate specific second messenger signalling pathways. This paper highlights the effects of oestrogens on different components of the skin and reviews some of the more recent developments in terms of receptor expression and cell signalling pathways.

Preoperative evaluation of live renal donors using multislice CT angiography.

AIM: To determine the accuracy of multidetector row CT renal angiography in the preoperative evaluation of live kidney donors, and to identify potential pitfalls when reporting. METHODS: Between July 1998 and June 2003, 74 consecutive live renal donors underwent contrast-enhanced multidetector row CT renal angiography before donor nephrectomy. The operative notes and radiological reports of all cases were reviewed retrospectively. Where a significant discrepancy was identified, the archived images were reviewed by two radiologists in the light of the intraoperative findings. RESULTS: A total of 12 discrepancies were identified in 11 of the 74 cases (15%). In the preoperative CT angiography reports, 4 accessory arteries, 6 early-branching renal arteries, 1 duplicated renal vein and 1 accessory ureter were not identified; 9 of these were evident on review, but were not detected at the time of reporting. In 3 cases (1 accessory artery, the duplicated renal vein and the accessory ureter), the anomaly was not visible on review of the CT angiographic data, even with the benefit of hindsight. Surgical feedback during the study period resulted in modifications to CT technique and improved performance. CONCLUSION: In the majority of cases, there was good correlation between preoperative CT renal angiography and operative findings. Most discrepancies were due either to an oversight by the reporting radiologist, or failure to fully appreciate the potential surgical significance of certain findings. Regular surgical feedback plays a valuable role in improving reporting accuracy and maintaining imaging standards.

Prospective manometric assessment of botulinum toxin and its correlation with healing of chronic anal fissure.

INTRODUCTION: The efficacy and pharmacokinetics of botulinum toxin for chronic anal fissure continues to be debated. Addressing both issues we prospectively assessed the manometric impact of botulinum toxin on internal anal sphincter pressure, correlating this impact with chronic anal fissure healing. METHODS: Sixty patients with chronic fissures were assessed. Fifty-seven patients had a total of 20 units of botulinum toxin injected into the intersphincteric groove at four o'clock and eight o'clock. Patients were prospectively assessed with a linear analog pain score, bleeding score, clinical fissure score, modified St. Mark's continence score, and anorectal manometry. Each parameter was reassessed two weeks following treatment and again at three months. RESULTS: Fifty-six patients (30 female), median age 43 (range, 17-80) years, were followed for a median of five (range, 3-15) months with fissure healing assessed 12 weeks after treatment. Physical healing and symptom control were dependent on the baseline maximum anal resting pressure and baseline fissure score (P = 0.003, P = 0.009, respectively). Although maximum anal resting pressure fell by 17 (mean, range, 0-71) percent, pressure reduction did not correlate with clinical outcome (P > 0.2). Seventeen patients reported a mean 17 percent increase in continence score. There was no correlation between deterioration in continence and baseline or subsequent reduction in maximum anal resting pressure. CONCLUSION: Patients with Grade 1 lower-pressure fissures are more likely to heal following treatment with 20 units of botulinum toxin. Healing does not appear to be dependent on a reduction in maximum anal resting pressure.

Manometric effect of topical glyceryl trinitrate and its impact on chronic anal fissure healing.

INTRODUCTION: The duration of physiologic action of topical glyceryl trinitrate in the management of anal fissure has been the source of some controversy. This study was designed to assess the manometric effect of glyceryl trinitrate on internal sphincter resting tone with continuous monitoring. METHODS: Twenty-seven patients with a chronic anal fissure were assessed with fissure, pain, bleeding, and continence scores. Twenty-two were randomized to 1 cm of topical 0.2 percent glyceryl trinitrate paste, applied to the lower anal canal. Five patients were randomized to 1 cm of water-soluble lubricating jelly to the lower anal canal. Continuous stationary six radial channel water perfusion anorectal manometry was performed for 5 minutes before treatment and then for a further 30 minutes. The 22 glyceryl trinitrate patients were then advised to apply topical 0.2 percent glyceryl trinitrate, three times daily, for eight weeks. Twenty-four hours after completing treatment, all baseline assessments were repeated. The lubricant jelly cohort was discharged from the study after the initial assessment. RESULTS: During the initial manometric assessment, 21 glyceryl trinitrate patients (95 percent) had 20 percent or more reduction in mean and maximum anal resting pressure after treatment. However, there was no statistical difference at 20 minutes compared with 0 minutes (P > 0.1). After eight-week treatment, 16 patients (73 percent) reported symptom resolution and 15 (67 percent) were found to be healed on examination. Clinical healing and resolution of symptoms positively correlated with a higher pretreatment maximum anal resting pressure in the mid anal canal (P < 0.0001), lower fissure score (P < 0.0001), and greater percentage reduction of the maximum resting pressure after application of glyceryl trinitrate (P < 0.001). The mean and maximum anal resting pressure at Week 8 was not significantly different from the baseline values (P > 0.05). During continuous manometry, the anal resting pressure did not significantly change in the patients treated with lubricating jelly. CONCLUSIONS: In those patients with a lower fissure score, a higher mid anal canal anal resting pressure, and a greater resting pressure reduction after glyceryl trinitrate application, a favorable clinical outcome can be expected with glyceryl trinitrate treatment. However, because the physiologic response has resolved in fewer than 20 minutes, the dosing regime should be reassessed.

Laparoscopic or transanal repair of rectocele? A retrospective matched cohort study.

PURPOSE: The aim of the study was to analyze the functional and physiologic outcome of patients undergoing laparoscopic rectocele repair compared to a matched cohort undergoing transanal repair. METHODS: Forty patients with a rectocele who had undergone laparoscopic pelvic floor repair by a laparoscopic gynecologist were matched for age and rectocele size with 40 patients who had undergone a transanal repair by a colorectal surgeon. All patients had clinical evidence of a symptomatic rectocele. All patients were assessed postoperatively with a quality of life (SF-36) score, a modified St. Mark's continence score, a urinary dysfunction score, a Watt's sexual dysfunction score, and a linear analog patient satisfaction score. Fifteen patients in each group had also undergone preoperative and postoperative anal manometry. RESULTS: At 44 months median follow-up, the transanal approach resulted in significantly more patients reporting bowel symptom alleviation (P < 0.002) and higher patient satisfaction (P < 0.003). The bowel symptom improvement was also sustained over a significantly longer period (P < 0.03). Only 11 patients (28 percent) in the laparoscopic group reported more than 50 percent improvement in their bowel symptoms compared to 25 patients (63 percent) in the transanal group. On univariate analysis of 50 percent bowel symptom improvement, a larger rectocele (P < 0.009), transanal repair (P < 0.02), and presenting with obstructive defecation rather than fecal incontinence (P < 0.03) were statistically significant. Rectocele size (P < 0.012) and treatment cohort (P < 0.006) remained significant on multivariate analysis. Postoperatively, bowel symptom alleviation correlated with patient satisfaction in both groups (P < 0.015). Although not statistically significant, five patients (13 percent) in the transanal group developed postoperative fecal incontinence, which was associated with a low maximum anal resting pressure preoperatively that was further diminished postoperatively (P > 0.06). Only one patient (3 percent) in the laparoscopic group reported a decline in fecal continence, but four patients (10 percent) reported worsening of their symptoms of obstructed defecation. Postoperative dyspareunia was reported by 24 patients in total (30 percent), with significantly more in the transanal group (P > 0.05). CONCLUSIONS: The transanal repair results in a statistically greater alleviation of bowel symptoms and greater patient satisfaction scores. However, this approach may have a greater degree of functional co-morbidity than the laparoscopic rectocele repair.

Long-term follow-up of dynamic graciloplasty for faecal incontinence.

OBJECTIVE: This paper presents the long-term morbidity, function and quality of life data for patients who have undergone dynamic graciloplasty (DGP) for faecal incontinence. PATIENTS AND METHODS: All patients (n = 38) who had undergone DGP at one institution between 1993 and 2003 are presented. Thirty-three were available for long-term follow-up (median 60 months) and completed a telephone questionnaire assessing quality of life (QOL), bowel and sexual function and patient satisfaction. All patients had interval anorectal physiology studies. RESULTS: At a median follow-up of 5 years, 72% had pain, swelling or paraesthesia in the donor leg and 27% had sexual dysfunction. Sixteen percent of patients had been converted to an end-colostomy for persisting incontinence and 11% for obstructed defaecation. All other patients have a normally functioning graciloplasty. Sixteen percent of patients reported a faecal continence score < 12. Of those patients with a functioning graciloplasty, 50% had obstructed defaecation and 64% reported that their bowel dysfunction had a negative impacted on their QOL. Age, medical comorbidity and anal manometry did not correlate with functional outcome. Quality of life scores and patient satisfaction scores correlated significantly with continence scores. There was a trend toward higher QOL and satisfaction scores with conversion to colostomy compared with a continence score > 12. Sixty percent of patients rated their satisfaction with DGP as 50% or better on a visual analogue scale, and this correlated strongly with the continence score at the time of the assessment (P < 0.001). CONCLUSION: Dynamic graciloplasty significantly improves patient quality of life and anal continence for some patients. Despite increased experience, morbidity remains high and long-term continence scores are poor in a majority of cases. Obstructed defaecation is a significant problem after graciloplasty and antegrade colonic enemas may be needed. Significant prognostic factors for obstructed defaecation remain to be identified. The mechanism of both continence failure and surgical morbidity remains poorly defined in many patients and requires further investigation. The individual patient can expect a 16% chance of normal faecal continence at 5 years, with at least one surgical morbidity as a result of the procedure.

Oestrogen receptor beta is the predominant oestrogen receptor in human scalp skin.

Oestrogens play a major role in non-classic target tissues in both sexes, yet there have been few studies on estrogens and skin. Recently a second oestrogen receptor (ERbeta) has been discovered. Therefore, we have compared the expression of oestrogen receptor alpha (ERalpha), beta (ERbeta), the androgen receptor (AR) and a cell proliferation marker in male and female non-balding scalp skin. ERbeta was the major steroid receptor expressed in human skin. It was highly expressed in epidermis, blood vessels and dermal fibroblasts, in contrast to ERalpha and AR. In the hair follicle, ERbeta expression was localized to nuclei of outer root sheath, epithelial matrix and dermal papilla cells, in contrast to ERalpha, and the AR, which was only expressed in dermal papilla cells. Serial sections also showed strong nuclear expression of ERbeta in the cells of the bulge, while neither ERalpha nor AR was expressed. In the sebaceous gland, ERbeta was expressed in both basal and partially differentiated sebocytes. ERalpha exhibited a similar pattern of expression, while the AR was expressed in the basal and very early differentiated sebocytes. There was no obvious difference in the expression of either oestrogen receptor in male or female skin. The wide distribution of ERbeta in human skin suggests that oestrogens may play an important role in the maintenance of skin and in the regulation of the pilosebaceous unit, and provides further evidence for oestrogen action in non-classic target tissues. The differential expression of ERalpha, ERbeta and AR in human skin suggests that the mechanisms by which steroid hormones mediate their effects may be more complex than previously thought.

The biological actions of estrogens on skin.

There is still extensive disparity in our understanding of how estrogens exert their actions, particularly in non-reproductive tissues such as the skin. Although it has been recognized for some time that estrogens have significant effects on many aspects of skin physiology and pathophysiology, studies on estrogen action in skin have been limited. However, estrogens clearly have an important function in many components of human skin including the epidermis, dermis, vasculature, hair follicle and the sebaceous, eccrine and apocrine glands, having significant roles in skin aging, pigmentation, hair growth, sebum production and skin cancer. The recent discovery of a second intracellular estrogen receptor (ERbeta) with different cell-specific roles to the classic estrogen receptor (ERalpha), and the identification of cell surface estrogen receptors, has provided further challenges to understanding the mechanism of estrogen action. It is now time to readdress many of the outstanding questions regarding the role of estrogens in skin and improve our understanding of the physiology and interaction of steroid hormones and their receptors in human skin. Not only will this lead to a better understanding of estrogen action, but may also provide a basis for further interventions in pathological processes that involve dysregulation of estrogen action.

Do androgens influence hair growth by altering the paracrine factors secreted by dermal papilla cells?

Androgens regulate many aspects of human hair growth in both sexes. After puberty they transform tiny vellus follicles in many areas, e.g. the face, to terminal ones producing long, thick, pigmented hairs. In genetically predisposed individuals, androgens also cause the reverse transformation of terminal scalp follicles into vellus ones, causing balding. In the current hypothesis for androgen action, androgens control most follicular cells indirectly acting via the mesenchyme-derived dermal papilla which regulates many aspects of follicular activity. In this model androgens binding to androgen receptors in dermal papilla cells alter their production of regulatory molecules which influence other follicular components; these molecules may be soluble paracrine factors and/or extracellular matrix proteins. This hypothesis is supported by immunohistochemical localisation of androgen receptors in dermal papilla cell nuclei and the demonstrations that androgen receptor content and testosterone metabolism patterns of cultured dermal papilla cells from various body sites reflect hair growth in androgen-insensitivity syndromes. The next question is whether androgens alter the paracrine factors secreted by dermal papilla cells. Cultured dermal papilla cells do release soluble, proteinaceous factors into their media which stimulate the growth of keratinocytes and other dermal papilla cells. This mitogenic potential can cross species from humans to rodents. Importantly, testosterone in vitro stimulates the mitogenic potential of beard cells, but in contrast inhibits production by balding scalp cells reflecting their in vivo androgenic responses. Since androgens in vitro do alter the secretion of paracrine factors the current focus lies in identifying specific factors produced, e.g. IGF-I and stem cell factor (SCF), using ELISA and RT-PCR, and comparing their expression in cells from follicles with varying responses to androgens in vivo or under androgen stimulation in vitro. This should lead to greater understanding of androgen action and enable the development of better treatment for androgen-potentiated disorders.

Androgen receptors are only present in mesenchyme-derived dermal papilla cells of red deer (Cervus elaphus) neck follicles when raised androgens induce a mane in the breeding season.

Red deer stags produce an androgen-dependent mane of long hairs only in the breeding season; in the non-breeding season, when circulating androgen levels are low, the neck hair resembles the rest of the coat. This study was designed to determine whether androgen receptors are present in deer follicles throughout the year or only in the mane (neck) follicles when circulating testosterone levels are high in the breeding season. Although androgens regulate much human hair growth the mechanisms are not well understood; they are believed to act on the hair follicle epithelium via the mesenchyme-derived dermal papilla. The location of androgen receptors in the follicle was investigated by immunohistochemistry and androgen binding was measured biochemically in cultured dermal papilla cells derived from mane and flank follicles during the breeding season and from neck follicles during the non-breeding season. Immunohistochemistry of frozen skin sections using a polyclonal antibody to the androgen receptor localised nuclear staining only in the dermal papilla cells of mane follicles. Saturation analysis assays of 14 primary dermal papilla cell lines using [(3)H]-mibolerone demonstrated high-affinity, low-capacity androgen receptors were present only in mane (breeding season neck) cells; competition studies with other steroids confirmed the specificity of the receptors. Androgen receptors were not detectable in cells from either the breeding season flank nor the non-breeding season neck follicles. The unusual biological model offered by red deer of androgen-dependent hair being produced on the neck in the breeding, but not the non-breeding season, has allowed confirmation that androgen receptors are required in follicle dermal papilla cells for an androgen response; this concurs with previous human studies. In addition, the absence of receptors in the non-breeding season follicles demonstrates that receptors are not expressed unless the follicle is responding to androgens. Androgen receptors may be induced in mane follicles by seasonal changes in circulating hormone(s).

The hair follicle: a paradoxical androgen target organ.

Androgens are the main regulator of normal human hair growth. After puberty, they promote transformation of vellus follicles, producing tiny, unpigmented hairs, to terminal ones, forming larger pigmented hairs, in many areas, e.g. the axilla. However, they have no apparent effect on the eyelashes, but can cause the opposite transformation on the scalp leading to the replacement of terminal hairs by vellus ones and the gradual onset of androgenetic alopecia. This paradox appears to be an unique hormonal effect. Hair follicles are mainly epithelial tissues, continuous with the epidermis, which project into the dermis. A mesenchyme-derived dermal papilla enclosed within the hair bulb at the base controls many aspects of follicle function. In the current hypothesis for androgen regulation, the dermal papilla is also considered the main site of androgen action with androgens from the blood binding to receptors in dermal papilla cells of androgen-sensitive follicles and causing an alteration of their production of paracrine factors for target cells e.g. keratinocytes. Studies of cultured dermal papilla cells from sites with different responses to androgens in vivo have confirmed the paradoxical responses. All dermal papilla cells from androgen-sensitive sites contain low capacity, high affinity androgen receptors. However, only some cells formed 5alpha-dihydrotestosterone, e.g. beard but not axillary cells, in line with hair growth in 5alpha-reductase deficiency. Incubation with androgens also stimulated the mitogenic capacity of beard cell media, but inhibited that produced by scalp cells. This suggests that the paradoxical differences are due to differential gene expression within hair follicles, presumably caused during embryogenesis.

Oestrogen receptor beta is not present in the pilosebaceous unit of red deer skin during the non-breeding season.

Androgens and oestrogens both have roles in skin physiology. Recently a second oestrogen receptor (ERbeta) has been identified in androgen-dependent tissues. The red deer grows a breeding season, androgen-dependent mane when plasma testosterone rises; this is replaced with small neck hairs during the non-breeding season. In non-breeding season deer skin, ERbeta was localised to the blood vessels and arrector pili muscle, but in contrast to human skin, not in the pilosebaceous unit or epidermis. The androgen receptor was not expressed. Further studies with breeding season skin may help to elucidate whether serum androgens or androgen receptor expression can modulate the expression of ERbeta in skin.

Evaluation of dynamic gadolinium-enhanced breath-hold MR angiography in the diagnosis of renal artery stenosis.

OBJECTIVE: The aim of our study was to evaluate a three-dimensional gadolinium-enhanced breath-hold MR angiography sequence using standard MR gradients in detecting renal artery stenosis. SUBJECTS AND METHODS: Forty-two patients referred for angiography for suspected renal artery stenosis underwent both conventional digital subtraction angiography (DSA) and MR angiography. MR angiography was performed on a 1.5-T scanner with standard gradients. A fast multiplanar spoiled gradient-echo sequence was used with the following parameters: TR/TE, 10.3/1.9; flip angle, 45 degrees; field of view, 36 x 32 cm; matrix size, 256 x 128; one excitation; volume thickness, 70 mm; and partitions, 28. Gadolinium was administered IV as a dynamic bolus of 30-40 ml. Conventional and MR angiographic images were interpreted by two radiologists in consensus. RESULTS: DSA revealed 87 renal arteries, of which 79 were in 35 patients with native kidneys and eight arteries were in seven patients with transplanted kidneys. Gadolinium-enhanced MR angiography showed 85 (98%) of 87 renal arteries. Seventeen patients had 20 significant (>50% stenosis) renal artery stenoses and five patients had five occluded renal arteries revealed by DSA. MR angiography revealed 85 renal arteries (98%), 20 stenoses (100%), and five occlusions (100%). Gadolinium-enhanced MR angiography led to one false-positive interpretation for renal artery stenosis and no false-negative interpretations. Thus, the sensitivity, specificity, and accuracy of MR angiography for renal artery stenosis were 100%, 98%, and 99%, respectively. CONCLUSION: The MR angiography pulse sequence we used was an effective and reliable technique for the diagnosis of renal artery stenosis. The sequence can be performed on widely available MR equipment that does not require fast gradient hardware.

A three-dimensional gadolinium-enhanced MR venography technique for imaging central veins.

OBJECTIVE: We evaluated the use of a three-dimensional gadolinium-enhanced MR venography technique in selected patients with suspected central venous abnormalities. SUBJECTS AND METHODS: Thirty-seven patients with suspected thrombosis, stenosis, occlusion, or compression of the axillary vein, subclavian vein, brachiocephalic vein, or superior or inferior vena cava or with suspected malfunction of central venous catheters were imaged. For all patients, we obtained a three-dimensional dynamic gadolinium-enhanced (bolus injection, 30 40 ml) breath-hold spoiled gradient-recalled acquisition in the steady state as well as conventional venous images from either Doppler sonography, CT, or digital subtraction venography. Breathhold fast multiplanar spoiled gradient-recalled acquisitions in the steady state were obtained using the following parameters: TR/TE, 10.3/1.9; flip angle, 45 degrees; matrix size, 256 x 128; number of excitations, one; field of view, 36-48 cm; number of partitions, 28; and slice thickness, 2.54 mm. MR venograms and conventional images were interpreted by two observers in consensus who were unaware of clinical information and the diagnosis. RESULTS: MR venograms were of diagnostic quality for all 37 patients. Thirteen patients had normal venous systems seen on both conventional and MR images. MR venography showed all nine venous stenoses, the one pericatheter fibrin sheath, and the one jugular vein thrombosis. Axillary or subclavian vein thrombosis was correctly diagnosed with MR venography in all four patients with this condition. Mediastinal venous compression was accurately depicted by MR venography in the five patients who had such compression. Finally, MR venography revealed the correct diagnosis in the three patients with inferior vena cava thrombus and tumor and the one patient with inferior vena cava compression. Thus, MR venography was 100% sensitive, specific, and accurate in the diagnosis of abnormalities affecting large central veins. CONCLUSION: Compared with conventional imaging, gadolinium-enhanced breathhold MR venography is easy to perform, well tolerated, and highly accurate in depicting central venous abnormalities.

Evaluation of the role of magnetic resonance myelography in lumbar spine imaging.

The purpose of our study was to evaluate the accuracy of MR myelography in depicting disc herniation in the lumbar spine when compared with conventional MRI in patients presenting with clinical evidence of disc herniation. One hundred patients referred for conventional MR imaging of the lumbar spine also had coronal MR (TR 9000 ms, TE 272 ms eff, NEX 3, echo train length 32) myelography performed. Three experienced observers compared magnetic resonance myelography (MRM) with conventional lumbar spine MR using the following variables: visibility of thecal sac and nerve roots, and the presence, location and severity of disc herniation. Disc protrusions were seen at 110 disc space levels on conventional MR images as opposed to 93 on MRM. However, only 72 % of lesions seen on conventional MR were diagnosed by MRM. Similarly, only 63.8 % of nerve root compression abnormalities seen at conventional MR were visualized when compared with conventional MRM. The sensitivity, specificity and accuracy of MRM when compared with conventional MR was 72, 93 and 85 %, respectively. The MRM technique yields images that resemble conventional myelography and may be used to help confirm abnormalities seen on conventional MR in selected cases; however, the large number of false-positive and false-negative examinations indicates that caution should be used in interpreting MRM images.