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Francesco Trimarchi

Publications and source records attributed to Francesco Trimarchi.

24 records · Page 2Linked to original sources

Twelve months of treatment with octreotide-LAR reduces joint thickness in acromegaly.

OBJECTIVE: To evaluate the role of age, gender, duration and control of acromegaly on the reversibility of arthropathy. PATIENTS AND DESIGN: 30 de novo patients with active acromegaly, 30 cured patients and 30 healthy subjects were studied in a tranverse and an open longitudinal study design. METHODS: Shoulder, wrist and knee thickening was measured by ultrasonography at study entry in all 90 subjects and after 12 Months of treatment with octreotide-LAR (OCT-LAR) at a dose of 10-40 mg every 28 days in the 30 de novo patients. RESULTS: Thickness at all joint sites was greater in the active than in the cured patients and controls (P<0.001), and was greater in the cured patients than in the controls (P<0.001). There was no gender difference, but joint thickness was less in the patients with disease duration >10 Years. Age significantly correlated with wrist (r=-0.55; P<0.001), right knee (r=-0.45; P=0.01), and left knee thickness (r=-0.42; P=0.02) in patients with active disease, and with wrist thickness (r=0.88; P<0.0001) in controls. Twelve Months of OCT-LAR treatment led to disease control in 18 patients (60%). There was a decrease in the thickness of the shoulder (15.1+/-3.2%), wrist (20.5+/-3.1%), right knee (22.2+/-3.4%) and left knee (18.2+/-2.8%) in all patients but the reduction in joint thickness at all sites was greater in the patients with controlled disease after OCT-LAR treatment than in the uncontrolled patients (P<0.01). Shoulder and right knee thickening normalized in respectively 11 (61.1%) and 16 (88.9%) well-controlled patients. CONCLUSIONS: Growth hormone and insulin-like growth factor-I (IGF-I) suppression by 12 Months' OCT-LAR treatment is accompanied by a significant decrease in the thickness of both weight-bearing and non-weight-bearing joints (mainly in patients whose disease is controlled) regardless of disease duration. These findings suggest that tIssue hypertrophy in the context of the acromegalic arthropathy can be improved by suppressing IGF-I levels.

Acromegaly↗

Adenoviral vectors can impair adrenocortical steroidogenesis: clinical implications for natural infections and gene therapy.

Recombinant adenoviral vectors are effective in transferring foreign genes to a variety of cells and tissue types, both in vitro and in vivo. However, during the gene transfer, they may alter the principal function and local environment of transfected cells. Increasing evidence exists for a selective adrenotropism of adenovirus during infections and gene transfer. Therefore, using bovine adrenocortical cells in primary culture, we analyzed the influence of different adenoviral deletion mutants on cell morphology and physiology. Transfection of cells with an E1/E3-deleted adenoviral vector, engineered to express a modified form of the Aequorea victoria green fluorescent protein, was highly efficient, as documented by fluorescent microscopy. Ultrastructural analysis, however, demonstrated nuclear fragmentation and mitochondrial alterations in addition to intranuclear viral particles. Basal secretion of 17-OH-progesterone, 11-deoxycortisol, and cortisol was significantly increased by E1/E3-deleted vectors; yet, the corticotropin-stimulated release of these steroids was decreased. Interestingly, neither purified viral capsids nor E3/E4-deleted adenoviral mutants altered basal and stimulated steroidogenesis of adrenocortical cells. An intact adrenal response is crucial for adaptation to stress and survival. Therefore, the implications of our findings need to be considered in patients with adenoviral infections and those undergoing clinical studies using adenoviral gene transfer. At the same time, the high level of transfection in adrenocortical cells might make appropriately modified adenoviral vectors suitable for gene therapy of adrenocortical carcinomas with poor prognosis.

Adenoviridae↗

Fahr's disease.

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Adult↗

Multifocal motor neuropathy and asymptomatic Hashimoto's thyroiditis: first report of an association.

Motor neuropathy with multifocal conduction blocks represents a recently identified autoimmune disorder of the peripheral nerve myelin. Association of motor neuropathies or neuronopathies with thyroid disorders, such as hyperthyroidism, hypothyroidism or thyroid neoplasms has been rarely described. We studied a 61-year-old man with a 2-year-history of slowly progressive weakness of the left limbs with atrophy and fasciculations. Nerve conduction velocity studies revealed multifocal motor conduction blocks. Serum IgM titer of antibodies against GM1 was elevated (1:1280; n.v. up to 1:640). Thyroid studies were compatible with Hashimoto's thyroiditis. Therapy with high dose intravenous immunoglobulins was followed by a prompt clinical recovery. Then the disease assumed an intravenous immunoglobulins dependent course with a full clinical, but transient, recovery. This is the first observation of an association of multifocal motor neuropathy with high titers of GM1 and Hashimoto's thyroiditis and reinforces the multifocal motor neuropathy autoimmune origin as well as the repeated clinical recoveries after intravenous immunoglobulins. This case also suggests to deeply investigate the thyroid function in patients with multifocal motor neuropathy.

Demyelinating Diseases↗

High-density lipoprotein-facilitated entry of thyroid hormones into cells: a mechanism different from the low-density lipoprotein-facilitated entry.

In human skin fibroblasts incubated with interstitial fluid concentrations of low-density lipoproteins (LDL) (22 microg/mL) that had been preincubated with [(125)I] thyroid hormone (TH), thyroxine (T(4)) whole-cell saturable up-take (CSU) is approximately 40% greater than in control fibroblasts. This effect of the LDL, which requires upregulation of low-density lipoprotein-receptors (LDL-R; K(d) approximately 20 microg/mL), is less for [(125)I]triiodothyronine (T(3)). We have evaluated high-density lipoproteins (HDL), and assessed whether lipoproteins target TH to the nucleus. In some experiments, fibroblasts were cholesterol-deprived (chol(-)) or cholesterol-enriched (chol(+)) to upregulate LDL-R or high-density lipoprotein-receptors (HDL-R), respectively. In chol(-) fibroblasts, 25 microg/mL of LDL increased both T(4) CSU and T(4) nuclear saturable uptake (NSU) by 48% or 30%, respectively; the latter becoming appreciable at approximately 180 minutes. Interstitial fluid concentrations of HDL (280 microg/mL or approximately 50-fold greater than K(d) of the HDL-R) inhibited both T(4) and T(3) CSU even in chol(+) fibroblasts. However, when chol(+) fibroblasts were incubated first with HDL, and after cell washings with [(125)I]T(4) or [(125)I]T(3), T(4) or T(3) CSU increased by 24% or 12%, respectively. The corresponding increase in chol(-) fibroblasts was 8% or 0%, and in nonmanipulated fibroblasts was 15% or 4%. Unlike LDL, the magnitude of the increase in T(4) or T(3) NSU caused by HDL matched the corresponding CSU, and was already evident at 30 minutes. In conclusion, cells have a LDL-facilitated, LDL-R-mediated mode of entry of TH (T(4) >> T(3)) that targets relatively late only part of TH to the nucleus, and an HDL-facilitated mode of entry (T(4) > T(3)) that targets immediately to the nucleus all of the TH, suggesting entry of TH in free form. This effect of HDL represents facilitated diffusion of TH through the cell membrane.

Cell Nucleus↗