Wilford Hall Ambulatory Surgical Center

CONTEXT: Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels, women, and older persons. OBJECTIVE: To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinics in Texas. PARTICIPANTS: A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51 st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles, respectively), and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile). INTERVENTION: Lovastatin (20-40 mg daily) or placebo in addition to a low-saturated fat, low-cholesterol diet. MAIN OUTCOME MEASURES: First acute major coronary event defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death. RESULTS: After an average follow-up of 5.2 years, lovastatin reduced the incidence of first acute major coronary events (1 83 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001), myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83; P=.002), unstable angina (87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P=.02), coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52-0.85; P=.001), coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, 0.61-0.92; P =.006), and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91; P = .003). Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in safety parameters between treatment groups. CONCLUSIONS: Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.

BACKGROUND: Androgens are involved in the development of prostate cancer. Finasteride, an inhibitor of 5alpha-reductase, inhibits the conversion of testosterone to dihydrotestosterone, the primary androgen in the prostate, and may reduce the risk of prostate cancer. METHODS: In the Prostate Cancer Prevention Trial, we randomly assigned 18,882 men 55 years of age or older with a normal digital rectal examination and a prostate-specific antigen (PSA) level of 3.0 ng per milliliter or lower to treatment with finasteride (5 mg per day) or placebo for seven years. Prostate biopsy was recommended if the annual PSA level, adjusted for the effect of finasteride, exceeded 4.0 ng per milliliter or if the digital rectal examination was abnormal. It was anticipated that 60 percent of participants would have prostate cancer diagnosed during the study or would undergo biopsy at the end of the study. The primary end point was the prevalence of prostate cancer during the seven years of the study. RESULTS: Prostate cancer was detected in 803 of the 4368 men in the finasteride group who had data for the final analysis (18.4 percent) and 1147 of the 4692 men in the placebo group who had such data (24.4 percent), for a 24.8 percent reduction in prevalence over the seven-year period (95 percent confidence interval, 18.6 to 30.6 percent; P<0.001). Tumors of Gleason grade 7, 8, 9, or 10 were more common in the finasteride group (280 of 757 tumors [37.0 percent], or 6.4 percent of the 4368 men included in the final analysis) than in the placebo group (237 of 1068 tumors [22.2 percent], P<0.001 for the comparison between groups; or 5.1 percent of the 4692 men included in the final analysis, P=0.005 for the comparison between groups). Sexual side effects were more common in finasteride-treated men, whereas urinary symptoms were more common in men receiving placebo. CONCLUSIONS: Finasteride prevents or delays the appearance of prostate cancer, but this possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high-grade prostate cancer.

BACKGROUND: No pharmacologic therapy has conclusively proved to be effective for the treatment of nonalcoholic steatohepatitis, which is characterized by insulin resistance, steatosis, and necroinflammation with or without centrilobular fibrosis. Pioglitazone is a thiazolidinedione that ameliorates insulin resistance and improves glucose and lipid metabolism in type 2 diabetes mellitus. METHODS: We randomly assigned 55 patients with impaired glucose tolerance or type 2 diabetes and liver biopsy-confirmed nonalcoholic steatohepatitis to 6 months of treatment with a hypocaloric diet (a reduction of 500 kcal per day in relation to the calculated daily intake required to maintain body weight) plus pioglitazone (45 mg daily) or a hypocaloric diet plus placebo. Before and after treatment, we assessed hepatic histologic features, hepatic fat content by means of magnetic resonance spectroscopy, and glucose turnover during an oral glucose tolerance test ([14C]glucose given with the oral glucose load and [3H]glucose given by intravenous infusion). RESULTS: Diet plus pioglitazone, as compared with diet plus placebo, improved glycemic control and glucose tolerance (P<0.001), normalized liver aminotransferase levels as it decreased plasma aspartate aminotransferase levels (by 40% vs. 21%, P=0.04), decreased alanine aminotransferase levels (by 58% vs. 34%, P<0.001), decreased hepatic fat content (by 54% vs. 0%, P<0.001), and increased hepatic insulin sensitivity (by 48% vs. 14%, P=0.008). Administration of pioglitazone, as compared with placebo, was associated with improvement in histologic findings with regard to steatosis (P=0.003), ballooning necrosis (P=0.02), and inflammation (P=0.008). Subjects in the pioglitazone group had a greater reduction in necroinflammation (85% vs. 38%, P=0.001), but the reduction in fibrosis did not differ significantly from that in the placebo group (P=0.08). Fatigue and mild lower-extremity edema developed in one subject who received pioglitazone; no other adverse events were observed. CONCLUSIONS: In this proof-of-concept study, the administration of pioglitazone led to metabolic and histologic improvement in subjects with nonalcoholic steatohepatitis. Larger controlled trials of longer duration are warranted to assess the long-term clinical benefit of pioglitazone. (ClinicalTrials.gov number, NCT00227110 [ClinicalTrials.gov] .).

PURPOSE: By 2030, the United States' population will increase to approximately 365 million, including 72 million older adults (age > or = 65 years) and 157 million minority individuals. Although cancer incidence varies by age and race, the impact of demographic changes on cancer incidence has not been fully characterized. We sought to estimate the number of cancer patients diagnosed in the United States through 2030 by age and race. METHODS: Current demographic-specific cancer incidence rates were calculated using the Surveillance Epidemiology and End Results database. Population projections from the Census Bureau were used to project future cancer incidence through 2030. RESULTS: From 2010 to 2030, the total projected cancer incidence will increase by approximately 45%, from 1.6 million in 2010 to 2.3 million in 2030. This increase is driven by cancer diagnosed in older adults and minorities. A 67% increase in cancer incidence is anticipated for older adults, compared with an 11% increase for younger adults. A 99% increase is anticipated for minorities, compared with a 31% increase for whites. From 2010 to 2030, the percentage of all cancers diagnosed in older adults will increase from 61% to 70%, and the percentage of all cancers diagnosed in minorities will increase from 21% to 28%. CONCLUSION: Demographic changes in the United States will result in a marked increase in the number of cancer diagnoses over the next 20 years. Continued efforts are needed to improve cancer care for older adults and minorities.

BACKGROUND: Elevated levels of C-reactive protein, even in the absence of hyperlipidemia, are associated with an increased risk of coronary events. Statin therapy reduces the level of C-reactive protein independently of its effect on lipid levels. We hypothesized that statins might prevent coronary events in persons with elevated C-reactive protein levels who did not have overt hyperlipidemia. METHODS: The level of C-reactive protein was measured at base line and after one year in 5742 participants in a five-year randomized trial of lovastatin for the primary prevention of acute coronary events. RESULTS: The rates of coronary events increased significantly with increases in the base-line levels of C-reactive protein. Lovastatin therapy reduced the C-reactive protein level by 14.8 percent (P<0.001), an effect not explained by lovastatin-induced changes in the lipid profile. As expected, lovastatin was effective in preventing coronary events in participants whose base-line ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol was higher than the median ratio, regardless of the level of C-reactive protein (number needed to treat for five years to prevent 1 event, 47; P=0.005). However, lovastatin was also effective among those with a ratio of total to HDL cholesterol that was lower than the median and a C-reactive protein level higher than the median (number needed to treat, 43; P=0.02). In contrast, lovastatin was ineffective among participants with a ratio of total to HDL cholesterol and a C-reactive protein level that were both lower than the median (number needed to treat, 983; P=0.80). CONCLUSIONS: Statin therapy may be effective in the primary prevention of coronary events among subjects with relatively low lipid levels but with elevated levels of C-reactive protein.

In Brief Study Design. Cohort study of patients with low back pain (LBP) receiving physical therapy. Objective. To examine the responsiveness characteristics of the numerical pain rating scale (NPRS) in patients with LBP using a variety of methods. Summary of Background Data. Although several studies have assessed the reliability and validity of the NPRS, few studies have characterized its responsiveness in patients with LBP. Methods. Determination of change on the NPRS during 1 and 4 weeks was examined by calculating mean change, standardized effect size, Guyatt Responsiveness Index, area under a receiver operating characteristic curve, minimum clinically important difference, and minimum detectable change. Change in the NPRS from baseline to the 1 and 4-week follow-up was compared to the average of the patient and therapist’s perceived improvement using the 15-point Global Rating of Change scale. Results. The majority of patients had clinically meaningful improvement after both 1 and 4 weeks of rehabilitation. The standard error of measure was equal to 1.02, corresponding to a minimum detectable change of 2 points. The area under the curve at the 1 and 4-week follow-up was 0.72 (0.62, 0.81) and 0.92 (0.86, 0.97), respectively. The minimum clinically important difference at the 1 and 4-week follow-up corresponded to a change of 2.2 and 1.5 points, respectively. Conclusions. Clinicians can be confident that a 2-point change on the NPRS represents clinically meaningful change that exceeds the bounds of measurement error. The purpose of this study was to examine the responsiveness of the numerical pain rating scale in patients with low back pain. The scale shows satisfactory internal and external responsiveness. Clinicians can be confident that a 2-point change represents clinically meaningful change that exceeds the bounds of measurement error.

Adjuvant radiotherapy after radical prostatectomy for a man with pT3N0M0 prostate cancer significantly reduces the risk of metastasis and increases survival.

Segmental duplications in the human genome are selectively enriched for genes involved in immunity, although the phenotypic consequences for host defense are unknown. We show that there are significant interindividual and interpopulation differences in the copy number of a segmental duplication encompassing the gene encoding CCL3L1 (MIP-1alphaP), a potent human immunodeficiency virus-1 (HIV-1)-suppressive chemokine and ligand for the HIV coreceptor CCR5. Possession of a CCL3L1 copy number lower than the population average is associated with markedly enhanced HIV/acquired immunodeficiency syndrome (AIDS) susceptibility. This susceptibility is even greater in individuals who also possess disease-accelerating CCR5 genotypes. This relationship between CCL3L1 dose and altered HIV/AIDS susceptibility points to a central role for CCL3L1 in HIV/AIDS pathogenesis and indicates that differences in the dose of immune response genes may constitute a genetic basis for variable responses to infectious diseases.

The effect of surface roughness on osteoblast proliferation, differentiation, and protein synthesis was examined. Human osteoblast-like cells (MG63) were cultured on titanium (Ti) disks that had been prepared by one of five different treatment regimens. All disks were pretreated with hydrofluroic acid-nitric acid and washed (PT). PT disks were also: washed, and then electropolished (EP); fine sandblasted, etched with HCl and H2SO4, and washed (FA); coarse sandblasted, etched with HCl and H2SO4, and washed (CA); or Ti plasma-sprayed (TPS). Standard tissue culture plastic was used as a control. Surface topography and profile were evaluated by brightfield and darkfield microscopy, cold field emission scanning electron microscopy, and laser confocal microscopy, while chemical composition was mapped using energy dispersion X-ray analysis and elemental distribution determined using Auger electron spectroscopy. The effect of surface roughness on the cells was evaluated by measuring cell number, [3H]thymidine incorporation into DNA, alkaline phosphatase specific activity, [3H]uridine incorporation into RNA, [3H]proline incorporation into collagenase digestible protein (CDP) and noncollagenase-digestible protein (NCP), and [35S]sulfate incorporation into proteoglycan. Based on surface analysis, the five different Ti surfaces were ranked in order of smoothest to roughest: EP, PT, FA, CA, and TPS. A TiO2 layer was found on all surfaces that ranged in thickness from 100 A in the smoothest group to 300 A in the roughest. When compared to confluent cultures of cells on plastic, the number of cells was reduced on the TPS surfaces and increased on the EP surfaces, while the number of cells on the other surfaces was equivalent to plastic. [3H]Thymidine incorporation was inversely related to surface roughness. Alkaline phosphatase specific activity in isolated cells was found to decrease with increasing surface roughness, except for those cells cultured on CA. In contrast, enzyme activity in the cell layer was only decreased in cultures grown on FA- and TPS-treated surfaces. A direct correlation between surface roughness and RNA and CDP production was found. Surface roughness had no apparent effect on NCP production. Proteoglycan synthesis by the cells was inhibited on all the surfaces studied, with the largest inhibition observed in the CA and EP groups. These results demonstrate that surface roughness alters osteoblast proliferation, differentiation, and matrix production in vitro. The results also suggest that implant surface roughness may play a role in determining phenotypic expression of cells in vivo.

OBJECTIVE: To relate in-hospital mortality to early transfusion of plasma and/or platelets and to time-varying plasma:red blood cell (RBC) and platelet:RBC ratios. DESIGN: Prospective cohort study documenting the timing of transfusions during active resuscitation and patient outcomes. Data were analyzed using time-dependent proportional hazards models. SETTING: Ten US level I trauma centers. PATIENTS: Adult trauma patients surviving for 30 minutes after admission who received a transfusion of at least 1 unit of RBCs within 6 hours of admission (n = 1245, the original study group) and at least 3 total units (of RBCs, plasma, or platelets) within 24 hours (n = 905, the analysis group). MAIN OUTCOME MEASURE: In-hospital mortality. RESULTS: Plasma:RBC and platelet:RBC ratios were not constant during the first 24 hours (P < .001 for both). In a multivariable time-dependent Cox model, increased ratios of plasma:RBCs (adjusted hazard ratio = 0.31; 95% CI, 0.16-0.58) and platelets:RBCs (adjusted hazard ratio = 0.55; 95% CI, 0.31-0.98) were independently associated with decreased 6-hour mortality, when hemorrhagic death predominated. In the first 6 hours, patients with ratios less than 1:2 were 3 to 4 times more likely to die than patients with ratios of 1:1 or higher. After 24 hours, plasma and platelet ratios were unassociated with mortality, when competing risks from nonhemorrhagic causes prevailed. CONCLUSIONS: Higher plasma and platelet ratios early in resuscitation were associated with decreased mortality in patients who received transfusions of at least 3 units of blood products during the first 24 hours after admission. Among survivors at 24 hours, the subsequent risk of death by day 30 was not associated with plasma or platelet ratios.

Coronal plane computerized tomographic (CT) scanning has dramatically improved the imaging of paranasal sinus anatomy as compared to sinus radiographs. Increasingly, subtle bony anatomic variations and mucosal abnormalities of this region are being detected. Data regarding the "background" prevalence of these findings are needed to determine their clinical relevance. A detailed analysis of coronal plane CT scans of the paranasal sinuses obtained in 202 consecutively imaged patients was conducted. Special attention was directed toward identifying bony anatomic variations and mucosal abnormalities. Anatomic variations studied included pneumatization of the middle turbinate, paradoxical curvature of the middle turbinate, Haller's cells, and pneumatization of the uncinate process. Such bony anatomic variations were detected in 131 (64.9%) of 202 patients and were found with a similar frequency in patients scanned for sinus complaints and in those scanned for nonsinus reasons. Mucosal abnormalities were detected in 168 (83.2%) of 202 patients. For those patients scanned during the evaluation of sinus-like complaints, mucosal abnormalities were noted in 153 (92.2%) of 166 cases, and were predominantly detected in the anterior ethmoid region. For patients scanned during nonsinus evaluations, mucosal abnormalities were detected in 15 (41.7%) of 36 cases, without predilection for the anterior ethmoid region. Discussion regarding the prevalence and clinical significance of paranasal sinus bony anatomic variations and mucosal abnormalities is included as a guide to assist the otolaryngologist and/or radiologist in the evaluation of coronal sinus CT scans.

BACKGROUND: Sudden death among military recruits is a rare but devastating occurrence. Because extensive medical data are available on this cross-sectional and diverse population, identification of the underlying causes of sudden death may promote health care policy to reduce the incidence of sudden death. OBJECTIVE: To determine the causes of nontraumatic sudden death among a cohort of military recruits. DESIGN: Retrospective cohort study using demographic and autopsy data from the Department of Defense Recruit Mortality Registry. SETTING: Basic military training. PATIENTS: All nontraumatic sudden deaths from a monitored 6.3 million men and women age 18 to 35 years. MEASUREMENTS: Descriptive analysis, crude mortality rates of causes of sudden death, and frequency of events as a function of cause of death. RESULTS: Of 126 nontraumatic sudden deaths (rate, 13.0/100,000 recruit-years), 108 (86%) were related to exercise. The most common cause of sudden death was an identifiable cardiac abnormality (64 of 126 recruits [51%]); however, a substantial number of deaths remained unexplained (44 of 126 recruits [35%]). The predominant structural cardiac abnormalities were coronary artery abnormalities (39 of 64 recruits [61%]), myocarditis (13 of 64 recruits [20%]), and hypertrophic cardiomyopathy (8 of 64 recruits [13%]). An anomalous coronary artery accounted for one third (21 of 64 recruits) of the cases in this cohort, and, in each, the left coronary artery arose from the right (anterior) sinus of Valsalva, coursing between the pulmonary artery and aorta. LIMITATIONS: This cohort underwent a preenlistment screening program that included history and physical examination; this may have altered outcomes. CONCLUSIONS: Cardiac abnormalities are the leading identifiable cause of sudden death among military recruits; however, more than one third of sudden deaths remain unexplained after detailed medical investigation.

BACKGROUND: Clinical predictors of advanced non-alcoholic liver disease (NAFLD) are needed to guide diagnostic evaluation and treatment. METHODS: To better understand the demographics of NAFLD and risk factors for advanced disease, this study analysed 827 patients with NAFLD at two geographically separate tertiary medical centres. RESULTS: The cohort was 51% female and had a median body mass index (BMI) of 33 kg/m(2); 3% had a normal BMI. Common co-morbidities included hypertension (60%) and diabetes (35%); insulin resistance was present in 91% and advanced fibrosis in 24% of patients. When comparing patients with no fibrosis or mild fibrosis to those with advanced fibrosis, BMI > or = 28 kg/m(2), age > 50 years, and aspartate transaminase/alanine aminotransferase (AST/ALT) ratio > or = 0.8, a quantitative assessment check index (QUICKI) score < 0.294 (equivalent to homeostasis model assessment (HOMA) > 6.2) and the presence of diabetes mellitus (DM) were individually associated by univariate analysis with odds ratios (ORs) of > or = 2.4 for advanced fibrosis. Based on the results of forced entry logistic regression analysis, three variables were combined in a weighted sum (BMI > or = 28 = 1 point, AAR of > or = 0.8 = 2 points, DM = 1 point) to form an easily calculated composite score for predicting advanced fibrosis called the BARD score. A score of 2-4 was associated with an OR for advanced fibrosis of 17 (confidence interval 9.2 to 31.9) and a negative predictive value of 96%. CONCLUSIONS: Insulin resistance and its co-morbidities are often present in patients with NAFLD. An easily calculated score based on readily available clinical data can reliably exclude the presence of advanced fibrosis in these patients, particularly among non-diabetics.

Bone formation was investigated in vitro by culturing stromal osteoblasts in three-dimensional (3-D), biodegradable poly(DL-lactic-co-glycolic acid) foams. Three polymer foam pore sizes, ranging from 150-300, 300-500, and 500-710 microns, and two different cell seeding densities, 6.83 x 10(5) cells/cm2 and 22.1 x 10(5) cells/cm2, were examined over a 56-day culture period. The polymer foams supported the proliferation of seeded osteoblasts as well as their differentiated function, as demonstrated by high alkaline phosphatase activity and deposition of a mineralized matrix by the cells. Cell number, alkaline phosphatase activity, and mineral deposition increased significantly over time for all the polymer foams. Osteoblast foam constructs created by seeding 6.83 x 10(5) cells/cm2 on foams with 300-500 microns pores resulted in a cell density of 4.63 x 10(5) cells/cm2 after 1 day in culture; they had alkaline phosphatase activities of 4.28 x 10(-7) and 2.91 x 10(-6) mumol/cell/min on Days 7 and 28, respectively; and they had a cell density that increased to 18.7 x 10(5) cells/cm2 by Day 56. For the same constructs, the mineralized matrix reached a maximum penetration depth of 240 microns from the top surface of the foam and a value of 0.083 mm for mineralized tissue volume per unit of cross sectional area. Seeding density was an important parameter for the constructs, but pore size over the range tested did not affect cell proliferation or function. This study suggests the feasibility of using poly(alpha-hydroxy ester) foams as scaffolding materials for the transplantation of autogenous osteoblasts to regenerate bone tissue.

Patients with acute heart failure (AHF) require urgent in-hospital treatment for relief of symptoms. The main reason for hospitalization is congestion, rather than low cardiac output. Although congestion is associated with a poor prognosis, many patients are discharged with persistent signs and symptoms of congestion and/or a high left ventricular filling pressure. Available data suggest that a pre-discharge clinical assessment of congestion is often not performed, and even when it is performed, it is not done systematically because no method to assess congestion prior to discharge has been validated. Grading congestion would be helpful for initiating and following response to therapy. We have reviewed a variety of strategies to assess congestion which should be considered in the care of patients admitted with HF. We propose a combination of available measurements of congestion. Key elements in the measurement of congestion include bedside assessment, laboratory analysis, and dynamic manoeuvres. These strategies expand by suggesting a routine assessment of congestion and a pre-discharge scoring system. A point system is used to quantify the degree of congestion. This score offers a new instrument to direct both current and investigational therapies designed to optimize volume status during and after hospitalization. In conclusion, this document reviews the available methods of evaluating congestion, provides suggestions on how to properly perform these measurements, and proposes a method to quantify the amount of congestion present.

OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a common cause of liver disease. Although usually indolent, this disease can progress to cirrhosis in some patients. There is currently no proven medical therapy for the treatment of NASH. The aim of our study was to evaluate the efficacy of combination alpha-tocopherol (vitamin E) and vitamin C in reducing histologic inflammation and fibrosis. METHODS: This was a prospective, double-blind, randomized, placebo-controlled trial with a total enrollment of 49 patients; 45 patients completed the study. All patients were randomized to receive either vitamins E and C (1000 IU and 1000 mg, respectively) or placebo daily for 6 months, based on their initial histologic diagnosis of NASH. Additionally, all patients were given standard weight-loss counseling and encouraged to follow a low fat diet (<30 fat g/day). The pre- and posttreatment liver biopsies were reviewed by a single pathologist, who was blinded to the patient's medication. Biopsies were scored based on a modification of the scoring system published by Brunt et al. (Am J Gastroenterol 1999;94:2467-74). A score of 0-4 was possible for fibrosis, and a score of 0-6 was possible for inflammation and hepatocyte degeneration and necrosis. In addition, body mass index, glycohemoglobin, lipids, and liver enzymes were followed throughout the study. RESULTS: Forty-five patients completed 6 months of therapy without significant side effects. Vitamin treatment resulted in a statistically significant improvement in fibrosis score (p=0.002). No changes were noted in inflammation with treatment. Vitamin E and vitamin C, in the doses used in this study, were well tolerated and were effective in improving fibrosis scores in NASH patients. No improvement in necroinflammatory activity or ALT was seen with this combination of drug therapy. A larger, multicenter, longer-term trial with vitamin E and vitamin C seems to be warranted.

The principal neutralizing determinant (PND) of human immunodeficiency virus HIV-1 is part of a disulfide bridged loop in the third variable region of the external envelope protein, gp120. Analysis of the amino acid sequences of this domain from 245 different HIV-1 isolates revealed that the PND is less variable than thought originally. Conservation to better than 80 percent of the amino acids in 9 out of 14 positions in the central portion of the PND and the occurrence of particular oligopeptide sequences in a majority of the isolates suggest that there are constraints on PND variability. One constraining influence may be the structural motif (beta strand--type II beta turn--beta strand--alpha helix) predicted for the consensus PND sequence by a neural network approach. Isolates with a PND similar to the commonly investigated human T cell lymphoma virus IIIB (HTLV-IIIB) and LAV-1 (BRU) strains were rare, and only 14 percent of sera from 86 randomly selected HIV-1 seropositive donors contained antibodies that recognized the PND of these virus isolates. In contrast, over 65 percent of these sera reacted with peptides containing more common PND sequences. These results suggest that HIV vaccine immunogens chosen because of their similarity to the consensus PND sequence and structure are likely to induce antibodies that neutralize a majority of HIV-1 isolates.

OBJECTIVE: To extend the knowledge on long-term effects of childhood abuse in psychiatric patients to a large sample, the authors explored childhood sexual and physical abuse in adult inpatients over 1,040 consecutive admissions. METHOD: The 947 patients were admitted to a tertiary-care military medical center. Each patient was interviewed, and abuse history, DSM-III-R diagnosis, and other characteristics were recorded. RESULTS: The prevalence of reported childhood abuse was 18% overall: 9% for sexual abuse (with or without physical abuse), 10% for physical abuse (with or without sexual abuse), and 3% for combined abuse. More female than male patients reported abuse. Alcohol use disorders were more common in victims of physical or combined abuse than in sexually abused or nonabused patients. Axis II diagnoses, particularly borderline personality disorder, were more frequent in abuse victims than in nonabused patients. Histories of drug and alcohol abuse were more common in patients reporting physical or combined abuse than in nonabused patients. Suicidality was also more frequent in abused than nonabused inpatients and was noted in 79% of the patients with histories of combined abuse. Combined abuse in women and physical abuse in men were associated with a family history of psychiatric illness, most commonly alcoholism in male relatives. CONCLUSIONS: These findings emphasize the need for greater attention to family dynamics, aggressive diagnosis and treatment of alcoholism within the family, and, especially, determination of patients' abuse histories, even if repeated questioning is necessary.

Splanchnic artery aneurysms were encountered in 45 patients. This experience and a comprehensive review of the literature since 1960 resulted in revision of many preexisting concepts concerning the pathogenesis and prognostic implications of these lesions. Most significant is that multiparity may result in medial degeneration with subsequent development of splenic artery aneurysms. A previously unrecognized association of renal artery fibromuscular disease and splenic artery aneurysms was documented. The established morbidity and mortality attributed to all aneurysms of the splanchnic arteries justifies prompt surgical treatment once their presence is known.

BACKGROUND: The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) is the first primary-prevention study in a cohort with average total cholesterol (TC) and LDL cholesterol (LDL-C) and below-average HDL cholesterol (HDL-C). Treatment with lovastatin (20 to 40 mg/d) resulted in a 25% reduction in LDL-C and a 6% increase in HDL-C, as well as a 37% reduction in risk for first acute major coronary event (AMCE), defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death. This article describes the relation between baseline and on-treatment lipid and apolipoprotein (apo) parameters and subsequent risk for AMCEs. METHODS AND RESULTS: With all available data from the entire 6605-patient cohort, a prespecified Cox backward stepwise regression model identified outcome predictors, and logistic regression models examined the relation between lipid variables and AMCE risk. Baseline LDL-C, HDL-C, and apoB were significant predictors of AMCE; only on-treatment apoB and the ratio of apoB to apoAI were predictive of subsequent risk; on-treatment LDL-C was not. When event rates were examined across tertiles of baseline lipids, a consistent benefit of treatment with lovastatin was observed. CONCLUSIONS: Persons with average TC and LDL-C levels and below-average HDL-C may obtain significant clinical benefit from primary-prevention lipid modification. On-treatment apoB, especially when combined with apoAI to form the apoB/AI ratio, may be a more accurate predictor than LDL-C of risk for first AMCE.