Evolution of Fabry disease in male patients: the Greek experience.

Fabry disease is a progressive metabolic disorder with a clinical course characterized by different phases and a variety of disease manifestations. The first symptoms generally appear in childhood or early adolescence and are followed by late life-threatening complications involving vascular, renal, cardiac, and cerebral systems. We report the clinical and biochemical characteristics of 16 male patients from 10 unrelated families who represent almost the entire cohort of known Fabry patients in Greece. Despite the presence of early symptoms in almost every patient (mean age at onset of symptoms 15.6 years), the diagnosis was delayed for a mean of about 18 years (mean age of diagnosis 36 years). Patients are currently monitored and the majority (15 out 16 patients) treated with Enzyme Replacement Therapy.

Fluorogenic substrate detection of viable intracellular and extracellular pathogenic protozoa.

Viable Leishmania promastigotes and amastigotes were detected by epifluorescence microscopy with fluorescein diacetate being used to mark living parasites and the nucleic acid-binding compound ethidium bromide to stain dead cells. This procedure is superior to other assays because it is faster and detects viable intracellular as well as extracellular Leishmania. Furthermore, destruction of intracellular pathogens by macrophages is more accurately determined with fluorescein diacetate than with other stains. The procedure may have applications in programs to develop drugs and vaccines against protozoa responsible for human and animal disease.

Thyroid hormone modulates the responsiveness of rat aorta to alpha1-adrenergic stimulation: an effect due to increased activation of beta2-adrenergic signaling.

AIM: The ability of the thyroid hormone to increase cardiac output and to lower systemic vascular resistance may provide a novel treatment for cardiovascular diseases. Therefore, understanding the mechanisms of thyroid hormone action on the heart and peripheral vasculature could be of clinical importance. We previously found that thyroid hormone modulates the alpha1-adrenergic effect on vascular reactivity of rat aortas. In the present study we further investigated possible mechanisms of this response. METHODS: Hyperthyroidism was induced on Wistar-Kyoto male rats with L-Thyroxine, (THYR) treatment for two weeks, N.=18 while untreated rats used as controls (NORM), N.=16. The thoracic aorta was dissected and cut into rings that were suspended in an isolated organ bath with Krebs-Henseleit buffer. Maximal tension, Tmax, in g was measured in response to Potassium Chloride (KCl) and Phenylephrine (PE) in rings in the presence of Ritodrine, a beta-2 agonist (NORM-RITO, N:=8, THYR-RITO, N.=9), or in the absence of Ritodrine (THYR, N.=9, NORM, N.=8). RESULTS: With KCL, Tmax was not different between the THYR, NORM, NORM-RITO, and THYR-RITO groups. With PE, there was a difference in Tmax between NORM-RITO and NORM, 0.66 (0.056) g vs 1.00 (0.066) g, P<0.05 and THYR and NORM, 0.75 (0.055) g vs 1.00 (0.066) g, P<0.05. No significant difference was observed between THYR-RITO AND THYR. Furthermore, Relax % was not significantly different between the NORM and the THYR, NORM-RITO, and THYR-RITO groups, 64.5%(3.7) vs 67.3%(6.7), 73.5% (4.3) and 81.8 %(4.7), P>0.05. CONCLUSIONS: PE induced vasoconstriction in isolated rat aortic rings was reduced after both ritodrine and thyroxine treatment. However, co-administration of thyroid hormone and ritodrine did not result in a synergistic reduction of PE induced vasoconstriction. Thus, thyroxine may modulate the alpha1-adrenergic vascular responsiveness by enhancing beta2-adrenergic stimulation.

Five-year survival in comparable HD and PD patients: one center's experience.

Several studies have yielded conflicting results regarding morbidity and mortality in peritoneal dialysis (PD) and hemodialysis (HD) patients. We performed a retrospective analysis in end-stage renal disease (ESRD) patients in our department, who were equally distributed between HD and PD, in order to compare 5-year survival probabilities and hospitalization rates in the two modalities. Of the total 94 new ESRD patients who initiated dialysis in our department from January 1995 to December 2000, 48 were allocated to PD and 46 to HD. All patients were followed up for five years. There were no significant differences regarding demographics and serious co-morbidities upon dialysis initiation between HD and PD patients. Unadjusted 5-year survival probability in as-treated analysis was higher in PD patients (0.79 vs 0.6, p=0.04), whereas there was no significant difference in intent-to-treat analysis between HD and PD patients (p=0.5). Hospitalization rates were similar in both modalities. Despite the small number of patients included in our study, it seems that when HD and PD are both available in one department they have equivalent results regarding morbidity and mortality rates. Therefore we suggest that, when possible, PD and HD should be equally offered to all ESRD patients.

Complement-mediated defect in clearance and sequestration of sensitized, autologous erythrocytes in rodent malaria.

We investigated the ability of malaria-infected and normal mice to clear particulate immune complexes consisting of autologous erythrocytes sensitized with either IgG or complement. Normal mice rapidly clear autologous erythrocytes optimally sensitized with IgG and the liver plays a major role in their sequestration. Clearance of optimally sensitized erythrocytes is complement-dependent because cobra venom factor-treated, normal mice failed to clear these cells rapidly, unless they had been pre-treated with fresh mouse serum. In the initial phase of Plasmodium berghei infection, clearance of the optimally sensitized erythrocytes was markedly increased over that observed in normal mice. 2 wk after infection, however, clearance was minimal. This defect was most likely the consequence of the hypocomplementemia observed at this stage of infection since sensitized erythrocytes were removed rapidly from the blood if they had been coated with C3 in vitro before injection into malarial mice.The functional activity of the complement receptors of phagocytic cells was assayed in malarial mice by the injection of autologous erythrocytes coated with C3 and C4 in the absence of antibody. The complement-coated erythrocytes were rapidly removed from the blood, accumulated in the liver, and then gradually returned to the circulation. Similar patterns were observed in normal animals, but the degree of clearance was considerably higher in the malarial mice late in infection. It appears, therefore, that complement receptors remain functional throughout the infection. Erythrocytes suboptimally sensitized with IgG were cleared minimally by normal mice. This clearance was not complement-dependent and was mediated mainly by the spleen. During malaria, clearance of these particles was initially enhanced but later it was abolished.The association of hypocomplementemia with a major splenic defect in clearance late in malaria infection may explain the accumulation of immune complexes in pathological sites observed in this disease.

Development, survival, and reproduction of the predatory mite Kampimodromus aberrans (Acari: Phytoseiidae) at different constant temperatures.

Development, survival, and reproduction of the predatory mite Kampimodromus aberrans Oudemans were studied at constant temperatures in the range from 15 to 35 degrees C under laboratory conditions. Larval developmental rate for both males and females increased gradually from 15 to 35 degrees C and decreased at higher temperatures. Lactin's nonlinear model described with adequate accuracy the relationship between developmental rate and temperature. The model predicted that lower and upper threshold temperatures for preimaginal development ranged from 9.8 to 11.8 degrees C and from 37.2 to 39.8 degrees C, respectively. The intrinsic rate of population increase (rm) at the different temperatures ranged from 0.0442 to 0.1575, with the highest value recorded at 25 degrees C. At 33 degrees C a negative rm value was estimated. The rm values determined at different temperatures were fitted to Lactin's nonlinear model, and the lower and upper threshold and the optimal temperatures for population increase were 10.5, 32.4, and 27.6 degrees C, respectively. These data indicate that K. aberrans may be better adapted to intermediate temperatures around 27 degrees C and, therefore, could be a useful biocontrol agent of spider mites during spring and early summer when such temperatures are prevalent in northern Greece. The results could also be useful in developing a population model for K. aberrans under field conditions.

A decision model to estimate a risk threshold for venous thromboembolism prophylaxis in hospitalized medical patients.

Essentials Low risk patients don't require venous thromboembolism (VTE) prophylaxis; low risk is unquantified. We used a Markov model to estimate the risk threshold for VTE prophylaxis in medical inpatients. Prophylaxis was cost-effective for an average medical patient with a VTE risk of ≥ 1.0%. VTE prophylaxis can be personalized based on patient risk and age/life expectancy. SUMMARY: Background Venous thromboembolism (VTE) is a common preventable condition in medical inpatients. Thromboprophylaxis is recommended for inpatients who are not at low risk of VTE, but no specific risk threshold for prophylaxis has been defined. Objective To determine a threshold for prophylaxis based on risk of VTE. Patients/Methods We constructed a decision model with a decision-tree following patients for 3 months after hospitalization, and a lifetime Markov model with 3-month cycles. The model tracked symptomatic deep vein thromboses and pulmonary emboli, bleeding events and heparin-induced thrombocytopenia. Long-term complications included recurrent VTE, post-thrombotic syndrome and pulmonary hypertension. For the base case, we considered medical inpatients aged 66 years, having a life expectancy of 13.5 years, VTE risk of 1.4% and bleeding risk of 2.7%. Patients received enoxaparin 40 mg day-1 for prophylaxis. Results Assuming a willingness-to-pay (WTP) threshold of $100 000/ quality-adjusted life year (QALY), prophylaxis was indicated for an average medical inpatient with a VTE risk of ≥ 1.0% up to 3 months after hospitalization. For the average patient, prophylaxis was not indicated when the bleeding risk was > 8.1%, the patient's age was > 73.4 years or the cost of enoxaparin exceeded $60/dose. If VTE risk was < 0.26% or bleeding risk was > 19%, the risks of prophylaxis outweighed benefits. The prophylaxis threshold was relatively insensitive to low-molecular-weight heparin cost and bleeding risk, but very sensitive to patient age and life expectancy. Conclusions The decision to offer prophylaxis should be personalized based on patient VTE risk, age and life expectancy. At a WTP of $100 000/QALY, prophylaxis is not warranted for most patients with a 3-month VTE risk below 1.0%.

Cardiovascular phenotyping of fetal mice by noninvasive high-frequency ultrasound facilitates recovery of ENU-induced mutations causing congenital cardiac and extracardiac defects.

As part of a large-scale noninvasive fetal ultrasound screen to recover ethylnitrosourea (ENU)-induced mutations causing congenital heart defects in mice, we established a high-throughput ultrasound scanning strategy for interrogating fetal mice in utero utilizing three orthogonal imaging planes defined by the fetus' vertebral column and body axes, structures readily seen by ultrasound. This contrasts with the difficulty of acquiring clinical ultrasound imaging planes which are defined by the fetal heart. By use of the three orthogonal imaging planes for two-dimensional (2D) imaging together with color flow, spectral Doppler, and M-mode imaging, all of the major elements of the heart can be evaluated. In this manner, 10,091 ENU-mutagenized mouse fetuses were ultrasound scanned between embryonic days 12.5 and 19.5, with 324 fetuses found to die prenatally and 425 exhibiting cardiovascular defects. Further analysis by necropsy and histology showed heart defects that included conotruncal anomalies, obstructive lesions, and shunt lesions as well as other complex heart diseases. Ultrasound imaging also identified craniofacial/head defects and body wall closure defects, which necropsy revealed as encephalocele, holoprosencephaly, omphalocele, or gastroschisis. Genome scanning mapped one ENU-induced mutation associated with persistence truncus arteriosus and holoprosencephaly to mouse chromosome 2, while another mutation associated with cardiac defects and omphalocele was mapped to mouse chromosome 17. These studies show the efficacy of this novel ultrasound scanning strategy for noninvasive ultrasound phenotyping to facilitate the recovery of ENU-induced mutations causing congenital heart defects and other extracardiac anomalies.

Effect of cyclosporine, mycophenolate mofetil, and their combination with steroids on apoptosis in a human cultured monocytic U937 cell line.

Transplant patient plasma produces an increased rate of mononuclear cell apoptosis despite a normal serum creatinine value. Immunosuppressive medications may be one factor that causes an altered apoptotic pattern. We evaluated the in vitro effects of various doses of cyclosporine, mycophenolate mofetil, and steroids on apoptosis of a cultured human monocytic U937 cell line, using estimates by fluorescence microscopy and annexin V assays. Increasing cyclosporine concentrations (100 to 800 ng/mL) progressively increased apoptosis rates (16% to 32%). The combination of steroid (0.01 microg/mL) and cyclosporine increased the apoptosis rate to 45%. Mycophenolate mofetil alone (0.3 microg/mL) led to an apoptosis rate of 34%. Therapeutic levels of mycophenolate mofetil from 3 to 7 microg/mL led to apoptosis rates from 56% to 67%. The combination of cyclosporine, steroid, and mycophenolate mofetil increased the rate of apoptosis to 95%. Immunosuppressive therapy may contribute to the high rate of apoptosis observed among mononuclear cells of transplanted patients. This effect may alter patient susceptibility to infections and contribute to a unique mechanism of immunosuppression.

Effectiveness of aluminum hydroxide timing administration in relation to meals in controlling hyperphosphatemia in dialysis patients.

Phosphate binder compounds contribute to the control of hyperphosphatemia in hemodialysis (HD) patients. However, the most effective schedule of administration of phosphate binders in relation to meals is not well documented. We examined the effectiveness of aluminum hydroxide intake as the sole phosphate binder in relation to meals. Eighty-five patients on regular HD (45 male, 40 female), age 21-72 years, with a duration of 6-216 months HD participated in the study. In all patients, phosphate binders were discontinued for a one month period. Thereafter, and according to the protocol, all patients were advised to take aluminum hydroxide [Al(OH)3 ] 30 min before, during and 30 min after meals for 3 periods of one month each, in a random order. One month washout period preceded the periods of Al(OH)3 ingestion. When Al(OH)3 was administered 30 min prior to the meals, serum phosphate decreased by 7.0% (0.59 mg/dL), while when administrated with or 30 min after meals, it decreased statistically significantly by 28.5% (2.08 mg/dL), and 16% (1.29 mg/dL) respectively. Our results suggest that the efficacy of Al(OH)3 to bind phosphate salts and thus to prevent the hyperphosphatemia in HD patients is higher when this drug is taken with meals.

Dot enzyme-linked immunosorbent assay (Dot-ELISA): a micro technique for the rapid diagnosis of visceral leishmaniasis.

A micro enzyme-linked immunosorbent assay utilizing antigen dotted onto nitrocellulose filter discs (Dot-ELISA) was developed for the rapid diagnosis of visceral leishmaniasis. Leishmania donovani promastigotes applied to filter discs in volumes of 1 microliter were placed in 96-well microtiter plates, blocked with bovine serum albumin, then incubated with 4-fold dilutions of patient sera. After incubation with peroxidase-conjugated anti-human antibody, washing and addition of precipitable substrate, positive reactions appeared as blue dots on a white background which were easily read by eye. The procedure is performed at room temperature, takes about 2 h and is economical. At a reciprocal diagnostic titer of greater than or equal to 32, 41 of 42 (98%) leishmaniasis patients were positive, and positive titers ranged from 512 to 524,288. Control sera from healthy individuals showed 1 of 50 (2%) false positive reactions. Sera from patients with African trypanosomiasis, Chagas' disease, and lupus erythematosus were cross-reactive in the Dot-ELISA. No cross-reactivity was noted with sera from patients with amebiasis, coccidioidomycosis, cutaneous leishmaniasis, viral hepatitis, hydatidosis, malaria, schistosomiasis, syphilis, toxoplasmosis or trichinosis. In replicate experiments, 90% of 167 sera tested did not vary in titer. This rapid and inexpensive test should prove to be an important field diagnostic technique for visceral leishmaniasis.

Idiopathic pulmonary hemorrhage in infancy. Clinical features and management with high frequency ventilation.

STUDY OBJECTIVES: To describe the clinical characteristics of infants with severe acute pulmonary hemorrhage and the effects of mechanical ventilation on gas exchange. SETTING: Tertiary care pediatric ICU in a university hospital. PATIENTS AND DESIGN: Case records of patients with severe acute pulmonary hemorrhage from January 1992 to July 1995 were reviewed. Acute pulmonary hemorrhage was defined as hemoptysis and/or epistaxis or blood obtained from endotracheal tube which could not be attributed to cardiac or vascular malformation, infectious process, or known trauma. INTERVENTIONS: Patients were initially managed with conventional ventilation. High frequency ventilation (HFV) was utilized when hypoxemia (PaO2/PAO2 < 0.2) and/or respiratory acidosis (PaCO2 > or = 60 mm Hg with pH < 7.25) persisted. MEASUREMENTS AND RESULTS: Six African-American male infants from Detroit, with a median age 2.3 months, presented with severe acute pulmonary hemorrhage. Chest radiographs showed diffuse bilateral infiltrates or opacification with a normal sized heart. All infants were managed with HFV, four by oscillation and two by jet. The indications for HFV were persistent hypoxemia (2), respiratory acidosis (1), and a combination of both (3). There was an improvement in pH and PaCO2, and a decreased need for oxygen 6 and 24 h after initiating HFV. PaO2/PAO2 and oxygenation index showed a tendency toward improvement. All infants survived, and there were no complications. No cause for pulmonary hemorrhage was found in any of the infants. CONCLUSIONS: Idiopathic acute pulmonary hemorrhage is a potentially life-threatening disorder encountered among inner-city infants. HFV is highly effective and safe in rapidly reversing the severe oxygenation and ventilation deficits in this setting.

Infection and replication of Leishmania tropica in mouse peritoneal macrophages elicited by sterile inflammatory agents and BCG.

C3HeB/FeJ peritoneal exudate macrophages elicited with a variety of sterile inflammatory agents or with Mycobacterium bovis strain BCG were exposed to Leishmania tropica amastigotes in vitro. The percentages of L. tropica-infected macrophages were similar in resident and inflammatory macrophage populations over 72 hours in culture. Inflammatory macrophages supported intracellular replication of L. tropica in excess of that by resident macrophages. These macrophages also failed to demonstrate cytotoxicity to tumor cells in vitro, a defined nonspecific effector function of activated macrophages. However, macrophages from BCG-treated mice were significantly more resistant to initial infection with L. tropica, killed intracellular amastigotes by 72 hours in culture and were cytotoxic to tumor cells, indicating full immunologic activation. The inability of inflammatory macrophages to kill L. tropica parasites suggests that inflammation may actually contribute to the pathogenesis of leishmaniasis.

Standardization of the dot enzyme-linked immunosorbent assay (Dot-ELISA) for human visceral leishmaniasis.

The Dot-ELISA, a rapid, visually read micro enzyme immunoassay for visceral leishmaniasis utilizing minute volumes of antigen "dotted" on nitrocellulose filter discs and precipitable chromogenic substrate, was analyzed under a variety of experimental parameters. Raising assay incubation temperatures from 23 degrees C to 28 degrees C resulted in titer increases in three of five leishmaniasis patient sera; at 37 degrees C, all five patient sera and one of five normal human sera showed titer increases. The amount of antigen used could be reduced 50% by incubating patient serum overnight at 4 degrees C. Antigen discs stored at - 20 degrees C were optimally reactive with leishmaniasis sera over a 270-day period. Antigen discs stored at 4 degrees C and 23 degrees C showed reproducible titer decreases at 90 days. Aging either peroxidase-conjugated antibody or substrate for up to 28 days at 4 degrees C did not adversely affect titers of positive and negative control sera and reagent controls. Activated substrate stored at 23 degrees C was optimally reactive in the assay for at least 24 hours. No changes in titers of positive and negative control sera or nonspecific reactions in reagent controls occurred when using different brands of microtiter plates. The long shelf lives and stabilities of Dot-ELISA antigen and reagents indicate this test should prove useful both in the laboratory and in the field.

Immune complex decomplementation of canine sera for use in a complement-fixation test for diagnosis of visceral leishmaniasis.

Canine sera frequently become anti-complementary when heat-inactivated at 56 degrees C for 30 min, and generally cannot be used in standard complement-fixation (CF) assays. Therefore, a procedure was developed for decomplementing canine sera by absorption with particulate immune complexes consisting of sheep erythrocyte stroma optimally sensitized with anti-sheep erythrocyte antibody (hemolysin). Canine sera incubated for 20 min at 30 degrees C with sensitized stroma consistently showed less than 10% residual complement and were not anti-complementary. This decomplementation procedure was applied in a complement-fixation (CF) test for detection of serum antibodies during canine visceral leishmaniasis. Two groups of German shepherd dogs were injected intravenously with Leishmania donovani or L. donovani chagasi amastigotes, and the course of infections was followed for 12 weeks. Using freeze-thaw sonicate preparations of L. donovani parasites as antigen, reciprocal CF antibody titers above 24 were detectable in sera 7 weeks after infection and gradually increased to a maximum titer of 775 at 12 weeks. Sera from control dogs had mean titers of 24. This improved methodology enhances the potential of the CF test in the serodiagnosis of canine leishmaniasis.

Rapid serodiagnosis of leptospirosis using the IgM-specific Dot-ELISA: comparison with the microscopic agglutination test.

The dot enzyme-linked immunosorbent assay (Dot-ELISA) was compared to the microscopic agglutination test (MA test) for the diagnosis of human leptospirosis. Of 177 sera from 68 soldiers who trained in the Republic of Panama, 102 sera were positive in the MA test and 93 of these sera were positive in the IgM-specific Dot-ELISA. Incidence of infection was 50 of 68 patients with the MA test and 48 of 68 in the IgM Dot-ELISA. Five MA test-positive sera were reactive only in the IgG-specific Dot-ELISA, suggesting previous exposure. All 21 infecting serovars of Leptospira interrogans, as determined by positive reactions in the MA test or culture of blood and urine specimens, were reactive in the Dot-ELISA. Of 75 sera negative in the MA test, 61 were nonreactive in the Dot-ELISA. However, 9 of these 14 Dot-ELISA-positive/MA test-negative sera were acute samples from patients whose later sera were MA test-positive. Positive reactions in the IgM Dot-ELISA occurred in 2 of 30 control, 4 of 10 Lyme disease, 1 of 11 relapsing fever, and 1 of 8 yaws sera; 10 syphilis patient sera were nonreactive. The IgM-specific Dot-ELISA appears to be sensitive and specific for the serodiagnosis of acute leptospirosis. In addition, this rapid test is inexpensive, simple to perform, utilizes minute volumes of killed leptospiral antigen and is easily adaptable to field use.

Human cutaneous leishmaniasis acquired in Texas.

Four cases of autochthonous human cutaneous leishmaniasis have been identified in south-central Texas since 1980. The patients presented with chronic ulcerating papules on the face, earlobe, and lateral thigh. In two patients, the infections healed without treatment. In the other two patients, the lesions healed following treatment with intramuscular sodium stibogluconate or topical antimony potassium tartrate. Serologic testing of family members, using four different techniques, indicates that asymptomatic infections may occur. These are the first reported cases of cutaneous leishmaniasis acquired in Texas since 1974. Organisms isolated from patients in 1974 and 1980 belonged to the Leishmania mexicana complex when tested by the isoenzyme technique. Although no animal reservoir or insect vector has been identified, six species of sand flies belonging to the genus Lutzomyia do inhibit this part of Texas. Accumulated evidence strongly suggests that cutaneous leishmaniasis is endemic in south-central Texas.

Evaluation of promastigote and amastigote antigens in the indirect fluorescent antibody test for American cutaneous leishmaniasis.

Leishmania braziliensis panamensis promastigotes, temperature-induced in vitro-cultivated amastigotes, Vero cell-derived amastigotes, and rodent lesion-derived amastigotes were evaluated as antigens in the indirect immunofluorescent antibody (IFA) test for American cutaneous leishmaniasis. Test sensitivity was determined using sera from 34 U.S. soldiers with leishmaniasis diagnosed by demonstrating parasites in their skin lesions. Sera were collected from 3 to 24 months after exposure to Leishmania. Positive IFA reactions among patient sera were 82% with promastigotes or lesion amastigotes, 79% with in vitro amastigotes, and 76% with Vero cell amastigotes (P = N.S.). Positive titers ranged from 1:8 to 1:128 using all antigens. Test specificity was determined with 30 sera from healthy individuals. False positive reactions ranged from 0-5% depending on the antigen and all titers were less than or equal to 1:8. Test cross-reactivity was assessed with 47 sera from patients with other diseases. Depending on the antigen, cross-reactions occurred with sera from patients with Chagas' disease, lupus erythematosus, malaria, toxoplasmosis and amebiasis. None of the antigens cross-reacted with sera from patients with viral hepatitis, coccidioidomycosis, syphilis, schistosomiasis, and trichinosis. In replicate experiments, 99-100% of the sera varied no more than +/- 1 titer dilution. As sensitivity, specificity, cross-reactivity, and reproducibility of the four antigens were statistically similar, promastigotes, which can be easily and economically cultured in large numbers in vitro are recommended for use in the IFA test for American cutaneous leishmaniasis.

Morphometric and anisotropic symmetries of the canine distal femur.

The purpose of this study was to investigate the homotypical variation in morphologic and anisotropic properties of trabecular bone from paired canine distal femurs. A microcomputed tomography system was used to produce three-dimensional digital reconstructions of the trabecular bone structures. The results showed that the mean bilateral differences in all bone morphology variables were less than 5%. Differences in measures of degree of anisotropy were also less than 5% between matched sites from left and right sides. In general, the bilateral difference in angle of orientation was less than 15 degrees. These data are valuable for calculating the appropriate sample size to use in experiments using the contralateral canine femur as a control. The results and general approach of the study may have significance for the future use of other contralateral trabecular bone sites as controls.

Hemodialysis for patients bleeding or at risk for bleeding, can be simple, safe and efficient.

AIM: Hemodialysis for patients bleeding or at risk for bleeding requires special modalities of treatment that are difficult to perform without potential side effects. A simple, safe and adequate method may be applied. METHODS: A modified way of extracorporeal circuit preparation, which focuses on minimizing the blood-air interface and negligible saline flushing of 50 ml/h, is applied for a maximum of 3-hour session with routine (not one-to-one) nursing attendance. Data from 16,954 sessions performed with patients bleeding or at risk for bleeding (15,730 retrospectively and 1,224 prospectively collected) were analyzed. RESULTS: Cumulative failure of treatment, as defined by clotting of the extracorporeal circuit requiring termination of the procedure or replacement of the clotted part, was not more than 5% as expected for anticoagulation-free hemodialysis. For the prospectively recorded sessions, blood flow was 234 +/- 30 ml/min with less than 250 ml/min in 42.4% of the sessions. Native blood access was used in 426 (34.8%), double-lumen catheter in 798 (65.2%), 42 were isolated ultrafiltration sessions and 64 blood, 21 plasma, 9 platelet units were transfused. Post/pre urea ratio was 0.50 +/- 0.12. Logistic regression showed that among the following: duration of the session, type of dialysis, ultrafiltration rate, hematocrit, number of platelets, serum total protein, transfusions, blood flow and type of access, only blood flow significantly affected failure incidence (coefficient B = -0.041, exp(B) = 0.96, p = 0.04). No complications due to treatment were noted. CONCLUSION: In patients with active, or at risk for, bleeding, hemodialysis without systemic anticoagulation can be adequately and safely performed almost as a routine session.