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Objective To analyse the content of the interventions reported in studies investigating the applicability and efficacy of Argentine tango in participants with Idiopathic Parkinson Disease. Methods Independent reviewers searched databases (PubMed, CINAHL, EMBASE, PsycINFO, and PEDro) from their inception to November 2019. Eligible studies were randomised, controlled and uncontrolled clinical trials, and case reports. Main outcome measure The Template for Intervention Description and Replication guidelines and checklist were used to assess quality and quantity of the content of Argentine tango interventions’ description. Results We found 21 papers investigating the applicability and efficacy of Argentine tango in participants with Idiopathic Parkinson Disease. Completeness of the reporting of intervention was satisfying. The intervention is intended to affect a variety of aspects of functioning relevant to individuals with Idiopathic Parkinson Disease. Detailed information on the intervention's procedure and dosing is usually provided. The delivery of the Tango dance program was predominantly extensive; however, the intervention has been provided with various approaches and showed to be very adaptable. Attrition- and adherence- rates described are acceptable. The Adapted Tango dance program is the earliest and most researched modality of tango intervention in participants with Idiopathic Parkinson Disease. Conclusions Argentine tango is appropriately described in the studies investigating the applicability and efficacy of the intervention in participants with Idiopathic Parkinson Disease. However, the reporting could be ameliorated.

Evaluating and testing hydration status is increasingly requested by rehabilitation, sport, military and performance-related activities. Besides commonly used biochemical hydration assessment markers within blood and urine, which have their advantages and limitations in collection and evaluating hydration status, there are other potential markers present within saliva, sweat or tear. This literature review focuses on body fluids saliva, sweat and tear compared to blood and urine regarding practicality and hydration status influenced by fluid restriction and/or physical activity. The selected articles included healthy subjects, biochemical hydration assessment markers and a well-described (de)hydration procedure. The included studies (n=16) revealed that the setting and the method of collecting respectively accessing body fluids are particularly important aspects to choose the optimal hydration marker. To obtain a sample of saliva is one of the simplest ways to collect body fluids. During exercise and heat exposures, saliva composition might be an effective index but seems to be highly variable. The collection of sweat is a more extensive and time-consuming technique making it more difficult to evaluate dehydration and to make a statement about the hydration status at a particular time. The collection procedure of tear fluid is easy to access and causes very little discomfort to the subject. Tear osmolarity increases with dehydration in parallel to alterations in plasma osmolality and urine-specific gravity. But at the individual level, its sensitivity has to be further determined.

Summary. Background: The management of venous thromboembolism (VTE) requires an initial treatment with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH), followed by oral anticoagulants (OA) for at least 3 months. OA treatment however, requires laboratory monitoring of anticoagulation, carries a definite risk of bleeding, and may be contraindicated in some patients. As an alternative to vitamin K antagonists, subcutaneous LMWH has been proposed and evaluated in randomized clinical trials, but they are all small studies that lack the power to establish if these two treatment modalities are equivalent in efficacy or safety. Objectives: The objective of this review was to evaluate the efficacy (VTE recurrence) and safety (bleeds and deaths) of long-term treatment of VTE with LMWH compared with OA. A secondary endpoint was to evaluate the effect of LMWH on cancer mortality. Methods: Computerized searches of MedLine and EmBase were performed. In addition, randomized clinical trials were located through personal communication with colleagues, and through the manual scanning of meeting proceedings and reference lists of relevant studies. When necessary, the authors of the selected papers were called to obtain additional information. Two reviewers (AI and FG) reviewed and extracted data independently using a standard form. The primary analysis was performed for efficacy and safety endpoints on an intention-to-treat basis for the study period of randomized treatment. A meta-regression analysis was used to investigate the relationship between daily dose and clinical outcome. Results: Seven studies that fulfillled our predefined criteria were identified, for a total of 1379 patients. When all studies were combined, a statistically non-significant reduction in the risk of VTE (OR 0.66; 95% confidence interval [CI] 0.41, 1.07) and in the risk of major bleeding (OR 0.45; 95% CI 0.18, 1.11) in favor of LMWH treatment was found. No difference in total mortality (OR 1.19; 95% CI 0.78, 1.83) or in cancer-related mortality was observed between the LMWH and the OA treatment. Conclusions: The results of this meta-analysis indicate that a 3-month course of LMWH is as effective and safe as a corresponding period of OA treatment, and may thus be considered as a valuable alternative option for patients in whom OA treatment appears contraindicated or problematic.

SummarySafety and efficacy of the thrombolytic agent pro-urokinase (pro-UK) in the treatment of deep vein thrombosis of the lower limbs (DVT) have been investigated in an open, uncontrolled, pilot study. Fifteen patients were infused with 800.000 IU (5 mg)/h of pro-UK over 24 h (120 mg), together with unfractionated heparin adjusted to maintain the activated partial thromboplastin time between 1.5 and 2.5 times the basal value. Efficacy was assessed comparing venographic changes in the 11 evaluable limbs before and after pro-UK infusion. The Marder score decreased from a median pre-thrombolysis value of 28 (range 4-40) to 16 (3-38) (p

Thiazolidinediones (TZD) have been shown to down-regulate prostate-specific antigen (PSA) levels in prostate cancer cell lines and decrease PSA velocity among prostate cancer patients; however, the effect of TZDs on serum PSA levels among men with diabetes at risk for prostate cancer is unknown. We conducted a retrospective cohort study of veterans receiving care for diabetes between 1999 and 2005 to determine if TZD use affects PSA levels in veterans at risk for prostate cancer. Eligible patients were male, ≥45 years old, taking at least one oral antidiabetic medication, and with two or more recorded PSA values. Patients with a prior history of prostate cancer or prostatectomy were excluded. Of the 13,791 patients included in the adjusted analysis, 2,016 (14.6%) were prescribed a TZD. No effect of cumulative TZD dose on change in PSA was detected (P = 0.26). Increased TZD exposure was not associated with a change in PSA, suggesting that TZD treatment for diabetes is unlikely to affect prostate cancer detection. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1937–8)

Sexuality and affectivity constitute a complex phenomenon involving many spheres: biological, psychological and social. To investigate these aspects, we distributed a dedicated questionnaire, followed by an interview, to 130 elderly residents in Milan and 100 in Monza. The answers indicated that the elderly communicate their emotions regarding the affective and sexual sphere, with different levels of desire for physical contact. The main variables were sex, age, marital status, co-morbidity and poly-pharmacotherapy, the perception of health status and of oneself, past experiences, cultural conditioning and social factors.

The mechanical response of the bovine periodontal ligament (PDL) subjected to uniaxial tension and compression is reported. Several sections normal to the longitudinal axis of bovine incisors and molars were extracted from different depths. Specimens with dimensions 10 x 5 x 2 mm including dentine, PDL and alveolar bone were obtained from these sections. Scanning electron microscopy suggested a strong similarity between the bovine PDL and the human PDL microstructure described in the literature. The prepared specimens were tested in a custom made uniaxial testing machine. They were clamped on their bone and dentine extremities and immersed in a saline solution at 37 degrees C. Stress-strain curves indicated that the PDL is characterized by a non-linear and time-dependent mechanical behaviour with the typical features of collagenous soft tissues. The curves exhibited hysteresis and preconditioning effects. The mechanical parameters evaluated in tension were maximum tangent modulus, strength, maximizer strain and strain energy density. For the molars, all these parameters increased with depth except for the apical region. For the incisors, all parameters increased with depth except ultimate strain which decreased. It was assumed that collagen fibre density and orientation were responsible for these findings.

Although intravenous (i.v.) heparin is widely used as the first line treatment for cerebral venous and sinus thrombosis (CVST), the most appropriate therapy for this disease is still controversial. We report 2 cases of CVST who were successfully treated by means of loco-regional thrombolysis with urokinase. In the first case we chose this treatment instead of i.v. heparin because clinical conditions of the patient appeared critical for life on hospital admission; in the second case loco-regional thrombolysis was performed because a full-dose heparin treatment over 8 days failed to improve the clinical picture of the patient. In the literature, there are no established criteria for the use of loco-regional thrombolysis in CVST. On the basis of our own experience and few previous reports on the matter, we suggest that loco-regional thrombolysis should be considered an appropriate treatment for CVST when patients are at life risk, when an involvement of deep cerebral veins is present or when, after full heparinization, patients are doing poorly clinically.

Resin-based laboratory dental composites for prosthetic restorations have been developed in the past years as a cost-effective alternative to conventional porcelain-fused-to-metal or full ceramic restorations. The fracture toughness at different stress states (K(Ic), K(IIc), and mixed-modes K(I), K(II) ) was assessed for three laboratory dental composite resins used for prosthetic restorations that were aged up to 12 months in a food simulating fluid (10% ethanol) at 37 degrees C. The materials were mainly di- methacrylate based resins reinforced with submicron glass filler particles. The Brazilian disk test was used on precracked chevron-notched specimens, and different stress states were obtained by angulating the precracked chevron notch relative to the diametral compressive loading direction. The stress intensity factors were calculated using Atkinson et al.'s relation. For all three materials, mode I fracture toughness values ranged between 0.48-0.64 MPa. m(0.5) and mode II values ranged between 0.93-1.2 MPa. m(0.5). Overall, aging time and storage media had little effect on toughness. Considering the inherently low toughness of these restorative materials, their use should be limited to low stress masticatory areas.

The cardioversion of atrial fibrillation is linked to a substantial risk of systemic embolization. In an effort to reduce it, the American College of Chest Physicians (ACCP) periodically publishes guidelines for the use of anticoagulation in the conversion of atrial fibrillation.Determination of the physician's compliance with the recommendations of the "Fourth ACCP Consensus Conference on Antithrombotic Therapy".The charts of people admitted to a community hospital in 1998 with a diagnosis of atrial fibrillation (n = 202) were evaluated retrospectively. Consideration was given to the ACCP's recommendation to give anticoagulants 3 weeks before and 4 weeks after elective cardioversion to patients who had been in atrial fibrillation for more than 2 days.Ninety-one of the 202 patients admitted with atrial fibrillation reported the onset of arrhythmia more than 48 hours before. Thirty-four of them underwent elective cardioversion and 13 cases (33%) went without anticoagulation in the preceding 2 weeks. Of these 13 cases, 8 were patients aged over 75 (range 78-88, mean 84). After sinus rhythm had been restored in 30 people (spontaneously in 5 of them), the anticoagulant therapy was not administered during the 4 recommended weeks in 10 people (33%), all of them over 75 (range 77.94, mean 84).Anticoagulation for cardioversion of atrial fibrillation is underused, especially among elderly patients. In order not to let age itself be an obstacle to the correct treatment of patients with high embolic risk, our efforts must be improved in order to identify the correct therapeutic choice in each particular case. Initiatives aimed at identifying and removing any impediment to the application of guidelines may contribute to stimulating physicians in the process of evaluating the quality of hospital treatment.

The last decade has witnessed substantial progress in the prevention and treatment of venous thromboembolism. However, the risk of deep vein thrombosis remains high in trauma patients and those undergoing orthopaedic surgery despite use of the best available prophylaxis. Existing antithrombotics also carry a significant risk of bleeding and other adverse effects, including heparin-induced thrombocytopenia (HIT). More effective and safer anticoagulants are therefore needed. Current approaches for improving the benefit:risk ratio of antithrombotic therapy include the development of indirect thrombin inhibitors with a high anti-Xa:anti-IIa activity ratio, and the use of direct thrombin inhibitors. Novel indirect thrombin inhibitors under investigation include pentasaccharide and the heparinoid danaparoid. These agents may offer reduced bleeding risk compared with conventional therapies, but there is no evidence of greater antithrombotic efficacy. However, due to low cross-reactivity with anti-heparin-platelet factor 4 antibodies, danaparoid and pentasaccharide may prove valuable in the management of HIT. Theoretically, the antithrombotic effect of direct thrombin inhibitors may be greater than that of indirect inhibitors because direct inhibitors are not dependent on endogenous cofactors and are able to inhibit both free and clot-bound thrombin. Direct inhibitors of the active site of thrombin and recombinant variants of hirudin, originally derived from the medicinal leech, are currently under investigation. Early data on lepirudin and desirudin suggest that recombinant hirudins may have clinical applications in thromboprophylaxis for high-risk patients, acute cardiology indications and HIT.

Diagnosis of acute deep vein thrombosis (DVT) and of pulmonary embolism (PE) is often difficult: symptomatic patients are usually investigated employing several diagnostic tests, which should be appropriately selected and sequenced, taking into account their sensitivity, specificity, safety and cost. The objective of this paper is to evaluate the performance of the new diagnostic tests and their combination in rational diagnostic strategies.A literature review was made using a Medline(R) database search for the period 1988-1998 on the following key words in various combinations: diagnosis, diagnostic strategy, venous thrombosis, pulmonary embolism, venous thromboembolism. Results of a new study by our group on diagnosis of DVT in hospitalized patients are also discussed.In patients with symptoms or signs suggestive of DVT, compression ultrasound (CUS) appears to be the diagnostic test of first choice, since it is a noninvasive test with high specificity and sensitivity for proximal DVT (about 97%). When CUS gives a negative result it is usually recommended that the test is repeated after one week, since its sensitivity for calf DVT is poor. The positive and negative predictive values (PPV and NPV) of CUS in symptomatic outpatients can be improved if adequate consideration is given to clinical diagnosis, using a standardized model (ref. #9), which allows symptomatic outpatients to be categorized as having a high, moderate or low probability of DVT. In case of agreement between clinical diagnosis and CUS results, no further testing is needed: patients with high or intermediate clinical probability and positive CUS results are treated, while in patients with low clinical probability and negative CUS results the diagnosis of DVT is excluded. In the case of discrepancy between clinical diagnosis and CUS results, D-dimer test and/or venography are requested. However in patients who develop signs or symptoms of DVT in the hospital the clinical model does not work, and diagnosis should be based on an appropriate mix of CUS, D-dimer (DD) test and venography. In patients presenting with signs or symptoms of pulmonary embolism, the ventilation/perfusion (V/P) lung scan remains a pivotal diagnostic test, and pulmonary angiography the reference standard, but both methods have limitations and in recent years other diagnostic tests such as echocardiography, helical (or spiral) computerized tomography, and magnetic resonance imaging have been introduced into clinical practice. Moreover, all four diagnostic tools mentioned for DVT diagnosis can be considered. Several diagnostic strategies have been proposed and evaluated in comparative studies but there is still debate over the most efficient test combination or sequence.Diagnostic strategies which include adequate consideration of clinical diagnosis using standardized models have the potential of being more efficient for outpatients (but not for inpatients) with symptoms or signs suggesting DVT of lower limbs. For patients with suspected PE, several diagnostic strategies have been assessed: V/P lung scan remains a pivotal diagnostic test, but its limitations have been increasingly recognized and newer non-invasive techniques are gaining credit. A consensus is still to be reached over the most appropriate combination of diagnostic tests.

Cerebral venous and sinus thrombosis (CVST) is still considered a severe clinical problem that is difficult to diagnose and manage and is linked to a poor prognosis. Nonetheless, conventional cerebral angiography and magnetic resonance imaging (MRI), or more recently, MR angiography allow a more rapid and precise diagnosis, and prognosis has improved with the use of anticoagulant treatment. We report 23 cases of CVST consecutively admitted to the Institute of Neurology of the University of Parma during the period 1990-1997. In all cases diagnosis was confirmed by means of MRI or conventional angiography of brain vessels. Among the patients, 22 were female and 1 was male. In all patients, plasma levels of protein C, protein S, antithrombin III (ATIII) and antiphospholipid antibodies (APA) were evaluated. In 15 of 23 patients, the presence of factor V Leiden mutation was also determined, and found positive in 3 patients (20%). Of the 22 female patients, 15 (68%) were on low-oestrogen (containing less than 50 microg oestrogen) oral contraceptive (OC) treatment. This percentage of OC use by patients with CVST is much higher than that of the rest of the female Italian population. OC use was associated with the presence of factor V Leiden mutation in two cases, with a deficiency of protein C in 1 case and a deficiency of protein S in another.Whether low-oestrogen Ocs may induce cerebral thromboembolic events is an open matter. According to our data, it may be argued that Ocs, even if at low oestrogen content, represent a major risk factor for CVST. The use of Ocs, as is the case for systemic venous thromboembolic events, may further increase the risk of CVST in women carrying the factor V Leiden mutation or other inherited hyperthrombotic conditions.

Low-molecular-weight heparins (LMWHs) are obtained by depolymerization from standard heparin and show substantial advantages compared with the parent compound, by virtue of their different pharmacokinetics and lower interaction with platelets, so that they are supplanting heparin in various clinical indications. In the prophylaxis of venous thromboembolism, LMWHs are more efficacious than unfractionated heparin in patients at high thrombotic risk, and equally efficacious in patients at moderate thrombotic risk, with the benefit of once-a-day administration. In the treatment of acute deep venous thrombosis and pulmonary embolism, LMWHs administered subcutaneously in fixed dose per kg of body weight show equivalent efficacy and safety than intravenous heparin in adjusted dose, and allow home treatment in selected cases. In the treatment of deep venous thrombosis after the acute phase, LMWHs are equally effective and safer than oral anticoagulants. In unstable angina and non Q myocardial infarction, nadroparine and enoxaparin plus aspirin have been shown to be more efficacious than unfractionated heparin plus aspirin. In acute ischemic stroke, preliminary results are promising, but the evidence of efficacy must be substantiated by other studies, which are currently in progress.

To establish if an association exists between use of oral contraceptives (OC) and the occurrence of cerebral arterial thromboembolism, cerebral venous thrombosis and retinal vein/artery thrombosis, we identified all women aged 15-44 years resident in the province of Parma, Italy, who were hospitalized because of a documented cerebral or retinal thromboembolic event during the period 1989-1993. The numbers of users and nonusers of OC were estimated from drug sale data and demographic statistics for the province. There were 21 cases of cerebral arterial thromboembolism during the study period: 10 in OC users and 11 in nonusers, for an estimated incidence rate of 1.70 and 0.35 per 10,000 woman-years OC of use and nonuse, respectively (RR=4.8, 95% CI = 1.8-9.0). Eight cases of cerebral venous thrombosis were observed: 6 in OC users and 2 in nonusers (both in puerperium), for an incidence rate of 1.00 and 0.06 per 10,000 woman-years, respectively (RR=16.7, 95% CI = 3.3-81.4). Finally, 13 cases of retinal vein/artery thrombosis were found: 1 in OC users and 12 in nonusers, for an incidence rate of 0.17 and 0.37 per 10,000 woman-years, respectively (RR=0.46, 95% CI = 0.06-3.7). In our population study the use of low oestrogen OC was associated with an increased risk of cerebral venous thrombosis and ischemic stroke, but not of retinal vein/artery thrombosis.

To assess the risk of thromboembolism in women using oral contraceptives (OCs), we identified through computer search in the hospitals of the province of Parma, Italy, all women aged 15-44 who were resident in the province and had a documented thromboembolic event in the years 1989-93. The number of users and nonusers of OCs was estimated by the drug sale data for the province and by the demographic statistics. In cases with venous thromboembolism (VT) the prevalence of concomitant deficiency of antithrombin III, protein C, protein S, and of factor V gene mutation Arg506GIn was evaluated. The incidence rate of VT was 37/59,603 woman-years in users (0.62 per 1000) and 13/303,954 woman-years in nonusers (0.042 per 1000), for a relative risk (RR) of 14.5 (95% confidence interval: 7.8-27.1; P0.001); the rate of stroke per 1000 woman-years was 0.17 in users and 0.036 in nonusers (RR = 4.6; 2.9-10.7; P0.01). A congenital thrombophilia involving the protein C anticoagulant system was documented in about 25% of young women developing venous thromboembolism while on OCs.

To evaluate the role of low-molecular weight heparin (LMWH) as an alternative to oral anticoagulants in the prevention of recurrent venous thromboembolism, we compared in a randomized trial conventional warfarin treatment with a three-month course of enoxaparin 4000 anti-Xa units once a day subcutaneously. 187 patients with symptomatic deep-vein thrombosis (DVT), diagnosed by strain-gauge plethysmography plus D-dimer latex assay and confirmed by venography in most cases, were treated with full-dose subcutaneous heparin for ten days and then randomized to secondary prophylaxis. During the 3-month treatment period, 6 of the 93 patients who received LMWH (6%) and 4 of the 94 patients on warfarin (4%) had symptomatic recurrence of venous thromboembolism confirmed by objective testing (p = 0.5; 95% confidence interval [CI] for the difference, -3% to 7%). Four patients in the LMWH group had bleeding complications as compared with 12 in the warfarin group (p = 0.04; 95% CI for the difference, 4% to 14%). In the 9-month follow-up period, during which 34 patients on warfarin prolonged treatment for other 3 months and 14 up to one year, 10 patients in the enoxaparin group and 4 patients in the warfarin group suffered a documented recurrence of venous thromboembolism. Of these 14 late recurrences, just one occurred in patients with postoperative DVT. After one year there were 16 recurrences (17%) in the LMWH group and 8 (9%) in the warfarin group (p = 0.07; 95% CI for the difference, 1% to 16%).(ABSTRACT TRUNCATED AT 250 WORDS)

In our Center for the Surveillance of Anticoagulant Treatment, most of the 1700 patients followed-up are traditionally treated with acenocoumarol, while warfarin is administered nowadays to an increasing proportion of patients. To assess if the difference in the pharmacokinetics of these two drugs may determine a different laboratory quality of treatment, a retrospective study was performed on the computerized files of all 142 patients on treatment with warfarin for more than 100 days and on a control group of 142 patients treated with acenocoumarol, matched for age, sex, disease state and duration of oral anticoagulant therapy (OAT). The study considered 7071 assays for a total of 432 patient-years of treatment. The overall quality of treatment was significantly better in patients treated with warfarin (72% of controls within the therapeutic range versus 67% on acenocoumarol, p0.001). Also the individual quality of therapy, which was assessed as the percentage of patients with 75% or more assays in range, was in favour of warfarin (50.7% vs 34.5%, p0.05). Warfarin therapy was more stable and fewer assays were required for treatment monitoring. Confounding factors possibly influencing the treatment stability, such as interfering drugs, diagnostic or therapeutical procedures requiring withdrawal of anticoagulation, were evaluated and no significant difference between the two groups was found. The difference in the laboratory quality of OAT was marked in patients treated for prevention of arterial thromboembolism, while it was negligible in patients with venous thromboembolic disease, whose mean duration of OAT was considerably shorter. Since there is no evidence that acenocoumarol is more efficacious or safer than warfarin, the latter seems to be preferable for patients who are candidate to very prolonged OAT.

Real time ultrasound (US) was used to examine 165 consecutive inpatients with clinically suspected deep vein thrombosis of lower limbs. In order to evaluate accuracy, the results of non-invasive techniques were compared with ascending venography, performed in all patients. Assessment included only femoro-popliteal veins, because of difficulty in visualizing calf vein with US. Diagnosis of thrombosis was based on noncompressibility of the examined veins; pulsed Doppler provided further information by evaluating blood flow. In our series Duplex ultrasound was very accurate in detecting acute thrombosis of the proximal veins, sensitivity being 97% and specificity 98%. With US it is also possible to detect conditions that mimic deep vein thrombosis, such as muscular rupture, hematoma, popliteal cyst or compressive tumors. In conclusion US is considered a valid alternative to contrast venography in the diagnosis of proximal vein thrombosis of lower limbs.

A case of warfarin-induced dermatitis in a 79 year-old patient with Protein S deficiency is described. Both total Protein S antigen and free Protein S were moderately reduced (about 50%). The skin lesion did not progress to frank necrosis and it was associated with elevated creatin phosphokinase (CPK) levels in plasma and with thrombosis of the anterior tibial vein localized to the area of dermatitis (probably warfarin-induced deep venous thrombosis). After warfarin withdrawal and beginning of heparin therapy, serum CPK rapidly normalized and the skin lesion improved.

Compression stockings are recommended for prophylaxis against venous thromboembolism in patients undergoing neurosurgery, but anticoagulant agents have not gained wide acceptance because of concern about intracranial bleeding.In a multicenter, randomized, double-blind trial, we assessed the efficacy and safety of enoxaparin in conjunction with the use of compression stockings in the prevention of venous thromboembolism in patients undergoing elective neurosurgery. Enoxaparin (40 mg once daily) or placebo was given subcutaneously for not less than seven days beginning within 24 hours after the completion of surgery. The primary end point was symptomatic, objectively confirmed venous thromboembolism or deep-vein thrombosis assessed by bilateral venography, which was performed in all patients on day 8+/-1. Bleeding side effects were carefully assessed.Among the 307 patients assigned to treatment groups, 129 of the 154 patients receiving placebo (84 percent) and 130 of the 153 patients receiving enoxaparin (85 percent) had venographic studies adequate for analysis. An additional patient in the placebo group died before venography of autopsy-confirmed pulmonary embolism. In this analysis, 42 patients given placebo (32 percent) and 22 patients given enoxaparin (17 percent) had deep-vein thrombosis (relative risk in the enoxaparin group, 0.52; 95 percent confidence interval, 0.33 to 0.82; P=0.004). The rates of proximal deep-vein thrombosis were 13 percent in patients receiving placebo and 5 percent in patients receiving enoxaparin (relative risk in the enoxaparin group, 0.41; 95 percent confidence interval, 0.17 to 0.95; P=0.04). Two patients in the placebo group died of autopsy-confirmed pulmonary embolism on days 9 and 16. Major bleeding occurred in four patients receiving placebo (intracranial bleeding in all four) and four patients (intracranial bleeding in three) receiving enoxaparin (3 percent of each group).Enoxaparin combined with compression stockings is more effective than compression stockings alone for the prevention of venous thromboembolism after elective neurosurgery and does not cause excessive bleeding.

271 patients with acute symptomatic deep venous thrombosis of lower limbs, confirmed by strain-gauge plethysmography and/or venography, were randomly assigned to receive intermittent subcutaneous heparin calcium or heparin sodium by continuous intravenous infusion for 6-10 days. Heparin dosage was adjusted to maintain activated partial thromboplastin time values (Thrombofax reagent) at 1.3-1.9 times the basal ones. Strain-gauge plethysmography was repeated at the end of heparin treatment, and evaluation of therapy was performed by comparing the indexes of venous hemodynamics and by assessing the incidence of pulmonary embolism and of bleeding complications. In the intravenous group, Maximal Venous Outflow (MVO) increased from 20.8 +/- 12.8 to 28.4 +/- 17.5 ml/min per 100 ml of tissue and Venous Capacitance (VC) from 1.39 +/- 0.92 to 1.94 +/- 1.0 ml/100 ml of tissue (mean +/- SD). In the subcutaneous group, MVO increased from 21.0 +/- 12.7 to 27.5 +/- 18.1 and VC from 1.60 +/- 0.86 to 2.06 +/- 1.0. The median improvement of MVO and VC were 22% and 36% respectively in the IV group and 20% and 24% in the SC group. Clinical pulmonary embolism occurred in 2 patients in the intravenous group (1 fatal) and in 4 in the subcutaneous group (1 fatal). 9 major bleeding complications occurred in the intravenous group (1 fatal) and 5 in the subcutaneous group (1 fatal). The differences were not significant at the statistical analysis. The results suggest that subcutaneous intermittent heparin has a comparable efficacy to continuous intravenous heparin in the treatment of deep venous thrombosis. To the same conclusion points an overview of the seven randomized trials which compared these treatment modalities.

A case of a 49-year-old woman affected by wide ulcerations on the face which have been caused by the patient herself, as she has admitted, is reported. The lesions were strictly limited to the area of innervation of the first and second branch of the trigeminal nerve. The patient presented parasthesias and analgesia in the trigeminal area as the consequence of a neurosurgical operation. She also suffered from important psychosis. All these elements enable us to diagnose "trigeminal trophic ulcers". The pathogenesis of this syndrome is discussed.

The possibility that platelets interfere in changes evoked by venous stasis in the hemostatic system of local blood was investigated in man with the tourniquet test. A significant rise in PF4 (anti-heparin) activity of PPP and an inconstant increase in PF3 availability were the only changes seen in samples after stasis, while platelet number, adhesiveness, ADP-aggregation, and platelet fibrinolytic components (antiplasmin and proactivator activities) remained unchanged.

Platelet function tests were investigated in 14 diabetic patients on long-term treatment with gliclazide. A significant decrease of ADP and adrenaline induced aggregation was found after 3, 6 and 12 months of therapy. A reduced adhesiveness, with significant differences after 6 and 12 months was also seen. Bleeding time was unaffected.

In a randomised trial we compared the effects of two different antithrombotic regimens on the incidence of venographically established deep venous thrombosis (DVT) in 83 patients undergoing surgery for fracture of the femoral neck. Group A received dextran 40 peroperatively plus 0.5 g aspirin a day beginning before operation and continuing for 10 days after. Group B received heparin calcium 5000 iu subcutaneously plus dihydroergotamine (DHE) 0.5 mg intramuscularly, given 8-hourly, beginning before operation and continuing for 10 days after. Two patients in Group A and three in Group B developed proximal DVT, while the incidence of all DVT was 33% in Group A and 29% in Group B, a difference which was not significant. Haemorrhagic complications were much more common in the dextran/aspirin group: the volume of drainage fluid, the number of patients transfused and quantity of blood transfused, and the drop in haemoglobin level were all significantly greater in Group A. We conclude that the DHE/heparin regime is preferable to dextran/aspirin because it is safer and no less effective.

Factor VIII coagulant activity (FVIII:C), ristocetin co-factor or Willebrand Factor activity (FVIII:WF) and antigen related to FVIII (FVIIIR:Ag) were measured in a group of patients with peripheral arterial disease (PAD) and in a comparable control group. No differences were recorded between patients and controls both in basal conditions and after a standardized venous occlusion (VO) test. VO induced a significant increase in all the FVIII components, comparable in the two groups, with only minor variations in the ratios between them, due to a relatively greater response of the two activities with regard to the protein (FVIIIR:Ag) concentration. FVIII:C was significantly correlated with FVIIIR:Ag and with FVIII:WF only in controls in basal conditions, while no correlation was found in PAD group, nor after VO in either group. Patients with atherosclerosis obliterans seem therefore to have normal levels of FVIII components and to mantain a normal capacity of responding to VO stimulation. FVIII coagulant activity can be acquired in local blood, or, in alternative, FVIII complex can be released as a whole from vascular walls following venous stasis.

The process of fibrin formation was systematically investigated in 25 patients with severe alcoholic cirrhosis. Results of functional tests are reported. A significant lengthening of the thrombin time was found which could not be completely attributed either to hypofibrinogenaemia or to an increase in physiological anticoagulants or to the presence of pathological antithrombins. A defect in fibrin polymerization was seen in the absence of significant levels of antipolymerizing agents. Indirect evidence pointed to an abnormal fibrinogen function. This was mainly suggested by the ‘polymerization curves’ of mixtures of normal and pathological plasmas and the changes in physico-chemical properties of the clot (optical and elastic properties; tensile strength). Altered synthesis in hepatocytes may lead to an ‘acquired dysfibrinogenaemia’ in the late stages of liver cirrhosis, although alteration of a normal fibrinogen molecule after secretion cannot be definitely excluded.

Efficacy and safety of a low molecular weight heparin (Alfa LMWH) was compared with unfractionated heparin (UFH) in the prevention of post-operative venous thromboembolism after hip fractures. Forty-nine patients were randomized to treatment with Alfa LMWH 7500 anti-Xa coagulometric units twice daily or with UFH 5000 IU t.i.d. Screening for thrombosis was performed with 125-I-fibrinogen leg scanning and strain-gauge plethysmography. Positive results were confirmed by venography. Five patients in the Alfa LMWH group (20 per cent) developed venographycally proven deep vein thrombosis (DVT) versus seven (29 per cent) in the UFH group. One pulmonary embolism and two deaths occurred in the UFH group and none in the LMWH group. No differences in haemorrhagic complications and blood loss indices were observed. Alfa LMWH appears to be a promising drug for prevention of venous thromboembolism after orthopaedic surgery. A "flexible" schedule of administration is proposed on the basis of the results of plasma anti-Xa assays.

The clinical diagnosis of deep vein thrombosis is unreliable and venography remains the best single method of investigation. In the last ten years several non-invasive procedures have been introduced in the vascular laboratories, sometime without adequate assessment of their reliability. We tested sensitivity and specificity of three different non-invasive procedures, namely phleboscintigraphy with 99Technetium, Doppler ultrasound technique and strain-gauge plethysmography in patients with clinically suspected deep vein thrombosis of lower limbs or pulmonary embolism. A total of 288 patients entered the study. Venography was used as the reference standard and was assessed independently, without knowledge of the results of non-invasive methods. In the first 36 patients phleboscintigraphy and Doppler ultrasound were evaluated: sensitivity and specificity of phleboscintigraphy resulted only a little more than 50%; the method was therefore considered unreliable and subsequently abandoned. Doppler ultrasound could be evaluated upon a total of 81 patients, showing an unsatisfactory sensitivity (63%), but a quite reliable specificity (86%). Best results were obtained with strain-gauge plethysmography, using maximal venous outflow and venous capacitance as diagnostic parameters. 209 patients entered this study, and a sensitivity of about 90% with a specificity of about 95% was observed. If we consider only acute proximal deep vein thrombosis, sensitivity approaches 97%, while it is only 60% in distal deep vein thrombosis.

Antithrombin III (ATIII) deficiency is inherited as an autosomal dominant trait. Three types of ATIII deficiency are recognized clinically. The prevalence of ATIII deficiency is uncertain; it has been estimated to occur in between one in 2,000 and one in 20,000 subjects. ATIII deficiency is found in between 4 and 6 percent of young patients with venous thrombosis, similar to but slightly lower than the prevalence of protein C and protein S deficiency in young subjects with thrombosis. The chances of finding a deficiency is increased if there is a history of familial or recurrent venous thrombosis. Cross-sectional reports in the literature are that between 30 and 80 percent of carriers have thrombosis. Thrombosis is uncommon in the first decade, but the risk rises sharply between the ages of 15 and 30. The major clinical manifestations of ATIII deficiency are young age at onset, idiopathic thrombosis, family history, and recurrent venous thromboembolism. Pregnancy and surgery are predisposing factors. Approaches to prophylaxis and treatment are discussed.

Six of eight examined members belonging to two generations of the same (NEG-TUR) family were shown to have functional changes in platelets and/or a moderate decrease of factor VIII activity (FVIII:C) in plasma, with normal values of factor VIII-related antigen (VIII R:AG). Platelet defects (mainly a reduced PF3 availability, present in five patients) and factor VIII decrease were combined differently in individual members. Only two male members with both the PF 3 and FVIII:C defects had moderate haemorrhagic symptoms following traumatic injuries. One of them had also an absent adhesiveness to glass, the other one an absent adhesiveness to collagen and a reduced platelet aggregation by ADP and by collagen. Bleeding time, platelet function tests (in the other members), and routine coagulation tests were within normal range; ristocetin aggregation was also normal in all members. We think that two inherited defects, a mild haemophilia A and a "sui generis" thrombocytopathy, co-exist in this family.

The anticoagulant effect of a Low Molecular Weight Heparin from Alfa Farmaceutici, Bologna, Italy, was studied in human volunteers of either sex. Assays of plasma anti Xa (S-2222) and anti IIa (cromozym TH) activities, and of PTT, were performed following single or repeated administration by intravenous (i.v.), subcutaneous (s.c.) or intramuscular (i.m.) route. Each set of experiments was carried out in groups of subjects ranging from 6 to 12. After i.v. adm. of 8000 and 16000 I.U. AXa peak level and half life in plasma of the anti Xa activity were about double than the corresponding values of anti IIa activity and the effect on PTT, when compared with the same reference material (heparin, Third Internat. Standard). Similar differences between these pharmacological effects were found in the response curves obtained after s.c. or i.m. adm. of 16000 and 8000 I.U. Appreciable anti Xa activity was found in plasma 16-20 hours after adm. of 16000 I.U., and 10 hours after 8000 I.U. After repeated i.m. or s.c. adm. for 7 days, no cumulative effect was observed with 16000 I.U. once daily. By giving 8000 b.i.d., mean peak levels of .35-.40 U/ml of anti Xa activity were reached in the first day and of .45-.55 U/ml in the following days, a residual activity in the order of .1-.2 U/ml being always detected in the samples drawn immediately before the following injection.

2 cases of acute idiopathic thrombotic thrombocytopenic purpura are reported. Both of them were treated with plasma exchange, antiplatelet drugs and prednisolone and both completely recovered. Plasma exchange appeared to be the critical treatment. In 1 of these cases the prostacyclinlike activity released from venous tissues and the ability of plasma to stimulate synthesis of prostacyclinlike activity from venous tissues exhausted after repeated washings were investigated. Both activities were detectable and comparable to those of a healthy control. These findings do not support the hypothesis of a major role played by the prostacyclin system in the pathogenesis of thrombotic thrombocytopenic purpura.

Forty-seven patients with chronic venous leg ulcers were included in a randomized clinical trial to evaluate the efficacy of systemically administered antibiotics in healing with condition. One group was treated by means of elastic support bandages only, whereas the other one received the same local treatment plus systemic antibiotics. No statistically relevant difference was noted between the two groups in healing rates of ulcers or in changes of the microbiologic flora. The results of our study do not support the routine administration of systemic antibiotics in the management of chronic venous leg ulcers.

In 1982 a programme of multi-disciplinary follow-up on 12 patients that underwent a gastric tube oesophagoplasty for long-gap oesophageal atresia was started. Radiological examination, performed on all gastric tubes but one (died a few days after surgery), assessed the morphology and dynamics of gastric tube, either distally or proximally based, and stomach 2 to 8 years after surgery. Endoscopic backward exploration was performed on 7 cases, to allow a closer analysis of stomach, gastric tube mucosa and upper oesophageal stump, demonstrating that the gastric transplant is viable and almost undamaged. No evidence of oesophagitis of the proximal stump was found. Histological stainings on biopsy specimens and on sections from one post-mortem examination, showed a mild degree of dystrophy in gastric tube mucosa, progressively shading into proper gastric mucosa. No evidence of a progressive change for the worse was found in any of the 7 tubes controlled.

The efficacy and safety of pentoxifylline (400 mg tid orally) and acenocoumarol, administered singly or in combination, in the treatment of intermittent claudication associated with chronic occlusive arterial disease were evaluated in a multi-center, randomized, factorial, blind clinical trial involving 146 patients. The response to treatment was assessed by measuring pain-free walking time on the treadmill and by Doppler ankle/arm systolic pressure ratio at rest and after treadmill. Both pentoxifylline and acenocoumarol were significantly more effective than placebo in increasing the proportion of patients who improved their performance on the treadmill after one year of treatment. Benefit from active treatment was also apparent from the results of Doppler examinations performed after physical exercise. No significant differences were observed in comparing the effect of one active drug versus the other or versus the combined treatment. Five major hemorrhagic complications were registered in anticoagulated patients, two fatal cerebral hemorrhages and one gastrointestinal bleeding occurring in the group treated with both active drugs. The investigators conclude that (1) pentoxifylline is effective and safe in the treatment of patients with intermittent claudication (2) the benefits of oral anticoagulant therapy are outweighed by the risk of serious bleeding, and (3) the risk of bleeding is probably increased by the combined treatment with pentoxifylline.

The Candida albicans infection represents a rather frequent complication in immunodeficient patients, while the evolution towards the growth of multiple intraparenchymal abscesses constitutes a very rare event. The authors describe the diagnostic-therapeutic pathway chosen in a case regarding a young patient in treatment for leukemia , who was affected by multiple splenic and renal abscesses caused by Candida albicans. After a preoperative diagnosis through ultrasonography and C.A.T., a splenectomy was undertaken. Next the only healthy part of the spleen was removed and grafted into the omentum. By using the intraoperative ultrasonography on both kidneys, the abscess cavities were precisely located, aspirated and finally stuck with a human fibrin glue.

Heparin administration for operations with extracorporeal circulation (ECC) usually is performed following prefixed, standardized protocols. These regimens secure an adequate level of anticoagulation, but they often involve prolonged periods of overheparinization associated with an undue risk of hemorrhage. The predictive value of preoperative studies in the anticoagulant effect of heparin was investigated in 10 patients. The study was performed both in vitro and in vivo using the Xa inhibitor assay as an index of the anticoagulation induced by heparin. Adding variable amounts of heparin in vitro to patient's plasma resulted in straight (at least up to 7 U. per milliliter) and parallel, but not coincident, dose/response curves, so confirming a different individual sensitivity to heparin. Disappearance curves of the anticoagulant effect in plasma following intravenous administration of a single standard dose of heparin in the same patients showed an even greater patient-to-patient variability, with "half-life" times ranging from 30 to 150 minutes. No relationship was found between the parameters (in vitro sensitivity to heparin and clearance rate from plasma in vivo). Moreover, neither of them could be correlated with the response to heparin, subsequently observed during ECC in the same patients. Preoperative investigations with the methods presently available are not adequate to choose individual heparin administration regimens for cardiac operations.

Strain-gauge plethysmography (SGP) is currently employed in the diagnosis of deep venous thrombosis (DVT), but its accuracy has not been adequately tested. In this study we evaluated SGP against venography in 209 consecutive patients referred to us because of clinically suspected DVT of lower limbs. Venography was performed bilaterally if symptoms or signs suggesting DVT were present in both limbs. It was always performed after SGP and independently assessed. A total of 269 limbs could be evaluated with both SGP and venography, which disclosed DVT in 128 limbs of 110 patients. There were 109 proximal and 19 distal DVT. Out of the 128 limbs with DVT, SGP was positive in 114 (sensitivity=89%) using Maximal Venous Outflow (MVO) as the diagnostic parameter, and positive in 116 (sensitivity=91%) using an index obtained multiplying MVO for Venous Capacitance (VC). Out of the 141 venographically negative limbs, there were 6 false positive results using MVO and 9 using MVO x VC (specificity=96% and 94% respectively). SGP sensitivity in acute proximal venous thrombosis was 97%, while it was about 60% in distal DVT. Most false positive results occurred in patients with edema of cardiac origin. SGP appears to be a useful diagnostic test in suspected DVT of lower limbs, particularly when both MVO and the index MVO x VC are used.