[Low levels of HDL cholesterol in hypothyroid patients with cardiovascular diseases]. / Ridotti livelli di colesterolo HDL nelle pazienti ipotiroidee con malattie cardiovascolari.

BACKGROUND: Hypothyroidism is a frequent cause of hyperlipidemia, particularly in women, but its true prevalence, both in the general population and in dyslipidemic subjects, is unknown. It is uncertain if low thyroid function significantly influence HDL metabolism and if sub-clinical disease may cause metabolic abnormalities and increase cardiovascular risk. METHODS: Three-hundred and three consecutive female patients (mean age 59.2 +/- 0.5 yrs), observed in a metabolic ward because of dyslipidemia, were evaluated. RESULTS: Forty-three women (14.1% of the total) showed sub-clinical hypothyroidism, while in 12 cases (4.0%) overt hypothyroidism was diagnosed; 8 further women (2.6%) had been previously diagnosed to be hypothyroid and were under hormone replacement therapy. On the whole, hypothyroid patients showed higher mean triglyceride levels and lower HDL-cholesterol than dyslipidemic euthyroid women, but the difference did not reach statistical significance. Total cholesterol concentration did not change with impaired thyroid function. Hypothyroid patients reported a clinical history of cardiovascular disease, or had severe atherosclerosis demonstrated, more often than euthyroid subjects (25.0% vs 19.7%, p = n.s.). When only women with arterial disease were considered, HDL plasma levels were significantly lower in the hypothyroid than in the euthyroid group (44.3 +/- 3.1 vs 56.2 +/- 1.7 mg/dl, respectively; p < 0.01). Hypertriglyceridemia and obesity often coexisted. CONCLUSIONS: In conclusion, among dyslipidemic women, unrecognised hypothyroidism is highly prevalent (both sub-clinical and manifest). In hypothyroid subjects atherosclerosis seem to associate with particularly low HDL plasma levels. This might precede atherosclerosis development (reinforced by concomitant thyroid failure) and represent a marker of the polymetabolic syndrome.

Therapeutic benefit of benfluorex in type II diabetic patients treated with sulfonylureas.

The objective of this study was to evaluate the effect of benfluorex in type II diabetic patients already treated with sulfonylureas (SU) in a randomized placebo-controlled trial. After a 4-week placebo run-in, 68 patients (49 men and 19 women; age range 40-70 years; known duration of diabetes 0.5-19 years) were randomized to double-blind 12-week treatment with benfluorex (B) or placebo (P). Primary end points were HbA1c and fasting blood glucose (FBG). Secondary end points were glucose tolerance (meal test over 120 min), plasma insulin, C-peptide, and lipid profile. Results were analyzed using both intention-to-treat analysis (ITT) in patients completing at least one treatment visit and per protocol analysis in those completing the whole study. There were no baseline differences between the two groups in any study parameter. Fifty-eight patients completed the study (28 B, 30 P), and 66 patients (33 B, 33 P) were eligible for ITT analysis. Over the 12-week treatment period, FBG decreased by 14.9% in the B group (-1.39 mmol/L, p < 0.001), and 3.2% in the P group (-0.28 mmol/L, NS) according to the ITT analysis and by 17.4% (p < 0.001) and 3.8% (NS), respectively, in the per protocol analysis. The difference in FBG outcome between the two groups was significant (p = 0.009 and p = 0.004, respectively). In patients completing the study, mean HbA1c decreased in the B group (-0.66%, p = 0.005) and remained stable in the P group (+0.14%, NS). HbA1c outcome differed between the two groups (p = 0.007). The decrease in AUCglucose was greater in the B group than in the P group (-210 +/- 220 versus -60 +/- 270 mmol/L x 120 min, p = 0.026). Plasma insulin and C-peptide changes did not differ between the two groups. Low-density lipoprotein (LDL) cholesterol decreased in B patients and was stable in P patients (-0.43 versus -0.05 mmol/L, p = 0.026). Of the 68 randomized patients, six on B and four on P reported at least one adverse event, causing dropout in five and two patients, respectively. In conclusion, benfluorex is an effective agent for combination therapy in type II diabetic patients poorly controlled on SUs alone.

Prevalence of abnormal thyrotropin concentrations measured by a sensitive assay in patients with type 2 diabetes mellitus.

The utilisation of assays for TSH with improved sensitivity has revealed that abnormal TSH results are frequently observed in patients with nonthyroidal illnesses, such as trauma, renal diseases, liver diseases or sepsis. The aim of this study was to investigate the prevalence of abnormal TSH concentrations, using a sensitive immunometric assay, in patients with type 2 (non-insulin-dependent) diabetes mellitus. The study population consisted of 290 type 2 diabetics, 159 females and 131 males aged 40 to 93 years (mean 60.6 +/- 11.9 years), hospitalised because of poor diabetic control or recent-onset diabetes (mean HbA1c value = 9.6 +/- 2.2%). All patients with TSH values outside the normal range (0.45 to 3.66 mlU/l) had FT4 assay and thyroid microsomal autoantibody assay performed on the same specimen of serum. Abnormal TSH concentrations were detected in 91 patients (31.4%). Subclinical hypothyroidism (high TSH, normal FT4) was most common (48.3%), followed by subclinical hyperthyroidism (low TSH, normal FT4) (24.2%) and by definite hypothyroidism (high TSH, low FT4) (23.1%). Definite hyperthyroidism (low TSH, raised FT4) was found in 4 patients (4.4%). None of the patients with low TSH values had increased FT3 concentrations. The prevalence of abnormal thyroid function test results was significantly higher in the female than in the male patients (40.9% vs. 19.8%, p < 0.0005) and in the insulin-treated patients than in those receiving oral hypoglycaemic agents (OHA) (37.3% vs. 23.1%, p < 0.02). Thirty patients with abnormal thyroid function test results (33.0%) had evidence of thyroid autoimmunity (titre of thyroid microsomal autoantibodies > 250 IU/l). Five thyroid microsomal antibody-negative patients had non-autoimmune thyroid diseases, 7 had nonthyroidal illnesses other than diabetes mellitus and 4 were receiving drugs known to affect the hypothalamic-pituitary-thyroid axis. Twenty-seven thyroid microsomal auto-antibody-negative patients with abnormal TSH values (17 with subclinical hypothyroidism and 10 with subclinical hyperthyroidism), who were not receiving drugs known to affect TSH secretion and were free of diseases other than diabetes mellitus, were retested after two months of adequate treatment of diabetes with OHA or insulin. TSH concentrations decreased in all but one patient with initial subclinical hypothyroidism and increased in all patients with initial subclinical hyperthyroidism. These changes were coupled with a significant fall of glycated haemoglobin values. In view of the transient changes in TSH secretion, we suggest that the diagnosis of thyroid dysfunction in type 2 diabetics should be delayed until improvement of the metabolic status.

[Biomechanical models of the human skull: stability of various segments in three simulations]. / Modello biomeccanico del cranio umano; stabilita' dei diversi segmenti in tre simulazioni.

Three simulations by a computer model of human skull, implemented on finite elements and virtual works principles, were performed by a 15 Kg loading of the structure according rules of mechanical stresses of chewing. First model had all elements in place, second was without vault and third was without orbital walls. Stability of the structure was evaluated in terms of "instability coefficient" as an index of sum of moduli and number of considered nodes such moduli give spatial displacement of nodes after loading and deformation of shell elements. All parts of the structure are involved in ensuring stability so that it decreases as different segments or elements are not considered during simulation. The vault plays a great role in total stability of the model while orbital walls appear as a mechanical link between anterior (frontal) and posterior (occipital) parts of the model.

[Biomechanical simulation model of the developmental morphology of the human skull. Further observations on the model construction]. / Modello biomeccanico di simulazione della morfologia evolutiva del cranio umano. Ulteriori osservazioni circa la costruzione del modello.

The implementation of a software simulation of a biomechanical model of the human skull, requires a high complexity construction made by a different ellipsoids and planes. At present our model is made by a facial, post-facial, occipital and palatal ellipsoids, a basal plane with a hole, walls of the nasal cavity and conic walls of the orbital cavities. Dimension of the model resemble closely an adult human skull. The physical constants given for the constituting material those of compact bone. The cavity of the model is closed except for the hole of the basal plane and for the posterior openings of the orbital cavities. The number of elements of the model is 416.

[Biomechanical model simulating the evolutionary morphology of the human cranium. Preliminary note]. / Modello biomeccanico di simulazione della morfologia evolutiva del cranio umano -nota preliminare-.

A simulation strategy as been pointed in order to evaluate the fate of the chewing stresses exerting at the molars. The human skull's structure is considered as analog of a built-up arch and/or vault system well adapted for such mechanical fitting. The shallow shell routine of Ices-STRUDL program was worked out. The preliminary results are reported.