Epstein-Barr virus-related lymphocyte stimulation inhibitor: a possible prognostic tool for undifferentiated nasopharyngeal carcinoma

It is demonstrated in this study that a serum factor, a lymphocyte stimulation inhibitor (LSI), which inhibits Epstein-Barr virus (EBV)-induced lymphocyte stimulation, is a potentially useful tool in the diagnosis and monitoring of nasopharyngeal carcinoma (NPC). In a study of 25 patients with undifferentiated NPC, 20 healthy controls, and 20 patients with other head and neck tumors, LSI was found only in the NPC patients with active disease. In a more complete study of 8 patients longitudinally followed up for at least 20 months, a comparison of LSI with antibodies to a variety of EBV antigens including viral capsid antigen, early antigen, and nuclear antigen indicated that LSI levels provided a reliable and sensitive indicator of disease activity that should be added to clinical markers currently in use as monitors of disease activity in NPC.     

Measuring physician mental workload: reliability and validity assessment of a brief instrument.

This study examined the reliability and validity of a brief six-item instrument to measure the mental workload experienced by residents for specific patient visits to an ambulatory care clinic. Participating in the study were twenty-two residents in postgraduate years 1 through 3 who were working in the general outpatient clinic of an inner city, private, nonprofit community hospital. Cronbach's alpha coefficient for the instrument was 0.80. Findings supported several theory-based hypotheses on determinants and performance consequences of mental workload. Mental workload was positively correlated with fatigue (r = 0.42, P = 0.03) and inversely correlated with residents' self-rated experience with patients' problems (r = -0.65, P less than 0.001). Residents' performance was measured through self-ratings and faculty physicians' ratings. Mental workload was inversely correlated with self-rated performance (r = -0.67, P less than 0.001). The correlation of mental workload with faculty physician ratings that reflected the technical dimension of patient care (physician examination, medications, and procedures) was r = -0.38 (P = 0.04). With mental workload squared, the correlation was r = -0.45 (P = 0.02) and the form of the relationship, consistent with the hypothesis, was a slightly downward sloping curve. Limitations of this research are discussed as well as suggestions for further research.     

Relationship between temporomandibular joint pain and magnetic resonance imaging findings of internal derangement

In terms of clinical decision-making in instances of temporomandibular disorders (TMD) and orofacial pain, there is controversy in the literature over the diagnostic significance of the temporomandibular joint (TMJ)-related variable disk-condyle relationship (DCR). The purpose of this study was to investigate whether in patients with TMJ-related pain, the variable of TMJ pain may be linked to magnetic resonance (MR) imaging findings of internal derangement (ID). The study comprised 163 consecutive TMJ pain patients. Criteria for including a patient were report of orofacial pain referred to the TMJ, and the presence of uni- or bilateral TMJ pain during palpation, during function, and/or during unassisted or assisted mandibular opening. Bilateral sagittal and coronal MR images were obtained to establish the prevalence of TMJ ID types. Analysis of the data revealed the presence of TMJ pain to be associated with significantly more MR imaging diagnoses of ID than an absence of ID (P<0.001), and disk displacement without reduction than disk displacement with reduction (P<0.001). Using chi-square analysis, the results showed a significant relationship between the presence of TMJ-related pain and the MR imaging diagnosis of TMJ ID (P=0.001), and TMJ ID type (P=0.000). Use of the Kappa statistical test indicated poor diagnostic agreement between the presence of TMJ pain and the MR imaging diagnosis of ID (K=0.16). The results suggest that the clinical variable of TMJ pain may have a significant effect on the prevalences of MR imaging diagnoses of TMJ ID. The data confirm the biological concept of DCR as a diagnostic approach in patients with signs and symptoms of TMJ-related pain.     

Somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: incidence, types, biological behavior, association with inherited syndromes, and functional activity

Somatostatin-producing neuroendocrine tumors (SOM-NETs) of the duodenum and pancreas appear to be heterogeneous. To determine their clinicopathological profiles, respective data were analyzed on a series of 82 duodenal and 541 pancreatic NETs. In addition, the clinical records of 821 patients with duodenal or pancreatic NETs were reviewed for evidence of a somatostatinoma syndrome. Predominant or exclusive expression of somatostatin was found in 21 (26%) duodenal and 21 (4%) pancreatic NETs. They were classified as sporadic (n=31) or neurofibromatosis type 1 (NF1)-associated duodenal NETs (n=3), gangliocytic paragangliomas (GCPGs; n=6), or poorly differentiated neuroendocrine carcinomas (pdNECs; n=2). In addition, five duodenal and four pancreatic SOM-NETs were found in five patients with multiple endocrine neoplasia type 1 (MEN1). Metastases occurred in 13 (43%) patients with sporadic or NF1-associated SOM-NETs, but in none of the duodenal or pancreatic MEN1-associated SOM-NETs or GCPGs. Sporadic advanced (stage IV) SOM-NETs were more commonly detected in the pancreas than in the duodenum. None of the patients (including the 821 patients for whom only the clinical records were reviewed) fulfilled the criteria of a somatostatinoma syndrome. Our data show that somatostatin expression is not only seen in sporadic NETs but may also occur in GCPGs, pdNECs, and hereditary NETs. Surgical treatment is effective in most duodenal and many pancreatic SOM-NETs. MEN1-associated SOM-NETs and GCPGs follow a benign course, while somatostatin-producing pdNECs are aggressive neoplasms. The occurrence of the so-called somatostatinoma syndrome appears to be extremely uncommon.     

Therapy-associated genetic aberrations in patients treated for non-Hodgkin lymphoma

Therapy-associated myelodysplastic syndromes and acute myeloid leukaemia (t-AML/MDS) following high dose chemotherapy are significant problems, with a cumulative incidence of 20% or more in myeloablative treatment regimen. Retrospective findings indicated that t-AML/MDS associated genetic aberrations can be observed directly after exposure to chemotherapy and can precede t-AML by several months. To determine the incidence of post-therapeutic aberrations and their predictive value, we prospectively investigated 316 samples of 95 patients with non-Hodgkin lymphoma (NHL) who were treated with intermediate and high dose chemotherapy (Arm A and B of the megaCHOEP (cyclophosphamide, doxorubicin, etoposide, vincristine, prednisolone) trial of the German High Grade NHL study group). Molecular aberrations ( RUNX1/RUNX1T1, PML-RARA, CBFB-MYH11, MLL-MLLT1, BCR-ABL1 ) were observed in 33·3% (Arm A) and 55·4% (Arm B) of patients and in 14·9% and 28·7% of respective samples. Cytogenetic analysis of 53 NHL patients after high dose therapy showed frequent chromosomal breakage. Clonal aberrations were found in three patients. None of these patients developed a t-AML/MDS during a 3-year clinical follow up period. We concluded that the high incidence of genetic aberrations reflected a dose-dependent, transient therapy-induced genetic damage which is not predictive of a t-AML/MDS.     

A single nucleotide polymorphism in the CYP4F2 but not CYP4A11 gene is associated with increased 20-HETE excretion and blood pressure

Arachidonic acid is a major fatty acid that can be metabolized by the cytochrome P450 enzyme to a number of bioactive eicosanoids. A major metabolite of this oxidation is 20-hydroxyeicosatetraenoic acid, which acts as a potent vasoconstrictor. However, in the kidney, its vasoconstrictor actions can be offset by its natriuretic properties. A guanine-to-adenine polymorphism in the CYP4F2 gene was associated with a reduction in 20-hydroxyeicosatetraenoic acid production in vitro. A thymidine-to-cytosine polymorphism in the CYP4A11 gene reduced catalytic activity by >50% in vitro and was associated with hypertension. The aim was to determine whether these 2 mutations are associated with urinary 20-hydroxyeicosatetraenoic acid excretion and blood pressure in humans. For the CYP4F2, 51% were homozygous for the G allele, 40% were carriers, and 9% were homozygous for the A allele. For CYP4A11, 72% were homozygous for the T allele, 25% were carriers, and 3% were homozygous for the C allele. The CYP4F2 GA/AA genotype was significantly associated with an increase in both 20-hydroxyeicosatetraenoic acid excretion and systolic blood pressure. The CYP4A11 CC/TC genotype was significantly associated with a reduction in 20-hydroxyeicosatetraenoic acid excretion but was not associated with blood pressure. We have demonstrated for the first time in humans that polymorphisms of the CYP4F2 and CYP4A11 genes have opposite effects on 20-hydroxyeicosatetraenoic acid excretion. The positive association between the CYP4F2 GA/AA genotype and both systolic blood pressure and 20-hydroxyeicosatetraenoic acid excretion strengthens a role for 20-hydroxyeicosatetraenoic acid in the modulation of blood pressure.