The approach to an isolated close anterior margin in breast conserving surgery.

INTRODUCTION: Although close radial margins after breast-conserving surgery routinely undergo re-excision, appropriate management of patients with close anterior margins remains a topic of controversy. An increasing body of literature suggests that re-excision of close anterior margins yields low rates of residual malignancy and may only be necessary in selected patients. The aim of this study was to examine the management of close anterior margins after breast conserving surgery in a single institution and to analyse the rate of residual disease in re-excised anterior margins. METHODS: All patients having breast conserving surgery at St Vincent's University Hospital from January 2008 to December 2012 were reviewed retrospectively. Data collected included patient demographics, tumour characteristics, margin positivity, re-excision rates and definitive histology of the re-excision specimens. A close margin was defined as les than 2 mm. RESULTS: A total of 930 patients were included with an average age of 65 years (range 29-94 years). Of these, 121 (13%) had a close anterior margin. Further re-excison of the anterior margin was carried out in 37 patients (30.6%) and a further 16 (13.2%) proceeded to mastectomy. Residual disease was found in 18.5% (7/36) of those who underwent re-excision and 7/16 (43.75%) of those who underwent mastectomy. Overall, 11.57% (14/121) of patients with close anterior margins were subsequently found to have residual disease. CONCLUSION: The low yield of residual disease in re-excised anterior margins specimens supports the concept that routine re-excision of close anterior margins is not necessary. Further research is required to definitively assess its influence on the risk of local recurrence.

Magnetic Stent Removal in a Nurse Led Clinic; a Nine Month Experience.

Ureteric stents are frequently inserted post endourological procedures. However, subsequent endoscopic stent removal requires a second procedure for the patient and the availability of necessary resources. Longer duration of indwelling stents can lead to increased risk of symptoms and complications. The use of magnetic stents removed with a magnetic retrieval device (BlackStar©), offers an alternative which obviates the need for cystoscopy. We assessed the outcomes for this novel method of stent removal in our institution. A retrospective analysis was performed of all patients undergoing magnetic stent insertion and subsequent removal in a nurse-led clinic over a nine-month period. Patients were followed up with a prospective validated Ureteral Stent Symptoms Questionnaire (USSQ)3. A cost analysis was also performed. In total, 59 patients were treated using magnetic stents. The complication rate was low (6.7%). The median duration of indwelling stent was 5.8 days (range 1-11 days). Patients reported haematuria and lower urinary tract symptoms but >90% experienced no functional impairment with minimal days of employment lost (mean 0.75 days). All patients reported satisfaction with nurse-led stent removal and 97% were happy to have stents removed via this method in the future. The total financial savings were estimated at €47,790 over this period. Nurse-led removal of magnetic stents is safe and well tolerated by patients and enables expedient stent removal. It also provides a significant cost benefit and frees up valuable endoscopic resources.

Running in the family: A rare diagnosis of familial papillary thyroid cancer.

INTRODUCTION: Whilst inherited medullary thyroid cancer has been extensively reported, familial non-medullary thyroid cancer is a rare and less well described clinical entity. Familial forms of the disease demonstrate more aggressive features than sporadic non-medullary thyroid cancer. PRESENTATION OF CASE: A 54 year old lady was referred with globus on a background of a longstanding goitre. Three first degree relatives had a history of non-medullary thyroid carcinoma. Investigations revealed a papillary thyroid carcinoma and the patient proceeded to total thyroidectomy and ipsilateral Level VI neck dissection, followed by adjuvant radioiodine ablation. DISCUSSION: Familial papillary thyroid carcinoma syndrome is defined as three or more first degree relatives diagnosed with the disease in the absence of other known associated syndromes. It is often associated with the presence of benign thyroid disorders, and is characterised by the early onset of multi-focal bilateral locally advanced tumours. CONCLUSION: Familial papillary thyroid cancer is a rare clinical entity but should be considered where ≥3 first degree relatives are diagnosed with non-medullary thyroid cancer. It is necessary to exclude other familial tumour syndromes to make the diagnosis. It demonstrates more aggressive features with higher rates of local recurrence than its sporadic counterpart, and therefore mandates more aggressive management than might otherwise be indicated. Screening of first degree relatives should be considered. SUMMARY: The case of a 54 year old female diagnosed with familial non-medullary thyroid carcinoma is reported.

Effect of gabapentin on pain after cardiac surgery: a randomised, double-blind, placebo-controlled trial.

This study evaluated whether perioperative administration of gabapentin in cardiac surgery patients could reduce postoperative opioid consumption, postoperative sleep or perceived quality of recovery. This randomised controlled trial assigned 60 patients undergoing cardiac surgery to receive 1200 mg of gabapentin or placebo two hours preoperatively, and then 600 mg of gabapentin or placebo twice a day for the next two postoperative days. Postoperative opioid use was measured by the amount of fentanyl used in the first 48 hours postoperatively. Pain at rest and with movement at 12, 24, 48 and 72 hours after surgery, sleep scores on postoperative days two and three and patient-perceived quality of recovery were also assessed. Fentanyl use, visual analog pain scores, sleep scores, adjunctive pain medication use and number of anti-emetics given were not significantly different between the gabapentin and placebo groups. The incidence of side-effects was similar between the gabapentin and placebo groups, and no difference was found between groups in relation to quality of recovery. These findings indicate that preoperative use of gabapentin followed by postoperative dosing for two days did not significantly affect the postoperative pain, sleep, opioid consumption or patient-perceived quality of recovery for patients undergoing cardiac surgery.

Experimental models for the investigation of female sexual function and dysfunction.

There have been limited anatomic and physiological investigations of the female sexual arousal response. A broader understanding of the physiologic mechanisms of female sexual arousal function is required to improve the management of women with sexual dysfunction. Three experimental test systems have been developed to understand better the biochemical and physiological mechanisms of female sexual arousal response. An in vivo animal model was developed to record physiological and hemodynamic changes in the clitoris and vagina following pelvic nerve stimulation and administration of vasoactive agents and physiological modulators. In vitro organ baths of clitoral and vaginal tissue were utilized to investigate mechanisms involved in the regulation of smooth muscle contractility. In addition, primary cell cultures of human and animal clitoral and vaginal smooth muscle cells were developed to investigate signal transduction pathways modulating smooth muscle tone. In vivo studies revealed hemodynamic changes in vagina and clitoris in response to pelvic nerve stimulation, vasodilators and physiological modulators. Organ bath studies have demonstrated that clitoral and vaginal smooth muscle tone is affected by non-adrenergic and non-cholinergic neurotransmitters, and the presence of functional alpha 1 and alpha 2 adrenergic receptors in these tissues has been established through biochemical studies. These changes are regulated by the tone of vascular and non-vascular smooth muscle in the vagina and clitoris. Primary cell culture studies have suggested that several physiological modulators such as vasoactive intestinal polypeptide (VIP), nitric oxide (NO), and prostaglandin E (PGE) regulate vaginal smooth muscle contractility. Data from experimental models have provided a preliminary understanding of the mechanisms of the female sexual arousal response.

TrkA amino acids controlling specificity for nerve growth factor.

Neurotrophins are important for the development and maintenance of the vertebrate nervous system, mediating their signal into the cell by specific interaction with tyrosine kinase receptors of the Trk family. The extracellular portion of the Trk receptors has been previously proposed to consist of a cysteine-rich motif, a leucine-rich motif, a second cysteine-rich motif followed by two immunoglobulin-like domains. Earlier studies have shown that a major neurotrophin-binding site in the Trk receptors resides in the second immunoglobulin-like domain. Although the individual amino acids in TrkA involved in binding to nerve growth factor (NGF) and those in TrkC involved in binding to neurotrophin-3 have been mapped in this domain, the Trk amino acids that provide specificity remained unclear. In this study, a minimum set of residues in the human TrkC second immunoglobulin-like domain, which does not bind nerve growth factor (NGF), were substituted with those from human TrkA. The resulting Trk variant recruited binding of NGF equivalent to TrkA, maintained neurotrophin-3 binding equivalent to TrkC, and also bound brain-derived neurotrophin, although with lower affinity compared with TrkB. This implies that the amino acids in the second immunoglobulin-like domain that determine Trk specificity are distinct for each Trk.

Management of patients with chronic obstructive pulmonary disease in ICU and promotion of smoking cessation.

Chronic obstructive pulmonary disease (COPD) is an increasingly significant health problem. Pathophysiological effects of smoking are outlined in this paper. Management of patients with COPD in ICU is discussed. Treatment options available to treat COPD patients are described. Health promotion and aids available to assist cessation of smoking are discussed.

Triage of abnormal postmenopausal bleeding: a comparison of endometrial biopsy and transvaginal sonohysterography versus fractional curettage with hysteroscopy.

OBJECTIVE: We sought to compare the combined diagnostic reliability of sonohysterography and endometrial biopsy with fractional curettage with hysteroscopy in the initial evaluation of postmenopausal women with abnormal uterine bleeding. STUDY DESIGN: This year-long, prospective, controlled, clinical investigation was initiated Sept. 1, 1995. All postmenopausal women with abnormal uterine bleeding were offered inclusion, with 104 enrolled. An endometrial biopsy was performed at the time of initial evaluation. Routine transvaginal ultrasonography was then used to measure the uterus, ovaries, and endometrial stripe thickness, followed immediately by sonohysterography to evaluate the symmetry of endometrial wall thickness and delineate any intraluminal masses. Definitive histopathologic sampling was obtained by fractional curettage with hysteroscopy and statistically compared with the diagnoses arrived at by endometrial biopsy and sonohysterography. RESULTS: The combination of endometrial biopsy and transvaginal sonohysterography positively correlated with the surgical findings >95% of the time, with a sensitivity and specificity of 94% and 96%, respectively (confidence interval 91% to 99%). No patients with endometrial hyperplasia or cancer were misdiagnosed. CONCLUSIONS: Sonohysterography combined with endometrial biopsy is a reliable office tool for evaluating postmenopausal women with abnormal uterine bleeding. Medical management of those patients identified as having no endometrial abnormalities can be considered with confidence, while saving the cost and surgical risk of fractional curettage. Patients with intraluminal masses should be referred for surgical management in a timely fashion.

High resolution mapping of the binding site of TrkA for nerve growth factor and TrkC for neurotrophin-3 on the second immunoglobulin-like domain of the Trk receptors.

Neurotrophic factors are important for survival and maintenance of neurons during developmental and adult stages of the vertebrate nervous system. The neurotrophins mediate their signal into the cell by specific interaction with tyrosine kinase receptors of the Trk family. The extracellular immunoglobulin-like domain of the Trk receptors adjacent to the membrane has previously been shown to be the dominant element for specific neurotrophin binding. Using computer graphics models of the human TrkA and TrkC immunoglobulin-like domains as a guide, the residues involved in binding to their respective neurotrophins were mapped by mutational analysis. TrkC primarily utilizes loop EF, between beta-strands E and F, for binding. In contrast, TrkA utilizes the EF loop as well as additional residues, the latter being prime candidates for determining the specificity of TrkA versus TrkC. When selected TrkC and TrkA mutants with reduced binding were expressed on NIH3T3 cells, neurotrophin-induced autophosphorylation was strongly reduced or absent.

X-ray structure of human relaxin at 1.5 A. Comparison to insulin and implications for receptor binding determinants.

The X-ray crystal structure of relaxin at 1.5 A resolution is reported for the physiologically active form of the human hormone. Relaxin is a small, two-chain polypeptide that is a member of the protein hormone family that also includes insulin and the insulin-like growth factors IGF-I and IGF-II. These hormones have biologically diverse activities but are structurally similar, sharing a distinctive pattern of cysteine and glycine residues. The predicted structural homology of relaxin to insulin is confirmed by this structural analysis; however, there are significant differences in the terminal regions of the b-chain. Although relaxin, like insulin, crystallizes as a dimer, the orientation of the molecules in the respective dimers is completely different. The region of the relaxin molecule proposed to be involved in receptor binding is part of the dimer interface, suggesting that some of the other residues contained in the dimer contact surface might be receptor binding determinants as well. The proposed receptor binding determinants for insulin likewise include residues at its dimer interface. However, because the dimer contacts of relaxin and insulin are quite different, it appears that these two structurally related hormones have evolved somewhat dissimilar mechanisms for receptor binding.

Effect of gamma-irradiation on the healing of gastric biopsy sites in monkeys. An experimental model for peptic ulcer disease and gastric protection.

The acute effects of gamma-irradiation on the gastric mucosa have been studied in a primate model. Fiberoptic gastroscopies were performed in 6 rhesus monkeys in the basal state as well as 3 h and 3, 7, and 9 days after total body irradiation (800 rads). Gastric biopsy specimens (diameter 1 mm) obtained during each session were examined using light microscopy and scanning electron microscopy; in addition, subsequent healing of the biopsy sites was assessed visually. Gastric biopsy sites were completely healed in 3 days in the basal state; in contrast, ulcer craters (diameter 1 mm) were still present at the site of the biopsies 3, 7, and 9 days after the biopsies were performed in irradiated animals. Light microscopic examination of the biopsy specimens demonstrated only lymphocytic infiltration of the lamina propria. In contrast, scanning electron microscopic examination revealed that the size and number of microvilli of the gastric surface epithelial cells were increased on the day of irradiation compared to basal; 3-9 days later, numerous gastric surface epithelial cells were damaged or had disappeared so that bare areas of the lamina propria were visible in the specimens taken outside of the ulcer craters. These changes may reflect inadequate protection of insufficient regeneration of gastric mucosal cells which, in turn, would explain the persistence of ulcers after gastric biopsies were performed in irradiated monkeys.

A nutrition curriculum for health education: its effect on students' knowledge, attitude, and behavior.

The objective of the study was to determine the effect of nutrition instruction, using the curriculum guides, Nutrition In A Changing World, A Curriculum for Junior High Health, and A Curriculum for Senior High Health, on improving the nutrition knowledge, selected food/nutrition attitudes, and dietary behavior of students enrolled in secondary level health courses. Three groups of students were utilized including one experimental and two control groups at each level (junior high and senior high). The experimental group was pretested, taught the nutrition curriculum, and posttested. One control group was posttested only to measure the effect of the pretest on posttest performance. A second control group was pretested and posttested. Neither control group received nutrition instruction until after the study was completed. The three instruments used to collect data were a nutrition knowledge test, a food/nutrition attitude instrument, and a food frequency form. The results indicate that, at all grade levels, the experimental group had significantly improved knowledge scores. Little change in attitude scale scores was noted in grades seven and eight, while ninth grade experimental students scored significantly higher on the posttest for all attitude scales. Little improvement was seen in the posttest food frequency scores.

Agnogenic myeloid metaplasia preceded by repeated leukemoid reactions and persistent acquired Pelger-Huët anomaly of granulocytes: case report with review of acquired Pelger-Huët anomaly.

A case report of agnogenic myeloid metaplasia (AMM) is presented in which a patient had a preliminary 18-month period characterized by leukemoid reactions to repeated infections alternating with normal health, throughout which an acquired Pelger-Huët anomaly persisted. This is the only reported case of the anomaly as a premonitory hematologic marker of AMM. The literature concerning the acquired Pelger-Hut anomaly is reviewed.

Two cases of acute leukaemia in pregnancy.

2 cases of acute leukaemia which developed in the course of pregnancy are reported. The first was a 34-year-old woman who presented with acute myeloblastic leukaemia late in the second trimester and received combination chemotherapy. A normal male infant was delivered. The second patient, aged 24 years, presented with acute lymphoblastic leukaemia early in the second trimester and was treated with the same regime. Pre-eclamptic toxaemia developed at 29 weeks gestation. Intra-uterine death was confirmed 1 week later.