MHC Class II alleles in ulcerative colitis-associated colorectal cancer.

OBJECTIVES: Patients with ulcerative colitis are at risk for colorectal cancer (CRC). Although prior studies have shown a link between HLA genotypes and ulcerative colitis (UC) susceptibility, none have investigated HLA genotypes and UC-CRC. We therefore investigated HLA-DR/DQ alleles in UC-CRC cases and UC-controls. Furthermore, since methylation of the Class II transactivator (CIITA) gene may silence HLA expression in tumours, we correlated HLA allele frequencies with CIITA gene methylation and HLA-DR expression. METHODS: Cases and controls were matched for duration/extent of ulcerative colitis, age, ethnicity and gender, but not for primary sclerosing cholangitis (PSC). DNA was extracted from archived tissue blocks from 114 UC-CRC cases and 114 UC-controls. HLA-DR/DQ genotyping was performed using sequence-specific-oligonucleotide polymerase chain reaction (SSO-PCR). CIITA methylation was determined using methylation-specific PCR. HLA-DR immunohistochemistry was done following standard protocols. RESULTS: UC-CRC cases were more likely than UC-controls to carry the DR17 or DR13 alleles (p<0.0001 or p = 0.02, respectively). Although CIITA methylation did not vary significantly between cases and controls, DR17 and DQ2 were associated with CIITA methylation (p = 0.04 and 0.02, respectively). UC-controls more frequently carried the DR7, DR1 or DQ5 alleles (p = 0.002, 0.05 or 0.01, respectively). After adjusting for PSC, DR17 remained significantly associated with an increased risk for UC-CRC while DR7 and DQ5 remained protective. CONCLUSIONS: We report a significant association between specific HLA alleles and either the risk for (DR17) or protection from (DR7, DQ5) UC-CRC. This suggests a possible genetic predisposition for increased UC-CRC risk. In addition, DQ2 and DR17 were associated with CIITA methylation.

Evaluation of two commercial systems for automated processing, reading, and interpretation of Lyme borreliosis Western blots.

The diagnosis of Lyme borreliosis (LB) is commonly made by serologic testing with Western blot (WB) analysis serving as an important supplemental assay. Although specific, the interpretation of WBs for diagnosis of LB (i.e., Lyme WBs) is subjective, with considerable variability in results. In addition, the processing, reading, and interpretation of Lyme WBs are laborious and time-consuming procedures. With the need for rapid processing and more objective interpretation of Lyme WBs, we evaluated the performances of two automated interpretive systems, TrinBlot/BLOTrix (Trinity Biotech, Carlsbad, CA) and BeeBlot/ViraScan (Viramed Biotech AG, Munich, Germany), using 518 serum specimens submitted to our laboratory for Lyme WB analysis. The results of routine testing with visual interpretation were compared to those obtained by BLOTrix analysis of MarBlot immunoglobulin M (IgM) and IgG and by ViraScan analysis of ViraBlot and ViraStripe IgM and IgG assays. BLOTrix analysis demonstrated an agreement of 84.7% for IgM and 87.3% for IgG compared to visual reading and interpretation. ViraScan analysis of the ViraBlot assays demonstrated agreements of 85.7% for IgM and 94.2% for IgG, while ViraScan analysis of the ViraStripe IgM and IgG assays showed agreements of 87.1 and 93.1%, respectively. Testing by the automated systems yielded an average time savings of 64 min/run compared to processing, reading, and interpretation by our current procedure. Our findings demonstrated that automated processing and interpretive systems yield results comparable to those of visual interpretation, while reducing the subjectivity and time required for Lyme WB analysis.

Defining the limitations of transcutaneous bilirubin measurement in late preterm newborns.

OBJECTIVE: The objective of this study is to determine the impact of postnatal age on the bias between transcutaneous (TcB) and total serum bilirubin (TSB), and evaluate a TcB screening protocol. STUDY DESIGN: Preterm and term infants had paired TcB and TSB performed on days 1 to 3 of life; a subset of preterm infants had measurements on days 4 to 7. Sensitivity and specificity of TcB (plotted on an age-specific TSB nomogram) for prediction of high-intermediate (HIR) or high-risk TSB were calculated. RESULTS: Median TcB bias was 2.6 and 2.5 mg dl-1 for term and preterm infants in the first 3 days of life, respectively. However, median bias was 2.2 mg dl-1 for preterm infants at 4 to 7 days of life. TcB in preterm infants predicted HIR or high-risk TSB with 94% sensitivity and 56% specificity. CONCLUSION: TcB screening protocols developed for term infants can be used for late preterm infants in the first 3 days of life.

Fractures after thyroidectomy in men: a population-based cohort study.

Bone mass is purportedly reduced by an endogenous or exogenous excess of thyroid hormone or, perhaps, by calcitonin deficiency. Patients who have undergone thyroidectomy could be subject to all of these effects, yet their practical implications in terms of fracture risk are poorly defined. Interpretation is further hampered by the focus on women, where results may be influenced by involutional osteoporosis. Consequently, we assessed the potential for fractures among the 136 Rochester, Minnesota men who underwent thyroidectomy between 1935 and 1979, relative to a group of age-matched control men from the community. With 2194 person-years of follow-up in each group, survival free of any fracture of vertebra, proximal humerus, distal forearm, pelvis, or proximal femur was similar in the two groups (p = 0.23), and the relative risk of any of these fractures for thyroidectomized patients versus their controls was increased only 1.5-fold (95% CI, 0.7-3.2). The difference was entirely accounted for by a statistically significant excess of proximal femur fractures in the men with thyroidectomy. Risk factors for fractures among men with thyroidectomy included greater age at surgery, greater extent of surgery, and the presence of risk factors for secondary osteoporosis. Thus, thyroidectomy, performed mainly for adenoma or goiter, seems to have little overall influence on the risk of age-related fractures in men. However, the association with hip fractures requires further evaluation.

Rates of cancellous bone remodeling and turnover in osteopenia associated with primary biliary cirrhosis.

Osteoporosis and fracturing are well-recognized manifestations of primary biliary cirrhosis (PBC), but the abnormalities of bone remodeling and turnover that result in bone loss are poorly understood. We used dynamic histomorphometric techniques to measure tissue level rates of cancellous bone resorption, formation, and turnover in 12 premenopausal women with PBC and in 12 normal premenopausal women. We compared these values with estimates of bone resorption and formation obtained concurrently in the same subjects by radiocalcium kinetics and biochemical markers. Rates of bone turnover were analyzed as a function of a risk score that reflects the severity of hepatic disease and cholestasis (Mayo proportional-hazards model). Positive correlations were observed between tissue level and whole skeletal estimates of bone remodeling. At the remodeling site (bone multicellular unit [BMU]), the depth of eroded lacunae was unaltered by PBC, but wall thickness was decreased. At the level of bone tissues, mean bone turnover was increased in PBC patients but varied widely and increased as hepatic disease and cholestasis worsened. We conclude that PBC causes a reduction in the volume of bone formed at the remodeling site and that the overall level of bone remodeling and turnover in PBC is strongly influenced by the severity of hepatic disease and cholestasis. We hypothesize that the rate of bone loss in PBC may be decreased by therapeutic agents that slow bone turnover, and that further bone loss may be halted by liver transplantation.

Management and extended outcome of patients with synchronous bilateral solid renal neoplasms in the absence of von Hippel-Lindau disease.

OBJECTIVE: To gain information regarding long-term follow-up in patients with synchronous bilateral solid renal neoplasms in whom renal-preserving surgery is imperative. PATIENTS AND METHODS: We examined our surgical experience and the survival outcome, as evaluated by Kaplan-Meier and log-rank analysis, of 94 patients (64 men and 30 women) who presented to the Mayo Clinic in Rochester, Minn, from 1973 to 1998 with bilateral synchronous solid renal neoplasms in the absence of von Hippel-Lindau disease. Follow-up of these patients ranged from 1 to 25 years, with a mean of 5.86 years and a median of 4.18 years. Tumors were staged according to the TNM classification. Pathologic staging and grading were usually performed on the kidney with the most extensive cancer. The Cox proportional hazards model was used to assess the relationship of grade (1-4), tumor size, and enucleation as opposed to extended (1 cm) partial nephrectomy on overall, cancer-specific, local recurrence-free, and metastasis-free survival. RESULTS: Seventy-one patients (76%) had bilateral synchronous renal cell carcinoma, and 14 patients (15%) had a unilateral renal cell carcinoma with a contralateral benign solid neoplasm. Nine patients (10%) had bilateral benign solid lesions. Sixty-six patients (70%) underwent a single procedure, whereas 28 (30%) underwent staged surgical procedures. Fifty-one patients (54%) are alive, and 43 (46%) have died. Twenty patients (21%) died of metastatic disease, and 5 (5%) had a local recurrence. Cancer-specific survival of the 85 patients with at least 1 renal cell carcinoma still under observation was 81% (+/- 4.9% SE) and 59% (+/- 8.1% SE) at 5 and 10 years, respectively, and survival to local recurrence was 96% (+/- 2.6% SE) at 5 years and 93% (+/- 3.7% SE) at 10 years with 14 patients still under observation. Grade 3 was a statistically significant factor for metastasis (P < .001). A significant difference in metastasis-free survival and cancer-specific survival was noted dependent on pathologic T stage (P < .001 and P = .02, respectively), with patients with local pT3 disease having a higher rate of metastasis and cancer-specific death. Multivariate analysis revealed that tumor grade was associated with metastasis-free survival (P = .002) and tumor size with cancer-specific survival (P = .04). There was no statistical significance on survival outcome end points according to procedure performed, i.e., enucleation vs extended partial nephrectomy. CONCLUSION: Long-term results of renal-preserving procedures for a series of patients with bilateral solid renal neoplasms indicate that grade, stage, and tumor size are significant predictors of outcome. Mean follow-up of over 5 years supports nephron-sparing techniques in selected patients because local recurrence was infrequent compared with distant metastasis.

Bone mass and muscle strength in female college athletes (runners and swimmers).

OBJECTIVE: To determine whether female college athletes had increased muscle strength and bone mass in comparison with age-matched nonathletic female subjects and, if so, whether participation in weight-bearing versus non-weight-bearing exercise made a difference. MATERIAL AND METHODS: We performed a comparative statistical analysis of the bone mineral density (BMD) of the total body, lumbar spine, and femoral neck, maximal oxygen uptake (VO2max), muscle strength, and level of physical activity in 21 runners, 22 swimmers, and 20 control subjects. The study participants were female college students, 18 to 24 years old, who had had more than 8 normal menstrual cycles during the past year. RESULTS: Statistical analyses showed significantly higher VO2max in the two athletic study groups than in the control subjects (P < 0.0001). No significant difference in BMD was noted among the three groups. Total body BMD (r = 0.30; P = 0.02) and femoral neck BMD (r = 0.39; P = 0.002) were positively correlated with weight-bearing activity but not with non-weight-bearing activity. VO2Max (an index of physical fitness) was positively correlated with femoral neck BMD (r = 0.33; P = 0.009) and trochanteric BMD (r = 0.29; P = 0.021). Shoulder muscle strength (determined by isokinetic dynamometry) was positively correlated with total body BMD (r = 0.34; P = 0.007) and lumbar spine BMD (r = 0.28; P = 0.028). Swimmers had higher muscle strength in the back and upper extremities than did runners and control subjects. Hip girdle muscle strength was not significantly different among the three groups. Total body BMD had a positive correlation with percentage of body fat and height. Lumbar spine BMD was higher in subjects who had previously used oral contraceptives. The athletes had a lower percentage of body fat, were less likely to have used oral contraceptives, and had fewer years of normal menses than did the control subjects. CONCLUSION: Our study shows that (1) total body BMD and femoral neck BMD were significantly higher in the study group that performed weight-bearing exercises than in control subjects, (2) swimming exercise had no effect on BMD, and (3) although swimming is not a bone-building exercise, it can significantly improve shoulder, back, and grip muscle strength.

A prospective, randomized study of cardiopulmonary bypass temperature and blood transfusion.

BACKGROUND: We hypothesized that normothermic cardiopulmonary bypass (CPB) would be associated with decreased blood loss and allogeneic transfusion requirements relative to hypothermic CPB. METHODS: After obtaining institutional review board approval and informed patient consent, we conducted a prospective, randomized study of 79 patients undergoing CPB for a primary cardiac operation at normothermic (37 degrees C) (n = 44) or hypothermic temperature (25 degrees C) (n = 35). Blood loss and transfusion requirements in the operating room and for the first 24 hours in the intensive care unit were determined. A paired t test and rank sum tests were used. A p value of less than 0.05 was considered significant. RESULTS: The normothermic and hypothermic CPB groups did not differ in demographic variables, CPB or cross-clamp duration, heparin sodium or protamine sulfate dose, prothrombin time, or thromboelastogram results. There were no differences between the two CPB groups in blood loss or transfusion requirements. CONCLUSIONS: We found that when there was no difference in duration of CPB, normothermic and hypothermic CPB groups demonstrated similar blood loss and transfusion requirements even though other studies have shown hypothermia induces platelet dysfunction and alters the activity of the coagulation cascade.

Referral selection bias in the Medicare hospital mortality prediction model: are centers of referral for Medicare beneficiaries necessarily centers of excellence?

OBJECTIVE: Although the Health Care Financing Administration (HCFA) uses Medicare hospital mortality data as a measure of hospital quality of care, concerns have been raised regarding the validity of this concept. A problem that has not been fully evaluated in these data is the potential confounding effect of illness severity factors associated with referral selection and hospital mortality on comparisons of risk-adjusted hospital mortality. We address this issue. DATA SOURCES AND STUDY SETTING: We analyzed the 1988 Medicare hospitalization data file (MEDPAR). We selected data on patients treated at the two Mayo Clinic-associated hospitals in Rochester, Minnesota, and a group of seven other hospitals that treat many patients from large geographic areas. These hospitals have had observed mortality rates substantially lower than those predicted by the HCFA model for the period 1987-1990. STUDY DESIGN: Using the multiple logistic regression model applied by HCFA to the 1988 data, we evaluated the relationship between distance from patient residence to the admitting hospital and risk-adjusted hospital mortality. PRINCIPAL FINDINGS: Among patients admitted to Mayo Rochester-affiliated hospitals, residence outside Olmsted County, Minnesota was independently associated with a 33 percent lower 30-day mortality rate (p < .001) than that associated with residence in Olmsted County. When patients at Mayo hospitals were stratified by residence (Olmsted County versus non-Olmsted County), the observed mortality was similar to that predicted for community patients (9.6 percent versus 10.2 percent, p = .26), whereas hospital mortality for referral patients was substantially lower than predicted (5.0 percent versus 7.5 percent, p = < .001). After incorporation of the HCFA risk adjustment methods, distance from patient residence to the hospitals was also independently associated with mortality among the Mayo Rochester-affiliated hospitals and seven other referral center hospitals. CONCLUSIONS: The HCFA Medicare hospital mortality model should be used with extreme caution to evaluate hospital quality of care for national referral centers because of residual confounding due to severity of illness factors associated with geographic referral that are inadequately captured in the extant prediction model.

Towards an optimal model for community-based diabetes care: design and baseline data from the Mayo Health System Diabetes Translation Project.

The objective of the Mayo Health System Diabetes Translation Project is to assess the impact of three different models of care on the overall quality of diabetes care in the community. The unit of study is the primary care practice with a different model of care implemented at each of three sites. The design incorporates a comparison of a diabetes guideline implementation team initiative (Practice model A), a guideline initiative combined with clinical use of a Diabetes Electronic Management System (DEMS) by primary care providers (Practice model B) and a guideline initiative combined with DEMS utilization combined with electronic review of DEMS patient encounters by an endocrinologist (Practice model C). Administrative data sets were used to define the patient population at each practice. Patients were designated as new, attending or non-attending based on their pattern of visits over the preceding 12 months. A random sample of 200 charts from attending patients at each site was audited at baseline for diabetes-related process and outcome measures. This audit will be repeated yearly during the 2 years of the project. Baseline data revealed significant differences across sites in adherence to certain key indicators of the quality of diabetes care including: frequency of documentation of eye examinations (19, 39 and 37% for sites A, B and C, respectively), haemoglobin A1c monitoring (64, 89 and 77%) and microalbumin monitoring (3, 15 and 6%). The interventions being assessed in this study include traditional (diabetes education; guideline implementation) and modern (DEMS; telemedicine specialist review) methods for improving the quality of diabetes care. In spite of variation in baseline quality indicators, the setting and design should lead to broad applicability of the results and help determine an optimal model of diabetes care in the community.

Comparison of cervical disk implants and cervical disk fusion treatments in human cadaveric models.

Articulating cervical disk implants have been proposed as an alternative to disk fusion in the treatment of cervical disk disease. To examine the mechanical effect of articulating cervical disk implants (ACDI) versus simulated cervical disk fusion, a mechanical test device was constructed and cadaveric tests were carried out. While results show little effect on the pressures above and below the treatment level, the percent hysteretic behavior of the specimens trended to be higher for the ACDI, indicating that these implants retain more of the natural energy absorption capability of the cervical spine.

Prospective comparison of plateletapheresis using four apheresis systems on the same donors.

To address the demand for higher plateletapheresis efficiency while maintaining consistent leukoreduction, manufacturers of apheresis systems have introduced new equipment or modifications to existing equipment. Using the same 20 donors, we compared the Fresenius AS104 (AS104), Fenwal Amicus, and COBE Spectra Version 7 Leukoreduction System (Turbo) to the COBE Spectra Version 5 Leukoreduction System (V5-LRS) and each other in regard to platelet (plt) collection efficiencies, processing times, and leukoreduction consistency. Using current pre-procedure platelet counts, target endpoints were set at 6-6.5 x 10(11) plt or 3.3-4.0 x 10(11) plt in up to 100 minutes processing time. Median platelet yields for V5-LRS, AS104, Amicus, and Turbo were 3.98, 3.63, 5.03, and 4.99 x 10(11) plt respectively; median collection efficiencies were 53, 46, 73, and 56% respectively; median collection rates were.049,.039,.065, and. 060 x 10(11) plt/minute respectively; double product frequencies were 35, 10, 40, and 30% respectively; and median processing times were 87, 92, 77, and 79 minutes, respectively. Amicus had a significantly higher collection efficiency and higher incidence of double products than all other systems. While AS104 had a significantly lower collection efficiency and lowest double product frequency than all other systems, Amicus and Turbo had significantly lower processing times than V5-LRS and AS104. AS104 leukoreduction was inconsistent, but V5-LRS, Amicus, and Turbo were consistently leukoreduced ((99.8% had <5 x 10(6) WBC at 95% confidence interval). The best overall performance was for the Amicus with Turbo a close second.

Intracoronary thrombus: still a risk factor for PTCA failure?

Pre-existing intracoronary thrombus has been associated with an increased risk of percutaneous transluminal coronary angioplasty (PTCA) failure. Whether intracoronary thrombus is an independent risk factor for failure is uncertain, as conflicting data exist in the literature. Additionally, given advances in patient selection and angioplasty balloon design, it is uncertain whether the current risk posed by intracoronary thrombus is as substantial as that in the early angioplasty experience. The primary objective of this study was to first assess whether pre-existing coronary thrombus was an independent predictor of angioplasty failure and if so, whether the risk due to thrombus had changed from the early angioplasty experience to the present time. Our prospectively collected angioplasty data base was used to identify individuals undergoing single-vessel angioplasty of a thrombus-containing segment from January 1, 1984 through December 1, 1991. Univariate and multivariate stepwise logistic regression techniques were utilized to analyze clinical, angiographic, and procedural characteristics associated with angioplasty failure. The study period was divided into three separate time periods and these used as variables in our multivariate analysis. In the study population that consisted of 2,699 patients with single-vessel angioplasty, univariate analysis demonstrated that among many factors, thrombus was importantly associated with angioplasty failure (P < 0.0001). A multivariate logistic model of angioplasty failure was developed and thrombus achieved independent predictive significance in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal oncocytoma: multifocality, bilateralism, metachronous tumor development and coexistent renal cell carcinoma.

PURPOSE: We analyzed a large series of cases of renal oncocytoma to define the incidence of coexistent renal cell carcinoma, multifocality, bilateralism and metachronous tumor development. MATERIALS AND METHODS: Between 1980 and 1997, 100 men and 38 women with a mean age of 68 years with oncocytoma, were treated surgically at our institution. We analyzed tumor characteristics and reviewed specimens for coexistent renal cell carcinoma. RESULTS: Tumors were discovered incidentally in 58% of the cases. Specimens were obtained from 84 radical and 70 partial nephrectomies. Tumor size ranged from 0.3 to 14.5 cm. (median 3.2). Oncocytoma was unilateral in 131 cases (95%) and bilateral in 7 (5%), while there were multiple oncocytomas in 8 (6%). Mean followup was 41 months (range 0 to 200). The disease specific survival rate was 100% and no patient had metastasis. In 6 patients (4%) metachronous oncocytoma developed during followup. No patient had locally recurrent oncocytoma after partial nephrectomy for a solitary renal oncocytoma. Renal cell carcinoma and oncocytoma were found in 14 patients (10%), including unilateral synchronous disease in 9 and bilateral synchronous disease in 5. CONCLUSIONS: Our data support the benign nature of renal oncocytoma. Multifocality, bilateralism and metachronous tumor develop in approximately 4 to 6% of all cases. Renal cell carcinoma coexisted in 10% of oncocytoma cases.

Pathologic staging of renal cell carcinoma: significance of tumor classification with the 1997 TNM staging system.

BACKGROUND: The TNM staging system for renal cell carcinoma was revised by the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) in 1997. The 1997 TNM staging system for renal cell carcinoma reclassifies tumors using criteria for size and for extent of renal vein/vena cava involvement that are different from the criteria used in the 1987 staging system. The current study investigated the prognostic significance of tumor classification and other factors using the new staging system. METHODS: Records from 1547 renal cell carcinoma patients (1039 males and 508 females; mean age, 63.4 years; mean follow-up, 7.1 years) who underwent surgical resection between 1970 and 1998 were analyzed retrospectively. Tumors were staged using the 1987 and 1997 TNM criteria, and Kaplan-Meier estimates of survival and disease recurrence were compared for both staging systems. The Peto-Peto log rank test and the generalized Wilcoxon test were used to assess univariate significance of prognostic factors on survival. Cox proportional hazards regression analysis was then completed to assess the significance of the revised staging system. RESULTS: Tumor classification using the 1987 TNM staging system (P = 0.0001) and the 1997 TNM staging system (P = 0.0001) was a significant predictor of cause specific survival. Using 1997 TNM staging criteria, 641 patients were reclassified from the T2 classification to the T1 classification, 114 patients were reclassified from the T3c classification to the T3b classification, 11 patients were reclassified from the T4b classification to the T3c classification, and 3 patients were reclassified from the T4b classification to the T3b classification. Patients with reclassified tumors had outcomes similar to patients with tumors that remained in the same tumor classification. Patient stratification was improved using the new staging system. Prognostic discrimination for cause specific survival at 10 years was noted for the 1987 and 1997 TNM classifications (T1, 97% vs. 91%; T2, 84% vs. 70%; T3a, 53% vs. 53%; T3b, 48% vs. 42%; and T3c, 29% vs. 43%). CONCLUSIONS: The revised classification of renal cell carcinoma was a significant predictor of cause specific survival for the cohort of patients described in this report. Using the new system, the stratification of patients was improved. Patients who had their tumors reclassified as a result of the new staging system had outcomes similar to those of patients who had tumors that remained in the same classification. Based on an analysis of this cohort, tumor classification is valid, and the T1 subclassification is warranted. However, additional revision may be required to optimize staging.

The accuracy of coagulation tests during spinal fusion and instrumentation.

UNLABELLED: Patients undergoing major spine surgery may acquire a perioperative coagulopathy from dilution of coagulation factors and/or platelets or fibrinolysis. The mechanisms of the coagulopathy and role of coagulation testing during these procedures are poorly defined. Theoretically, coagulation tests could be used perioperatively to determine which patients are at risk for significant bleeding and guide transfusion therapy. We retrospectively evaluated the sensitivity, specificity, and accuracy of coagulation tests in predicting excessive surgical bleeding in 244 consecutive patients undergoing thoracic, lumbar, or sacral spinal fusion with or without instrumentation. Excessive bleeding was reported by the surgeon in 39 of the patients and was defined as recurrent microvascular bleeding despite adequate use of electrocautery and suture or decreased clot formation of blood pooled within the surgical field. Patients with excessive clinical bleeding sustained larger estimated blood losses than those with normal hemostasis. The total number of allogeneic red blood cells, platelets, and fresh frozen plasma units were also larger in patients with excessive bleeding noted during surgery. The intraoperative coagulation tests with the most sensitivity and specificity were the international normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT). The INR had a sensitivity of 94%, a specificity of 88%, and an accuracy of 0.9 at a value of 1.4 (normal, 0.8-1.2). The PT had a sensitivity of 90%, a specificity of 64%, and an accuracy of 0.73 at a value of 13.5 s (normal, 8.4-12.0 s). The aPTT had a sensitivity of 85%, a specificity of 64%, and an accuracy of 0.71 at a value of 30.9 s (normal, 23-37 s). The thromboelastogram values were of marginal use. We conclude that the INR, PT, and aPTT may be helpful in guiding transfusion therapy in patients undergoing major spine surgery. IMPLICATIONS: Patients undergoing major surgery to the spine often acquire a perioperative coagulopathy. The prothrombin time and activated partial thromboplastin time had the greatest sensitivity and specificity for predicting bleeding in major surgery of the spine. The test values that differentiated normal from excessively bleeding patients could be used to guide transfusion therapy during surgery.

Comparison of blood-conservation strategies in cardiac surgery patients at high risk for bleeding.

BACKGROUND: Aprotinin and tranexamic acid are routinely used to reduce bleeding in cardiac surgery. There is a large difference in agent price and perhaps in efficacy. METHODS: In a prospective, randomized, partially blinded study, 168 cardiac surgery patients at high risk for bleeding received either a full-dose aprotinin infusion, tranexamic acid (10-mg/kg load, 1-mg x kg(-1) x h(-1) infusion), tranexamic acid with pre-cardiopulmonary bypass autologous whole-blood collection (12.5% blood volume) and reinfusion after cardiopulmonary bypass (combined therapy), or saline infusion (placebo group). RESULTS: There were complete data in 160 patients. The aprotinin (n = 40) and combined therapy (n = 32) groups (data are median [range]) had similar reductions in blood loss in the first 4 h in the intensive care unit (225 [40-761] and 163 [25-760] ml, respectively; P = 0.014), erythrocyte transfusion requirements in the first 24 h in the intensive care unit (0 [0-3] and 0 [0-3] U, respectively; P = 0.004), and durations of time from end of cardiopulmonary bypass to discharge from the operating room (92 [57-215] and 94 [37, 186] min, respectively; P = 0.01) compared with the placebo group (n = 43). Ten patients in the combined therapy group (30.3%) required transfusion of the autologous blood during cardiopulmonary bypass for anemia. CONCLUSIONS: The combination therapy of tranexamic acid and intraoperative autologous blood collection provided similar reduction in blood loss and transfusion requirements as aprotinin. Cost analyses revealed that combined therapy and tranexamic acid therapy were the least costly therapies.

Osteoporosis and calcification of the aorta.

In an age-stratified random sample of 200 Rochester, Minnesota women, the prevalence of aortic calcification rose with aging, as did the prevalence of vertebral fractures, while bone mass fell. The statistically significant positive association of aortic calcification with vertebral fractures and the negative associations with bone mass at six skeletal sites were mainly accounted for by age. After age-adjustment, the only association remaining was a negative one between calcified aortic plaques and bone mineral density (BMD) of the lumbar spine (P < 0.05). Aortic calcification was not associated with any measures of calcium metabolism, after adjusting for age, except for a slight negative association between linear aortic calcifications and 25(OH) vitamin D levels (P < 0.05). BMD values of the lumbar spine were somewhat greater than predicted for age in women with severe aortic calcification, but similar findings were seen at other skeletal sites and none of the differences was statistically significant. While overestimation of bone mass was generally minimal, severe aortic calcification may distort lumbar spine assessments in a minority of postmenopausal women.

RBC alloantibody specificity and antigen potency in Olmsted County, Minnesota.

BACKGROUND: While RBC antigen frequencies for whites of Northern European ancestry are known, the relative frequencies of RBC antibodies within this population have not been determined. The distribution of RBC alloantibodies by sex and age was studied, as were the immunogenicity of RBC antigens and the occurrence of RBC alloantibody clusters in a geographically defined population. STUDY DESIGN AND METHODS: RBC alloimmunization among patients and donors in Olmsted County, MN, was determined for the period from 1975 to 1995. Alloantibody frequencies were used to calculate the potency of each antigen relative to K. Cluster analysis was applied to the data to identify natural groupings of antibodies. RESULTS: The frequency and potency of 33 alloantibodies from 1345 alloimmunized subjects were estimated. The most frequent alloantibodies were E (20.8%), Le(a) (18.6%), K (14.7%), D (12.9%), Le(b) (9.4%), M (7.2%), P(1) (6.7%), Fy(a) (6.3%), C (6.8%), and c (3.5%). The most potent antigens were Wr(a) (0.363), C(w) (0.078), Le(a) (0.03), E (0.028), V (0.025), Js(a) (0.023), Kp(b) (0.023), Go(a) (0.023), JMH (0.023), and Rd (0.023). Greater frequency of overall alloimmunization (M:F = 1:2.7), anti-D (p<0.0001), and anti-Le(a) (p = 0.003) was seen among females. Warm autoantibodies were more frequent among males with positive antibody screens (p<0.0001). No other gender differences were observed. Alloimmunization increased with age for K, Kp(a), Fy(a), D, C, E, and warm autoantibodies. Frequencies of alloimmunization to Le(a), Le(b), M, and P(1) decreased with age. The cluster analysis showed grouping of the antibodies to C and D as well as to Le(a) and Le(b), but the other RBC alloantibodies did not form clusters. CONCLUSION: Less than 1 percent of residents tested had positive antibody screens. Anti-E and anti-Le(a) were more common than anti-K. Wr(a) and C(w) were more potent antigens than K. Most antibodies showed an increase in frequency with increasing age. Except for anti-C and -D and anti-Le(a) and -Le(b), RBC alloantibodies did not occur in clusters.

Influence of breastfeeding and other reproductive factors on bone mass later in life.

The influence of reproductive factors on bone mass at six skeletal sites was assessed in an age-stratified random sample of white women residing in Rochester, Minnesota. After age-adjustment, whether or not women had ever breastfed, total duration of breastfeeding and duration of breastfeeding per child were not associated with reduced bone mineral, but breastfeeding for more than 8 months was associated with greater bone mineral at some sites. There were no consistent effects on bone mineral, after adjusting for age, of gravidity or parity, age at menarche, age at first delivery, use of oral contraceptives or estrogen replacement therapy, various sex hormones, nor any of the other reproductive factors assessed. There was a strong protective effect of obesity, which was also correlated with a number of the reproductive variables. While animal studies suggest that pregnancy and lactation may be associated with calcium loss from the skeleton, these data indicate that such factors have little long-term impact on bone mass in humans and little potential for identifying women at high risk of osteoporosis later in life.