Coming to America: Betel Nut and Oral Submucous Fibrosis

BackgroundOral submucous fibrosis (OSF) is an insidious precancerous disease affecting the oral cavity, pharynx and upper digestive tract. Its etiology is linked directly to betel nut use, which is common to the Indian subcontinent. With the increase in immigration of people from the Indian subcontinent to the United States, many American dental professionals will encounter this disease in the near future. The author provides a general overview of OSF.MethodsThe author provides a literature review of OSF, including its epidemiology, etiology, clinical presentation, histopathology and treatment modalities.ResultsOSF is a precancerous oral disease linked definitively to the use of betel nut. It is endemic to people in the Indian subcontinent. Patients' primary complaint is progressive trismus. Treatment is based on disease severity.Clinical ImplicationsOSF is a debilitating but preventable oral disease. Its incidence in the United States will increase as the South Asian immigrant population expands. Consequently, American dental professionals may encounter patients with this disease, and it is important that they are aware of it. In addition, for dental care professionals practicing in a South Asian American community, public health education is important to inform the population about the deleterious oral health effects of betel nut consumption.     

Effects of histamine H1R—H4R—agonist on the airway epithelium of rabbits

ObjectiveTo explore the exact role of histamine receptors in respiratory system.MethodsThe cohort comprised of six groups (group I control and group II-VI treated) containing five rabbits in each group. Control-group received vehicle (sterile distilled water) and treated groups received subcutaneous histamine (100 μg/kg, b.i.d.), and H1R-agonist (HTMT), H2R-agonist (amthamine), H3R-agonist (R-(?)-α-methylhistamine) and H4R-agonist (clobenpropit) each in a dose of 10 μg/kg, b.i.d. for 30 subsequent days. After completion of treatment, animals were euthanized and perfused with 10% buffered formalin. Small tissue blocks of trachea and lungs were processed for paraffin embedding. Observations were recorded in sample photomicrographs taken from 10 μm thick. Haematoxylin and eosin stained sections.ResultsIt was observed that trachea and bronchi from histamine, H1R and H4R groups had only patches of hyperplastic and hypertrophied epithelium and in general, cells in the affected region were taller heaped up. The bronchiolar epithelia from all treated groups showed hypertrophy and hyperplasia throughout with most of the cells having rounded profile and appeared to bud out from the basal cells.ConclusionsIt is concluded that histamine receptors on induction via its specific agonist can induce hypertrophy, hyperplasia of respiratory tract epithelia suggesting its role akin to growth stimulating factor and warranting further long-term study.     

Mutation of the GABAA receptor M1 transmembrane proline increases GABA affinity and reduces barbiturate enhancement

All GABA(A) receptor (GABAR) subunits include an invariant proline in a consensus motif in the first transmembrane segment (M1). In receptors containing bovine alpha1, beta1 and gamma2 subunits, we analyzed the effect of mutating this M1 proline to alanine in the alpha1 or beta1 subunit using 3 different expression systems. The beta1 subunit mutant, beta1(P228A), reduced the EC(50) for GABA about 10-fold in whole cell recordings in HEK293 cells and L929 fibroblasts. The corresponding alpha1 subunit mutant (alpha1(P233A)) also reduced the GABA EC(50) when expressed in Xenopus oocytes; alpha1(P233A)beta1gamma2S receptors failed to assemble in HEK293 cells. Binding of [(3)H]flumazenil and [(3)H]muscimol to transfected HEK293 cell membranes showed similar levels of receptor expression with GABARs containing beta1 or beta1(P228A) subunits and no change in the affinity for [(3)H]flumazenil; however, the affinity for [(3)H]muscimol was increased 6-fold in GABARs containing beta1(P228A) subunits. In L929 cells, presence of the beta1(P228A) subunit reduced enhancement by barbiturates without affecting enhancement by diazepam or alfaxalone. Single channel recordings from alpha1beta1gamma2S and alpha1beta1(P228A)gamma2L GABARs showed similar channel kinetics, but beta-mutant containing receptors opened at lower GABA concentrations. We conclude that the beta1 subunit M1 segment proline affects the linkage between GABA binding and channel gating and is critical for barbiturate enhancement. Mutation of the M1 proline in the alpha1 subunit also inhibited receptor assembly.     

Biliary,fecal and plasma deoxycholic acid in rabbit,hamster, guinea pig,and rat: comparative study and implication in colon cancer

Bile acids are believed to play a role in the etiology of colorectal cancer, and high fecal excretion of secondary bile acids was correlated with increased incidence of colon cancer. Recently, it was also reported that there is an increase in plasma of the secondary bile acid, deoxycholic acid in men with colorectal adenomas. Since deoxycholic acid is formed in the colon and absorbed into the portal systemic circulation, it was suggested that the blood concentration of this bile acid reflects the level of exposure of colonic cells to deoxycholic acid. The objective of this study was to investigate whether plasma deoxycholic acid level represents the fecal content of this bile acid in several animal species with different bile acid composition and deoxycholic acid contribution to the bile acid pool. Eight rabbits, hamsters, guinea pigs, and rats were used in this study. Blood samples and feces were collected on days 1, 3, 5 and 7. Bile samples were obtained only on day 7. The plasma, fecal and biliary bile acids were analyzed by gas chromatography-mass spectrometry. Bile acid composition and deoxycholic acid content varied greatly between the animal species studied. There was a variation in the concentration of total bile acids in the plasma and feces obtained at different times during the experiments, however, the bile acids profile remained constant throughout the study. The data obtained shows that although plasma bile acid profile was not similar to fecal bile acids profile, however, there was a significant correlation between the level of plasma and fecal deoxycholic acid. Plasma deoxycholic acid concentration might be a reliable biomarker for the degree of exposure of colon cells to this bile acid, and may be useful in further studies on the role of secondary bile acids in colon carcinogenesis.     

Interferon in the treatment of hairy-cell leukemia

The introduction of alpha interferon in 1984 initiated a new and exciting turnaround in the treatment of hairy-cell leukemia. Until that time splenectomy was the only known effective therapy for this disease. Interferon proved to benefit hairy-cell leukemia patients with active disease, whether or not they had undergone prior splenectomy. However, most interferon-induced responses were partial and were of relatively short duration. Purine analogues such as cladribine and pentostatin have since been found to be more effective than alpha interferon and, therefore, have now replaced interferon as first-line therapy for hairy-cell leukemia. At the present time, interferon has a relatively limited role in the treatment of hairy-cell leukemia and it is reserved for a group of selected patients who have failed nucleoside analogue therapy. In this chapter, we discuss the efficacy of interferon and its response duration, toxicity and possible mechanism of action in patients with hairy-cell leukemia.     

Spontaneous common bile duct perforation in adult: a case report and review

Common bile duct perforation has been reported in adults after invasive procedures. Spontaneous common bile duct perforation is a rare entity as a cause of acute abdomen in adults. A few cases due to choledocholithiasis have been reported as a cause of spontaneous perforation. We report an adult patient who presented with acute abdomen after spontaneous common bile duct perforation due to unknown etiology who was treated successfully.     

Large-Scale pathology-based cancer data - a reflection of population-based cancer data

Pathology-based cancer data is a high quality reflection of the patterns of cancer in the population it represents, provided the demographic details of the patients are carefully recorded. Relative frequency data is neither a replacement for population-based data nor a suggested alternative; it simply enhances the quality of population data and in very large data sets reflects the cancer patterns observed in the representative populations. Aware of the standard shortfalls of pathology-based data, the department of pathology, The Aga Khan University Hospital (AKUH) standardized its data, representing 53.4% of the cancer data of Karachi Division (Pakistan) and also reflecting the cancer pattern of other provinces of Pakistan. This data was compared with 4 different population and institutional-based data sets. The findings substantiate the observation that despite the problems of interpretation of data from pathology laboratories, they are an invaluable source of information on cancer patterns in much of the world where incidence data are unavailable . If developing countries, unable to organize National Population- Based Registry should as an alternate develop National Pathology-based Registers a well targeted and monitored, a Cancer Control Program would be possible. A good quality, large-scale pathology data with demographic details of the patient recorded can also be extended to give coverage to the population.     

Two cases of spinal meningeal melanocytoma

Meningeal melanocytoma is a rare pigmented tumor originating from the melanocytes that generally occurs in the posterior fossa and the spinal cord. Although it is known as a relatively benign tumor, some recurrences have been reported. We report two cases of spinal meningeal melanocytoma with immunohistochemical and ultrastructural studies. In addition, we include a summary of published cases since the first case of Limas and Tio in 1972.     

Diabetes care management participation in a primary care setting and subsequent hospitalization risk.

Scant evidence exists that examines the impact of participation in primary care diabetes management programs and their educational components on the risk of subsequent significant patient morbidity. This study examined the association between participation in a diabetes management program in a primary care setting and the risk of subsequent hospitalization. Ten thousand nine hundred eighty patients with diabetes mellitus receiving some type of treatment in a large primary care clinic network in Houston, TX were examined for incidence of hospitalization in the year 2002. Information from the year preceding the hospitalization was obtained on several demographic, clinical, and diabetes care management participation related variables. Multivariate logistic regressions were used to examine the relationship between primary care diabetes management participation as well as individual educational components and the likelihood of subsequent-year hospitalization. Patients participating in some type of primary care diabetes management were 16% less likely to have an incidence of hospitalization (p = 0.05). When individual educational components of the diabetes care management program were examined, diabetes education sessions were more beneficial than certified diabetes educator visits in reducing the incidence of hospitalization. Patients with controlled blood glucose levels and a diabetes education session seemed to have the most significant reduction in hospitalization risk (odds ratio [OR] = 0.62; 95% CI: 0.40, 0.95). There seem to be beneficial effects associated with participation in primary care diabetes management programs in terms of reduced hospitalization risk. Attendance at diabetes educational sessions in primary care settings coupled with maintenance of blood glucose control seem to be associated with greatest risk reduction.