Advanced thyroid carcinoma: an experience of 385 cases.

AIMS: To report clinical outcomes of a large series of cases with advanced thyroid cancer. STUDY DESIGN: Three hundred and eighty-five patients at the UICC stages III and IV were selected for the study with thyroid cancer. RESULTS: Papillary carcinoma and sclerosing carcinoma have better survival than the Hürthle cell and insular types. Lymphatic metastasis does not appear to worsen the prognosis. All the tumour forms offer the chance of long survival. CONCLUSIONS: Surgical treatment is the primary treatment of thyroid carcinoma. The combined treatments of surgery, metabolic beam therapy, suppressive hormone therapy, radiotherapy and chemotherapy cure a high percentage of patients with the tumour at an advanced stage.     

Poor Intraoperative Blood Glucose Control Is Associated with a Worsened Hospital Outcome after Cardiac Surgery in Diabetic Patients

Background: Tight perioperative control of blood glucose improves the outcome of diabetic patients undergoing cardiac surgery. Because stress response and cardiopulmonary bypass can induce profound hyperglycemia, intraoperative glycemic control may become difficult. The authors undertook a prospective cohort study to determine whether poor intraoperative glycemic control is associated with increased intrahospital morbidity.

Methods: Two hundred consecutive diabetic patients undergoing on-pump heart surgery were enrolled. A standard insulin protocol based on subcutaneous intermediary insulin was given the morning of the surgery. Intravenous insulin therapy was initiated intraoperatively from blood glucose concentrations of 180 mg/dl or greater and titrated according to a predefined protocol. Poor intraoperative glycemic control was defined as four consecutive blood glucose concentrations greater than 200 mg/dl without any decrease in despite insulin therapy. Postoperative blood glucose concentrations were maintained below 140 mg/dl by using aggressive insulin therapy. The main endpoints were severe cardiovascular, respiratory, infectious, neurologic, and renal in-hospital morbidity.

Results: Insulin therapy was required intraoperatively in 36% of patients, and poor intraoperative glycemic control was observed in 18% of patients. Poor intraoperative glycemic control was significantly more frequent in patients with severe postoperative morbidity (37% vs. 10%; P < 0.001). The adjusted odds ratio for severe postoperative morbidity among patients with a poor intraoperative glycemic control as compared with patients without was 7.2 (95% confidence interval, 2.7-19.0).     

Early neonatal inflammation affects adult pain reactivity and anxiety related traits in mice: genetic background counts

Protracted or recurrent pain and inflammation in the early neonatal period may cause long-lasting changes in central neural function. However, more research is necessary to better characterize the long-term behavioral sequelae of such exposure in the neonatal period. Objectives: (1) to study whether timing of postnatal exposure to persistent inflammation alters responsiveness to thermal pain in the adult animal; (2) to assess whether animals experiencing early postnatal chronic inflammation display altered anxiety related behavior; (3) to study the importance of genetic background. Newborn mice (outbred strain, CD1 and F1 hybrid strain, B6C3F1) received an injection of Complete Freund's Adjuvant (CFA) or saline on either postnatal day 1 or 14 (PND1; PND14) into the left hind paw. Pain to radiant heat and anxiety were examined in 12-week-old adult animals. Adult baseline PWL was significantly decreased in CD1 mice exposed to CFA on PND 1 and 14 as compared to their saline treated counterparts. B6C3F1 mice exposed to CFA on PND14 showed markedly reduced baseline PWL compared to the PND14 saline group. Persistent inflammation experienced by B6C3F1 mice on PND1 failed to affect baseline adult thermal responsiveness. Adult mice, CD1 and B6C3F1, displayed low anxiety traits only if they had been exposed to persistent inflammation on PND1 and not on PND14. Our research suggests a role for genetic background in modulating long-term behavioral consequences of neonatal persistent inflammation: the data support the hypothesis that pain experienced very early in life differentially affects adult behavioral and emotional responsiveness in outbred (CD1) and hybrid mice (B6C3F1).     

Free insulin-like growth factor-I and cognitive function in older persons living in community.

CONTEXT: Increasing evidences from experimental and human studies suggest that the activity of the growth hormone (GH/insulin-like growth factor-I) axis may contribute to the age-related cognitive decline and poor cognition in late life. OBJECTIVE: The aim of the present study was to evaluate the relationship of total serum free IGF-I and its binding protein-3 with cognitive performance in older persons aged 80 years or older. DESIGN: Data are from baseline evaluation of the ilSIRENTE study (n=353). Cognitive performance was evaluated using five items enclosed in the Minimum Data Set for Home Care assessment form: short-term memory, procedural memory, cognitive skills in daily decision making, verbal expression, comprehension. Free insulin-like growth factor-I (free IGF-I) and IGF-binding protein-3 (IGFBP-3) in blood were measured. Analysis of covariance (ANCOVA) was used to examine the relationship between cognitive impairment and the serum free IGF-I and IGFBP-3 concentrations, after adjustment for potential confounding variables. RESULTS: After adjustment for potential confounders, which included age, gender, education, cerebrovascular disease, ischemic heart disease, congestive heart failure, hypertension, diabetes, depression, Parkinson diseases, thyroid diseases, smoking status, alcohol abuse, body mass index, and number of medications, individuals with verbal expression problems (n=20) and individuals with comprehension problems (n=24) had a significantly lower serum levels of readily dissociable IGF-I than participants without cognitive impairments. The serum IGFBP-3 presented the same behavior of free IGF-I. CONCLUSION: The present study suggests that among old-old subjects living in the community lower levels of total serum free IGF-I and IGFBP-3 are associated with impairment of cognitive performance. This finding suggests that the GH/IGF-I axis may play an important role in the age-related decline of cognitive performance.     

Esthesioneuroblastoma: endonasal endoscopic treatment.

Objectives: To illustrate endoscopic techniques used in the treatment of esthesioneuroblastoma and to advocate this method of management followed by radiation therapy in selected cases. Methods: A retrospective case series of 10 patients with esthesioneuroblastomas treated between 1999 and 2004 at a tertiary referral center using endonasal techniques. Results: Mean age of patients at presentation was 56.2 years (median 57 years). Seven patients were female and 3 patients were male. Kadish staging at presentation was: A - 3 patients, B - 5 patients, C - 2 patients. Dulguerov stage at presentation was: T1 - 4 patients, T2 - 4 patients, T3 - 2 patients. The period of follow-up ranged from 11 months to 74 months (mean 38.1 months, median 39 months). To date no recurrence has developed in any patient. Conclusions: Our experience suggests that endoscopic surgery can be an effective method of management. Strict attention to selection criteria, careful surgical techniques, and regular follow-up are key elements for success.     

Significance of cyclin D1 expression in meningiomas: a preliminary study.

Forty-four evaluable patients with intracranial meningiomas were assessed for the expression of the cell-cycle regulator cyclin D1 and of proteins involved in proliferation and apoptosis such as PCNA, MIB-1, p53 and bcl-2. Analyses were carried out by western blot and immunohistochemistry after immediate processing of fresh tumor specimens. By western blot, expression of cyclin D1 significantly correlated with p53 (p=0.02) and with proliferative activity, as assessed by PCNA expression (p=0.0009). By immunohistochemistry, a significant relationship between cyclin D1 and the proliferation marker MIB-1 was confirmed (p=0.05), whereas significance with bcl-2 expression was not found (p=0.01). Moreover, although the association with tumor grade appeared of borderline statistical significance (p=0.07), all the grade II/III meningiomas showed increased expression of cyclin D1 and high proliferative activity. In conclusion, data from this preliminary study seem to suggest a potential value of the combined expression of cyclin D1 and proliferation indicators in defining subgroups of meningiomas with a more aggressive biological behavior.     

Dolichol content in isolated sinusoidal liver cells after in vivo chronic treatment with thioacetamide.

The content of dolichol, an isoprenoid present in all biological membranes, was determined in isolated sinusoidal liver cells after treatment of rats for 2 and 4 months with a low dosage of the hepatotoxin thioacetamide. The significant decrease in dolichol observed in hepatocytes after 2 months might be explained by peroxidation of the isoprenoid. At the same time point, retinol was retained, and decreased only after 4 months of treatment. After 4 months of treatment therefore both lipids decreased. In a subfraction of hepatic stellate cells, Ito-1 cells, the main storage site of vitamin A, dolichol decreased significantly only after 4 months. A remarkable difference from hepatocytes is that in Ito-1 cells retinol content significantly decreased after 2 months of treatment. In another subfraction, Ito-2 cells, the content of the two isoprenoids decreased in parallel. This heterogeneous subfraction might represent those transitional hepatic stellate cells that, while losing retinol, are in the process of differentiating into myofibroblasts secreting extracellular matrix components. In Kupffer cells and sinusoidal endothelial cells, impairment of dolichol might be observed later, only after 4 months of treatment, while retinol decreases uniformly over time. Starting after two months of treatment, the decrease of dolichol and the increase of retinol in hepatocytes, at the same time as retinol decreases in hepatic stellate cells, might be taken as an early index of incipient liver injury due to thioacetamide. This hypothesis is discussed with regard to a role of dolichol in the modulation of membrane fluidity for intracellular and intercellular retinol transport.     

Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB).

PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder. INTRODUCTION: Paget's disease of bone (PDB) is a relatively common disease of bone metabolism reported to affect up to 3% of whites over 55 years of age. The disorder is genetically heterogeneous, and at present, there is scientific evidence that at least eight different human chromosomal loci are correlated with its pathogenesis. Mutations of the sequestosome1 (SQSTM1) gene were identified as responsible for most of the sporadic and familial forms of Paget in patients of French Canadian and British descent. Such mutations were located at exon 7 and 8 levels, encoding for the ubiquitin protein-binding domain (UBA) and representing a mutational hot spot area. MATERIALS AND METHODS: To verify the involvement of this gene in Italian subjects affected by PDB, we performed mutational analysis in 62 sporadic PDB cases. RESULTS: We described three different mutations at exon 8 level: P392L, already described in the French Canadian population and families predominantly of British descendent, and two novel mutations consisting of the amino acid substitutions M404V and G425R. No significant differences in the clinical history of PDB have been observed in patients with SQSTM1 mutations in respect to those without. CONCLUSIONS: Even though our findings suggest a minor involvement of the SQSTM1 gene in the pathogenesis of sporadic Italian Paget's cases, the identification of different significant mutations within the SQSTM1 gene in unrelated, but clinically similar individuals, offers extremely convincing evidence for a causal relationship between this gene and PDB. Longitudinal studies are needed to assess the penetrance of genotype/phenotype correlations. Our findings confirm the evidence of a clustered mutation area at this level in this disorder.     

Functional decline in frail community-dwelling stroke patients

Patients who suffer a stroke event are at high risk of functional decline after the post-acute rehabilitation period. The aim of the present study was the evaluation of factors associated with functional decline in a large sample of older patients with stroke living in the community. The study population consisted of all patients admitted to home care programs after a post-acute rehabilitation program--with at least 1 year of follow-up--in twenty-two Italian Home Health Agencies from 2000 to 2002 (n=1338). For the present study we selected 355 (26%) patients with diagnosis of stroke. After 1 year of in-home care program, 149 out of 355 stroke survivors (42%) had presented a worsening in the activities of daily living (ADL) scale score. In the final adjusted model, patients with cognitive impairment (OR 2.59, 95% CI, 1.45-4.64), pressure ulcer (OR 2.74, 95% CI, 1.45-5.18), urinary incontinence (OR 1.64, 95% CI, 1.01-3.29), or hearing impairment (OR 1.83, 95% CI, 1.02-3.29) were more likely to significantly decline in physical functioning after a period of 1 year in-home care program. Our study documents that functional decline of stroke patients was largely dependent on specific subjects' clinical characteristics. Three of four concomitant disabling conditions associated in our sample with functional decline--pressure ulcer, urinary incontinence, hearing--can be prevented and eventually treated or modified. Appropriate post-acute rehabilitation programs and adequate home care interventions focused on the prevention and treatment of these conditions might be correlated to better outcomes in older post-stroke patients.     

Prognostic value of pharmacological stress echocardiography in diabetic and nondiabetic patients with known or suspected coronary artery disease.

OBJECTIVES: We sought to compare the prognostic value of pharmacological stress echocardiography (SE) in diabetic and nondiabetic patients with known or suspected coronary artery disease. BACKGROUND: Although SE is a useful tool for risk stratification of patients with diabetes, it has not been established whether it retains the same prognostic information in diabetic patients compared with nondiabetic patients. METHODS: A total of 5,456 patients (749 diabetics) undergoing dipyridamole (n = 3,306) or dobutamine (n = 2,150) SE were prospectively followed up for the occurrence of hard events (death and/or nonfatal myocardial infarction). RESULTS: During a median time of 31 months, 411 deaths and 236 infarctions occurred. There were 132 events in diabetic patients and 515 in nondiabetic patients (18% vs. 11%, respectively; p < 0.0001). Moreover, 1,607 (29%) patients underwent coronary revascularization and were censored. Ischemia at SE, resting wall motion score index, and age were independent predictors of death and hard events in both diabetic and nondiabetic patients. Compared with a normal test, ischemia and scar test patterns were associated to significantly lower age-corrected five-year hard event-free survival in diabetic as well as nondiabetic patients. However, a normal test was associated with a greater than two-fold annual event rate in diabetic patients as compared with nondiabetics who were either younger (2.6% vs. 1.0%) or older (5.5% vs. 2.2%) than 65 years of age. CONCLUSIONS: Stress echocardiography is equally effective in risk stratifying diabetic and nondiabetic patients independently of age. However, the normal test result predicts a less favorable outcome in diabetic than in nondiabetic patients.