The relation of low levels of bone mineral density with coronary artery calcium and mortality.

Osteoporosis and atherosclerosis are two prevalent major healthcare concerns that frequently coexist. The clinical outcome of 5590 consecutive subjects who underwent coronary artery calcium (CAC) scanning and thoracic bone mineral density (BMD) measurement was assessed. A significant link between low BMD levels and CAC with increased risk of mortality in both genders across ethnicities noted. INTRODUCTION: While a relation of CAC with lower levels of BMD reported previously; it is unclear whether low levels of BMD would be an independent risk factor for CAC and mortality. This study investigated the relation of BMD levels with CAC and mortality in both genders across ethnicities. METHODS: This study consisted of 5590 consecutive at-risk subjects without known coronary artery disease (CAD), age 57 ± 12, and 69% male, who underwent non-enhanced cardiac computed tomography, and were followed for mean of 8 years. The subjects' CAC (Agatston score) and thoracic BMD levels (mg/cm3) were measured. CAC stratified based on the severity to CAC 0, 1-100, 101-400, and 400+. Low-BMD levels defined as BMD levels below median (180 mg/cm3). Physician verified that all-cause mortality was assessment hard-endpoint. Multivariate regression analysis, adjusted for age, gender, and other cardiovascular risk factors, was used to assess the relationship between BMD and CAC. RESULTS: The BMD levels were proportionally lowering with the severity of CAC in both genders, especially in postmenopausal women (p < 0.05). The risk of each standard deviation reduce in BMD levels increased with the severity of CAC, as compared to CAC = 0 across ethnicities (p < 0.05). Low BMD levels were an independent predictor of mortality and event-free survival rate decreased from 99% in those within normal BMD levels to 93% in those with low BMD levels (p = 0.0001). Furthermore, a significant link between low BMD levels and CAC > 0 with increased risk of mortality was noted (p = 0.0001). The relative risk of death was 2.8, 5.9, and 14.3-folds higher in CAC 1-100, 101-400, and 400+ with low BMD levels, compared to CAC = 0 and within normal BMD levels, respectively (p < 0.05). CONCLUSIONS: The lower BMD levels are independently associated with the severity of CAC that predicts mortality.

Lack of influence of fetal hemoglobin levels or erythrocyte indices on the severity of sickle cell anemia.

Persons with sickle cell anemia who have elevated fetal hemoglobin or lowered erythrocyte mean corpuscular volume are reputed to have less severe clinical manifestations and a greater probability of survival. This study examines the relationship between seven clinical indicators of morbidity in sickle cell anemia and seven hematological parameters that were collected from 214 patients. Risks of sickle cell crisis, acute chest syndrome, hospital admissions, cerebrovascular accident, aseptic necrosis, meningitis/septicemia, and death were used as indicators of morbidity. The hematological parameters included percent fetal hemoglobin, absolute fetal hemoglobin, percent hemoglobin A2, hemoglobin concentration, packed cell volume, mean corpuscular volume, and mean corpuscular hemoglobin concentration. Statistical analyses of the data showed no relationship between the hematological parameters and six of the seven clinical indicators of the severity of sickle cell anemia. The only significant finding was an increased risk of stroke in those patients with lower levels of fetal hemoglobin. Therefore, with this exception, there is no predictable relationship between morbidity and mortality in sickle cell anemia and levels of fetal hemoglobin or erythrocyte indices. Thus, the general belief that there is an association between severity of sickle cell anemia and the levels of fetal hemoglobin has not been established.

Precision and reproducibility of quantitative coronary angiography with applications to controlled clinical trials. A sampling study.

Most computer methods that quantify coronary artery disease from angiograms are designed to analyze frames recorded during the end-diastolic portion of the cardiac cycle. The purpose of this study was to determine if end diastole is the best portion of the cardiac cycle to sample, or if other sampling schemes produce more precise and/or reproducible estimates of coronary disease. 20 cinecoronary angiograms were selected at random from a controlled clinical trial testing the effects of plasma lipid lowering on atherosclerosis. Sampling schemes included sequential and random sampling of two to five frames within the complete cardiac cycle, systole, and diastole. Three vessel measures and percent stenosis were evaluated for each sampling scheme. From the sampling experiment, it was determined that sampling sequentially end diastole yielded the most precise estimates (i.e., exhibiting minimum variability within a cycle) of the vessel measures. With regard to reproducibility (i.e., similar values across cycles), sampling randomly within the cycle was best. Overall, the average diameter of a vessel segment was the most precise and the most reproducible of the measures. Sample size calculations are given for each of these measures under the best sampling scheme.

Evidence for joint genetic control of insulin sensitivity and systolic blood pressure in hispanic families with a hypertensive proband.

BACKGROUND: The clustering of hypertension, insulin resistance, and obesity remains unexplained. We tested for genetic and nongenetic influences on the association among these traits in Hispanic families with hypertension. METHODS AND RESULTS: Blood pressure and body mass index (BMI) were measured in 331 members of 73 Hispanic families in which an index case (proband) had hypertension. Insulin sensitivity (S(I)) was measured by euglycemic clamp in 287 probands and their spouses (parents' generation) or their adult offspring. Correlation analysis examined relationships among traits within and between generations. Path analysis estimated genetic and nongenetic contributions to variability in systolic blood pressure (SBP), S(I), and the correlation between them. In the offspring, there was a significant correlation between individuals for each trait, as well as significant correlations within and between individuals for all possible pairs of traits. Between generations, SBP, S(I), and BMI in parents correlated with the same traits in their offspring; BMI in parents correlated with S(I) and SBP in offspring; and S(I) in parents correlated with SBP in offspring. Path analysis estimated that among offspring, genetic effects unrelated to BMI accounted for 60.8% of the variation in SBP, 36.8% of the variation in S(I), and 31.5% of the correlation between SBP and S(I) after adjustment for age and sex. Heritable effects related to BMI accounted for an additional 14.0% of variation in SBP, 26.8% of variation in S(I), and 56.3% of variation in their correlation. CONCLUSIONS: Clustering of hypertension and insulin resistance in Hispanic Americans is accounted for in part by heritable factors both associated with and independent of BMI.

Coincident linkage of fasting plasma insulin and blood pressure to chromosome 7q in hypertensive hispanic families.

BACKGROUND: Insulin resistance (IR) and hyperinsulinemia are phenotypically associated with hypertension. We have previously provided evidence that blood pressure (BP) and IR cosegregate in Hispanic families, suggesting that this association has a genetic component. In the present study, we provide further support for the hypothesis of a genetic basis for the BP-IR relationship from a genetic linkage study. METHODS AND RESULTS: A 10-cM genome scan was conducted in 390 Hispanic family members of 77 hypertensive probands. Detailed measurements of BP, glucose, insulin levels, and insulin sensitivity (euglycemic clamp) were performed in adult offspring of probands. Multipoint variance component linkage analysis was used. A region on chromosome 7q seemed to influence both IR and BP. The greatest evidence for linkage was found for fasting insulin (lod score=3.36 at 128 cM), followed by systolic BP (lod score=2.06 at 120 cM). Fine mapping with greater marker density in this region increased the maximum lod score for fasting insulin to 3.94 at 125 cM (P=0.00002); lod score for systolic BP was 2.51 at 112 cM. Coincident mapping at this locus also included insulin sensitivity measured by the homeostasis assessment model (HOMA) and serum leptin concentrations. Insulin sensitivity by euglycemic clamp did not map to the same locus. CONCLUSIONS: Our results demonstrate that a major gene determining fasting insulin is located on chromosome 7q. Linkage of BP, HOMA, and leptin levels to the same region suggests this locus may broadly influence traits associated with IR and supports a genetic basis for phenotypic associations in IR syndrome.

Response of pancreatic beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes.

The purpose of this study was to examine the response of pancreatic beta-cells to changes in insulin sensitivity in women at high risk for type 2 diabetes. Oral glucose tolerance tests (OGTTs) and frequently sampled intravenous glucose tolerance tests (FSIGTs) were conducted on Latino women with impaired glucose tolerance and a history of gestational diabetes before and after 12 weeks of treatment with 400 mg/day troglitazone (n = 13) or placebo (n = 12). Insulin sensitivity was assessed by minimal model analysis, and beta-cell insulin release was assessed as acute insulin responses to glucose (AIRg) and tolbutamide (AIRt) during FSIGTs and as the 30-min incremental insulin response (30-min dINS) during OGTTs. Beta-cell compensation for insulin resistance was assessed as the product (disposition index) of minimal model insulin sensitivity and each of the 3 measures of beta-cell insulin release. In the placebo group, there was no significant change in insulin sensitivity or in any measure of insulin release, beta-cell compensation for insulin resistance, or glucose tolerance. Troglitazone treatment resulted in a significant increase in insulin sensitivity, as reported previously. In response, AIRg did not change significantly, so that the disposition index for AIRg increased significantly from baseline (P = 0.004) and compared with placebo (P = 0.02). AIRt (P = 0.001) and 30-min dINS (P = 0.02) fell with improved insulin sensitivity during troglitazone treatment, so that the disposition index for each of these measures of beta-cell function did not change significantly from baseline (P > 0.20) or compared with placebo (P > 0.3). Minimal model analysis revealed that 89% of the change from baseline in insulin sensitivity during troglitazone treatment was accounted for by lowered plasma insulin concentrations. Neither oral nor intravenous glucose tolerance changed significantly from baseline or compared with placebo during troglitazone treatment. The predominant response of beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes was a reduction in insulin release to maintain nearly constant glucose tolerance.

Effect of troglitazone on insulin sensitivity and pancreatic beta-cell function in women at high risk for NIDDM.

We conducted a randomized placebo-controlled study to determine the effects of the thiazolidinedione compound troglitazone on whole-body insulin sensitivity (SI), pancreatic beta-cell function, and glucose tolerance in 42 Latino women with impaired glucose tolerance (IGT) and a history of gestational diabetes mellitus (GDM), characteristics that carry an 80% risk of developing NIDDM within 5 years. After baseline oral (OGTT) and intravenous (IVGTT) glucose tolerance testing, subjects were assigned to take placebo or 200 or 400 mg troglitazone daily for 12 weeks (14 subjects per treatment group). An OGTT and IVGTT were repeated during the 12th week of treatment. Five subjects failed to complete the trial for personal reasons, and medication compliance averaged 90% in the remaining subjects, none of whom experienced a serious adverse event. SI, calculated by minimal model analysis of IVGTT results, changed by only 4 +/- 14% during 12 weeks of placebo administration, but increased 40 +/- 22 and 88 +/- 22% above basal during treatment with 200 and 400 mg troglitazone, respectively (P = 0.01 among groups). Troglitazone administration was also associated with a dose-dependent reduction in the total insulin area during IVGTTs, which was highly significant (P < 0.001), and with a reduction during OGTTs, which approached statistical significance (P = 0.09). Glucose tolerance improved slightly in all groups, but the magnitude of change did not differ significantly among groups, whether it was assessed as the number of subjects who continued to manifest IGT at 12 weeks (P = 0.64 among groups), the change in total glucose area during OGTTs (P = 0.58), or the change in fractional glucose disappearance rates during IVGTTs (P = 0.28). Among the women who received troglitazone, the greatest improvement in SI occurred in the women who had the highest diastolic blood pressures and the best IVGTT insulin responses during baseline testing. Our findings indicate that troglitazone improved whole-body insulin sensitivity and lowered circulating insulin concentrations in women with prior GDM who are at very high risk for NIDDM. The lack of improvement in glucose tolerance despite improved insulin sensitivity may be a manifestation of the beta-cell defect that predisposes the women to NIDDM. The overall pattern of response to troglitazone in our high-risk patients indicates that the drug is an ideal agent with which to test whether the amelioration of insulin resistance can delay or prevent diabetes in women with limited beta-cell reserve.

Low survival rate after cardiopulmonary resuscitation in a county hospital.

BACKGROUND: The standard of practice in hospitals in the United States is to perform cardiopulmonary resuscitation on all patients who suffer a cardiac arrest unless a specific order has been written to the contrary. In recent decades, however, data showing a low rate of survival to discharge under certain conditions have accumulated, leading some to question this policy. The objective of this study was to examine variables predictive of patient survival following cardiopulmonary resuscitation using standardized methods of measuring severity of illness. METHODS: All patients were identified who underwent cardiopulmonary resuscitation on the medicine service at Los Angeles County (California) Hospital from August 15, 1990, to February 15, 1991. Severity of illness was evaluated by examining diagnosis, Acute Physiology and Chronic Health Evaluation II score, and organ system failure. Cases were followed up prospectively until death or hospital discharge, and data concerning post-arrest mental status, utilization of resources, and disposition were gathered. RESULTS: Of the 131 patients identified, 22 patients (16.8%) survived for 24 hours but died before discharge; only four patients (3.1%) survived to discharge. CONCLUSIONS: This study suggests that in some settings (eg, institutions that are for sick patients under conditions where monitoring is limited because of scarcity of resources), survival after full cardiopulmonary arrest may be even lower than previously documented.

Effects of pharmacological doses of nandrolone decanoate and progressive resistance training in immunodeficient patients infected with human immunodeficiency virus.

This nonplacebo-controlled, open label, randomized study was conducted to test the hypotheses that pharmacological doses of nandrolone decanoate would increase lean body tissue, muscle mass, and strength in immunodeficient human immunodeficiency virus-infected men, and that these effects would be enhanced with progressive resistance training (PRT). Thirty human immunodeficiency virus-positive men with fewer than 400 CD4 lymphocytes/mm3 were randomly assigned to receive weekly injections of nandrolone alone or in combination with supervised PRT at 80% of the one-repetition maximum three times weekly for 12 weeks. Total body weight increased significantly in both groups (3.2 +/- 2.7 and 4.0 +/- 2.0 kg, respectively; P < 0.001), with increases due primarily to augmentation of lean tissue. Lean body mass determined by dual energy x-ray absorptiometry increased significantly more in the PRT group (3.9 +/- 2.3 vs. 5.2 +/- 5.7 kg, respectively; P = 0.03). Body cell mass by bioelectrical impedance analysis increased significantly (P < 0.001) in both groups (2.6 +/- 1.0 vs. 2.9 +/- 0.8 kg), but to a similar magnitude (P = NS). Significant increases in cross-sectional area by magnetic resonance imaging of total thigh muscles (1538 +/- 767 and 1480 +/- 532 mm2), quadriceps (705 +/- 365 and 717 +/- 288 mm2), and hamstrings (842 +/- 409 and 771 +/- 295 mm2) occurred with both treatment strategies (P < 0.001 for the three muscle areas); these increases were similar in both groups (P = NS). By the one-repetition method, strength increased in both upper and lower body exercises, with gains ranging from 10.3-31% in the nandrolone group and from 14.4-53.0% in the PRT group (P < 0.006 with one exception). Gains in strength were of significantly greater magnitude in the PRT group (P < or = 0.005 for all comparisons), even after correction for lean body mass. Thus, pharmacological doses of nandrolone decanoate yielded significant gains in total weight, lean body mass, body cell mass, muscle size, and strength. The increases in lean body mass and muscular strength were significantly augmented with PRT.

Influence of lifestyle modification on atherosclerotic progression determined by ultrasonographic change in the common carotid intima-media thickness.

The Monitored Atherosclerosis Regression Study (MARS) was a randomized, double-blind, placebo-controlled angiographic trial of lipid-lowering therapy in subjects with coronary artery disease. Subjects were counseled to follow a low-fat, low-cholesterol diet. At every clinic visit, data were obtained on body weight, dietary intake, alcohol consumption, and tobacco use. Semiannual determinations of early preintrusive atherosclerosis were made with high-resolution B-mode ultrasonography of the carotid artery intima-media thickness (IMT). We evaluated the effects of lifestyle modification (diet, alcohol, smoking, and weight loss) on the rate of carotid artery IMT progression on the 94 subjects randomly assigned to the placebo group. Dietary cholesterol, insoluble fiber, body mass index, and smoking were significant predictors of the annual rate of carotid artery IMT progression (P < 0.05). For subjects experiencing IMT progression, increased intakes of monounsaturated fat relative to saturated fat and stearic acid (18:0) consumption were significant predictors of a reduction in the annual rate of carotid artery IMT progression; for subjects experiencing IMT regression, male sex was a significant predictor of a reduction in the annual rate of carotid artery IMT regression. Modifications reducing body mass index by 5 kg/m2, quitting a 10 cigarette/d smoking habit, and reducing dietary cholesterol intake by 100 mg/d on average would reduce the annual rate of carotid wall IMT progression by 0.13 mm/y, which is equivalent to the maximum rate of IMT progression observed in the MARS placebo group. Progression of early preintrusive atherosclerosis can be reduced and overall regression can occur with dietary and lifestyle modification.

Seroepidemiologic studies of cytomegalovirus and Epstein-Barr virus infections in relation to human immunodeficiency virus type 1 infection in selected recipient populations. Transfusion Safety Study Group.

Antibodies to human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) were evaluated among 1,171 persons with and without antibodies to human immunodeficiency virus type 1 (anti-HIV-1). These included 97 blood donors, 577 persons given blood components or products, and 497 controls. A significantly higher proportion of anti-HIV-1 positive than -negative donors were anti-CMV-positive, a finding associated with homosexual contact among some of the former. Among subjects with treated clotting disorders, there was no difference in prevalence of anti-CMV or anti-EBV between anti-HIV-1-positive and -negative persons. The prevalence of antibodies to EBV early antigens showed no relationship to anti-HIV-1 status. Anti-CMV positivity in anti-HIV-1-negative donors was associated with an increase in mean CD8 counts and lower mean CD4/CD8 ratio. Anti-CMV and anti-EBV positivity in anti-HIV-1-positive subjects with treated clotting disorders was not associated with a lower CD4 or higher CD8 count than HIV-1 infection alone. Subjects who developed AIDS after enrollment had no significant difference in median time from entry to diagnosis when analyzed by serologic evidence of CMV and EBV antibody status at entry, and a few subjects had AIDS at entry without serologic evidence of prior CMV or EBV infection. The overall results are consistent with acquisition and progression of HIV-1 independently of coincident CMV or EBV infection.

Fecal alpha 1-antitrypsin and hemoglobin excretion in healthy human milk-, formula-, or cow's milk-fed infants.

There is concern that whole cow's milk feedings may be associated with intestinal abnormalities in infants. We studied this issue by measuring random fecal samples for alpha 1-antitrypsin (FA1AT) and hemoglobin (FH) concentrations in 820 healthy infants up to 12 months of age. Subjects were fed either human milk, formula, or fresh whole cow's milk. Solid foods were given ad libitum. Fecal samples were also tested for occult blood with Hematest reagent tablets. None of the infants younger than 6 months of age were receiving fresh whole cow's milk. We found small but statistically significant differences in mean FA1AT between the three feeding groups (P less than .0001): human milk (n = 354) greater than formula (n = 320) greater than cow's milk (n = 146). The younger subjects fed either formula or human milk tended to have higher FA1AT concentrations than did the age-matched subjects who were not consuming solid foods (P less than or equal to .005). Daily FA1AT excretion, FA1AT concentration, and daily stool output were subsequently determined on a separate group of 40 infants 8 to 12 months of age to ascertain whether differences in total daily FA1AT excretion occur in children fed different types of milk. Total daily FA1AT excretion was similar in the three milk feeding groups. An inverse correlation between FA1AT concentration and daily stool output was also found (P less than .001). The overall rate of detectable FH in 792 stool smears was 2.1% and unrelated to type of milk feeding. Of 705 stool smears, 3.5% had positive Hematest reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of three methods for the measurement of corneal thickness.

Four subjects who had never worn contact lenses underwent measurement of their corneal thickness by each of three measurement methods: Haag-Streit pachometer with/and without Mishima-Hedby attachment and the Syber specular microscope. Data were collected on three separate sessions, and at each session triplicate measurement trials were made for each method. The resulting 108 measurements were analyzed statistically. Significant differences were found among the measurement methods. Two of the methods were found to be consistent from session to session. In addition, the specular microscope was found to be the most precise method within a session. It was concluded that the specular microscope, which highly trained technicians can utilize to make the measurements, offers a valuable alternative to the measurement of corneal thickness in long-term prospective studies.

Immunopathology of acute experimental histoplasmic choroiditis in the primate.

The immunopathologic features of experimental acute histoplasmic choroiditis were studied in the nonhuman primate. Using an indirect immunoperoxidase technique, a panel of hybridoma-derived anti-human monoclonal antibodies, recognizing distinct lymphoid cell and macrophage surface antigens, have been adapted for use in the primate system. Twenty-two individual foci of histoplasmic choroiditis from five eyes were studied at time periods from 20 to 60 days post intracarotid injection of yeast phase Histoplasma capsulatum. A mononuclear and granulocytic cell infiltration was seen in all lesions. The predominant cell type was the CAPPEL+ T lymphocyte (suppressor/cytotoxic subset). Other cell types found in smaller numbers were OKT4+ T cells (helper/inducer subset), OK7+ (peripheral B lymphocytes), IgD+ (mantle B cells) and OKM1+ cells (macrophages and polymorphonuclear leukocytes). Herein, we present immunopathologic data on the acute phase of experimental ocular histoplasmosis.

Fat and cholesterol intake of attendees at two national USA cardiovascular annual meetings.

Using a 1-page bar-coded food frequency questionnaire, the food habits of 996 adults who participated in diet screening at the annual meetings of the American Heart Association (1989) and the American College of Cardiology (1990) were analyzed for sex, age and regional differences. Estimated nutrient intakes were also compared with those from the Department of Agriculture's 1985 and 1986 Continuing Survey of Food Intake of Individuals. The average diet reported in this study satisfied National Cholesterol Education Program guidelines for cholesterol intake, but was higher than that recommended for total and saturated fats. In addition, dietary fat intake was influenced by sex, age and geographic region. Reduction in total and saturated fat intake was confined to men greater than 35 years of age; intake of these nutrients was highest among young, Mid-western women. These results suggest the need for diet intervention programs, targeted specifically to young adults with additional consideration given to regional variation. Repeated surveys of cardiac care givers might be used as an early indicator of the nationwide effectiveness of dietary intervention programs.

Evaluation of an expert system on lymph node pathology.

BACKGROUND: Pathfinder is an Expert System that assists pathologists in making accurate diagnoses in the domain of lymph-node pathology. Pathfinder provides a differential diagnosis based on the initial histological feature(s) observed by the pathologist, and suggests to the user additional histological features for observation that are likely to narrow the differential diagnosis. PURPOSE: To evaluate the diagnostic accuracy of pathologists with and without the Pathfinder. METHODS: Thirty H&E stained slides from 30 lymph node biopsy specimens on which a Consensus diagnosis was made by two experts were reviewed by 19 pathologists to evaluate Pathfinder. After a period of training, 10 pathologists using Pathfinder (Interactive Computer Method) and 9 pathologists using the Routine Method (diagnosis without computer) determined a differential diagnosis for 15 slides (Test 1). Pathologists were then crossed over, trained, and evaluated the remaining 15 slides (Test 2). For each test, the proportion of "correct" diagnoses was compared between methods. In addition, the information integration attributes (making logical diagnosis given a set of specific histologic features) of Pathfinder and pathologists were compared. Finally, feature identification and quantification skills of pathologists were determined and correlated with the percent correct diagnosis. RESULTS: The diagnostic accuracy using Pathfinder was greater than that using the Routine Method (40% v 32%, P = .02). Diagnostic accuracy for the group of pathologists who made diagnosis using the Routine Method in Test 1 increased when they made diagnosis using Pathfinder in Test 2 (27% to 44%, P < .0001). The proportion of correct diagnosis for the group of pathologists who used Pathfinder in Test 1 remained virtually unchanged when they gave up Pathfinder in Test 2 (35% to 37%). The percentage of incompatible feature identification ("atypical proliferation" diagnosis) was significantly lower after using Pathfinder (P < .0001). In addition, information integration attributes of Pathfinder were significantly superior than that of the pathologists (P < .0001). CONCLUSIONS: Pathfinder is a valuable tool that assists pathologists in making accurate diagnosis because it has superior attributes than pathologists to integrate information and to screen for observations incompatible with any specific disease.

Cardiac output by thermodilution technique. Effect of injectate's volume and temperature on accuracy and reproducibility in the critically Ill patient.

We compared determinations of cardiac output using various combinations of injectate volumes and temperatures to results obtained with 10 ml of iced (0 degrees C) injectate (standard technique) in 33 critically ill patients. The use of a 10-ml injectate at room temperature resulted in comparable reproducibility (12.7 vs 10.8 percent; not significant) and a small and nonsignificant error (-0.013 +/- 0.543 L/min). Five milliliters at room temperature resulted in markedly decreased reproducibility (17.9 vs 8.9 percent; p less than 0.05); however, the error associated with the technique was still not significant (0.136 +/- 0.829 L/min). When a 5-ml injectate at 0 degrees C was used, a reproducibility comparable to that of 10 ml at 0 degrees C was obtained (12.3 vs 7.5 percent; not significant). The results underestimated values obtained with 10 ml at 0 degrees C (-0.360 +/- 0.857 L/minute); however, the difference did not reach statistical significance. The use of 3 ml at 0 degrees C was associated with a substantial increase in variability, with a coefficient of variation of 32.0 percent (10.4 percent for 10 ml of iced injectate; p less than 0.01); however, the differences between the average value of cardiac output obtained with this technique and the standard technique were only minimal (error, -0.063 +/- 0.455; not significant). We reached the following conclusions: (1) the use of 10 ml at room temperature and 5 ml at 0 degrees C as the indicator for thermodilution determinations of cardiac output results in small and insignificant differences in reproducibility and accuracy from the standard technique; (2) five milliliters at room temperature and 3 ml at 0 degrees C are associated with markedly decreased reproducibility; however, the error in values for cardiac output obtained with these techniques is not statistically significant; and (3) the ability to use injectate at room temperature and in small volume should substantially simplify the technique, lowering its cost, and should prevent volume overloading.

Scanning laser entoptic perimetry for the screening of macular and peripheral retinal disease.

OBJECTIVE: To determine the effectiveness of scanning laser entoptic perimetry as a noninvasive platform for screening for retinal damage in visually asymptomatic patients within the central 120 degrees (diameter) of vision. DESIGN: A masked study comparing entoptic perimetry with fundus photographs. SETTING: The Shiley Eye Center and the AIDS Ocular Research Unit at the University of California, San Diego. PATIENTS: Fifty-eight patients recruited during ophthalmologic visits for treatment or follow-up of ocular disease. MEASUREMENTS: For each testing session, we compared the presence of a disturbance in the entoptic stimulus with the presence of retinal disease within the central 120 degrees of vision, centered on the fovea. RESULTS: Scanning laser entoptic perimetry has a sensitivity and specificity of more than 90%, a positive predictive value of 100%, and a negative predictive value of 89% for screening retinal lesions within the central 120 degrees diameter of vision. CONCLUSION: Scanning laser entoptic perimetry may be an effective and inexpensive screening test for diagnosing retinal disease in hospitals and community clinics. Arch Ophthalmol. 2000;118:1205-1210

Prognosis in uveal melanoma with extrascleral extension.

Two thirds of 60 patients followed up after enucleation for uveal melanoma with extrascleral extension eventually died of metastatic disease. Large intraocular tumor size, more malignant cell types, optic nerve invasion, and surgical transection or nonencapsulation of the extraocular tumor margin were found to be significantly correlated with development of metastases. Advanced age at enucleation and large intraocular tumor size were significantly associated with early metastatic death. Recurrence of tumor in the orbit was identified in 10% of the patients and was significantly correlated with large intraocular tumor size and optic nerve invasion. Early exenteration, performed in seven cases, did not improve prognosis. Application of Bayesian methods produced a multifactorial model for prediction of metastatic disease within 13 years after enucleation.

A study of optical zone size and incision redeepening in experimental radial keratotomy.

The effects of optical clear zone size and incision redeepening following four- and eight-incision radial keratotomy were studied in a series of human cadaver eyes. Keratometry was measured with both the Terry keratometer and corneascope photographs. After eight incisions, induced corneal flattening for each clear zone (Terry keratometry readings) was 3.0 mm, 9.06 diopters; 4.0 mm, 6.44 D; 5.0 mm, 5.23 D; and 6.0 mm, 2.29 D. Differences were statistically significant, except for the 4.0-mm and 5.0-mm zones. Induced corneal flattening following eight incisions (corneoscopy) was 3.0 mm, 9.83 D; 4.0 mm, 8.87 D; 5.0 mm, 6.04 D; and 6.0 mm, 2.59 D. Differences were statistically significant, except for the 3.0-mm and 4.0-mm zones. Peripheral redeepening of the incisions did not significantly increase the amount of corneal flattening for any optical zone, as measured by the Terry keratometer. However, the 3.0-mm optical zone flattened an additional 1.23 D after the redeepening incisions, as measured by corneoscopy. The redeepening incisions were complicated by perforations in 38% of the eyes. Titrating the effect of radial keratotomy by varying the size of the optical zone appears to be valid, but the value of peripheral redeepening in the acute laboratory situation is not supported by these data.