Clinical and radiographical outcome after surgical treatment of periprosthetic type B proximal femur fractures: a retrospective study.

PURPOSE: Periprosthetic fractures after hip prosthesis represent a constantly increasing clinical problem and a challenging complication to treat surgically. Among these, type B proximal femur fractures should be diagnosed correctly to be treated surgically. The aim of this study was to re-evaluate the type of surgical treatment of periprosthetic fractures. METHODS: We examined the cases treated between January 2012 and February 2018, classifying them according to the U.C.S. AO/OTA. We evaluated the radiographic outcome according to the Beals and Tower criteria. Patients still alive were also re-evaluated according to the H.H.S. and the WOMAC score. RESULTS: We treated 48 patients (12 men, 35 women, average age 81 years), divided into 24 type B1, 14 type B2 and 10 type B3 fractures. The overall consolidation rate was 95.4%, while the major complication (implant dislocation, pseudoarthrosis and deep infection) rate was 12.5%. Clinically, it was possible to reassess 34 patients with a mean follow-up of 38.4 months, an average HHS of 75.89 and a mean WOMAC score of 79.93. CONCLUSIONS: Periprosthetic type B fractures are difficult to manage and require careful preoperative planning and appropriate intraoperative management. However, the overall clinical and radiographic result was satisfactory, although patients should still be aware of the risk of complications associated with this type of fracture.

Modulation of hemostatic balance with antithrombin III replacement therapy in a case of liver cirrhosis associated with recurrent venous thrombosis.

Patients with liver failure can present both thrombotic and hemorrhagic complications because of the deficiency in coagulation factors and inhibitors (protein C and S, antithrombin III) and impairment of fibrinolytic balance. Here we report the case of a 63-year-old man with liver cirrhosis, recurrent thrombosis, and features of low-grade consumption coagulopathy, showing severe antithrombin III deficiency (about 30% of normal values). Treatment with antithrombin III (2000 U/day) and low doses of heparin (5000 U b.i.d.) was successful in modulating the coagulation system toward an antithrombotic effect. After discharge from hospital the ambulatory treatment with antithrombin III concentrates (2000 U twice a week) allowed the attainment of antithrombin III activity of about 60% and prevented the patient from recurrence of venous thrombosis.

Forearm blood flow reserve and cardiac and renal indexes of pressure load in normotensive and hypertensive individuals.

In response to hypertension, arterioles remodel their structure, the heart develops myocardial hypertrophy, and the kidney reduces creatinine clearance and increases albuminuria. To better understand the interrelations among the target organs involved in hypertension, we evaluated minimal forearm vascular resistances--a hemodynamic index of arteriolar structure derived from mean blood pressure and maximal postischemic forearm blood flow--the echocardiographic indexes of cardiac structure, and urinary albumin excretion and creatinine clearance in 29 male mild to moderate non-macroalbuminuric essential hypertensive patients on no drugs and 11 age- and sex-matched normotensive control subjects. Minimal forearm resistances were elevated in hypertensive patients and correlated with left ventricular mass, wall thickness, and mean arterial pressure. Patients with abnormal minimal forearm resistances (2 SD above normal) were characterized by higher pressure, greater wall thickness, lower creatinine clearance, and higher albumin excretion, suggesting that maximal forearm flow capacity does relate to the hemodynamic load exerted on both the kidney and heart. However, the correlation with cardiac structure and mean arterial pressure explained only part of the variability of minimal forearm resistances. Furthermore, no correlation among these parameters was found when hypertensive patients were evaluated separately from normotensive subjects, possibly because of heterogeneous factors active on arteriolar structure and unrelated to the pressor load. Overall, the data suggest that the development of abnormal minimal forearm resistances in the course of the hypertensive process is related to the pressor load, but its details need further understanding.

The metabolism of human serum albumin in renal failure on conservative and dialysis therapy.

The pathophysiology of albumin metabolism in uremia was investigated by turnover measurements in a large series of uremic patients, either on conservative management or on dialysis therapy. A total of 62 turnover studies were performed in patients on dietary treatment, divided into two groups according to the duration of the low protein diet: 35 subjects from 6 to 30 days, 27 subjects from 6 months to 5 years. Albumin catabolism and distribution were measured by the two-tracer technique (131I-albumin and 125I-iodide, simultaneously injected iv), while albumin synthesis was directly determined in 10 patients by the use of 14C-carbonate and 131I-albumin. Sixteen turnover studies were also performed in a group of end-stage uremics on dialysis therapy by a two-tracer procedure especially designed to determine albumin catabolism in the course of a single peritoneal or hemodialytic treatment. The main features of albumin metabolism observed in the patients on dietary management were: normal intravascular albumin mass, marked reduction of the extravascular and total albumin pools, with proportionally reduced catabolism. No significant turnover difference was found between the short-term diet group and the patients on low-protein diet from 6 months to 5 years. As to the uremics on dialysis therapy, catabolic rate of albumin was 3-fold increased in three patients showing clinical features of "hypercatabolism" in the early phase of uremia, or during relapse from it. Albumin turnover rate returned to normal when measured during clinical steady-state conditions. All these findings suggest that a marked body protein depletion exists in chronic uremia, and that dietary treatment per se is not responsible for such a depleted state. Instead, the depletion of protein stores observed in the steady phase of chronic uremia may have been originated by the exaggerated increased catabolism in the early phase of renal failure, not compensated by a proportional increase of the synthetic rate, due to both the state of uremic intoxication and to the reduced dietary protein intake during the early phase.

Local insulin infusion stimulates expression of plasminogen activator inhibitor-1 and tissue-type plasminogen activator in normal subjects.

PURPOSE: Plasma levels of plasminogen activator inhibitor-1 are increased in obesity, hypertension, and diabetes. Their correlation with insulin levels supports the hypothesis that hypofibrinolysis may affect the development of atherosclerotic complications in patients with insulin resistance. To investigate the effect of insulin on fibrinolysis, we evaluated levels of plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) antigens during insulin infusion in the forearm vascular beds of 8 healthy subjects. MATERIALS AND METHODS: Insulin was infused in the brachial artery of each subject to raise local venous concentrations to approximately 100 microU/mL. Blood samples were obtained from the brachial artery and vein at baseline, after 30, 60, 90, and 120 minutes of infusion, and 30 minutes after the end of the infusion. RESULTS: Following intra-arterial infusion of insulin, forearm blood flow (mean +/- SD) increased progressively from 2.7 +/- 0.6 to 4.0 +/- 0.6 mL/dL/min (P <0.01) and did not return to baseline after the end of the infusion. Plasminogen activator inhibitor-1 balance increased (345 +/- 160 versus 8 +/- 152 fmol/dL/min, P <0.02) at 60 minutes, reaching baseline levels after the end of the infusion. After 90 minutes, tPA balance increased (40 +/- 26 versus 7 +/- 29 fmol/dL/min, P <0.01) with a profile similar to forearm blood flow. CONCLUSIONS: Local hyperinsulinemia induces regional vasodilation and expression of PAI-1 and tPA antigens. An alteration of this physiological process could be involved in the development of hypofibrinolysis and atherosclerosis in states of insulin resistance.

Coagulation and fibrinolytic system impairment in insulin dependent diabetes mellitus.

Selected coagulation and fibrinolytic parameters were assessed in 40 insulin dependent diabetes mellitus patients with varying degrees of metabolic control; 30 healthy subjects matched for age and sex formed the control group. Activated Partial Thromboplastin Time, Prothrombin Time, Fibrinogen, Factor VII, Antithrombin III, Protein C, Plasminogen, alpha 2-Plasmin Inhibitor, Plasminogen Activator Inhibitor-1, tissue-Plasminogen Activator were functionally evaluated. Antigenic levels of tissue-Plasminogen Activator, Thrombin-Antithrombin complexes and fibrinolytic specific product B beta 15-42 were also determined. Compared to the control group diabetic patients displayed significantly higher levels of Fibrinogen (p < 0.01), Factor VII (p < 0.01), Thrombin-Antithrombin complexes (p < 0.01) and Plasminogen Activator Inhibitor-1 activity (p < 0.01). Regardless of the normal level of the tissue-Plasminogen Activator-related antigen, diabetic patients had tissue-Plasminogen Activator activity lower than the control group (p < 0.05). Coagulation Factor VII and Thrombin-Antithrombin complexes were increased only in the patients with poor metabolic control (p < 0.01). Activated Partial Thromboplastin Time, Prothrombin Time, Antithrombin III, Protein C, Plasminogen, alpha 2-Plasmin Inhibitor, B beta 15-42 fibrin peptide were found to be in the normal range. Fibrinogen correlated positively with fasting blood glucose (p < 0.05) and Thrombin-Antithrombin complexes with glycosylated haemoglobin (p < 0.05), whereas Factor VII was positively correlated with glycemia (p < 0.01) and glycosylated haemoglobin (p < 0.05). Higher levels of Fibrinogen were found in patients affected by nephropathy (p < 0.005) or neuropathy (p < 0.05). These results demonstrate an impairment of the haemostatic balance in diabetic patients, that is a possible hypercoagulable state, which represents an important factor in the pathogenesis of atherosclerotic complications.

Efficacy of intravenous immunoglobulin therapy in a case of autoimmune-mediated chronic active hepatitis.

In a patient suffering from histologically-documented immuno-mediated chronic active hepatitis, intravenous immunoglobulin (IVIG) treatment was initiated as an obligatory alternative therapy because of femur head aseptic necrosis which had followed long-term therapy with steroids. The first cycle of IVIG was followed by remission of most symptoms, normalization of liver enzymes, disappearance of circulating immunecomplexes (CIC), and a negative lupus band test. Improvement in the patient's condition was demonstrated, in liver histology, by the disappearance of peri-portal mononuclear cells infiltrates, while immunohistochemistry showed the disappearance of the intracellular IgG deposits.

Oral contraceptives and venous thromboembolic disease: the effect of the oestrogen dose.

PIP: Low-dose oral contraceptives when tested for vascular or thrombotic effects not only show no risk of venous thromboembolic disease, but this method could possibly reduce the chance of thromboembolic disease as compared with pills which have a higher estrogen dose. It has also been found that pills containing lower doses of estrogen have no effect on the coagulatory system. Concerns raised about the connection between oral contraceptive use and the risk of cardiovascular disease called for testing in the late 1960s. Epidemiological studies confirmed the risk of oral contraceptive use and cardiovascular disease especially venous thromboembolism. A further association was identified between the amount of estrogens contained in oral contraceptives and the risk of disease. Estrogens affect the hemostatic system; decreases in antithrombin III activity in addition to platelet adhesiveness and blood viscosity have been observed in oral contraceptive users. Although both a decreased influence on the hemostatic system and the risk of thromboembolic disease have been found in pills with lower doses of estrogen, further research on the effect of the clotting system by low-dose oral contraceptives is needed.^ieng

Fibrinopeptide A plasma levels during low-estrogen oral contraceptive treatment.

In a group of healthy women taking oral contraceptives containing 30 micrograms ethinylestradiol combined with two different progestogens (desogestrel and gestoden), Fibrinopeptide A (FPA) plasma levels were evaluated both before and after 3, 6 and 9 months of therapy. FPA levels, which represent an index of thrombin action in vivo, were also determined in untreated subjects during the follicular and the luteal phases of the menstrual cycle. While no modifications of FPA levels were found during the menstrual cycle, a significant increase of this peptide was observed during oral contraceptive treatment. These data suggest that low-dose oral contraceptives, by enhancing the rate of conversion of fibrinogen to fibrin by thrombin, increase the risk of venous thrombosis. Since some mechanisms which compete with the thrombin activity are also increased by oral contraceptives, the significance of this change in the induction of thrombosis cannot be completely clarified.

A 12-month clinical investigation with a 24-day regimen containing 15 microg ethinylestradiol plus 60 microg gestodene with respect to hemostasis and cycle control.

The effects of a 24-day regimen containing 15 microg ethinyl estradiol (EE) plus 60 microg gestodene on cycle control and on hemostasis, were evaluated in 58 healthy women (age 19-47 years). All women received the pill for 12 months. Withdrawal bleeding at every cycle during the tablet-free interval was experienced by 84.5% of the women. The overall incidence of irregular bleedings was 19.3%. Hemostasis was evaluated in 20 women. No changes in plasma fibrinogen concentrations, nor in prothrombin fragment F1+2 were observed. A slight increase in thrombin-antithrombin III complexes was observed after 6 and 12 months of oral contraceptive use. Antithrombin III activity significantly increased after one-year of pill intake. The concentrations of tissue plasminogen activator and plasminogen activator inhibitor, both antigen and activity, did not change. These results show that very low doses of EE, such as 15 microg, do not impair hemostasis in healthy females. However, the reduction for the EE dose is responsible of some of the effects on cycle control.

Acetylcholine-mediated vasodilatation and tissue-type plasminogen activator release in normal and hypertensive men.

Muscarinic agents release tissue plasminogen activator (t-PA) in the forearm circulation of normal subjects, but no information exists about their effect in those hypertensive patients in whom the response to endothelial-mediated vasodilators is blunted. Acetylcholine, an endothelium-dependent vasodilator and a muscarinic agonist that releases t-PA from in-vitro systems, and sodium nitroprusside, an endothelium-independent vasodilator, were infused into the brachial artery at rates calculated to cause a similar degree of vasodilatation. The study was performed in five elderly, smoking hypertensive patients in whom the clustering of detrimental factors for endothelial function permitted prediction of defective endothelial-mediated vasorelaxation, and five young, normotensive, nonsmoking male volunteers. Forearm blood flow was assessed by venous plethysmography; t-PA and plasminogen activator inhibitor 1 (PAI-1) antigen values were expressed as flow-dependent (net release, the product of venoarterial concentration gradient and forearm blood flow) or independent (absolute and fractional concentration gradients) indices. In patients, acetylcholine did not change flow and net release and concentration gradients of t-PA, suggesting that vasodilatation as such, possibly by increasing fluid shear stress, may induce t-PA release in human forearm. In normal subjects, acetylcholine and sodium nitroprusside increased t-PA antigen net release at the highest infusion rate, an effect attributable to forearm hyperperfusion, since absolute and fractional gradients did not change significantly. PAI-1 antigen did not change during either infusion in both controls and patients, indicating the absence of an endothelial pool to be mobilized acutely.

Elastase- and plasmin-mediated fibrinolysis in rheumatoid arthritis.

Selected coagulation and fibrinolytic factors were evaluated in plasma and synovial fluid (SF) of 10 rheumatoid arthritis (RA) patients. Increased levels of fibrinogen were observed in plasma (p < 0.01), but only a trace amount of structurally intact fibrinogen was detected in the SF of RA patients, while immunostaining showed deposits of insoluble fibrin in their synovial membranes. Reduced levels of protein C, antithrombin III and coagulation factors II, V, VII, VIII, IX, XII and XIII (p < 0.01), and high levels of thrombin-antithrombin III (TAT) complexes (p < 0.01), were found in SF as compared to their corresponding plasma levels. The increased levels of fibrinogen, TAT complexes, B beta 15-42 peptide and plasminogen activator inhibitor-1 (PAI-1) in plasma (p < 0.01) are consistent with an enhanced fibrin turnover and endothelial perturbation due to a systemic inflammatory state. Plasminogen and alpha 2-plasmin inhibitor activity in SF were significantly reduced as compared to the plasma levels (p < 0.01), whereas an increase in PAI-1 activity was found in SF as compared to plasma (p < 0.01). The detection of D-dimer and B beta 15-42 peptide (p < 0.01) in SF suggests an involvement of plasmin in the degradation of fibrin generated in synovial tissue. The high levels of elastase-alpha 1-proteinase inhibitor complexes and of thrombin-increasable fibrinopeptide A, as well as the pattern of fibrinogen degradation as identified in SF by double-dimension immunoelectrophoresis, suggest that elastase released from exudated granulocytes may play an important role in fibrino(geno)lysis and tissue damage in RA joints.

Inappropriate antidiuretic hormone secretion in a patient with systemic sarcoidosis.

A 59 year old man presenting fever, serum hyponatremia and hypoosmolality in association with hyperosmotic urine was hospitalized in our unit in February 1988. We demonstrated evidence of systemic sarcoidosis and inappropriate secretion of antidiuretic hormone (ADH). The patient was treated with corticosteroid therapy for a period of about 1 year, with regression of signs of the inappropriate vasopressin secretion as well as the symptomatology related to systemic sarcoidosis. This study identified systemic sarcoidosis as a definite cause of "syndrome of inappropriate ADH secretion".

Combined factor VIII and IX inhibitors in a non-haemophilic patient: successful treatment with immunosuppressive drugs.

A rare case of a patient with Sjogren syndrome and spontaneously acquired inhibitors of both factor VIII and factor IX is reported. Complete remission was obtained by means of immunosuppressive drugs.

Cooperative association of plasminogen with fibrinogen.

We have examined the association of both Glu- and Lys-plasminogen to fibrinogen by ultracentrifugal sedimentation equilibrium in neutral isotonic buffer in the presence of aprotinin. The fibrinogen and plasminogens, which were homogenous, did not exhibit any self-association. In each association study, five different molar ratios of plasminogen to fibrinogen were examined. The data were analyzed by mathematical modeling using nonlinear least-squares curve fitting. Analyses of molecular species present showed that up to 4 mol of either Glu- or Lys-plasminogen was associated with each mol of fibrinogen. For the binding of Glu-plasminogen, the values of the successive changes of the standard free energy of association were found to be -5.48, -7.73, -8.88, and -11.41 kcal/mol (Ka = 2.16 X 10(4), 1.32 X 10(6), 1.06 X 10(7), and 1.08 X 10(9) M-1). For the experimental conditions used here, the association of Lys-plasminogen appears to be described by virtually the same fitting parameters. The very marked cooperativity of association found here would appear to imply that there are significant alterations of the structure of fibrinogen as a result of each successive molecule of plasminogen bound.

Mechanisms of albumin loss during peritoneal dialysis in man.

Albumin loss in the dialysate was evaluated during a total of 5 peritoneal dialyses carried out on 3 uraemic patients. The measurements were made by two different methods, the first based on the evaluation in the dialysate of intravenously injected radioiodinated albumin, the second one based on a radioimmunoassay of the protein in the dialysate. The results obtained showed three main mechanisms of protein loss during peritoneal dialysis: 1) albumin shift from extravascular sites adjacent to the peritoneum, 2) direct passage of albumin from blood stream to peritoneal cavity, and 3) tendency of the inter-dialysis peritoneal fluid to equilibrate with plasma proteins. Furthermore, the observations made on a patient with evident peritonitis proved the importance of the intrinsic biological properties of the peritoneum in determining the amplitude of protein wasting by the dialysate.

Coagulation factor XIII in patients with acute and chronic renal disease.

The behavior of coagulation factor XIII (fibrin-stabilizing factor, FSF) was studied in patients with renal disease. Specific antiserum against the active subunit (FSFA) was employed to set up a method for the direct measurement of the active fraction in plasma, according to the electroimmunodiffusion technique. The plasma FSFA levels were measured in the following patients: (I) 31 patients with chronic renal disease and serum creatinine not higher than 1.5 mg/dl; (II) 41 patients with chronic renal failure on conservative therapy; (III) 53 uremic patients on maintenance hemodialysis; (IV) 10 patients with acute renal failure. FSFA concentration (93.3 +/- 17.6% of a reference plasma in a group of 15 healthy controls) was found to be significantly higher than normal in the patients with chronic renal disease and serum creatinine lower than 1.5 mg/dl (127 +/- 39.8%, p less than 0.005). The FSFA levels were similarly increased in the 41 patients with chronic renal failure on conservative management (134.9 +/- 35.8%, p less than 0.001), and in the 53 end-stage uremics on maintenance hemodialysis (132.8 +/- 29.5%, p less than 0.001). Whereas, FSFA concentration was found to be markedly reduced in the 10 patients with acute renal failure (35.8 +/- 14.6%, p less than 0.001). In the patients with chronic renal disease (groups I, II, and III) plasmatic FSFA higher in those patients with serum triglycerides above the upper normal limit, and a significant positive correlation was found between serum triglycerides and FSFA plasma levels.

Demeclocycline-induced phosphate diabetes in a patient with inappropriate ADH secretion and systemic sarcoidosis.

We report a case of phosphate diabetes in a patient with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with sarcoidosis. Our patient was affected by systemic sarcoidosis and he fits the criteria of Schwartz for the diagnosis of SIADH. He presented with phosphate diabetes which appeared during demeclocycline (DMC) therapy and persisted for about 1 month from the end of DMC. It constitutes the fourth case of phosphate diabetes induced by tetracycline described in the literature and it is the third case of SIADH associated with sarcoidosis.