Breast Cancer in the Bahamas in 2009-2011.

BACKGROUND: Breast cancer is the most common form of cancer affecting women in the Bahamas, which consists of many islands. This is the first attempt to identify which island has the highest occurrence of breast cancer. OBJECTIVE: The aim of this study was to describe the sociodemographical and spatial features of breast cancer in the Bahamas in 2009-2011. METHODS: A review of the medical records of all women with a confirmed diagnosis of breast cancer during the period January 1, 2009-December 31, 2011, was undertaken. Data were first obtained from the National Oncology Board of the Bahamas and validated by a review of the medical records. The patient address was geocoded and mapped using ArcGIS 10.0 Environmental Systems Research Institute (ESRI) to satellite images obtained from The Nature Conservancy in the Bahamas. RESULTS: We recruited 270 patients who satisfied the entry criteria. The cumulative incidences of breast cancer for the years 2009-2011 were 51.4, 45.4, and 51.4, respectively. Breast cancer occurred most often in women of African origin with a mean age at diagnosis of 56.6 ± 13.8 years. Ductal carcinoma was the most common histological type observed with most cancers occurring in Grade II or higher and presenting as late stage (≥ Stage II). Surgery was the preferred method of treatment with modified radical mastectomy being the procedure of choice. Spatial distribution of cases across the Bahamas revealed one cluster, which is present on the island of New Providence. Further analysis of New Providence showed a consistently skewed kernel density in the central and eastern regions, compared with a scattered distribution in the southern and western regions. CONCLUSION: The island of New Providence had the highest occurrence of breast cancer among all the islands of the Bahamas. The increasing incidence of breast cancer in young women is likely to impose a significant burden on the future of Bahamian health care.

Short anterior instrumented fusion and posterior convex non-instrumented fusion of hemivertebra for congenital scoliosis in very young children.

A variety of treatments has been described in the literature for the treatment of HV. We report the results of early surgical anterior instrumented fusion with partial preservation of the HV and posterior non-instrumented fusion in the treatment of progressive congenital scoliosis in children below the age of six. Between 1996 and 2006, 31 consecutive patients with 33 lateral HV and progressive scoliosis underwent short segment fusions. Mean age at surgery was 2 years and 10 months. Mean follow-up period was 6.1 years. The major scoliotic curve improved from 41 degrees preoperatively to 17 degrees on follow-up. Preoperative segmental Cobb angle averaging 39 degrees was corrected to 15 degrees after surgery, being 15 degrees at the last follow-up (62% of improvement). Compensatory cranial and caudal curves corrected by 47 and 45%, respectively. The angle of segmental kyphosis averaged 16 degrees before surgery, 11 degrees after surgery, and 11 degrees at follow-up. There were two wound infections requiring surgical debridment, one intraoperative fracture of the vertebral body and one case lost correction due to implant failure. All went on to stable bony union. There were no neurological complications. Early diagnosis and early and aggressive surgical treatment are mandatory for a successful treatment of congenital scoliosis and prevention of the development of secondary compensatory deformities. Anterior instrumentation is a safe and effective technique capable of transmitting a high amount of convex compression allowing short segment fusion, which is of great importance in the growing spine.

Assignment of two loci for autosomal dominant adolescent idiopathic scoliosis to chromosomes 9q31.2-q34.2 and 17q25.3-qtel.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity, affecting up to 4% of children worldwide. Familial inheritance of AIS is now recognised and several potential candidate loci have been found. METHODS: We studied 25 multi-generation AIS families of British descent with at least 3 affected members in each family. A genomewide screen was performed using microsatellite markers spanning approximately 10-cM intervals throughout the genome. This analysis revealed linkage to several candidate chromosomal regions throughout the genome. Two-point linkage analysis was performed in all families to evaluate candidate loci. After identification of candidate loci, two-point linkage analysis was performed in the 10 families that segregated, to further refine disease intervals. RESULTS: Significant linkage was obtained in a total of 10 families: 8 families to the telomeric region of chromosome 9q, and 2 families to the telomeric region of 17q. A significant LOD score was detected at marker D9S2157 Z(max) = 3.64 ( theta= 0.0) in a four-generation family (SC32). Saturation mapping of the 9q region in family SC32 defined the critical disease interval to be flanked by markers D9S930 and D9S1818, spanning approximately 21 Mb at 9q31.2-q34.2. In addition, seven other families segregated with this locus on 9q. In two multi-generation families (SC36 and SC23) not segregating with the 9q locus, a maximum combined LOD score of Z(max) = 4.08 ( = 0.0) was obtained for marker AAT095 on 17q. Fine mapping of the 17q candidate region defined the AIS critical region to be distal to marker D17S1806, spanning approximately 3.2 Mb on chromosome 17q25.3-qtel. CONCLUSION: This study reports a common locus for AIS in the British population, mapping to a refined interval on chromosome 9q31.2-q34.2 and defines a novel AIS locus on chromosome 17q25.3-qtel.

Correlation between mouse potency and in vitro relative potency for human papillomavirus Type 16 virus-like particles and Gardasil vaccine samples.

An in vitro relative potency (IVRP) assay has been developed as an alternative to the mouse potency assay used to release Merck's human papillomavirus (HPV) vaccine, Gardasil, for early phase clinical trials. The mouse potency assay is a classical, in vivo assay, which requires 4-6 weeks to complete and exhibits variability on the order of 40% relative standard deviation (RSD). The IVRP assay is a sandwich-type immunoassay that is used to measure relative antigenicity of the vaccine product. The IVRP assay can be completed in three days, has a variability of approximately 10% RSD and does not require the sacrifice of live animals. Because antigen detection is achieved using H16.V5, a neutralizing monoclonal antibody, which binds to a clinically-relevant epitope, the relative antigenicity measured by the IVRP assay is believed to be a good predictor of in vivo potency. In this study, the relationship between immunogenicity, as measured by the mouse potency assay and antigenicity as measured by the IVRP assay, is demonstrated. Freshly manufactured and aged samples produced using two different manufacturing processes were tested using both methods. The results demonstrate that there is an inverse correlation between the IVRP and mouse potency assays. Additionally, clinical results indicate IVRP is predictive of human immunogenicity. Thus, antigenicity, as defined by the H16.V5 epitope, can be used as a surrogate for immunogenicity and the IVRP assay is suitable for use as the sole potency test for Gardasil samples.

The objective measurement of spinal orthosis use for the treatment of adolescent idiopathic scoliosis.

STUDY DESIGN: Technology development and prospective study. OBJECTIVES: Develop instrumentation for discrete, reliable, and objective measurement of brace use patterns between routine follow-ups and without patient involvement. BACKGROUND DATA: To understand spinal bracing efficacy and clinical effectiveness in the conservative treatment of adolescent idiopathic scoliosis, it is essential to measure and record such confounding variables as spinal physiology, force distribution, and compliance. Historically, compliance was measured using patient interviews, pad/strap forces, or temperature. These measurements were subjective, limited to laboratory or short-term monitoring only, required patient intervention, or lacked date/time recording. METHODS: Custom-fitted nonperforated thoracic lumbar sacral orthoses were instrumented with discrete data loggers to measure and record temperature at the skin-brace interface at 16-minute date/time-stamped intervals for up to 88-day periods without patient involvement. Ten female patients (age 15 years, SD 1.2) with adolescent idiopathic scoliosis who had spinal bracing as part of their treatment regimen took part in the study over 14 months, SD 4.5 months. RESULTS: Compliance with the treatment regimen ranged from 8% to 90%, average 65%. Patients tended to overestimate their compliance by 150% (SD 50%). There was no significant difference between weekday and weekend compliance but wear patterns differed. Night wear was significantly greater than day wear (P < 0.01). Patients with very good compliance only removed their brace for washing or exercise periods, but where poor compliance was evident, the brace was only worn sporadically during the day. CONCLUSIONS: Temperature provides a clear signal of the time in brace and can be used for long-term data logging using discrete instrumentation, providing a tool to help identify and understand the reasons behind poor compliance.

Quantitative measurement of spinal brace use and compliance in the treatment of adolescent idiopathic scoliosis.

The objective measurement of compliance with spinal bracing in adolescents with idiopathic scoliosis (AIS) is fundamental in the validation of clinical trials of bracing effectiveness, and in helping clinicians better understand reasons behind poor compliance. Current technology has been developed and tested for discrete, reliable and objective measurement of the times of day a brace is worn and consistency in its use. TLSOs were instrumented with data loggers measuring temperature at the skin/brace interface at 16 minutes intervals over a period of 88 days; between routine follow up and without patient interference. 10 female patients (age 14 years, sd 1.1) with AIS using spinal bracing as part of their treatment regime took part in the study over 15 months. Skin/brace interface temperature during periods of wear in the UK was >30 degrees C, ambient 23 degrees C, sd 4. Compliance ranged from 8-90%, average 65%. Patients tended to over estimate their compliance by 150% (sd 50%). There was no significant difference between weekday and weekend compliance but wear patterns differed. Nightwear was significantly greater than daywear. Patients with very good compliance only removed their brace for washing or exercise periods but where poor compliance was evident, the brace was only worn sporadically during the day. Temperature provides a clear signal of brace use and can be used for long-term data logging using discrete instrumentation, providing a tool to help identify and understand the reasons behind poor compliance.

Biographical sketch of Kenneth G. McKenzie (1892-1964).

This article is an expanded version of the opening address Dr. Morley delivered at a University of Toronto symposium, "Seventy-Five Years of Neurosurgery in Canada," celebrating the 75th Anniversary of the appointment of Kenneth G. McKenzie, Canada's first career neurosurgeon, to the University of Toronto and the Toronto General Hospital in 1923. Kenneth G. McKenzie (1892-1964) was the first surgeon in Canada to limit his practice to neurosurgery. This article contains a brief biographical study of the man, his upbringing, and management of his professional life at Toronto General Hospital. Some of his published neurosurgical articles are also reviewed.

Modulation of spinal deformities in patients with neurofibromatosis type 1.

STUDY DESIGN: A consecutive case retrospective chart and radiographic review. OBJECTIVES: To determine the incidence of nine radiographic dystrophic features acquired during the process of modulation, and to analyze the statistical correlation of these acquired dystrophic features with clinical progression of a spinal deformity. SUMMARY OF BACKGROUND DATA: In patients with neurofibromatosis, spinal deformities with seemingly few initial dystrophic features have shown a tendency to acquire dystrophic changes during long-term follow-up periods. Similarly, deformities with dystrophic changes can acquire further dystrophic features. This phenomenon is termed "modulation," a feature unique to spinal deformities in neurofibromatosis. These dystrophic changes may evolve slowly or aggressively, and may spread to other regions as well. METHODS: A review was done of the clinical records, photographs, radiographs, and other imaging studies of 457 patients referred between 1982 and 1995 with the diagnosis of neurofibromatosis Type 1. One hundred twenty-eight patients were diagnosed with a spinal deformity. Ninety-one patients who had a complete set of clinical and radiographic data were included in the study. Location and type of curve as well as the extent of spinal deformity were studied for their effect on the tendency for modulation. Initial spinal radiographs were analyzed for nine radiographic dystrophic features: rib penciling, vertebral rotation, posterior vertebral scalloping, anterior vertebral scalloping, lateral vertebral scalloping, vertebral wedging, spindling of the transverse process, widened interpedicular distance, and enlarged intervertebral foramina. Subsequent radiographs were analyzed critically for evolution, progression, or spread of these features. Correlation of acquisition in these dystrophic features with clinical progression in the spinal deformity, as measured in increments of scoliosis and kyphosis, was analyzed. RESULTS: In 81% of patients with spinal deformity diagnosed before 7 years of age and in 25% of patients with such a diagnosis after 7 years of age, evidence of modulation was observed. Location, side, and extent of the deformity and patient gender did not influence the propensity of the deformity to modulate. Correlation of modulation with clinical progression of the deformity showed rib penciling to be the only singular factor statistically influencing risk of progression. Of the deformities that acquired three or more penciled ribs, 87% showed significant clinical progression. No other radiographic dystrophic feature individually influenced progression. However, when three or more of the dystrophic skeletal features were acquired, the risk of progression reached statistical significance in 85% of patients. CONCLUSIONS: Spinal deformities in patients with neurofibromatosis 1 should be regarded as deformities in evolution. One should resist assigning these evolving deformities to either the dystrophic or nondystrophic end of the spectrum without considering the possibility of modulation across the spectrum. A spinal deformity that develops before 7 years of age should be followed closely for evolving dystrophic features (i.e., modulation). When a curve acquires either three penciled ribs or a combination of three dystrophic features, clinical progression is almost a certainty.

Retrograde coronary venous infusion of ethanol for ablation of canine ventricular myocardium.

INTRODUCTION: Permanent cure of reentrant ventricular tachycardia (VT) associated with coronary artery disease is difficult to achieve. Retrograde coronary venous infusion of ethanol for ablation of ventricular myocardium associated with reentrant tachyarrhythmias has several potential advantages, including use of physiologic mapping techniques and production of deeper, wider necrotic zones. METHODS AND RESULTS: Nine anesthetized dogs had baseline hemodynamic measurement, left ventriculography, coronary arteriography, occlusive coronary venography, and programmed electrical stimulation of the right ventricular apex and outflow tract. A balloon-tipped infusion catheter was advanced into a distal coronary venous branch, the balloon slowly inflated, and pure ethanol infused at volumes of 1.5, 3, or 5 cc. Hemodynamic measurements, angiography, ventriculography, and programmed electrical stimulation were repeated immediately and 1 week following ablation. Formalin-perfused hearts were serially sectioned and lesion volumes determined. Histologic examination of ablation beds then was performed. No significant difference was found in any hemodynamic measurement before or after ablation. Coronary arteriograms and left ventriculograms were unchanged after ablation. Nonsustained VT occurred in eight dogs during ethanol infusion; however, VT was not inducible in any dog before or after ablation. Infusion volumes of 3 cc or more were required to produce transmural lesions. CONCLUSION: Retrograde coronary venous infusions of ethanol using a balloon-tipped infusion catheter were effective in ablating ventricular myocardium. Retrograde chemical ablation did not itself result in inducible VT or adversely affect hemodynamic measurements or coronary arteries. Transmural myocardial necrosis, necessary in the ablation of VT associated with coronary artery disease, can be produced by higher infusion volumes.

Nebulized lidocaine in the treatment of refractory tussive syncope.

Tussive syncope is a rare condition that often responds to treatment of the underlying cause of coughing. Therefore, the workup and diagnosis of the cause is essential. However, at times, the cough is refractory to conventional treatment. The use of nebulized lidocaine in such instances may be an important adjunctive therapy.

Synthetic porous ceramic compared with autograft in scoliosis surgery. A prospective, randomized study of 341 patients.

We have evaluated the use of a synthetic porous ceramic (Triosite) as a substitute for bone graft in posterior spinal fusion for idiopathic scoliosis. In a prospective, randomised study 341 patients at five hospitals in the UK and France were randomly allocated either to autograft from the iliac crest or rib segments (171) or to receive Triosite blocks (170). All patients were assessed after operation and at 3, 6, 12 and 18 months. The two groups were similar with regard to all demographic and baseline variables, but the 184 treated in France (54%) had Cotrel-Dubouset instrumentation and the 157 treated in the UK usually had Harrington-Luque implants. In the Triosite group the average Cobb angle of the upper curve was 56 degrees, corrected to 24 degrees (57%). At 18 months, the average was 26 degrees (3% loss). In the autograft group the average preoperative upper curve of 53 degrees was corrected to 21 degrees (60%). At 18 months the mean curve was 25 degrees (8% loss). Pain levels after operation were similar in the two groups, being mild in most cases. In the Triosite group only three patients had problems of wound healing, but in the autograft group, 14 patients had delayed healing, infection or haematoma in the spinal wound. In addition, 15 autograft patients had pain at the donor site at three months. Seven had infections, two had haematoma and four had delayed healing. The haematological and serum biochemistry results showed no abnormal trends and no significant differences between the groups. There were no adverse events related to the graft material and no evidence of allergenicity. Our results suggest that Triosite synthetic porous ceramic is a safe and effective substitute for autograft in these patients. Histological findings on biopsy indicate that Triosite provides a favourable scaffolding for the formation of new bone and is gradually incorporated into the fusion mass.

Structure-activity relationship for two lipoxygenase inhibitors and their potential for inducing nephrotic syndrome.

In a study of structure-activity relationship with drug-induced nephropathy two lipoxygenase inhibitors, the N-hydroxyurea derivative 70C ((E)-N-{3-[3-(4-fluorophenoxy) phenyl]-1-(R, S)-methylprop-2-enyl}-N-hydroxyurea) and the N-hydroxamic acid analogue 360C ((E)-N-{3-[3-(4-fluorophenoxy) phenyl]-1-(R, S)-methylprop-2-enyl}-N-hydroxamic acid), were administered to rats. 70C and 360C were dosed to female Wistar rats at 100 mg/kg po daily for 7 days. Another group of rats was given a single intravenous bolus dose of puromycin aminonucleoside (PAN) at 100 mg/kg. Urine samples were collected from all groups during the study and plasma samples were collected after 7 days. Kidneys were excised and fixed for examination by electron microscopy. 70C- and PAN-treated groups both showed early changes in the glomeruli, in which the visceral cells appeared enlarged and showed varying degrees of foot process loss. This foot process loss was associated with decreases in total plasma protein and albumin and increases in the plasma cholesterol, triglycerides, creatinine, and urea were recorded. Marked proteinuria was observed in both the 70C and PAN groups. The foot process loss together with increased proteinuria, hypoalbuminemia, hypercholesterolemia, and lipemia are all characteristic of the human condition, Minimal Change Nephrotic Syndrome. All the biochemical and morphological investigations showed that 360C-treated rats were similar to the control group, suggesting that the hydroxyurea moiety of 70C is responsible, either directly or indirectly, for the induction of the nephrotic syndrome seen in rats.

Noninvasive positive pressure ventilation: what is its role in treating acute respiratory failure?

Noninvasive positive pressure ventilation (NIPPV) is a viable option in treating appropriately selected patients with acute respiratory failure. It is often well tolerated, and it avoids endotracheal intubation with its potential complications. Moreover, gas exchange is reportedly improved. Several issues relating to the use of NIPPV are unresolved, however. The optimal interface, best ventilator mode, and patient selection criteria have not been firmly established. Also, studies are needed to compare the efficacy, safety, and cost-effectiveness of NIPPV and standard endotracheal ventilation. Despite these unresolved issues, NIPPV clearly represents an important addition to the techniques available in managing acute respiratory failure. Except in situations in which immediate endotracheal intubation is required, it may become first-line therapy in elderly patients in whom resuscitation status is unsettled.

Rescue of hybrid sterility in crosses between D. melanogaster and D. simulans.

The genetic analysis of reproductive isolation between species of Drosophila has now reached the resolution necessary to start answering one of the fundamental questions of evolution: what is the genetic basis of species differences? A.H. Sturtevant, one of the founders of Drosophila genetics, was fascinated by this question and thought he had found a way to analyse it when he realized that 'Drosophila melanogaster' was actually two species: D. melanogaster and D. simulans. By passing genes between these two species he hoped to investigate their genetic differences directly. No doubt he was disappointed to find that the D. melanogaster/D. simulans hybridization resulted only in unisexual sterile hybrids, a disappointment appreciated all the more by modern evolutionary biologists. Seventy-five years after Sturtevant's description of D. melanogaster/D. simulans hybrid sterility, we have discovered a strain of D. simulans that produces fertile female hybrids in crosses with D. melanogaster. Our discovery promises to bring the enormous resolution of D. melanogaster genetics to the study of reproductive isolation and species differences.

Bronchiolitis obliterans organizing pneumonia in an AIDS patient.

We present a case of bronchiolitis obliterans organizing pneumonia in a patient with acquired immune deficiency syndrome. Only three cases have previously been reported in patients infected with human immunodeficiency virus. In these four cases, bronchiolitis obliterans organizing pneumonia was similar in presentation, radiographic features and clinical course to that occurring in patients not infected with human immunodeficiency virus.

Use of capnography for assessment of the adequacy of alveolar ventilation during weaning from mechanical ventilation.

A prospective study was conducted to determine the reliability of noninvasive end-tidal CO2 (PETCO2) monitoring as a reflection of arterial CO2 tension (PaCO2) during weaning from mechanical ventilation (MV). Simultaneous PaCO2 and PETCO2 determinations were compared during MV and again during a spontaneous breathing trial just before returning the patient to MV. Three groups of patients recovering from acute respiratory failure were evaluated. Group 1 consisted of 16 patients (28 observations) without parenchymal lung disease. Group 2 consisted of 22 patients (31 observations) with alveolar filling diseases. Group 3 was composed of 13 patients (22 observations) with emphysema. Significant Pearson correlation coefficients were demonstrated between PaCO2 and PETCO2 during both MV and spontaneous breathing in all three groups. Significant correlation was also demonstrated between the change in PaCO2 and the change in PETCO2 associated with weaning for each group; however, the degree of correlation varied between groups. Our data suggest that capnography offers a reasonable estimate of PaCO2 and changes in PaCO2 during weaning in patients without parenchymal lung disease. However, PETCO2 is less sensitive to changes in PaCO2 for patients with parenchymal lung disease, particularly patients with emphysema. Interpretation of capnographic data requires a full understanding of its limitations. An approach to capnographic monitoring during weaning is discussed.

Subcutaneous emphysema of the upper limb: an air-gun injury.

We describe a case of subcutaneous emphysema of the hand and forearm from an air-gun.