Analysis of influenza data generated by four epidemiological surveillance laboratories in Mexico, 2010-2016.

The disease caused by the influenza virus is a global public health problem due to its high rates of morbidity and mortality. Thus, analysis of the information generated by epidemiological surveillance systems has vital importance for health decision making. A retrospective analysis was performed using data generated by the four molecular diagnostic laboratories of the Mexican Social Security Institute between 2010 and 2016. Demographics, influenza positivity, seasonality, treatment choices and vaccination status analyses were performed for the vaccine according to its composition for each season. In all cases, both the different influenza subtypes and different age groups were considered separately. The circulation of A/H1N1pdm09 (48.7%), influenza A/H3N2 (21.1%), influenza B (12.6%), influenza A not subtyped (11%) and influenza A/H1N1 (6.6%) exhibited well-defined annual seasonality between November and March, and there were significant increases in the number of cases every 2 years. An inadequate use of oseltamivir was determined in 38% of cases, and the vaccination status in general varied between 12.1 and 18.5% depending on the season. Our results provide current information about influenza in Mexico and demonstrate the need to update both operational case definitions and medical practice guidelines to reduce the inappropriate use of antibiotics and antivirals.

Autodisplay of an avidin with biotin-binding activity on the surface of Escherichia coli.

OBJECTIVES: To display a recombinant avidin fused to the autotransporter ShdA to bind biotinylated molecules on the surface of Escherichia coli. RESULTS: Two chimeric protein constructs containing avidin fused to the autotransporter ShdA were expressed on the surface of Escherichia coli DH5α. One fusion protein contained 476 amino acids of the ShdA α and ß domains, whereas the second consisted of a 314 amino acid from α and truncated ß domains. Protein production was verified by SDS-PAGE using an antibody to the molecular FLAG-tag. The surface display of the avidin-shdA fusion protein was confirmed by confocal microscopy and flow cytometry analysis, and the biotin-binding activity was evaluated by fluorescence microscopy and flow cytometry using biotin-4-fluorescein and biotinylated-ovalbumin (OVA). CONCLUSIONS: Expression of a recombinant avidin with biotin-binding activity on the surface of E. coli was achieved using the autotransporter ShdA. This system is an alternative to bind biotinylated molecules to E. coli.

Establishment and cryptic transmission of Zika virus in Brazil and the Americas.

Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.

Complete Genome Sequence of Human Respiratory Syncytial Virus Isolated in Mexico.

Human respiratory syncytial virus (HRSV) is a member of the Paramyxoviridae family, which causes lower respiratory tract infections in neonates and children younger than 5 years. Here, we report the complete genome sequence of HRSV, isolated from a nasopharyngeal swab of a pregnant woman with cardiac complications.

Targeting platinum resistant disease in ovarian cancer.

Ovarian cancer is an extremely aggressive disease in which the vast majority of patients face a very poor prognosis. Although most patients initially respond to current chemotherapeutic regimens that include a combination of platinum- based therapy (cisplatin/carboplatin) and paclitaxel, the vast majority of them quickly relapse and develop increased resistance to available treatments. Thus, intrinsic and acquired chemotherapy resistance is a major obstacle in the treatment of ovarian cancer patients. Consequently, the priorities for basic and translational ovarian cancer research need to include the identification of novel therapies directed against key molecular targets and signaling pathways in platinum resistant disease. At the same time, we need to develop novel systems for drug delivery aimed at increasing the efficacy and reducing the toxicity of platinum-based treatments. Improving the current responses to platinum chemotherapy is critical not only for achieving a better outcome clinically, including a longer survival, but also for allowing patients to have a better quality of life while in treatment.

Is dissection of level IV necessary in patients with T1-T3 N0 tongue cancer?

OBJECTIVE: Dissection of the lower jugular level of lymph nodes (level IV), as part of an elective neck dissection, has been advocated recently for all patients with oral tongue cancer because of the possibility of "skip metastases" to levels III and IV. The current study was undertaken to evaluate the need to perform a dissection of level IV in patients with oral tongue cancer with no clinical evidence of nodal metastases. METHODS: Fifty-one patients with T1-3, N0 squamous cell carcinoma of the oral tongue were treated with a partial glossectomy and a selective neck dissection of levels I, II, and III. When enlarged nodes were encountered during surgery in level II or III, the dissection was extended to include the nodes in level IV. Involvement of level IV was determined either by the presence of carcinoma on pathological examination or by the development of recurrence in the untreated level IV during a follow-up period of at least 2 years. RESULTS: Level IV was resected as part of the specimen in 17 of the 51 patients and metastatic tumor was found in this level in only one patient. At an average follow-up of 4.1 years, only one patient recurred at level IV, which had been addressed at the initial neck dissection. Consequently, the rate of metastases to undissected level IV was 2%. CONCLUSIONS: Metastases to level IV lymph nodes is rare in patients with T1-T3, N0 oral tongue cancer. Dissection of these nodes only when there is intraoperative suspicion of metastases in levels II or III does not increase the risk or recurrence of tumor in the neck.

Early oral feeding following total laryngectomy.

OBJECTIVES: The time to begin oral feeding after total laryngectomy remains a subject of debate among head and neck surgeons. The prevailing assumption is that early initiation of oral feeding may cause pharyngocutaneous fistula; thus, the common practice of initiating oral feeding after a period of 7 to 10 days. The objective of the study was to demonstrate the feasibility and safety of oral feeding 48 hours after total laryngectomy. STUDY DESIGN: Two-part study includes, first, a sequential study and, second, a prospective analysis of our practice. METHODS: Patients undergoing total laryngectomy without partial pharyngectomy or radiation treatment (except irradiation through small ports for a T1 or T2 glottic carcinoma) were included. In the first, sequential part of the study (part I), a group of 18 patients who were fed 7 to 10 days after total laryngectomy (control group) was compared with a group of 20 patients who received oral feeding within 48 hours. To confirm the results of part I, a prospective analysis of this practice was conducted (part II) in which 35 additional patients who met the above criteria were fed within 48 hours after surgery. RESULTS: In part I, pharyngocutaneous fistula occurred in one patient (5%) in the early feeding group and in two patients (11%) in the control group. In part II, pharyngocutaneous fistula occurred in one patient (2.8%). Overall, fistula occurred in two patients in the combined early feeding group (3.6%). This rate of pharyngocutaneous fistula compares favorably with the fistula rate in the control group of 18 patients. Pharyngeal stricture that required dilation occurred in three of our patients in the study group and two in the control group (5.5% vs. 11%, respectively). The length of hospital stay was significantly shortened from 12 to 7 days. CONCLUSION: Our results indicate that in this patient population initiation of oral feeding 48 hours after total laryngectomy is a safe clinical practice.

Treatment of giant cell granuloma of the maxilla with intralesional injection of steroids.

BACKGROUND: Giant cell granuloma is rare in the head and neck region and most commonly affects the maxilla and mandible. Although it is a benign disease process, it may be locally destructive. Surgery is the treatment currently recommended. Because of the location of the disease, surgery may be disfiguring. Because it is a benign process, less radical nonsurgical treatment alternatives are desirable. METHODS: A case report of a giant cell granuloma treated with steroid injections. RESULTS: After six weekly intralesional steroid injections, a giant cell granuloma of the maxilla became calcified and smaller. After a follow-up period of 2 years, there was no evidence of regrowth, and the bony osteolytic lesion had filled with bone. A review of the literature revealed two case reports of successful steroid injections with similar response. CONCLUSIONS: Steroid injections are a viable alternative in the treatment of giant cell granuloma, which may avoid surgery.

Tumor grade, microvessel density, and activities of malate dehydrogenase, lactate dehydrogenase, and hexokinase in squamous cell carcinoma.

Squamous cell carcinomas were evaluated with respect to tumor differentiation (through use of hematoxylin and eosin stain), microvessel density (through use of CD-34 immunocytochemical stain), and magnitudes of malate dehydrogenase (MDH), hexokinase, and lactate dehydrogenase (LDH) enzyme activities. Direct correlations were found between tumor grade, MDH activity, and microvessel density. Direct correlations were also found between hexokinase activity and MDH activity and microvessel density. Inverse correlations were found between LDH activity and both tumor grade and MDH activity. These results suggest that the high rate of glucose utilization (indicated by hexokinase activity) found in more poorly differentiated tumors has a higher component of aerobic oxidative metabolism (indicated by MDH activity) and a relatively lower contribution from anaerobic metabolism (indicated by LDH activity) than do the rates found in more differentiated tumors. It is also suggested that as the glycolytic rate increases, more pyruvate goes into the Krebs cycle than into lactate. The availability of glucose-derived pyruvate for oxidative metabolism would mean less of a dependency on glutamine as a carbon source in squamous cell carcinoma.

Enhanced visualization of parathyroid tissue by infusion of a visible dye conjugated to an antiparathyroid antibody.

BACKGROUND: The antiparathyroid antibody BB5-G1 conjugated to cibacron blue, a blue dye, was intravenously infused to enhance parathyroid visualization. Previously, we demonstrated selective staining of human parathyroid implants in athymic nude mice after infusion of the conjugate. METHODS: Mice possessing implanted parathyroid tissue were randomized into the following: group I, infused with cibacron blue alone; group II, infused with the antibody/dye conjugate; and group III, infused with radiolabeled BB5-G1 alone. Implants were surgically explored. Three blinded observers ranked parathyroid visualization in the operative fields, and corresponding histologic sections were computer analyzed. RESULTS: Group II implants were easily visualized; groups I and III showed no staining. Group III showed high gamma counts. Subjective rankings and computer rankings correlated well (p < .05). Group II showed a higher mean staining intensity of 27.45 picogram protein product (PPP)/cell compared with 7.76 PPP/cell of group I (p = .002). CONCLUSION: Cibacron blue/BB5-G1 consistently enhances visualization of implanted parathyroid tissue.

Quantitative biochemical analysis of samples from squamous cell carcinoma.

Samples of tumor, tumor stroma, and mixed tumor and stroma were microdissected from three squamous cell carcinomas, as well as from adjacent nontumor tissue and assayed for malate dehydrogenase or lactate dehydrogenase activity as indicators of the relative contribution of aerobic and anaerobic processes, respectively, to energy metabolism. Malate and lactate dehydrogenase activities were greater in tumor tissue than in tumor stroma in all three tumors. However, the magnitudes of malate and lactate dehydrogenase activities were different among the tumors, suggesting that tumors vary in the degree to which aerobic and anaerobic reactions contribute to energy production. These results indicate that a quantitative assessment of enzymes involved in energy production may be a useful probe in the understanding of tumor metabolism.

Neck dissection in the treatment of cancer of major salivary glands.

The treatment of the neck nodes in salivary gland tumors has changed considerably in the last two decades. The current thinking and the rationale for it are discussed in detail in this article.

Nodal metastases: predictive factors.

Squamous cell carcinoma of the upper respiratory and digestive tract has a high risk for neck metastasis, which reduces the probability of regional control and survival. We analyzed the literature and our own experience to review the possible risk factors for the occurrence of metastasis. The most significant risk factors were: tumor site and size, grade of histologic differentiation, tumor thickness (tongue and floor of mouth carcinoma), vascular embolization, and perineural infiltration. A series of biomarkers has been studied over the last 10 years, but no one has proved to be significant enough for clinical use. Based on several multivariate analysis, it is recommended elective treatment of the neck for high-risk patients.

Evaluation of Tomudex in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a Southwest Oncology Group study.

A phase II trial of Tomudex (raltitrexed, ZD 1694), a new thymidylate synthase inhibitor, was performed in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. This trial demonstrated that Tomudex was well tolerated in this patient population. Nausea and vomiting were minimal, and hematologic toxicities were relatively infrequent. Only one patient was withdrawn from the study due to toxicity (grade 4 diarrhea). One patient exsanguinated from a rent in the carotid artery in an area of tumor involvement, and was categorized as a grade 5 toxicity. Thus 25/27 patients were able to complete at least 2 cycles of treatment. Tomudex demonstrated a 3.7% response rate (95% CI 0.1-19%), with a median survival of 6 months in this highly resistant disease population. Tomudex is not considered active enough as monotherapy for further evaluation in this disease population.

Parathyroid visualization with cibacron blue/BB5-G1.

BB5-G1 is a murine monoclonal antibody with proven affinity for human parathyroid tissue. The authors conjugated BB5-G1 to cibacron blue, a water-soluble dye, in an attempt to enhance intraoperative parathyroid visualization. Athymic nude mice possessing intramuscularly implanted human parathyroid tissue were infused with the conjugate, then surgically explored. Intraoperative findings were video-captured, then analyzed by three independent observers and by computer, generating subjective and objective data quantifying parathyroid visualization. Parathyroid tissue implants were stained and were easily visualized. The implants in the test mice displayed higher computer-generated color intensity ratings (mean, 10.25 units) compared to control mice (mean, 6.10 units) (p<0.5). Histologic sections confirmed the presence of dye and antibody within parathyroid tissue. This represents the first study to use such a conjugate to selectively enhance parathyroid visualization.

Management of cervical lymph nodes in squamous carcinomas of the head and neck.

Due to the overwhelming prognostic significance of regional metastases, proper management of cervical lymph nodes in cases of squamous cell carcinoma of the head and neck is essential for an optimal outcome. Better understanding of the predictability of incidence and patterns of metastases of these tumors in recent years has led us away from the radical neck dissection as the only surgical therapeutic or staging procedure done on the neck. Recent studies suggest that selective removal of lymph node groups at risk in clinically negative necks, or modified neck dissections that save important structures, like the jugular vein, XI nerve, and sternocleidomastoid muscle, in clinically positive necks, are appropriate in many patients. Careful selection of the type of neck dissection and judicious use of postoperative radiation therapy can optimize cure rates as well as functional and cosmetic results.

Accumulation of the p53 tumor-suppressor gene product in oral leukoplakia.

OBJECTIVES: (1) To determine whether the protein of the suppressor gene p53 accumulates in leukoplakia of the oral cavity in individuals who use snuff; and (2) to determine whether a correlation exists between the accumulation of p53 protein and the degree of epithelial dysplasia present in oral leukoplakia. DESIGN: Retrospective analysis of archival tissue specimens. SETTING: The University Hospital, a tertiary referral hospital affiliated with the Oklahoma University Medical Center, Oklahoma City, Oklahoma. PATIENTS: In the first part of the study, biopsy specimens of leukoplakia from 12 persons who used snuff were compared with specimens from uninvolved oral mucosa of the same persons and with biopsy specimens from 12 nontobacco-using persons. In the second part of the study, accumulation of p53 protein was determined in 42 archival paraffin-embedded specimens from oral leukoplakia and correlated with the degree of epithelial dysplasia. METHODS: Accumulation of p53 protein was assessed by immunoperoxidase staining with four different primary antibodies. Positive cells were counted in five consecutive high-power fields. RESULTS: In part one, the average number of positive cells in the leukoplakia of snuff-users (21.89 +/- 4.33; mean +/- SE) was higher than that of normal-appearing mucosa (4.00 +/- 1.0; p < 0.05) and that of nontobacco-using controls (7.00 +/- 5.04). In part two, the average number of positive cells was higher in the moderately dysplastic (140.36 +/- 30.03) and severely dysplastic lesions (232.86 +/- 26.85) than in the mildly dysplastic lesions (14.53 +/- 3.33; p < 0.05). The correlation between the degree of epithelial dysplasia and the number of cells positive is strong (Spearman's correlation coefficient = 0.853). CONCLUSIONS: The accumulation of p53 protein in leukoplakia of snuff-users is higher than in normal-appearing oral mucosa from both snuff-users and nontobacco-using controls. A strong correlation exists between the degree of epithelial dysplasia present in oral leukoplakia and the number of cells staining positive for p53. The accumulation of p53 protein holds potential as an intermediate end point in studies of chemoprevention of oral cancer.

Reasons for placement, replacement, and age of gold restorations in selected practices.

A total of 745 gold restorations were surveyed concerning the reasons for their placement and replacement. Cast gold restorations (n = 480) were placed due to primary caries (23%), replacement of amalgam (39%), and composite restorations (9%), or due to failure of existing gold restorations (29%). The main reasons for replacement of cast gold restorations were fracture of tooth (36%) and secondary caries (22%). The main reasons for the placement of compacted gold restorations (n = 265) were treatment of primary caries (40%), failure of an existing compacted gold restoration (26%), removal of another type of restoration (18%), and repair of a defective margin of a casting (16%). The main reasons for replacement of compacted gold restorations were inclusion into larger restorations (29%) and secondary caries (21%). The longevity of failed gold restorations was recorded for 111 restorations. The mean age for failed cast and compacted gold restorations was about 18.5 years (range 5-41 years). The ages of 2564 gold restorations in situ, 1689 castings, and 875 compacted gold restorations were recorded. The median and mean ages for gold castings were about 15 and 16 years and for compacted gold restorations about 17 and 18 years.