A Convolutional-Transformer Model for FFR and iFR Assessment from Coronary Angiography.

The quantification of stenosis severity from X-ray catheter angiography is a challenging task. Indeed, this requires to fully understand the lesion's geometry by analyzing dynamics of the contrast material, only relying on visual observation by clinicians. To support decision making for cardiac intervention, we propose a hybrid CNN-Transformer model for the assessment of angiography-based non-invasive fractional flow-reserve (FFR) and instantaneous wave-free ratio (iFR) of intermediate coronary stenosis. Our approach predicts whether a coronary artery stenosis is hemodynamically significant and provides direct FFR and iFR estimates. This is achieved through a combination of regression and classification branches that forces the model to focus on the cut-off region of FFR (around 0.8 FFR value), which is highly critical for decision-making. We also propose a spatio-temporal factorization mechanisms that redesigns the transformer's self-attention mechanism to capture both local spatial and temporal interactions between vessel geometry, blood flow dynamics, and lesion morphology. The proposed method achieves state-of-the-art performance on a dataset of 778 exams from 389 patients. Unlike existing methods, our approach employs a single angiography view and does not require knowledge of the key frame; supervision at training time is provided by a classification loss (based on a threshold of the FFR/iFR values) and a regression loss for direct estimation. Finally, the analysis of model interpretability and calibration shows that, in spite of the complexity of angiographic imaging data, our method can robustly identify the location of the stenosis and correlate prediction uncertainty to the provided output scores.

The IGF system in thyroid cancer: new concepts.

In recent years, the activation of the insulin-like growth factor (IGF) system in cancer has emerged as a key factor for tumour progression and resistance to apoptosis. Therefore, a variety of strategies have been developed to block the type I IGF receptor (IGF-I-R), which is thought to mediate the biological effects of both IGF-I and IGF-II. However, recent data suggest that the IGF signalling system is complex and that other receptors are involved. To unravel the complexity of the IGF system in thyroid cancer, IGF-I and IGF-II production, and the expression and function of their cognate receptors were studied. Both IGFs were found to be locally produced in thyroid cancer: IGF-I by stromal cells and IGF-II by malignant thyrocytes. Values were significantly higher in malignant tissue than in normal tissue. IGF-I-Rs were overexpressed in differentiated papillary carcinomas but not in poorly differentiated or undifferentiated tumours, whereas insulin receptors (IRs) were greatly overexpressed in all tumour hystotypes, with a trend for higher values in dedifferentiated tumours. As a consequence of IR overexpression, high amounts of IR/IGF-I-R hybrids (which bind IGF-I with high affinity) were present in all thyroid cancer histotypes. Because of recent evidence that isoform A of IR (IR-A) is a physiological receptor for IGF-II in fetal life, the relative abundance of IR-A in thyroid cancer was measured. Preliminary data indicate that overexpressed IRs mainly occur as IR-A in thyroid cancer. These data indicate that both IR/IGF-I-R hybrids and IR-A play an important role in the overactivation of the IGF system in thyroid cancer and in IGF-I mitogenic signalling in these tumours. J Clin PATHOL: Mol Pathol

Intravenous versus oral initial load of propafenone for conversion of recent-onset atrial fibrillation in the emergency room: a randomized trial.

BACKGROUND: Non-valvular paroxysmal atrial fibrillation is a common clinical condition associated with a high risk of thromboembolism and hemodynamic problems which increase with the duration of arrhythmia. Therefore, even if arrhythmia ceases spontaneously within 24 hours in about half of the patients, a higher early conversion rate is desirable. Propafenone either by intravenous or oral load has been shown effective in conversion to sinus rhythm. METHODS: We consecutively randomized all emergency patients with non-valvular atrial fibrillation lasting no more than 48 hours to either intravenous or oral initial load of propafenone. They all received further oral doses if still on atrial fibrillation after the initial load. Exclusion criteria were: mean ventricular rate < 65 b/min, age > 75 years, recent acute myocardial infarction, overt heart failure, conduction defects, ventricular preexcitation, thyroid dysfunction, renal or hepatic insufficiency, pregnancy, current treatment with propafenone or other antiarrhythmic drugs, and intolerance to propafenone. Primary and secondary end-points were the conversion to sinus rhythm within 12 and 48 hours of randomization respectively. RESULTS: Ninety-seven patients were randomized to intravenous (n = 49) or oral (n = 48) treatment. Overall, sinus rhythm restoration occurred in 83.3% of patients within 12 hours and in 98.9% at 24 hours. Recovery rate resulted significantly greater for intravenous treatment at 1 and 3 hours (p < 0.001 and p = 0.001, respectively). At 6, 12 and 24 hours no significant difference between the two groups was observed (p = 0.77, p = 0.81 and p = 0.99, respectively). No patient needed treatment suspension. CONCLUSIONS: In patients with recent-onset non-valvular atrial fibrillation treated with propafenone within 48 hours, conversion to sinus rhythm occurred in more than 80% within 12 hours. Even if intravenous initial load appears to be slightly more rapid, the oral way is easier to administer and cheaper. The choice may depend on the specific organization of the single emergency room.

A quantitative reverse transcription and polymerase chain reaction assay for human IGF-II allows direct comparison of IGF-II mRNA levels in cancerous breast, bladder, and prostate tissues.

Previously, we showed by in situ hybridization that insulin-like growth factor (IGF)-II is upregulated in approximately 50% of prostate, breast, and bladder tumours. In this study, a quantitative competitive reverse transcription and polymerase chain reaction (QC RT-PCR) assay was established and used to quantify human IGF-II mRNA levels in cells and tissues. In this QC RT-PCR assay, a competitor IGF-II RNA, prepared from a newly constructed plasmid encoding the human IGF-II sequence with a 110-bp fragment inserted, was added to RNA samples prior to RT-PCR. The human IGF-II specific QC RT-PCR assay has allowed us to readily compare the levels of IGF-II mRNA in human tissues and cultured cells. Consistent with our previous observations by in situ hybridization, IGF-II mRNA was up-regulated in 50% of cancerous breast tissues examined as compared to the matching benign tissues, and IGF-II mRNA levels were higher in bladder tumours than breast and prostate tumours. In summary, we present here quantitative data confirming that a subclass of breast cancer samples has elevated levels of IGF-II transcripts by the new competitive RT-PCR assay.

Promoter usage for insulin-like growth factor-II in cancerous and benign human breast, prostate, and bladder tissues, and confirmation of a 10th exon.

Upregulation of insulin-like growth factor (IGF)-II expression has been reported for a variety of childhood and adulthood tumors. We determined IGF-II gene promoter usage in human cancerous and benign tissues by semiquantitative RT-PCR using P1-P4-specific primers. Although the human IGF-II gene structure is commonly thought to consist of nine exons and four promoters, we detected substantial utilization of a previously reported exon 4b, which is downstream of exon 4. Thus, exon 4b was intensively studied using 4b-specific primers. IGF-II gene promoter usage is highly variable in malignant and benign breast, prostate, and bladder tissues. While a majority of samples utilized P2-P4 promoters in a variety of combinations, when quantitated, P3 and P4 promoters were much more active than P2 promoter. This study not only demonstrated that IGF-II gene promoter usage is highly variable in malignant and benign tissues, but suggested that alternatively spliced exon 4b should be recognized as a 10th exon.

Insulin receptor activation by IGF-II in breast cancers: evidence for a new autocrine/paracrine mechanism.

IGF-II, produced by breast cancer epithelial and stromal cells, enhances tumor growth by activating the IGF-I receptor (IGF-I-R) via autocrine and paracrine mechanisms. Previously we found that the insulin receptor (IR), which is related to the IGF-I-R, is overexpressed in breast cancer cells. Herein, we find that, in breast cancer the IR is activated by IGF-II. In eight human breast cancer cell lines studied there was high affinity IGF-II binding to the IR, with subsequent IR activation. In these lines, IGF-II had a potency up to 63% that of insulin. In contrast, in non malignant human breast cells, IGF-II was less than 1% potent as insulin. Via activation of the IR tyrosine kinase IGF-II stimulated breast cancer cell growth. Moreover, IGF-II also activated the IR in breast cancer tissue specimens; IGF-II was 10-100% as potent as insulin. The IR occurs in two isoforms generated by alternative splicing of exon 11; these isoforms are IR-A (Ex11-) and IR-B (Ex11+). IR-A was predominantly expressed in breast cancer cells and specimens and the potency of IGF-II was correlated to the expression of this isoform (P<0.0001). These data indicate, therefore, that the IR-A, which binds IGF-II with high affinity, is predominantly expressed in breast cancer cells and represents a new autocrine/paracrine loop involved in tumor biology.

Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells.

Insulin-like growth factor II (IGF-II) is a peptide growth factor that is homologous to both insulin-like growth factor I (IGF-I) and insulin and plays an important role in embryonic development and carcinogenesis. IGF-II is believed to mediate its cellular signaling via the transmembrane tyrosine kinase type 1 insulin-like growth factor receptor (IGF-I-R), which is also the receptor for IGF-I. Earlier studies with both cultured cells and transgenic mice, however, have suggested that in the embryo the insulin receptor (IR) may also be a receptor for IGF-II. In most cells and tissues, IR binds IGF-II with relatively low affinity. The IR is expressed in two isoforms (IR-A and IR-B) differing by 12 amino acids due to the alternative splicing of exon 11. In the present study we found that IR-A but not IR-B bound IGF-II with an affinity close to that of insulin. Moreover, IGF-II bound to IR-A with an affinity equal to that of IGF-II binding to the IGF-I-R. Activation of IR-A by insulin led primarily to metabolic effects, whereas activation of IR-A by IGF-II led primarily to mitogenic effects. These differences in the biological effects of IR-A when activated by either IGF-II or insulin were associated with differential recruitment and activation of intracellular substrates. IR-A was preferentially expressed in fetal cells such as fetal fibroblasts, muscle, liver and kidney and had a relatively increased proportion of isoform A. IR-A expression was also increased in several tumors including those of the breast and colon. These data indicate, therefore, that there are two receptors for IGF-II, both IGF-I-R and IR-A. Further, they suggest that interaction of IGF-II with IR-A may play a role both in fetal growth and cancer biology.

Overexpression of membrane glycoprotein PC-1 in MDA-MB231 breast cancer cells is associated with inhibition of insulin receptor tyrosine kinase activity.

MDA-MB231 human breast cancer cells are unresponsive to insulin and contain a glycoprotein inhibitor of insulin-stimulated insulin receptor (IR) tyrosine kinase activity. Prior studies in both fibroblasts from insulin- resistant non-insulin-dependent diabetes mellitus patients and transfected cells indicate that overexpression of membrane glycoprotein PC-1 reduces IR tyrosine kinase activity. In the present study, we measured PC-1 content and activity in MDA-MB231 and four other human breast cancer cell lines. We observed that PC-1 expression was 3- to 30-fold higher in MDA-MB231 cells when compared with the other breast cell lines. Wheat germ agglutinin extracts of MDA-MB231 cells inhibited IR tyrosine kinase activity. Treatment of these extracts with an antibody to PC-1 significantly reduced their ability to inhibit insulin-stimulated IR tyrosine kinase activity. In addition, when cell clones with different PC-1 activity were selected from MDA-MB231 cells, we found an inverse correlation (r = -0.741, P = 0.006) between the PC-1 activity and the insulin-stimulated IR autophosphorylation. A similar inverse correlation was observed in cell clones derived from the insulin-responsive breast cancer cell line MCF-7. By both immunoprecipitation and cross-linking studies we found PC-1 to be associated with IR. These studies indicate, therefore, that overexpression of PC-1 in MDA-MB231 cells may account, at least in part, for the reduced IR tyrosine kinase activity and suggest that PC-1 is a specific modulator of the IR activity in breast cancer cells.

Interleukin-1 blocks insulin and insulin-like growth factor-stimulated growth in MCF-7 human breast cancer cells by inhibiting receptor tyrosine kinase activity.

Interleukins-1 (IL-1s) are known to inhibit the growth of cultured breast cancer cells. We examined the effects of IL-1 alpha and IL-1 beta on insulin and insulin-like growth factor I (IGF-I) stimulation of cell growth and found that both IL-1s inhibited anchorage-dependent and independent growth of MCF-7 breast cancer cells. In cells incubated with IL-1 beta (100 U/ml), insulin receptor (IR) protein and messenger RNA were increased by 100%, while IGF-I receptor protein and transcript were not significantly changed. These data were confirmed by binding studies. Incubation of MCF-7 cells with IL-1s led, however, to a significant inhibition of IR and IGF-I receptor autophosphorylation (-55%) and phosphotransferase activity (-65%). Also, in 3T3/ HIR rat fibroblasts, transfected with and overexpressing IR, IL-1s decreased insulin-stimulated cell growth in soft agar and IR tyrosine kinase activity. The present findings suggest that IL-1s antagonize the insulin and IGF-I mitogenic effects in MCF-7 cells by blocking the receptor tyrosine kinase activity that is crucial for the mitogenic effect of these factors.

Relationship between body surface area and arterial concentrations of bupivacaine following lumbar epidural anesthesia.

BACKGROUND AND OBJECTIVES: Most prior studies have shown no relationship between body mass or body surface area (BSA) and maximum plasma concentration of local anesthetic agent (Cmax) following neural block. METHODS: Forty-nine patients, aged 55 or older, undergoing elective total hip arthroplasty, had arterial plasma bupivacaine concentrations measured (gas chromatography) at 10-minute intervals for the first 60 minutes following lumbar epidural injection of 25 mL 0.75% bupivacaine plain. Hemodynamic stability was maintained with either low-dose epinephrine (EPI) or phenylephrine (PHE) intravenous infusions. RESULTS: A significant relationship between arterial bupivacaine concentration and BSA was noted for both EPI and PHE groups at each observation point (P < .05). In addition, Cmax for each group was correlated to both BSA and body mass (P < .05). Arterial plasma bupivacaine concentrations were significantly higher in patients at 10, 20, 30, and 40 minutes following epidural injection in patients receiving PHE than EPI (P < .05). CONCLUSIONS: Between 20% and 40% of the variability in the arterial concentrations of bupivacaine following lumbar epidural injection in elderly patients can be accounted for by differences in BSA.

Deliberate hypotensive epidural anesthesia for patients with normal and low cardiac output.

The use of hypotensive anesthesia is contraindicated in patients with ventricular dysfunction, even though afterload reduction often improves ventricular performance. The purpose of this study was to prospectively assess systemic hemodynamic responses to deliberate hypotension with epidural anesthesia in patients with chronic left ventricular dysfunction. Hemodynamic measurements were performed in 29 patients undergoing total hip arthroplasty under deliberate hypotensive epidural anesthesia using low-dose intravenous epinephrine infusion to maintain mean arterial pressure (MAP) at 50-60 mm Hg. Intraoperative MAP decreased from 100 +/- 16 to 56 +/- 9 mm Hg by 30 min after epidural injection (P < 0.0005). Concurrently, cardiac index (CI) increased from a preanesthetic baseline value of 2.9 +/- 0.5 to 3.3 +/- 0.9 L.min-1.m-2 at 30 min (P < 0.005) after epidural injection and stroke volume index (SVI) increased from 41 +/- 8 to 50 +/- 14 mL.beat-1.m-2 30 min after epidural injection (P < 0.005). Heart rate and central venous and pulmonary artery diastolic pressures were maintained under hypotension with epidural anesthesia in all patients. During deliberate hypotension with epidural anesthesia, patients with a history of congestive heart failure or low preanesthetic CI (< or = 2.5 L.kg-1.m-2) increased their CI and SVI into the normal range. There were no significant perioperative complications in either of these groups. Hypotensive epidural anesthesia can be used successfully in patients with low cardiac output from ventricular dysfunction undergoing total hip arthroplasty.

Single versus staged epidural injections of 0.75% bupivacaine: pharmacokinetic and pharmacodynamic effects.

Epidural anesthesia may be performed as a single injection or by staged doses. Thirty patients undergoing primary total hip replacement were randomly assigned to have epidural anesthesia using a single injection or a staged technique with 25 mL of 0.75% bupivacaine. Arterial plasma bupivacaine concentrations were significantly higher in the single injection group for the first 15 min but were not significantly different thereafter. Peak bupivacaine concentrations did not differ significantly between groups, but the time to achieve the peak concentration was delayed by staging injections (P = 0.001). Hemodynamic effects were similar between groups. Resolution of thoracic sensory block through T12 and duration of motor block measured by Bromage scale were both significantly longer in the staged injection group (P < 0.01). The method of epidural injection may affect resolution of neural block and the time to reach peak arterial plasma concentration of local anesthetic.

Acute exacerbation of carpal tunnel syndrome after radial artery cannulation.

Acute carpal tunnel syndrome that follows radial artery cannulation has been described. To determine the incidence and predisposing factors, we prospectively studied 151 patients who had perioperative radial artery cannulation. Postoperatively 9 of the 151 patients had symptoms of carpal tunnel syndrome with positive Phalen and Tinel signs on the side on which the radial artery catheter had been inserted. Eight of 12 patients with a prior history of carpal tunnel syndrome had acute exacerbation of symptoms postoperatively. By contrast, only 1 of 139 patients with no prior history of the disorder had symptoms. Fourteen patients had multiple arterial artery punctures or perforations of the posterior wall of the radial artery. In three of these, postoperative symptoms of carpal tunnel syndrome developed but did not reach statistical significance. The only patient with postoperative acute carpal tunnel syndrome but no prior history of the syndrome had multiple arterial punctures. The use of perioperative anticoagulation, the use of wrist-extension splints, and the duration of radial artery cannulation did not influence acute exacerbation of carpal tunnel syndrome. Patients with a prior history of carpal tunnel syndrome are at increased risk of recurrent symptoms after radial artery cannulation. We found no statistically significant relationship between traumatic cannulations and the development of symptoms of carpal tunnel syndrome.

Pulse oximeter waveforms from the finger and toe during lumbar epidural anesthesia.

BACKGROUND AND OBJECTIVES: To determine whether lumbar epidural anesthesia affects pulse oximeter signals in the upper or lower extremity, 13 ASA I patients were studied. METHODS: Temperature and pulse oximeter probes were placed on the finger and the toe. RESULTS: After epidural injection, the amplitude of the pulse oximeter waveform on the toe increased eight-fold but declined by 50% in the finger. The increase in amplitude of the pulse oximeter waveform in the foot preceded the temperature rise. CONCLUSIONS: More reliable pulse oximeter signals may be obtained from the toe than the finger during lumbar epidural anesthesia. Furthermore, the increase in the pulse amplitude from the toe may aid in the early detection of successful epidural block.

The effect of two levels of hypotension on intraoperative blood loss during total hip arthroplasty performed under lumbar epidural anesthesia.

The degree of induced hypotension necessary to achieve a significant reduction in intraoperative blood loss has never been defined. Forty patients undergoing primary total hip arthroplasty during epidural anesthesia by a single surgeon were randomly assigned to have mean arterial pressure maintained at 50 +/- 5 mm Hg or 60 +/- 5 mm Hg throughout surgery. Intraoperative blood loss was 179 +/- 73 mL in the 50 mm Hg group and 263 +/- 98 mL in the 60 mm Hg group (P = 0.004). Subjectively, there was more bleeding during surgery in the 60 mm Hg group during dissection of the hip joint (P = 0.0026) and while reaming the acetabulum (P = 0.0001) and femur (P = 0.0001). No difference in transfusion requirements, postoperative hematocrit, or duration of surgery was noted. A difference in mean arterial blood pressure of 10 mm Hg from 50 to 60 mm Hg during surgery for total hip arthroplasty under epidural anesthesia has a measurable effect on intraoperative blood loss.

The effect of cardiac output on intraoperative blood loss during total hip arthroplasty.

BACKGROUND AND OBJECTIVES: It is not clear whether cardiac output affects intraoperative blood loss under epidural hypotensive anesthesia. METHODS: Thirty patients undergoing primary total hip arthroplasty were randomly assigned to receive intravenous infusions of either low-dose epinephrine or phenylephrine to maintain mean arterial pressure at 50 to 60 mm Hg throughout surgery under lumbar epidural anesthesia. Patients were monitored with radial artery and thermodilution pulmonary artery catheters. Hemodynamic parameters were measured every 10 minutes during surgery, and blood loss was estimated by a blinded observer weighing sponges. RESULTS: Mean arterial pressure was similar between groups. Cardiac output remained unchanged in patients receiving low-dose epinephrine but declined significantly in patients receiving phenylephrine (p = 0.0001). Blood loss was 228 and 236 mL in patients receiving low-dose epinephrine and phenylephrine, respectively (p = 0.86). No correlation was observed between cardiac output and blood loss at any point during surgery. CONCLUSIONS: Cardiac output is not a factor influencing blood loss during hypotensive epidural anesthesia in elderly patients undergoing primary total hip arthroplasty.

The hemodynamic and fibrinolytic response to low dose epinephrine and phenylephrine infusions during total hip replacement under epidural anesthesia.

Lower rates of deep vein thrombosis have been noted following total hip replacement under epidural anesthesia in patients receiving exogenous epinephrine throughout surgery. To determine whether this is due to enhanced fibrinolysis or to circulatory effects of epinephrine, 30 patients scheduled for primary total hip replacement under epidural anesthesia were randomly assigned to receive intravenous infusions of either low dose epinephrine or phenylephrine intraoperatively. All patients received lumbar epidural anesthesia with induced hypotension and were monitored with radial artery and pulmonary artery catheters. Patients receiving low dose epinephrine infusion had maintenance of heart rate and cardiac index whereas both heart rate and cardiac index declined significantly throughout surgery in patients receiving phenylephrine (p = 0.0001 and p = 0.0001, respectively). Tissue plasminogen activator (t-PA) activity increased significantly during surgery (p < 0.005) and declined below baseline postoperatively (p < 0.005) in both groups. Low dose epinephrine was not associated with any additional augmentation of fibrinolytic activity perioperatively. There were no significant differences in changes in D-Dimer, t-PA antigen, alpha 2-plasmin inhibitor-plasmin complexes or thrombin-antithrombin III complexes perioperatively between groups receiving low dose epinephrine or phenylephrine. The reduction in deep vein thrombosis rate with low dose epinephrine is more likely mediated by a circulatory mechanism than by augmentation of fibrinolysis.

Intraoperative adjusted-dose heparin thromboembolic prophylaxis in primary total hip arthroplasty.

Intraoperative, fixed, intermittent, low-dose intravenous heparin prophylaxis has been reported to significantly reduce the incidence of thromboembolic disease from 24.3% to 8.3% after primary total hip arthroplasty (THA). This study examined the potential efficacy of adjusted-dose intraoperative heparin administration, keeping the activated clotting time at 30%-50% greater than normal. It was hypothesized that prolongation of clotting parameters in a uniform manner would further decrease the incidence of thromboembolic disease postoperatively. Sixty-one patients completed the protocol. The overall incidence of thromboembolic disease was 9.8%. Five patients had a positive postoperative venogram: four in the calf and one in the proximal deep thigh vein. One patient had a symptomatic nonfatal pulmonary embolus diagnosed by ventilation-perfusion scan. There were no complications related to heparin administration. This approach was therefore equally as effective as the fixed-dose regimen, and it further confirmed the efficacy and safety of an intraoperative heparin prophylaxis regimen. The extra efforts required to maintain a constant intraoperative level of anticoagulation did not prove advantageous over the simpler, fixed-dose regimen in reducing the incidence of thromboembolic disease after primary THA.

A simple preoperative method of screening for alcoholism.

The patient with an alcohol problem represents a higher risk to the aesthetic surgeon. Problems may develop intraoperatively, or in the immediate postoperative period due to lack of compliance, ultimately a higher risk of patient dissatisfaction. Identification of this group of patients is helpful preoperatively. We propose a screening method consisting of two well-conceived questions and confirmation by appropriate laboratory data.

Intraoperative heparin thromboembolic prophylaxis in primary total hip arthroplasty. A prospective, randomized, controlled, clinical trial.

Venous thromboembolic disease remains the most common and potentially fatal complication after total hip arthroplasty (THA). Proximal femoral deep vein thrombosis (DVT) is especially prone to propagate and embolize. The authors' hypothesis was that intraoperative intravenous heparin administration could reduce proximal DVT in THA. There were 286 patients who entered into a prospective, double-blind, randomized clinical trial at the authors' institution between June 1988 and May 1990. All patients had unilateral primary THA under hypotensive epidural anesthesia. The epidural catheter was placed at least 60 minutes before heparin administration. Intravenous heparin was given during surgery only. All patients received aspirin twice daily (650 mg/day) after surgery. Detection of DVT was by contrast venography on Postoperative Day 6 or 7. The study was divided into three phases. There was four groups: control (intraoperative saline), 30 minutes (1000 U heparin at beginning of surgery followed by 500 U every 30 minutes), continuous adjusted (1000 U or 1500 U initial bolus followed by continuous heparin infusion maintaining anticoagulation at 30%-50% elevation from baseline), and fixed dose (1000 U bolus before hip dislocation, and 500 U bolus before femoral canal preparation). Proximal femoral DVT was effectively reduced from 9.1% in the control group to 1.7% in the heparin groups (1.7% in 30 minute, 1.6% in continuous adjusted, 1.7% in fixed dose) (p less than 0.02). The overall DVT rate was also significantly reduced from 24.3% to 10% (p less than 0.01). No adverse effects from heparin administration were noted. Postoperative drainage, hematocrit levels on Postoperative Day 2 and at discharge, and transfusion requirements were not significantly different among the groups. The current recommended protocol is 1000 U bolus five minutes before hip dislocation, followed by 500 U bolus five minutes before femoral preparation. This, in conjunction with hypotensive epidural anesthesia and postoperative aspirin, is effective in reducing proximal DVT to less than 2% in primary THA.