Neuroendocrine cells and associated malignancies of the oral mucosa: a review

J Oral Pathol Med (2010) 39 121–127 Neuroendocrine cells of the oral mucosa constitute an under‐recognized component of the diffuse neuroendocrine system with diverse subpopulations and elusive biologic roles in the oral cavity. Primary malignant oral tumors that show a neuroendocrine phenotype display histomorphologic heterogeneity thereby giving rise to a spectrum of lesions in this rare category of oral malignancy. These lesions can be divided into neuroendocrine carcinomas (NECs) of small cell or non‐small cell type. The former is further subdivided into the Merkel cell type or the pulmonary type while the latter includes atypical carcinoid tumor and large cell NEC. All histologic subtypes of oral NEC appear to have a strong predilection for men in their fifth or sixth decade and arise predominantly in the non‐keratinized oral mucosa. The biologic behavior of oral Merkel cell carcinomas appears to be more aggressive than those of skin. It remains to be determined whether histologic categorization of the remaining tumor subtypes is predictive of patient survival in oral neuroendocrine tumors.     

Response of First-Line Antibiotic Therapy in Patients with Febrile Neutropenia During Treatment of Hematological Disorders

Patients with hematological disorders develop febrile neutropenia (FN); most of these events remain undetermined in origin. We performed a prospective study to determine the microbiological characteristics of infections and their response to the first-line antibiotic therapy in FN. The study was conducted at National Institute of Blood Disease and Bone Marrow Transplant. Two-hundred episodes of FN were assessed for the bacterial growth, antimicrobial susceptibility pattern and response to the first-line treatment of FN. All patients were given Ceftazidime and Amikacin Bosch Pharmaceutical (Pvt. Ltd), as first-line antibiotic in FN. Out of 200 episodes we had 108 clinically and microbiologically documented infections. The isolated frequencies for gram negative and gram positive organisms were n = 52 and 49 (48 and 45 %) respectively. Among gram negative micro-organisms, Escherichia coli (E. coli) was isolated in 15 (28.8 %), Klebsiella pneumonae in 4 (7.6 %) and Pseudomonas aeruginosa in 10 (19.2 %) were in highest frequencies. Methicillin sensitive staphylococci emerged as the frequently isolated gram-positive bacteria. Eight-one episodes (45.3 %) responded to the first-line treatment and death reported in 20 cases (10 %). Our study showed almost equal trend of gram positive and gram negative bacteria isolated from patients suffering from neutropenic fever. Empirical use of Ceftazidime and Amikacin as first-line antibiotics was able to cover the infection only in 45.3 % of episodes suffering from FN.     

Preliminary safety evaluation of a taurocholate‐conjugated low‐molecular‐weight heparin derivative (LHT7): a potent angiogenesis inhibitor

In our previous studies, taurocholic acid (TA)‐conjugated low‐molecular‐weight heparin derivative (LHT7) has been proven to be a potent anti‐angiogenic agent by demonstrated successful blockage capability of vascular endothelial growth factors (VEGF). Preliminary safety evaluations were conducted based on its mechanism of action and chemical behavior. For this purpose, acute toxicity study, and hematological and serological evaluations were carried out. Additionally, in order to evaluate mechanism‐related side effects, both blood pressure and the occurrence of proteinuria were measured using a treatment regime of multiple high doses of LHT7 in a biodistribution study. LD₅₀ values for LHT7 in female and male mice were 56.9 and 64.7 mg kg^–1 doses, respectively. There were no vital fluctuations in the serological and hematological parameters, except for the elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at 100 and 200 mg kg^–1 doses of LHT7, representing vital changes in the liver function. Moreover, the results of mechanism‐related studies showed that blood pressure at 50 mg kg^–1 did not change but showed elevated levels of protein in urine. In the biodistribution study, a slight accumulation of LHT7 in the kidney and the liver were observed at the 50 mg kg^–1 repeated dose owing to the presence of bile acid. No fatal damage was observed in this study; most observations were related to the chemical composition or the mechanism of action of the material. Copyright © 2014 John Wiley & Sons, Ltd.     

Racial/Ethnic Differences in the Association between Arrest and Unprotected Anal Sex among Young Men Who Have Sex with Men: The P18 Cohort Study

This analysis aimed to determine whether the relationship between a history of arrest and unprotected anal sex (UAS) is the same for Black/Latino gay, bisexual, and other young men who have sex with men (YMSM) as compared to White/Asian/Pacific Islander (API) YMSM in New York City (NYC). Baseline audio-computer-assisted self-interview (ACASI) and interviewer-administered survey data from a sample of 576 YMSM aged 18–19 years old who self-reported being HIV-negative were analyzed. Data included history of arrest and incarceration as well as UAS in the past 30 days. Race/ethnicity was an effect modifier of the association between arrest and UAS among YMSM: White/API YMSM with a lifetime arrest history were more than three times as likely to report UAS, and Black/Latino YMSM with a lifetime history of arrest were approximately 70 % less likely to report UAS as compared with White/API YMSM with no reported arrest history. Race/ethnicity may modify the relationship between arrest and sexual risk behavior because the etiology of arrest differs by race, as partially evidenced by racial/ethnic disparities in police stop, arrest, and incarceration rates in NYC. Arrest could not only be an indicator of risky behavior for White/API YMSM but also an indicator of discrimination for Black/Latino YMSM. Further research is needed to assess whether the differential associations observed here vis-à-vis race/ethnicity are robust across different populations and different health outcomes.     

Intracranial haemorrhage in typhoid fever

Intracranial haemorrhage in typhoid fever is very rare. We report another case of non-traumatic intracranial hemorrhage in a 6-year-old boy suffering from typhoid fever, unconsciousness, seizure and non-coherent speech. Investigations revealed severe thrombocytopenia and prolonged prothrombin time. CT scan of brain showed intraparenchymal haemorrhage in frontal regions bilaterally with perilesional oedema, subarachnoid bleed and extension into the lateral ventricles. No aneurysm or arterio-venous malformation was seen on MR angiography. The patient recovered without any neurological deficit.     

Intact T cell responses in ataxia telangiectasia

Ataxia telangiectasia (A-T) is an autosomal recessive multisystem disorder associated with a variable immune deficiency. The mechanism for this remains unclear. Qualitative and quantitative defects of cellular immunity have been previously reported. However, despite laboratory evidence of significant immune abnormalities, opportunistic infections are uncommon. To address this discrepancy, we analyzed cytokine production by quantitative real-time PCR and T cell function at the single cell level by flow cytometry in four A-T patients. CD4 and CD8 T cell subsets from these patients displayed intact signaling in response to anti-CD3 stimulation, similar to controls. Stimulated T cells from A-T patients also produced normal to increased levels of Th1 (IL-2, IFN-gamma) and Th2 (IL-10, IL-4) cytokines, relative to control values. Our results suggest that T cells from A-T patients may be more functionally intact than previously observed. This helps to explain the paucity of opportunistic infections encountered, unlike that encountered in other primary immunodeficiencies.