Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy

Subclinical hypothyroidism (sHT) is associated with enhanced cardiovascular risk. To test the hypothesis that patients with sHT are characterized by endothelial dysfunction and impaired nitric oxide (NO) availability, in 14 patients [serum cholesterol, 218 +/- 41 mg/dl (5.6 +/- 0.9 mM)] and 28 euthyroid subjects, subdivided into groups A and B [serum cholesterol, 170 +/- 19 mg/dl (4.4 +/- 0.5 mM) and 217 +/- 21 mg/dl (5.6 +/- 0.5 mM), respectively], we studied the forearm blood flow (strain-gauge plethysmography) response to intrabrachial acetylcholine, an endothelium-dependent vasodilator, at baseline and during infusion of N(G)-monomethyl-L-arginine (L-NMMA), a NO synthase inhibitor. Response to sodium nitroprusside and minimal forearm vascular resistances were also evaluated. In sHT patients, vasodilation to acetylcholine was reduced, compared with group B (+358 +/- 29% vs. +503 +/- 19%, P = 0.0003) and group A (663 +/- 65%, P = 0.02 vs. group B and P = 0.0002 vs. sHT). L-NMMA blunted the vasodilation to acetylcholine in groups A and B (49.1 +/- 6.3% and 42.7 +/- 5.5% maximal forearm blood flow reduction, respectively, P < 0.0001 vs. acetylcholine), whereas it was ineffective in sHT patients (12.8 +/- 2.5%). Response to sodium nitroprusside and minimal vascular resistances were similar. In sHT (n = 9) patients, 6 months of euthyroidism by levothyroxine replacement increased acetylcholine-vasodilation and restored L-NMMA inhibition. Patients with sHT are characterized by endothelial dysfunction resulting from a reduction in NO availability, an alteration partially independent of dyslipidemia and reversed by levothyroxine supplementation.     

Positron emission tomography (PET): evaluation of chronic periaortitis

OBJECTIVE: To evaluate the presence and extent of large-vessel inflammation in patients with chronic periaortitis (CP) using (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET). METHODS: A consecutive case series consisting of 7 patients with CP seen over a 3-year period and a control group of 14 patients with malignancy were evaluated with FDG-PET. For every case we selected 2 age- and sex-matched controls who underwent PET imaging for malignancy. The diagnosis of CP was made by means of computed tomography. PET imaging was performed at diagnosis before therapy was started. Measurement of vascular uptake was graded using a 4-point semiquantitative scale. RESULTS: All patients had evidence of grade 2+ or 3+ vascular uptake in the abdominal aorta and/or iliac artery. No controls showed vascular uptake greater than 1+. Vascular uptake in the thoracic aorta and/or in its branches was seen in 3 (43%) of 7 patients. Vascular uptake in abdominal aorta and/or iliac artery was observed in patients with CP but not in controls (100% versus 0%). There was also a significantly more frequent FDG uptake in the large thoracic arteries in case-patients compared with controls (43% versus 0%; P = 0.03). CONCLUSION: FDG-PET scan shows in patients with CP the presence of a large-vessel vasculitis involving abdominal aorta and common iliac arteries, which in some patients is also extended to thoracic aorta and/or its branches.     

Effect of oral contraceptives on endothelial function in the peripheral microcirculation of healthy women

OBJECTIVES: We assessed whether third-generation oral contraceptive (OC) treatment (30 microg ethinylestradiol + 75 microg gestodene daily) could affect the endothelial function of healthy women. METHODS: In 20 young healthy women (HW) and 10 hypercholesterolemic women (CW) we assessed forearm blood flow (strain-gauge plethysmography) changes induced by the intrabrachial infusion of acetylcholine (ACH) (0.15-15 microg/100 ml forearm tissue/min) and sodium nitroprusside (SNP) (1-4 microg/100 ml forearm tissue/min). ACH was repeated during the nitric oxide synthase inhibitor intra-arterial NG-monomethyl-L-arginine (L-NMMA) (100 microg/100 ml forearm tissue/min) or the antioxidant vitamin C (8 mg/100 ml forearm tissue/min). HW repeated the protocol after 6-month OC (n = 10) or placebo (n = 10) treatment. RESULTS: In HW the maximal vasodilation to ACH, similar between placebo and OC subgroups, was significantly reduced in CW (P < 0.01). Vasodilation to ACH was blunted (P < 0.01) by L-NMMA and unaffected by vitamin C, in both OC and placebo groups. In CW the vasodilation to ACH, not modified by L-NMMA, was improved by vitamin C (P < 0.01). OC treatment raised (P < 0.01) plasma total and low-density lipoprotein cholesterol, and values were similar to those shown by CW. Both OC and placebo intake did not change the response to ACH and the modulation induced by L-NMMA or vitamin C. Vasodilation to SNP was similar in all groups. CONCLUSIONS: In HW 6-month treatment with third-generation OC, although associated with an abnormal lipid profile, does not adversely affect endothelium-dependent vasodilation. This neutral effect could be the balance between a deleterious effect of hypercholesterolemia and a protective effect of OC on endothelial function.     

Does intraperitoneal insemination in the absence of prior sensitization carry with it a risk of subsequent immunity to sperm?

To evaluate the occurrence of antisperm antibodies in women, with no prior sensitization, 112 couples undergoing intraperitoneal insemination were tested for serum antisperm antibodies with the sperm immobilization test (SIT) and the immunobead test (IBT). A serum sample was taken from each of the 112 patients immediately before the first intraperitoneal insemination. Another sample was taken from 58 patients who underwent a second insemination procedure. In 16 of the 58 patients the IBT results were positive for one or more immunoglobulin classes. Five patients showed positive SITs. In 7 out of these 16 subjects (12%) the antibodies were bound to the head and to the shaft of the sperm tail. Five of the six patients submitted to a third intraperitoneal insemination procedure showed unchanged SIT values and IBT binding percentages. In one subject, SIT (6 months after the third insemination) became negative. Antibody production may be either a transient response to massive antigen stimulation or the first step toward systemic immunity.     

Vertebral arterio-venous fistula presenting with intracranial hemorrhage

Vertebral arteriovenous fistulas are rare lesions consisting of an abnormal shunt between the extracranial vertebral artery and the neighboring veins. The authors present a case of post-surgical high-flow left vertebral arteriovenous fistula presenting with intracranial hemorrhage. The patient underwent endovascular balloon occlusion of the fistula: after endovascular treatment a reduction of the flow was evident but the patient presented neurological deterioration related the occurrence of intraventricular-subarachnoid hemorrhage. Intracranial hemorrhage is a potential manifestation of high-flow vertebral AVF and a possible complication of endovascular fistula balloon occlusion. Direct endovascular occlusion of the vertebral artery may be primarily considered in selected cases.     

Hyperhomocyst(e)inemia: is this a novel risk factor in hypertension?

Homocysteine is an intermediate sulfur-containing amino acid formed during intracellular metabolism of methionine. Circulating homocyst(e)ine can be increased by genetic deficiency of enzymatic pathways involved in its catabolism as well as by environmental factors including nutritional deficiencies, life style factors, physiological conditions, drugs and some diseases, which mainly induce deficiency of folate, vitamin B12 and vitamin B6. Therefore plasma homocyst(e)ine can be reduced by vitamin therapy with folate and vitamin B12. Although hyperhomocyst(e)inemia exerts a prothrombotic and proatherosclerotic effect, its relevance in the genesis of the atherosclerotic lesions, as well in the first occurrence of cardiovascular events in normotensive and even more so in hypertensive patients is still to be established. However available data indicate that hyperhomocyst(e)inemia could be an independent risk factor for the recurrence of cardiovascular events in patients with coronary artery disease and in elderly high risk patients. Finally, the possibility that a reduction in plasma homocyst(e)ine induced by vitamin therapy can diminish the risk of cardiovascular events is under evaluation in several controlled longitudinal studies focusing mainly on secondary prevention.     

Reproductive functions in female patients treated with adjuvant and neoadjuvant chemotherapy for localized osteosarcoma of the extremity

BACKGROUND: The side effects of chemotherapy on ovarian and reproductive functions in female patients who received adjuvant and/or neoadjuvant treatment for localized osteosarcoma of the extremities at our institution in the last 21 years (1974-1995) were assessed. METHODS: Ninety-two patients with a mean actual age of 26 (14-51) were interviewed. They had been followed 3 to 16 years after treatment (mean: 9.6 yrs). Twenty-four of them had received chemotherapy before puberty and 68 after puberty. RESULTS: Amenorrhea during chemotherapy occurred in 69% of postpuberal patients but only in 2 patients aged 39 and 43, respectively, was permanent. After the end of treatment, the patients' menstrual activity started again, and only a slight number of cases showed increases of menstrual irregularities. Twenty-two patients married after treatment; 20 patients started a pregnancy at a mean age of 27. Of these 20 patients, 3 had voluntary abortions and 17 succeeded. At the time of article submission, three were pregnant, 14 had 19 full term pregnancies, and no birth defects nor congenital anomalies were registered in their 19 full term newborns. CONCLUSIONS: In this group of female patients, chemotherapy seemed to alter neither their reproductive function nor the health of their newborns.     

Adjuvant and neoadjuvant chemotherapy for osteosarcoma of the extremities: 27 year experience at Rizzoli Institute, Italy

Around 1148 patients with non-metastatic osteosarcoma of the extremity were treated in a single institution between 1972 and 1999 with 4 different protocol of adjuvant and 7 different protocols of neoadjuvant chemotherapy. The rate of limb salvage increased from 20% to 71%. The 5-year event-free survival (EFS) and overall survival (OS) were 57% and 66%, respectively. The 10-year EFS and OS were 52% and 57%, respectively, and the results significantly correlated with serum alkaline phosphatase levels; the type of chemotherapy (adjuvant vs neoadjuvant); and with histologic response to pre-operative treatment. Aggressive chemotherapy and surgery could cure about the 60% of patients with osteosarcoma of the extremity. However, since local or systemic relapses, myocardiopathies and a second malignancy are possible even 5 or more years since the beginning of treatment, a long-term follow-up is recommended.