Insights on Human Small Heat Shock Proteins and Their Alterations in Diseases.

The family of the human small Heat Shock Proteins (HSPBs) consists of ten members of chaperones (HSPB1-HSPB10), characterized by a low molecular weight and capable of dimerization and oligomerization forming large homo- or hetero-complexes. All HSPBs possess a highly conserved centrally located α-crystallin domain and poorly conserved N- and C-terminal domains. The main feature of HSPBs is to exert cytoprotective functions by preserving proteostasis, assuring the structural maintenance of the cytoskeleton and acting in response to cellular stresses and apoptosis. HSPBs take part in cell homeostasis by acting as holdases, which is the ability to interact with a substrate preventing its aggregation. In addition, HSPBs cooperate in substrates refolding driven by other chaperones or, alternatively, promote substrate routing to degradation. Notably, while some HSPBs are ubiquitously expressed, others show peculiar tissue-specific expression. Cardiac muscle, skeletal muscle and neurons show high expression levels for a wide variety of HSPBs. Indeed, most of the mutations identified in HSPBs are associated to cardiomyopathies, myopathies, and motor neuropathies. Instead, mutations in HSPB4 and HSPB5, which are also expressed in lens, have been associated with cataract. Mutations of HSPBs family members encompass base substitutions, insertions, and deletions, resulting in single amino acid substitutions or in the generation of truncated or elongated proteins. This review will provide an updated overview of disease-related mutations in HSPBs focusing on the structural and biochemical effects of mutations and their functional consequences.

Adjuvant treatment and analysis of failures in patients with high-risk FIGO Stage Ib-II endometrial cancer: an Italian multicenter retrospective study (CTF study).

OBJECTIVES: The purpose of this retrospective study was to assess the clinical outcome of patients with high-risk, early-stage endometrioid endometrial cancer (stage Ib or II with myometrial invasion >50%, grade 2-3). METHODS: We assessed 192 patients who underwent hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy, had histologically negative pelvic nodes, and had negative CT findings for aortic node involvement. RESULTS: Tumor relapsed in 36 patients after a median time of 21.2 months. The recurrence was vaginal in 7 (19.4%), distant in 16 (44.4%), aortic in 8 (22.2%), and involved multiple sites in 5 (13.9%). There was a trend to a lower vaginal recurrence rate in the 143 patients who received adjuvant radiotherapy (+chemotherapy) compared with the 46 who did not (2.1% versus 8.7%). Distant or aortic recurrences were lower in the 37 patients who received adjuvant chemotherapy (+radiotherapy) than in the 152 who did not (2.7% versus 18.4%, p=0.02). Of the 29 patients who received sequential adjuvant chemotherapy and radiotherapy, none developed local recurrence and only one had distant recurrence. There was a trend for a better 5-year progression-free survival and overall survival for the patients who received chemotherapy (+radiotherapy) compared with those who did not (86.0% versus 71.3%, and 92.3% versus 75.6%, respectively). CONCLUSIONS: Our data appear to suggest that adjuvant chemotherapy reduces the risk of distant or aortic recurrences and that sequential adjuvant chemotherapy and radiotherapy achieve an excellent local and distant control of disease in these clinical settings.

A 4-year evaluation of toxoplasmosis seroprevalence in the general population and in women of reproductive age in central Italy.

This study aimed to estimate possible changes in seroprevalence of anti-Toxoplasma gondii IgG and IgM antibodies in people living in the area of Massa and Carrara (central Italy), in recent years. Serum samples from over 13 000 individuals were tested for both IgG and IgM anti- Toxoplasma antibodies using an immunoenzymatic method (Access® Toxo IgG, and Access® Toxo IgM II, Beckman Coulter Inc., USA). Our survey showed a decreasing trend of overall seroprevalence of 24.4% [95% confidence interval (CI) 22.62­25.71] in 2010 compared to 31.0% (95% CI 29.29­32.72) in 2007. A positive trend according to age was found, with low positivity observed in younger age groups. For women of reproductive age the prevalence of IgG antibodies was 30.2% (95% CI 28.44­31.96) in 2007 and 23.6% (95% CI 22.05­25.20) in 2010. IgM seroprevalence in women of this age group also progressively decreased from 1.6% to 0.97% during the study period. Our study confirms a decline of toxoplasmosis in Western countries.

Thalidomide for improving cutaneous and pulmonary sarcoidosis in patients resistant or with contraindications to corticosteroids.

BACKGROUND: Limited data report thalidomide improves cutaneous sarcoidosis; no benefit has been reported for pulmonary localization. OBJECTIVES: To evaluate feasibility and efficacy of prolonged treatment with thalidomide for cutaneous sarcoidosis associated to pulmonary involvement in patients with resistance or contraindications to steroids. METHODS: Nineteen patients were treated with thalidomide for 24 months starting with 200 mg/d for first 2 weeks, followed by 100 mg/d for 11 weeks and a maintenance dose of 100mg on alternate days for 35 weeks, and a gradual scaling down until therapy interruption. Criteria of efficacy were: skin score, serum ACE levels (s-ACE), chest X-ray (CXR), lung function tests (LFTs), and diffusing lung capacity for CO (DLCO). The skin score was computed as arithmetic sum of seven score parameters (min: 0, max: 28). RESULTS: Skin score significantly decreased (P<0.001). Lower skin scores occurred after 3 and 6 months (P<0.05). s-ACE levels decreased over time at the third month (P<0.001). CXR assessed by radiological stage significantly improved during the first 6 months (P<0.001). DLCO showed a continuous trend of improvement. Minor side effects that have forced the suspension of the drug were drowsiness/sedation (74%), constipation (68%), and weight gain (53%). Deep vein thrombosis of the lower limbs occurred in one patient (who did not drop out the study). Eight patients (42%) abandoned thalidomide for axonal sensitive peripheral neuropathy (PN) between the ninth and the 24th month of treatment. CONCLUSIONS: Thalidomide, long-term at mid-low doses, can be considered as an effective therapeutic alternative in chronic sarcoidosis with resistance or contraindications to steroids.

Seroprevalence for toxoplasmosis in individuals living in north west Tuscany: access to Toxo-test in central Italy.

This survey aimed to estimate the prevalence of anti-Toxoplasma IgG and IgM antibodies in people living in north west Tuscany (central Italy) and to investigate the adherence to antenatal screening programs and access to the Toxo-test as well. Sera from a large sample of individuals suspected to have acute infection or from pregnant women (10,352 subjects) aged between 1 day and over 70 years were analysed for both IgG and IgM anti-Toxoplasma antibodies using an immunoenzymatic method or a chemo-luminescent immunoassay. Overall, the seroprevalence of IgG antibodies was 21.4% (95% CI 20.62-22.20). A positive trend according to age was found, with low positivity observed in younger age groups. Among women of reproductive age the prevalence of IgG antibodies was 19.4% (95% CI 18.64-20.26). The overall IgM seroprevalence was 1.07% (95% CI 0.87-1.27). A low IgM prevalence was also observed in women of reproductive age (0.8%; 95% CI 0.65-1.03). Our study seems to indicate that primary prevention is widespread among women. However, an epidemiological surveillance system for toxoplasmosis should be implemented, to assess the risk of congenital toxoplasmosis and to determine the true burden of disease in adults.

Nutraceutical value and safety of tomato fruits produced by mycorrhizal plants.

Tomato fruit has assumed the status of 'functional food' due to the association between its consumption and a reduced likelihood of certain types of cancers and CVD. The nutraceutical value of tomatoes can be affected by the cultivation conditions, e.g. the phytochemical content of the fruits may increase with the establishment of beneficial mycorrhizal symbioses in the plants. A multidisciplinary study was carried out to gain knowledge on the antioxidant, oestrogenic/anti-oestrogenic and genotoxic activity of tomato fruits produced by mycorrhizal plants. The present results showed that the symbiosis positively affected the growth and mineral nutrient content of tomato plants and enhanced the nutritional and nutraceutical value of tomato fruits through modifications of plant secondary metabolism, which led to increased levels of lycopene in fruits obtained from mycorrhizal plants, compared with controls. Moreover, such changes did not result in the production of mutagenic compounds, since tomato extracts induced no in vitro genotoxic effects. Fruit extracts, both hydrophilic and the lipophilic fractions, originating from mycorrhizal plants strongly inhibited 17-ß-oestradiol-human oestrogen receptor binding, showing significantly higher anti-oestrogenic power compared with controls. The present study shows that beneficial plant symbionts, such as mycorrhizal fungi, can lead to the production of safe and high-quality food, which is an important societal issue strongly demanded by both consumers and producers.

Association of Mycobacterium tuberculosis complex isolates of BOVIS and Central Asian (CAS) genotypic lineages with extrapulmonary disease.

The association between isolate genotype, defined as in the international spoligotype database SpolDB4, and extrapulmonary tuberculosis was determined among 1009 patients in a population-based, 4-year survey performed in Tuscany, Italy. Extrapulmonary disease occurred in 24.2% of patients. A statistically significant association with extrapulmonary disease was found for the BOVIS (adjusted OR 3.2; 95% CI 1.2-8.1) and for the Central Asian (CAS) lineages (adjusted OR 2.3; 95% CI 1.0-5.1). These findings support the view that Mycobacterium tuberculosis strains within individual genotypic lineages might have evolved unique pathogenic characteristics that are capable of influencing the clinical outcome of the infection.

Ankyloglossia: a morphofunctional investigation in children.

OBJECTIVES: To provide diagnostic criteria for ankyloglossia in children by anatomical measurements; to investigate the correlation between severity of ankyloglossia and a series of morphofunctional findings; to evaluate the potential mismatch between a clinical suspect of ankyloglossia and the authentic anatomical diagnosis. DESIGN: Two different techniques of anatomical measurements and a clinical evaluation of a series of morphofunctional findings were performed. SUBJECTS AND METHODS: In 200 children referred for evaluation and treatment of tongue-tie, the length of the frenulum and the interincisal distance were measured in maximum opening of the mouth and with the tip of the tongue touching the palatal papilla. Occlusion, type of bite, tongue resting position, swallowing mechanism, oral floor mobility, frenulum insertion modality and speech were investigated. Any correlation between these morphofunctional findings and anatomical measures was investigated. RESULTS: Children with a frenulum length more than 2 cm and an interincisal distance of more than 2.3 cm were normal. In both measurements, significant correlations among mean values and other variables were observed. Moreover, three levels -- mild, moderate and severe -- of ankyloglossia were assessed. CONCLUSIONS: Length of frenulum and interincisal distance allow an assessment of severity of ankyloglossia in children. Ankyloglossia was not associated with infantile swallowing.

Oxidative and genotoxic damage after radio-iodine therapy of Graves' hyperthyroidism.

PURPOSE: To evaluate genetic damage and oxidative stress following a single therapeutic dose of 131I in Graves' disease patients monitored up to 180 days after treatment. MATERIALS AND METHODS: Genetic damage induction was estimated as the increase in micronuclei in peripheral lymphocytes of patients. As indicators of radiogenic oxidative stress, vitamin E and lipoperoxide levels were assessed in the plasma of patients, as well as the release of plasmic clastogenic factors measured by the induction of micronuclei in vitro in peripheral lymphocytes of a healthy donor. RESULTS: Vitamin E depletion lasted at least 3 days and the basal level was restored within 7 days. No statistically significant variations were observed in lipoperoxide plasma levels. A sharp increase of micronuclei in the peripheral lymphocytes of patients was correlated (p < 0.001) with the release of clastogenic factor in the plasma. The highest micronucleus value was negatively correlated (p < 0.03) with the lowest vitamin E level observed in each patient. CONCLUSIONS: Micronuclei induction was the direct consequence not only of the energy deposition of 131I on the genetic material, but also of oxidative stress, likely via the release of clastogenic factor.

[Surgical treatment of umbilical hernia in children. Our experience]. / La correzione chirurgica dell'ernia ombelicale in età pediatrica. Esperienza personale.

AIM: To identify the main parameters which, differently correlated, indicate in which case, age and modality umbilical hernia in children should be surgically repaired. METHODS: The authors report personal experience on 319 children with umbilical hernia observed in the last 7 years. In 72 cases, on the basis of the evaluation of some parameters, a surgical correction was performed with the technique described. RESULTS: All the procedures were performed in "day surgery". There were no early complications, neither anesthetic nor surgical. All children showed a good recovery of all functions (feeding, intestinal canalization, walking about) and activities. No middle and long-term complications were observed. CONCLUSIONS: Umbilical hernia needs a surgical repair only in a few cases and after a careful evaluation of some parameters (age, sex, kind of hernia, size and consistency of the hernial porta, protrusion and expansion). The surgical procedure should guarantee either the safe and prompt repair or the cosmetic result; the use of some devices (anesthetic and surgical) allow to obtain excellent results.

Is pretreatment hemoglobin level a predictor of complete response to salvage chemotherapy for recurrent platinum-pretreated ovarian carcinoma?

PURPOSE OF INVESTIGATION: The aim of this retrospective study was to correlate some patient characteristics at relapse, including also baseline hemoglobin levels, with complete response rate and survival following second-line chemotherapy for recurrent platinum-pretreated ovarian carcinoma. METHODS: The investigation was conducted on 63 patients who received salvage chemotherapy with different agents for clinically detectable recurrent ovarian carcinoma following initial surgery and first-line platinum-based chemotherapy. Some patient characteristics at relapse (patient age, serum CA 125 level, baseline hemoglobin level, number of recurrence sites, ascites, platinum-free interval, and treatment-free interval) were related to complete response rate to salvage chemotherapy and survival after recurrence. Median baseline hemoglobin level was 11.6 g/dl (range, 7.5-15.0 g/dl). RESULTS: Second-line chemotherapy obtained a complete response in 17 (27.0%) patients and a partial response in 11 (17.5%), whereas stable disease and progressive disease were detected in 19 (30.1%) and 16 (25.4%) patients, respectively. By univariate analysis, complete response rate was related to baseline hemoglobin level (p = 0.0019), platinum-free interval (p = 0.0012) and treatment-free interval (p = 0.0048). Multiple logistic regression showed that platinum-free interval (p = 0.0107) and baseline hemoglobin level (0.0312) were independent predictors of complete response. Patients with baseline hemoglobin levels >11.6 g/dl had a 5.338 higher chance of obtaining a complete response when compared to those with lower hemoglobin values. The platinum-free interval was the only independent prognostic variable for survival after recurrence (p = 0.0141), whereas baseline hemoglobin level was not related to survival at univariate nor at multivariate analysis. CONCLUSIONS: Baseline hemoglobin level is an independent predictor of complete response to salvage chemotherapy in patients with recurrent platinum-pretreated ovarian carcinoma. Attention must be paid to anemia correction in these patients, with the aim of improving both the chance of response to salvage treatment and the quality of life.

[Anastomotic false-diverticulum causing an atypical dumping syndrome. A case report]. / Dumping sindrome atipica da pseudodivericolo anastomotico. Descrizione di un caso.

Aim of the study is to evaluate the causes of dumping syndromes following partial gastrectomies, and to report an unusual feature of dumping. A case of early dumping due to diverticular-like dilation of gastro-jejunal anastomosis is described with preoperative imaging and intraoperative picture. The surgical correction led to complete clinical remission; the common causes and physiopathological bases of dumping are reviewed and the role of en-Y gastro-jejunal reconstruction is underlined in order to reduce the risk of developing the syndrome.

A comparison of ultrasonography and magnetic resonance imaging in the evaluation of temporomandibular joint involvement in rheumatoid arthritis and psoriatic arthritis.

OBJECTIVE: To define the diagnostic value of ultrasonographic (US) examination in comparison with magnetic resonance imaging (MRI) for the assessment of temporomandibular joint (TMJ) involvement in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: MRI and US examinations were performed in 33 patients (22 with RA and 11 with PsA). Alterations of the disc, alterations of the condyle and joint effusion were evaluated. RESULTS: Pathological changes of the TMJ were observed by MRI in 24 patients and by US in 31 patients. The sensitivity and specificity of US were calculated in comparison with MRI. The sensitivity was 72.2% and the specificity was 60% in the assessment of pathological changes of the TMJ. The sensitivity was 69.6% with specificity of 30.0% in the assessment of alterations of the disc; the sensitivity was 70.6% with specificity of 75.0% in the assessment of joint effusion. Significant concordance was not observed in the assessment of condylar alterations. CONCLUSIONS: US imaging appears able to detect different pathological changes of the TMJ and may be considered an important diagnostic tool for clinical evaluation of the TMJ in RA and PsA.

[The use of surgical endo-prosthesis in the treatment of choledocolithiasis in the elderly. Personal experience]. / L'uso delle endoprotesi chirurgiche nel trattamento della litiasi della VBP nell'anziano. Esperienze personali.

BACKGROUND: The usefulness of biliary endoprostheses in some selected elderly patients affected by hepato-choledocolithiasis is described. METHODS: In the Department of Surgery, University of Perugia, 119 elderly patients were surgically treated for choledocholithiasis from January 1999 to December 2000. In 44 selected cases#151;oldest patients with thinner hypovascularized ectasic choledochal wall#151; a permanent transpapillary polyurethane prosthesis was placed, after choledocolithotomy with or without sphinterotomy; sometimes prosthesis was placed under the duodenal mucosa. RESULTS: Endoprosthesis had a long duration and gave good results in canalization and periprosthetic flow, in absence of biliary stasis and/or angiocholitis. Only one patient had prostheses displacement. CONCLUSIONS: On the basis of personal experience and considering physiopathology and pathogenesis of biliary stones in the elderly, the authors underline, in selected cases, the need of stenting the hepatocholedochal lumen with the aim of avoiding collapse.

The prognostic relevance of histological type in uterine sarcomas: a Cooperation Task Force (CTF) multivariate analysis of 249 cases.

PURPOSE OF INVESTIGATION: The objective of this retrospective multicenter study was to assess the prognostic relevance of histologic type in uterine sarcomas. METHODS: The hospital reports of 249 patients with uterine sarcomas were reviewed. Surgery was the initial therapy for all patients. Histologic type was leiomyosarcoma in 95 cases, low-grade endometrial stromal sarcoma (ESS) in 19, high-grade ESS in 34, and carcinosarcoma in 101. Postoperative treatment was given without well-defined protocols. Median follow-up of survivors was 97 months. RESULTS: In the whole series 2-year, 5-year, and 10-year survival rates were 53.5%, 41.6%, and 35.8%, respectively, and median survival was 31 months. At univariate analysis survival was significantly related to stage (p = 0.0001), mitotic count (p = 0.0001), and histologic type (low-grade ESS vs leiomyosarcoma vs carcinosarcoma vs high-grade ESS, median: not reached vs 27 months vs 21 months vs 16.5 months, p = 0.0011), but not to postoperative therapy and patient age. The Cox model revealed that tumor stage, mitotic count and histologic type were independent prognostic variables for survival. In detail, the risk of death was significantly lower for low-grade ESS (risk ratio [RR] = 0.257; 95% confidence interval [CI] = 0.071-0.931) and carcinosarcoma (RR = 0.509; 955 CI = 0.324-0.799) when compared to leiomyosarcoma. Conversely, no significant difference in survival was found between leiomyosarcoma and high-grade ESS. CONCLUSIONS: Histologic type is an independent prognostic variable for survival in uterine sarcomas. Low-grade ESS has the best clinical outcome, whereas leiomyosarcoma has the poorest one. It is noteworthy that, when adjusting for stage and mitotic count, leiomyosarcoma has a significantly worse prognosis than carcinosarcoma.

Regional lymph node dissection in the treatment of renal cell carcinoma: is it useful in patients with no suspected adenopathy before or during surgery?

OBJECTIVES: To evaluate the role of regional lymph node dissection (LND) in a series of patients with renal cell carcinoma (RCC) with no suspicion of nodal metastases before or during surgery. PATIENTS AND METHODS: A series of 167 patients with RCC, free from distant metastases at diagnosis, and who underwent radical nephrectomy at our hospital between January 1990 and October 1997, was reviewed. The mean (median, range) follow-up was 51 (45, 19-112) months. Of the 167 patients, 108 underwent radical nephrectomy alone and 59 had radical nephrectomy with regional LND limited to the anterior, posterior and lateral sides of the ipsilateral great vessel, from the level of the renal pedicle to the inferior mesenteric artery. Of these 59 patients, 49 had no evidence of nodal metastases before or during surgery. The probability of survival was estimated by the Kaplan-Meier method, using the log-rank test to estimate differences among levels of the analysed variables. RESULTS: The overall 5-year survival was 79%; the 5-year survival rate for the 108 patients who underwent radical nephrectomy alone was 79% and for the 49 who underwent LND was 78%. Of the 49 patients with no suspicion of lymph node metastases, one (2%) was found to have histologically confirmed positive nodes. CONCLUSION: These results suggest that there is no clinical benefit in terms of overall outcome in undertaking regional LND in the absence of enlarged nodes detected before or during surgery.

The clinical relevance of serum CYFRA 21-1 assay in patients with ovarian cancer.

CYFRA 21-1 assay, which detects serum fragments of cytokeratin 19, has been widely assessed as a serum marker of several malignancies. Preoperative serum CYFRA 21-1 levels were retrospectively measured in 60 patients with ovarian cancer and in 59 control patients with benign ovarian disease. CYFRA 21-1 levels were also serially measured in 90 serum samples drawn from patients with advanced (FIGO stage III-IV) ovarian cancer followed after surgery and chemotherapy. Preoperative serum CYFRA 21-1 levels were higher in patients with ovarian cancer compared with controls (median, range = 2.6, 0.1-51.4 ng/ml versus 0.4, 0.0-3.6 ng/ml, P < 0.0001), and among the former, antigen values were higher in the 39 patients with advanced-stage than in the 21 patients with early (FIGO stage I-II) disease (P < 0.0001). In advanced ovarian cancer patients, the 25%, 50%, and 75% quantiles of preoperative CYFRA 21-1 levels were 1.9, 4.8 and 14.4 ng/ml, respectively. Preoperative CYFRA 21-1 levels were lower in the 11 patients who achieved a pathologic complete response at second-look compared with those who had clinically or surgically detectable persistent disease after first-line chemotherapy (median, range 1.9, 0.6-9.2 ng/ml versus 10.2, 0.1-51.4 ng/ml, P = 0.007). The pathologic complete response rate was significantly greater in patients with low preoperative CYFRA 21-1 levels compared with those with elevated CYFRA 21-1 levels at any cut-off limit for the antigen (1.9, 4.8 and 14.4 ng/ml). However, Cox regression analysis failed to detect a significant association between preoperative CYFRA 21-1 assay and survival. As for the follow-up of advanced ovarian cancer patients, CYFRA 21-1 levels were higher in the 42 samples drawn from patients with clinically detectable disease compared with the 48 specimens collected from patients with no clinical evidence of disease (median, range = 1.15, 0.3-40.7 ng/ml versus 0.4, 0.1-9.1 ng/ml, P < 0.0001). In conclusion, preoperative serum CYFRA 21-1 assay appears to be predictive of response to chemotherapy, but not prognostic of survival, for patients with advanced ovarian cancer. Moreover, the serial measurement of CYFRA 21-1 levels might have a potential clinical relevance for the assessment of disease status in patients followed after surgery and chemotherapy.

Immunohistochemical study of 49 cutaneous melanomas: p53, PCNA, Bcl-2 expression and multidrug resistance.

AIMS AND BACKGROUND: Thickness and level of invasion are the main morphological elements for an approximate but not sufficiently sensitive prognostic evaluation of cutaneous melanomas. By using immunohistochemical methods it is possible to detect biological markers related to prognosis. We have studied p53, PCNA, Bcl-2 and P-gp expression in 49 primary cutaneous melanomas. MATERIALS: We used the immunophosphatase APAAP immunohistochemical method. The percentage of labeled cells (according to four classes of positivity: <5%; 5-25%; 25-50%; >50%) and the localization of immunoreactivity were expressed for each marker. Statistical analysis was performed to determine the correlations between markers and level or thickness of melanomas. RESULTS: We found a good correlation between p53 expression and melanoma thickness (P <0.005), PCNA and P-gp expression. No relationship was observed between Bcl-2 expression and the different variables considered or other markers. CONCLUSIONS: Our data seem to indicate an unfavorable prognostic role of higher nuclear p53 expression. However, we believe that our results need to be integrated with patients' clinical follow-up and with the study of the expression of these markers in benign melanocytic lesions to gain more accurate information about their prognostic significance.

Hemostatic alterations in patients with acute, unilateral vestibular paresis.

OBJECTIVES: The etiopathogenesis of acute unilateral peripheral vestibulopathy (APV) still remains a matter of debate; ischemic changes in the circulation of the labyrinth may play a role. We consequently looked for possible hemostasis alterations in a group of patients with APV of an unknown nature. METHODS: We evaluated blood parameters known to be involved in circulation disorders, including total and HDL cholesterol, triglycerides, apolipoprotein A and B, lipoprotein(a), homocysteine, folate, prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer, antithrombin III, protein C, protein S, activated protein C resistance, and anticardiolipin IgG and IgM antibodies. A series of 23 patients affected with APV were consecutively referred to our department, in the acute phase, before treatment, and in the follow-up phase after 4 to 6 weeks of pharmacologic washout. The aforementioned blood parameters were also measured in a series of 15 patients with Menière's disease. RESULTS: The patients with APV in the acute phase compared with the patients with Menière's disease in the acute phase exhibited increased plasma levels of fibrinogen (mean, 338.3 +/- 135.9 SD vs 271.3 +/- 69.8 SD mg/dL, P = 0.05), increased plasma levels of D-dimer (mean, 320 +/- 207.8 SD vs 226.7 +/- 138.7 SD NG/mL), enhanced plasma levels of lipoprotein(a) (41.4 +/- 38.6 SD vs 16 +/- 18.2 SD mg/dL, F = 5.67, P = 0.02), high leukocyte count (9.1 +/- 2.7 SD vs 6.5 +/- 1.3 SD x 10(3)/microL; F = 8.42, P < 0.006), and low serum folate concentration (5.3 +/- 1.8 SD vs 7.1 +/- 2.7 NG/mg; F = 4.34, P = 0.04). During follow-up the prothrombin time was prolonged (F = 4.34, P = 0.04) and leukocyte count decreased (F = 7.39, P < 0.019) in the APV patients, whereas fibrinogen, D-dimer, lipoprotein(a), and folate were unchanged. CONCLUSION: Our results provide evidence suggesting an involvement of the hemostatic system in APV.

Influence of endogenous androgens on carotid wall in postmenopausal women.

OBJECTIVE: There is increasing evidence of a direct association between normal androgen levels and reduced cardiovascular morbidity and mortality in women. After menopause the influence of estrogens declines, whereas that of androgens increases. Therefore, we investigated the effects of androgens on atherosclerosis in postmenopausal women, by using carotid artery intimal-medial thickness as a marker of vascular damage. DESIGN: Blood pressure, body mass index, waist-to-hip ratio, serum dehydroepiandrosterone sulfate, androstenedione, total and free testosterone, estrone, insulin, lipid profile, and glucose were evaluated in 44 women in stable physiological menopause. All subjects underwent carotid ultrasound (Biosound 2000 II s.a. high-resolution unit). RESULTS: Spearman correlation coefficients indicated that serum androstenedione and free testosterone were negatively associated with several carotid intimal-medial thickness measures with correlation coefficients (r) ranging from 0.477 to 0.397 (p < 0.01-0.04). Moreover, age-adjusted androstenedione and free testosterone highest tertiles showed intimal-medial thickness values significantly (p < 0.03-0.05) lower than the other tertiles. There was a favorable association between hormones and the most important cardiovascular risk factors. This association, however, did not reach statistical significance. Stepwise multiple regression analysis showed that the inverse relationships between the hormones (androstenedione and free testosterone) and several intimal-medial thickness measures were maintained (F: 4.15-6.07, p < 0.05-0.02) after adjustment for major cardiovascular risk factors. CONCLUSIONS: Our data demonstrate that in postmenopausal women endogenous steroid precursors and androgens are inversely related to carotid intimal-medial thickness, an established marker of atherosclerosis. In addition, these hormones show favorable associations with cardiovascular risk factors. Therefore, our study suggests that, after menopause, normal androgen levels may benefit the carotid artery wall.