Human papillomavirus subtype 16 is common in Pakistani women with cervical carcinoma.

INTRODUCTION: Human papillomavirus (HPV) is recognized as a major causative agent for cervical carcinomas. Based on their oncogenic potential, HPV subtypes have been divided into high- and low-risk. In Pakistan, screening for HPV in female patients is not commonly practiced, and as a consequence, the degree of HPV prevalence and its correlation with cervical cancer is unknown. OBJECTIVE: In this study, we have attempted to estimate the prevalence of HPV infection, and also the HPV subtype profile, among Pakistani women with cervical cancer from varied geographical, racial, and social backgrounds within Pakistan. METHODOLOGY: Women visiting two tertiary care hospitals in Karachi, diagnosed with carcinoma of the cervix within the past 15 years, were analyzed for HPV subtypes in their cancer specimens. Retrospectively, 60 paraffin-embedded cervical cancer biopsies were examined for the presence of HPV DNA. After DNA extraction from these samples, polymerase chain reaction (PCR) was used to amplify the HPV L1 gene using the consensus (general) primers, and primers specific for subtypes 16 and 18. RESULTS: Of the 60 samples analyzed, only one sample was HPV negative; the rest of the samples were positive for the presence of HPV. Of the 59 HPV positive samples, 56 showed the presence of HPV16 and one sample was positive for HPV18; HPV subtype could not be determined in two samples. CONCLUSION: Our results show a strong relationship between HPV infection and cervical cancer among Pakistani women. These results underscore the need to implement regular HPV screening for Pakistani women. An early diagnosis of HPV infection will allow better health management to reduce the risk of developing cervical cancer.     

High epidermal growth factor receptor amplification rate but low mutation frequency in Middle East lung cancer population

Epidermal growth factor receptor (EGFR) exon 18-21 mutations were shown to be highly predictive of response to gefitinib (Iressa) therapy in lung cancer. Studies on Western and Japanese lung cancers have indicated substantial differences in the EGFR mutation frequency between these populations. To investigate the prevalence of EGFR in another distinct ethnic group, EGFR alterations were studied in 47 consecutive non small cell lung cancers from Saudi Arabia by immunohistochemistry, fluorescence in situ hybridization, and DNA sequencing. Detectable EGFR expression was seen in 69.8% of 43 interpretable cancers. Epidermal growth factor receptor amplification, present in 15.3% of 39 analyzable cancers, was strongly associated with high levels of EGFR expression (P = .0047). Only 1 exon 18-21 mutation was seen among 34 lung cancers that could be successfully sequenced. It is concluded that EGFR exon 18-21 mutations are rare in Middle East patients with lung cancer and occur in a similar range as in Western patients. The remarkable high rate of EGFR gene amplifications could potentially facilitate studies on the predictive role of gene copy number changes for response to anti-EGFR therapies in Middle East patient sets.     

High throughput tissue microarray analysis of FHIT expression in diffuse large cell B-cell lymphoma from Saudi Arabia.

Recent studies have suggested a potential prognostic role of alterations of the fragile histidine triad (FHIT) gene in diffuse large B-cell lymphoma. To evaluate possible mechanisms of FHIT inactivation and to further clarify its potential prognostic relevance, we analyzed a set of 114 diffuse large B-cell lymphoma with clinical follow-up information. Tissue microarrays were analyzed by immunohistochemistry for protein expression, and corresponding DNA samples were analyzed for FHIT promotor hypermethlyation. Reduced or absent FHIT expression was found in 75 of 114 diffuse large B-cell lymphoma (66%), but was unrelated to clinical tumor stage or patient prognosis. FHIT promotor hypermethylation was observed in 29 of 93 (23%) interpretable diffuse large B-cell lymphoma. Hypermethylation was not significantly correlated to protein expression loss, which could be explained by competing mechanisms for FHIT inactivation in a substantial fraction of non FHIT hypermethylated diffuse large B-cell lymphoma. Hypermethylation was significantly associated with poor prognosis of diffuse large B-cell lymphoma patients and predominantly seen in nongerminal center diffuse large B-cell lymphoma (27%), but less frequent (13%) in germinal center diffuse large B-cell lymphoma. In summary, these data suggest that promotor hypermethylation is responsible for reduced FHIT expression in a substantial subset of diffuse large B-cell lymphoma, which is primarily composed of nongerminal center subtype with poor patient prognosis.     

The effect of cyclosporin A on alveolar bone in rats subjected to experimental periodontal disease

Cyclosporine A (CsA), broadly used in organ transplantation, may contribute to pathogenesis of osteoporosis. The aim of this study was to investigate the effects of CsA on alveolar bone in rats subjected or not to experimental periodontal disease using biochemical, radiographic, and histometric analysis. Forty Wistar rats were divided into 4 equal groups: Group I (Control), Group II (CsA was injected subcutaneously in a daily dose of 10 mg/kg), Group III (Ligature was placed around the mandibular molars), Group IV (Ligature+CsA). After 60 days, rats were decapitated, serum alkaline phosphatase and calcium levels were measured. Radiographic-alveolar bone loss (ABL), histometric-ABL, and percentage of new alveolar bone formation (NABF%) were determined on mandibular molars. Significant increase in serum alkaline phosphatase levels (p < 0.001), no significant difference in calcium levels were observed (p > 0.05) in Group IV compared to Group III. Radiographic and histometric-ABL were significantly less (p < 0.001), NABF% was significantly greater (p < 0.05) in Group IV than in Group III. No significant difference in any of the parameters between Group II and Group I was found. It can be concluded that in the presence of periodontal disease, CsA treatment may bring out an imbalance in the alveolar bone homeostasis by decreasing resorption and stimulating formation of alveolar bone in rats.     

Suicide in women with gynecologic cancer

Objective(s)

To characterize the suicide rates among patients with gynecologic cancer in the Unites States and to identify factors associated with high suicide rates.

Method(s)

Subjects with a diagnosis of gynecologic cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) program for the period 1988-2007. Comparison with women in the general US population was based on WHO data 2005, matched for age in 10-year categories. Cox regression models were used to perform multivariate modeling for factors associated with suicide.

Result(s)

Among 252,235 patients followed for 1,207,278 person-years, the suicide rate was 8.3 per 100,000 person-years, with a standardized mortality ratio (SMR) of 1.4 (95% CI 1.2-1.7, p < 0.001). The highest suicide rates were observed in patients with ovarian cancer and within the first year following diagnosis. Suicide risk was associated with younger age at diagnosis, high grade disease and absence of surgical intervention.

Conclusion(s)

Patients with gynecologic cancer have an increased suicide risk when compared to the general population. Suicide rates vary by cancer site and time since diagnosis. Effective screening and appropriate treatment of psychosocial stress among women with gynecologic cancer are warranted.     

Allergy is an important factor in asthma exacerbation: A Pro/Con Debate

Allergy and allergens have been implicated in asthma and it has historically been assumed that deteriorating asthma is related to allergen exposure. In the current pro/con debate some leading academics and researchers in the field consider this notion in the light of recent evidence. They conclude that allergy does not directly cause exacerbations but suggest that it may contribute to acute asthma in a different fashion. Possibilities that are proposed by the authors include specific allergy phenotypes acting as risk factors for virus‐associated exacerbations or alternatively that allergy may be implicated in the blunted innate immune responses detected in asthma.     

Ketamine: a controversial drug for neonates

Ketamine is widely used for anesthesia and analgesia in neonates and children. It provides potent sedation, analgesia, and amnesia, a short duration of action, supporting hemodynamic and respiratory stability. Noncompetitive antagonism of NMDA receptors produces its primary therapeutic effects, but it also alters receptor function at dopaminergic, serotonergic, cholinergic, and opioidergic sites. Recent interest in ketamine stems from its potential to block excitotoxic cell death, although concerns have been raised about anesthetic neurotoxicity in neonatal animal models. The development of ketamine, its clinical profile, toxic effects in the immature brain, and future applications in neonates and children are reviewed in this article.     

Molecular epidemiology of macrolide-resistant Streptococcus pneumoniae isolates in Europe

In many European countries, the level of pneumococcal resistance to macrolides has now passed the level of resistance to penicillin G. A total of 82 erythromycin A-resistant isolates of Streptococcus pneumoniae were collected by 11 laboratories in seven European countries. All of the isolates were tested for antimicrobial susceptibility, analyzed for clonal relatedness by multilocus sequence typing, and characterized for macrolide resistance genotypes. The prevalence of the macrolide resistance genotypes varied substantially between countries. In France (87.5% of all strains), Spain (77.3%), Switzerland (80%), and Poland (100%), strains were predominantly erm(B) positive, whereas higher levels of mef(A)-positive strains were reported from Greece (100%) and Germany (33.3%). Macrolide resistance was caused by the oligoclonal spread of some multilocus sequence types, but significant differences in clonal distribution were noted between France and Spain, countries from which high levels of macrolide resistance have been reported. Overall, sequence type 81 (Spain23F-1 clone) was by far the most widespread. The mainly erm(B)-positive serotype 14 clone (sequence type 143), first reported in Poland in the mid-1990s, is now widespread in France.