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1.  Influence of oral mucosal lesions and oral symptoms on oral health related quality of life in dermatological patients: a cross sectional study in Sudan 
BMC Oral Health  2012;12:19.
There are only few studies considering the impact of oral mucosal lesions (OML) on the oral quality of life of patients with different dermatological conditions. This study aimed to assess the relationship between oral health-related quality of life (OHRQoL) and OML and reported oral symptoms, perceived general and oral health condition and caries experience in adult skin diseased patients attending an outpatient dermatologic clinic in Sudan.
A cross-sectional survey was carried out with 544 diagnosed skin diseased patients (mean age 37.1 years, 50 % females), during the period October 2008 to January 2009. The patients were orally examined and OML and caries experience was recorded. The patients were interviewed using the Sudanese Arabic version of the OIDP. OHRQoL was evaluated by socio-demographic and clinical correlates according to number of types of OML diagnosed (no OML, one type of OML, > one type of OML) and number and types of oral symptoms.
An oral impact (OIDP > 0) was reported by 190 patients (35.6 %) (mean OIDP total score 11.6, sd = 6.7). The prevalence of any oral impact was 30.5 %, 36.7 % and 44.1 %, in patients with no OML, one type of OML and more than one type of OML, respectively. Number of types of OML and number and types of oral symptoms were consistently associated with the OIDP scores. Patients who reported bad oral health, patients with ≥ 1 dental attendance, patients with > 1 type of OML, and patients with ≥ 1 type of oral symptoms were more likely than their counterparts in the opposite groups to report any OIDP. The odds ratios (OR) were respectively; 2.9 (95 % CI 1.9-4.5), 2.3 (95 % CI 1.5-3.5), 1.8 (95 % CI 1.1-3.2) and 6.7 (95 % CI 2.6-17.5). Vesiculobullous and ulcerative lesions of OML disease groups associated statistically significantly with OIDP.
OIDP was more frequently affected among skin diseased patients with than without OML. The frequency of the impacts differed according to the number of type of OML, oral symptoms, and OML disease groups. Dentists and dermatologists should pay special attention to skin diseased patients because they are likely to experience oral impacts on daily performances.
PMCID: PMC3461441  PMID: 22768994
dermatology; oral mucosal lesions; oral impact on daily performance; quality of life
2.  Oral mucosal lesions and their association with tobacco use and qat chewing among Yemeni dental patients 
Objectives: This study aimed to assess the prevalence of oral mucosal lesions (OMLs) in patients attending outpatient dental clinics in Sana`a university, Yemen, and to evaluate the association of such lesions with age, gender, and oral habits. Materials and Methods: This cross-sectional study included 409 subjects (272 males, 137 females, age: 15-86 years). Detailed clinical examination was performed in accordance with international criteria. Patient history included age, gender, education, denture wearing and risk habits (tobacco use and qat chewing). Data were analyzed using SPSS 19.00. Results: The prevalence of OMLs was 58.4% with a significant difference between men (63.6%) and women (48.2%; P < 0.05). The most common lesions were fissured tongue (37.2%), hairy tongue (15.9%), tumors and tumor-like lesions (9.8%), qat-induced white lesions (9.3%) and racial pigmentation (5.9%). Overall OMLs prevalence was linked to risk habits and age; qat chewing was statistically significant risk factor for having fissured tongue (OR: 1.77), hairy tongue (OR: 2.74), and white lesions (OR: 2.39) (P < 0.05). Cigarette smoking was statistically significant risk factor for having hairy tongue (OR: 2.82), white lesions (OR: 3.60) and tumors and tumor-like lesions (OR: 2.91) (P < 0.01). The increase in age was statistically significant risk factor for having tumors and tumor-like lesions (OR: 1.04; P < 0.001). Conclusions: The current results indicate that the occurrence of OMLs among Yemeni adults is high and emphasize that risk habits and age have some relationship with the presence of OMLs.
Key words:Oral mucosa, oral lesions, prevalence, smoking, qat chewing.
PMCID: PMC4312669  PMID: 25674309
3.  Prevalence of Oral Mucosal Lesions in Patients with Type 2 Diabetes Attending Hospital Universiti Sains Malaysia 
Diabetes mellitus is associated with a greater likelihood of developing certain oral mucosal disorders. This study was aimed at assessing the prevalence of oral mucosal lesions (OMLs) in patients with type 2 diabetes (DM2) and to investigate the association of such lesions with metabolic control of the disease.
This cross-sectional study involved 391 patients with DM2 and 391 non-diabetic control subjects. Demographic information and data on the duration and type of diabetes, glycosylated hemoglobin (HbA1c) values, medical history, and current use of medication were obtained from medical records. Detailed oral examination was performed in accordance with international criteria.
The prevalence of OMLs was significantly higher among diabetic patients (45.5%) than among control subjects (38.4%) (P = 0.042). Patients with diabetes had a higher prevalence of geographic tongue (GT) (P = 0.017), denture stomatitis (P = 0.018), and angular cheilitis (P = 0.006) than controls. Overall, diabetic patients with poor metabolic control had a significantly higher prevalence of OMLs and xerostomia than patients with moderately and well-controlled disease (P < 0.05).
The prevalence of OMLs was significantly higher in diabetic patients than in control subjects. Higher occurrence of OMLs was significantly associated with poor metabolic control.
PMCID: PMC3773351  PMID: 24043995
diabetes mellitus type 2; prevalence; mouth mucosa; oral pathology
4.  Oral mucosal lesions in elderly dental patients in Sana’a, Yemen 
With aging, the oral mucosa becomes more susceptible to external stimuli. The aims of this study were to obtain baseline data on the prevalence of oral mucosal lesions (OMLs) in a population of elderly Yemeni patients and to investigate differences in the presentation of these findings in relation to age, gender, education level, and the wearing of dentures.
Patients and Methods:
The prevalence of OMLs was assessed by clinical examination of a sample of 310 elderly Yemeni patients aged 60 years and older. A single examiner performed detailed oral examinations of the oral cavity according to international criteria and the World Health Organization codes.
The overall prevalence of OMLs was 77.1%, with a significant difference (P < 0.05) between men (80.3%) and women (69.6%). The prevalence rate of OMLs indicated a significant decrease with advancing age. The most frequently observed lesions were fissured tongue (34.2%), benign tumors (17.1%), hairy tongue (16.5%), and qat-induced white lesions (12.6%). Hairy tongue, qat-induced white lesions, and shammah keratosis were associated with men (P < 0.01, P < 0.05, and P < 0.05, respectively), whereas geographic tongue was associated with women (P < 0.05). The presence of one or more lesions was significantly associated with low education level (P < 0.05). Certain OMLs showed a significant association with smoking and qat chewing (P < 0.05). No association was found between the occurrence of OMLs and denture wearing (P > 0.05).
The present study has shown a high prevalence of oral lesions among Yemeni elders.
PMCID: PMC4428014  PMID: 25984462
Elderly; oral lesions; prevalence; Yemen
5.  Smoking, alcohol consumption and denture use in patients with oral mucosal lesions 
Epidemiologic researches about oral mucosal lesions have been performed in different populations. But, in dermatology outpatients, oral mucosal lesions have not been investigated previously.
We aimed to determine the prevalence of oral mucosal lesions among dermatology outpatients and the relationship between OML and smoking, alcohol intake, denture and dental filling use and skin diseases.
Randomly selected 1041 dermatology outpatients were examined for dermatological diseases and oral mucosal lesions. All of the patients were questioned about smoking, alcohol intake, denture and dental filling use.
In 235 patients, oral mucosal lesions were recorded. 268 (25.7%) of the patients had history of smoking, 42 (4%) drinking alcohol and 180 (17.3%) denture and dental filling. 32 (64%) of the smokers, 54 (30%) of denture users and 10 (23.8%) alcohol consumers had at least one OML. Age and smoking were found as significant risk factors for oral mucosal lesions. Fissured tongue was the most common oral lesion and it was seen significantly higher in patients with denture. Smoking was risk factor for coated tongue and linea alba.
Oral mucosa should be examined carefully even if the patients do not attend with the complaint of oral lesions, especially in elderly patients, smokers and denture users.
PMCID: PMC3241948  PMID: 22408705
oral mucosal lesions; dermatological outpatients; alcohol
6.  Prevalence study of oral mucosal lesions, mucosal variants, and treatment required for patients reporting to a dental school in North India: In accordance with WHO guidelines 
The aim of the study was to evaluate the prevalence of oral mucosal lesions (OML) in adult patients reporting to the dental outpatient department at the Institute of Dental Studies and Technologies, Modinagar, Uttar Pradesh, India. The purpose was to determine the priorities in oral health education, preventive measures, and identify the group in urgent need of treatment.
Materials and Methods:
The study was conducted over a period of 6 months in 2010, when 8866 subjects were offered structured interviews and standardized extraoral and intraoral examinations according to the World Health Organization (WHO) guidelines.
Overall prevalence of OML was 1736 (16.8%), the most prevalent being smoker's palate (10.44%) followed by leukoplakia (2.83%), oral submucous fibrosis (1.97%), oral candidiasis (1.61%), recurrent aphthous stomatitis (1.53%), oral lichen planus (0.8%) and others (0.78%). The highest prevalence of the tobacco habit in both forms was recorded in the group aged 40–44 yearsand those aged between 60 and 64 years who wore dentures. Lesions were most prevalent in those aged 40–44 years with a significant predominance of males at 3:1 (M = 12.6% and F = 4.3%). Patients who consumed tobacco in any form or wore dentures had a significantly higher prevalence of OML (P < 0.001). The highest number of lesions were on the palate (59.7%) followed by buccal mucosa (19.9%). Various normal mucosal variants were recorded. Fordyce's granules (0.13%), fissured tongue (3.3%), leukoedema (1.47%), and lingual varices (2.73%) were also recorded. The tongue showed the highest number of variants (64.4%). Patients were grouped according to the treatment needed under the WHO criteria. One hundred and ninety-seven patients were given oral hygiene instructions only, whereas 1422 patients were advised on change of habit and a follow-up and 674 patients needed definitive treatment.
This study thus highlights diagnostic criteria, multifactorial risk factors to make standard measurements of OML a basis for planning and evaluating oral health programs for data collection.
PMCID: PMC3663163  PMID: 23723730
Epidemiology; mucosal variants; oral mucosal lesions; prevalence; treatment; World Health Organization
7.  High Prevalence of Tobacco Use and Associated Oral Mucosal Lesion Among Interstate Male Migrant Workers in Urban Kerala, India 
Kerala is a highly urbanized state in India and interstate migrant laborers working there forms a marginalized community. It was generally perceived that use of tobacco and alcohol was high among the workers, but there are no epidemiological studies assessing the actual burden.
To estimate the prevalence of use of tobacco and also the prevalence of oral mucosal lesions associated with such use consumption among the adult male interstate migrant workers in North Kerala.
Materials and Methods:
A cross sectional study was carried out among male migrant workers above 18 years working in different factories in urban parts of Kannur district. Total of 244 participants attending routine health check-up camp were assessed for the use of tobacco/alcohol, type, frequency and duration of their use by a questionnaire. The trained dental interns conducted oral cavity examination for detecting oral mucosal lesions associated with tobacco use.
The prevalence of current use of smoked tobacco, smokeless tobacco and alcohol use were 41.8%, 71.7% and 56.6%, respectively among migrants. Oral mucosal lesions (OML) were seen in 36.3% of participants. Among smokeless tobacco users, 44.6% had lesions. Adjusted odds ratio for OML was 4.5 (CI: 1.9 - 19.84) among smokeless tobacco users.
The current use of smokeless tobacco and oral mucosal lesions are highly prevalent among migrant workers.
PMCID: PMC4736070  PMID: 26855720
Tobacco; Oral Mucosal Lesions; Kerala; India
8.  Pseudomonas aeruginosa fur Overlaps with a Gene Encoding a Novel Outer Membrane Lipoprotein, OmlA 
Journal of Bacteriology  1999;181(4):1099-1109.
A novel outer membrane lipoprotein in Pseudomonas aeruginosa is encoded by the omlA gene, which was identified immediately upstream of the fur (ferric uptake regulator) gene. The omlA and fur genes were divergently transcribed and had overlapping promoter regions. The proximal fur P2 promoter and the omlA promoter shared a 5-bp DNA motif for their −10 promoter elements. The distal fur P1 promoter was located within the omlA coding sequence, and the omlA and fur T1 mRNAs overlapped by 154 nucleotides. Optimal expression of both fur and omlA required roughly 200 bp of DNA upstream of the promoter regions, suggesting the presence of cis-acting transcriptional activation elements located within the omlA and fur genes, respectively. The levels of Fur and OmlA proteins had no influence on omlA or fur expression, excluding any trans-acting cross-regulation between fur and omlA. Expression of omlA was constitutive regardless of growth phase, oxygen tension, iron concentration, pH, and temperature. OmlA contained a signal sequence typical of bacterial lipoproteins, with a cysteine as a putative cleavage and lipid attachment site. Inhibition of signal peptidase II by globomycin resulted in failure to process OmlA, thus giving strong evidence that OmlA is a lipoprotein. Cell fractionation followed by Western blot analysis indicated that all OmlA protein is localized in the outer membrane. Mature OmlA was an acidic (pI = 4.5) protein of 17.3 kDa and had close to 40% amino acid sequence identity to SmpA (small protein A) of Escherichia coli, Vibrio cholerae, and Haemophilus influenzae, a protein of unknown function. All P. aeruginosa strains tested as well as Pseudomonas fluorescens were found to produce OmlA. A mutant strain with impaired production of OmlA but no change in the expression of the overlapping fur gene was constructed. The omlA mutant was hypersusceptible to anionic detergents such as sodium dodecyl sulfate and deoxycholate, and it showed increased susceptibility to various antibiotics, including nalidixic acid, rifampin, novobiocin, and chloramphenicol. A structural role of OmlA in maintaining the cell envelope integrity is proposed.
PMCID: PMC93485  PMID: 9973334
9.  Clinical and histological characterization of oral pemphigus lesions in patients with skin diseases: a cross sectional study from Sudan 
BMC Oral Health  2013;13:66.
Pemphigus is a rare group of life-threatening mucocutaneous autoimmune blistering diseases. Frequently, oral lesions precede the cutaneous ones. This study aimed to describe clinical and histological features of oral pemphigus lesions in patients with skin disease has been canceled aged 18 years and above, attending outpatient’s facility of Khartoum Teaching Hospital - Dermatology Clinic, Sudan. In addition, the study aimed to assess the diagnostic significance of routine histolopathology along with immunohistochemical (IHC) examination of formalin-fixed, paraffin-embedded biopsy specimens in patients with oral pemphigus.
A cross-sectional hospital-based study was conducted from October 2008 to January 2009. A total of 588 patients with confirmed skin has been canceled disease diagnosis completed an oral examination and a personal interview. Clinical evaluations supported with histopathology were the methods of diagnosis. IHC was used to confirm the diagnosis. Location, size, and pain of oral lesions were used to measure the oral disease activity.
Twenty-one patients were diagnosed with pemphigus vulgaris (PV), 19 of them (mean age: 43.0; range: 20–72 yrs) presented with oral manifestations. Pemphigus foliaceus was diagnosed in one patient. In PV, female: male ratio was 1.1:1.0. Buccal mucosa was the most commonly affected site. Exclusive oral lesions were detected in 14.2% (3/21). In patients who experienced both skin and oral lesion during their life time, 50.0% (9/18) had oral mucosa as the initial site of involvement, 33.3% (6/18) had skin as the primary site, and simultaneous involvement of both skin and oral mucosa was reported by 5.5% (1/18). Two patients did not provide information regarding the initial site of involvement. Oral lesion activity score was higher in those who reported to live outside Khartoum state, were outdoor workers, had lower education and belonged to Central and Western tribes compared with their counterparts. Histologically, all tissues except one had suprabasal cleft and acantholytic cells. IHC revealed IgG and C3 intercellularly in the epithelium.
PV was the predominating subtype of pemphigus in this study. The majority of patients with PV presented with oral lesions. Clinical and histological pictures of oral PV are in good agreement with the literature. IHC confirmed all diagnoses of PV.
PMCID: PMC3871015  PMID: 24261459
Oral pemphigus; Skin disease; Histology; Immunohistochemistry; Sudan
10.  Oral lesions and dental status among institutionalized orphans in Yemen: A matched case-control study 
The aim of this study was to assess the prevalence of oral mucosal lesions (OMLs) and dental caries and to evaluate oral health practices among institutionalized orphan-children in Sana’a city, Yemen.
Subjects and Methods:
A sample of 202 institutionalized male-orphan-children in the main orphanage in Sana’a city, were matched to 202 non-orphan schoolchildren. Clinical examination included assessment of OMLs based on standard international diagnostic criteria and evaluation of dental status using the Decayed/decayed, Missed/missed and Filled/filled (DMFT/dmft) index according to World Health Organization recommendations. Demographic data and oral hygiene practices were obtained by interviewing each subject using special questionnaire form.
Majority of children were in the 12-15 year age group. Nine types of lesions were reported among orphans; the most common lesions were fissured tongue (24.3%), herpes labialis (7.9%) and traumatic ulcers (2.5%). The occurrence of herpes labialis was found to be significantly higher in orphans than in controls (P < 0.01). The prevalence of dental caries was insignificantly lower among the orphans (84.7%) compared with the non-orphans (89.61%; P = 0.136). The mean dmft score was significantly lower in orphans than in controls (2.28 vs. 3.82; P = 0.001).
The institutionalized children in this orphanage had a high prevalence of OMLs but low prevalence of dental caries, though they revealed poor oral hygiene practices. Effective oral health promotion strategies need to be implemented to improve the oral health and oral health practices of children living in orphanages.
PMCID: PMC4012124  PMID: 24808701
Dental caries; institutionalized orphans; oral lesions
11.  Prevalence of oral mucosal lesions in a brazilian military police population 
Data obtained from oral health surveys are very important for identifying disease-susceptible groups and for developing dental care and prevention programs. So, the purpose of the current article was to investigate the prevalence of oral mucosa lesions (OMLs) in a population of Brazilian police.
Material and Methods
Interviews and oral cavity examinations were performed on a sample of 395 police officers who were randomly selected by the calibrated researcher. The number of individuals was obtained by a sample calculation using the finite population correction. The diagnostic criteria were based on the WHO (1997) criteria and adapted to Brazilian surveys.
In total, 8.61% of the population presented some OML. Traumatic injuries and benign migratory glossitis (BMG) were the most prevalent lesions.
The prevalence of potentially malignant disorders was lower than among the Brazilian population.The most prevalent lesion among the police officers was related to trauma. Patients dissatisfied with oral health had a higher risk of presenting OMLs.
Key words:Mouth disease, mouth mucosa, military personnel, public health, oral pathology, oral leukoplakia.
PMCID: PMC4483325  PMID: 26155334
12.  Development of oligomannose-coated liposome-based nasal vaccine against human parainfluenza virus type 3 
Human parainfluenza viruses (HPIVs) are the etiologic agents of lower respiratory infections and pneumonia in infants, young children and immunocompromised hosts. The overarching goal for the prevention of HPIV infection is the development of an effective vaccine against HPIVs. In the present study, we investigated the effectiveness of oligomannose-coated liposomes (OMLs) as an antigen-delivery system in combination with a synthetic double-stranded RNA analog for the induction of mucosal and systematic immunity against HPIV3. Full-length hemagglutinin-neuraminidase (HN) protein was synthesized using the wheat germ cell-free protein production system and then encapsulated into OML to serve as the antigen. Intranasal administration of the HN-filling OML (OML-HN) with the synthetic double-stranded RNA adjuvant, polyriboinosinic-polyribocytidylic acid [poly(I:C)] generated significant viral-specific systemic and mucosal immune responses as evidenced by the prominent induction of serum IgG and nasal wash IgA, respectively. On the other hand, no significant immune responses were observed in mice immunized with OML-HN without the adjuvant. Furthermore, serum from mice immunized with OML-HN plus poly(I:C) significantly suppressed viral infection in cell culture model. Our results provide the first evidence that intranasal co-administration of OML-encapsulated HN with the poly(I:C) adjuvant augments the viral-specific immunity against HPIV3.
PMCID: PMC3840497  PMID: 24324462
HPIV3; HN; vaccine; oligomannose-coated liposome; adjuvant
13.  A Study on Oral Mucosal Lesions in 3500 Patients with Dermatological Diseases in South India 
Oral mucosal lesions that are observed in the dermatological diseases are categorized under mucocutaneous conditions. The oral lesions in dermatological diseases may be the early aspects of the disease manifestation or the most significant clinical appearance or the only sign/and or symptom of such dermatological diseases and occasionally lesions occur simultaneously in the skin as well as mucous membrane.
This present study attempts to find out the prevalence of oral mucosal lesions in patients with dermatological diseases.
Subjects and Methods:
The study includes 3500 patients who attended out-patient Department of Dermatology. Patients with oral manifestation were subjected for clinical examination in the Department of Oral Pathology. Diagnostic procedures were performed to confirm the clinical oral diagnosis. The results of the study were analyzed by SPSS software version 19.0 (Armonk, NY) and presented as descriptive statistics. Correlation of oral manifestions with their respective dermatological disease was statistically analysed by Pearson's correlation test.(P < 0.05 were considered as statistically significant)
The prevalence rate of oral mucosal lesions in the present study was 1.8% (65/3500). The most frequent lesions observed were psoriasis 32.3% (21/65), lichen planus 18.4% (12/65), Stevens Johnson Syndrome 18.4% (12/65), pemphigus 10.7% (7/65), toxic epidermal necrolysis 4.6% (3/65), systemic lupus erythematosus 3% (2/65), discoid lupus erythematosus 1.5% (1/65), pemphigoid 1.5% (1/65). Gender distribution in the study population was statistically significant (P < 0.001). Employed and unemployed individuals in the study population were statistically significant (P < 0.001). Pearson's correlation analysis of oral manifestations with their respective dermatological disease showed r = 0.466 and signifies a positive correlation and is statistically significant at the 0.01 level (two-tailed).
The prevalence rate of oral mucosal lesions in patients with dermatological diseases was relatively low. However, predominant oral mucosal lesions observed in the study were autoimmune in origin with a high morbidity and mortality index. Hence, multidisciplinary approach will definitely help in the prognosis of patients.
PMCID: PMC4145524  PMID: 25184094
Autoimmune disease; Dermatological manifestations; Immunofluorescence; India; Oral lesions; Prevalence
14.  Extracorporeal Photophoresis 
Executive Summary
To assess the effectiveness, safety and cost-effectiveness of extracorporeal photophoresis (ECP) for the treatment of refractory erythrodermic cutaneous T cell lymphoma (CTCL) and refractory chronic graft versus host disease (cGvHD).
Cutaneous T Cell Lymphoma
Cutaneous T cell lymphoma (CTCL) is a general name for a group of skin affecting disorders caused by malignant white blood cells (T lymphocytes). Cutaneous T cell lymphoma is relatively uncommon and represents slightly more than 2% of all lymphomas in the United States. The most frequently diagnosed form of CTCL is mycosis fungoides (MF) and its leukemic variant Sezary syndrome (SS). The relative frequency and disease-specific 5-year survival of 1,905 primary cutaneous lymphomas classified according to the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification (Appendix 1). Mycosis fungoides had a frequency of 44% and a disease specific 5-year survival of 88%. Sezary syndrome had a frequency of 3% and a disease specific 5-year survival of 24%.
Cutaneous T cell lymphoma has an annual incidence of approximately 0.4 per 100,000 and it mainly occurs in the 5th to 6th decade of life, with a male/female ratio of 2:1. Mycosis fungoides is an indolent lymphoma with patients often having several years of eczematous or dermatitic skin lesions before the diagnosis is finally established. Mycosis fungoides commonly presents as chronic eczematous patches or plaques and can remain stable for many years. Early in the disease biopsies are often difficult to interpret and the diagnosis may only become apparent by observing the patient over time.
The clinical course of MF is unpredictable. Most patients will live normal lives and experience skin symptoms without serious complications. Approximately 10% of MF patients will experience progressive disease involving lymph nodes, peripheral blood, bone marrow and visceral organs. A particular syndrome in these patients involves erythroderma (intense and usually widespread reddening of the skin from dilation of blood vessels, often preceding or associated with exfoliation), and circulating tumour cells. This is known as SS. It has been estimated that approximately 5-10% of CTCL patients have SS. Patients with SS have a median survival of approximately 30 months.
Chronic Graft Versus Host Disease
Allogeneic hematopoietic cell transplantation (HCT) is a treatment used for a variety of malignant and nonmalignant disease of the bone marrow and immune system. The procedure is often associated with serious immunological complications, particularly graft versus host disease (GvHD). A chronic form of GvHD (cGvHD) afflicts many allogeneic HCT recipients, which results in dysfunction of numerous organ systems or even a profound state of immunodeficiency. Chronic GVHD is the most frequent cause of poor long-term outcome and quality of life after allogeneic HCT. The syndrome typically develops several months after transplantation, when the patient may no longer be under the direct care of the transplant team.
Approximately 50% of patients with cGvHD have limited disease and a good prognosis. Of the patients with extensive disease, approximately 60% will respond to treatment and eventually be able to discontinue immunosuppressive therapy. The remaining patients will develop opportunistic infection, or require prolonged treatment with immunosuppressive agents.
Chronic GvHD occurs in at least 30% to 50% of recipients of transplants from human leukocyte antigen matched siblings and at least 60% to 70% of recipients of transplants from unrelated donors. Risk factors include older age of patient or donor, higher degree of histoincompatibility, unrelated versus related donor, use of hematopoietic cells obtained from the blood rather than the marrow, and previous acute GvHD. Bhushan and Collins estimated that the incidence of severe cGvHD has probably increased in recent years because of the use of more unrelated transplants, donor leukocyte infusions, nonmyeloablative transplants and stem cells obtained from the blood rather than the marrow. The syndrome typically occurs 4 to 7 months after transplantation but may begin as early as 2 months or as late as 2 or more years after transplantation. Chronic GvHD may occur by itself, evolve from acute GvHD, or occur after resolution of acute GvHD.
The onset of the syndrome may be abrupt but is frequently insidious with manifestations evolving gradually for several weeks. The extent of involvement varies significantly from mild involvement limited to a few patches of skin to severe involvement of numerous organ systems and profound immunodeficiency. The most commonly involved tissues are the skin, liver, mouth, and eyes. Patients with limited disease have localized skin involvement, evidence of liver dysfunction, or both, whereas those with more involvement of the skin or involvement of other organs have extensive disease.
Cutaneous T Cell Lymphoma
The optimal management of MF is undetermined because of its low prevalence, and its highly variable natural history, with frequent spontaneous remissions and exacerbations and often prolonged survival.
Nonaggressive approaches to therapy are usually warranted with treatment aimed at improving symptoms and physical appearance while limiting toxicity. Given that multiple skin sites are usually involved, the initial treatment choices are usually topical or intralesional corticosteroids or phototherapy using psoralen (a compound found in plants which make the skin temporarily sensitive to ultraviolet A) (PUVA). PUVA is not curative and its influence on disease progression remains uncertain. Repeated courses are usually required which may lead to an increased risk of both melanoma and nonmelanoma skin cancer. For thicker plaques, particularly if localized, radiotherapy with superficial electrons is an option.
“Second line” therapy for early stage disease is often topical chemotherapy, radiotherapy or total skin electron beam radiation (TSEB).
Treatment of advanced stage (IIB-IV) MF usually consists of topical or systemic therapy in refractory or rapidly progressive SS.
Bone marrow transplantation and peripheral blood stem cell transplantation have been used to treat many malignant hematologic disorders (e.g., leukemias) that are refractory to conventional treatment. Reports on the use of these procedures for the treatment of CTCL are limited and mostly consist of case reports or small case series.
Chronic Graft Versus Host Disease
Patients who develop cGvHD require reinstitution of immunosuppressive medication (if already discontinued) or an increase in dosage and possibly addition of other agents. The current literature regarding cGvHD therapy is less than optimal and many recommendations about therapy are based on common practices that await definitive testing. Patients with disease that is extensive by definition but is indolent in clinical appearance may respond to prednisone. However, patients with more aggressive disease are treated with higher doses of corticosteroids and/or cyclosporine.
Numerous salvage therapies have been considered in patients with refractory cGvHD, including ECP. Due to uncertainty around salvage therapies, Bhushan and Collins suggested that ideally, patients with refractory cGvHD should be entered into clinical trials.
Two Ontario expert consultants jointly estimated that there may be approximately 30 new erythrodermic treatment resistant CTCL patients and 30 new treatment resistant cGvHD patients per year who are unresponsive to other forms of therapy and may be candidates for ECP.
Extracorporeal photopheresis is a procedure that was initially developed as a treatment for CTCL, particularly SS.
Current Technique
Extracorporeal photopheresis is an immunomodulatory technique based on pheresis of light sensitive cells. Whole blood is removed from patients followed by pheresis. Lymphocytes are separated by centrifugation to create a concentrated layer of white blood cells. The lymphocyte layer is treated with methoxsalen (a drug that sensitizes the lymphocytes to light) and exposed to UVA, following which the lymphocytes are returned to the patient. Red blood cells and plasma are returned to the patient between each cycle.
Photosensitization is achieved by administering methoxsalen to the patient orally 2 hours before the procedure, or by injecting methoxsalen directly ino the leucocyte rich fraction. The latter approach avoids potential side effects such as nausea, and provides a more consistent drug level within the machine.
In general, from the time the intravenous line is inserted until the white blood cells are returned to the patient takes approximately 2.5-3.5 hours.
For CTCL, the treatment schedule is generally 2 consecutive days every 4 weeks for a median of 6 months. For cGvHD, an expert in the field estimated that the treatment schedule would be 3 times a week for the 1st month, then 2 consecutive days every 2 weeks after that (i.e., 4 treatments a month) for a median of 6 to 9 months.
Regulatory Status
The UVAR XTS Photopheresis System is licensed by Health Canada as a Class 3 medical device (license # 7703) for the “palliative treatment of skin manifestations of CTCL.” It is not licensed for the treatment of cGvHD.
UVADEX (sterile solution methoxsalen) is not licensed by Health Canada, but can be used in Canada via the Special Access Program. (Personal communication, Therakos, February 16, 2006)
According to the manufacturer, the UVAR XTS photopheresis system licensed by Health Canada can also be used with oral methoxsalen. (Personal communication, Therakos, February 16, 2006) However, oral methoxsalen is associated with side effects, must be taken by the patient in advance of ECP, and has variable absorption in the gastrointestinal tract.
According to Health Canada, UVADEX is not approved for use in Canada. In addition, a review of the Product Monographs of the methoxsalen products that have been approved in Canada showed that none of them have been approved for oral administration in combination with the UVAR XTS photophoresis system for “the palliative treatment of the skin manifestations of cutaneous T-cell Lymphoma”.
In the United States, the UVAR XTS Photopheresis System is approved by the Food and Drug Administration (FDA) for “use in the ultraviolet-A (UVA) irradiation in the presence of the photoactive drug methoxsalen of extracorporeally circulating leukocyte-enriched blood in the palliative treatment of the skin manifestations of CTCL in persons who have not been responsive to other therapy.”
UVADEX is approved by the FDA for use in conjunction with UVR XTS photopheresis system for “use in the ultraviolet-A (UVA) irradiation in the presence of the photoactive drug methoxsalen of extracorporeally circulating leukocyte-enriched blood in the palliative treatment of the skin manifestations of CTCL in persons who have not been responsive to other therapy.”
The use of the UVAR XTS photopheresis system or UVADEX for cGvHD is an off-label use of a FDA approved device/drug.
Summary of Findings
The quality of the trials was examined.
As stated by the GRADE Working Group, the following definitions were used in grading the quality of the evidence.
Cutaneous T Cell Lymphoma
Overall, there is low-quality evidence that ECP improves response rates and survival in patients with refractory erythrodermic CTCL (Table 1).
Limitations in the literature related to ECP for the treatment of refractory erythrodermic CTCL include the following:
Different treatment regimens.
Variety of forms of CTCL (and not necessarily treatment resistant) - MF, erythrodermic MF, SS.
SS with peripheral blood involvement → role of T cell clonality reporting?
Case series (1 small crossover RCT with several limitations)
Small sample sizes.
Response criteria not clearly defined/consistent.
Unclear how concomitant therapy contributed to responses.
Variation in definitions of concomitant therapy
Comparison to historical controls.
Some patients were excluded from analysis because of progression of disease, toxicity and other reasons.
Unclear/strange statistics
Quality of life not reported as an outcome of interest.
The reported CR range is ~ 16% to 23% and the overall reported CR/PR range is ~ 33% to 80%.
The wide range in reported responses to ECP appears to be due to the variability of the patients treated and the way in which the data were presented and analyzed.
Many patients, in mostly retrospective case series, were concurrently on other therapies and were not assessed for comparability of diagnosis or disease stage (MF versus SS; erythrodermic versus not erythrodermic). Blood involvement in patients receiving ECP (e.g., T cell clonality) was not consistently reported, especially in earlier studies. The definitions of partial and complete response also are not standardized or consistent between studies.
Quality of life was reported in one study; however, the scale was developed by the authors and is not a standard validated scale.
Adverse events associated with ECP appear to be uncommon and most involve catheter related infections and hypotension caused by volume depletion.
GRADE Quality of Studies – Extracorporeal Photopheresis for Refractory Erythrodermic Cutaneous T-Cell Lymphoma
Chronic Graft-Versus-Host Disease
Overall, there is low-quality evidence that ECP improves response rates and survival in patients with refractory cGvHD (Table 2).
Patients in the studies had stem cell transplants due to a variety of hematological disorders (e.g., leukemias, aplastic anemia, thalassemia major, Hodgkin’s lymphoma, non Hodgkin’s lymphoma).
In 2001, The Blue Cross Blue Shield Technology Evaluation Centre concluded that ECP meets the TEC criteria as treatment of cGvHD that is refractory to established therapy.
The Catalan health technology assessment (also published in 2001) concluded that ECP is a new but experimental therapeutic alternative for the treatment of the erythrodermal phase of CTCL and cGvHD in allogenic HPTC and that this therapy should be evaluated in the framework of a RCT.
Quality of life (Lansky/Karnofsky play performance score) was reported in 1 study.
The patients in the studies were all refractory to steroids and other immunosuppressive agents, and these drugs were frequently continued concomitantly with ECP.
Criteria for assessment of organ improvement in cGvHD are variable, but PR was typically defined as >50% improvement from baseline parameters and CR as complete resolution of organ involvement.
Followup was variable and incomplete among the studies.
GRADE Quality of Studies – ECP for Refractory cGvHD
As per the GRADE Working Group, overall recommendations consider 4 main factors.
The tradeoffs, taking into account the estimated size of the effect for the main outcome, the confidence limits around those estimates and the relative value placed on the outcome.
The quality of the evidence (Tables 1 and 2).
Translation of the evidence into practice in a specific setting, taking into consideration important factors that could be expected to modify the size of the expected effects such as proximity to a hospital or availability of necessary expertise.
Uncertainty about the baseline risk for the population of interest.
The GRADE Working Group also recommends that incremental costs of healthcare alternatives should be considered explicitly alongside the expected health benefits and harms. Recommendations rely on judgments about the value of the incremental health benefits in relation to the incremental costs. The last column in Table 3 is the overall trade-off between benefits and harms and incorporates any risk/uncertainty.
For refractory erythrodermic CTCL, the overall GRADE and strength of the recommendation is “weak” – the quality of the evidence is “low” (uncertainties due to methodological limitations in the study design in terms of study quality and directness), and the corresponding risk/uncertainty is increased due to an annual budget impact of approximately $1.5M Cdn (based on 30 patients) while the cost-effectiveness of ECP is unknown and difficult to estimate considering that there are no high quality studies of effectiveness. The device is licensed by Health Canada, but the sterile solution of methoxsalen is not licensed.
With an annual budget impact of $1.5 M Cdn (based on 30 patients), and the current expenditure is $1.3M Cdn (for out of country for 7 patients), the potential cost savings based on 30 patients with refractory erythrodermic CTCL is about $3.8 M Cdn (annual).
For refractory cGvHD, the overall GRADE and strength of the recommendation is “weak” – the quality of the evidence is “low” (uncertainties due to methodological limitations in the study design in terms of study quality and directness), and the corresponding risk/uncertainty is increased due to a budget impact of approximately $1.5M Cdn while the cost-effectiveness of ECP is unknown and difficult to estimate considering that there are no high quality studies of effectiveness. Both the device and sterile solution are not licensed by Health Canada for the treatment of cGvHD.
If all the ECP procedures for patients with refractory erythrodermic CTCL and refractory cGvHD were performed in Ontario, the annual budget impact would be approximately $3M Cdn.
Overall GRADE and Strength of Recommendation (Including Uncertainty)
PMCID: PMC3379535  PMID: 23074497
15.  Epidemiology of Pemphigus in Tehran, Iran: A 20-Year Retrospective Study  
Background and aims
Pemphigus is a chronic autoimmune and vesiculobollous disease that can affect skin and different mucous membrane surfaces. Primary manifestations occur in oral cavity in almost 60% of cases. The purpose of the present study was to evaluate the epidemiology of pemphigus in Tehran, Iran in a 20-year period.
Materials and methods
A retrospective study was conducted on the records of 1560 patients diagnosed with different types of pemphigus in Razi Hospital of Dermatology in Tehran from March 1985 to March 2005. A questionnaire was prepared to collect information regarding age, sex, bedridden duration, pemphigus subtype, sites of involvement, recurrence and mortality rate. Data was analyzed using chi-square test with significant level of P < 0.05.
There was a female predominance with a male to female ratio of 1:1.53. In nearly half of the patients, only the oral mucous membranes were affected. One hundred and fifty had only skin lesions and 261 cases had both skin and oral mucosal lesions. Involvement of esophageal and vaginal mucous membranes without skin lesions was observed in 150 patients and 298 cases had esophageal and vaginal mucosal involvement as well as skin lesions. Pemphigus vulgaris was the most common type, with the mean age of 44.6 years. Oral mucous membrane was the most frequent location where pemphigus vulgaris was observed. 1265 patients recovered which 52.2% of them had only oral lesions. Average of bedridden duration was 2.9 months. The highest recurrence rate was seen in patients with skin lesions exclusively. There was a significant difference between recurrences of lesions and location of involvement (P < 0.05). Thirty six patients had died from of the disease.
The mean age of the disease onset in the present study was found to be a decade earlier than the other parts of the world. Recurrence and mortality rates were lower in patients with only oral lesions and their prognosis was better.
PMCID: PMC3529885  PMID: 23277844
Epidemiology; Iran; pemphigus; vesiculobullous
16.  Lower extremity strength and power asymmetry assessment in healthy and mobility-limited populations: reliability and association with physical functioning 
Background and aims
This study assessed the reliability of evaluating asymmetrical strength and power deficits in the lower limbs of healthy middle-aged, healthy older and mobility-limited elders. We also explored the relationship between limb asymmetry and physical functioning.
We evaluated baseline knee extension strength and power asymmetry data from a cohort of older adults (n=57; 74.2±0.9 yrs, 26 male) who participated in a lower body strength training study (TS) and from a cross-sectional study of community dwelling volunteers. Cross-sectional participants were recruited into: healthy middle-aged (MH) (n=31; 47.4±4.8 yrs, 14 male), healthy older (OH) (n=28; 74.0±3.6 yrs, 16 male) and mobility-limited older (OML) (n=34; 77.8±4.5 yrs, 16 male) groups. Knee extensor strength (1RM) and power asymmetry at 40% and 70% of 1RM were evaluated for test-retest reliability using intraclass correlation coefficients (ICCs).
Knee extension 1RM, and peak power at 40% and 70% asymmetry ICCs exhibited excellent to good reliability in the TS and OML groups (TS= 0.8, 0.7 and 0.7, respectively; OML= 0.7, 0.7, and 0.9, respectively) but not in the MH and OH groups. No consistent association between lower limb asymmetry and measures of physical functioning was observed.
Assessment of lower limb strength and power asymmetry is more reliable in mobility-limited elders when compared to healthy middle-aged and older subjects. The relationship of lower limb asymmetry to physical functioning is poor, in contrast to associations between the absolute strength and power of the individual limbs and physical functioning.
PMCID: PMC4423605  PMID: 19940556
Asymmetry; mobility-limited; power; reliability; strength
17.  Liposomes and nanotechnology in drug development: focus on oncotargets 
Nanotechnology is the development of an engineered device at the atomic, molecular, and macromolecular level in the nanometer range. Advances in nanotechnology have proven beneficial in therapeutic fields such as drug-delivery and gene/protein delivery. Antigen delivery systems are important for inducing and modifying immune responses. In cellular immunity, cytotoxic T lymphocytes (CTLs) are important in the host defense against tumors. Key to the development of CTL-inducible vaccines is the ability to deliver antigens to antigen-presenting cells efficiently and to induce the subsequent activation of T cell-mediated immunity without adjuvants, as they can induce excessive inflammation leading to systemic febrile disease. Since expression and cloning methods for tumor-associated antigens have been reported, cancer vaccines that induce effective cell immunity may be promising therapeutic candidates, but Th2 cells are undesirable for use in cancer immunotherapy. Peptide vaccines have immunological and economic advantages as cancer vaccines because CTL epitope peptides from tumor-associated antigens have high antigen-specificity. However, cancer vaccines have had limited effectiveness in clinical responses due to the ability of cancer cells to “escape” from cancer immunity and a low efficiency of antigen-specific CTL induction due to immunogenic-free synthetic peptides. In contrast, carbohydrate-decorated particles such as carbohydrate-coated liposomes with encapsulated antigens might be more suitable as antigen delivery vehicles to antigen-presenting cells. Oligomannose-coated liposomes (OML) can eliminate established tumors in mouse cancer models. In addition, OMLs with an encased antigen can induce antigen-specific CTLs from peripheral blood mononuclear cells obtained from patients. Feasibility studies of OML-based vaccines have revealed their potential for clinical use as vaccines for diseases where CTLs act as effector cells. Furthermore, use of the hepatitis B core particle, in which tumor-antigen epitopes are set, has consistently been shown to induce strong CTL responses without the use of an adjuvant. Thus, nanoparticles may provide a new prophylactic strategy for infectious disease and therapeutic approaches for cancer via the induction of T-cell immunity.
PMCID: PMC3446859  PMID: 23028222
adult T cell leukemia; cytotoxic T lymphocytes; oligomannose-coated liposomes; vaccine
18.  The pattern of skin diseases in the Qassim region of Saudi Arabia: What the primary care physician should know 
Annals of Saudi Medicine  2010;30(6):448-453.
Epidemiological studies to determine the burden of skin diseases are important for proper health care planning. The purpose of this study was to find the pattern of skin diseases in our patients attending university-affiliated dermatologic clinics in the Qassim region.
We conducted a prospective study of all Saudi patients attending the Qassim University Medical College-affiliated dermatology clinics of the Ministry of Health for a period of 12 months from 1 March 2008 to 28 February 2009.
The study included 3051 patients comprising 1786 (58.5%) males and 1265 (41.5%) females. Males outnumbered females (P<.05) (male-to-female ratio, 1.4:1). The mean age (standard error of the mean) of the patients was 25.3 (0.27) years. About 71% of the patients were between 5 and 34 years of age. The top five skin diseases were eczema/ dermatitis (19.5%), viral infections (16.6%), pilosebaceous disorders (14.4%), pigmentary lesions (11.2%) and hair disorders (7.6%). The major disorder in males was viral skin infections (20.0%), while eczema/dermatitis (20.7%) constituted the most prevalent skin disease in females. Seasonal variations were recorded in cases of pigmentary lesions, papulosquamous disorders and protozoal infections.
Infectious skin diseases, eczema/dermatitis, pilosebaceous disorders, pigmentary lesions and hair disorders ranked as the top five skin diseases. Appropriate training programs for diagnosing and managing common skin diseases should be initiated for primary health care physicians and other general practitioners so as to decrease referrals to dermatology clinics.
PMCID: PMC2994160  PMID: 21060156
19.  Prevalence of Oral, Skin, and Oral and Skin Lesions of Lichen Planus in Patients Visiting a Dental School in Southern India 
Indian Journal of Dermatology  2012;57(2):107-109.
Lichen planus (LP) is a mucocutaneous disease that is relatively common among adult population. LP can present as skin and oral lesions. This study highlights the prevalence of oral, skin, and oral and skin lesions of LP.
The aim of this study was to evaluate the prevalence of oral, skin, and oral and skin lesions of LP from a population of patients attending the Department of Oral Medicine and Radiodiagnosis, Pushpagiri College of Dental Sciences, Tiruvalla, Kerala, India.
Materials and Methods:
A cross-sectional study was designed to evaluate the prevalence of oral, skin, and oral and skin lesions of LP. This is a ongoing prospective study with results of 2 years being reported. LP was diagnosed on the basis of clinical presentation and histopathological analysis of mucosal and skin biopsy done for all patients suspected of having LP. Statistical analysis was carried out using SPSS (Statistical package for social sciences) software version 14. To test the statistical significance, chi-square test was used.
Out of 18,306 patients screened, 8,040 were males and 10,266 females. LP was seen in 118 cases (0.64%). Increased prevalence of LP was observed in middle age adults (40–60 years age group) with lowest age of 12 years and highest age of 65 years. No statistically significant differences were observed between the genders in skin LP group (P=0.12) and in oral and skin LP groups (P=0.06); however, a strong female predilection was seen in oral LP group (P=0.000036). The prevalence of cutaneous LP in oral LP patients was 0.06%.
This study showed an increased prevalence of oral LP than skin LP, and oral and skin LP with a female predominance.
PMCID: PMC3352630  PMID: 22615505
Lichen planus; mucocutaneous; precancerous
20.  Dermatological Findings in Turkish Paediatric Haematology-Oncology Patients 
The Eurasian Journal of Medicine  2016;48(2):107-111.
Diagnoses of skin, mucosae, hair and nail manifestations in malignant diseases are often challenging because of life-threatening drug reactions, opportunistic infections or skin involvement of primary processes. Description of morphology, configuration and distribution of lesions is important in order to differentiate the self-healing eruptions from serious side effects of chemotherapy. There are case reports from Turkey including dermatological manifestations of malignancies and case series in adult patients but there are no published large group studies assessing all manifestations in children. The aim of this study was to evaluate the morphological features of dermatological findings in children with haemato-oncological diseases.
Materials and Methods:
The study was performed at the Erciyes University, Faculty of Medicine Pediatric Hematology-Oncology Clinic, Turkey. Three dermatologists daily consulted all patients admitted to the clinic during a one-year period.
The study group comprised of 157 children (79 female/78 male) aged 1–16 years (mean 7.19±4.63). Detailed dermatological examinations were performed, including oral-genital mucosae, hair and nails. Thorough skin examination revealed that 70% of the patients exhibited at least one dermatological finding. Generalized xerosis and hyperpigmentation were the most common findings among patients undergoing chemotherapy (24.19%). Multiple nevi on at least 10 covered areas were very frequent among patients undergoing long-term chemotherapy (18.47%). Three were identified as dysplastic nevus, but malignant transformation was not observed during the one-year study period.
Regular dermatological consultation may help resolve the diagnostic and therapeutic problems in paediatric haemato-oncology clinics.
PMCID: PMC4970547  PMID: 27551173
Children; dermatologic findings; haemato-oncologic diseases; paediatric dermatology
21.  Synaptic characteristics of dentate gyrus axonal boutons and their relationships with aging, menopause, and memory in female rhesus monkeys 
Age-related memory impairment occurs in many mammalian species including humans. Moreover, women undergoing the menopausal transition often complain of problems with memory. We recently reported that rhesus monkeys display age- and menopause-related recognition memory impairment on a hippocampus-reliant test (delayed nonmatching-to-sample; DNMS). In the same monkeys, perforated synapse densities in the dentate gyrus outer molecular layer (OML) correlated with DNMS recognition accuracy, while total axospinous synapse density was similar across age and menses groups. The current study examined whether synaptic characteristics of OML axonal boutons are coupled with age- or menopause-related memory deficits. Using serial section electron microscopy, we measured the frequencies of single-synapse boutons (SSBs), multiple-synapse boutons (MSBs), and boutons with no apparent synaptic contacts (non-synaptic boutons, NSBs) in the OML. Aged females had double the percentage of NSBs as compared to young females and this measure correlated positively and inversely with DNMS acquisition (number of trials to criterion) and delay performance (average accuracy), respectively. Aged compared to young females also had a lower frequency of MSBs and a lower number of synaptic contacts per MSB, and the latter variable inversely correlated with DNMS acquisition. Although proportions of NSBs, SSBs and MSBs were similar across menses groups, compared to pre-menopausal monkeys, peri/post-menopausal monkeys had fewer MSBs contacting one or more segmented perforated synapse and the abundance of this bouton subtype positively correlated with DNMS performance. These results suggest that age- and menopause-related shifts in OML synaptic subtypes may be coupled with deficits in task acquisition and recognition memory.
PMCID: PMC3103072  PMID: 21613486
delayed nonmatching-to-sample test; menopause; multiple-synapse bouton; serial sections; recognition memory
22.  Characterization of the omlA gene from different serotypes of Actinobacillus pleuropneumoniae: A new insight into an old approach 
Genetics and Molecular Biology  2013;36(2):243-251.
The OmlA protein is a virulence factor of Actinobacillus pleuropneumoniae, an important pathogen in pigs. The polymorphisms present in the omlA gene sequence of 15 reference serotypes of A. pleuropneumoniae and non-serotypable isolates were assessed to determine the possible evolutionary relationship among them and to validate the importance of this gene as a molecular marker for the characterization of this bacterium. Divergence among the 15 serotypes of A. pleuropneumoniae probably resulted initially from two major evolutionary events that led to subsequent differentiation into nine groups. This differentiation makes it possible to characterize most of the serotypes by using bionformatics, thereby avoiding problems with immunological cross-reactivity. A conserved α-helix common to all the serotypes was most likely involved in connecting the protein to the outer membrane and acting as a signal peptide. A previously unknown gene duplication was also identified and could contribute to the genetic variability that makes it difficult to serotype some isolates. Our data support the importance of the omlA gene in the biology of A. pleuropneumoniae and provide a new area of research into the OmlA protein.
PMCID: PMC3715291  PMID: 23885207
Actinobacillus pleuropneumoniae; omlA gene; phylogenetic reconstruction; porcine pleuropneumonia
23.  A Case-Control Study of Oral Epithelial Proliferative Markers among Sudanese Toombak Dippers Using Micronuclei Assay, Argyrophilic Nucleolar Organizer Region, Papanicolaou and Crystal Violet Methods 
Rare Tumors  2013;5(3):e31.
The use of Toombak has been reported to play a major role in the etiology of oral cancer in Sudan. The cellular proliferative activity on the oral epithelium of 210 Toombak dippers was assessed by applying the micronuclei frequency, mean argyrophilic nucleolar organizer region (AgNOR) counts, Papanicolaou method, and 1% crystal violet stain. Participants were divided into 3 groups: 200 were apparently healthy individuals, 100 were Toombak users (cases), 100 were non-tobacco users (control) and 10 were patients with oral squamous cell carcinomas. Cytological atypia was identified among 4 (4%). Toombak users and was not found among the control group (P<0.04). The micronuclei frequencies were higher in Toombak users (1.026) than in the control group (0.356) (P<0.0001). The mean AgNOR counts in Toombak users (2.423) were higher than control group (1.303) (P<0.0001). Neither Toombak users nor control group showed mitotic figures in 1% crystal violet method. The results of this research showed that Toombak dipping is a high risk factor for increase in the cellular proliferation in the oral mucosa. The cytological proliferative marker methods used are useful for screening Toombak users.
PMCID: PMC3804806  PMID: 24179643
micronuclei; Toombak; crystal violet; AgNOR; oral cancer
24.  Pattern of Skin Diseases at University of Benin Teaching Hospital, Benin City, Edo State, South-South Nigeria: A 12 Month Prospective Study 
Global Journal of Health Science  2012;4(3):148-157.
Background and Objective:
This study aims to look at the pattern and incidence of skin diseases seen in Dermatology/Venereology clinic at the University of Benin Teaching Hospital, Benin City, Edo State, South-South Zone, Nigeria and compare it with other zones of Nigeria.
Materials and Methods:
This was a prospective study on pattern and incidence of skin diseases in new patients presenting at the Dermatology/Venereology outpatient clinic of the University of Benin Teaching Hospital, Benin City, Edo State, South-South, Nigeria, from September 2006 to August 2007. All patients were seen by the researchers. Diagnosis were made clinically and sometimes with the support of histopathology.
A total number of 4786 patients were seen during the study period and these comprised 2647 HIV/AIDS patients and 2112 pure Dermatological patients. Out of 4786 patients, 755 (15.8%) were new patients. The new patients comprised 96 (12.7%) children patients (< 15 years) and 659 (83.7%) adult patients (>15years). The ages of the patients ranged from 2 weeks to 80 years and more than two-third were < 40 years. There were 354 males (46.9%) and 401 females (53.1%). This represents female: male ratio of 1.1: 1. Eczematous dermatitis accounted for 20.9% of the skin diseases and was the most common of the skin diseases observed. This is consistent with observation from other zones in Nigeria. Other skin diseases observed in order of frequencies include: Papulosqamous disorder (9.0%), Infectious skin diseases like fungal, viral, bacterial and parasitic infestation, at 7.9%, 7.7%, 2.3% and 2.1% respectively. Pigmentary disorders (5.0%), hair disorders (4.2%) and Benign neoplastic skin disease (6.5%). All the patients that had neurofibromatosis were females (1.9%). HIV-related skin diseases were observed to have increased remarkably (7.9%) with Kaposi’s sarcoma, papular pruritic eruptions and drug eruptions being the commonest mode of presentation.
The current pattern of skin diseases in Benin City, South-South Nigeria seems to follow a similar pattern observed in other Geo-political zones in Nigeria. The eczematous dermatitis took the lead and the impact of HIV-related skin diseases were vividly noticed to be on the increase. Connective tissue disorder and cutaneous malignancies were low in their occurrences. Our findings showed no major differences in the pattern of skin diseases when compared with other zones of Nigeria. Allergic skin diseases were observed to be on the increase in all the geo-political zones; possibly due to increase in urbanization and its attending socio-economic burden.
PMCID: PMC4776906  PMID: 22980241
skin diseases; eczematous dermatitis; infectious skin diseases
25.  DNA methylome analysis identifies epigenetic silencing of FHIT as a determining factor for radiosensitivity in oral cancer: an outcome-predicting and treatment-implicating study 
Oncotarget  2014;6(2):915-934.
Radioresistance is still an emerging problem for radiotherapy of oral cancer. Aberrant epigenetic alterations play an important role in cancer development, yet the role of such alterations in radioresistance of oral cancer is not fully explored. Using a methylation microarray, we identified promoter hypermethylation of FHIT (fragile histidine triad) in radioresistant OML1-R cells, established from hypo-fractionated irradiation of parental OML1 radiosensitive oral cancer cells. Further analysis confirmed that transcriptional repression of FHIT was due to promoter hypermethylation, H3K27me3 and overexpression of methyltransferase EZH2 in OML1-R cells. Epigenetic interventions or depletion of EZH2 restored FHIT expression. Ectopic expression of FHIT inhibited tumor growth in both in vitro and in vivo models, while also resensitizing radioresistant cancer cells to irradiation, by restoring Chk2 phosphorylation and G2/M arrest. Clinically, promoter hypermethylation of FHIT inversely correlated with its expression and independently predicted both locoregional control and overall survival in 40 match-paired oral cancer patient samples. Further in vivo therapeutic experiments confirmed that inhibition of DNA methylation significantly resensitized radioresistant oral cancer cell xenograft tumors. These results show that epigenetic silencing of FHIT contributes partially to radioresistance and predicts clinical outcomes in irradiated oral cancer. The radiosensitizing effect of epigenetic interventions warrants further clinical investigation.
PMCID: PMC4359265  PMID: 25460508
Epigenetics; FHIT; oral cancer; radiotherapy; resistance

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