Heterogeneity in amount of growth factors secreted by platelets in platelet-rich plasma samples from alopecia patients

Platelet α-granules release growth factors (GFs) that promote healing and tissue regeneration. Platelet-rich plasma (PRP) is shown to be beneficial in treating alopecia, and however, clinical response can be inconsistent. Due to several fold enrichment of platelets secreting large quantities of GFs following PRP injections, heterogeneity in amounts of GFs secreted by platelets may contribute to inconsistent clinical responses. Herein, we evaluated factors that could potentially contribute to heterogeneous secretion of GFs by platelets. We measured platelet secretion of transforming growth factor beta1 (TGFβ1), platelet-derived growth factor (PDGF-BB), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF2) in aliquots of de-identified PRP samples from female patients undergoing therapy in the hair disease clinic. Although secretion of GFs by platelets was comparable in PRP samples of patients with non-cicatricial and cicatricial alopecia, a Shapiro-Wilk test for normal distribution indicated significant variability across all patient samples. The amount of GF secreted by platelets was comparable when PRP prepared from two FDA-cleared devices with distinct techniques were compared. We provide evidence of platelets secreting heterogeneous amounts of GFs within each sample as high and low secretion of random factors could be simultaneously detected. These results suggest inherent heterogeneity in secretion of GFs by platelets in patient samples that are not influenced by the device used to prepare PRP. Since some GFs could have antagonistic effects on hair growth, a balance between amounts of growth promoting and inhibiting factors may be crucial in determining clinical response to PRP therapy.     

Total hemolytic complement (CH50) and its fractions (C3 and C4) in the sera of patients with carcinoma of the oral cavity,uterine cervix,and breast

The total hemolytic complement activity of CH50 and its fractions C3 and C4 was determined in the sera of 196 patients with carcinoma of the oral cavity, 172 patients with carcinoma of the uterine cervix, and 166 patients with breast cancer. The values were compared with those of 18 patients with mammary dysplasia, 32 patients with mild to moderate dysplasia of the cervix, and 100 healthy, normal age- and sex-matched controls. No alterations in CH50, C3, and C4 were observed in the sera of patients with benign lesions, whereas a significant rise in the three factors was observed in all the cancer patients studied. The complement activity increased significantly with the progression of the disease up to stage III and remained persistently elevated thereafter. Patients who had a clinical cure had normal levels of CH50, C3, and C4, whereas the values remained elevated in patients who were still undergoing treatment for residual lesions.     

Subtype‐specific differences in transmission cluster dynamics of HIV‐1 B and CRF01_AE in New South Wales,Australia

IntroductionThe human immunodeficiency virus 1 (HIV‐1) pandemic is characterized by numerous distinct sub‐epidemics (clusters) that continually fuel local transmission. The aims of this study were to identify active growing clusters, to understand which factors most influence the transmission dynamics, how these vary between different subtypes and how this information might contribute to effective public health responses.MethodsWe used HIV‐1 genomic sequence data linked to demographic factors that accounted for approximately 70% of all new HIV‐1 notifications in New South Wales (NSW). We assessed differences in transmission cluster dynamics between subtype B and circulating recombinant form 01_AE (CRF01_AE). Separate phylogenetic trees were estimated using 2919 subtype B and 473 CRF01_AE sequences sampled between 2004 and 2018 in combination with global sequence data and NSW‐specific clades were classified as clusters, pairs or singletons. Significant differences in demographics between subtypes were assessed with Chi‐Square statistics.ResultsWe identified 104 subtype B and 11 CRF01_AE growing clusters containing a maximum of 29 and 11 sequences for subtype B and CRF01_AE respectively. We observed a > 2‐fold increase in the number of NSW‐specific CRF01_AE clades over time. Subtype B clusters were associated with individuals reporting men who have sex with men (MSM) as their transmission risk factor, being born in Australia, and being diagnosed during the early stage of infection (p < 0.01). CRF01_AE infections clusters were associated with infections among individuals diagnosed during the early stage of infection (p < 0.05) and CRF01_AE singletons were more likely to be from infections among individuals reporting heterosexual transmission (p < 0.05). We found six subtype B clusters with an above‐average growth rate (>1.5 sequences / 6‐months) and which consisted of a majority of infections among MSM. We also found four active growing CRF01_AE clusters containing only infections among MSM. Finally, we found 47 subtype B and seven CRF01_AE clusters that contained a large gap in time (>1 year) between infections and may be indicative of intermediate transmissions via undiagnosed individuals.ConclusionsThe large number of active and growing clusters among MSM are the driving force of the ongoing epidemic in NSW for subtype B and CRF01_AE.     

Effect of a selective cyclooxygenase-2 inhibitor, nimesulide, on the growth of lung tumors and their expression of cyclooxygenase-2 and peroxisome proliferator- activated receptor-gamma.

PURPOSE: The objectives of this study were to evaluate the effect of a cyclooxygenase (COX)-2 inhibitor, nimesulide, on the growth inhibition of s.c. human lung A549 adenocarcinoma tumors and to assess the effect of nimesulide on the expression of COX-2 and peroxisome proliferator-activated receptor (PPAR)-gamma in lung tumors harvested from mice. EXPERIMENTAL DESIGN: Female nu/nu mice were xenografted with s.c. A549 lung tumors, and 1 day after tumor implantation, the mice were fed with a diet containing nimesulide at 250-1500 ppm doses. Tumor dimensions were monitored twice weekly, and tumor samples isolated from mice were used to determine prostaglandin E(2) (PGE(2)) levels by enzyme immunoassay, expression of COX-2 and PPAR-gamma by Western blotting and immunohistochemistry. Furthermore, the induction of apoptosis in tumor specimens was determined by terminal deoxynucleotidyl transferase-mediated nick end labeling staining. RESULTS: Nimesulide treatment showed a dose-dependent growth-inhibitory effect of A549 tumors with a maximum of 77.7% inhibition at 1500 ppm of nimesulide. Western blotting experiments showed similar expression of COX-2 in both control and nimesulide (250-1500 ppm)-treated mice tumor tissues. PPAR-gamma was found to be overexpressed as a result of 1500 ppm nimesulide treatment and was not detected in tumors from control or 250-1000 ppm nimesulide-treated mice. Nimesulide (1500 ppm) significantly reduced intratumor PGE(2) levels (P < 0.001) and induced apoptosis in 25% of tumor cells as compared with control tumors. CONCLUSIONS: Nimesulide (1500 ppm) induced growth inhibition of A549 lung tumors is associated with the reduction of intratumor PGE(2) levels but without affecting the expression of COX-2. Nimesulide-induced enhancement of the expression of PPAR-gamma may also contribute to its antitumor effect, which needs to be further investigated.     

Drug induced oral erythema multiforme: Case report

Introduction:Drug induced oral erythema multiforme a rare clinical entity which involves only the lips and oral mucosa without skin involvement. These lesions are difficult in diagnosing with other oral ulcerative lesions with similar clinical manifestations.Patient concerns:This article presents 2 case reports of Oral erythema multiforme in which drugs were the precipitating factor. Its etiopathogenesis, differential diagnosis and treatment modalities of the disease is discussed.Diagnosis:Based on patient''s complaints, drug history and clinical appearance, provisional diagnosis of drug induced erythema multiforme was considered.Intervention:For case 1, patient was instructed to discontinue usage of drug and prescribed systemic steroid (Prednisolone 10 mg/d) for a week along with germicidal drugs to prevent secondary infection. Medication was tapered to 5 mg/d after first week.For case 2, patient was instructed to discontinue the drug and systemic steroid prednisolone 20 mg /d for 1 week with tapering dose of 10 mg/d for the second week was administered.Outcome:For case 1 and case 2 healing of the lesions were evident on third week of follow up.Conclusion:Medications should be taken under medical supervision. Over the counter drugs might lead to allergic reactions like drug induced oral erythema multiforme, which is a rare variant and needs to be differentiate from other oral ulcerative lesion for prompt management and follow-up.     

Clinical and functional outcomes in Middle Eastern patients with idiopathic pulmonary fibrosis

Background: Baseline clinical and physiological variables have been described as relevant predictors of survival among patients with idiopathic pulmonary fibrosis (IPF). However, substantial heterogeneity in both survival time and mortality has been observed with many of these predictive factors. The incidence and mortality rates of IPF vary from country to country, with race potentially contributing to such variations. Objective: We sought to describe baseline clinical features to determine their predictive value among Middle Eastern patients diagnosed with IPF. Methods: We retrospectively examined 61 patients diagnosed with IPF at a university hospital in Riyadh, Saudi Arabia. Results: At presentation, most patients exhibited either dyspnea or cough. The median survival time for all patients was 92 months. Diminished survival was significantly associated with finger clubbing (P = 0.01). Factors not influencing survival were age, gender, percent predicted forced vital capacity, percent predicted forced expiratory volume in 1 s, percent predicted total lung capacity, percent predicted diffusion capacity of the lung for carbon monoxide and resting oxygen saturation. Conclusions: Finger clubbing is a significant predictive variable and was associated with a 5‐fold increase in mortality. Other baseline demographic characteristics as well as pulmonary function tests were not predictive of prognosis in Middle Eastern patients with IPF. It appears that IPF patients of Middle Eastern descent have a longer median survival curve compared to other races. Please cite this paper as: Alhamad EH, Masood M, Shaik SA and Arafah M. Clinical and functional outcomes in Middle Eastern patients with idiopathic pulmonary fibrosis. The Clinical Respiratory Journal 2008; 2: 220–226.     

Genomic and Functional Portrait of a Highly Virulent,CTX-M-15-Producing H30-Rx Subclone of Escherichia coli Sequence Type 131

Escherichia coli sequence type 131 (ST131) is a pandemic clone associated with multidrug-resistant, extraintestinal infections, attributable to the presence of the CTX-M-15 extended-spectrum β-lactamase gene and mutations entailing fluoroquinolone resistance. Studies on subclones within E. coli ST131 are critically required for targeting and implementation of successful control efforts. Our study comprehensively analyzed the genomic and functional attributes of the H30-Rx subclonal strains NA097 and NA114, belonging to the ST131 lineage. We carried out whole-genome sequencing, comparative analysis, phenotypic virulence assays, and profiling of the antibacterial responses of THP1 cells infected with these subclones. Phylogenomic analysis suggested that the strains were clonal in nature and confined entirely to a single clade. Comparative genomic analysis revealed that the virulence and resistance repertoires were comparable among the H30-Rx ST131 strains except for the commensal ST131 strain SE15. Similarly, seven phage-specific regions were found to be strongly associated with the H30-Rx strains but were largely absent in the genome of SE15. Phenotypic analysis confirmed the virulence and resistance similarities between the two strains. However, NA097 was found to be more robust than NA114 in terms of virulence gene carriage (dra operon), invasion ability (P < 0.05), and antimicrobial resistance (streptomycin resistance). RT² gene expression profiling revealed generic upregulation of key proinflammatory responses in THP1 cells, irrespective of ST131 lineage status. In conclusion, our study provides comprehensive, genome-inferred insights into the biology and immunological properties of ST131 strains and suggests clonal diversification of genomic and phenotypic features within the H30-Rx subclone of E. coli ST131.     

Juvenile Ossifying Fibroma of the Maxilla: A Case Report

Ossifying fibroma is a benign neoplasm of the bone, usually involving the posterior tooth bearing area of the mandible, predominantly seen in females in 2nd–4th decade of life with 5:1 prediliction. Fibro-osseous lesions other than FD seem to arise from the periodontal membrane. These lesions are usually asymptomatic, well defined clinically and radiologically amenable for enucleation. Fibro-osseous lesions of the jaws, including Juvenile Ossifying Fibroma (JOF), pose diagnostic and therapeutic difficulties due to their clinical, radiological and histological variability. Ossifying fibromas which appear as fast growing mass between 5 and 15 years of age, radiologically well bordered, and consistent with ossifying fibroma histologically, are referred as juvenile (aggressive) ossifying fibroma. We report a case of JOF of left side of the maxilla in an 11 year old girl which is an uncommon site of occurrence.