Nerve-Sparing Gynecologic Surgery Enabled by A Near-Infrared Nerve-Specific Fluorophore Using Existing Clinical Fluorescence Imaging Systems.

Patients undergoing gynecological procedures suffer from lasting side effects due to intraoperative nerve damage. Small, delicate nerves with complex and nonuniform branching patterns in the female pelvic neuroanatomy make nerve-sparing efforts during standard gynecological procedures such as hysterectomy, cystectomy, and colorectal cancer resection difficult, and thus many patients are left with incontinence and sexual dysfunction. Herein, a near-infrared (NIR) fluorescent nerve-specific contrast agent, LGW08-35, that is spectrally compatible with clinical fluorescence guided surgery (FGS) systems is formulated and characterized for rapid implementation for nerve-sparing gynecologic surgeries. The toxicology, pharmacokinetics (PK), and pharmacodynamics (PD) of micelle formulated LGW08-35 are examined, enabling the determination of the optimal imaging doses and time points, blood and tissue uptake parameters, and maximum tolerated dose (MTD). Application of the formulated fluorophore to imaging of female rat and swine pelvic neuroanatomy validates the continued clinical translation and use for real-time identification of important nerves such as the femoral, sciatic, lumbar, iliac, and hypogastric nerves. Further development of LGW08-35 for clinical use will unlock a valuable tool for surgeons in direct visualization of important nerves and contribute to the ongoing characterization of the female pelvic neuroanatomy to eliminate the debilitating side effects of nerve damage during gynecological procedures.

Postapproval Monitoring Practices at Biomedical Research Facilities.

Federal regulations and policies require institutions to establish procedures for ongoing IACUC oversight of approved animal care and use program activities including animal procedures. To fulfill these requirements, research institutions implement postapproval monitoring (PAM) programs designed to assure compliance in animal activities. Although several references commenting on the requirement to conduct PAM are available, few publications discuss actual best practices for accomplishing PAM. Here we use information collected through a survey of large academic research institutions to identify common practices for conducting PAM reviews. Many similarities and differences exist between institutions, which may or may not influence the overall quality of an institution's PAM program.

Discrimination between bycatch and other causes of cetacean and pinniped stranding.

The challenge of identifying cause of death in discarded bycaught marine mammals stems from a combination of the non-specific nature of the lesions of drowning, the complex physiologic adaptations unique to breath-holding marine mammals, lack of case histories, and the diverse nature of fishing gear. While no pathognomonic lesions are recognized, signs of acute external entanglement, bulging or reddened eyes, recently ingested gastric contents, pulmonary changes, and decompression-associated gas bubbles have been identified in the condition of peracute underwater entrapment (PUE) syndrome in previous studies of marine mammals. We reviewed the gross necropsy and histopathology reports of 36 cetaceans and pinnipeds including 20 directly observed bycaught and 16 live stranded animals that were euthanized between 2005 and 2011 for lesions consistent with PUE. We identified 5 criteria which present at significantly higher rates in bycaught marine mammals: external signs of acute entanglement, red or bulging eyes, recently ingested gastric contents, multi-organ congestion, and disseminated gas bubbles detected grossly during the necropsy and histologically. In contrast, froth in the trachea or primary bronchi, and lung changes (i.e. wet, heavy, froth, edema, congestion, and hemorrhage) were poor indicators of PUE. This is the first study that provides insight into the different published parameters for PUE in bycatch. For regions frequently confronted by stranded marine mammals with non-specific lesions, this could potentially aid in the investigation and quantification of marine fisheries interactions.

A new clinical algorithm scoring for management of suspected foreign body aspiration in children.

BACKGROUND: Foreign Body Aspiration (FBA) is a serious problem in children and delays in diagnosis and management can be devastating. The history is often vague, with subtle physical and chest radiograph abnormalities. This study aims to determine the indications for bronchoscopy in children with suspected FBA and evaluate the key clinical and statistically significant predictors of FBA, based on the patients' historical, physical and radiological findings at presentation. METHODS: This is a retrospective observational study, including patients who were admitted between January 2001 to January 2011 with suspected FBA. Their presenting history, physical exam, radiological and bronchoscopic findings were analyzed. RESULTS: Three hundred children with a mean age of 2.1 ± 1.7 years were included. In children with both abnormal physical and radiological findings, 47.2% had proven FBA. If either was abnormal, the likelihood reduced to 32-33.3%; if both were normal, only 7.4% had a FB. Witnessed choking (adjusted OR 2.1, 95% CI 1.03-4.3; P = 0.041), noisy breathing/stridor/dysphonia (adjusted OR 2.7, 95% CI 1.2-6.2; P = 0.015), new onset/recurrent /persistent wheeze (adjusted OR 4.6, 95% CI 1.8-11.8; P = 0.002), abnormal radiological findings (adjusted OR 4.0, 95% CI 1.9-8.5; P < 0.001), and unilateral reduced air entry (adjusted OR 2.9, 95% CI 1.5-5.5; P = 0.001) were significant predictors of FBA (P < 0.05). When three or more risk factors were present, the cumulative proportion of children with proven FBA increased significantly. The discriminative ability of the model was found to be good; the area under the ROC curve value was 0.76 (95% CI 0.70, 0.82). The predicted cutoff score derived using ROC analysis was found to co-relate well with known clinically significant predictors of FBA. This supports our algorithm and scoring system. CONCLUSIONS: A high index of suspicion is required in diagnosing airway FB. Our proposed clinical algorithm and scoring system hopes to empower physicians to accurately predict patients with a high likelihood of FBA.

Heparin versus normal saline for patency of arterial lines.

BACKGROUND: For most patients who require intensive care, the success of clinical decision making and interventions is dependent on the accuracy of different physiological variables measured or obtained from samples using an arterial catheter. Maintaining the patency of these catheters is therefore essential for obtaining accurate measures, minimizing patient discomfort and reducing expenses incurred when an occluded catheter requires replacement. Uncertainty exists amongst clinicians as to best practice surrounding the contents of the arterial catheter flush solution (heparin or saline). The use of heparin is more expensive and is accompanied by significant risks such as haemorrhage, hypersensitivity and heparin-induced thrombocytopenia (HIT). OBJECTIVES: The objective of this review was to evaluate whether normal saline is as efficacious and safe as heparin in maintaining the patency of arterial intravascular catheters in adult patients without a haematological disorder. SEARCH METHODS: Randomized clinical trials (RCTs) were identified through electronic database searches: Cochrane Central Register of Controlled Trials (CENTRAL) 2013, Issue 1, part of The Cochrane Library; MEDLINE (Ovid, 1966 to March 2013); EMBASE (Ovid, 1988 to March 2013) and CINAHL (1988 to March 2013), using specific strategies as advised by the Cochrane Anaesthesia Group search specialist. We contacted trial authors to ask for additional information as needed. SELECTION CRITERIA: Randomized controlled trials and quasi-randomized studies irrespective of blinding or language that compared an arterial catheter flush solution comprising any dose of heparin versus an infusion of normal saline only. DATA COLLECTION AND ANALYSIS: Two review authors independently screened for methodological quality and extracted data from all identified studies that met the protocol inclusion criteria. MAIN RESULTS: A total of seven studies (606 participants) met the inclusion criteria and measured the primary outcome of interest. All studies were at unclear to high risk of bias. Given the high degree of clinical and statistical heterogeneity of the included studies, no meta-analysis was completed. The results from individual studies that compared heparin at a dose of 1 to 2 IU/mL under continuous pressure were imprecise and do not provide definitive evidence of a difference. The observed difference with a dose of heparin increased to 4 IU/mL came from only one study of 30 participants, and the quality of the reported data was poor. Similarly. consistency in assessment and reporting of adverse events such as haematoma, insertion site infection and limb ischaemia was poor. Further research with well-defined primary and secondary outcome measures using a stratified sampling process that accommodates for the different heparin doses commonly used in clinical practice is needed to confirm the trends seen in research results now reported in the literature. AUTHORS' CONCLUSIONS: The available evidence is of poor quality because of risk of bias and does not provide sufficient information to support the effects of adding heparin (1 to 2 IU/mL) to a maintenance solution (pressurized to deliver 3 mL of flush solution per hour) of 0.9% normal saline in maintaining the patency and functionality of arterial catheters.

Characterization of colorectal symptoms in women with vesicovaginal fistulas.

OBJECTIVE: To characterize colorectal symptoms in women with a history of an obstetric vesicovaginal fistula (VVF). METHODS: Patients under evaluation with a VVF during two 2-week surgical service trips to Evangel Hospital VVF Center in Jos, Nigeria, in 2010 were assessed for symptoms of fecal incontinence (FI) using the Vaizey and Colorectal-Anal Impact (CRAIQ) questionnaires. Women with rectovaginal fistulas were excluded. Each participant's impression of overall health was assessed using a visual analog scale (VAS) from 0 (poor) to 15 (excellent). A study nurse translated questionnaires into native languages. RESULTS: The mean age of the 83 women included was 29 years. Three women (3.6%) reported FI and 42 (50.6%) reported constipation. All of the women with FI reported that it affected their quality of life on the CRAIQ. Average VAS score was 10.8 overall and 6.8 for women with FI. CONCLUSION: In this population of women with VVF but no rectovaginal fistulas, we found a low prevalence of fecal incontinence and a high prevalence of constipation. Despite significant pelvic floor trauma resulting in VVF, the majority of patients appeared to have an intact bowel continence mechanism.

Knowledge, attitude and practices of Qatari patients with type 2 diabetes mellitus.

OBJECTIVES: Patient compliance with their medications and their ability for self-management in type 2 diabetes mellitus (T2DM) is a growing cause of concern to healthcare providers. Knowledge about diabetes, attitude towards the condition and time management with respect to the condition (practice), collectively known as KAP, are known to affect compliance and play an important part in diabetes management. We aimed to describe the knowledge, attitude, practice and psychological status of adult Qatari patients with T2DM, and to explore the interaction between these and other patient-related factors which could impact on the ability of the patients to manage their diabetes and to achieve desirable health outcomes. METHODS: A questionnaire (the Diabetes Habits and Beliefs Questionnaire, DHBQ) was used to investigate the level and relationship between knowledge, attitude, general practice and psychological status of patients with T2DM. The data was collected in face-to-face interviews with patients visiting the diabetic clinic at a tertiary hospital in Qatar during the period January 2008 to March 2009. KEY FINDINGS: There were significant differences in attitude and knowledge between educational levels. Knowledge and attitude were highly correlated and the psychological status of the patient was positively associated with both knowledge and attitude. There was generally poor practice of regularly inspecting feet to detect signs of neuropathy, taking medication in relation to meals, modifying doses when necessary and setting goals for therapy. CONCLUSIONS: The data provided can assist pharmacists and other healthcare practitioners in tailoring educational programmes aimed at improving diabetes control.

The utility of an electronic adherence assessment device in type 2 diabetes mellitus: a pilot study of single medication.

OBJECTIVES: The primary objective of this pilot study was to determine if the Medication Event Monitoring System (MEMS) is capable of providing meaningful estimates of compliance within the indigenous Qatari population. The secondary objective was to highlight any specific problems which might be associated with the use of MEMS within this population. METHOD: A sample of adult diabetic Qatari patients attending an outpatient diabetic clinic were administered a Knowledge, Attitude, and Practices (KAP) questionnaire and then dispensed one of their regular medications in a MEMS((R))-fitted bottle. Data contained in the MEMS((R)) were downloaded after the patients returned for a refill and adherence was estimated using 2 methods: pill count and MEMS((R)) data. RESULTS: A total of 54 patients agreed to participate in this pilot study. Adherence to daily doses was 67.7% and with regimen 13.7%. No correlation was found between adherence assessed by pill count and MEMS((R)). The association between KAP and adherence was generally poor. A number of other issues and challenges in the use of MEMS((R)) that could affect its utility were noted and will be discussed. CONCLUSIONS: Our results revealed problems associated with the use of MEMS((R)) that could affect its usefulness in assessing adherence in this part of the world. Some issues identified in this pilot study included retrieving the MEMS((R)), registering extra opening of MEMS((R)), desire to hoard medicine by taking doses at different frequency than recorded in MEMS((R)). All these issues could be closely associated with the attitudes and practices of the patients, as demonstrated by our KAP analysis and correlations.

Exploring the extent of postmenopausal osteoporosis among Saudi Arabian women using dynamic simulation.

The prevalence of postmenopausal osteoporosis among Saudi Arabian women is difficult to estimate because it is a large country with a diverse widely dispersed population. There have been reports of localized prevalence estimates but these are difficult to compare. In the absence of reliable national data, a theoretical approach may be useful. We have extended our mathematical model of the WHO scheme for osteoporosis diagnosis so that it is capable of predicting the prevalence of postmenopausal osteoporosis in a population of women on a year-by-year basis. These calculations are based on the area under a theoretical Gaussian bone mineral density (BMD) distribution bounded by the WHO thresholds for osteoporosis and osteopenia. This simulation approach confirms the pivotal role played by the standard deviation of BMD in the young, healthy normal reference group and it permits the model's sensitivity to other parameters (amplitude and time constant of the postmenopausal decline in BMD) and circumstances (age-related changes in standard deviation) to be accurately quantified: For Saudi Arabian women aged 50-70 yr, we estimate the prevalence of osteoporosis to be approximately 23%. The precise value depends strongly on the underlying standard deviation of BMD across the various age groups, which still remains to be accurately determined within the Saudi Arabian population.

Hurthle cell neoplasm of the thyroid gland.

BACKGROUND: A clinicopathological analysis and long-term follow up of 32 patients with Hurthle cell neoplasm (HCN) was undertaken to contrast the clinical and histological features between benign versus malignant HCN of thyroid and to examine the effect of treatment on the outcome. METHODS: This is a retrospective study of 32 patients with HCN who were identified out of an archival clinical/pathological/imaging database of 3752 thyroid cancer patients seen between 1976 and June 2006. All patients underwent thyroid surgery. Data for the non-surgical treatment along with follow up were also analysed. RESULTS: Seventeen patients were classified as malignant HCN (MHCN) and 15 as benign HCN (BHCN). Among the MHCN, there were 11 women and 6 men, whereas among BHCN there were 14 women and 1 man. Three patients designated MHCN presented with metastases, one with pulmonary metastases and two others with skeletal metastases who developed lung metastases 9-19 months later. The mean tumour size was 4.43 +/- 0.66 cm for MHCN, and 2.57 +/- 0.32 cm for BHCN (P = 0.03). Multicentric tumour foci were evident in five cases (29%) of MHCN but none among the BHCN (P = 0.03). At neck exploration cervical lymph node dissection was carried out in nine MHCN patients with findings of tumour metastases in 33%. Postoperatively, three MHCN patients had no thyroid remnant on ultrasound and computed tomography of neck and undetectable serum thyroglobulin; these were considered to be in remission. Fourteen other MHCN patients with postoperative thyroid remnant and/or distant metastases received 131I treatment. Eight of these patients had negative whole-body scans after 131I treatment and undetectable thyroglobulin. Accordingly, 11 MHCN patients (64.7%) showed evidence of remission and 6 patients did not respond to 131I treatment. After a mean follow up of 35 months, all BHCN patients are alive with no evidence of disease. Of the MHCN, 11 (64.7%) were in remission and 35% had evidence of persistence/recurrence. One patient who had recurrence is dead. A lack of effectiveness of 131I therapy in two patients with distant metastases is an important finding. CONCLUSION: Features of MHCN consisted of a large tumour size, unequivocal capsular and vascular invasion, multicentric tumour foci, metastatic lymph node deposits in one-third of patients and presence of distant metastasis in a few. Findings of dominant Hurthle cell cytology in a fine-needle aspiration biopsy from a thyroid nodule should prompt surgical resection of the lesion to assess malignancy.

Erotomania revisited: thirty-four years later.

Erotomania (also known as De Clerambault's syndrome) is usually described as a rare delusional syndrome that characteristically involves a woman who believes that a man, typically of higher social, economic or political status, is in love with her. Two cases are reviewed here that have been followed for over 30 years, making these some of the longest, single-case longitudinal studies yet reported. De Clerambault's syndrome remains a ubiquitous nosological psychiatric entity with uncertain prognosis. In 1980, we reported in this journal one woman diagnosed as having erotomania. At that time, she had been followed for approximately eight years. She has now been studied for over 30 years. In De Clerambault's original work, as reported by Enoch and Trethowan, a woman whose chronic, erotic delusion remained unchanged was followed for 37 years. Despite some psychological advances, our original patient, like De Clerambault's, has remained essentially entrapped by her psychotic thought disorder and erotomania. A thorough review of the literature to date was contained in our 1980 article and so, to avoid repetition, we refer the interested reader to that reference. At this time, the original patient's history will be presented along with the course of her disorder and treatment implications. Secondly, another patient will be presented and her case reviewed. Finally, we will argue that this disorder is not as rare as has been claimed and call for the continued recognition of this syndrome as its own entity despite recent opinions that such use be discontinued.

Stress fractures around the knee.

Stress fractures of the lower extremities are common, especially in the younger athletic population. The current literature consists mainly a variety of case reports but is devoid of any sizeable series of knee stress fracture investigations. Diagnosing a stress fracture around the knee can be a challenge. The proximity of the stress fracture to the knee joint may lead the clinician to investigate intra-articular or other periarticular pathology. The differential diagnosis can be large, including bursitis, tendonitis, mechanical causes, insufficiency fracture, and tumor. A high index of suspicion is necessary to confirm the underlying diagnosis. A patient's medical history combined with a physical examination and imaging modalities will aid the physician in arriving at the diagnosis of stress fracture.

The frequency distribution of age at natural menopause among Saudi Arabian women.

OBJECTIVE: Hormonal changes at the menopause are associated with the onset of a number of medical conditions. The distribution of age-at-menopause (AAM) within a given population can, therefore, indicate how the disease prevalence changes with age. The objective of this study was to estimate the distribution of AAM among Saudi Arabian women, in order to predict local trends in the prevalence of osteoporosis. METHODS: Patient age, AAM, medical history and associated information for 858 Saudi Arabian women were extracted from a Dual Energy Absorptiometry database at King Faisal Specialist Hospital and Research Centre, resulting in an AAM distribution for 391 postmenopausal women with natural menopause. This was preprocessed using a Fast Fourier Transform 0.15 cycles/year low-pass filter, eliminating last-digit-preference errors and high frequency noise, and facilitating quantitative comparison with other published results. RESULTS: Mean AAM was 48.94 years (S.E. 0.290 years) with a median of 50 years (25th/75th percentiles: 45 and 53 years, respectively). The AAM distribution was described by a quadruple-Gaussian curve with a major peak at almost 51 years and minor peaks at approximately 36, 44 and 59 years. Although both the central peaks were similar to that observed in other populations (UK, USA and Finland), the early menopause peak at 36 years was larger. The peak over 55 years may be unique to the Kingdom of Saudi Arabia. It may reflect local cultural and childbearing practices. CONCLUSIONS: Although the median menopause age and general shape of the AAM distribution in Saudi Arabia appear similar to that observed in the West, the parameters governing the distribution are different, and there is evidence that it may have a unique fourth peak.

A multi-exponential model of postmenopausal decline in vertebral bone mineral density: a new approach to the BMD reference range.

Although the postmenopausal decline in female bone mineral density (BMD) at the lumbar spine is central to the World Health Organization (WHO) diagnosis of osteoporosis, it has eluded an exact mathematical description. We present a simple mathematical model based on the assumption that bone loss can be described as an exponential decay process that begins at menopause. Women whose menopause begins in the same year of age are assigned a unique exponential function, and results from all women are combined to predict the average cross-sectional BMD on a year-by-year basis. This model has been successfully validated using data from a cross-sectional study of 8,789 female volunteers. No additional "aging" term is required. The normal time-constant was estimated to be 5.8 yr, but natural variation can have a substantial asymmetric effect on the curve. Similarly, variation in the distribution of the age at menopause also has a profound influence and can introduce artifacts when different populations of women are being compared. Using published data from Finland, it was confirmed that a simulation approach can predict the BMD decline observed in typical cross-sectional studies, suggesting the possibility of a cheaper and more convenient way to establish local dual-energy X-ray absorptiometry (DXA) reference curves.

Preprocessing histograms of age at menopause using the fast Fourier transform.

OBJECTIVE: In epidemiological and biological studies, the interpretation of frequency distributions (histograms) of the age at menopause (AAM) is hampered by the presence of background noise such as the last-digit-preference (LDP) of each woman. The objective of this study was to develop a standard method of preprocessing the AAM histogram such that noise can be effectively eliminated, thereby enabling a more thorough investigation of the underlying properties of the distribution. METHODS: The Fast Fourier transform (FFT) is a technique which eliminates individual sources of noise based on their characteristic frequencies. Its effectiveness in eliminating noise from AAM data was explored using both simulated and published data, especially in regard to the elimination of cyclical LDP errors. RESULTS: By preprocessing the histogram 'signal' using a low-pass filter of 0.15 cycles per year (cpy), common LDP noise is eliminated. Furthermore, this preprocessing also eliminates other forms of high-frequency noise, revealing a true AAM 'signal' which comprises three separate low-frequency components. The two major peaks correspond in the time domain to Gaussian functions with means at approximately 51 and approximately 43 years and peak-widths of approximately 6 years; a smaller peak also exists at approximately 35 years. CONCLUSIONS: The FFT is an effective tool in preprocessing AAM frequency distributions to reveal their underlying shape, which appears similar across several previously published studies and is characterized by three distinct peaks. These currently have no definitive interpretation, but call into question the analysis of epidemiological risk factors for AAM using statistical techniques which assume a single distribution.

Design and development of an Internet registry for congenital heart defects.

BACKGROUND: Congenital Heart Defects (CHD) are conditions that encompass more than 50 diagnoses and are due to developmental abnormalities early in fetal life. The King Faisal Specialist Hospital and Research Centre in the Kingdom of Saudi Arabia treats approximately 100 new cases per month. We recently developed a new CHD Registry that captures, stores and processes our data via the Internet. METHODS: The Registry was developed using Hypertext Markup Language (HTML), Microsoft Active Server Pages and Microsoft Structured Query Language (SQL). RESULTS: Details of CHD cases are captured in a World Wide Web (WWW) Registry, permitting any browser-enabled PC or Mac to participate fully in all registry functions, including data-entry, viewing, editing, searching, reporting, validating, charting, and exporting data subsets to statistics packages. It includes "administrative" features and an active security system. The paper forms have been designed to reflect the "look and feel" of the Web pages. Automatic validation procedures are also included. CONCLUSIONS: Our Registry has been in operation for 3 years. It serves 10 PCs and contains more than 3,000 registered cases of CHD. It is the first CHD Registry to be fully functional on the Internet. It is also the first dedicated CHD registry, and the first to routinely report on the full spectrum of CHD diagnoses. The WWW offers several logistical advantages to disease registries, especially those that represent large regions. It also offers the possibility of sharing resources between registries, facilitating the aggregation and analysis of disease data on a world-wide scale. This is useful for rare diseases such as CHD (see http://rc.kfshrc.edu.sa/chdr/demo/).