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1.  Gentamicin Pharmacokinetics and Pharmacodynamics during Short-daily Hemodialysis 
American journal of nephrology  2012;36(2):144-150.
Gentamicin pharmacokinetics have not been described in patients undergoing short-daily hemodialysis (SDHD). The aim of this study is to describe gentamicin pharmacokinetics and dialytic clearance (Cldial) in SDHD patients and simulate gentamicin exposure after six dosing regimens to help guide future dosing.
Six anuric patients undergoing SDHD were enrolled. Patients received IV infusion of 2 mg/kg gentamicin on day 1 after first HD session followed by HD sessions on days 2, 3, and 4. Blood samples for determination of gentamicin concentrations were serially collected. Gentamicin pharmacokinetic parameters and Cldial and inter-individual variability terms (IIV) were estimated using NONMEM VII. Influence of patient weight on systemic clearance (Cls) and central volume of distribution (Vc) and influence of urea removal estimates on Cldial were assessed. The model was used to simulate gentamicin concentrations after six dosing regimens including pre- and post-dialysis as well as daily and every other day dosing.
A two-compartment model with first-order elimination from central compartment described gentamicin pharmacokinetics. Population estimates for Cls and Cldial were 7.6 and 134 ml/min, respectively. Patient weight was statistically significantly associated with Cls and Vc
Pre-dialysis every other day regimens were as effective (Cmax ≥ 8 mg/L and AUC48 hrs ≥ 140 and less toxic (Cmin < 2 mg/L and AUC48 hrs < 240 than post-dialysis regimens.
Estimated gentamicin Cldial is higher than previous estimates with thrice-weekly regimens. Pre-dialysis every other day dosing may be recommended during SDHD.
PMCID: PMC4303467  PMID: 22813936
gentamicin; hemodialysis; pharmacokinetics; renal failure
2.  Granulocyte colony-stimulating factor receptor signalling via Janus kinase 2/signal transducer and activator of transcription 3 in ovarian cancer 
British Journal of Cancer  2013;110(1):133-145.
Ovarian cancer remains a major cause of cancer mortality in women, with only limited understanding of disease aetiology at the molecular level. Granulocyte colony-stimulating factor (G-CSF) is a key regulator of both normal and emergency haematopoiesis, and is used clinically to aid haematopoietic recovery following ablative therapies for a variety of solid tumours including ovarian cancer.
The expression of G-CSF and its receptor, G-CSFR, was examined in primary ovarian cancer samples and a panel of ovarian cancer cell lines, and the effects of G-CSF treatment on proliferation, migration and survival were determined.
G-CSFR was predominantly expressed in high-grade serous ovarian epithelial tumour samples and a subset of ovarian cancer cell lines. Stimulation of G-CSFR-expressing ovarian epithelial cancer cells with G-CSF led to increased migration and survival, including against chemotherapy-induced apoptosis. The effects of G-CSF were mediated by signalling via the downstream JAK2/STAT3 pathway.
This study suggests that G-CSF has the potential to impact on ovarian cancer pathogenesis, and that G-CSFR expression status should be considered in determining appropriate therapy.
PMCID: PMC3887286  PMID: 24220695
ovarian cancer; cytokine; cytokine receptor; JAK/STAT; G-CSF; G-CSFR; STAT3
3.  Bilateral same-session intravitreal injections of anti-vascular endothelial growth factors 
To document the indications, safety and possible complications of bilateral same-session intravitreal anti-vascular endothelial growth factor (VEGF) injections performed in the ophthalmic operating room.
A retrospective case series study. Consecutive records of seventy four patients receiving simultaneous bilateral intravitreal injections of either ranibizumab or bevacizumab, between September 2010 and September 2013, were reviewed and the outcomes were assessed. Data collected included number of injections, indications for injections, pre-injection and post-injection visual acuity (VA), pre-injection and post-injection intraocular pressure and ocular and systemic complications/complaints after each injection.
A total of 342 injections were administered to 74 patients, with a mean of 4.62 injections per patient. Seventy-three patients received bevacizumab (Avastin; Genentech Inc., South San Francisco, California, USA) alone, and only one patient received both bevacizumab and ranibizumab (Lucentis; Genentech Inc.) distributed between the injections. Pre- and post-injection VA follow-up measurements were available for 65 patients. Mean follow up period was 22mo. The indications for initiating therapy were choroidal neovascular membrane from age-related macular degeneration (3 patients) and diabetic macular edema (71 patients). The mean Snellen VA before each injection was 6/22. The next post-injection follow-up mean Snellen VA was 6/20. One patient had a painful, culture-positive endophthalmitis in one eye 3d after bilateral bevacizumab. Another patient had a painless subconjunctival hemorrhage in one eye. No other ocular or systemic adverse side effects/complaints have been registered in this study group.
Bilateral same-session intravitreal injections using a separate povidone-iodine preparation, speculum, needle, and syringe for each eye are well-tolerated. None of the subjects in this study requested to switch to alternating unilateral injections. Proper patient counseling as to the risk of complications with this procedure is necessary.
PMCID: PMC4270969  PMID: 25540758
anti-vascular endothelial growth factor; diabetic macular edema; age-related macular degeneration; endophthalmitis; visual acuity
4.  Effect of chronic usage of tramadol on motor cerebral cortex and testicular tissues of adult male albino rats and the effect of its withdrawal: histological, immunohistochemical and biochemical study 
This study was designed to demonstrate the histopathological and biochemical changes in rat cerebral cortex and testicles due to chronic usage of tramadol and the effect of withdrawal. Thirty adult male rats weighing 180-200 gm were classified into three groups; group I (control group) group II (10 rats received 50 mg/kg/day of tramadol intraperitoneally for 4 weeks) and group III (10 rats received the same dose as group II then kept 4 weeks later to study the effect of withdrawal). Histological and immunohistochemical examination of cerebral cortex and testicular specimens for Bax (apoptotic marker) were carried out. Testicular specimens were examined by electron microscopy. RT-PCR after RNA extraction from both specimens was done for the genes of some antioxidant enzymes .Also, malondialdehyde (MDA) was measured colourimetrically in tissues homogenizate. The results of this study demonstrated histological changes in testicular and brain tissues in group II compared to group I with increased apoptotic index proved by increased Bax expression. Moreover in this group increased MDA level with decreased gene expression of the antioxidant enzymes revealed oxidative stress. Group III showed signs of improvement but not returned completely normal. It could be concluded that administration of tramadol have histological abnormalities on both cerebral cortex and testicular tissues associated with oxidative stress in these organs. Also, there is increased apoptosis in both organs which regresses with withdrawal. These findings may provide a possible explanation for delayed fertility and psychological changes associated with tramadol abuse.
PMCID: PMC4270590  PMID: 25550769
Tramadol; testis; brain; Bax; apoptosis; oxidative stress
6.  Numerical Investigation of the Effect of Stenosis Geometry on the Coronary Diagnostic Parameters 
The Scientific World Journal  2014;2014:354946.
The present study deals with the functional severity of a coronary artery stenosis assessed by the fractional flow reserve (FFR). The effects of different geometrical shapes of lesion on the diagnostic parameters are unknown. In this study, 3D computational simulation of blood flow in three different geometrical shapes of stenosis (triangular, elliptical, and trapezium) is considered in steady and transient conditions for 70% (moderate), 80% (intermediate), and 90% (severe) area stenosis (AS). For a given percentage AS, the variation of diagnostic parameters which are derived from pressure drop across the stenosis was found in three different geometrical shapes of stenosis and it was observed that FFR is higher in triangular shape and lower in trapezium shape. The pressure drop coefficient (CDP) was higher in trapezium shape and lower in triangular model whereas the LFC shows opposite trend. From the clinical perspective, the relationship between percentage AS and FFR is linear and inversely related in all the three models. A cut-off value of 0.75 for FFR was observed at 76.5% AS in trapezium model, 79.5% in elliptical model, and 82.7% AS for the triangular shaped model. The misinterpretation of the functional severity of the stenosis is in the region of 76.5%-82.7 % AS from different shapes of stenosis models.
PMCID: PMC4167444  PMID: 25258722
7.  Sex differences and estrous cycle in female rats interact with the effects of fluoxetine treatment on fear extinction 
Behavioural brain research  2013;253:217-222.
A common treatment for anxiety disorders is chronic administration of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine. Recent data suggest that SSRIs modulate fear responses after conditioned fear extinction and that gonadal hormones influence fear extinction. In this study we investigated the influence of sex and the estrous cycle on the effects of acute (experiment 1) and chronic (experiment 2) fluoxetine treatment on fear extinction. In experiment 1, rats received tone-footshock pairings during day 1. On day 2, rats received either fluoxetine (10mg/kg in 0.5mL) or vehicle prior to extinction learning. On day 3, extinction memory was assessed during extinction recall. In experiment 2, rats were exposed to a similar behavioral protocol, except that fluoxetine and vehicle were administered for 14 consecutives days after conditioning (days 2–15). Extinction learning and extinction recall occurred on days 15 and 16, respectively. Acute administration of fluoxetine increased fear responses equally in males and females during extinction learning and extinction recall. Chronic administration of fluoxetine reduced fear responses during extinction learning and extinction recall in female but not in male rats and this effect seems to be modulated by the estrous cycle. The SSRI-induced reduction of freezing during extinction learning and recall suggest a general anxiolytic effect of the drug treatment rather than a specific effect on extinction learning per se. Our data show evidence of sex-specific anxiolytic effects of 14-day treatment of fluoxetine while the acute anxiogenic effect of SSRI seems independent of sex effects.
PMCID: PMC4106477  PMID: 23886596
fear; estrous cycle; estrogen; fluoxetine; gonadal hormones; anxiety disorders
8.  An Efficient Sonochemical Synthesis of Novel Schiff's Bases, Thiazolidine, and Pyrazolidine Incorporating 1,8-Naphthyridine Moiety and Their Cytotoxic Activity against HePG2 Cell Lines 
The Scientific World Journal  2014;2014:587059.
Novel Schiff's bases 4a–e, 5a, 5b, and 6, thiazolidine 7a–d, and pyrazolidine 8 have been synthesized using the versatile synthon 4-hydroxy-2,7-dimethyl-1,8-naphthyridine 1. Reactions carried out under ultrasound irradiation showed higher rates and yields than those done under silent conditions. The newly synthesized compounds were evaluated for HepG2 cell growth inhibition. The results obtained revealed that the tested compounds possess inhibitory effect on the growth of HepG2 liver cancer cells. The results were compared to doxorubicin as a reference drug (IC50: 0.04). Compounds 4a and 7b showed the highest inhibition activity against the HepG2 cell line (IC50: 0.047 and 0.041 µM, resp.) among all the tested compounds.
PMCID: PMC3956519  PMID: 24723815
9.  Response of Nitrogen and Potassium Fertigation to “Waris” Almond (Prunus dulcis) under Northwestern Himalayan Region of India 
The Scientific World Journal  2014;2014:141328.
A field experiment was conducted on almond (Prunus dulcis) to study the effect of N&K fertigation on growth, yields and leaf nutrient status over two seasons (2011 and 2012) in Srinagar, Jammu and Kashmir, India. There were six treatments, namely, T1—100% recommended dose of fertilizers as soil application, T2—100% RDF through fertigations, T3—75% RDF through fertigation, T4—75% RDF through fertigation (split application), T5—50% RDF through fertigation and T6—50% RDF through fertigation (split application) with three replications under randomized block design. The results indicated that the maximum tree height (3.21 m and 3.56 m), nut weight (2.73 g and 1.94 g), nut yield (2.41 kg/tree and 5.98 kg/tree; 2.67 t/ha and 6.64 t/ha), and leaf nutrient content (2.34 and 2.38% N; 0.14 and 0.17% P; 1.37 and 1.41% K) were recorded in T4 treatment, whereas the highest TCSA of main trunk, primary, secondary, and tertiary branches (72.67 and 90.28 cm2; 16.75 and 24.26 cm2; 3.83 and 7.49 cm2; 0.47 and 1.23 cm2), canopy volume (7.15 and 8.11 m3), and fruit number (990 and 3083/tree) were recorded in T2 in almond variety Waris.
PMCID: PMC3919101  PMID: 24587708
10.  Surveillance of antimicrobial resistance among clinical isolates recovered from a tertiary care hospital in Al Qassim, Saudi Arabia 
The emergences of antimicrobial-resistances have become an important issue in global healthcares. Limitations in surveying hinder the actual estimates of resistance in many countries.
The aim
the present study was designed to retrospectically survey antimicrobial susceptibility for resistance profiling of dominant pathogens in a tertiary-care center in Buraidah, Saudi Arabia from January-2011 to December-2011.
Materials and Methods
the design was cross-sectional and spanned records of a 1000 bacterial non-related isolates. Antibiograms were based on the 2012 Clinical and Laboratory Standards Institute guidelines.
showed that Staphylococcus aureus, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Escherichia coli, were the most resistant. All isolates of S. aureus, S. epidermidis, and Staphylococcus haemolyticus, were resistant to penicillin (100%), and oxacillin with 52%, 75%, and 82%, respectively. Interestingly, an increasing trend of resistance-pattern was seen for the three species against gentamicin 26%, 50%, 68% ciprofloxacin 22%, 50%, 68%, tetracycline 30%, 44%, 27%, erythromycin 26%, 64%, 73%, and clindamycin 20%, 47%, 50% suggesting potential between-species transfer of resistances. Acinetobacter baumannii was resistances to all antibiotics tested including ciprofloxacin (90%), ceftazidime (89%), cefepime (67%), Trimethoprim/sulfamethoxazole (66%), amikacin (63%), gentamicin (51%), tetracycline (43%), piperacillin-tazobactam (42%), and imipenem (9%). A similar pattern was seen by P. aeruginosa. Furthermore, a typical pattern of resistance in K. pneumoniae carbapenemase–producing organisms was observed.
we have shown staphylococci, Acinetobacter baumannii, Pseudomonas aeruginosa, and enteric bacteria were the most resistant species in this region.
PMCID: PMC4039578  PMID: 24899874
Antimicrobial-Resistance; nosocomial-pathogens; AST-surveillance program; infection control
11.  Pharmacokinetics of Procainamide and N-acetylprocainamide during Continuous Renal Replacement Therapy 
Procainamide and its major metabolite, N-acetyl procainamide (NAPA), prolong the QTc interval and can promote potentially fatal ventricular arrhythmias. Excretion of procainamide and NAPA is reduced in patients with chronic kidney disease (CKD) resulting in drug accumulation and toxicity. The elimination of procainamide or NAPA in patients undergoing continuous renal replacement therapy (CRRT) has not been evaluated increasing the risk for subtherapeutic or toxic dosing regimens. This case report describes a patient undergoing CRRT who was administered procainamide for recurring ventricular tachycardia (VT) over approximately a 36 hour period. The patient required increased vasopressor therapy and developed QTc prolongation during procainamide administration. The VT resided following pacemaker adjustments, procainamide administration, and multiple direct current cardioversion attempts. Procainamide and NAPA concentrations were determined over a 120 hour period as part of routine clinical care and a pharmacokinetic (PK) model was developed using NONMEM. The developed PK model was used to simulate several procainamide dosing regimens to optimize therapy during CRRT. Based on the model-based simulations, a 50% reduction in the procainamide maintenance dose (2 mg/min) in CKD patients on CRRT can achieve therapeutic plasma procainamide and combined procainamide/NAPA concentrations.
PMCID: PMC3851309  PMID: 23562328
12.  Relative expression of CsZCD gene and apocarotenoid biosynthesis during stigma development in Crocus sativus L. 
Crocus sativus is a triploid sterile plant characterized by its red stigmas, which produce significant quantities of carotenoid derivatives formed from the oxidative cleavage of β-carotene and zeaxanthin. The accumulation of three major carotenoid derivatives- crocin, picrocrocin, and safranal- is responsible for the color, bitter taste, and aroma of saffron, which is obtained from the dried stigma of Crocus. Maximum apocarotenoid accumulation occurs during fully developed scarlet stage of stigma development. Zeaxanthin is the precursor for biosynthesis of apocarotenoids. Crocus zeaxanthin 7, 8 (7, 8)-cleavage dioxygenase gene (CsZCD) encodes a chromoplast enzyme that initiates the biogenesis of these apocarotenoids by cleaving zeaxanthin. The Reverse Transcription-PCR analysis revealed that CsZCD gene expression followed different patterns during stigma development. Highest levels of CsZCD gene expression was observed in fully developed scarlet stage of stigma. Real Time PCR analysis showed that there is a sharp increase in gene expression from yellow to orange and orange to scarlet stages of stigma development. Increase in CsZCD gene expression parallels with the apocarotenoid content during the development of stigma, suggesting its regulatory role for apocarotenoid biosynthesis and stigma development in saffron.
Electronic supplementary material
The online version of this article (doi:10.1007/s12298-012-0131-9) contains supplementary material, which is available to authorized users.
PMCID: PMC3550554  PMID: 24082500
Saffron; CsZCD; Real time PCR; Gene expression; Apocarotenoid
13.  Hallermann-Streiff Syndrome 
Indian Journal of Dermatology  2013;58(5):383-384.
Hallermann-Streiff syndrome (HSS) is a rare disorder characterized by dyscephalia, with facial and dental abnormalities. We report a 12-year-old female child who presented with abnormal facial features, dental abnormalities and sparse scalp hair.
PMCID: PMC3778780  PMID: 24082185
Abnormal facial features; dental anomalies; Hallermann-Streiff syndrome
14.  Stable T-bet+GATA-3+ Th1/Th2 Hybrid Cells Arise In Vivo, Can Develop Directly from Naive Precursors, and Limit Immunopathologic Inflammation 
PLoS Biology  2013;11(8):e1001633.
The stable lineage commitment of naïve T helper cells to a hybrid Th1/2 phenotype reveals the cell-intrinsic reconciliation of two opposing T cell differentiation programs and provides a self-limiting mechanism to dampen immunopathology.
Differentiated T helper (Th) cell lineages are thought to emerge from alternative cell fate decisions. However, recent studies indicated that differentiated Th cells can adopt mixed phenotypes during secondary immunological challenges. Here we show that natural primary immune responses against parasites generate bifunctional Th1 and Th2 hybrid cells that co-express the lineage-specifying transcription factors T-bet and GATA-3 and co-produce Th1 and Th2 cytokines. The integration of Th1-promoting interferon (IFN)-γ and interleukin (IL)-12 signals together with Th2-favoring IL-4 signals commits naive Th cells directly and homogeneously to the hybrid Th1/2 phenotype. Specifically, IFN-γ signals are essential for T-bet+GATA-3+ cells to develop in vitro and in vivo by breaking the dominance of IL-4 over IL-12 signals. The hybrid Th1/2 phenotype is stably maintained in memory cells in vivo for months. It resists reprogramming into classic Th1 or Th2 cells by Th1- or Th2-promoting stimuli, which rather induce quantitative modulations of the combined Th1 and Th2 programs without abolishing either. The hybrid phenotype is associated with intermediate manifestations of both Th1 and Th2 cell properties. Consistently, hybrid Th1/2 cells support inflammatory type-1 and type-2 immune responses but cause less immunopathology than Th1 and Th2 cells, respectively. Thus, we propose the self-limitation of effector T cells based on the stable cell-intrinsic balance of two opposing differentiation programs as a novel concept of how the immune system can prevent excessive inflammation.
Author Summary
T helper (Th) cells, a subgroup of white blood cells important in the immune system, can differentiate into diverse lineages, for example Th1 and Th2, whose effector mechanisms target different types of pathogens but cause problems if not properly regulated. Lineage commitment is driven by cytokine signals that control the expression of distinct lineage-specifying “master regulator” transcription factor molecules. Lineage commitment is thought to reflect alternative cell-fate decisions because the initiated differentiation programs have self-amplifying and mutually repressive features. Here we show that the Th1 and Th2 differentiation programs are more compatible with each other than previously thought. Individual naive T cells can simultaneously integrate Th1- and Th2-polarizing signals and develop into hybrid Th1/2 cells that stably co-express both the Th1 master regulator T-bet and the Th2 master regulator GATA-3. We find that hybrid Th1/2 cells arise naturally during parasite infections and that the two opposing differentiation programs can stably co-exist in resting memory Th1/2 cells for periods of months. Th1- or Th2-polarizing stimuli induced quantitative modulations in the hybrid state but did not extinguish either program. The cell-intrinsic antagonism gives the hybrid Th1/2 cells properties that are quantitatively intermediate between those of Th1 and Th2 cells. Thus, in typical Th1 and Th2 immune responses, hybrid Th1/2 cells cause less immunopathology than their classic Th1 or Th2 counterparts, demonstrating a cell-intrinsic self-limiting mechanism that can prevent excessive inflammation.
PMCID: PMC3747991  PMID: 23976880
15.  Unusual complications of arterial closure devices: a word of warning 
BMJ Case Reports  2011;2011:bcr0320114006.
The authors describe two patients who underwent transfemoral endovascular procedures followed by the use of the Angio-seal arterial percutaneous closure device. In the first patient, distal migration of the device occurred with consequent occlusion of the ipsilateral popliteal artery 2 days post procedure. In the second patient, thrombotic occlusion of the femoral artery occurred and the patient presented with acute leg ischaemia 3 weeks post procedure. Surgical removal of the closure device with consequent revascularisation of the affected leg was achieved in both patients. This report aims to alert clinicians to the possibility of device-induced arterial occlusion, dislodgment and their sequelae.
PMCID: PMC3132625  PMID: 22693293
16.  Granulosis rubra nasi 
Granulosis rubra nasi is a rare disorder of the eccrine glands, inherited as an autosomal dominant trait. It is clinically characterized by hyperhidrosis of the central part of the face, most conspicuous on the tip of the nose, followed by appearance of diffuse erythema over the nose, cheeks, chin, and upper lip. It is commonly seen in childhood, but can also occur in adults. This is a case report of a 27-year-old male patient who presented with excessive sweating over the nose. Physical examination of the nose revealed erythema and multiple telangiectatic vesicles. Biopsy findings supported the diagnosis of granulosis rubra nasi. This case is being reported for its rarity since to the best of our knowledge, it has not been reported in Indian subjects so far.
PMCID: PMC3752478  PMID: 23984236
Disorder of eccrine glands; granulosis rubra nasi; telengiectasia
17.  Slowly Rising Hilly Young Population of Himachal: A Step Towards Stabilization 
Socioeconomic development is the best contraceptive. Himachal Pradesh has made developments in all the fields, especially reducing the size of the family via family planning program.
The objectives of this analysis are to describe the various methods of family planning used from 2003 to 2010 and their impact in averting the births in the state and in stabilizing the population.
Materials and Methods:
We collected secondary data of the family planning program and the various methods employed from the total population (Census 2011) covered under family planning program (FPP) of the state. We analyzed and compared the results with India. We measured the impact of the program due to FP methods adopted. We employed the standardized program indicators- total fertility rate, birth rate, death rate, growth rate and census trend towards population growth; fertility rate (in %), birth rate and death rate (per thousand of the population per year) from 3.8, 31.5 and 11.1 in 1981 to 1.9, 17.2 and 7.2 in 2009. We entered dataset by double data entry technique and analyzed descriptively using Epi info version 3.3.2 and stat calc software.
The state has the population of 6,856,509, sex ratio in age 0-6 years is 906/1000 males. The unmet need for family planning services is 15%. The impact of family planning program has resulted in averting of 3,387,744 of pregnancies from 2003 to 2010. The total fertility rate (TFR) has come down to 1.9 in 2008 from 3.8 children per woman in 1981. The death rate has declined from 11.1 per 1000 live births in 1981 to 7.2 per 1000 live births in 2009. The trend in decadal growth rate of the state is observable as 23.0% in 1971 while in 2011, it is 12.8%; more towards young population and for geriatric one as well but not exploding like India.
Total population is on the increase with reference to the population of reproductive age bracket (15-49 years) and also geriatric population above 60 steadily despite good social and health indicators. Bulging reproductive age group with mild upward shift of the geriatric population is the root cause for increasing population in hills of Himachal Pradesh.
PMCID: PMC3793445  PMID: 24116319
Geriatric population; Hills population; Himachal Pradesh; Reproductive age group
18.  Scarf osteotomy in the management of symptomatic adolescent hallux valgus 
This study was designed to assess the utility of the scarf osteotomy in the management of symptomatic adolescent hallux valgus.
Materials and methods
This is a case series of 29 patients (39 feet) with a mean follow up of 38.6 months (range 6–60 months). The mean age at the time of surgery was 14.1 years (range 10–17 years). American Orthopaedic Foot and Ankle Society (AOFAS) scores were collected at final follow up, along with a rating of the overall satisfaction. Any complications were recorded. Pre- and post-surgical radiographic angles were measured and analysed using the Student’s t-test. The angles measured were the hallux valgus angle (HVA), the inter-metatarsal angle (IMA) and the distal metatarsal articular angle (DMAA). A second surgeon independently reviewed the angles in order to assess the inter-rater reliability using the Pearson product moment correlation.
The mean AOFAS score at final follow up was 94.2 (range 54–100). Of all patients, 93 % were either satisfied or very satisfied with their final outcome. One patient has been listed for revision surgery after symptomatic recurrence at 3 years follow up. The pre-operative HVA, IMA and DMAA were 34.8°, 15.9° and 16.0°, respectively. The post-operative values were 16.3°, 8.8° and 9.2°, respectively (p < 0.001 for each). Pearson’s r coefficient values demonstrated good inter-rater reliability of measurement.
We have presented the results of the largest case series of scarf osteotomies for adolescent hallux valgus reported in the literature up to now, as far as we are aware. AOFAS scores at final follow up are comparable to the smaller studies previously reported and provide evidence that good outcomes and high levels of patient satisfaction can be achieved. Early follow up demonstrates a low level of symptomatic recurrence, but longer term data are still required.
PMCID: PMC3364345  PMID: 23730347
Adolescent; Hallux; Valgus; Scarf; Osteotomy; Bunions
19.  Angiosarcoma originating from an ovarian mature teratoma, a rare disease with complex treatment modalities☆ 
► Ovarian angiosarcomas are rare and clinically aggressive neoplasms. ► In addition to surgery, taxol is the most studied adjuvant chemotherapy. ► Anti-angiogenic therapies can be considered as an option.
PMCID: PMC3862320  PMID: 24371690
Angiosarcoma; Teratoma; Anti-angiogenic therapy
20.  Intermediate Outcomes of a Chronic Disease Self-Management Program for Spanish-Speaking Older Adults in South Florida, 2008–2010 
The prevalence and negative health effects of chronic diseases are disproportionately high among Hispanics, the largest minority group in the United States. Self-management of chronic conditions by older adults is a public health priority. The objective of this study was to examine 6-week differences in self-efficacy, time spent performing physical activity, and perceived social and role activities limitations for participants in a chronic disease self-management program for Spanish-speaking older adults, Tomando Control de su Salud (TCDS).
Through the Healthy Aging Regional Collaborative, 8 area agencies delivered 82 workshops in 62 locations throughout South Florida. Spanish-speaking participants who attended workshops from October 1, 2008, through December 31, 2010, were aged 55 years or older, had at least 1 chronic condition, and completed baseline and post-test surveys were included in analysis (N = 682). Workshops consisted of six, 2.5-hour sessions offered once per week for 6 weeks. A self-report survey was administered at baseline and again at the end of program instruction. To assess differences in outcomes, a repeated measures general linear model was used, controlling for agency and baseline general health.
All outcomes showed improvement at 6 weeks. Outcomes that improved significantly were self-efficacy to manage disease, perceived social and role activities limitations, time spent walking, and time spent performing other aerobic activities.
Implementation of TCDS significantly improved 4 of 8 health promotion skills and behaviors of Spanish-speaking older adults in South Florida. A community-based implementation of TCDS has the potential to improve health outcomes for a diverse, Spanish-speaking, older adult population.
PMCID: PMC3760083  PMID: 23987252
21.  The Role of KRAS Mutational Analysis to Determine the Site of Origin of Metastatic Carcinoma to the Lung: A Case Report 
Case Reports in Pathology  2012;2012:425967.
Metastatic carcinomas involving the lung are a common specimen encountered in surgical pathology. These metastases may have different morphologic, and architectural patterns and may mimic primary pulmonary adenocarcinoma, especially the intra-alveolar (lepidic) pattern of spread which may simulate a primary pulmonary bronchioloalveolar carcinoma (adenocarcinoma in situ). We present the case of a metastatic pancreatic adenocarcinoma that morphologically mimicked bronchioloalveolar carcinoma of the lung in that the tumor had an exclusive intra-alveolar pattern of spread and had an immunophenotype that was noninformative as to the site of origin (cytokeratin 7+, cytokeratin 20−, TTF-1−). In this case, we used KRAS gene mutation analysis to support that the lung carcinoma represented a metastatic pancreatic carcinoma as they both possessed identical codon 12 KRAS mutations. We show that this method may be a useful way to prove site of origin of metastatic carcinoma—particularly if standard morphologic or immunohistochemical analysis is not definitive.
PMCID: PMC3483662  PMID: 23119210
22.  IgG4 Inflammatory Pseudotumor of the Kidney 
Case Reports in Urology  2012;2012:919087.
Hyper-IgG4 disease is a rare systemic disorder that usually affects middle age males. It is characterized by elevated serum IgG4 levels and infiltration of organs by IgG4 positive plasma cells associated with fibrosis. Patients usually present with mass or masses in the involved organ that mimic neoplasia. While initially described in the pancreas, IgG4-related inflammatory tumors have been now described in many organs. We describe an unusual case of an IgG4-related pseudotumor of the kidney.
PMCID: PMC3472528  PMID: 23094189
23.  Development of replication-defective lymphocytic choriomeningitis virus vectors for the induction of potent CD8+ T cell immunity 
Nature medicine  2010;16(3):339-345.
Lymphocytic choriomeningitis virus (LCMV) exhibits natural tropism for dendritic cells and represents the prototypic infection that elicits protective CD8+ T cell (cytotoxic T lymphocyte (CTL)) immunity. Here we have harnessed the immunobiology of this arenavirus for vaccine delivery. By using producer cells constitutively synthesizing the viral glycoprotein (GP), it was possible to replace the gene encoding LCMV GP with vaccine antigens to create replication-defective vaccine vectors. These rLCMV vaccines elicited CTL responses that were equivalent to or greater than those elicited by recombinant adenovirus 5 or recombinant vaccinia virus in their magnitude and cytokine profiles, and they exhibited more effective protection in several models. In contrast to recombinant adenovirus 5, rLCMV failed to elicit vector-specific antibody immunity, which facilitated re-administration of the same vector for booster vaccination. In addition, rLCMV elicited T helper type 1 CD4+ T cell responses and protective neutralizing antibodies to vaccine antigens. These features, together with low seroprevalence in humans, suggest that rLCMV may show utility as a vaccine platform against infectious diseases and cancer.
PMCID: PMC3247638  PMID: 20139992
24.  Scintimammography in conjunction with ultrasonography for local breast cancer recurrence in post-mastectomy breast 
The British Journal of Radiology  2010;83(995):934-939.
The aim of this study was to compare the usefulness of 99Tcm-methoxy-isobutyl-isonitrile (MIBI) scintimammography and ultrasonography, alone and in combination, for the detection of chest wall recurrence in the post-mastectomy breast. A total of 41 consecutive post-mastectomy patients (mean age 46.6 years; median age 45 years) with clinical suspicion of breast cancer recurrence were evaluated. For scintimammography all patients received a 740–900 MBq iv injection of 99Tcm-MIBI; planar images were taken 5–10 min post-injection followed by supine single photon emission CT. Breast ultrasonography was performed in each patient using a 7.5 MHz transducer. Both MIBI uptake and ultrasound findings were documented using standard protocols. All patients had fine needle aspiration cytology biopsy (FNAC), core biopsy or excision biopsy for final tissue diagnosis. Of the 41 patients, 24 had true positive signs of local breast cancer recurrence upon ultrasonography, 10 were diagnosed as true negatives, a sensitivity of 86%, specificity 77%, positive predictive value (PPV) 89%, negative predictive value (NPV) 71% and accuracy 83% (p = 0.001). By comparison, scintimammography findings were found to be true positive in 25 patients and true negative in 12 patients — sensitivity 89%, specificity 92%, PPV 96%, NPV 80% and accuracy 90% (p = 0.001). Using a combination of these two modalities, the combined sensitivity was 100%, specificity 77%, PPV 90%, NPV 100% and accuracy 93%. The high NPV of the two studies in combination implies a potential use of this approach to exclude recurrent disease in patients with a low initial index of suspicion and/or when histology is indeterminate.
PMCID: PMC3473732  PMID: 20965904
Leukemia & lymphoma  2010;51(4):664-670.
For patients with relapsed Hodgkin Lymphoma, high dose chemotherapy with stem cell rescue may improve survival over chemotherapy alone. We assessed outcomes of HDCT-SCT in 37 consecutive adolescent and young adult patients with relapsed HL whose malignancy was categorized based on sensitivity to chemotherapy. We determined whether current outcomes supported the use of HDCT-SCT in all of our patients or just those patients with lower risk characteristics such as chemosensitivity. With a median follow up of 6.5 years, the 2 year overall survival was 89% (95% CI: 62%–97%) for the chemo-sensitive patients (n=21). Whereas for patients with resistant disease (n=16) OS was 53% (95%CI: 25%–74%). Both autologous and allogeneic transplants were well tolerated, with 100 day treatment related mortality under 10%. Our data show encouraging outcomes for patients with chemosensitive relapsed HL who receives HSCT and supports the value of the procedure even when the disease is chemoresistant.
PMCID: PMC2932472  PMID: 20367182
Hodgkin’s Lymphoma; Stem Cell Transplant; Salvage Therapy

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