Outcomes in Severe Upper GI Hemorrhage from Dieulafoy's Lesion with Monitoring of Arterial Blood Flow.

BACKGROUND: Dieulafoy's lesion (DL) is a rare but increasingly recognized cause of severe upper GI hemorrhage (SUGIH). There is little consensus regarding the endoscopic approach to management of bleeding from DL. AIMS: Our purposes were to compare 30-day outcomes of patients with SUGIH from DL with Doppler endoscopic probe (DEP) monitoring of blood flow and guided treatment versus standard visually guided hemostasis (VG). METHODS: Eighty-two consecutive DL patients with SUGIH were identified in a large CURE Hemostasis database from previous prospective cohort studies and two recent RCTs at two university-based medical centers. 30-day outcomes including rebleeding, surgery, angiography, death, and severe medical complications were compared between the two treatment groups. RESULTS: 40.2% of DL bleeds occurred in inpatients. 43.9% of patients had cardiovascular disease, and 48.7% were taking medications associated with bleeding. For the entire cohort, 41.3% (26/63) of patients treated with VG had a composite 30-day outcome as compared to 10.5% (2/19) of patients treated with DEP (p = 0.017). Rebleeding occurred within 30 days in 33.3% and 10.5% of those treated with VG and DEP, respectively (p = 0.051). After propensity score matching, the adjusted 30-day composite outcome occurred in 39.0% in the VG group compared to 2.6% in the DEP group (p < 0.001). Adjusted 30-day rebleeding occurred in 25.3% in the VG group versus 2.6% in the DEP group (p < 0.001). DISCUSSION: DL patients with SUGIH were frequently inpatients and had severe cardiovascular comorbidities and recurrent bleeding. Lesion arterial blood flow monitoring and obliteration are an effective way to treat bleeding from DL which reduces negative 30-day clinical outcomes.

Independent risk factors of 30-day outcomes in 1264 patients with peptic ulcer bleeding in the USA: large ulcers do worse.

BACKGROUND: Predictors of worse outcomes (rebleeding, surgery and death) of peptic ulcer bleeds (PUBs) are essential indicators because of significant morbidity and mortality rates of PUBs. However those have been infrequently reported since changes in medical therapy (PPI, proton pump inhibitors) and application of newer endoscopic haemostatic technique. AIMS: To determine: (i) independent risk factors for 30-day rebleeding, surgery, and death and (ii) whether ulcer size is an independent predictor of major outcomes in patients with severe PUB after successful endoscopic haemostasis and treatment with optimal medical (high dose IV PPI) vs. prior treatment (high dose IV histamine 2 antagonists - H2RAs). METHODS: A large prospectively followed population of patients hospitalised with severe PUBs between 1993 and 2011 at two US tertiary care academic medical centres, stratified by stigmata of recent haemorrhage (SRH) was studied. Using multivariable logistic regression analyses, independent risk factors for each outcome (rebleeding, surgery and death) up to 30 days were analysed. Effects for medical treatment (H2RA patients 1993-2005 vs. PPIs 2006-2011) were also analysed. RESULTS: A total of 1264 patients were included. For ulcers ≥10 mm, the odds of 30-day rebleeding increased 6% per each 10% increase in ulcer size (OR 1.06, 95% CI 1.02-1.10, P = 0.0053). Other risk factors for 30-day rebleeding were major SRH, in-patient start of bleeding, and prior GI bleeding. Major SRH and ulcer size≥10 mm were predictors of 30-day surgery. Risk factors for 30-day death were major SRH, in-patient bleeding, and any initial platelet transfusion or fresh frozen plasma transfusion ≥2 units. Among patients with major SRH and out-patient start of bleeding, larger ulcer size was also a risk factor for death (OR 1.08 per 10% increase in ulcer size, 95% CI 1.02-1.14, P = 0.0095). Ulcer size was a significant independent variable for both time periods. CONCLUSIONS: Ulcer size is a risk factor for worse outcomes after PUB and should be carefully recorded at initial endoscopy to improve patient triage and management.

Liver transplantation in recipients receiving renal replacement therapy: outcomes analysis and the role of intraoperative hemodialysis.

The Model for End-Stage Liver Disease (MELD) system has dramatically increased the number of recipients requiring pretransplant renal replacement therapy (RRT) prior to liver transplantation (LT). Factors affecting post-LT outcomes and the need for intraoperative RRT (IORRT) were analyzed in 500 consecutive recipients receiving pretransplant RRT, including comparisons among recipients not receiving IORRT (No-IORRT, n = 401), receiving planned IORRT (Pl-IORRT, n = 70), and receiving emergent, unplanned RRT after LT initiation (Em-IORRT, n = 29). Despite a median MELD of 39, overall 30-day, 1-, 3- and 5-year survivals were 93%, 75%, 68% and 65%, respectively. Em-IORRT recipients had significantly more intraoperative complications (arrhythmias, postreperfusion syndrome, coagulopathy) compared with both No-IORRT and Pl-IORRT and greater 30-day graft loss (28% vs. 10%, p = 0.004) and need for retransplantation (24% vs. 10%, p = 0.099) compared with No-IORRT. A risk score based on multivariate predictors of IORRT accurately identified recipients with chronic (sensitivity 84%, specificity 72%, concordance-statistic [c-statistic] 0.829) and acute (sensitivity 93%, specificity 61%, c-statistic 0.776) liver failure requiring IORRT. In this largest experience of LT in recipients receiving RRT, we report excellent survival and propose a practical model that accurately identifies recipients who may benefit from IORRT. For this select group, timely initiation of IORRT reduces intraoperative complications and improves posttransplant outcomes.

The prevalence, and predictive value, of abnormal anal cytology to diagnose anal dysplasia in a population of HIV-positive men who have sex with men.

Due to the increasing incidence of anal cancer in HIV-positive men who have sex with men, and the potential to detect and treat high-grade anal dysplasia--the putative anal cancer precursor--we have introduced an anal cytology screening service. Patients with abnormal anal cytology have follow-up high-resolution anoscopy (HRA) with biopsy of lesions clinically suspicious for high-grade dysplasia. In total, 244 men were screened and 235 (96%) of the samples were adequate for cytological interpretation using the Bethesda 2001 system. One hundred and sixty-four (67%) men had abnormal anal cytology, and 93 of them had follow-up HRA and anal biopsy. The positive predictive value for any anal cytological abnormality to predict any degree of anal dysplasia was 95.7+/-2.1%, and for any anal cytological abnormality to predict high-grade anal dysplasia was 55.9+/-5.1%. Abnormal anal cytology was highly predicative of anal dysplasia on biopsy.

Rejection and steroid dependence: unique risk factors in the development of pediatric posttransplant de novo autoimmune hepatitis.

Posttransplant de novo autoimmune hepatitis (d-AIH) is increasingly described as a long-term complication after pediatric liver transplantation (LT). d-AIH is characterized by graft dysfunction, the development of autoimmune antibodies and histologic evidence of hepatitis in liver transplant recipients without previous history of autoimmune liver disease. This study is a matched case-control, univariate analysis aimed at identifying risk factors for the development of d-AIH and evaluating response to treatment. From 1984 to 2003, 619 children received 788 LTs at a single center. Forty-one patients developed d-AIH and were matched with controls for year of LT, age at time of LT and diagnosis. The following variables were insignificant in the development of d-AIH: age, gender, race, initial diagnosis, ischemia time, graft type, Epstein-Barr virus and cytomegalovirus status, HLA typing and primary immunosuppression. Compared to controls, d-AIH patients were less likely to be on monotherapy immunosuppression or weaned off prednisone at the time of diagnosis. The d-AIH group relative to the controls had statistically significant greater numbers of rejection episodes. d-AIH was treated with prednisone and/or MMF in 39 of 41 patients and lead to significant improvements in liver function tests. Thirty-nine patients are alive at a mean of 4.0 years follow-up after diagnosis. Three have required retransplantation.

Change in mandibular trabecular pattern and hip fracture rate in elderly women.

OBJECTIVES: To determine if alterations of trabecular pattern, or the rate of change of jaw trabeculae, are associated with rate of hip fracture. METHODS: Participants in a population-based study of residents of a California retirement community (Leisure World Cohort Study) were asked for permission to obtain their dental radiographs. Periapical radiographs were retrieved on 598 women (average age at time of first radiograph=77 years). Several measurements of trabecular pattern (strut analysis), textural properties (run-length analysis) and Fourier analysis were made in several anatomical regions of the jaw. These trabecular features and clinical information self-reported by subjects in the early 1980s were examined for association with hip fracture rate using Cox proportional-hazard regression. RESULTS: Rate of hip fracture increased with decreasing average length of node-to-terminus struts in the mandibular incisor region. Each 0.01 mm per year decrease in the average length of node-to-terminus struts increased hip fracture rate by a factor of 2.9 (P=0.02, accuracy=73%). Inclusion of clinical parameters improved the predictive model compared with use of the radiographic parameter alone (accuracy=79%). Similar results were seen for percent change per year in this parameter. CONCLUSIONS: Changes in radiographic trabecular structure, augmented with clinical information, are predictive of hip fracture in elderly women. Further refinement of both the radiographic and clinical parameters may lead to a screening process accessible to a large number of women and to early diagnosis and treatment of osteoporosis.

Early graft function after pediatric liver transplantation: comparison between in situ split liver grafts and living-related liver grafts.

BACKGROUND: The systematic application of living-related and cadaveric, in situ split-liver transplantation has helped to alleviate the critical shortage of suitable-sized, pediatric donors. Undoubtedly, both techniques are beneficial and advantageous; however, the superiority of either graft source has not been demonstrated directly. Because of the potential living-donor risks, we reserve the living donor as the last graft option for pediatric recipients awaiting liver transplantation. Inasmuch as no direct comparison between these two graft types has been performed, we sought to perform a comparative analysis of the functional outcomes of left lateral segmental grafts procured from these donor sources to determine whether differences do exist. METHODS: A retrospective analysis of all liver transplants performed at a single institution between February 1984 and January 1999 was undertaken. Only pediatric (<18 years) recipients of left lateral segmental grafts procured from either living-related (LRD) or cadaveric, in situ split-liver (SLD) donors were included. A detailed analysis of preoperative, intraoperative, and postoperative variables was undertaken. Survival was estimated using the Kaplan-Meier method, and comparison of variables between groups was undertaken using the t test of Wilcoxon rank sum test. RESULTS: There were no significant differences in the preoperative variables between the 39 recipients of SLD grafts and 34 recipients of LRD grafts. The donors did differ significantly in mean age, ABO blood group matching, and preoperative liver function testing. Postoperative liver function testing revealed significant early differences in aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, prothrombin time, and alkaline phosphatase, with grafts from LRD performing better than those from SLD. SLD grafts also had significantly longer ischemia times and a higher incidence of graft loss owing to primary nonfunction and technical complications (9 vs. 2, P<0.05). However, six of these graft losses in the SLD group were because of technical or immunologic causes, which, theoretically, should not differ between the two groups. Furthermore, these graft losses did not negatively impact early patient survival as most patients were successfully rescued with retransplantation (30-day actuarial survival, 97.1% SLD vs. 94.1% LRD, P=0.745). In the surviving grafts, the early differences in liver function variables normalized. CONCLUSIONS: Inherent differences in both donor sources exist and account for differences seen in preoperative and intraoperative variables. Segmental grafts from LRD clearly performed better in the first week after transplantation as demonstrated by lower liver function variables and less graft loss to primary nonfunction. However, the intermediate function (7-30 days) of both grafts did not differ, and the early graft losses did not translate into patient death. Although minimal living-donor morbidity was seen in this series, the use of this donor type still carries a finite risk. We therefore will continue to use SLD as the primary graft source for pediatric patients awaiting liver transplantation.

Preoperative factors associated with outcome and their impact on resource use in 1148 consecutive primary liver transplants.

BACKGROUND: Hepatic transplantation is a highly effective but costly treatment for end-stage hepatic dysfunction. One approach to improve efficiency in the use of scarce organs for transplantation is to identify preoperative factors that are associated with poor outcome posttransplantation. This may assist both in selecting patients optimal for transplantation and in identifying strategies to improve survival. METHODS: In the present work, we retrospectively reviewed consecutive liver transplants performed at the University of California at Los Angeles during a 6-year period and determined preoperative variables that were associated with outcome in primary grafts. In addition, we used the hospital's cost accounting database to determine the impact of these variables on the degree of resource use by high-risk patients. RESULTS: We found five variables to have independent prognostic value in predicting graft survival after primary liver transplantation: (1) donor age, (2) recipient age, (3) donor sodium, (4) recipient creatinine, and (5) recipient ventilator requirement pretransplant. Recipient ventilator requirement and elevated creatinine were associated with significant increases in resource use during the transplant admission. CONCLUSIONS: Patients at high risk for graft failure and costly transplants can be identified preoperatively by a set of parameters that are readily available, noninvasive, and inexpensive. Selection of recipients on the basis of these data would improve the efficiency of liver transplantation and reduce its cost.

A 10-year experience of liver transplantation for hepatitis C: analysis of factors determining outcome in over 500 patients.

OBJECTIVE: To determine the factors affecting the outcome of orthotopic liver transplantation (OLT) for end-stage liver disease caused by hepatitis C virus (HCV) and to identify models that predict patient and graft survival. SUMMARY BACKGROUND DATA: The national epidemic of HCV infection has become the leading cause of hepatic failure that requires OLT. Rapidly increasing demands for OLT and depleted donor organ pools mandate appropriate selection of patients and donors. Such selection should be guided by a better understanding of the factors that influence the outcome of OLT. METHODS: The authors conducted a retrospective review of 510 patients who underwent OLT for HCV during the past decade. Seven donor, 10 recipient, and 2 operative variables that may affect outcome were dichotomized at the median for univariate screening. Factors that achieved a probability value less than 0.2 or that were thought to be relevant were entered into a stepdown Cox proportional hazard regression model. RESULTS: Overall patient and graft survival rates at 1, 5, and 10 years were 84%, 68%, and 60% and 73%, 56%, and 49%, respectively. Overall median time to HCV recurrence was 34 months after transplantation. Neither HCV recurrence nor HCV-positive donor status significantly decreased patient and graft survival rates by Kaplan-Meier analysis. However, use of HCV-positive donors reduced the median time of recurrence to 22.9 months compared with 35.7 months after transplantation of HCV-negative livers. Stratification of patients into five subgroups, based on time of recurrence, revealed that early HCV recurrence was associated with significantly increased rates of patient death and graft loss. Donor, recipient, and operative variables that may affect OLT outcome were analyzed. On univariate analysis, recipient age, serum creatinine, donor length of hospital stay, donor female gender, United Network for Organ Sharing (UNOS) status of recipient, and presence of hepatocellular cancer affected the outcome of OLT. Elevation of pretransplant HCV RNA was associated with an increased risk of graft loss. Of 15 variables considered by multivariate Cox regression analysis, recipient age, UNOS status, donor gender, and log creatinine were simultaneous significant predictors for patient survival. Simultaneously significant factors for graft failure included log creatinine, log alanine transaminase, log aspartate transaminase, UNOS status, donor gender, and warm ischemia time. These variables were therefore entered into prognostic models for patient and graft survival. CONCLUSION: The earlier the recurrence of HCV, the greater the impact on patient and graft survival. The use of HCV-positive donors may accelerate HCV recurrence, and they should be used judiciously. Patient survival at the time of transplantation is predicted by donor gender, UNOS status, serum creatinine, and recipient age. Graft survival is affected by donor gender, warm ischemia time, and pretransplant patient condition. The authors' current survival prognostic models require further multicenter validation.

Predictors of utilities for health states in early stage prostate cancer.

PURPOSE: When faced with treatment choices for early stage prostate cancer, patients must balance the survival benefit of a treatment with its morbidity. Little is known about how patients balance these trade-offs. To further our understanding of patient decision making we assessed patient utilities for prostate cancer treatment related morbidities. We determined whether patient utilities were predicted by sociodemographic characteristics or baseline genitourinary function. MATERIALS AND METHODS: We evaluated 401 men undergoing prostate needle biopsy for suspicion of prostate cancer at university, Veterans Affairs and public hospitals. Study design included a prospective cross-sectional cohort with correlation and multivariate analysis. Subjects were studied with 2 established health related quality of life instruments. Patient utilities were assessed with an interactive software application. RESULTS: On multivariate analysis utility for current general health was a significant predictor of utilities for treatment related morbidities. Surprisingly baseline urinary, sexual and bowel function scores did not correlate well with respective utilities for potential incontinence, impotence or radiation proctitis. In other words, men with good and imperfect baseline function were equally willing to risk impairment to preserve life. CONCLUSIONS: Men who perceived that general health was better appear to place higher value on quantity of life, while those who already are suffering from poor general health place higher value on quality of life. Ethnicity appears to modify some effects of other variables on patient preference. Utility assessment provides a quantitative tool to aid physicians in counseling patients when making treatment decisions for localized prostate cancer.

Effectiveness and safety of brimonidine as adjunctive therapy for patients with elevated intraocular pressure in a large, open-label community trial.

PURPOSE: To determine the effectiveness and safety of brimonidine when used in combination with one or more glaucoma medications in patients with glaucoma or ocular hypertension. METHODS: Post hoc analysis of a multicenter, 2-month, open-label, prospective, clinical trial in which 2,335 patients received brimonidine as monotherapy, replacement therapy, or combination therapy. Patients who received brimonidine as combination therapy (n = 554) were examined in the current analysis. Efficacy was determined by the reduction in intraocular pressure (IOP) from baseline before the addition of brimonidine. Safety and tolerability parameters included adverse events and quality-of-life measures (e.g., ocular comfort, energy level, breathing ability, night vision). RESULTS: Addition of brimonidine to preexisting regimens resulted in an overall mean additional reduction in IOP of 17.9% (4.26 mm Hg) at month 2 (P < 0.001). Significant additional IOP lowering was provided by brimonidine in combination with each preexisting regimen evaluated (P < or = 0.061). When brimonidine was added to monotherapy with a nonselective beta-blocker, the mean additional IOP reduction was 15.5% (3.61 mm Hg, P < 0.001). Addition of brimonidine to latanoprost monotherapy provided a 32.2% (5.89 mm Hg) mean additional IOP reduction (P < 0.001). Addition of brimonidine to combination regimens that included latanoprost provided additional mean decreases in LOP ranging from 15.5% (3.63 mm Hg, P < 0.002) to 20.1% (6.62 mm Hg, P < 0.001). All quality-of-life parameters remained high or improved during the study. Mild to moderate adverse events were reported in 5.23% of patients (29 of 552); 98.1% of physicians rated brimonidine adjunctive therapy as good or excellent. CONCLUSIONS: Brimonidine, when added to existing glaucoma regimens, safely and effectively lowered IOP in this community-based trial.

Breast cancer. Cyr61 is overexpressed, estrogen-inducible, and associated with more advanced disease.

To identify genes involved in breast cancer, polymerase chain reaction-selected cDNA subtraction was utilized to construct a breast cancer-subtracted library. Differential screening of the library isolated the growth factor-inducible immediate-early gene Cyr61, a secreted, cysteine-rich, heparin binding protein that promotes endothelial cell adhesion, migration, and neovascularization. Northern analysis revealed that Cyr61 was expressed highly in the invasive breast cancer cell lines MDA-MB-231, T47D, and MDA-MB-157; very low levels were found in the less tumorigenic MCF-7 and BT-20 breast cancer cells and barely detectable amounts were expressed in the normal breast cells, MCF-12A. Univariate analysis showed a significant or borderline significant association between Cyr61 expression and stage, tumor size, lymph node positivity, age, and estrogen receptor levels. Interestingly, expression of Cyr61 mRNA increased 8- to 12-fold in MCF-12A and 3- to 5-fold in MCF-7 cells after 24- and 48-h exposure to estrogen, respectively. Induction of Cyr61 mRNA was blocked by tamoxifen and ICI182,780, inhibitors of the estrogen receptor. Stable expression of Cyr61 cDNA under the regulation of a constitutive promoter in MCF-7 cells enhanced anchorage-independent cell growth in soft agar and significantly increased tumorigenicity and vascularization of these tumors in nude mice. Moreover, overexpression of Cyr61 in MCF-12A normal breast cells induced their tumor formation and vascularization in nude mice. In summary, these results suggest that Cyr61 may play a role in the progression of breast cancer and may be involved in estrogen-mediated tumor development.

Does liver transplantation affect growth pattern in Alagille syndrome?

Alagille syndrome (AGS) is frequently associated with growth failure, which has been attributed to concurrent congenital anomalies, cholestasis, and malabsorption and/or malnutrition. However, the underlying cause of the growth failure is not well understood. Our objective is to analyze the growth pattern in 26 patients with AGS and the possible effect that orthotopic liver transplantation (OLT) may have on this pattern. The standardized height, weight, and growth velocity of 26 pair-matched patients with AGS were compared. Thirteen patients underwent OLT. Repeated-measure ANOVA methods were used for the statistical analysis. The overall mean standardized height (z score) was -2.92 in the OLT group versus -1.88 in the non-OLT group (P =.03). The overall mean standardized weight was -1. 21 in the non-OLT group and -1.67 in the OLT group (P =.23). In 15 patients, birth weight was 2.82 +/- 0.4 kg, for a mean standardized weight of -0.95, and weight at diagnosis was 4.53 +/- 2.12 kg, for a mean standardized weight of -1.56. Bone age was delayed in the 9 patients who underwent bone-age analysis. Growth hormone therapy administered to 2 patients did not improve growth. Patients with AGS had growth failure secondary to other factors in addition to liver disease. Growth failure beginning in the prenatal period supports a genetic basis for this feature. Growth improvement up to normal levels should not be expected as a benefit of OLT in these patients. Growth failure as a primary indication for OLT should be cautiously examined in patients with AGS.

Antibody responses to Bordetella pertussis antigens and clinical correlations in elderly community residents.

A serological study to determine the frequency of Bordetella pertussis infection in 100 adults aged >/=65 years was carried out over a 3-year period. Ten serum samples (collected every 4 months) from each subject were examined for IgA and IgG antibodies to the following B. pertussis antigens: pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin, and fimbriae-2. A >/=2-fold titer increase in ELISA units from one time period to the next was considered serological evidence of infection. The rate of serologically defined infection (i.e., in which there was an increase in titer against any antigen) was 19.7 per 100 person-years. With the use of more specific criteria that indicate definite B. pertussis infection (>/=2-fold increase in titer to PT) and probable B. pertussis infection (>/=2-fold increase in titer to PT or >/=2-fold increase to fimbriae-2), the rates were 3.3 and 8.0 per 100 person-years, respectively. Fifty percent of individuals with definite B. pertussis infections had time-associated symptomatology. Antibody patterns over time suggest that antibody to FHA and perhaps to pertactin is stimulated by infections with other organisms, as well as B. pertussis infections. Our data suggest that symptomatic pertussis occurs in elderly individuals. Consideration should be given to immunization of the elderly with acellular pertussis vaccines.

A laser-powered hydrokinetic system for caries removal and cavity preparation.

BACKGROUND: Laser systems have been developed for the cutting of dental hard tissues. The erbium, chromium:yttrium-scandium-gallium-garnet, or Er,Cr:YSGG, laser system used in conjunction with an air-water spray has been shown to be efficacious in vitro for cavity preparation. METHODS: The authors randomly selected subjects for cavity preparation with conventional air turbine/bur dental surgery or an Er,Cr:YSGG laser-powered system using a split-mouth design. They prepared Class I, III and V cavities, placed resin restorations and evaluated subjects on the day of the procedure and 30 days and six months postoperatively for pulp vitality, recurrent caries, pain and discomfort, and restoration retention. Sixty-seven subjects completed the study. RESULTS: There were no statistical differences between the two treatment groups for the parameters measured with one exception; there was a statistically significant decrease in discomfort levels for the laser system at the time of cavity preparation for subjects who declined to receive local anesthetic. CONCLUSIONS: The Er,Cr:YSGG laser system is effective for preparation of Class I, III and V cavities and resin restorations are retained by lased tooth surfaces. CLINICAL IMPLICATIONS: Hard-tissue cutting lasers are being introduced for use in operative dentistry. In this study, an Er,Cr:YSGG laser has been shown to be effective for cavity preparation and restoration replacement.

Outcomes and factors impacting local recurrence of ductal carcinoma in situ.

BACKGROUND: The optimal management of ductal carcinoma in situ (DCIS) remains controversial. Investigators have focused on identifying patients who are eligible for treatment by excision alone. A retrospective analysis of patients with DCIS treated by various modalities was conducted to compare outcomes and determine factors significant for local recurrence (LR). METHODS: Between 1985-1992, 88 consecutive diagnoses of DCIS were identified in 85 patients. Seventy-four percent were detected mammographically. The most common histologic subtypes were comedo (54%) and cribriform (23%). Tumor sizes were < 2.5 cm (49%), > 2.5-5 cm (26%), > 5 cm (23%), and unknown (2%). Final resection margins were tumor free (75%), close/positive (23%), and unknown (2%). Treatment methods included mastectomy (30%), localized surgery and radiation therapy (LSR) (43%), or wide localized surgery alone (LS) (27%). Radiation therapy (RT) was comprised of 50 grays to the breast, and 53% of treated patients received local "boost" irradiation. RESULTS: The median follow up was 8.3 years. The overall recurrence rate was 13. 6%, whereas the median time to LR was 27.8 months. Recurrence rates according to treatment modality were: LS: 25%; LSR: 13%; and mastectomy: 4%. However, if surgical margins were tumor free, LSR had a LR rate of 3.4%. After RT, no LR occurred prior to 15 months, and 4 of 5 tumors were noninvasive. Nine patients treated by excision alone conformed to the criteria of Lagios et al. criteria and LR occurred in three of nine tumors. Of the factors analyzed, margin status was found to be the best predictor for LR (P = 0.05). CONCLUSIONS: If surgical margins are tumor free, the LSR regimen is equivalent to mastectomy for local tumor control. Annual mammograms may be adequate for the follow-up of patients with irradiated breasts, but biannual studies still are recommended for patients treated with excision alone.

Prolonged afebrile nonproductive cough illnesses in American soldiers in Korea: a serological search for causation.

A serological study was undertaken to investigate infections in active-duty United States soldiers with illnesses characterized by prolonged, afebrile, nonproductive coughs. Fifty-four soldiers were enrolled with such illness of >/=2 weeks' duration (case patients) along with 55 well soldiers (control subjects). Serum samples were tested for IgG and IgA antibody to 3 Bordetella pertussis antigens, pertussis agglutinins, IgM antibodies to Mycoplasma pneumoniae, IgM and IgG antibodies to Chlamydia pneumoniae, and IgM antibody to adenoviruses. Forty-six case patients (85%) had evidence of recent infection with Bordetella species, M. pneumoniae, or C. pneumoniae, and many had evidence of mixed infections; there were 27 Bordetella species, 20 C. pneumoniae, and 33 M. pneumoniae recent infections. Fifteen case patients had high titers of IgG or IgA to B. pertussis filamentous hemagglutinin without high titers of antibodies to other B. pertussis antigens, which suggested the presence of cross-reacting antibodies to M. pneumoniae and perhaps C. pneumoniae or unidentified infectious agent or agents. Since illnesses due to Bordetella species, M. pneumoniae, and C. pneumoniae can all be treated with macrolide antibiotics and B. pertussis illness can be prevented by immunization, and since military readiness was affected in 63% of the cases, it seems important to conduct further studies in military populations.

The effectiveness and safety of brimonidine as mono-, combination, or replacement therapy for patients with primary open-angle glaucoma or ocular hypertension: a post hoc analysis of an open-label community trial. Glaucoma Trial Study Group.

The purpose of this study was to determine the effectiveness and safety of brimonidine 0.2% (Alphagan, Allergan Inc., Irvine, CA) as mono-, combination, or replacement therapy for reducing intraocular pressure (IOP) in patients with primary open-angle glaucoma or ocular hypertension. The study method was an open-label, comparative clinical evaluation involving 2335 patients. During the 2-month trial, data were collected at baseline (visit 1), month 1 (visit 2), and month 2 (visit 3). Various parameters were evaluated, including glaucoma medications (visit 1), IOP (visit 1-visit 3), and adverse events. A subset cohort of 1254 patients was selected that met specific study criteria. Data from these 1254 patients were used to evaluate adverse events and the change in IOP from visit 1 to visit 3. Patient data were grouped according to specific drug regimen, and drug regimens were categorized into supergroups of mono-, combination, and replacement therapy. The results of the study revealed that the overall mean change in IOP for 1) monotherapy (n = 240) was -5.07 mm Hg (-20.2%), 2) combination therapy (n = 554) was -4.01 mm Hg (-16.9%), 3) replacement therapy (n = 460) was -2.33 mm Hg (-9.8%), and 4) overall (n = 1254) was -3.59 mm Hg (-14.9%) (p < 0.001 for all changes). Overall, 6.0% of the subjects reported adverse events, with no hypersensitivity or unexpected systemic or ocular adverse events. Eighty-five percent (85%) of clinicians rated brimonidine as "good" to "excellent". In conclusion, brimonidine is safe and effectively lowers IOP when used as mono-, combination, or replacement therapy as observed in a large community population.

Assessing the accuracy of a food frequency questionnaire for estimating usual intake of phytoestrogens.

The primary objective of this study was to assess the accuracy of a modified Block food frequency questionnaire (FFQ) with respect to its ability to assess usual dietary intakes of daidzein and genistein. Participants were a convenience sample of 51 Japanese and 18 Caucasian women. All interviews were conducted between February 1997 and October 1997. At each of the four study visits, participants provided a 24-hour urine specimen and a 48-hour dietary recall. At the first visit, participants also completed an interviewer-administered modified Block FFQ. The daidzein and genistein intakes estimated using the FFQ were moderately correlated with the mean estimates of daidzein and genistein intake calculated from four 48-hour dietary recalls (correlation for daidzein = 0.49-0.58 and correlation for genistein = 0.45-0.54) and estimates of urinary concentrations of these compounds calculated from four collections (correlations for daidzein and genistein = 0.49 and 0.30, respectively). The accuracy of the modified Block FFQ for assessment of usual daidzein and genistein intakes is supported by this study. These results support the use of this instrument in epidemiological studies as an easy and low-cost method to assess the usual dietary daidzein or genistein intake.

Selecting donors of platelets for refractory patients on the basis of HLA antibody specificity.

BACKGROUND: Patients who are refractory to platelet transfusion as a result of HLA alloimmunization are generally given HLA-matched or crossmatched platelets. However, HLA-matched platelets that are matched at HLA-A and -B loci (A-matched) or those without any mismatched or cross-reactive antigens (BU-matched) are frequently unavailable. A disadvantage of crossmatching is that crossmatched platelets have a shelf life of only 5 days, so that crossmatch tests must be performed frequently for patients requiring long-term platelet transfusions. An alternative method is the selection of platelets according to the patient's HLA antibody specificity, called the antibody specificity prediction (ASP) method. STUDY DESIGN AND METHODS: An anti-human globulin-enhanced microlymphocytotoxicity test modified by a double addition of serum and a computer program were used to determine the specificity of patients' HLA antibodies. Platelet crossmatching was performed with a solid-phase adherence assay. The percentage of platelet recovery (PPR) was determined in 1621 platelet transfusions in an observational study in 114 patients, and the PPR of platelets selected by the ASP method was compared with the PPR of those that were HLA-matched, crossmatched, or randomly selected. The numbers of potential donors in files of HLA-typed donors as identified by HLA matching vs. the ASP method were determined. RESULTS: After adjustments for covariates, the mean +/- SEM PPR was similar for HLA-matched (21 +/-4%), cross-matched (23+/-4%), and ASP-selected (24+/-3%) platelets and was significantly lower for randomly selected (15+/-1.4%) platelets. For 29 alloimmunized HLA-typed patients, the mean number of potential donors found in a file of 7247 HLA-typed donors was 6 who were an HLA-A match (median = 1), 33 who were an HLA-BU match (median = 20), and 1426 who were identified by the ASP method (median = 1365). CONCLUSION: The ASP method of donor selection for refractory alloimmunized patients appears as effective as HLA matching or crossmatching. Far more donors are identified in a file of HLA-typed donors by the ASP method than by HLA matching, and this indicates that the ASP method provides important advantages regarding the availability of compatible platelet components.