Common oral lesions: Part II. Masses and neoplasia

Certain common oral lesions appear as masses, prompting concern about oral carcinoma. Many are benign, although some (e.g., leukoplakia) may represent neoplasia or cancer. Palatal and mandibular tori are bony protuberances and are benign anomalies. Oral pyogenic granulomas may appear in response to local irritation, trauma, or hormonal changes of pregnancy. Mucoceles represent mucin spillage into the oral soft tissues resulting from rupture of a salivary gland duct. Oral fibromas form as a result of irritation or masticatory trauma, especially along the buccal occlusal line. Oral cancer may appear clinically as a subtle mucosal change or as an obvious mass. Oral leukoplakia is the most common premalignant oral lesion. For persistent white or erythematous oral lesions, biopsy should be performed to rule out neoplastic change or cancer. Most oral cancers are squamous cell carcinomas. Tobacco and heavy alcohol use are the principal risk factors for oral cancer. Family physicians should be able to recognize these lesions and make appropriate referrals for biopsy and treatment.     

Diagnosis of aortic dissection: The value and limitations of transesophageal echocardiography

Aortic dissection requires prompt and reliable diagnosis. The purpose of this study was to assess the accuracy and limitations of transesophageal echocardiography (TEE) for the diagnosis of aortic dissection. Twenty seven patients with clinically suspected aortic dissection were investigated by means of TEE. TEE results were compared to intraoperative findings (n=18), necropsy (n=4), and magnetic resonance imaging (n=5). The DeBakey classification was used for differentiation of dissection type. Twenty-three patients (85%) were correctly identified as having aortic dissection. Four false-positive TEE findings (15%) were confined to the nondissecting aneurysm of the ascending aorta in elderly patients. Retrospectively we found that protruding atherosclerotic plaques were recognized as small intimal flaps. Type of dissection was correctly diagnosed in all 23 patients, the primary entry site was identified in 15 patients (65%), aortic regurgitation was found in 55.5% of patients, and pericardial effusion was detected in 33.3%. We conclude that TEE allows accurate diagnosis and classification of aortic dissection. However, some cases could be overdiagnosed in lesions of the ascending aorta, especially in nondissecting aneurysms. Another limitation of TEE is the inability to define the primary entry site in some cases. Still, overall results may favor TEE as the primary bedside diagnostic procedure to identify patients requiring urgent surgical intervention.Presented at the 35th World Congress, International College of Angiology, Copenhagen, Denmark, July 1993     

Idh1 mutations contribute to the development of T-cell malignancies in genetically engineered mice

Gain-of-function mutations in isocitrate dehydrogenase 1 (IDH1) are key drivers of hematopoietic malignancies. Although these mutations are most commonly associated with myeloid diseases, they also occur in malignancies of the T-cell lineage. To investigate their role in these diseases and provide tractable disease models for further investigation, we analyzed the T-cell compartment in a conditional knock-in (KI) mouse model of mutant Idh1. We observed the development of a spontaneous T-cell acute lymphoblastic leukemia (T-ALL) in these animals. The disease was transplantable and maintained expression of mutant IDH1. Whole-exome sequencing revealed the presence of a spontaneous activating mutation in Notch1, one of the most common mutations in human T-ALL, suggesting Idh1 mutations may have the capacity to cooperate with Notch1 to drive T-ALL. To further investigate the Idh1 mutation as an oncogenic driver in the T-cell lineage, we crossed Idh1-KI mice with conditional Trp53 null mice, a well-characterized model of T-cell malignancy, and found that T-cell lymphomagenesis was accelerated in mice bearing both mutations. Because both IDH1 and p53 are known to affect cellular metabolism, we compared the requirements for glucose and glutamine in cells derived from these tumors and found that cells bearing the Idh1 mutation have an increased dependence on both glucose and glutamine. These data suggest that mutant IDH1 contributes to malignancy in the T-cell lineage and may alter the metabolic profile of malignant T cells.Somatic mutations in isocitrate dehydrogenase 1 (IDH1) are frequently observed in a number of malignancies, including glioma, cholangiocarcinoma, chondrosarcoma, and several hematological malignancies (1). IDH1 is a cytoplasmic enzyme that catalyzes the NADP-dependent conversion of isocitrate to α-ketoglutarate (αKG). Mutations in IDH1 at arginine 132 (R132) cause an enzymatic gain of function that results in the NADPH-dependent conversion of αKG to d-2-hydroxyglutarate (2HG) (2). This metabolite is normally maintained at very low levels in cells and tissues and is not part of any known productive metabolic pathway. However, in cells and tissues of patients with IDH1 mutant tumors, 2HG builds up to high levels and is thought to contribute to tumorigenesis by inhibiting a class of αKG-dependent enzymes (1). The precise effects important for driving tumorigenesis downstream of IDH1 mutations are not fully understood and may differ between disease states.In the hematopoietic system, IDH1 mutations are most often associated with myeloid diseases, where they are commonly found in myelodysplastic syndrome and acute myeloid leukemia (3). However, IDH1 mutations are also found in a small proportion of adult T-cell acute lymphoblastic leukemia (T-ALL) (4, 5). T-ALL is an aggressive malignancy of developing T cells and is responsible for ∼25% of adult ALL (6, 7). T-ALL is thought to arise via a multistep process of oncogenic mutation that leads to the transformation of immature T cells. The genetic landscape of the disease has been characterized, and a large number of driver mutations have been identified (6). The most common genetic feature of T-ALL is the presence of activating mutations in Notch1, which are present in more than 50% of patients (8). Interestingly, IDH1 mutations seem to be confined to a subset of adult patients with T-ALL bearing an immature T-cell gene expression signature and harboring other oncogenic mutations in genes more commonly associated with myeloid malignancy, including Flt3 and DNMT3A (4, 9). This subset of T-ALL has recently been recognized as a distinct disease entity called early T-cell precursor T-ALL and is associated with therapy resistance and a particularly poor outcome (10). The role of IDH1 mutations in this subset of T-ALL is not understood.Using a myeloid lineage-specific conditional Idh1-R132-KI mouse model, we previously showed that mutant IDH1 partially blocks differentiation and produces a hematopoietic phenotype similar to human myelodysplastic syndrome (11). In this study, we crossed the Idh1-R132-KI mouse with Vav-cre animals to introduce the IDH1 R132 mutation into the entire hematopoietic system to investigate the role of Idh1 mutations in T-cell malignancy.     

Dietary acculturation of Hispanic immigrants in Mississippi

OBJECTIVE: Assisting Hispanic immigrants in making culturally acceptable food choices may affect their health for generations. As a relatively new enclave of Hispanics, Scott County, Mississippi, was chosen to study dietary acculturation and health concerns of immigrants. MATERIAL AND METHODS: The research method consisted of interviews with community representatives (N=11), a focus group (N=6), and interviews with Hispanic immigrants (N=18). RESULTS: Community representatives mentioned availability influenced immigrants' food choices and suggested promoting cultural awareness and offering nutrition classes on local ingredients. Food cost, health concepts, food selection, and eating habits of children were salient themes from the focus group and interviews with Hispanics. Hispanic participants mentioned long work hours affect food selection and that U.S. produce lacks freshness and flavor. CONCLUSIONS: Results indicate that an intervention must be formulated that preserves healthful dietary practices and minimizes the negative health aspects of acculturation to the "American diet"     

The attractiveness of family medicine among Polish medical students

Background: In many developed countries tuning supply and demand of medical doctors is a continuous challenge to meet the ever changing needs of community and individual patients. The long study period for medical doctors creates the opportunity to observe the current career preferences of medical students and evolution in time.

Objectives: To investigate the career choices of Polish students in different stages of their medical education.

Methods: Medical students at five Polish medical universities were questioned about their career aspirations in the first, third and sixth year.

Results: A total of 2020 students were recruited for the survey. Among first year students 17% preferred family medicine as final career option, compared to 20% in the third year, and 30% in the sixth year (significant trend, P < 0.0001). In particular, female students prefer family medicine: 71% women versus 62% women in the group with a preference for a non-family medicine orientation (P = 0.008). Medical students rejecting a career as a family doctor stated that the impossibility to work in a hospital environment was the determining factor.

Conclusion: The opportunity for professional development seems to be an important determining factor in the choice of a medical specialty in Poland. The proportion of Polish students choosing family medicine increases during their progress in medical education, with one third of students interested in a career in family medicine by year six.     

Interhospital transfer of blunt multiply injured patients to a level 1 trauma center does not adversely affect outcome

Background

Stops at nontrauma centers for severely injured patients are thought to increase deaths and costs, potentially because of unnecessary imaging and indecisive/delayed care of traumatic brain injuries (TBIs).

Methods

We studied 754 consecutive blunt trauma patients with an Injury Severity Score greater than 20 with an emphasis on 212 patients who received care at other sites en route to our level 1 trauma center.

Results

Referred patients were older, more often women, and had more severe TBI (all P < .05). After correction for age, sex, and injury pattern, there was no difference in the type of TBI, Glasgow Coma Scale (GCS) upon arrival at the trauma center, or overall mortality between referred and directly admitted patients. GCS at the outside institution did not influence promptness of transfer.

Conclusions

Interhospital transfer does not affect the outcome of blunt trauma patients. However, the unnecessarily prolonged stay of low GCS patients in hospitals lacking neurosurgical care is inappropriate.