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1.
J Inorg Biochem ; 256: 112545, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38581803

ABSTRACT

Trinuclear ruthenium(II) polypyridyl complexes anchored to benzimidazole-triazine / trisamine scaffolds were investigated as photosensitizers for photodynamic therapy. The trinuclear complexes were noted to produce a significant amount of singlet oxygen in both DMF and aqueous media, are photostable and show appreciable emission quantum yields (ɸem). In our experimental setting, despite the moderate phototoxic activity in the HeLa cervical cancer cell line, the phototoxic indices (PI) of the trinuclear complexes are superior relative to the PIs of a clinically approved photosensitizer, Photofrin®, and the pro-drug 5-aminolevulinic acid (PI: >7 relative to PI: >1 and PI: 4.4 for 5-aminolevulinic acid and Photofrin®, respectively). Furthermore, the ruthenium complexes were noted to show appreciable long-term cytotoxicity upon light irradiation in HeLa cells in a concentration-dependent manner. Consequently, this long-term activity of the ruthenium(II) polypyridyl complexes embodies their ability to reduce the probability of the recurrence of cervical cancer. Taken together, this presents a strong motivation for the development of polymetallic complexes as anticancer agents.


Subject(s)
Coordination Complexes , Photochemotherapy , Photosensitizing Agents , Ruthenium , Uterine Cervical Neoplasms , Humans , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/chemical synthesis , HeLa Cells , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/pathology , Ruthenium/chemistry , Female , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Photochemotherapy/methods , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Pyridines/chemistry , Pyridines/pharmacology , Singlet Oxygen/metabolism
2.
Mol Cancer Res ; 21(4): 345-358, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36622795

ABSTRACT

Cervical cancer is a leading cause of cancer-related deaths in women globally and 99% of cases are caused by persistent infection with high-risk strains of the human papillomavirus (HPV). The HPV oncoproteins E6 and E7 establish the cancer phenotype by cooperating with host proteins and identifying them may have important therapeutic benefits. T-box transcription factor 3 (TBX3) is a critical developmental regulator, and when it is overexpressed postnatally, it contributes to several cancers, but little is known about its expression and role in cervical cancer. The current study shows that TBX3 is upregulated in cervical cancer cell lines as well as precancerous and cervical cancer patient tissue and is associated with larger and more invasive tumors. Knockdown and overexpression cell culture models show that TBX3 promotes HPV-positive cell proliferation, migration, and spheroid growth; however, TBX3 inhibits these processes in HPV-negative cells. Importantly, we show that the tumor promoting activity of TBX3 in cervical cancer is dependent on E6/E7. IMPLICATIONS: In summary, our study highlights the importance of TBX3 as a cooperating partner of E6/E7 in HPV-positive cervical cancer and identifies TBX3 as a potential therapeutic target to treat this neoplasm.


Subject(s)
Oncogene Proteins, Viral , Papillomavirus Infections , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/pathology , Oncogene Proteins, Viral/genetics , Oncogene Proteins, Viral/metabolism , Human Papillomavirus Viruses , Papillomavirus E7 Proteins/genetics , Papillomavirus Infections/pathology , Cell Proliferation , T-Box Domain Proteins/genetics
3.
In Vitro Cell Dev Biol Anim ; 58(8): 679-692, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35947290

ABSTRACT

Amphibians have regenerative capacity and are resistant to developing cancer. This suggests that the developing blastema, located at the tissue regeneration site, may secrete anti-cancer factors. Here, we investigate the anti-cancer potential of tadpole tail blastema extracts (TAD) from the stream frog, Strongylopus grayii, in embryonal rhabdomyosarcoma (ERMS) cells. ERMS originates in skeletal muscle tissue and is a common pediatric soft tissue sarcoma. We show using MTT assays that TAD inhibited ERMS cell viability in a concentration-dependent manner, and phase contrast/fluorescent microscopy revealed that it induced morphological markers of senescence and apoptosis. Western blotting showed that this was associated with DNA damage (γH2AX) and activation of the p38/MAPK stress signaling pathway as well as molecular markers of senescence (p16INK4a), apoptosis (cleaved PARP), and inhibition of cell cycle promoters (cyclin A, CDK2, and cyclin B1). Furthermore, proteomics followed by gene ontology analyses showed that TAD treatment inhibited known tumor promoters and proteins required for cancer cell survival. Lastly, using the LINCS drug perturbation library, we show that there is an overlap between the proteomics signature induced by TAD and common anti-cancer drugs. Taken together, this study provides novel evidence that TAD exhibits cytotoxicity in ERMS cells.


Subject(s)
Antineoplastic Agents , Rhabdomyosarcoma, Embryonal , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Carcinogens , Cell Line, Tumor , Cyclin A , Cyclin B1 , Cyclin-Dependent Kinase Inhibitor p16 , Larva , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Rhabdomyosarcoma, Embryonal/drug therapy , Rhabdomyosarcoma, Embryonal/genetics , Rhabdomyosarcoma, Embryonal/pathology
4.
Tumour Virus Res ; 13: 200238, 2022 06.
Article in English | MEDLINE | ID: mdl-35460940

ABSTRACT

Cervical cancer is the fourth most common female cancer worldwide and results in over 300 000 deaths globally. The causative agent of cervical cancer is persistent infection with high-risk subtypes of the human papillomavirus and the E5, E6 and E7 viral oncoproteins cooperate with host factors to induce and maintain the malignant phenotype. Cervical cancer is a largely preventable disease and early-stage detection is associated with significantly improved survival rates. Indeed, in high-income countries with established vaccination and screening programs it is a rare disease. However, the disease is a killer for women in low- and middle-income countries who, due to limited resources, often present with advanced and untreatable disease. Treatment options include surgical interventions, chemotherapy and/or radiotherapy either alone or in combination. This review describes the initiation and progression of cervical cancer and discusses in depth the advantages and challenges faced by current cervical cancer therapies, followed by a discussion of promising and efficacious new therapies to treat cervical cancer including immunotherapies, targeted therapies, combination therapies, and genetic treatment approaches.


Subject(s)
Oncogene Proteins, Viral , Papillomavirus Infections , Uterine Cervical Neoplasms , Female , Humans , Oncogene Proteins, Viral/genetics , Papillomaviridae/genetics , Papillomavirus E7 Proteins/genetics , Papillomavirus Infections/complications , Uterine Cervical Neoplasms/therapy
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 246: 119010, 2021 Feb 05.
Article in English | MEDLINE | ID: mdl-33035886

ABSTRACT

During the investigation of fungal isolation from fruit, the major genera were Aspergillus, Penicillium, cladosporium, Alternaria, fusarium, Colletotrichum were found. Among them Aspergillus (15 species) was found major dominant on different fruits. Fifteen different Aspergillus species viz. Aspergillus brasiliensis, Aspergillus phoenicis, Aspergillus carbonarius, four Aspergillus flavus, Aspergillus acidus, two Aspergillus awamori, Aspergillus aculeatus, Aspergillus eucalypticola, Aspergillus oryzae and two Aspergillus Spp. have been differentiate and identify using morphology (microscopic technique), Fourier Transforms Infrared spectroscopy (FTIR), Raman Spectroscopy (RS) and UV-visible spectrophotometry (UV-vis). The fungal mass in powder form was used in present study. In FTIR the finger print region is important for the characterization of Aspergillus because this region is unique and contains peaks indicating the presence of DNA. From the results were found Fourier transform infrared (FTIR) technique and Raman spectroscopy a useful tool, sensitive, fast, economical, accurate, not require sample preparation and successfully used to identify fungi.


Subject(s)
Fruit , Microscopy , Aspergillus , Fungi , Spectroscopy, Fourier Transform Infrared
6.
Environ Sci Pollut Res Int ; 27(23): 29156-29170, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32436090

ABSTRACT

Tree species (including Eucalyptus camaldulensis, Ziziphus spina-christi, Albizia lebbeck, Prosopis juliflora, Pithecellobium dulce, and Ficus altissima) were investigated to elucidate their appropriates for green belt application. Leaf samples were collected from four different locations in Riyadh: (1) residential; (2) dense traffic; (3) industrial; and (4) reference sites located approximately 20 km away from the city of Riyadh. Leaves collected from the industrial site showed the highest leaf area reduction. The smallest reduction of leaf areas was observed for F. altissima (11.6%), while the highest reduction was observed for P. juliflora (34.8%). Variations in the air pollution tolerance index (APTI) coupled with the anticipated performance index (API) for each species were examined. The APTI value of Z. spina-christi was highest (58.5) at the industrial site while the lowest APTI value was for P. juliflora (14) at the reference site. Correlation coefficient and linear regression analyses determined that the correlation between the ascorbic acid content and APTI is positive and significantly strong. Our findings indicate that urban green planning in Riyadh should include growing F. altissima on roadsides as well as in heavy industrial locations followed by Z. spina-christi and A. lebbeck according to their API and APTI performances.


Subject(s)
Air Pollutants/analysis , Air Pollution/analysis , Cities , Environmental Monitoring , Plant Leaves/chemistry , Saudi Arabia , Trees
7.
Gene ; 726: 144223, 2020 Feb 05.
Article in English | MEDLINE | ID: mdl-31669645

ABSTRACT

TBX3, a member of the ancient and evolutionary conserved T-box transcription factor family, is a critical developmental regulator of several structures including the heart, mammary glands, limbs and lungs. Indeed, mutations in the human TBX3 lead to ulnar mammary syndrome which is characterized by several clinical malformations including hypoplasia of the mammary and apocrine glands, defects of the upper limb, areola, dental structures, heart and genitalia. In contrast, TBX3 has no known function in adult tissues but is frequently overexpressed in a wide range of epithelial and mesenchymal derived cancers. This overexpression greatly impacts several hallmarks of cancer including bypass of senescence, apoptosis and anoikis, promotion of proliferation, tumour formation, angiogenesis, invasion and metastatic capabilities as well as cancer stem cell expansion. The debilitating consequences of having too little or too much TBX3 suggest that its expression levels need to be tightly regulated. While we have a reasonable understanding of the mutations that result in low levels of functional TBX3 during development, very little is known about the factors responsible for the overexpression of TBX3 in cancer. Furthermore, given the plethora of oncogenic processes that TBX3 impacts, it must be regulating several target genes but to date only a few have been identified and characterised. Interestingly, while there is compelling evidence to support oncogenic roles for TBX3, a few studies have indicated that it may also have tumour suppressor functions in certain contexts. Together, the diverse functional elasticity of TBX3 in development and cancer is thought to involve, in part, the protein partners that it interacts with and this area of research has recently received some attention. This review provides an insight into the significance of TBX3 in development and cancer and identifies research gaps that need to be explored to shed more light on this transcription factor.


Subject(s)
Disease/genetics , Gene Expression Regulation, Developmental/genetics , T-Box Domain Proteins/genetics , Animals , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/pathology , Humans , Transcription Factors/genetics
8.
Opt Express ; 26(19): 25199-25210, 2018 Sep 17.
Article in English | MEDLINE | ID: mdl-30469625

ABSTRACT

We study optomechanically induced transparency (OMIT) in a compound system consisting of coupled optical resonators and a mechanical mode, focusing on the unconventional role of loss. We find that optical transparency can emerge at the otherwise strongly absorptive regime in the OMIT spectrum, by using an external nanotip to enhance the optical loss. In particular, loss-induced revival of optical transparency and the associated slow-to-fast light switch can be identified in the vicinity of an exceptional point. These results open up a counterintuitive way to engineer micro-mechanical devices with tunable losses for e.g., coherent optical switch and communications.

9.
Metab Brain Dis ; 32(6): 2155-2159, 2017 12.
Article in English | MEDLINE | ID: mdl-28875386

ABSTRACT

Troyer Syndrome (TRS) is a rare autosomal recessive complicated spastic paraplegia disorder characterized by various neurological and musculoskeletal manifestations. Pathogenicity stems from mutations in SPG20 which encodes Spartin, a multifunctional protein that is thought to be essential for neuron viability. Here we report on the clinical and molecular characterization of TRS in five patients from an extended consanguineous family in the United Arab Emirates. Molecular analysis involved Whole Exome Sequencing and Sanger sequencing for identification and confirmation of the causative variant respectively. In silico tools including CADD and Polyphen-2 were used to assess pathogenicity of the variant. The clinical description of these patients included spastic paraparesis, motor and cognitive delay, gait abnormalities, musculoskeletal features, as well as white matter abnormalities and emotional liability. Molecular analysis revealed a novel homozygous missense mutation in SPG20 (c.1324G > C; p.Ala442Pro) occurring at an evolutionarily conserved residue in the Plant-Related Senescence domain of Spartin. The mutation segregated with the clinical phenotype in all patients. In silico algorithms predict the mutation to be disease causing, and the variant had not been previously reported in public or ethnic specific variant repositories.


Subject(s)
Mutation , Proteins/genetics , Spastic Paraplegia, Hereditary/genetics , Adolescent , Cell Cycle Proteins , Child , Child, Preschool , Female , Humans , Male , Pedigree
10.
Ann Dermatol Venereol ; 144(3): 212-215, 2017 Mar.
Article in French | MEDLINE | ID: mdl-27765414

ABSTRACT

BACKGROUND: Imiquimod is a local immune-response modifier that works by stimulating innate and acquired immunity. It is frequently used to treat superficial basal cell carcinoma, the most common form of skin cancer. Marked local inflammatory reaction is common during treatment. We report a case of the rare condition, multiple eruptive milia, during topical imiquimod therapy. PATIENTS AND METHODS: A 67-year-old male patient presented infiltrating basal cell carcinoma above the left eyebrow. The patient underwent surgery and skin grafting. He presented superficial relapse at the periphery of the graft and was initially treated with Aldara®. Fifteen days after initiation, Aldara® was withdrawn due to a critical inflammatory reaction. A few weeks after complete healing, an erythematous annular plaque of milia, excluding the graft zone, appeared. This element was confirmed by histopathology. DISCUSSION: The most common local side effects reported with Aldara® are erythema, irritation and crusting. Reports of eruptive milia following Aldara® therapy are rare and they are never mentioned in the summary of product characteristics. Application of imiquimod in fact induces local inflammatory reaction due to stimulation of local cytokines, which can result in marked reaction in the infundibular epithelium of hair follicles and thus in the production of abnormal keratin that can cause pilosebaceous duct obstruction and thus the formation of epidermoid cysts. This pathological mechanism explains the absence of lesions on the skin graft of the inner arm. CONCLUSION: The occurrence of eruptive milia during treatment with Aldara® is rarely described. The timing of occurrence of these eruptive milia as well as the mechanism of action of the drug made such a reaction highly probable in our patient.


Subject(s)
Aminoquinolines/adverse effects , Antineoplastic Agents/adverse effects , Carcinoma, Basal Cell , Keratosis/chemically induced , Skin Neoplasms , Administration, Cutaneous , Aged , Aminoquinolines/administration & dosage , Antineoplastic Agents/administration & dosage , Carcinoma, Basal Cell/drug therapy , Carcinoma, Basal Cell/pathology , Carcinoma, Basal Cell/surgery , Diagnosis, Differential , Eyebrows , Humans , Imiquimod , Male , Pruritus/chemically induced , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Skin Neoplasms/surgery
11.
Ir J Med Sci ; 186(2): 333-337, 2017 May.
Article in English | MEDLINE | ID: mdl-26860117

ABSTRACT

BACKGROUND: Intellectual disability (ID) features in numerous heritable medical conditions that result from ATRX mutations. Alpha-thalassemia mental retardation syndrome (ATR-X syndrome) is the most notable manifestation of ATRX dysfunction. In addition to ID, genitourinary and craniofacial abnormalities are regularly observed with or without alpha-thalassemia. AIMS: The study sought to characterize two cases of ATR-X in a Yemeni family clinically and molecularly. METHODS: PCR amplification and Sanger sequencing were used to study the ATRX gene in a Yemeni family. Also, methylation-sensitive PCR was used to perform X-inactivation studies. CADD, SNAP2 and PolyPhen-2 helped to predict the functional consequences of the variant. RESULTS: Molecular testing revealed a novel hemizygous missense mutation (c.5666T>G) in the ATRX gene in the two Yemeni brothers. This mutation was found in a heterozygous state in the mother, with the chromosome harboring the mutated allele being under strongly skewed X-inactivation. CONCLUSIONS: The mutated gene is predicted to have a disrupted SNF-2 domain at a conserved residue; p.Leu1889Trp, which is deemed functionally damaging. This report offers, for the first time, full clinical and molecular characterization of a novel ATRX variant in an Arab family.


Subject(s)
Mental Retardation, X-Linked/genetics , Mutation, Missense/genetics , alpha-Thalassemia/genetics , Alleles , Heterozygote , Humans , Infant , Intellectual Disability/genetics , Male
12.
J Reprod Immunol ; 116: 42-5, 2016 08.
Article in English | MEDLINE | ID: mdl-27175516

ABSTRACT

BACKGROUND AND OBJECTIVES: Pemphigoid gestationis (PG) is a rare autoimmune-mediated blistering disease that mainly affects pregnant women in their 2nd or 3rd trimester and immediate postpartum period. In addition to the clinical assessment, the diagnosis of PG is usually confirmed by histological and immunological studies. PG usually flares up at the time of delivery and spontaneously improves postpartum. Prompt recognition and appropriate management may reduce morbidity associated with this disorder. This study aimed to determine the clinical, histopathological features and treatment of PG of Saudi patients. MATERIALS AND METHODS: A retrospective study of 32 patients with pemphigoid gestationis (PG) was conducted from 1990 to 2014 at King Khalid University Hospital and Derma Medical Center, Riyadh, Saudi Arabia. Data regarding epidemiology, medical histories, clinical course, diagnostic test results and management were collected and analyzed. RESULTS: A total of 32 patients with PG were analyzed. The mean age was 31.9 years. Seventy-four percent of the patients were multigravidas, and 2 patients were primigravidas. One hundred percent of the cases were singleton pregnancies. Eighty-four percent of the cases had the onset of PG during the 2nd and 3rd trimesters. One hundred percent of patients complained of pruritus, and 94% reported this as the first symptom. Erythematous plaques and vesiculobullous eruption were the most common skin presentation. The primary sites of involvement were the abdomen, trunk, lower (mainly thighs) and upper limbs. The face and mucus membranes were rarely involved. Fifty percent of patients had recurrent symptoms with their next pregnancy. Direct immunofluorescence revealed a linear deposition of the third component of the complement along the basement membrane zone in all cases (C3),while most of the cases showed positive linear deposition of IgG. Seventy five percent of our patients had a good response to oral corticosteroids, and only one patient needed IVIG. The vast majority of the patients (61%) became free of symptoms within 1-2 months of treatment. In 53% of the patients, maternal and fetal outcomes were good with no complications. Six pregnancies were complicated by preterm labor, 2 experienced IUGR (intrauterine growth restriction), and 2 had an abortion or stillbirth. CONCLUSION: Our study does not differ dramatically when comparing the onset of PG, the high frequency of multigravida women, the clinical course and good patient outcomes but we observed that the first attack extended from primigravida to 11th pregnancy and slight increase in recurrence rate. Finally the timely diagnosis and appropriate management of PG may improve both maternal and neonatal outcome.


Subject(s)
Pemphigoid Gestationis/immunology , Pregnancy Complications/immunology , Skin/immunology , Adolescent , Adult , Basement Membrane/metabolism , Complement C3/metabolism , Female , Gravidity , Humans , Pemphigoid Gestationis/epidemiology , Pregnancy , Pregnancy Complications/epidemiology , Pregnancy Trimester, Third , Retrospective Studies , Saudi Arabia/epidemiology , Skin/pathology , Young Adult
13.
J Trauma Acute Care Surg ; 77(1): 166-9, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24977773

ABSTRACT

BACKGROUND: Head injury is the most common cause of neurologic disability and mortality in children. Previous studies have demonstrated that depressed skull fractures (SFs) represent approximately one quarter of all SFs in children and approximately 10% percent of hospital admissions after head injury. We hypothesized that nondepressed SFs (NDSFs) in children are not associated with adverse neurologic outcomes. METHODS: Medical records were reviewed for all children 5 years or younger with SFs who presented to our Level I trauma center during a 4-year period. Data collected included patient demographics, Glasgow Coma Scale (GCS) score at admission, level of consciousness at the time of injury, type of SF (depressed SF vs. NDSF), magnitude of the SF depression, evidence of neurologic deficit, and the requirement for neurosurgical intervention. RESULTS: We evaluated 1,546 injured young children during the study period. From this cohort, 563 had isolated head injury, and 223 of them had SF. Of the SF group, 163 (73%) had NDSFs, of whom 128 (78%) presented with a GCS score of 15. None of the NDSF patients with a GCS score of 15 required neurosurgical intervention or developed any neurologic deficit. Of the remaining 35 patients with NDSF and GCS score less than 15, 7 (20%) had a temporary neurologic deficit that resolved before discharge, 4 (11%) developed a persistent neurologic deficit, and 2 died (6%). CONCLUSION: Children 5 years or younger with NDSFs and a normal neurologic examination result at admission do not develop neurologic deterioration. LEVEL OF EVIDENCE: Epidemiological study, level III.


Subject(s)
Skull Fractures/complications , Skull Fractures/diagnosis , Child , Child, Preschool , Female , Glasgow Coma Scale , Humans , Infant , Infant, Newborn , Length of Stay , Male , Neurologic Examination , Skull Fractures/therapy
15.
J Surg Res ; 185(1): 273-7, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23835072

ABSTRACT

INTRODUCTION: We previously developed an evidence-based clinical pathway for children with advanced appendicitis. The pathway standardized the choice and duration of antibiotic therapy and established discharge criteria. Initially, the pathway led to a 50% decrease in the rate of superficial and deep surgical site infections and a significant decrease in hospital length of stay. Four years after implementation, we noted an increase in the infectious complication rate and the emergence of resistant bacteria to commonly used antibiotics. In this study, we prospectively collected peritoneal fluid cultures at the time of appendectomy in an effort to optimize our antibiotic therapy and decrease complication rates. METHODS: Microbiology analysis of peritoneal fluid cultures obtained at the time of appendectomy was performed in patients with an intraoperative diagnosis of advanced appendicitis. Clinical information, including demographics, laboratory data, and postoperative outcomes were collected and compared to the historic cohort. X(2), Student's t-test, and Fisher exact test were used where appropriate. RESULTS: The historic and prospective cohorts were similar with respect to clinical and demographic data. The postoperative intra-abdominal abscess rate remained unchanged (28% from 24%, P = 0.603). Escherichia coli and Pseudomonas aeruginosa were the most commonly isolated aerobic bacteria from peritoneal fluid in the prospective cohort. Thirty-two percent of these patients had Pseudomonas spp., and 12% had Enterococcus spp. or Escherichia coli resistant to cefoxitin in their peritoneal fluid cultures. DISCUSSION: A significant proportion (40%) of children with advanced appendicitis had organisms either not susceptible or resistant to our first line antibiotic in their peritoneal fluid cultures. Our clinical pathway now recommends piperacillin-tazobactam as the most effective empiric therapy for advanced appendicitis in children. Microbiologic analysis of peritoneal fluid at appendectomy may be used to tailor antibiotic therapy in advanced appendicitis.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Appendicitis/drug therapy , Appendicitis/surgery , Critical Pathways , Evidence-Based Practice/methods , Adolescent , Appendectomy , Child , Child, Preschool , Cohort Studies , Escherichia coli Infections/drug therapy , Female , Humans , Infant , Length of Stay , Male , Outcome and Process Assessment, Health Care , Postoperative Complications/drug therapy , Pseudomonas Infections/drug therapy , Surgical Wound Infection/drug therapy
16.
J Pediatr Surg ; 48(7): 1551-6, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23895971

ABSTRACT

BACKGROUND/PURPOSE: Pilomatricomas, or calcifying epitheliomas of Malherbe, are among the most common superficial cutaneous soft tissue lesions in children. Familiarity with the presenting signs and symptoms allows for the diagnosis to be made on physical examination alone in most patients, avoiding expensive and unnecessary diagnostic imaging. METHODS: A retrospective IRB-approved review of surgical pathology archives and medical records of all patients undergoing excision of pilomatricomas between 1982 and 2010 was performed to determine the characteristics of the pilomatricoma tumors. Data regarding gender, age, location, size of tumor, and histopathology were collected. RESULTS: There were 916 pilomatricomas resected in 802 patients. Fifty-five percent of the patients were girls (441 patients). The median age at the time of resection was 6 years (range 5 months to 18 years). Multiple lesions were found in 43 patients (5%). The most common location was head and neck (n = 529, 58%), followed by upper limbs (n = 214, 23%), trunk (n = 130, 14%), and lower limbs (n = 43, 5%). Information on size was available for 674 lesions; mean lesion diameter was 14.0 ± 7.4 mm. Twenty-eight patients (3%) had either recurrent (n = 11) or metachronous (n = 17) lesions resected at our institution, with a median interval of 12 months after initial resection (range 5 weeks to 5 years). No cases of pilomatrix carcinoma were observed. CONCLUSION: The majority of pilomatricomas occur in the head and neck, although they can present in any location. Approximately 5% of children have multiple lesions. Pilomatricomas occur slightly more commonly in girls, and 66% of lesions occur in children < 10 years of age. Complete surgical excision is necessary to prevent recurrence. Recurrences and pilomatrix carcinoma are very rare if complete excision is achieved.


Subject(s)
Hair Diseases/pathology , Pilomatrixoma/pathology , Skin Neoplasms/pathology , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Retrospective Studies
17.
J Surg Res ; 184(1): 347-51, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23731683

ABSTRACT

BACKGROUND: In 2006, an evidence-based protocol for the management of children with appendicitis was established at our institution. Discharge criteria for patients with advanced appendicitis were based on a combination of clinical parameters and laboratory values. The purpose of this study is to evaluate the utility of laboratory values in guiding patient management with a discharge protocol for advanced appendicitis. MATERIALS AND METHODS: We reviewed charts of patients with advanced appendicitis as defined by the surgeon intraoperatively from 2008-2009. We evaluated the sensitivity and specificity of the laboratory values at discharge for predicting postoperative intra-abdominal abscess (IAA) formation using a receiver operator curve. A logistic regression analysis was performed to identify predictors of IAA formation. RESULTS: We identified 450 patients (mean age 8.9 ± 3.9 y). The postoperative IAA rate was 25%. The sensitivity and specificity for developing an abscess with a white blood cell count >12,000/UL were 52% and 82%, respectively (AUC 0.72, 95% CI 0.67-0.78, P < 0.001). The sensitivity and specificity for bands >3% were 47% and 70% (AUC 0.60, 95% CI 0.53-0.67, P = 0.002), respectively. On logistic regression analysis, an elevated white blood cell count was independently associated with an increased likelihood of a postoperative IAA (OR 1.27, 95% CI 1.19-1.35, P < 0.001). CONCLUSIONS: The absence of leukocytosis is useful for identifying children with a decreased risk of postappendectomy IAA formation who otherwise meet clinical discharge parameters. A band count is not as predictive of risk. The use of laboratory evaluation as a component of discharge criteria in advanced appendicitis can stratify a subset of patients who are at increased IAA risk and may benefit from continued antibiotic therapy.


Subject(s)
Appendectomy , Appendicitis/diagnosis , Appendicitis/surgery , Critical Pathways/standards , Patient Discharge/standards , Abdominal Abscess/diagnosis , Abdominal Abscess/epidemiology , Acute Disease , Algorithms , Appendicitis/epidemiology , Child , Child, Preschool , Evidence-Based Medicine , Female , Humans , Logistic Models , Male , Practice Guidelines as Topic , ROC Curve , Retrospective Studies , Risk Factors , Sensitivity and Specificity , Surgical Wound Infection/diagnosis , Surgical Wound Infection/epidemiology
18.
Orbit ; 31(6): 394-9, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23231063

ABSTRACT

AIMS: To define a computed tomography protocol that may be used in future clinical practice for the reliable detection and analysis of cribra orbitalia. MATERIALS AND METHODS: Two osteological assemblages from the Museum of London were used to select 13 cribratous skulls and 5 non-cribratous skulls. Area of cribra orbitalia was measured using image analysis. Morphology of cribra orbitalia, orbital roof density and the associated optic canal diameter was analysed using computed tomography reconstructions. RESULTS: The presence of cribra orbitalia was associated with changes in the internal diploë layer as well as the cortical bone table. A novel radiological grading system and protocol was developed to identify the pathology. A decrease in the orbital roof density by 210 Hounsfield units and a reduction in the optic canal diameter, up to 1 mm, were found to be associated with the presence of cribra orbitalia. CONCLUSIONS: The occurrence of cribra orbitalia is found to be associated with stenosis of the optic canal, and could explain a proportion of cases ofoptic nerve entrapment. This study provides a guideline for radiologists and oculoplastic surgeons to help detect the presence of cribra orbitalia in suspected patients.


Subject(s)
Orbit/pathology , Skull/pathology , Tomography, X-Ray Computed/methods , Cadaver , Humans , London , Orbit/diagnostic imaging , Paleopathology , Radiographic Image Interpretation, Computer-Assisted , Skull/diagnostic imaging
19.
J Pediatr Surg ; 47(6): 1261-6, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22703803

ABSTRACT

BACKGROUND: Open biopsy has been the mainstay for definitive diagnosis of neuroblastoma in pediatric patients. However, needle core biopsy may represent a faster, less invasive, and safer alternative to open biopsy in children. The purpose of this study was to compare safety and efficacy between needle core and open biopsy in the diagnosis of patients with intermediate- and high-risk neuroblastoma at our institution. METHODS: We retrospectively reviewed the medical records of children with intermediate- and high-risk neuroblastoma who underwent open or needle core biopsies from 2002 to 2010. Data collected included patient demographics, tumor size, sample adequacy for diagnosis and risk stratification (histology and cytogenetics), length of hospital stay, time to initiate chemotherapy after biopsy, need for repeat biopsy, and both intraoperative and postoperative complications. Mann-Whitney U and Fisher's exact tests were used for statistical analysis. RESULTS: During the study period, 7 patients underwent needle core primary biopsies (5 intermediate-risk primary tumors and 2 high-risk primary tumors), and 4 patients underwent needle core biopsy for metastatic tumors, whereas 21 patients had open biopsies (10, intermediate risk; 11, high risk). Median age at biopsy and median tumor size were similar in both groups. There was no significant difference in adequacy of biopsy, need for repeat biopsy, time to initiate chemotherapy, length of stay, or minor complications. The rate of major complications differed significantly between the 2 groups with 0% after needle core biopsy vs 48% after open biopsy (P = .027). CONCLUSIONS: In children, needle core biopsy is comparable in efficacy with open biopsy in the diagnosis of intermediate- and high-risk neuroblastoma with significantly lower rates of major postoperative complications. These findings warrant a larger scale evaluation of diagnostic needle core biopsies in pediatric patients with solid tumor.


Subject(s)
Abdominal Neoplasms/diagnosis , Biopsy/methods , Neuroblastoma/diagnosis , Thoracic Neoplasms/diagnosis , Abdominal Neoplasms/drug therapy , Abdominal Neoplasms/genetics , Abdominal Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biopsy/adverse effects , Biopsy/statistics & numerical data , Biopsy, Needle/adverse effects , Biopsy, Needle/statistics & numerical data , Child , Child, Preschool , Female , Gene Amplification , Genes, myc , Humans , Infant , Length of Stay/statistics & numerical data , Male , Neuroblastoma/drug therapy , Neuroblastoma/genetics , Neuroblastoma/pathology , Postoperative Complications/epidemiology , Retrospective Studies , Risk , Thoracic Neoplasms/drug therapy , Thoracic Neoplasms/genetics , Thoracic Neoplasms/pathology , Tumor Burden
20.
Orbit ; 31(3): 159-61, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22551366

ABSTRACT

AIMS: To describe the morphometric relationships and bony composition of the nasolacrimal fossa in a Caucasian population with particular reference to the lacrimo-maxillary suture (LMS). METHODS: Forty-seven orbits from 24 formalin fixed cadavers were exenterated. Morphometric measurements were taken between anatomical landmarks forming the lacrimal fossa on the medial orbital wall. RESULTS: The mean recorded distance from the anterior lacrimal crest (ALC) to the posterior lacrimal crest (PLC) and the LMS were 8.8 mm (± 1.6) and 4.3 mm (± 1.1), respectively. In 25.5% of the orbits the LMS was at the mid-vertical line (MVL), defined as a line equidistant from the ALC and PLC. In 42.5% the LMS was located anterior to the MVL toward the ALC. In 66% of the orbits the LMS was at or within one standard deviation (SD) of the MVL. The LMS was >1 SD away from the MVL toward the ALC and PLC in 19% and 15% of orbits, respectively. CONCLUSIONS: In a quarter of the orbits in our Caucasian population the nasolacrimal fossa was formed equally by the maxillary and lacrimal bones. However, in nearly a third of the cases the LMS was located closer to the PLC, indicating predominance of the thicker maxillary bone. This may result in greater difficulty in initiating the surgical osteotomy when performing a dacryocystorhinostomy. These data contribute to our understanding of the variation in lacrimal fossa anatomy and encourage further studies in different racial groups.


Subject(s)
Maxilla/anatomy & histology , Nasolacrimal Duct/anatomy & histology , Orbit/anatomy & histology , White People , Cadaver , Female , Humans , Male
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