Use of thyroid hormones in hypothyroid and euthyroid patients: A THESIS questionnaire survey of UK endocrinologists.

OBJECTIVE: Management of hypothyroidism is controversial because of medication cost pressures and scientific uncertainty on how to address treatment dissatisfaction experienced by some patients. The objective was to investigate the experience and preferences of UK endocrinologists in use of thyroid hormones. DESIGN: Web-based survey. PATIENTS: UK endocrinologists were invited to participate. MEASUREMENTS: Responses to questionnaire. RESULTS: The response rate was 21% (272/1295). While levothyroxine monotherapy is regarded as the treatment of choice for hypothyroidism, 51% of respondents stated that combined treatment with levothyroxine and liothyronine could be considered for levothyroxine-treated patients whose symptoms persist despite normalisation of serum thyroid stimulating hormone (TSH) concentration. However, only 40% are currently prescribing such treatment, and just 23% would consider taking it themselves. A small minority prescribe desiccated thyroid extract, and those most likely to do so are aged over 60 years. Most respondents stated that they have no influence over brand or formulation of levothyroxine dispensed to their patients and expect no major differences in efficacy between different formulations. A total of 9% would prescribe levothyroxine for euthyroid enlarging goitre, and 29% for euthyroid female infertility with high titre thyroid peroxidase antibodies, despite recent trials finding no benefit. CONCLUSIONS: UK endocrine practice in management of hypothyroidism is broadly in line with international guidance. However, a minority of respondents would consider thyroid hormone supplementation in euthyroid individuals for female infertility, enlarging goitre, and other indications in which evidence of efficacy is lacking. Willingness to consider prescribing combined levothyroxine and liothyronine, for hypothyroid symptoms which persist despite normalised TSH, has increased in comparison to previous international surveys, despite inconsistent evidence of benefit.

Meta-analysis of colorectal cancer follow-up after potentially curative resection.

BACKGROUND: After potentially curative resection of primary colorectal cancer, patients may be monitored by measurement of carcinoembryonic antigen and/or CT to detect asymptomatic metastatic disease earlier. METHODS: A systematic review and meta-analysis was conducted to find evidence for the clinical effectiveness of monitoring in advancing the diagnosis of recurrence and its effect on survival. MEDLINE (Ovid), Embase, the Cochrane Library, Web of Science and other databases were searched for randomized comparisons of increased intensity monitoring compared with a contemporary standard policy after resection of primary colorectal cancer. RESULTS: There were 16 randomized comparisons, 11 with published survival data. More intensive monitoring advanced the diagnosis of recurrence by a median of 10 (i.q.r. 5-24) months. In ten of 11 studies the authors reported no demonstrable difference in overall survival. Seven RCTs, published from 1995 to 2016, randomly assigned 3325 patients to a monitoring protocol made more intensive by introducing new methods or increasing the frequency of existing follow-up protocols versus less invasive monitoring. No detectable difference in overall survival was associated with more intensive monitoring protocols (hazard ratio 0·98, 95 per cent c.i. 0·87 to 1·11). CONCLUSION: Based on pooled data from randomized trials published from 1995 to 2016, the anticipated survival benefit from surgical treatment resulting from earlier detection of metastases has not been achieved.

Proposed treatment strategy for reactive hypoglycaemia.

Background/aim: Managing reactive hypoglycaemia (RH) poses challenges due to limited and often ineffective treatment options. We report a case series and draw on this to propose a stepwise treatment approach consisting of lifestyle modifications, metformin, GLP-1 analogues, and the use of flash glucose monitoring technology. Method: A retrospective review was conducted to analyse the management of 11 cases presenting with recurrent RH symptoms. Result: Two patients experienced successful resolution of symptoms through lifestyle modifications. Metformin alone was effective in treating seven out of nine patients who received pharmacological treatment. Two patients with previous upper gastrointestinal surgery showed a partial response to metformin and benefited further from additional long-acting GLP-1 analogue. Pharmacological intervention led to significant reductions in insulin and C-peptide levels in repeat mixed meal tolerance tests (P-values 0.043 for insulin and 0.006 for C-peptide). Finally, flash glucose monitoring technology was useful in early detection and preventing episodes of hypoglycaemia in one of these patients with persistent symptoms. Conclusion: These findings highlight the potential efficacy of escalated treatment strategies for RH, including the use of metformin, GLP-1 analogues, and flash glucose monitoring technology.

Impact of adjuvant chemotherapy in completely resected stage IIIA non-small cell lung cancer.

AIM: Outcome of patients with locally advanced non-small-cell lung cancer (NCSLC) is generally poor, with five-year survival rate of only 23%, when patients are treated with surgery only. The presentation of positive adjuvant therapy trials in NSCLC has changed clinical practice, doubling the number of patients with completely resected NSCLC referred for adjuvant chemotherapy since 2004. Furthermore, few large studies described a large number of stage III patients in non-Asiatic patients and they showed controversial results about survival in completely resected stage IIIA NSCLC. The objective of this study was to evaluate the impact of adjuvant chemotherapy in completely resected stage IIIA NCSLC, administered on a routine basis, outside clinical trials. METHODS: This is a retrospective study of patients with stage IIIA NCSLC treated between 1990 and 2008, and included in a continuous, consecutive database. Inclusion criteria were: age >18 years, complete surgical resection, and pathologically confirmed as stage IIIA. The following clinical data were obtained: age, gender, performance status, histological type, chemotherapy regimens, status at last follow-up and hospital where the treatment occurred. Kaplan-Meier's method was used to determine actuarial survival. Differences in survival were determined by Breslow and log rank analyses. RESULTS: According to these inclusion criteria, 415 patients were considered for the present study. The median follow-up time of all patients was 38.2 months. The adjuvant chemotherapeutic treatment affected survival significantly (P <0.001). Also the type of chemotherapeutic treatment affected survival (P ≤0.001). CONCLUSION: Cisplatin-based adjuvant chemotherapy was beneficial in patients who had a completed resected stage IIIA carcinoma.

Pulmonary metastasectomy from head and neck tumors.

AIM: Isolated pulmonary metastases from head and neck cancer occur in 20%-30% of patients affected by head and neck neoplasms. Surgical resection is well accepted as a standard approach to treat metastases from head and neck cancer isolated to the lungs. Many studies reported overall five-year survival ranging from 20% to 30%. The aim of this study is to determine demographics and clinical treatment-related variables associated with long-term (60-month) overall survival in patients with lung metastases undergoing pulmonary metastasectomy from head and neck tumors. METHODS: A retrospective review was performed of patients who were admitted with lung metastases and underwent thoracotomy for resection after treatment of the primary tumor. Data were collected regarding primary tumor features, demographics, treatment, and outcome. RESULTS: Median follow-up time of all patients was 36.4 months (range: 0-288 months). The postoperative complication rate was 14.4%, and the 30-day mortality rate was 0%. The 60-month overall survival rate for all patients was 35.5%. Multivariate analysis identified the number of nodules at CT scan, the disease-free interval, and histological type as independent prognostic factors for overall survival. CONCLUSION: Lung metastasectomy is a safe and potentially curative procedure for patients with treated primary tumors. A select group of patients can achieve long-term survival after lung resection.

Three-dimensional radiographic assessment of the mandibular interforaminal donor site in different vertical facial growth types.

PURPOSE: To assess volumetrically, the impact of vertical facial growth types (VFGT) on the mandibular interforaminal region as a potential bone donor site. MATERIAL AND METHODS: 60 cone beam computed tomography (CBCT) scans of adult individuals were classified in three groups according to their SN-GoGn angle: hypodivergent group (hG) (N=20), normodivergent group (NG) (N=19) and hyperdivergent group (HG) (N=21). Total harvestable bone volume (TBV), cortico-cancellous bone volume (CBV-cBV), and cortical bone surface (CBS) were evaluated. ANOVA test followed by Tukey post hoc tests were used to compare the mean continuous outcomes according to their VFGT. RESULTS: The whole sample showed a mean TBV of 1376.32±541.01mm3, CBV of 468.52±121.54mm3 and cBV of 908.73±474.71mm3. The mean CBS amounted to 782.58±146.80mm2. The comparison between the groups stated a significantly different mean TBV and cBV (-p-value<0.001). The mean CBS was significantly different (-p-value=0.015): the smallest for the NG, but not significantly different (-p-value<0.001): the highest for the HG, intermediate for the NG and the smallest for the hG. CONCLUSION: Hypodivergent individuals have the thickest cancellous bone suitable for an onlay bone graft, while hyperdivergent individuals have the thinnest bone ideal for a 3D grafting approach.

Imaging and lung cancer.

Lung cancer remains the most common cause of cancer-related mortality in Scotland, accounting for 28.9% of all cancer deaths in 2007. Current guidelines recommend assessment of patient fitness and operability by a multidisciplinary team when selecting management options. Two of the most important prognostic markers are the stage of disease and ECOG performance status. In 1996, the International Association for the Study of Lung Cancer (IASLC) launched a worldwide TNM staging project to create international databases that would be used to continue the excellent efforts of Dr. Cliff Mountain, who pioneered this approach to lung cancer staging in 1973. Successive iterations of tumor, nodule, metastasis (TNM) staging for lung cancer have addressed shortcomings identified by the oncology community. Similarly, the IASLC recognized that it is important that further revisions continue to be made to ensure that the international staging system for lung cancer remains fit for its purpose. The last work of the International Staging Committee (ISC) was the conduct of the study that informed the seventh edition of the international staging system for lung cancer, in 2010. This review of image and staging in non small cell lung cancer (NSCLC), includes a summary of the different noninvasive tests currently available for staging non small cell lung cancer.

ErbB receptors and fatty acid synthase expression in aggressive head and neck squamous cell carcinomas.

SUMMARY: Overexpression of ErbB receptors is frequent in head and neck squamous cell carcinomas (HNSCC) and seems to be correlated with tumor progression and metastasis. Fatty acid synthase (FASN), the key lipogenic enzyme responsible for the endogenous synthesis of fatty acids, is regulated by ErbB2 and overexpressed in several human malignancies. METHODS: This study was performed to examine the immunohistochemical expression patterns of ErbB1, ErbB2, ErbB3, ErbB4, and FASN in a tissue microarray, containing 33 representative areas from aggressive primary HNSCC (whose patients had distant metastasis), and 21 matched lung metastasis. RESULTS: Strong correlation among the expression of ErbB family receptors was found (ErbB1-ErbB2 P = 0.008, ErbB1-ErbB4 P = 0.018, EbB2-ErbB3 P = 0.001, ErbB2-ErbB4 P = 0.006, ErbB3-ErbB4 P=0.012) in the HNSCC. FASN expression was significantly associated with ErbB2 (P = 0.024). Lymphatic permeation was correlated with ErbB3 (P = 0.033) and histological grade with ErbB4 staining (P = 0.050). ErbB1 and ErbB2 were found mainly in patients with smoking habit (P = 0.011 and P = 0.027), and ErbB2 was associated with alcohol consumption and clinical stage (P = 0.014 and P = 0.031). Finally, FASN was overexpressed in lung metastasis, in comparison with matched HNSCC samples (P = 0.006). CONCLUSIONS: The results showed that high FASN immunohistochemical expression is a feature of HNSCC lung metastasis, and ErbB1-ErbB2, ErbB1-ErbB4, ErbB2-ErbB3, ErbB2-ErbB4, and ErbB3-ErbB4 expression levels are correlated in the respective primary tumors, being ErbB2 the preferred coexpression partner of all the other ErbB receptors.

The defensive role of lysozyme in human gingiva in inflammatory periodontal disease.

BACKGROUND AND OBJECTIVE: The presence of lysozyme in human gingiva has not previously been demonstrated. In this study, we looked for evidence for the potential role of lysozyme as a protector of gingival elastic fibres. The objective of this study was also to determine the ex vivo susceptibility to hydrolysis of gingival elastic fibres from patients with or without periodontal disease by human leukocyte elastase and by human cathepsin G. MATERIALS AND METHODS: Using gingival tissue sections from eight control, 10 gingivitis and 10 periodontitis patients, we evaluated the area fraction occupied by gingival elastic fibres (after selective staining) by the use of automated image analysis. In the ex vivo experiments, serial tissue sections from four control, four gingivitis, four young periodontitis and four aged periodontitis patients were submitted to the action of human leukocyte elastase and cathepsin G, after which enzymatic activities were determined by image analysis. Indirect immunodetection of lysozyme was also done on tissue sections for all patients included in this study. RESULTS: Large variations of the area fraction occupied by elastic fibres were observed in human gingiva from young and aged patients with and without periodontal disease. In control and gingivitis patients, leukocyte elastase and cathepsin G had high comparable elastin solubilizing activities. With young and aged periodontitis patients, the two serine proteinases had weak elastin solubilizing activities. Lysozyme appeared to be present at the periphery of gingival elastic fibres in periodontitis patients. CONCLUSION: Lysozyme can be considered an important natural protector of elastic fibres in pathological gingiva.

Pertinent cell population to characterize periodontal disease.

The purpose of this in situ study is to quantify the inflammatory cell subsets and the area fraction (AA%) occupied by collagen fibers in human healthy and diseased (four different stages) gingival connective tissue in order to establish a possible correlation between periodontal disease resulting in collagen breakdown and specific inflammatory cell subsets. Paraffin gingival tissue sections from eight healthy controls (group 0), 10 patients with gingivitis (group 1), 10 patients with moderate periodontitis (group 2) and 10 patients with severe periodontitis (group 3) were immunohistochemically investigated using antibodies against CD-45+, CD-3+, CD-8+, CD-20+, CD-68+, and EMA+ (plasma cells). The AA% occupied by gingival collagen fibers significantly decreased from 54.12% in group (0) to 38.58% in group (1), to 31.87% in group (2), and to 25.46% in group (3). In progressive lesions of periodontal disease, CD-3(+) and CD-8+ cell numbers were increased in early stages within the connective tissue, while CD-20+ cell numbers were increased only in late stages. On the other hand, EMA+, CD-68+ and CD-45+ cell numbers were progressively increased from group (0) to group (3). We demonstrated that CD-68+ monocyte/macrophages, CD-45+ leukocyte common antigen and notably EMA+ plasma cells are pertinently correlated with the severity of periodontal disease and related collagen breakdown.

Management of neuroendocrine tumors: a meeting of experts from Latin America.

A panel of experts from Latin America convened in Brazil, in May of 2007, for consensus recommendations regarding the management of neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas. The recently introduced World Health Organization classification of NETs represents a step forward, but the former classification of carcinoids into foregut, midgut and hindgut is still likely to be useful in the near future. Macroscopic description of the tumor should be followed by light microscopic examination and immunohistochemical staining, whereas other techniques might not be widely available in Latin America. Surgery remains the mainstay of treatment for patients with potentially curable tumors, and adequate selection is paramount in order to optimize treatment results. Regarding systemic therapy, patients with well-differentiated tumors or islet-cell carcinomas may be categorized as having indolent disease, while patients with poorly differentiated, anaplastic, and small-cell carcinomas, or with atypical carcinoids, may be approached initially as having aggressive disease. Somatostatin analogues play a cytostatic role in indolent tumors, and chemotherapy may play a role against other, more aggressive NETs. Obviously, there is an urgent need for novel therapies that are effective against NETs.

In vitro breast cancer cell lethality of Brazilian plant extracts.

In this study we screened the cytotoxicity of 1220 plant extracts obtained from 351 plants belonging to 74 families occurring in the Amazon and Atlantic rain forests against MCF-7 human breast adenocarcinoma cell lines. All extracts were tested at a dose of 100 microg/mL. Only 11 aqueous or organic extracts belonging to the Annonaceae, Apocynaceae, Araceae, Clusiaceae, Flacourtiaceae, Leguminosae, Olacaceae and Violaceae showed marked lethal activity. Vismia guianensis and Annona hypoglauca extracts showed the greatest lethal activity.

Analysis of the toxic potential of Palicourea corymbifera (Müll. Arg.) Standl. in laboratory animals.

Palicourea species may produce bovine toxicity. Palicourea corymbifera grows in terra firme forests within the Amazon rain forest and in Tropical America, particularly in spots that gave place to gazing areas. The lyophilized extract done with the aerial organs of P. corymbifera were analyzed in male and female mice. Results revealed a significant toxicity: LD50 was 1.10 (1.04-1.15)g/kg for male mice, and 1.05 (1.00-1.10)g/kg for female mice. Locomotion was affected as well as there were reflexes linked to environmental stimuli in addition to changes in posture. Progressive central nervous system stimulus signs such as trembling and convulsions were detected, the latter followed by the animal's death. Macroscopic histopathological exams performed on the liver, kidneys and lungs of mice submitted to necropsy did not indicate the existence of lesions. General activity of animals, measured in an open field, was reduced as a result of the administration of the extract. Duration of locomotion and rearing frequency were reduced, in opposition to an increase in the duration of immobility. Thin layer chromatography analysis showed that monofluoroacetic acid is present in the lyophilized extract, but other qualitative techniques as gas chromatography/mass spectrometry and 19F nuclear magnetic resonance showed that the MFAA was not present in the extract, and that the toxicity is related to other compound, although the toxic profile is very similar to that of MFAA. P. corymbifera was shown to be significantly toxic to laboratory animals and investigation of the possible toxic substance shall be done.

In vitro prostate cancer cell growth inhibition by Brazilian plant extracts.

In the present study, 1220 plant extracts obtained from 352 plants belonging to 73 families that grow in the Amazon and Atlantic rain forests were screened for cytotoxicity against PC-3 prostate cancer cell lines. Extracts were tested in the single dose of 100 microg/mL. Activity was observed in 17 aqueous or organic extracts belonging to Annonaceae, Apocynaceae, Araceae, Capparaceae, Commelinaceae, Flacourtiaceae, Lecythidaceae, Leguminosae, Passifloraceae, Rutaceae, and Violaceae.

Tumor-induced alterations in tissue lipoprotein lipase activity and mRNA levels.

To elucidate the mechanisms of hypertriglyceridemia observed in the tumor-bearing rat, tissue lipoprotein lipase (LPL) activity and LPL mRNA levels were examined in the fed and fasted states at different degrees of tumor burden and after tumor removal. LPL activity in the epididymal fat pad and cardiac muscle in the 24-h-fasted rats was significantly decreased with increasing tumor burden (r = -0.53, P less than 0.05 and r = -0.72, P less than 0.01, respectively). Tumor removal completely reversed these changes. In contrast, no change in LPL activity was detected in the fed state since food intake stimulated LPL activity to the same extent in both tumor-bearing (TBR) and control rats. LPL activity in the diaphragm and skeletal muscle was only marginally altered in TBR, as compared to controls. LPL mRNA from the epididymal fat pad and cardiac muscle migrated to the same site on agarose gel and hybridized to a LPL-specific complementary DNA probe. The decline in LPL activity in epididymal fat pad observed in TBR was associated with a decrease in LPL mRNA levels. In contrast, there was no significant difference in LPL mRNA levels in cardiac muscle between the two groups despite significantly suppressed enzyme activity in tumor bearers. This study provides evidence that hypertriglyceridemia in TBR is due in part to tumor-dependent suppression of adipose and cardiac LPL activity in the fasted state, which is stimulated by the presence of tumor. Unlike cardiac LPL, the tumor-induced changes in adipose LPL activity are regulated at the mRNA level in this tumor model.

Biotribocorrosion (tribo-electrochemical) characterization of anodized titanium biomaterial containing calcium and phosphorus before and after osteoblastic cell culture.

The purpose of this study was to investigate the relationship between the osteoblastic cells behavior and biotribocorrosion phenomena on bioactive titanium (Ti). Ti substrates submitted to bioactive anodic oxidation and etching treatments were cultured up to 28 days with MG63 osteoblast-like cells. Important parameters of in vitro bone-like tissue formation were assessed. Although no major differences were observed between the surfaces topography (both rough) and wettability (both hydrophobic), a significant increase in cell attachment and differentiation was detected on the anodized substrates as product of favorable surface morphology and chemical composition. Alkaline phosphatase production has increased (≈20 nmol/min/mg of protein) on the anodized materials, while phosphate concentration has reached the double of the etched material and calcium production increased (over 20 µg/mL). The mechanical and biological stability of the anodic surfaces were also put to test through biotribocorrosion sliding solicitations, putting in evidence the resistance of the anodic layer and the cells capacity of regeneration after implant degradation. The Ti osteointegration abilities were also confirmed by the development of strong cell-biomaterial bonds at the interface, on both substrates. By combining the biological and mechanical results, the anodized Ti can be considered a viable option for dentistry.

Lead neuropathy in adults and children.

All parts of the nervous systems can be affected, depending on the level and duration of exposure, by increased levels of lead. The occurrence of motor neuron disease, peripheral neuropathy, and encephalopathy are not mutually exclusive disorders for those individuals suffering from the toxic effects of lead. We present data that support the concept that increased absorption of lead produces changes in both central and peripheral nervous systems. Clinical and electrical evidence of subclinical involvement of peripheral nerves appears to be common to adults and children who are exposed to lead. These observations, accumulated from several possible sources of environmental hazard, also suggest that measurement of motor nerve conduction velocity may serve as an additional factor in the diagnosis of otherwise unrecognized toxic effects of lead.

Prognostic factors to predict outcome following the administration of hypertonic/hyperoncotic solution in hypovolemic patients.

Hypertonic solutions effectively improve hemodynamic parameters in patients admitted to the emergency room. However, no significant differences in outcome were observed compared with standard isotonic treatment in most previously published studies. This study evaluates pretreatment prognostic factors that predict a beneficial effect of hypertonic solution in patients admitted to the emergency room with hemorrhagic hypovolemia in a prospective double-blind fashion. The patients (n = 212) were randomized upon admission to receive 250 mL intravenous (i.v.) bolus of hypertonic 7.5% NaCl + 6% dextran (HSD, n = 101), or isotonic 0.9% NaCl solutions (IS, n = 111) as the first treatment, followed by standard resuscitation. Pretreatment factors assessed were sex, age, cause of hypovolemia, revised trauma score (RTS), Glasgow index, and mean arterial pressure (MAP) on admission. Both groups were compared for survival at 24 h and 30 days postadmission. Infused volumes were registered. HSD administration significantly increased MAP and reduced i.v. crystalloid infusions to maintain hemodynamic parameters, compared with IS. There was no difference between groups in the number of blood transfusions administered. Overall complication rates in both groups were similar (24%). There was a significant difference (p < .03) in overall (30 days) survival rate between HSD (73%) and IS (64%) groups. The 24 h survival rate was significantly lower in IS (72%) compared with HSD (87%); p < .01. Multivariate analyses showed that RTS and MAP were identified as independent predictors for 24 h survival in the group that received HSD. When evaluated for overall survival rate, hypertonic infusion benefited significantly only patients with MAP < 70 mmHg (p < .01).

Follow-up in lung cancer: how often and for what purpose?

OBJECTIVES: The present study evaluates the cost-effectiveness of two follow-up routines: a strict follow-up with frequent visits, imaging, and laboratory examinations was compared to a follow-up with infrequent visits that were scheduled mainly on the basis of the patient's symptoms. METHODS: A retrospective evaluation was undertaken of 130 patients who underwent a complete resection of non-small cell lung cancer (NSCLC). All patients had complete follow-up for at least 2 years after their operation. The patients were separated into two groups: strict (n = 67), with a routine follow-up policy; and symptom (n = 63), seen on a symptom-oriented basis. The costs of the follow-up routines and the yield of each schedule were compared between the two groups. RESULTS: There were no significant differences in the disease-free interval until the first detection of recurrence. In most patients, metastatic diseases were diagnosed on the basis of symptoms, rather than by routine tests. The patients who had recurrent cancer diagnosed after surgery had a dismal survival rate irrespective of the follow-up schedule. The majority of patients with recurrence died of malignancy within a 2-year period. The costs of strict vs symptom follow-up were significantly different, because of the greater number of routine imaging procedures performed in patients having strict follow-up. On the other hand, when we analyzed only the frequency of hospitalization and the cost per day of hospital treatment for medical problems other than cancer recurrence, the patients in the strict group had a less expensive follow-up than the patients in the symptom group. CONCLUSIONS: The present study showed that a more cost-effective routine follow-up scheme should be advised for patients with completely resected NSCLC, without affecting overall outcome. Routine imaging follow-up is of questionable value, and it may be indicated only in academic settings.